Global Civil Aviation Black Carbon Particle Mass and Number Emissions

NASA Astrophysics Data System (ADS)

Stettler, M. E. J.

2015-12-01

Black carbon (BC) is a product of incomplete combustion emitted by aircraft engines. In the atmosphere, BC particles strongly absorb incoming solar radiation and influence cloud formation processes leading to highly uncertain, but likely net positive warming of the earth's atmosphere. At cruise altitude, BC particle number emissions can influence the concentration of ice nuclei that can lead to contrail formation, with significant and highly uncertainty climate impacts. BC particles emitted by aircraft engines also degrade air quality in the vicinity of airports and globally. A significant contribution to the uncertainty in environmental impacts of aviation BC emissions is the uncertainty in emissions inventories. Previous work has shown that global aviation BC mass emissions are likely to have been underestimated by a factor of three. In this study, we present an updated global BC particle number inventory and evaluate parameters that contribute to uncertainty using global sensitivity analysis techniques. The method of calculating particle number from mass utilises a description of the mobility of fractal aggregates and uses the geometric mean diameter, geometric standard deviation, mass-mobility exponent, primary particle diameter and material density to relate the particle number concentration to the total mass concentration. Model results show good agreement with existing measurements of aircraft BC emissions at ground level and at cruise altitude. It is hoped that the results of this study can be applied to estimate direct and indirect climate impacts of aviation BC emissions in future studies.

Quantifying Particle Numbers and Mass Flux in Drifting Snow

NASA Astrophysics Data System (ADS)

Crivelli, Philip; Paterna, Enrico; Horender, Stefan; Lehning, Michael

2016-12-01

We compare two of the most common methods of quantifying mass flux, particle numbers and particle-size distribution for drifting snow events, the snow-particle counter (SPC), a laser-diode-based particle detector, and particle tracking velocimetry based on digital shadowgraphic imaging. The two methods were correlated for mass flux and particle number flux. For the SPC measurements, the device was calibrated by the manufacturer beforehand. The shadowgrapic imaging method measures particle size and velocity directly from consecutive images, and before each new test the image pixel length is newly calibrated. A calibration study with artificially scattered sand particles and glass beads provides suitable settings for the shadowgraphical imaging as well as obtaining a first correlation of the two methods in a controlled environment. In addition, using snow collected in trays during snowfall, several experiments were performed to observe drifting snow events in a cold wind tunnel. The results demonstrate a high correlation between the mass flux obtained for the calibration studies (r ≥slant 0.93) and good correlation for the drifting snow experiments (r ≥slant 0.81). The impact of measurement settings is discussed in order to reliably quantify particle numbers and mass flux in drifting snow. The study was designed and performed to optimize the settings of the digital shadowgraphic imaging system for both the acquisition and the processing of particles in a drifting snow event. Our results suggest that these optimal settings can be transferred to different imaging set-ups to investigate sediment transport processes.

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

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/

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.

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.

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.

Light nuclei of even mass number in the Skyrme model

NASA Astrophysics Data System (ADS)

Battye, R. A.; Manton, N. S.; Sutcliffe, P. M.; Wood, S. W.

2009-09-01

We consider the semiclassical rigid-body quantization of Skyrmion solutions of mass numbers B=4,6,8,10, and 12. We determine the allowed quantum states for each Skyrmion and find that they often match the observed states of nuclei. The spin and isospin inertia tensors of these Skyrmions are accurately calculated for the first time and are used to determine the excitation energies of the quantum states. We calculate the energy level splittings, using a suitably chosen parameter set for each mass number. We find good qualitative and encouraging quantitative agreement with experiment. In particular, the rotational bands of beryllium-8 and carbon-12, along with isospin 1 triplets and isospin 2 quintets, are especially well reproduced. We also predict the existence of states that have not yet been observed and make predictions for the unknown quantum numbers of some observed states.

Seasonal variations of number size distributions and mass concentrations of atmospheric particles in Beijing

NASA Astrophysics Data System (ADS)

Yu, Jianhua; Guinot, Benjamin; Yu, Tong; Wang, Xin; Liu, Wenqing

2005-06-01

Particle number and mass concentrations were measured in Beijing during the winter and summer periods in 2003, together with some other parameters including black carbon (BC) and meteorological conditions. Particle mass concentrations exhibited low seasonality, and the ratio of PM2.5/PM10 in winter was higher than that in summer. Particle number size distribution (PSD) was characterized by four modes and exhibited low seasonality. BC was well correlated with the number and mass concentrations of accumulation and coarse particles, indicating these size particles are related to anthropogenic activities. Particle mass and number concentrations (except ultra-fine and nucleation particles) followed well the trends of BC concentration for the majority of the day, indicating that most particles were associated with primary emissions. The diurnal number distributions of accumulation and coarse mode particles were characterized by two peaks.

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.

Energy and Mass-Number Dependence of Hadron-Nucleus Total Reaction Cross Sections

NASA Astrophysics Data System (ADS)

Kohama, Akihisa; Iida, Kei; Oyamatsu, Kazuhiro

2016-09-01

We thoroughly investigate how proton-nucleus total reaction cross sections depend on the target mass number A and the proton incident energy. In doing so, we systematically analyze nuclear reaction data that are sensitive to nuclear size, namely, proton-nucleus total reaction cross sections and differential elastic cross sections, using a phenomenological black-sphere approximation of nuclei that we are developing. In this framework, the radius of the black sphere is found to be a useful length scale that simultaneously accounts for the observed proton-nucleus total reaction cross section and first diffraction peak in the proton elastic differential cross section. This framework, which is shown here to be applicable to antiprotons, is expected to be applicable to any kind of projectile that is strongly attenuated in the nucleus. On the basis of a cross-section formula constructed within this framework, we find that a less familiar A1/6 dependence plays a crucial role in describing the energy dependence of proton-nucleus total reaction cross sections.

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.

What's your number? The effects of trial order on the one-target advantage.

PubMed

Bested, Stephen R; Khan, Michael A; Lawrence, Gavin P; Tremblay, Luc

2018-05-01

When moving our upper-limb towards a single target, movement times are typically shorter than when movement to a second target is required. This is known as the one-target advantage. Most studies that have demonstrated the one-target advantage have employed separate trial blocks for the one- and two-segment movements. To test if the presence of the one-target advantage depends on advance knowledge of the number of segments, the present study investigated whether the one-target advantage would emerge under different trial orders/sequences. One- and two-segment responses were organized in blocked (i.e., 1-1-1, 2-2-2), alternating (i.e., 1-2-1-2-1-2), and random (i.e., 1-1-2-1-2-2) trial sequences. Similar to previous studies, where only blocked schedules have typically been utilized, the one-target advantage emerged during the blocked and alternate conditions, but not in the random condition. This finding indicates that the one-target advantage is contingent on participants knowing the number of movement segments prior to stimulus onset. Copyright © 2018 Elsevier B.V. All rights reserved.

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.

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...

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.

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.

Characterization of Incidental Renal Mass With Dual-Energy CT: Diagnostic Accuracy of Effective Atomic Number Maps for Discriminating Nonenhancing Cysts From Enhancing Masses.

PubMed

Mileto, Achille; Allen, Brian C; Pietryga, Jason A; Farjat, Alfredo E; Zarzour, Jessica G; Bellini, Davide; Ebner, Lukas; Morgan, Desiree E

2017-10-01

The purpose of this study was to assess the diagnostic accuracy of effective atomic number maps reconstructed from dual-energy contrast-enhanced data for discriminating between nonenhancing renal cysts and enhancing masses. Two hundred six patients (128 men, 78 women; mean age, 64 years) underwent a CT renal mass protocol (single-energy unenhanced and dual-energy contrast-enhanced nephrographic imaging) at two different hospitals. For each set of patients, two blinded, independent observers performed measurements on effective atomic number maps from contrast-enhanced dual-energy data. Renal mass assessment on unenhanced and nephrographic images, corroborated by imaging and medical records, was the reference standard. The diagnostic accuracy of effective atomic number maps was assessed with ROC analysis. Significant differences in mean effective atomic numbers (Z eff ) were observed between nonenhancing and enhancing masses (set A, 8.19 vs 9.59 Z eff ; set B, 8.05 vs 9.19 Z eff ; sets combined, 8.13 vs 9.37 Z eff ) (p < 0.0001). An effective atomic number value of 8.36 Z eff was the optimal threshold, rendering an AUC of 0.92 (95% CI, 0.89-0.94), sensitivity of 90.8% (158/174 [95% CI, 85.5-94.7%]), specificity of 85.2% (445/522 [95% CI, 81.9-88.2%]), and overall diagnostic accuracy of 86.6% (603/696 [95% CI, 83.9-89.1%]). Nonenhancing renal cysts, including hyperattenuating cysts, can be discriminated from enhancing masses on effective atomic number maps generated from dual-energy contrast-enhanced CT data. This technique may be of clinical usefulness when a CT protocol for comprehensive assessment of renal masses is not available.

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

Targeted cancer therapy--are the days of systemic chemotherapy numbered?

PubMed

Joo, Won Duk; Visintin, Irene; Mor, Gil

2013-12-01

Targeted therapy or molecular targeted therapy has been defined as a type of treatment that blocks the growth of cancer cells by interfering with specific cell molecules required for carcinogenesis and tumor growth, rather than by simply interfering with all rapidly dividing cells as with traditional chemotherapy. There is a growing number of FDA approved monoclonal antibodies and small molecules targeting specific types of cancer suggestive of the growing relevance of this therapeutic approach. Targeted cancer therapies, also referred to as "Personalized Medicine", are being studied for use alone, in combination with other targeted therapies, and in combination with chemotherapy. The objective of personalized medicine is the identification of patients that would benefit from a specific treatment based on the expression of molecular markers. Examples of this approach include bevacizumab and olaparib, which have been designated as promising targeted therapies for ovarian cancer. Combinations of trastuzumab with pertuzumab, or T-DM1 and mTOR inhibitors added to an aromatase inhibitor are new therapeutic strategies for breast cancer. Although this approach has been seen as a major step in the expansion of personalized medicine, it has substantial limitations including its high cost and the presence of serious adverse effects. The Cancer Genome Atlas is a useful resource to identify novel and more effective targets, which may help to overcome the present limitations. In this review we will discuss the clinical outcome of some of these new therapies with a focus on ovarian and breast cancer. We will also discuss novel concepts in targeted therapy, the target of cancer stem cells. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Relationships among particle number, surface area, and respirable mass concentrations in automotive engine manufacturing.

PubMed

Heitbrink, William A; Evans, Douglas E; Ku, Bon Ki; Maynard, Andrew D; Slavin, Thomas J; Peters, Thomas M

2009-01-01

This study investigated the relationships between particle number, surface area, and respirable mass concentration measured simultaneously in a foundry and an automotive engine machining and assembly center. Aerosol concentrations were measured throughout each plant with a condensation particle counter for number concentration, a diffusion charger for active surface area concentration, and an optical particle counter for respirable mass concentration. At selected locations, particle size distributions were characterized with the optical particle counter and an electrical low pressure impactor. Statistical analyses showed that active surface area concentration was correlated with ultrafine particle number concentration and weakly correlated with respirable mass concentration. Correlation between number and active surface area concentration was stronger during winter (R2 = 0.6 for both plants) than in the summer (R2 = 0.38 and 0.36 for the foundry and engine plant respectively). The stronger correlation in winter was attributed to use of direct-fire gas fired heaters that produced substantial numbers of ultrafine particles with a modal diameter between 0.007 and 0.023 mu m. These correlations support findings obtained through theoretical analysis. Such analysis predicts that active surface area increasingly underestimates geometric surface area with increasing particle size, particularly for particles larger than 100 nm. Thus, a stronger correlation between particle number concentration and active surface area concentration is expected in the presence of high concentrations of ultrafine particles. In general, active surface area concentration may be a concentration metric that is distinct from particle number concentration and respirable mass concentration. For future health effects or toxicological studies involving nano-materials or ultrafine aerosols, this finding needs to be considered, as exposure metrics may influence data interpretation.

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

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

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.

Studies on effective atomic numbers, electron densities from mass attenuation coefficients near the K edge in some samarium compounds.

PubMed

Akman, F; Durak, R; Turhan, M F; Kaçal, M R

2015-07-01

The effective atomic numbers and electron densities of some samarium compounds were determined using the experimental total mass attenuation coefficient values near the K edge in the X-ray energy range from 36.847 up to 57.142 keV. The measurements, in the region from 36.847 to 57.142 keV, were done in a transmission geometry utilizing the Kα2, Kα1, Kβ1 and Kβ2 X-rays from different secondary source targets excited by the 59.54 keV gamma-photons from an Am-241 annular source. This paper presents the first measurement of the effective atomic numbers and electron densities for some samarium compounds near the K edge. The results of the study showed that the measured values were in good agreement with the theoretically calculated ones. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effect of Reynolds number on flow and mass transfer characteristics of a 90 degree elbow

NASA Astrophysics Data System (ADS)

Fujisawa, Nobuyuki; Ikarashi, Yuya; Yamagata, Takayuki; Taguchi, Syoichi

2016-11-01

The flow and mass transfer characteristics of a 90 degree elbow was studied experimentally by using the mass transfer measurement by plaster dissolution method, the surface flow visualization by oil film method and stereo PIV measurement. The experiments are carried out in a water tunnel of a circular pipe of 56mm in diameter with a working fluid of water. The Reynolds number was varied from 30000 to 200000. The experimental result indicated the change of the mass transfer coefficient distribution in the elbow with increasing the Reynolds number. This phenomenon is further examined by the surface flow visualization and measurement of secondary flow pattern in the elbow, and the results showed the suggested change of the secondary flow pattern in the elbow with increasing the Reynolds numbers.

Relation between number of component views and accuracy of left ventricular mass determined by three-dimensional echocardiography.

PubMed

Chuang, Michael L; Salton, Carol J; Hibberd, Mark G; Manning, Warren J; Douglas, Pamela S

2007-05-01

Three-dimensional echocardiography (3DE) allows the accurate determination of left ventricular (LV) mass, but the optimal number of component or extracted 2-dimensional (2D) image planes that should be used to calculate LV mass is not known. This study was performed to determine the relation between the number of 2D image planes used for 3DE and the accuracy of LV mass, using cardiovascular magnetic resonance (CMR) imaging as the reference standard. Three-dimensional echocardiography data sets were analyzed using 4, 6, 8, 10 and 20 component 2D planes as well as biplane 2D echocardiography and CMR in 25 subjects with a variety of LV pathologies. Repeated-measures analysis of variance and the Bland-Altman method were used to compare measures of LV mass. To further assess the potential clinical impact of reducing the number of component image planes used for 3DE, the number of discrepancies between CMR and each of the 3DE estimates of LV mass at prespecified levels (i.e., > or =5%, > or =10%, and > or =20% difference from CMR LV mass) was tabulated. The mean LV mass by magnetic resonance imaging was 177 +/- 56 g (range 91 to 316). Biplane 2-dimensional echocardiography significantly underestimated CMR LV mass (p <0.05), but LV mass by 3DE was not statistically different from that by CMR regardless of the number of planes used. However, error variability and Bland-Altman 95% confidence intervals decreased with the use of additional image planes. In conclusion, transthoracic 3DE measures LV mass more accurately than biplane 2-dimensional echocardiography when > or =6 component 2D image planes are used. The use of >6 planes further increases the accuracy of 3DE, but at the cost of greater analysis time and potentially increased scanning times.

A statistical approach to detection of copy number variations in PCR-enriched targeted sequencing data.

PubMed

Demidov, German; Simakova, Tamara; Vnuchkova, Julia; Bragin, Anton

2016-10-22

Multiplex polymerase chain reaction (PCR) is a common enrichment technique for targeted massive parallel sequencing (MPS) protocols. MPS is widely used in biomedical research and clinical diagnostics as the fast and accurate tool for the detection of short genetic variations. However, identification of larger variations such as structure variants and copy number variations (CNV) is still being a challenge for targeted MPS. Some approaches and tools for structural variants detection were proposed, but they have limitations and often require datasets of certain type, size and expected number of amplicons affected by CNVs. In the paper, we describe novel algorithm for high-resolution germinal CNV detection in the PCR-enriched targeted sequencing data and present accompanying tool. We have developed a machine learning algorithm for the detection of large duplications and deletions in the targeted sequencing data generated with PCR-based enrichment step. We have performed verification studies and established the algorithm's sensitivity and specificity. We have compared developed tool with other available methods applicable for the described data and revealed its higher performance. We showed that our method has high specificity and sensitivity for high-resolution copy number detection in targeted sequencing data using large cohort of samples.

The Mass of Graviton and Its Relation to the Number of Information according to the Holographic Principle

PubMed Central

Gkigkitzis, Ioannis

2014-01-01

We investigate the relation of the mass of the graviton to the number of information N in a flat universe. As a result we find that the mass of the graviton scales as mgr∝1/N. Furthermore, we find that the number of gravitons contained inside the observable horizon is directly proportional to the number of information N; that is, N gr ∝ N. Similarly, the total mass of gravitons that exist in the universe is proportional to the number of information N; that is, Mgr∝N. In an effort to establish a relation between the graviton mass and the basic parameters of the universe, we find that the mass of the graviton is simply twice the Hubble mass m H as it is defined by Gerstein et al. (2003), times the square root of the quantity q − 1/2, where q is the deceleration parameter of the universe. In relation to the geometry of the universe we find that the mass of the graviton varies according to the relation mgr∝Rsc, and therefore m gr obviously controls the geometry of the space time through a deviation of the geodesic spheres from the spheres of Euclidean metric. PMID:27433513

Sperm competition games: sperm size (mass) and number under raffle and displacement, and the evolution of P2.

PubMed

Parker, G A; Immler, S; Pitnick, S; Birkhead, T R

2010-06-07

We examine models for evolution of sperm size (i.e. mass m) and number (s) under three mechanisms of sperm competition at low 'risk' levels: (i) raffle with no constraint on space available for competing sperm, (ii) direct displacement mainly by seminal fluid, and (iii) direct displacement mainly by sperm mass. Increasing sperm mass increases a sperm's 'competitive weight' against rival sperm through a diminishing returns function, r(m). ESS total ejaculate expenditure (the product m(*)s(*)) increases in all three models with sperm competition risk, q. If r(m), or ratio r'(m)/r(m), is independent of ESS sperm numbers, ESS sperm mass remains constant, and the sperm mass/number ratio (m(*)/s(*)) therefore decreases with risk. Dependency of sperm mass on risk can arise if r(m) depends on competing sperm density (sperm number / space available for sperm competition). Such dependencies generate complex relationships between sperm mass and number with risk, depending both on the mechanism and how sperm density affects r(m). While numbers always increase with risk, mass can either increase or decrease, but m(*)/s(*) typically decreases with risk unless sperm density strongly influences r(m). Where there is no extrinsic loading due to mating order, ESS paternity of the second (i.e. last) male to mate (P(2)) under displacement always exceeds 0.5, and increases with risk (in the raffle P(2)=0.5). Caution is needed when seeking evidence for a sperm size-number trade off. Although size and number trade-off independently against effort spent on acquiring matings, their product, m(*)s(*), is invariant or fixed at a given risk level, effectively generating a size-number trade off. However, unless controlled for the effects of risk, the relation between m(*) and s(*) can be either positive or negative (a positive relation is usually taken as evidence against a size-number trade off). Copyright (c) 2010 Elsevier Ltd. All rights reserved.

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.

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.

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

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.

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

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

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

Is a top-heavy initial mass function needed to reproduce the submillimetre galaxy number counts?

NASA Astrophysics Data System (ADS)

Safarzadeh, Mohammadtaher; Lu, Yu; Hayward, Christopher C.

2017-12-01

Matching the number counts and redshift distribution of submillimetre galaxies (SMGs) without invoking modifications to the initial mass ffunction (IMF) has proved challenging for semi-analytic models (SAMs) of galaxy formation. We adopt a previously developed SAM that is constrained to match the z = 0 galaxy stellar mass function and makes various predictions which agree well with observational constraints; we do not recalibrate the SAM for this work. We implement three prescriptions to predict the submillimetre flux densities of the model galaxies; two depend solely on star formation rate, whereas the other also depends on the dust mass. By comparing the predictions of the models, we find that taking into account the dust mass, which affects the dust temperature and thus influences the far-infrared spectral energy distribution, is crucial for matching the number counts and redshift distribution of SMGs. Moreover, despite using a standard IMF, our model can match the observed SMG number counts and redshift distribution reasonably well, which contradicts the conclusions of some previous studies that a top-heavy IMF, in addition to taking into account the effect of dust mass, is needed to match these observations. Although we have not identified the key ingredient that is responsible for our model matching the observed SMG number counts and redshift distribution without IMF variation - which is challenging given the different prescriptions for physical processes employed in the SAMs of interest - our results demonstrate that in SAMs, IMF variation is degenerate with other physical processes, such as stellar feedback.

Direct targeting of human plasma for matrix-assisted laser desorption/ionization and analysis of plasma proteins by time of flight-mass spectrometry.

PubMed

Jin, Ya; Manabe, Takashi

2005-07-01

A method to analyze human plasma proteins without fractionation, directly applying a plasma-matrix mixture on the target plate of a matrix-assisted laser desorption/ionization-time of flight-mass spectrometer (MALDI-TOF-MS), has been described. Peaks of ionized plasma proteins could not be detected applying a mixture of an undiluted plasma sample and a matrix solution, but they appeared when the plasma was diluted before mixing with the matrix. Tenfold diluted plasma provided well-resolved protein peaks in the m/z range from 4000 to 30,000. The addition of a simple post-crystallization washing procedure performed on the target plate further improved the quality of mass spectra. We numbered 58 peaks in the range of 4-160 kDa and 32 out of which were assigned to the plasma protein species which have been reported. Especially high sensitivity and resolution were obtained in the region < 30 kDa, where multiple isoforms of apolipoprotein A-I, apolipoprotein A-II, apolipoprotein C-I, apolipoprotein C-II, apolipoprotein C-III, and transthyretin could be assigned. Various post-translational modifications are involved in the isoforms, e.g., proteolytic cleavage, glycosylation and chemical modifications. This method will become complementary with the present electrophoretic techniques, especially for the analysis of low-molecular-mass proteins.

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.

MaNGA: Target selection and Optimization

NASA Astrophysics Data System (ADS)

Wake, David

2015-01-01

The 6-year SDSS-IV MaNGA survey will measure spatially resolved spectroscopy for 10,000 nearby galaxies using the Sloan 2.5m telescope and the BOSS spectrographs with a new fiber arrangement consisting of 17 individually deployable IFUs. We present the simultaneous design of the target selection and IFU size distribution to optimally meet our targeting requirements. The requirements for the main samples were to use simple cuts in redshift and magnitude to produce an approximately flat number density of targets as a function of stellar mass, ranging from 1x109 to 1x1011 M⊙, and radial coverage to either 1.5 (Primary sample) or 2.5 (Secondary sample) effective radii, while maximizing S/N and spatial resolution. In addition we constructed a 'Color-Enhanced' sample where we required 25% of the targets to have an approximately flat number density in the color and mass plane. We show how these requirements are met using simple absolute magnitude (and color) dependent redshift cuts applied to an extended version of the NASA Sloan Atlas (NSA), how this determines the distribution of IFU sizes and the resulting properties of the MaNGA sample.

MaNGA: Target selection and Optimization

NASA Astrophysics Data System (ADS)

Wake, David

2016-01-01

The 6-year SDSS-IV MaNGA survey will measure spatially resolved spectroscopy for 10,000 nearby galaxies using the Sloan 2.5m telescope and the BOSS spectrographs with a new fiber arrangement consisting of 17 individually deployable IFUs. We present the simultaneous design of the target selection and IFU size distribution to optimally meet our targeting requirements. The requirements for the main samples were to use simple cuts in redshift and magnitude to produce an approximately flat number density of targets as a function of stellar mass, ranging from 1x109 to 1x1011 M⊙, and radial coverage to either 1.5 (Primary sample) or 2.5 (Secondary sample) effective radii, while maximizing S/N and spatial resolution. In addition we constructed a "Color-Enhanced" sample where we required 25% of the targets to have an approximately flat number density in the color and mass plane. We show how these requirements are met using simple absolute magnitude (and color) dependent redshift cuts applied to an extended version of the NASA Sloan Atlas (NSA), how this determines the distribution of IFU sizes and the resulting properties of the MaNGA sample.

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.

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.

Mass, surface area and number metrics in diesel occupational exposure assessment.

PubMed

Ramachandran, Gurumurthy; Paulsen, Dwane; Watts, Winthrop; Kittelson, David

2005-07-01

While diesel aerosol exposure assessment has traditionally been based on the mass concentration metric, recent studies have suggested that particle number and surface area concentrations may be more health-relevant. In this study, we evaluated the exposures of three occupational groups-bus drivers, parking garage attendants, and bus mechanics-using the mass concentration of elemental carbon (EC) as well as surface area and number concentrations. These occupational groups are exposed to mixtures of diesel and gasoline exhaust on a regular basis in various ratios. The three groups had significantly different exposures to workshift TWA EC with the highest levels observed in the bus garage mechanics and the lowest levels in the parking ramp booth attendants. In terms of surface area, parking ramp attendants had significantly greater exposures than bus garage mechanics, who in turn had significantly greater exposures than bus drivers. In terms of number concentrations, the exposures of garage mechanics exceeded those of ramp booth attendants by a factor of 5-6. Depending on the exposure metric chosen, the three occupational groups had quite different exposure rankings. This illustrates the importance of the choice of exposure metric in epidemiological studies. If these three occupational groups were part of an epidemiological study, depending on the metric used, they may or may not be part of the same similarly exposed group (SEG). The exposure rankings (e.g., low, medium, or high) of the three groups also changes with the metric used. If the incorrect metric is used, significant misclassification errors may occur.

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.

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.

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.

Non-targeted screening of house dust samples using accurate mass TOFMS

EPA Science Inventory

House dust exists as an environmental repository of chemicals to which we are exposed in our homes. A growing number of studies have targeted select persistent organic and inorganic pollutants found in house dust. Many have concluded that dust exists as an important human expos...

Genomic Copy Number Dictates a Gene-Independent Cell Response to CRISPR/Cas9 Targeting.

PubMed

Aguirre, Andrew J; Meyers, Robin M; Weir, Barbara A; Vazquez, Francisca; Zhang, Cheng-Zhong; Ben-David, Uri; Cook, April; Ha, Gavin; Harrington, William F; Doshi, Mihir B; Kost-Alimova, Maria; Gill, Stanley; Xu, Han; Ali, Levi D; Jiang, Guozhi; Pantel, Sasha; Lee, Yenarae; Goodale, Amy; Cherniack, Andrew D; Oh, Coyin; Kryukov, Gregory; Cowley, Glenn S; Garraway, Levi A; Stegmaier, Kimberly; Roberts, Charles W; Golub, Todd R; Meyerson, Matthew; Root, David E; Tsherniak, Aviad; Hahn, William C

2016-08-01

The CRISPR/Cas9 system enables genome editing and somatic cell genetic screens in mammalian cells. We performed genome-scale loss-of-function screens in 33 cancer cell lines to identify genes essential for proliferation/survival and found a strong correlation between increased gene copy number and decreased cell viability after genome editing. Within regions of copy-number gain, CRISPR/Cas9 targeting of both expressed and unexpressed genes, as well as intergenic loci, led to significantly decreased cell proliferation through induction of a G2 cell-cycle arrest. By examining single-guide RNAs that map to multiple genomic sites, we found that this cell response to CRISPR/Cas9 editing correlated strongly with the number of target loci. These observations indicate that genome targeting by CRISPR/Cas9 elicits a gene-independent antiproliferative cell response. This effect has important practical implications for the interpretation of CRISPR/Cas9 screening data and confounds the use of this technology for the identification of essential genes in amplified regions. We found that the number of CRISPR/Cas9-induced DNA breaks dictates a gene-independent antiproliferative response in cells. These observations have practical implications for using CRISPR/Cas9 to interrogate cancer gene function and illustrate that cancer cells are highly sensitive to site-specific DNA damage, which may provide a path to novel therapeutic strategies. Cancer Discov; 6(8); 914-29. ©2016 AACR.See related commentary by Sheel and Xue, p. 824See related article by Munoz et al., p. 900This article is highlighted in the In This Issue feature, p. 803. 2016 American Association for Cancer Research.

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.

Constraints on the Dark Matter Particle Mass from the Number of Milky Way Satellites

DTIC Science & Technology

2010-04-12

but our lower mass limits do not necessarily apply to mixed dark matter cosmologies . Higgs decay produced sterile neutrinos can, however, constitute...simulations of the growth of Milky Way-sized halos in cold and warm dark matter cosmologies . The number of dark matter satellites in our simulated Milky...tions of WDM cosmologies due to numerical artifacts produced by discrete sampling of the gravitational poten- tial with a finite number of particles

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.

Mother and offspring fitness in an insect with maternal care: phenotypic trade-offs between egg number, egg mass and egg care

PubMed Central

2014-01-01

Background Oviparous females have three main options to increase their reproductive success: investing into egg number, egg mass and/or egg care. Although allocating resources to either of these three components is known to shape offspring number and size, potential trade-offs among them may have key impacts on maternal and offspring fitness. Here, we tested the occurrence of phenotypic trade-offs between egg number, egg mass and maternal expenditure on egg care in the European earwig, Forficula auricularia, an insect with pre- and post-hatching forms of maternal care. In particular, we used a series of laboratory observations and experiments to investigate whether these three components non-additively influenced offspring weight and number at hatching, and whether they were associated with potential costs to females in terms of future reproduction. Results We found negative associations between egg number and mass as well as between egg number and maternal expenditure on egg care. However, these trade-offs could only be detected after statistically correcting for female weight at egg laying. Hatchling number was not determined by single or additive effects among the three life-history traits, but instead by pairwise interactions among them. In particular, offspring number was positively associated with the number of eggs only in clutches receiving high maternal care or consisting of heavy eggs, and negatively associated with mean egg mass in clutches receiving low care. In contrast, offspring weight was positively associated with egg mass only. Finally, maternal expenditure on egg care reduced their future reproduction, but this effect was only detected when mothers were experimentally isolated from their offspring at egg hatching. Conclusions Overall, our study reveals simultaneous trade-offs between the number, mass and care of eggs. It also demonstrates that these factors interact in their impact on offspring production, and that maternal expenditure on egg

Liquid chromatography-mass spectrometry in metabolomics research: mass analyzers in ultra high pressure liquid chromatography coupling.

PubMed

Forcisi, Sara; Moritz, Franco; Kanawati, Basem; Tziotis, Dimitrios; Lehmann, Rainer; Schmitt-Kopplin, Philippe

2013-05-31

The present review gives an introduction into the concept of metabolomics and provides an overview of the analytical tools applied in non-targeted metabolomics with a focus on liquid chromatography (LC). LC is a powerful analytical tool in the study of complex sample matrices. A further development and configuration employing Ultra-High Pressure Liquid Chromatography (UHPLC) is optimized to provide the largest known liquid chromatographic resolution and peak capacity. Reasonably UHPLC plays an important role in separation and consequent metabolite identification of complex molecular mixtures such as bio-fluids. The most sensitive detectors for these purposes are mass spectrometers. Almost any mass analyzer can be optimized to identify and quantify small pre-defined sets of targets; however, the number of analytes in metabolomics is far greater. Optimized protocols for quantification of large sets of targets may be rendered inapplicable. Results on small target set analyses on different sample matrices are easily comparable with each other. In non-targeted metabolomics there is almost no analytical method which is applicable to all different matrices due to limitations pertaining to mass analyzers and chromatographic tools. The specifications of the most important interfaces and mass analyzers are discussed. We additionally provide an exemplary application in order to demonstrate the level of complexity which remains intractable up to date. The potential of coupling a high field Fourier Transform Ion Cyclotron Resonance Mass Spectrometer (ICR-FT/MS), the mass analyzer with the largest known mass resolving power, to UHPLC is given with an example of one human pre-treated plasma sample. This experimental example illustrates one way of overcoming the necessity of faster scanning rates in the coupling with UHPLC. The experiment enabled the extraction of thousands of features (analytical signals). A small subset of this compositional space could be mapped into a mass

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.

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.

Source apportionment of PM2.5 chemically speciated mass and particle number concentrations in New York City

NASA Astrophysics Data System (ADS)

Masiol, M.; Hopke, P. K.; Felton, H. D.; Frank, B. P.; Rattigan, O. V.; Wurth, M. J.; LaDuke, G. H.

2017-01-01

The major sources of fine particulate matter (PM2.5) in New York City (NYC) were apportioned by applying positive matrix factorization (PMF) to two different sets of particle characteristics: mass concentrations using chemical speciation data and particle number concentrations (PNC) using number size distribution, continuously monitored gases, and PM2.5 data. Post-processing was applied to the PMF results to: (i) match with meteorological data, (ii) use wind data to detect the likely locations of the local sources, and (iii) use concentration weighted trajectory models to assess the strength of potential regional/transboundary sources. Nine sources of PM2.5 mass were apportioned and identified as: secondary ammonium sulfate, secondary ammonium nitrate, road traffic exhaust, crustal dust, fresh sea-salt, aged sea-salt, biomass burning, residual oil/domestic heating and zinc. The sources of PNC were investigated using hourly average number concentrations in six size bins, gaseous air pollutants, mass concentrations of PM2.5, particulate sulfate, OC, and EC. These data were divided into 3 periods indicative of different seasonal conditions. Five sources were resolved for each period: secondary particles, road traffic, NYC background pollution (traffic and oil heating largely in Manhattan), nucleation and O3-rich aerosol. Although traffic does not account for large amounts of PM2.5 mass, it was the main source of particles advected from heavily trafficked zones. The use of residual oil had limited impacts on PM2.5 mass but dominates PNC in cold periods.

A Novel c-VEP BCI Paradigm for Increasing the Number of Stimulus Targets Based on Grouping Modulation With Different Codes.

PubMed

Wei, Qingguo; Liu, Yonghui; Gao, Xiaorong; Wang, Yijun; Yang, Chen; Lu, Zongwu; Gong, Huayuan

2018-06-01

In an existing brain-computer interface (BCI) based on code modulated visual evoked potentials (c-VEP), a method with which to increase the number of targets without increasing code length has not yet been established. In this paper, a novel c-VEP BCI paradigm, namely, grouping modulation with different codes that have good autocorrelation and crosscorrelation properties, is presented to increase the number of targets and information transfer rate (ITR). All stimulus targets are divided into several groups and each group of targets are modulated by a distinct pseudorandom binary code and its circularly shifting codes. Canonical correlation analysis is applied to each group for yielding a spatial filter and templates for all targets in a group are constructed based on spatially filtered signals. Template matching is applied to each group and the attended target is recognized by finding the maximal correlation coefficients of all groups. Based on the paradigm, a BCI with a total of 48 targets divided into three groups was implemented; 12 and 10 subjects participated in an off-line and a simulated online experiments, respectively. Data analysis of the offline experiment showed that the paradigm can massively increase the number of targets from 16 to 48 at the cost of slight compromise in accuracy (95.49% vs. 92.85%). Results of the simulated online experiment suggested that although the averaged accuracy across subjects of all three groups of targets was lower than that of a single group of targets (91.67% vs. 94.9%), the average ITR of the former was substantially higher than that of the later (181 bits/min vs. 135.6 bit/min) due to the large increase of the number of targets. The proposed paradigm significantly improves the performance of the c-VEP BCI, and thereby facilitates its practical applications such as high-speed spelling.

Investigation of Aerosol Surface Area Estimation from Number and Mass Concentration Measurements: Particle Density Effect.

PubMed

Ku, Bon Ki; Evans, Douglas E

2012-04-01

For nanoparticles with nonspherical morphologies, e.g., open agglomerates or fibrous particles, it is expected that the actual density of agglomerates may be significantly different from the bulk material density. It is further expected that using the material density may upset the relationship between surface area and mass when a method for estimating aerosol surface area from number and mass concentrations (referred to as "Maynard's estimation method") is used. Therefore, it is necessary to quantitatively investigate how much the Maynard's estimation method depends on particle morphology and density. In this study, aerosol surface area estimated from number and mass concentration measurements was evaluated and compared with values from two reference methods: a method proposed by Lall and Friedlander for agglomerates and a mobility based method for compact nonspherical particles using well-defined polydisperse aerosols with known particle densities. Polydisperse silver aerosol particles were generated by an aerosol generation facility. Generated aerosols had a range of morphologies, count median diameters (CMD) between 25 and 50 nm, and geometric standard deviations (GSD) between 1.5 and 1.8. The surface area estimates from number and mass concentration measurements correlated well with the two reference values when gravimetric mass was used. The aerosol surface area estimates from the Maynard's estimation method were comparable to the reference method for all particle morphologies within the surface area ratios of 3.31 and 0.19 for assumed GSDs 1.5 and 1.8, respectively, when the bulk material density of silver was used. The difference between the Maynard's estimation method and surface area measured by the reference method for fractal-like agglomerates decreased from 79% to 23% when the measured effective particle density was used, while the difference for nearly spherical particles decreased from 30% to 24%. The results indicate that the use of particle density

Influence of mileage accumulation on the particle mass and number emissions of two gasoline direct injection vehicles.

PubMed

Maricq, M Matti; Szente, Joseph J; Adams, Jack; Tennison, Paul; Rumpsa, Todd

2013-10-15

Gasoline direct injection (GDI) is a new engine technology intended to improve fuel economy and greenhouse gas emissions as required by recently enacted legislative and environmental regulations. The development of this technology must also ensure that these vehicles meet new LEV III and Tier 3 emissions standards as they phase in between 2017 and 2021. The aim of the present paper is to examine, at least for a small set, how the PM emissions from GDI vehicles change over their lifetime. The paper reports particle mass and number emissions of two GDI vehicles as a function of mileage up to 150K miles. These vehicles exhibit PM emissions that are near or below the upcoming 3 mg/mi FTP and 10 mg/mi US06 mass standards with little, if any, deterioration over 150K miles. Particle number emissions roughly follow the previously observed 2 × 10(12) particles/mg correlation between solid particle number and PM mass. They remained between the interim and final EU stage 6 solid particle count standard for gasoline vehicles throughout the mileage accumulation study. These examples demonstrate feasibility to meet near-term 3 mg/mi and interim EU solid particle number standards, but continued development is needed to ensure that this continues as further fuel economy improvements are made.

[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.

Gas Turbine Engine Nonvolatile Particulate Matter Mass Emissions: Correlation with Smoke Number for Conventional and Alternative Fuel Blends.

PubMed

Christie, Simon; Lobo, Prem; Lee, David; Raper, David

2017-01-17

This study evaluates the relationship between the emissions parameters of smoke number (SN) and mass concentration of nonvolatile particulate matter (nvPM) in the exhaust of a gas turbine engine for a conventional Jet A-1 and a number of alternative fuel blends. The data demonstrate the significant impact of fuel composition on the emissions and highlight the magnitude of the fuel-induced uncertainty for both SN within the Emissions Data Bank as well as nvPM mass within the new regulatory standard under development. Notwithstanding these substantial differences, the data show that correlation between SN and nvPM mass concentration still adheres to the first order approximation (FOA3), and this agreement is maintained over a wide range of fuel compositions. Hence, the data support the supposition that the FOA3 is applicable to engines burning both conventional and alternative fuel blends without adaptation or modification. The chemical composition of the fuel is shown to impact mass and number concentration as well as geometric mean diameter of the emitted nvPM; however, the data do not support assertions that the emissions of black carbon with small mean diameter will result in significant deviations from FOA3.

A comparative investigation of ultrafine particle number and mass emissions from a fleet of on-road diesel and CNG buses.

PubMed

Jayaratne, E R; He, C; Ristovski, Z D; Morawska, L; Johnson, G R

2008-09-01

Particle number, particle mass, and CO2 concentrations were measured on the curb of a busy urban busway used entirely by a mix of diesel and CNG operated buses. With the passage of each bus, the ratio of particle number concentration and particle mass concentration to CO2 concentration in the diluted exhaust plume were used as measures of the particle number and mass emission factors, respectively. With all buses accelerating pastthe monitoring point, the results showed that the median particle mass emission from CNG buses was less than 9% of that from diesel buses. However, the median particle number emission from CNG buses was 6 times higher than the diesel buses, and the particles from the CNG buses were mainly in the nanoparticle size range. Using a thermodenuder to remove the volatile material from the sampled emissions showed that the majority of particles from the CNG buses, but not from the diesel buses, were volatile. Approximately, 82% of the particles from the CNG buses and 38% from the diesel buses were removed by heating the emissions to 300 degrees C.

Comparison of two estimation methods for surface area concentration using number concentration and mass concentration of combustion-related ultrafine particles

NASA Astrophysics Data System (ADS)

Park, Ji Young; Raynor, Peter C.; Maynard, Andrew D.; Eberly, Lynn E.; Ramachandran, Gurumurthy

Recent research has suggested that the adverse health effects caused by nanoparticles are associated with their surface area (SA) concentrations. In this study, SA was estimated in two ways using number and mass concentrations and compared with SA (SA meas) measured using a diffusion charger (DC). Aerosol measurements were made twice: once starting in October 2002 and again starting in December 2002 in Mysore, India in residences that used kerosene or liquefied petroleum gas (LPG) for cooking. Mass, number, and SA concentrations and size distributions by number were measured in each residence. The first estimation method (SA PSD) used the size distribution by number to estimate SA. The second method (SA INV) used a simple inversion scheme that incorporated number and mass concentrations while assuming a lognormal size distribution with a known geometrical standard deviation. SA PSD was, on average, 2.4 times greater (range = 1.6-3.4) than SA meas while SA INV was, on average, 6.0 times greater (range = 4.6-7.7) than SA meas. The logarithms of SA PSD and SA INV were found to be statistically significant predictors of the logarithm of SA meas. The study showed that particle number and mass concentration measurements can be used to estimate SA with a correction factor that ranges between 2 and 6.

Investigation of Aerosol Surface Area Estimation from Number and Mass Concentration Measurements: Particle Density Effect

PubMed Central

Ku, Bon Ki; Evans, Douglas E.

2015-01-01

For nanoparticles with nonspherical morphologies, e.g., open agglomerates or fibrous particles, it is expected that the actual density of agglomerates may be significantly different from the bulk material density. It is further expected that using the material density may upset the relationship between surface area and mass when a method for estimating aerosol surface area from number and mass concentrations (referred to as “Maynard’s estimation method”) is used. Therefore, it is necessary to quantitatively investigate how much the Maynard’s estimation method depends on particle morphology and density. In this study, aerosol surface area estimated from number and mass concentration measurements was evaluated and compared with values from two reference methods: a method proposed by Lall and Friedlander for agglomerates and a mobility based method for compact nonspherical particles using well-defined polydisperse aerosols with known particle densities. Polydisperse silver aerosol particles were generated by an aerosol generation facility. Generated aerosols had a range of morphologies, count median diameters (CMD) between 25 and 50 nm, and geometric standard deviations (GSD) between 1.5 and 1.8. The surface area estimates from number and mass concentration measurements correlated well with the two reference values when gravimetric mass was used. The aerosol surface area estimates from the Maynard’s estimation method were comparable to the reference method for all particle morphologies within the surface area ratios of 3.31 and 0.19 for assumed GSDs 1.5 and 1.8, respectively, when the bulk material density of silver was used. The difference between the Maynard’s estimation method and surface area measured by the reference method for fractal-like agglomerates decreased from 79% to 23% when the measured effective particle density was used, while the difference for nearly spherical particles decreased from 30% to 24%. The results indicate that the use of

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.

Effect of Schmidt number on mass transfer across a sheared gas-liquid interface in a wind-driven turbulence.

PubMed

Takagaki, Naohisa; Kurose, Ryoichi; Kimura, Atsushi; Komori, Satoru

2016-11-14

The mass transfer across a sheared gas-liquid interface strongly depends on the Schmidt number. Here we investigate the relationship between mass transfer coefficient on the liquid side, k L , and Schmidt number, Sc, in the wide range of 0.7 ≤ Sc ≤ 1000. We apply a three-dimensional semi direct numerical simulation (SEMI-DNS), in which the mass transfer is solved based on an approximated deconvolution model (ADM) scheme, to wind-driven turbulence with mass transfer across a sheared wind-driven wavy gas-liquid interface. In order to capture the deforming gas-liquid interface, an arbitrary Lagrangian-Eulerian (ALE) method is employed. Our results show that similar to the case for flat gas-liquid interfaces, k L for the wind-driven wavy gas-liquid interface is generally proportional to Sc -0.5 , and can be roughly estimated by the surface divergence model. This trend is endorsed by the fact that the mass transfer across the gas-liquid interface is controlled mainly by streamwise vortices on the liquid side even for the wind-driven turbulence under the conditions of low wind velocities without wave breaking.

Effect of Schmidt number on mass transfer across a sheared gas-liquid interface in a wind-driven turbulence

PubMed Central

Takagaki, Naohisa; Kurose, Ryoichi; Kimura, Atsushi; Komori, Satoru

2016-01-01

The mass transfer across a sheared gas-liquid interface strongly depends on the Schmidt number. Here we investigate the relationship between mass transfer coefficient on the liquid side, kL, and Schmidt number, Sc, in the wide range of 0.7 ≤ Sc ≤ 1000. We apply a three-dimensional semi direct numerical simulation (SEMI-DNS), in which the mass transfer is solved based on an approximated deconvolution model (ADM) scheme, to wind-driven turbulence with mass transfer across a sheared wind-driven wavy gas-liquid interface. In order to capture the deforming gas-liquid interface, an arbitrary Lagrangian-Eulerian (ALE) method is employed. Our results show that similar to the case for flat gas-liquid interfaces, kL for the wind-driven wavy gas-liquid interface is generally proportional to Sc−0.5, and can be roughly estimated by the surface divergence model. This trend is endorsed by the fact that the mass transfer across the gas-liquid interface is controlled mainly by streamwise vortices on the liquid side even for the wind-driven turbulence under the conditions of low wind velocities without wave breaking. PMID:27841325

Smokers respond to anti-tobacco mass media campaigns in NSW by calling the Quitline.

PubMed

Cotter, Trish; Perez, Donna A; Dessaix, Anita L; Bishop, James F

2008-01-01

One aim of the anti-tobacco mass media campaigns in NSW is to increase the numbers of smokers calling the Quitline to seek assistance to quit. Investigation of the relationship between the weight of television advertising (Target Audience Rating Points: TARPs) and number of calls to the Quitline. There is a high correlation between weekly Quitline calls and TARPs. Anti-tobacco mass media campaign advertising that promotes the Quitline number encourages smokers to seek assistance to quit.

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...

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.

Accurate inclusion mass screening: a bridge from unbiased discovery to targeted assay development for biomarker verification.

PubMed

Jaffe, Jacob D; Keshishian, Hasmik; Chang, Betty; Addona, Theresa A; Gillette, Michael A; Carr, Steven A

2008-10-01

Verification of candidate biomarker proteins in blood is typically done using multiple reaction monitoring (MRM) of peptides by LC-MS/MS on triple quadrupole MS systems. MRM assay development for each protein requires significant time and cost, much of which is likely to be of little value if the candidate biomarker is below the detection limit in blood or a false positive in the original discovery data. Here we present a new technology, accurate inclusion mass screening (AIMS), designed to provide a bridge from unbiased discovery to MS-based targeted assay development. Masses on the software inclusion list are monitored in each scan on the Orbitrap MS system, and MS/MS spectra for sequence confirmation are acquired only when a peptide from the list is detected with both the correct accurate mass and charge state. The AIMS experiment confirms that a given peptide (and thus the protein from which it is derived) is present in the plasma. Throughput of the method is sufficient to qualify up to a hundred proteins/week. The sensitivity of AIMS is similar to MRM on a triple quadrupole MS system using optimized sample preparation methods (low tens of ng/ml in plasma), and MS/MS data from the AIMS experiments on the Orbitrap can be directly used to configure MRM assays. The method was shown to be at least 4-fold more efficient at detecting peptides of interest than undirected LC-MS/MS experiments using the same instrumentation, and relative quantitation information can be obtained by AIMS in case versus control experiments. Detection by AIMS ensures that a quantitative MRM-based assay can be configured for that protein. The method has the potential to qualify large number of biomarker candidates based on their detection in plasma prior to committing to the time- and resource-intensive steps of establishing a quantitative assay.

Particulate Matter Mass and Number Concentrations Inside a Naturally Ventilated School Building Located Adjacent to an Urban Roadway

NASA Astrophysics Data System (ADS)

Chithra, V. S.; Shiva Nagendra, S. M.

2014-09-01

This work presents the temporal characteristics of Particulate Matter (PM) mass and number concentrations measured inside a naturally ventilated school building, located close to a busy roadway in Chennai city. Two environmental dust monitor instruments (GRIMM Model 107 and Model 108) were used for measuring PM mass and number concentrations. The 1-h mean values of PM10, PM2.5 and PM1 mass concentrations were found to be 262 ± 161, 68 ± 24, 40 ± 15 µg/m3 and 81 ± 26, 56 ± 2, 45 ± 19 µg/m3 during working hours (8am-4pm) and non-working hours (4pm-8am)/holidays, respectively. The PM number concentrations inside the room during working hours were found to be 2.4 × 105, 2.2 × 103 and 8.1 × 102 particles/l in the size range of 0.3-1, 1-3 and 3-10 µm, respectively. The present study reveals that during working hours, indoor PM concentrations of the classroom were influenced by the activities of occupants and during non working hours it was affected by outdoor vehicular emissions.

Effective Atomic Number, Mass Attenuation Coefficient Parameterization, and Implications for High-Energy X-Ray Cargo Inspection Systems

NASA Astrophysics Data System (ADS)

Langeveld, Willem G. J.

The most widely used technology for the non-intrusive active inspection of cargo containers and trucks is x-ray radiography at high energies (4-9 MeV). Technologies such as dual-energy imaging, spectroscopy, and statistical waveform analysis can be used to estimate the effective atomic number (Zeff) of the cargo from the x-ray transmission data, because the mass attenuation coefficient depends on energy as well as atomic number Z. The estimated effective atomic number, Zeff, of the cargo then leads to improved detection capability of contraband and threats, including special nuclear materials (SNM) and shielding. In this context, the exact meaning of effective atomic number (for mixtures and compounds) is generally not well-defined. Physics-based parameterizations of the mass attenuation coefficient have been given in the past, but usually for a limited low-energy range. Definitions of Zeff have been based, in part, on such parameterizations. Here, we give an improved parameterization at low energies (20-1000 keV) which leads to a well-defined Zeff. We then extend this parameterization up to energies relevant for cargo inspection (10 MeV), and examine what happens to the Zeff definition at these higher energies.

Measurements of production cross sections of 10Be and 26Al by 120 GeV and 392 MeV proton bombardment of 89Y, 159Tb, and natCu targets

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

Sekimoto, S.; Okumura, S.; Yashima, H.

2015-08-12

The production cross sections of 10Be and 26Al were measured by accelerator mass spectrometry using 89Y, 159Tb, and natCu targets bombarded by protons with energies E p of 120 GeV and 392 MeV. The production cross sections obtained for 10Be and 26Al were compared with those previously reported using E p = 50 MeV–24 GeV and various targets. It was found that the production cross sections of 10Be monotonically increased with increasing target mass number when the proton energy was greater than a few GeV. On the other hand, it was also found that the production cross sections of 10Bemore » decreased as the target mass number increased from that of carbon to those near the mass numbers of nickel and zinc when the proton energy was below approximately 1 GeV. They also increased as the target mass number increased from near those of nickel and zinc to that of bismuth, in the same proton energy range. Similar results were observed in the production cross sections of 26Al, though the absolute values were quite different between 10Be and 26Al. As a result, the difference between these production cross sections may depend on the impact parameter (nuclear radius) and/or the target nucleus stiffness.« less

Small genomes and large seeds: chromosome numbers, genome size and seed mass in diploid Aesculus species (Sapindaceae).

PubMed

Krahulcová, Anna; Trávnícek, Pavel; Krahulec, František; Rejmánek, Marcel

2017-04-01

Aesculus L. (horse chestnut, buckeye) is a genus of 12-19 extant woody species native to the temperate Northern Hemisphere. This genus is known for unusually large seeds among angiosperms. While chromosome counts are available for many Aesculus species, only one has had its genome size measured. The aim of this study is to provide more genome size data and analyse the relationship between genome size and seed mass in this genus. Chromosome numbers in root tip cuttings were confirmed for four species and reported for the first time for three additional species. Flow cytometric measurements of 2C nuclear DNA values were conducted on eight species, and mean seed mass values were estimated for the same taxa. The same chromosome number, 2 n = 40, was determined in all investigated taxa. Original measurements of 2C values for seven Aesculus species (eight taxa), added to just one reliable datum for A. hippocastanum , confirmed the notion that the genome size in this genus with relatively large seeds is surprisingly low, ranging from 0·955 pg 2C -1 in A. parviflora to 1·275 pg 2C -1 in A. glabra var. glabra. The chromosome number of 2 n = 40 seems to be conclusively the universal 2 n number for non-hybrid species in this genus. Aesculus genome sizes are relatively small, not only within its own family, Sapindaceae, but also within woody angiosperms. The genome sizes seem to be distinct and non-overlapping among the four major Aesculus clades. These results provide an extra support for the most recent reconstruction of Aesculus phylogeny. The correlation between the 2C values and seed masses in examined Aesculus species is slightly negative and not significant. However, when the four major clades are treated separately, there is consistent positive association between larger genome size and larger seed mass within individual lineages. © The Author 2017. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For

Small genomes and large seeds: chromosome numbers, genome size and seed mass in diploid Aesculus species (Sapindaceae)

PubMed Central

Krahulcová, Anna; Trávníček, Pavel; Rejmánek, Marcel

2017-01-01

Background and Aims Aesculus L. (horse chestnut, buckeye) is a genus of 12–19 extant woody species native to the temperate Northern Hemisphere. This genus is known for unusually large seeds among angiosperms. While chromosome counts are available for many Aesculus species, only one has had its genome size measured. The aim of this study is to provide more genome size data and analyse the relationship between genome size and seed mass in this genus. Methods Chromosome numbers in root tip cuttings were confirmed for four species and reported for the first time for three additional species. Flow cytometric measurements of 2C nuclear DNA values were conducted on eight species, and mean seed mass values were estimated for the same taxa. Key Results The same chromosome number, 2n = 40, was determined in all investigated taxa. Original measurements of 2C values for seven Aesculus species (eight taxa), added to just one reliable datum for A. hippocastanum, confirmed the notion that the genome size in this genus with relatively large seeds is surprisingly low, ranging from 0·955 pg 2C–1 in A. parviflora to 1·275 pg 2C–1 in A. glabra var. glabra. Conclusions The chromosome number of 2n = 40 seems to be conclusively the universal 2n number for non-hybrid species in this genus. Aesculus genome sizes are relatively small, not only within its own family, Sapindaceae, but also within woody angiosperms. The genome sizes seem to be distinct and non-overlapping among the four major Aesculus clades. These results provide an extra support for the most recent reconstruction of Aesculus phylogeny. The correlation between the 2C values and seed masses in examined Aesculus species is slightly negative and not significant. However, when the four major clades are treated separately, there is consistent positive association between larger genome size and larger seed mass within individual lineages. PMID:28065925

Cosmological Constraints from Galaxy Clustering and the Mass-to-number Ratio of Galaxy Clusters

NASA Astrophysics Data System (ADS)

Tinker, Jeremy L.; Sheldon, Erin S.; Wechsler, Risa H.; Becker, Matthew R.; Rozo, Eduardo; Zu, Ying; Weinberg, David H.; Zehavi, Idit; Blanton, Michael R.; Busha, Michael T.; Koester, Benjamin P.

2012-01-01

We place constraints on the average density (Ω m ) and clustering amplitude (σ8) of matter using a combination of two measurements from the Sloan Digital Sky Survey: the galaxy two-point correlation function, wp (rp ), and the mass-to-galaxy-number ratio within galaxy clusters, M/N, analogous to cluster M/L ratios. Our wp (rp ) measurements are obtained from DR7 while the sample of clusters is the maxBCG sample, with cluster masses derived from weak gravitational lensing. We construct nonlinear galaxy bias models using the Halo Occupation Distribution (HOD) to fit both wp (rp ) and M/N for different cosmological parameters. HOD models that match the same two-point clustering predict different numbers of galaxies in massive halos when Ω m or σ8 is varied, thereby breaking the degeneracy between cosmology and bias. We demonstrate that this technique yields constraints that are consistent and competitive with current results from cluster abundance studies, without the use of abundance information. Using wp (rp ) and M/N alone, we find Ω0.5 m σ8 = 0.465 ± 0.026, with individual constraints of Ω m = 0.29 ± 0.03 and σ8 = 0.85 ± 0.06. Combined with current cosmic microwave background data, these constraints are Ω m = 0.290 ± 0.016 and σ8 = 0.826 ± 0.020. All errors are 1σ. The systematic uncertainties that the M/N technique are most sensitive to are the amplitude of the bias function of dark matter halos and the possibility of redshift evolution between the SDSS Main sample and the maxBCG cluster sample. Our derived constraints are insensitive to the current level of uncertainties in the halo mass function and in the mass-richness relation of clusters and its scatter, making the M/N technique complementary to cluster abundances as a method for constraining cosmology with future galaxy surveys.

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

Bone Mass Measurement: What the Numbers Mean

MedlinePlus

... or more osteoporotic fractures. Low Bone Mass Versus Osteoporosis The information provided by a BMD test can ... 15-7877-E Last Reviewed 2015-06 NIH Osteoporosis and Related Bone Diseases ~ National Resource Center 2 ...

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

Regular expansion solutions for small Peclet number heat or mass transfer in concentrated two-phase particulate systems

NASA Technical Reports Server (NTRS)

Yaron, I.

1974-01-01

Steady state heat or mass transfer in concentrated ensembles of drops, bubbles or solid spheres in uniform, slow viscous motion, is investigated. Convective effects at small Peclet numbers are taken into account by expanding the nondimensional temperature or concentration in powers of the Peclet number. Uniformly valid solutions are obtained, which reflect the effects of dispersed phase content and rate of internal circulation within the fluid particles. The dependence of the range of Peclet and Reynolds numbers, for which regular expansions are valid, on particle concentration is discussed.

The effects of variations in the number and sequence of targeting signals on nuclear uptake

PubMed Central

1988-01-01

To determine if the number of targeting signals affects the transport of proteins into the nucleus, Xenopus oocytes were injected with colloidal gold particles, ranging in diameter from 20 to 280 A, that were coated with BSA cross-linked with synthetic peptides containing the SV-40 large T-antigen nuclear transport signal. Three BSA conjugate preparations were used; they had an average of 5, 8, and 11 signals per molecule of carrier protein. In addition, large T-antigen, which contains one signal per monomer, was used as a coating agent. The cells were fixed at various times after injection and subsequently analyzed by electron microscopy. Gold particles coated with proteins containing the SV-40 signal entered the nucleus through central channels located within the nuclear pores. Analysis of the intracellular distribution and size of the tracers that entered the nucleus indicated that the number of signals per molecule affect both the relative uptake of particles and the functional size of the channels available for translocation. In control experiments, gold particles coated with BSA or BSA conjugated with inactive peptides similar to the SV-40 transport signal were virtually excluded from the nucleus. Gold particles coated with nucleoplasmin, an endogenous karyophilic protein that contains five targeting signals per molecule, was transported through the nuclear pores more effectively than any of the BSA-peptide conjugates. Based on a correlation between the peri-envelope density of gold particles and their relative uptake, it is suggested that the differences in the activity of the two targeting signals is related to their binding affinity for envelope receptors. It was also determined, by performing coinjection experiments, that individual pores are capable of recognizing and transporting proteins that contain different nuclear targeting signals. PMID:3170630

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.

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.

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

Target genes discovery through copy number alteration analysis in human hepatocellular carcinoma.

PubMed

Gu, De-Leung; Chen, Yen-Hsieh; Shih, Jou-Ho; Lin, Chi-Hung; Jou, Yuh-Shan; Chen, Chian-Feng

2013-12-21

High-throughput short-read sequencing of exomes and whole cancer genomes in multiple human hepatocellular carcinoma (HCC) cohorts confirmed previously identified frequently mutated somatic genes, such as TP53, CTNNB1 and AXIN1, and identified several novel genes with moderate mutation frequencies, including ARID1A, ARID2, MLL, MLL2, MLL3, MLL4, IRF2, ATM, CDKN2A, FGF19, PIK3CA, RPS6KA3, JAK1, KEAP1, NFE2L2, C16orf62, LEPR, RAC2, and IL6ST. Functional classification of these mutated genes suggested that alterations in pathways participating in chromatin remodeling, Wnt/β-catenin signaling, JAK/STAT signaling, and oxidative stress play critical roles in HCC tumorigenesis. Nevertheless, because there are few druggable genes used in HCC therapy, the identification of new therapeutic targets through integrated genomic approaches remains an important task. Because a large amount of HCC genomic data genotyped by high density single nucleotide polymorphism arrays is deposited in the public domain, copy number alteration (CNA) analyses of these arrays is a cost-effective way to reveal target genes through profiling of recurrent and overlapping amplicons, homozygous deletions and potentially unbalanced chromosomal translocations accumulated during HCC progression. Moreover, integration of CNAs with other high-throughput genomic data, such as aberrantly coding transcriptomes and non-coding gene expression in human HCC tissues and rodent HCC models, provides lines of evidence that can be used to facilitate the identification of novel HCC target genes with the potential of improving the survival of HCC patients.

Accurate clinical detection of exon copy number variants in a targeted NGS panel using DECoN.

PubMed

Fowler, Anna; Mahamdallie, Shazia; Ruark, Elise; Seal, Sheila; Ramsay, Emma; Clarke, Matthew; Uddin, Imran; Wylie, Harriet; Strydom, Ann; Lunter, Gerton; Rahman, Nazneen

2016-11-25

Background: Targeted next generation sequencing (NGS) panels are increasingly being used in clinical genomics to increase capacity, throughput and affordability of gene testing. Identifying whole exon deletions or duplications (termed exon copy number variants, 'exon CNVs') in exon-targeted NGS panels has proved challenging, particularly for single exon CNVs.  Methods: We developed a tool for the Detection of Exon Copy Number variants (DECoN), which is optimised for analysis of exon-targeted NGS panels in the clinical setting. We evaluated DECoN performance using 96 samples with independently validated exon CNV data. We performed simulations to evaluate DECoN detection performance of single exon CNVs and to evaluate performance using different coverage levels and sample numbers. Finally, we implemented DECoN in a clinical laboratory that tests BRCA1 and BRCA2 with the TruSight Cancer Panel (TSCP). We used DECoN to analyse 1,919 samples, validating exon CNV detections by multiplex ligation-dependent probe amplification (MLPA).  Results: In the evaluation set, DECoN achieved 100% sensitivity and 99% specificity for BRCA exon CNVs, including identification of 8 single exon CNVs. DECoN also identified 14/15 exon CNVs in 8 other genes. Simulations of all possible BRCA single exon CNVs gave a mean sensitivity of 98% for deletions and 95% for duplications. DECoN performance remained excellent with different levels of coverage and sample numbers; sensitivity and specificity was >98% with the typical NGS run parameters. In the clinical pipeline, DECoN automatically analyses pools of 48 samples at a time, taking 24 minutes per pool, on average. DECoN detected 24 BRCA exon CNVs, of which 23 were confirmed by MLPA, giving a false discovery rate of 4%. Specificity was 99.7%.  Conclusions: DECoN is a fast, accurate, exon CNV detection tool readily implementable in research and clinical NGS pipelines. It has high sensitivity and specificity and acceptable false discovery rate

Microfluidic bead-based diodes with targeted circular microchannels for low Reynolds number applications.

PubMed

Sochol, Ryan D; Lu, Albert; Lei, Jonathan; Iwai, Kosuke; Lee, Luke P; Lin, Liwei

2014-05-07

Self-regulating fluidic components are critical to the advancement of microfluidic processors for chemical and biological applications, such as sample preparation on chip, point-of-care molecular diagnostics, and implantable drug delivery devices. Although researchers have developed a wide range of components to enable flow rectification in fluidic systems, engineering microfluidic diodes that function at the low Reynolds number (Re) flows and smaller scales of emerging micro/nanofluidic platforms has remained a considerable challenge. Recently, researchers have demonstrated microfluidic diodes that utilize high numbers of suspended microbeads as dynamic resistive elements; however, using spherical particles to block fluid flow through rectangular microchannels is inherently limited. To overcome this issue, here we present a single-layer microfluidic bead-based diode (18 μm in height) that uses a targeted circular-shaped microchannel for the docking of a single microbead (15 μm in diameter) to rectify fluid flow under low Re conditions. Three-dimensional simulations and experimental results revealed that adjusting the docking channel geometry and size to better match the suspended microbead greatly increased the diodicity (Di) performance. Arraying multiple bead-based diodes in parallel was found to adversely affect system efficacy, while arraying multiple diodes in series was observed to enhance device performance. In particular, systems consisting of four microfluidic bead-based diodes with targeted circular-shaped docking channels in series revealed average Di's ranging from 2.72 ± 0.41 to 10.21 ± 1.53 corresponding to Re varying from 0.1 to 0.6.

Mass and number size distributions of emitted particulates at five important operation units in a hazardous industrial waste incineration plant.

PubMed

Lin, Chi-Chi; Huang, Hsiao-Lin; Hsiao, Wen-Yuan

2016-01-01

Past studies indicated particulates generated by waste incineration contain various hazardous compounds. The aerosol characteristics are very important for particulate hazard control and workers' protection. This study explores the detailed characteristics of emitted particulates from each important operation unit in a rotary kiln-based hazardous industrial waste incineration plant. A dust size analyzer (Grimm 1.109) and a scanning mobility particle sizer (SMPS) were used to measure the aerosol mass concentration, mass size distribution, and number size distribution at five operation units (S1-S5) during periods of normal operation, furnace shutdown, and annual maintenance. The place with the highest measured PM10 concentration was located at the area of fly ash discharge from air pollution control equipment (S5) during the period of normal operation. Fine particles (PM2.5) constituted the majority of the emitted particles from the incineration plant. The mass size distributions (elucidated) made it clear that the size of aerosols caused by the increased particulate mass, resulting from work activities, were mostly greater than 1.5 μm. Whereas the number size distributions showed that the major diameters of particulates that caused the increase of particulate number concentrations, from work activities, were distributed in the sub micrometer range. The process of discharging fly ash from air pollution control equipment can significantly increase the emission of nanoparticles. The mass concentrations and size distributions of emitted particulates were different at each operation unit. This information is valuable for managers to take appropriate strategy to reduce the particulate emission and associated worker exposure.

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.

800-MeV proton irradiation of thorium and depleted uranium targets

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

Russell, G.J.; Brun, T.O.; Pitcher, E.J.

As part of the Los Alamos Fertile-to-Fissile-Conversion (FERFICON) program in the late 1980`s, thick targets of the fertile materials thorium and depleted uranium were bombarded by 800-MeV protons to produce the fissile materials {sup 233}U and {sup 239}Pu, respectively. The amount of {sup 233}U made was determined by measuring the {sup 233}Pa activity, and the yield of {sup 239}Pu was deduced by measuring the activity of {sup 239}Np. For the thorium target, 4 spallation products and 34 fission products were also measured. For the depleted uranium target, 3 spallation products and 16 fission products were also measured. The number ofmore » fissions in each target was deduced from fission product mass-yield curves. In actuality, axial distributions of the products were measured, and the distributions were then integrated over the target volume to obtain the total number of products for each reaction.« less

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.

A study on the relationship between mass concentrations, chemistry and number size distribution of urban fine aerosols in Milan, Barcelona and London

NASA Astrophysics Data System (ADS)

Rodríguez, S.; van Dingenen, R.; Putaud, J.-P.; Dell'Acqua, A.; Pey, J.; Querol, X.; Alastuey, A.; Chenery, S.; Ho, K.-F.; Harrison, R.; Tardivo, R.; Scarnato, B.; Gemelli, V.

2007-05-01

A physicochemical characterization, including aerosol number size distribution, chemical composition and mass concentrations, of the urban fine aerosol captured in MILAN, BARCELONA and LONDON is presented in this article. The objective is to obtain a comprehensive picture of the microphysical processes involved in aerosol dynamics during the: 1) regular evolution of the urban aerosol (daily, weekly and seasonal basis) and in the day-to-day variations (from clean-air to pollution-events), and 2) the link between "aerosol chemistry and mass concentrations" with the "number size distribution". The mass concentrations of the fine PM2.5 aerosol exhibit a high correlation with the number concentration of >100 nm particles N>100 (nm) ("accumulation mode particles") which only account for <20% of the total number concentration N of fine aerosols; but do not correlate with the number of <100 nm particles ("ultrafine particles"), which accounts for >80% of fine particles number concentration. Organic matter and black-carbon are the only aerosol components showing a significant correlation with the ultrafine particles, attributed to vehicles exhausts emissions; whereas ammonium-nitrate, ammonium-sulphate and also organic matter and black-carbon correlate with N>100 (nm) and attributed to condensation mechanisms, other particle growth processes and some primary emissions. Time series of the aerosol DpN diameter (dN/dlogD mode), mass PM2.5 concentrations and number N>100 (nm) concentrations exhibit correlated day-to-day variations, which point to a significant involvement of condensation of semi-volatile compounds during urban pollution events. This agrees with the observation that ammonium-nitrate is the component exhibiting the highest increases from mid-to-high pollution episodes, when the highest DpN increases are observed. The results indicates that "fine PM2.5 particles urban pollution events" tend to occur when condensation processes have made particles grow large enough

Long-term observations of tropospheric particle number size distributions and equivalent black carbon mass concentrations in the German Ultrafine Aerosol Network (GUAN)

NASA Astrophysics Data System (ADS)

Birmili, Wolfram; Weinhold, Kay; Rasch, Fabian; Sonntag, André; Sun, Jia; Merkel, Maik; Wiedensohler, Alfred; Bastian, Susanne; Schladitz, Alexander; Löschau, Gunter; Cyrys, Josef; Pitz, Mike; Gu, Jianwei; Kusch, Thomas; Flentje, Harald; Quass, Ulrich; Kaminski, Heinz; Kuhlbusch, Thomas A. J.; Meinhardt, Frank; Schwerin, Andreas; Bath, Olaf; Ries, Ludwig; Gerwig, Holger; Wirtz, Klaus; Fiebig, Markus

2016-08-01

The German Ultrafine Aerosol Network (GUAN) is a cooperative atmospheric observation network, which aims at improving the scientific understanding of aerosol-related effects in the troposphere. The network addresses research questions dedicated to both climate- and health-related effects. GUAN's core activity has been the continuous collection of tropospheric particle number size distributions and black carbon mass concentrations at 17 observation sites in Germany. These sites cover various environmental settings including urban traffic, urban background, rural background, and Alpine mountains. In association with partner projects, GUAN has implemented a high degree of harmonisation of instrumentation, operating procedures, and data evaluation procedures. The quality of the measurement data is assured by laboratory intercomparisons as well as on-site comparisons with reference instruments. This paper describes the measurement sites, instrumentation, quality assurance, and data evaluation procedures in the network as well as the EBAS repository, where the data sets can be obtained (target="_blank">doi:10.5072/guan).

Experimental scaling law for mass ablation rate from a Sn plasma generated by a 1064 nm laser

NASA Astrophysics Data System (ADS)

Burdt, Russell A.; Yuspeh, Sam; Sequoia, Kevin L.; Tao, Yezheng; Tillack, Mark S.; Najmabadi, Farrokh

2009-08-01

The ablation depth in planar Sn targets irradiated with a pulsed 1064 nm laser was investigated over laser intensities from 3×1011 to 2×1012 W/cm2. The ablation depth was measured by irradiating a thin layer of Sn evaporated onto a Si wafer, and looking for signatures of Si ions in the expanding plasma with spectroscopic and particle diagnostics. It was found that ablation depth scales with laser intensity to the (5/9)th power, which is consistent with analytical models of steady-state laser ablation, as well as empirical formulae from previous studies of mass ablation rate in overlapping parameter space. In addition, the scaling of mass ablation rate with atomic number of the target as given by empirical formulae in previous studies using targets such as C and Al, are shown to remain valid for the higher atomic number of the target (Z =50) used in these experiments.

Unlocking the secrets to protein–protein interface drug targets using structural mass spectrometry techniques

PubMed Central

Dailing, Angela; Luchini, Alessandra; Liotta, Lance

2016-01-01

Protein–protein interactions (PPIs) drive all biologic systems at the subcellular and extracellular level. Changes in the specificity and affinity of these interactions can lead to cellular malfunctions and disease. Consequently, the binding interfaces between interacting protein partners are important drug targets for the next generation of therapies that block such interactions. Unfortunately, protein–protein contact points have proven to be very difficult pharmacological targets because they are hidden within complex 3D interfaces. For the vast majority of characterized binary PPIs, the specific amino acid sequence of their close contact regions remains unknown. There has been an important need for an experimental technology that can rapidly reveal the functionally important contact points of native protein complexes in solution. In this review, experimental techniques employing mass spectrometry to explore protein interaction binding sites are discussed. Hydrogen–deuterium exchange, hydroxyl radical footprinting, crosslinking and the newest technology protein painting, are compared and contrasted. PMID:26400464

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.

Aerodynamic Characteristics of a Revised Target Drone Vehicle at Mach Numbers from 1.60 to 2.86

NASA Technical Reports Server (NTRS)

Blair, A. B., Jr.; Babb, C. Donald

1968-01-01

An investigation has been conducted in the Langley Unitary Plan wind tunnel to determine the aerodynamic characteristics of a revised target drone vehicle through a Mach number range from 1.60 to 2.86. The vehicle had canard surfaces and a swept clipped-delta wing with twin tip-mounted vertical tails.

Occupational Exposure to Cobalt and Tungsten in the Swedish Hard Metal Industry: Air Concentrations of Particle Mass, Number, and Surface Area

PubMed Central

Bryngelsson, Ing-Liss; Pettersson, Carin; Husby, Bente; Arvidsson, Helena; Westberg, Håkan

2016-01-01

Exposure to cobalt in the hard metal industry entails severe adverse health effects, including lung cancer and hard metal fibrosis. The main aim of this study was to determine exposure air concentration levels of cobalt and tungsten for risk assessment and dose–response analysis in our medical investigations in a Swedish hard metal plant. We also present mass-based, particle surface area, and particle number air concentrations from stationary sampling and investigate the possibility of using these data as proxies for exposure measures in our study. Personal exposure full-shift measurements were performed for inhalable and total dust, cobalt, and tungsten, including personal real-time continuous monitoring of dust. Stationary measurements of inhalable and total dust, PM2.5, and PM10 was also performed and cobalt and tungsten levels were determined, as were air concentration of particle number and particle surface area of fine particles. The personal exposure levels of inhalable dust were consistently low (AM 0.15mg m−3, range <0.023–3.0mg m−3) and below the present Swedish occupational exposure limit (OEL) of 10mg m−3. The cobalt levels were low as well (AM 0.0030mg m−3, range 0.000028–0.056mg m−3) and only 6% of the samples exceeded the Swedish OEL of 0.02mg m−3. For continuous personal monitoring of dust exposure, the peaks ranged from 0.001 to 83mg m−3 by work task. Stationary measurements showed lower average levels both for inhalable and total dust and cobalt. The particle number concentration of fine particles (AM 3000 p·cm−3) showed the highest levels at the departments of powder production, pressing and storage, and for the particle surface area concentrations (AM 7.6 µm2·cm−3) similar results were found. Correlating cobalt mass-based exposure measurements to cobalt stationary mass-based, particle area, and particle number concentrations by rank and department showed significant correlations for all measures except for particle

20180318 - Structure identification by Mass Spectrometry Non-Targeted Analysis using the US EPA’s CompTox Chemistry Dashboard (ACS Spring)

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...

Characteristics of particle number and mass emissions during heavy-duty diesel truck parked active DPF regeneration in an ambient air dilution tunnel

NASA Astrophysics Data System (ADS)

Yoon, Seungju; Quiros, David C.; Dwyer, Harry A.; Collins, John F.; Burnitzki, Mark; Chernich, Donald; Herner, Jorn D.

2015-12-01

Diesel particle number and mass emissions were measured during parked active regeneration of diesel particulate filters (DPF) in two heavy-duty diesel trucks: one equipped with a DPF and one equipped with a DPF + SCR (selective catalytic reduction), and compliant with the 2007 and 2010 emission standards, respectively. The emission measurements were conducted using an ambient air dilution tunnel. During parked active regeneration, particulate matter (PM) mass emissions measured from a 2007 technology truck were significantly higher than the emissions from a 2010 technology truck. Particle number emissions from both trucks were dominated by nucleation mode particles having a diameter less than 50 nm; nucleation mode particles were orders of magnitude higher than accumulation mode particles having a diameter greater than 50 nm. Accumulation mode particles contributed 77.8 %-95.8 % of the 2007 truck PM mass, but only 7.3 %-28.2 % of the 2010 truck PM mass.

A novel quantitation approach for maximizing detectable targets for offensive/volatile odorants with diverse functional groups by thermal desorption-gas chromatography-mass spectrometry

NASA Astrophysics Data System (ADS)

Kim, Yong-Hyun; Kim, Ki-Hyun

2016-07-01

A multitude of analytical systems are needed to analyze diverse odorants with various functionalities. In this study, an experimental method was developed to assess the maximum covering range of odorants using a single experimental setup consisting of a thermal desorber-gas chromatography-mass spectrometry system. To this end, a total of 20 offensive odorants (aldehyde, ketone, ester, alcohol, aromatic, sulfide, amine, and carboxyl) were selected and tested by a single system. The analytical results of standards and environmental samples were evaluated in a number of respects. In the analysis of the standards, all targets were quantified via Carbopack (C + B + X) tube sampling while operating the thermal desorber at -25 °C. The method detection limits of 18 targets (exception of 2 out of the 20 targets: acetaldehyde and methanethiol) were excellent (mean 0.04 ± 0.03 ppb) in terms of their odor threshold values (74.7 ± 140 ~ 624 ± 1,729 ppb). The analysis of organic fertilizer plant samples at a pig farm (slurry treatment facility, compost facility, and ambient air) confirmed the presence of 18 odorants from 0.03 ppb (dimethyldisulfide, ambient sample) to 522 ppb (methyl ethyl ketone, slurry treatment facility). As such, our method allowed simultaneous quantitation of most key odorants with sufficient reliability and sensitivity.

Target analysis of primary aromatic amines combined with a comprehensive screening of migrating substances in kitchen utensils by liquid chromatography-high resolution mass spectrometry.

PubMed

Sanchis, Yovana; Coscollà, Clara; Roca, Marta; Yusà, Vicent

2015-06-01

An analytical strategy including both the quantitative target analysis of 8 regulated primary aromatic amines (PAAs), as well as a comprehensive post-run target screening of 77 migrating substances, was developed for nylon utensils, using liquid chromatography-orbitrap-high resolution mass spectrometry (LC-HRMS) operating in full scan mode. The accurate mass data were acquired with a resolving power of 50,000 FWHM (scan speed, 2 Hz), and by alternating two acquisition events, ESI+ with and without fragmentation. The target method was validated after statistical optimization of the main ionization and fragmentation parameters. The quantitative method presented appropriate performance to be used in official monitoring with recoveries ranging from 78% to 112%, precision in terms of Relative Standard Deviation (RSD) was less than 15%, and the limits of quantification were between 2 and 2.5 µg kg(-1). For post-target screening, a customized theoretical database was built for food contact material migrants, including bisphenols, phthalates, and other amines. For identification purposes, accurate exact mass (<5 ppm) and some diagnostic ions including fragments were used. The strategy was applied to 10 real samples collected from different retailers in the Valencian Region (Spain) during 2014. Six out of eight target PAAs were detected in at least one sample in the target analysis. The most frequently detected compounds were 4,4'-methylenedianiline and aniline, with concentrations ranging from 2.4 to 19,715 µg kg(-1) and 2.5 to 283 µg kg(-1), respectively. Two phthalates were identified and confirmed in the post-run target screening analysis. Copyright © 2015 Elsevier B.V. All rights reserved.

Bamgineer: Introduction of simulated allele-specific copy number variants into exome and targeted sequence data sets.

PubMed

Samadian, Soroush; Bruce, Jeff P; Pugh, Trevor J

2018-03-01

Somatic copy number variations (CNVs) play a crucial role in development of many human cancers. The broad availability of next-generation sequencing data has enabled the development of algorithms to computationally infer CNV profiles from a variety of data types including exome and targeted sequence data; currently the most prevalent types of cancer genomics data. However, systemic evaluation and comparison of these tools remains challenging due to a lack of ground truth reference sets. To address this need, we have developed Bamgineer, a tool written in Python to introduce user-defined haplotype-phased allele-specific copy number events into an existing Binary Alignment Mapping (BAM) file, with a focus on targeted and exome sequencing experiments. As input, this tool requires a read alignment file (BAM format), lists of non-overlapping genome coordinates for introduction of gains and losses (bed file), and an optional file defining known haplotypes (vcf format). To improve runtime performance, Bamgineer introduces the desired CNVs in parallel using queuing and parallel processing on a local machine or on a high-performance computing cluster. As proof-of-principle, we applied Bamgineer to a single high-coverage (mean: 220X) exome sequence file from a blood sample to simulate copy number profiles of 3 exemplar tumors from each of 10 tumor types at 5 tumor cellularity levels (20-100%, 150 BAM files in total). To demonstrate feasibility beyond exome data, we introduced read alignments to a targeted 5-gene cell-free DNA sequencing library to simulate EGFR amplifications at frequencies consistent with circulating tumor DNA (10, 1, 0.1 and 0.01%) while retaining the multimodal insert size distribution of the original data. We expect Bamgineer to be of use for development and systematic benchmarking of CNV calling algorithms by users using locally-generated data for a variety of applications. The source code is freely available at http://github.com/pughlab/bamgineer.

Self-management education en masse: effectiveness of the Back Pain: Don't Take It Lying Down mass media campaign.

PubMed

Buchbinder, Rachelle

2008-11-17

Despite the availability of a range of Australian self-management support programs targeting the individual patient and/or health professional, three-quarters of Australians have at least one long-term medical condition, suggesting that a more comprehensive public health approach is needed. Use of mass media to deliver community health messages is a well established public health strategy. It may enhance more targeted approaches with its ability to reach large numbers of people simultaneously, including those difficult to identify, high-risk groups and those difficult to reach through traditional medical delivery. By simultaneously influencing large numbers of people, well designed health messages have the potential to promote and maintain behavioural change over time. Back Pain: Don't Take It Lying Down (1997-1999), a mass media campaign of the Victorian WorkCover Authority, can be seen as a prototype of a successful public health strategy designed to enhance people's self-management abilities. One of the main messages of the campaign was that there is a lot you can do to help yourself, which emphasises shifting the responsibility of control onto the individual. The success of the campaign makes a compelling evidence-based case for using a similar strategy to enhance the self-management abilities of the population.

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...

What computational non-targeted mass spectrometry-based metabolomics can gain from shotgun proteomics.

PubMed

Hamzeiy, Hamid; Cox, Jürgen

2017-02-01

Computational workflows for mass spectrometry-based shotgun proteomics and untargeted metabolomics share many steps. Despite the similarities, untargeted metabolomics is lagging behind in terms of reliable fully automated quantitative data analysis. We argue that metabolomics will strongly benefit from the adaptation of successful automated proteomics workflows to metabolomics. MaxQuant is a popular platform for proteomics data analysis and is widely considered to be superior in achieving high precursor mass accuracies through advanced nonlinear recalibration, usually leading to five to ten-fold better accuracy in complex LC-MS/MS runs. This translates to a sharp decrease in the number of peptide candidates per measured feature, thereby strongly improving the coverage of identified peptides. We argue that similar strategies can be applied to untargeted metabolomics, leading to equivalent improvements in metabolite identification. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Analysis of turbulent heat transfer, mass transfer, and friction in smooth tubes at high Prandtl and Schmidt numbers

NASA Technical Reports Server (NTRS)

Deissler, Robert G

1955-01-01

The expression for eddy diffusivity from a previous analysis was modified in order to account for the effect of kinematic viscosity on the turbulence in the region close to a wall. By using the modified expression, good agreement was obtained between predicted and experimental results for heat and mass transfer at Prandtl and Schmidt numbers between 0.5 and 3000. The effects of length-to-diameter ratio and of variable viscosity were also investigated for a wide range of Prandtl numbers.

Real time determination of the laser ablated mass by means of electric field-perturbation measurement

NASA Astrophysics Data System (ADS)

Pacheco, P.; Álvarez, J.; Sarmiento, R.; Bredice, F.; Sánchez-Aké, C.; Villagrán-Muniz, M.; Palleschi, V.

2018-04-01

A Nd:YAG ns-pulsed laser was used to ablate Al, Cd and Zn targets, which were placed between the plates of a planar charged capacitor. The plasma generates a transient redistribution of the electrical charges on the plates that can be measured as a voltage drop across a resistor connected to the ground plate. This signal is proportional to the capacitor applied voltage, the distance between the plates and the total number of ions produced in the ablation process which in turn is related to the laser energy and the ablated mass. After a series of pulses, the targets were weighed on a thermogravimetric balance to measure the ablated mass. Our results show that the electrical signal measured on the resistor is univocally related to the ablated mass from the target. Therefore, after a proper calibration depending on the material and the experimental geometry, the electrical signal can be used for real time quantitative measurement of the ablated mass in pulsed laser generated plasma experiments. The experiments were repeated on an aluminum target, with and without the presence of the external electric field in order to determine the possible influence of the applied electric field on the ablated mass.

Targeted analyte deconvolution and identification by four-way parallel factor analysis using three-dimensional gas chromatography with mass spectrometry data.

PubMed

Watson, Nathanial E; Prebihalo, Sarah E; Synovec, Robert E

2017-08-29

Comprehensive three-dimensional gas chromatography with time-of-flight mass spectrometry (GC 3 -TOFMS) creates an opportunity to explore a new paradigm in chemometric analysis. Using this newly described instrument and the well understood Parallel Factor Analysis (PARAFAC) model we present one option for utilization of the novel GC 3 -TOFMS data structure. We present a method which builds upon previous work in both GC 3 and targeted analysis using PARAFAC to simplify some of the implementation challenges previously discovered. Conceptualizing the GC 3 -TOFMS instead as a one-dimensional gas chromatograph with GC × GC-TOFMS detection we allow the instrument to create the PARAFAC target window natively. Each first dimension modulation thus creates a full GC × GC-TOFMS chromatogram fully amenable to PARAFAC. A simple mixture of 115 compounds and a diesel sample are interrogated through this methodology. All test analyte targets are successfully identified in both mixtures. In addition, mass spectral matching of the PARAFAC loadings to library spectra yielded results greater than 900 in 40 of 42 test analyte cases. Twenty-nine of these cases produced match values greater than 950. Copyright © 2017 Elsevier B.V. All rights reserved.

Mass Producing Targets for Nuclear Fusion

NASA Technical Reports Server (NTRS)

Wang, T. G.; Elleman, D. D.; Kendall, J. M.

1983-01-01

Metal-encapsulating technique advances prospects of controlling nuclear fusion. Prefilled fusion targets form at nozzle as molten metal such as tin flows through outer channel and pressurized deuterium/tritium gas flows through inner channel. Molten metal completely encloses gas charge as it drops off nozzle.

Development of a suspect and non-target screening approach to detect veterinary antibiotic residues in a complex biological matrix using liquid chromatography/high-resolution mass spectrometry.

PubMed

Solliec, Morgan; Roy-Lachapelle, Audrey; Sauvé, Sébastien

2015-12-30

Swine manure can contain a wide range of veterinary antibiotics, which could enter the environment via manure spreading on agricultural fields. A suspect and non-target screening method was applied to swine manure samples to attempt to identify veterinary antibiotics and pharmaceutical compounds for a future targeted analysis method. A combination of suspect and non-target screening method was developed to identify various veterinary antibiotic families using liquid chromatography coupled with high-resolution mass spectrometry (LC/HRMS). The sample preparation was based on the physicochemical parameters of antibiotics for the wide scope extraction of polar compounds prior to LC/HRMS analysis. The amount of data produced was processed by applying restrictive thresholds and filters to significantly reduce the number of compounds found and eliminate matrix components. The suspect and non-target screening was applied on swine manure samples and revealed the presence of seven common veterinary antibiotics and some of their relative metabolites, including tetracyclines, β-lactams, sulfonamides and lincosamides. However, one steroid and one analgesic were also identified. The occurrence of the identified compounds was validated by comparing their retention times, isotopic abundance patterns and fragmentation patterns with certified standards. This identification method could be very useful as an initial step to screen for and identify emerging contaminants such as veterinary antibiotics and pharmaceuticals in environmental and biological matrices prior to quantification. Copyright © 2015 John Wiley & Sons, Ltd.

Identifying Complex Mixtures in the Environment with Cheminformatics and Non-targeted High Resolution Mass Spectrometry (SETAC NA Focused Topic Meeting : Risk Assessment of Chemical Mixtures)

EPA Science Inventory

Non-target high resolution mass spectrometry techniques combined with advanced cheminformatics offer huge potential for exploring complex mixtures in our environment – yet also offers plenty of challenges. Peak inventories of several non-target studies from within Europe reveal t...

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.

Low Mass-Damping Vortex-Induced Vibrations of a Single Cylinder at Moderate Reynolds Number.

PubMed

Jus, Y; Longatte, E; Chassaing, J-C; Sagaut, P

2014-10-01

The feasibility and accuracy of large eddy simulation is investigated for the case of three-dimensional unsteady flows past an elastically mounted cylinder at moderate Reynolds number. Although these flow problems are unconfined, complex wake flow patterns may be observed depending on the elastic properties of the structure. An iterative procedure is used to solve the structural dynamic equation to be coupled with the Navier-Stokes system formulated in a pseudo-Eulerian way. A moving mesh method is involved to deform the computational domain according to the motion of the fluid structure interface. Numerical simulations of vortex-induced vibrations are performed for a freely vibrating cylinder at Reynolds number 3900 in the subcritical regime under two low mass-damping conditions. A detailed physical analysis is provided for a wide range of reduced velocities, and the typical three-branch response of the amplitude behavior usually reported in the experiments is exhibited and reproduced by numerical simulation.

Halobacterium salinarum NRC-1 PeptideAtlas: strategies for targeted proteomics

PubMed Central

Van, Phu T.; Schmid, Amy K.; King, Nichole L.; Kaur, Amardeep; Pan, Min; Whitehead, Kenia; Koide, Tie; Facciotti, Marc T.; Goo, Young-Ah; Deutsch, Eric W.; Reiss, David J.; Mallick, Parag; Baliga, Nitin S.

2009-01-01

The relatively small numbers of proteins and fewer possible posttranslational modifications in microbes provides a unique opportunity to comprehensively characterize their dynamic proteomes. We have constructed a Peptide Atlas (PA) for 62.7% of the predicted proteome of the extremely halophilic archaeon Halobacterium salinarum NRC-1 by compiling approximately 636,000 tandem mass spectra from 497 mass spectrometry runs in 88 experiments. Analysis of the PA with respect to biophysical properties of constituent peptides, functional properties of parent proteins of detected peptides, and performance of different mass spectrometry approaches has helped highlight plausible strategies for improving proteome coverage and selecting signature peptides for targeted proteomics. Notably, discovery of a significant correlation between absolute abundances of mRNAs and proteins has helped identify low abundance of proteins as the major limitation in peptide detection. Furthermore we have discovered that iTRAQ labeling for quantitative proteomic analysis introduces a significant bias in peptide detection by mass spectrometry. Therefore, despite identifying at least one proteotypic peptide for almost all proteins in the PA, a context-dependent selection of proteotypic peptides appears to be the most effective approach for targeted proteomics. PMID:18652504

Synthesis efficiency of heavy carbon clusters from ETFE ablated by different numbers of laser pulse in vacuum

NASA Astrophysics Data System (ADS)

Shibagaki, K.; Takada, N.; Sasaki, K.; Kadota, K.

2002-09-01

We have carried out mass spectral analysis of positive ions produced by laser ablation of a copolymer of ethylene and tetrafluoroethylene (ETFE: [CH 2CH 2CF 2CF 2] n) in vacuum using time-of-flight mass spectrometry (TOF-MS). The surfaces of the ETFE targets irradiated by different numbers of laser pulse were analyzed by X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM). Heavy carbon cluster ions C n+ with n≥30 were observed in the mass spectra. The fractional abundance of heavy clusters in the mass spectrum decreased with the number of laser pulse. On the other hand, carbon became rich in the atomic composition of the laser-irradiated surface, and the eroded area on the surface increased with the number of laser pulse. From these results, it is suggested that the carbon-rich material surface results in the less efficient production of heavy carbon clusters. In addition, it is also suggested that clustering reactions in eroded craters do not contribute to the synthesis of heavy clusters.

Differential Predictors of Transient Stress versus Posttraumatic Stress Disorder: Evaluating Risk Following Targeted Mass Violence

PubMed Central

Miron, Lynsey R.; Orcutt, Holly K.; Kumpula, Mandy J.

2014-01-01

Schools have become a common incident site for targeted mass violence, including mass shootings. Although exposure to mass violence can result in significant distress, most individuals are able to fully recover over time, while a minority develop more pervasive pathology, such as PTSD. The present study investigated how several pre- and post-trauma factors predict posttraumatic stress symptoms (PTSS) in both the acute and distal aftermath of a campus mass shooting using a sample with known levels of pre-trauma functioning (N = 573). While the largest proportion of participants evidenced resilience following exposure to the event (46.1%), many reported high rates of PTSS shortly after the shooting (42.1%) and a smaller proportion (11.9%) met criteria for probable PTSD both in the acute and more distal aftermath of the event. While several pre-shooting factors predicted heightened PTSS after the shooting, prior trauma exposure was the only pre-shooting variable shown to significantly differentiate between those who experienced transient versus prolonged distress. Among post-shooting predictors, individuals reporting greater emotion dysregulation and peritraumatic dissociative experiences were over 4 times more likely to have elevated PTSS 8 months post-shooting compared to those reporting less dysregulation and dissociative experiences. Individuals with less exposure to the shooting and greater satisfaction with social support were more likely to recover from acute distress. Results suggest that, while pre-trauma factors may differentiate between those who are resilient in the aftermath of a mass shooting from those who experience heightened distress, several event-level and post-trauma coping factors help distinguish between those who eventually recover and those whose PTSD symptoms persist over time. PMID:25311288

Differential predictors of transient stress versus posttraumatic stress disorder: evaluating risk following targeted mass violence.

PubMed

Miron, Lynsey R; Orcutt, Holly K; Kumpula, Mandy J

2014-11-01

Schools have become a common incident site for targeted mass violence, including mass shootings. Although exposure to mass violence can result in significant distress, most individuals are able to fully recover over time, while a minority develop more pervasive pathology, such as PTSD. The present study investigated how several pre- and posttrauma factors predict posttraumatic stress symptoms (PTSS) in both the acute and distal aftermath of a campus mass shooting using a sample with known levels of pretrauma functioning (N=573). Although the largest proportion of participants evidenced resilience following exposure to the event (46.1%), many reported high rates of PTSS shortly after the shooting (42.1%) and a smaller proportion (11.9%) met criteria for probable PTSD both in the acute and more distal aftermath of the event. While several preshooting factors predicted heightened PTSS after the shooting, prior trauma exposure was the only preshooting variable shown to significantly differentiate between those who experienced transient versus prolonged distress. Among postshooting predictors, individuals reporting greater emotion dysregulation and peritraumatic dissociative experiences were over four times more likely to have elevated PTSS 8months postshooting compared with those reporting less dysregulation and dissociative experiences. Individuals with less exposure to the shooting, fewer prior traumatic experiences, and greater satisfaction with social support were more likely to recover from acute distress. Overall, results suggest that, while pretrauma factors may differentiate between those who are resilient in the aftermath of a mass shooting and those who experience heightened distress, several event-level and posttrauma coping factors help distinguish between those who eventually recover and those whose PTSD symptoms persist over time. Copyright © 2014. Published by Elsevier Ltd.

Polymer-based metal nano-coated disposable target for matrix-assisted and matrix-free laser desorption/ionization mass spectrometry.

PubMed

Bugovsky, Stefan; Winkler, Wolfgang; Balika, Werner; Koranda, Manfred; Allmaier, Günter

2016-07-15

The ideal MALDI/LDI mass spectrometry sample target for an axial TOF instrument possesses a variety of properties. Primarily, it should be chemically inert to the sample, i.e. analyte, matrix and solvents, highly planar across the whole target, without any previous chemical contact and provide a uniform surface to facilitate reproducible measurements without artifacts from previous sample or matrix compounds. This can be hard to achieve with a metal target, which has to be extensively cleaned every time after use. Any cleaning step may leave residues behind, may change the surface properties due to the type of cleaning method used or even cause microscopic scratches over time hence altering matrix crystallization behavior. Alternatively, use of disposable targets avoids these problems. As each possesses the same surface they therefore have the potential to replace the conventional full metal targets so commonly employed. Furthermore, low cost single-use targets with high planarity promise an easier compliance with GLP guidelines as they alleviate the problem of low reproducibility due to inconsistent sample/matrix crystallization and changes to the target surface properties. In our tests, polymeric metal nano-coated targets were compared to a stainless steel reference. The polymeric metal nano-coated targets exhibited all the performance characteristics for a MALDI MS sample support, and even surpassed the - in our lab commonly used - reference in some aspects like limit of detection. The target exhibits all necessary features such as electrical conductivity, vacuum, laser and solvent compatibility. Copyright © 2016 Elsevier Inc. All rights reserved.

Technology platform development for targeted plasma metabolites in human heart failure.

PubMed

Chan, Cy X'avia; Khan, Anjum A; Choi, Jh Howard; Ng, Cm Dominic; Cadeiras, Martin; Deng, Mario; Ping, Peipei

2013-01-01

Heart failure is a multifactorial disease associated with staggeringly high morbidity and motility. Recently, alterations of multiple metabolites have been implicated in heart failure; however, the lack of an effective technology platform to assess these metabolites has limited our understanding on how they contribute to this disease phenotype. We have successfully developed a new workflow combining specific sample preparation with tandem mass spectrometry that enables us to extract most of the targeted metabolites. 19 metabolites were chosen ascribing to their biological relevance to heart failure, including extracellular matrix remodeling, inflammation, insulin resistance, renal dysfunction, and cardioprotection against ischemic injury. In this report, we systematically engineered, optimized and refined a protocol applicable to human plasma samples; this study contributes to the methodology development with respect to deproteinization, incubation, reconstitution, and detection with mass spectrometry. The deproteinization step was optimized with 20% methanol/ethanol at a plasma:solvent ratio of 1:3. Subsequently, an incubation step was implemented which remarkably enhanced the metabolite signals and the number of metabolite peaks detected by mass spectrometry in both positive and negative modes. With respect to the step of reconstitution, 0.1% formic acid was designated as the reconstitution solvent vs. 6.5 mM ammonium bicarbonate, based on the comparable number of metabolite peaks detected in both solvents, and yet the signal detected in the former was higher. By adapting this finalized protocol, we were able to retrieve 13 out of 19 targeted metabolites from human plasma. We have successfully devised a simple albeit effective workflow for the targeted plasma metabolites relevant to human heart failure. This will be employed in tandem with high throughput liquid chromatography mass spectrometry platform to validate and characterize these potential metabolic

Reproducibility of lung tumor position and reduction of lung mass within the planning target volume using active breathing control (ABC).

PubMed

Cheung, Patrick C F; Sixel, Katharina E; Tirona, Romeo; Ung, Yee C

2003-12-01

The active breathing control (ABC) device allows for temporary immobilization of respiratory motion by implementing a breath hold at a predefined relative lung volume and air flow direction. The purpose of this study was to quantitatively evaluate the ability of the ABC device to immobilize peripheral lung tumors at a reproducible position, increase total lung volume, and thereby reduce lung mass within the planning target volume (PTV). Ten patients with peripheral non-small-cell lung cancer tumors undergoing radiotherapy had CT scans of their thorax with and without ABC inspiration breath hold during the first 5 days of treatment. Total lung volumes were determined from the CT data sets. Each peripheral lung tumor was contoured by one physician on all CT scans to generate gross tumor volumes (GTVs). The lung density and mass contained within a 1.5-cm PTV margin around each peripheral tumor was calculated using CT numbers. Using the center of the GTV from the Day 1 ABC scan as the reference, the displacement of subsequent GTV centers on Days 2 to 5 for each patient with ABC applied was calculated in three dimensions. With the use of ABC inspiration breath hold, total lung volumes increased by an average of 42%. This resulted in an average decrease in lung mass of 18% within a standard 1.5-cm PTV margin around the GTV. The average (+/- standard deviation) displacement of GTV centers with ABC breath hold applied was 0.3 mm (+/- 1.8 mm), 1.2 mm (+/- 2.3 mm), and 1.1 mm (+/- 3.5 mm) in the lateral direction, anterior-posterior direction, and superior-inferior direction, respectively. Results from this study indicate that there remains some inter-breath hold variability in peripheral lung tumor position with the use of ABC inspiration breath hold, which prevents significant PTV margin reduction. However, lung volumes can significantly increase, thereby decreasing the mass of lung within a standard PTV.

Genomic Copy Number Dictates a Gene-Independent Cell Response to CRISPR/Cas9 Targeting | Office of Cancer Genomics

Cancer.gov

The CRISPR/Cas9 system enables genome editing and somatic cell genetic screens in mammalian cells. We performed genome-scale loss-of-function screens in 33 cancer cell lines to identify genes essential for proliferation/survival and found a strong correlation between increased gene copy number and decreased cell viability after genome editing. Within regions of copy-number gain, CRISPR/Cas9 targeting of both expressed and unexpressed genes, as well as intergenic loci, led to significantly decreased cell proliferation through induction of a G2 cell-cycle arrest.

Quasi-targeted analysis of hydroxylation-related metabolites of polycyclic aromatic hydrocarbons in human urine by liquid chromatography-mass spectrometry.

PubMed

Tang, Caiming; Tan, Jianhua; Fan, Ruifang; Zhao, Bo; Tang, Caixing; Ou, Weihui; Jin, Jiabin; Peng, Xianzhi

2016-08-26

Metabolite identification is crucial for revealing metabolic pathways and comprehensive potential toxicities of polycyclic aromatic hydrocarbons (PAHs) in human body. In this work, a quasi-targeted analysis strategy was proposed for metabolite identification of monohydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) in human urine using liquid chromatography triple quadruple mass spectrometry (LC-QqQ-MS/MS) combined with liquid chromatography high resolution mass spectrometry (LC-HRMS). Potential metabolites of OH-PAHs were preliminarily screened out by LC-QqQ-MS/MS in association with filtering in a self-constructed information list of possible metabolites, followed by further identification and confirmation with LC-HRMS. The developed method can provide more reliable and systematic results compared with traditional untargeted analysis using LC-HRMS. In addition, data processing for LC-HRMS analysis were greatly simplified. This quasi-targeted analysis method was successfully applied to identifying phase I and phase II metabolites of OH-PAHs in human urine. Five metabolites of hydroxynaphthalene, seven of hydroxyfluorene, four of hydroxyphenanthrene, and three of hydroxypyrene were tentatively identified. Metabolic pathways of PAHs in human body were putatively revealed based on the identified metabolites. The experimental results will be valuable for investigating the metabolic processes of PAHs in human body, and the quasi-targeted analysis strategy can be expanded to the metabolite identification and profiling of other compounds in vivo. Copyright © 2016 Elsevier B.V. All rights reserved.

The Daya Bay antineutrino detector filling system and liquid mass measurement

NASA Astrophysics Data System (ADS)

Band, H. R.; Cherwinka, J. J.; Draeger, E.; Heeger, K. M.; Hinrichs, P.; Lewis, C. A.; Mattison, H.; McFarlane, M. C.; Webber, D. M.; Wenman, D.; Wang, W.; Wise, T.; Xiao, Q.

2013-09-01

The Daya Bay Reactor Neutrino Experiment has measured the neutrino mixing angle θ13 to world-leading precision. The experiment uses eight antineutrino detectors filled with 20-tons of gadolinium-doped liquid scintillator to detect antineutrinos emitted from the Daya Bay nuclear power plant through the inverse beta decay reaction. The precision measurement of sin22θ13 relies on the relative antineutrino interaction rates between detectors at near (400 m) and far (roughly 1.8 km) distances from the nuclear reactors. The measured interaction rate in each detector is directly proportional to the number of protons in the liquid scintillator target. A precision detector filling system was developed to simultaneously fill the three liquid zones of the antineutrino detectors and measure the relative target mass between detectors to < 0.02%. This paper describes the design, operation, and performance of the system and the resulting precision measurement of the detectors' target liquid masses.

Heat-Treatment-Responsive Proteins in Different Developmental Stages of Tomato Pollen Detected by Targeted Mass Accuracy Precursor Alignment (tMAPA).

PubMed

Chaturvedi, Palak; Doerfler, Hannes; Jegadeesan, Sridharan; Ghatak, Arindam; Pressman, Etan; Castillejo, Maria Angeles; Wienkoop, Stefanie; Egelhofer, Volker; Firon, Nurit; Weckwerth, Wolfram

2015-11-06

Recently, we have developed a quantitative shotgun proteomics strategy called mass accuracy precursor alignment (MAPA). The MAPA algorithm uses high mass accuracy to bin mass-to-charge (m/z) ratios of precursor ions from LC-MS analyses, determines their intensities, and extracts a quantitative sample versus m/z ratio data alignment matrix from a multitude of samples. Here, we introduce a novel feature of this algorithm that allows the extraction and alignment of proteotypic peptide precursor ions or any other target peptide from complex shotgun proteomics data for accurate quantification of unique proteins. This strategy circumvents the problem of confusing the quantification of proteins due to indistinguishable protein isoforms by a typical shotgun proteomics approach. We applied this strategy to a comparison of control and heat-treated tomato pollen grains at two developmental stages, post-meiotic and mature. Pollen is a temperature-sensitive tissue involved in the reproductive cycle of plants and plays a major role in fruit setting and yield. By LC-MS-based shotgun proteomics, we identified more than 2000 proteins in total for all different tissues. By applying the targeted MAPA data-processing strategy, 51 unique proteins were identified as heat-treatment-responsive protein candidates. The potential function of the identified candidates in a specific developmental stage is discussed.

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.

A study on the relationship between mass concentrations, chemistry and number size distribution of urban fine aerosols in Milan, Barcelona and London

NASA Astrophysics Data System (ADS)

Rodríguez, S.; van Dingenen, R.; Putaud, J.-P.; Dell'Acqua, A.; Pey, J.; Querol, X.; Alastuey, A.; Chenery, S.; Ho, K.-F.; Harrison, R. M.; Tardivo, R.; Scarnato, B.; Gianelle, V.

2007-01-01

A physicochemical characterization of the urban fine aerosol (aerosol number size distribution, chemical composition and mass concentrations) in Milan, Barcelona and London is presented in this article. The objective is to obtain a comprehensive picture on the involvement of the microphysical processes of the aerosol dynamic in the: 1) regular evolution of the urban aerosol (daily, weekly and seasonal basis) and in the day-to-day variations (from clean-air to pollution-events), and 2) link between "aerosol chemistry and mass concentrations" with the "number size distribution". The mass concentrations of the fine PM2.5 aerosol exhibit a high correlation with the number concentration of particles >100 nm (which only accounts for <20% of the total number concentration N of fine aerosols) and do not correlate with the number of particles <100 nm ("ultrafine particles", which accounts for >80% of fine particles). Organic matter (OM) and black-carbon (BC) are the only aerosol components showing a significant correlation with ultrafine particles (attributed to vehicles emissions), whereas ammonium-nitrate, ammonium-sulphate and also OM and BC correlate with N>100(nm) (attributed to gas-to-particle transformation mechanisms and some primary emissions). Time series of the aerosol DpN diameter (dN/dlogD mode), mass PM2.5 concentrations and number N>100(nm) concentrations, exhibit correlated day-to-day variations which point to a significant involvement of condensation of semi-volatile compounds during urban pollution events. This agrees with the fact that ammonium-nitrate is the component exhibiting the highest increases from mid-to-high pollution episodes, when the highest DpN increases are observed. The results indicates that "fine PM2.5 particles urban pollution events" tend to occur when condensation processes have made particles grow enough to produce significant concentrations of N>100(nm). In contrast, because the low contribution of ultrafine particles to the fine

Scout-MRM: Multiplexed Targeted Mass Spectrometry-Based Assay without Retention Time Scheduling Exemplified by Dickeya dadantii Proteomic Analysis during Plant Infection.

PubMed

Rougemont, Blandine; Bontemps Gallo, Sébastien; Ayciriex, Sophie; Carrière, Romain; Hondermarck, Hubert; Lacroix, Jean Marie; Le Blanc, J C Yves; Lemoine, Jérôme

2017-02-07

Targeted mass spectrometry of a surrogate peptide panel is a powerful method to study the dynamics of protein networks, but chromatographic time scheduling remains a major limitation for dissemination and implementation of robust and large multiplexed assays. We unveil a Multiple Reaction Monitoring method (Scout-MRM) where the use of spiked scout peptides triggers complex transition lists, regardless of the retention time of targeted surrogate peptides. The interest of Scout-MRM method regarding the retention time independency, multiplexing capability, reproducibility, and putative interest in facilitating method transfer was illustrated by a 782-peptide-plex relative assay targeting 445 proteins of the phytopathogen Dickeya dadantii during plant infection.

Multiplexed targeted mass spectrometry assays for prostate cancer-associated urinary proteins

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

Shi, Tujin; Quek, Sue-Ing; Gao, Yuqian

Biomarkers for effective early diagnosis and prognosis of prostate cancer are still lacking. Multiplexed assays for cancer-associated proteins could be useful for identifying biomarkers for cancer detection and stratification. Herein, we report the development of sensitive targeted mass spectrometry assays for simultaneous quantification of 10 prostate cancer-associated proteins in urine. The diagnostic utility of these markers was evaluated with an initial cohort of 20 clinical urine samples. Individual marker concentration was normalized against the measured urinary prostate-specific antigen level as a reference of prostate-specific secretion. The areas under the receiver-operating characteristic curves for the 10 proteins ranged from 0.75 formore » CXCL14 to 0.87 for CEACAM5. Furthermore, MMP9 level was found to be significantly higher in patients with high Gleason scores, suggesting a potential of MMP9 as a marker for risk level assessment. Taken together, our work illustrated the feasibility of accurate multiplexed measurements of low-abundance cancer-associated proteins in urine and provided a viable path forward for preclinical verification of candidate biomarkers for prostate cancer.« less

Automating data analysis for two-dimensional gas chromatography/time-of-flight mass spectrometry non-targeted analysis of comparative samples.

PubMed

Titaley, Ivan A; Ogba, O Maduka; Chibwe, Leah; Hoh, Eunha; Cheong, Paul H-Y; Simonich, Staci L Massey

2018-03-16

Non-targeted analysis of environmental samples, using comprehensive two-dimensional gas chromatography coupled with time-of-flight mass spectrometry (GC × GC/ToF-MS), poses significant data analysis challenges due to the large number of possible analytes. Non-targeted data analysis of complex mixtures is prone to human bias and is laborious, particularly for comparative environmental samples such as contaminated soil pre- and post-bioremediation. To address this research bottleneck, we developed OCTpy, a Python™ script that acts as a data reduction filter to automate GC × GC/ToF-MS data analysis from LECO ® ChromaTOF ® software and facilitates selection of analytes of interest based on peak area comparison between comparative samples. We used data from polycyclic aromatic hydrocarbon (PAH) contaminated soil, pre- and post-bioremediation, to assess the effectiveness of OCTpy in facilitating the selection of analytes that have formed or degraded following treatment. Using datasets from the soil extracts pre- and post-bioremediation, OCTpy selected, on average, 18% of the initial suggested analytes generated by the LECO ® ChromaTOF ® software Statistical Compare feature. Based on this list, 63-100% of the candidate analytes identified by a highly trained individual were also selected by OCTpy. This process was accomplished in several minutes per sample, whereas manual data analysis took several hours per sample. OCTpy automates the analysis of complex mixtures of comparative samples, reduces the potential for human error during heavy data handling and decreases data analysis time by at least tenfold. Copyright © 2018 Elsevier B.V. All rights reserved.

Discovery of safety biomarkers for atorvastatin in rat urine using mass spectrometry based metabolomics combined with global and targeted approach.

PubMed

Kumar, Bhowmik Salil; Lee, Young-Joo; Yi, Hong Jae; Chung, Bong Chul; Jung, Byung Hwa

2010-02-19

In order to develop a safety biomarker for atorvastatin, this drug was orally administrated to hyperlipidemic rats, and a metabolomic study was performed. Atorvastatin was given in doses of either 70 mg kg(-1) day(-1) or 250 mg kg(-1) day(-1) for a period of 7 days (n=4 for each group). To evaluate any abnormal effects of the drug, physiological and plasma biochemical parameters were measured and histopathological tests were carried out. Safety biomarkers were derived by comparing these parameters and using both global and targeted metabolic profiling. Global metabolic profiling was performed using liquid chromatography/time of flight/mass spectrometry (LC/TOF/MS) with multivariate data analysis. Several safety biomarker candidates that included various steroids and amino acids were discovered as a result of global metabolic profiling, and they were also confirmed by targeted metabolic profiling using gas chromatography/mass spectrometry (GC/MS) and capillary electrophoresis/mass spectrometry (CE/MS). Serum biochemical and histopathological tests were used to detect abnormal drug reactions in the liver after repeating oral administration of atorvastatin. The metabolic differences between control and the drug-treated groups were compared using PLS-DA score plots. These results were compared with the physiological and plasma biochemical parameters and the results of a histopathological test. Estrone, cortisone, proline, cystine, 3-ureidopropionic acid and histidine were proposed as potential safety biomarkers related with the liver toxicity of atorvastatin. These results indicate that the combined application of global and targeted metabolic profiling could be a useful tool for the discovery of drug safety biomarkers. Copyright 2009 Elsevier B.V. All rights reserved.

Highly multiplexed targeted proteomics using precise control of peptide retention time.

PubMed

Gallien, Sebastien; Peterman, Scott; Kiyonami, Reiko; Souady, Jamal; Duriez, Elodie; Schoen, Alan; Domon, Bruno

2012-04-01

Large-scale proteomics applications using SRM analysis on triple quadrupole mass spectrometers present new challenges to LC-MS/MS experimental design. Despite the automation of building large-scale LC-SRM methods, the increased numbers of targeted peptides can compromise the balance between sensitivity and selectivity. To facilitate large target numbers, time-scheduled SRM transition acquisition is performed. Previously published results have demonstrated incorporation of a well-characterized set of synthetic peptides enabled chromatographic characterization of the elution profile for most endogenous peptides. We have extended this application of peptide trainer kits to not only build SRM methods but to facilitate real-time elution profile characterization that enables automated adjustment of the scheduled detection windows. Incorporation of dynamic retention time adjustments better facilitate targeted assays lasting several days without the need for constant supervision. This paper provides an overview of how the dynamic retention correction approach identifies and corrects for commonly observed LC variations. This adjustment dramatically improves robustness in targeted discovery experiments as well as routine quantification experiments. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

panelcn.MOPS: Copy-number detection in targeted NGS panel data for clinical diagnostics.

PubMed

Povysil, Gundula; Tzika, Antigoni; Vogt, Julia; Haunschmid, Verena; Messiaen, Ludwine; Zschocke, Johannes; Klambauer, Günter; Hochreiter, Sepp; Wimmer, Katharina

2017-07-01

Targeted next-generation-sequencing (NGS) panels have largely replaced Sanger sequencing in clinical diagnostics. They allow for the detection of copy-number variations (CNVs) in addition to single-nucleotide variants and small insertions/deletions. However, existing computational CNV detection methods have shortcomings regarding accuracy, quality control (QC), incidental findings, and user-friendliness. We developed panelcn.MOPS, a novel pipeline for detecting CNVs in targeted NGS panel data. Using data from 180 samples, we compared panelcn.MOPS with five state-of-the-art methods. With panelcn.MOPS leading the field, most methods achieved comparably high accuracy. panelcn.MOPS reliably detected CNVs ranging in size from part of a region of interest (ROI), to whole genes, which may comprise all ROIs investigated in a given sample. The latter is enabled by analyzing reads from all ROIs of the panel, but presenting results exclusively for user-selected genes, thus avoiding incidental findings. Additionally, panelcn.MOPS offers QC criteria not only for samples, but also for individual ROIs within a sample, which increases the confidence in called CNVs. panelcn.MOPS is freely available both as R package and standalone software with graphical user interface that is easy to use for clinical geneticists without any programming experience. panelcn.MOPS combines high sensitivity and specificity with user-friendliness rendering it highly suitable for routine clinical diagnostics. © 2017 The Authors. Human Mutation published by Wiley Periodicals, Inc.

panelcn.MOPS: Copy‐number detection in targeted NGS panel data for clinical diagnostics

PubMed Central

Povysil, Gundula; Tzika, Antigoni; Vogt, Julia; Haunschmid, Verena; Messiaen, Ludwine; Zschocke, Johannes; Klambauer, Günter; Wimmer, Katharina

2017-01-01

Abstract Targeted next‐generation‐sequencing (NGS) panels have largely replaced Sanger sequencing in clinical diagnostics. They allow for the detection of copy‐number variations (CNVs) in addition to single‐nucleotide variants and small insertions/deletions. However, existing computational CNV detection methods have shortcomings regarding accuracy, quality control (QC), incidental findings, and user‐friendliness. We developed panelcn.MOPS, a novel pipeline for detecting CNVs in targeted NGS panel data. Using data from 180 samples, we compared panelcn.MOPS with five state‐of‐the‐art methods. With panelcn.MOPS leading the field, most methods achieved comparably high accuracy. panelcn.MOPS reliably detected CNVs ranging in size from part of a region of interest (ROI), to whole genes, which may comprise all ROIs investigated in a given sample. The latter is enabled by analyzing reads from all ROIs of the panel, but presenting results exclusively for user‐selected genes, thus avoiding incidental findings. Additionally, panelcn.MOPS offers QC criteria not only for samples, but also for individual ROIs within a sample, which increases the confidence in called CNVs. panelcn.MOPS is freely available both as R package and standalone software with graphical user interface that is easy to use for clinical geneticists without any programming experience. panelcn.MOPS combines high sensitivity and specificity with user‐friendliness rendering it highly suitable for routine clinical diagnostics. PMID:28449315

Measurement uncertainty of ester number, acid number and patchouli alcohol of patchouli oil produced in Yogyakarta

NASA Astrophysics Data System (ADS)

Istiningrum, Reni Banowati; Saepuloh, Azis; Jannah, Wirdatul; Aji, Didit Waskito

2017-03-01

Yogyakarta is one of patchouli oil distillation center in Indonesia. The quality of patchouli oil greatly affect its market price. Therefore, testing quality of patchouli oil parameters is an important concern, one through determination of the measurement uncertainty. This study will determine the measurement uncertainty of ester number, acid number and content of patchouli alcohol through a bottom up approach. Source contributor to measurement uncertainty of ester number is a mass of the sample, a blank and sample titration volume, the molar mass of KOH, HCl normality, and replication. While the source contributor of the measurement uncertainty of acid number is the mass of the sample, the sample titration volume, the relative mass and normality of KOH, and repetition. Determination of patchouli alcohol by Gas Chromatography considers the sources of measurement uncertainty only from repeatability because reference materials are not available.

Effective Majorana mass matrix from tau and pseudoscalar meson lepton number violating decays

NASA Astrophysics Data System (ADS)

Abada, Asmaa; De Romeri, Valentina; Lucente, Michele; Teixeira, Ana M.; Toma, Takashi

2018-02-01

An observation of any lepton number violating process will undoubtedly point towards the existence of new physics and indirectly to the clear Majorana nature of the exchanged fermion. In this work, we explore the potential of a minimal extension of the Standard Model via heavy sterile fermions with masses in the [0.1 - 10] GeV range concerning an extensive array of "neutrinoless" meson and tau decay processes. We assume that the Majorana neutrinos are produced on-shell, and focus on three-body decays. We conduct an update on the bounds on the active-sterile mixing elements, |{U}_{ℓ }{{}{_{α}}}_4{U}_{ℓ }{{}{_{β}}}_4| , taking into account the most recent experimental bounds (and constraints) and new theoretical inputs, as well as the effects of a finite detector, imposing that the heavy neutrino decay within the detector. This allows to establish up-to-date comprehensive constraints on the sterile fermion parameter space. Our results suggest that the branching fractions of several decays are close to current sensitivities (likely within reach of future facilities), some being already in conflict with current data (as is the case of K + → ℓ α + ℓ β + π -, and τ - → μ +π-π-). We use these processes to extract constraints on all entries of an enlarged definition of a 3 × 3 "effective" Majorana neutrino mass matrix m ν αβ .

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.

Beam heating of thick targets for on-line mass separators

NASA Astrophysics Data System (ADS)

Eaton, T. W.; Ravn, H. L.; Isolde Collaboration

1987-05-01

Energy deposition computations have been made on a variety of target materials utilized for the production of radioisotopes by means of 600-MeV protons. Results have shown that, when a proton current of 100 μA is assumed, dispersed target materials, such as uranium carbide powder and magnesium oxide, are best able to withstand the energy absorption and consequent beam heating without the need of additional cooling. Modified foil targets of titanium, zirconium and tantalum also appear capable of withstanding a full beam current, whilst liquid metal targets in their present form appear to have limitations in terms of the maximum allowable beam current. A redesign of the target container is proposed which allows higher proton currents to be used with these targets also.

Assessment of meat authenticity using bioinformatics, targeted peptide biomarkers and high-resolution mass spectrometry.

PubMed

Ruiz Orduna, Alberto; Husby, Erik; Yang, Charles T; Ghosh, Dipankar; Beaudry, Francis

2015-01-01

In recent years a significant increase of food fraud has been observed, ranging from false label claims to the use of additives and fillers to increase profitability. Recently in 2013 horse and pig DNAs were detected in beef products sold from several retailers. Mass spectrometry (MS) has become the workhorse in protein research, and the detection of marker proteins could serve for both animal species and tissue authentication. Meat species authenticity is performed in this paper using a well-defined proteogenomic annotation, carefully chosen surrogate tryptic peptides and analysis using a hybrid quadrupole-Orbitrap MS. Selected mammalian meat samples were homogenised and proteins were extracted and digested with trypsin. The samples were analysed using a high-resolution MS. Chromatography was achieved using a 30-min linear gradient along with a BioBasic C8 100 × 1 mm column at a flow rate of 75 µl min(-1). The MS was operated in full-scan high resolution and accurate mass. MS/MS spectra were collected for selected proteotypic peptides. Muscular proteins were methodically analysed in silico in order to generate tryptic peptide mass lists and theoretical MS/MS spectra. Following a comprehensive bottom-up proteomic analysis, we detected and identified a proteotypic myoglobin tryptic peptide (120-134) for each species with observed m/z below 1.3 ppm compared with theoretical values. Moreover, proteotypic peptides from myosin-1, myosin-2 and β-haemoglobin were also identified. This targeted method allowed comprehensive meat speciation down to 1% (w/w) of undesired product.

Characteristics of Ambient Black Carbon Mass and Size-Resolved Particle Number Concentrations during Corn Straw Open-Field Burning Episode Observations at a Rural Site in Southern Taiwan.

PubMed

Cheng, Yu-Hsiang; Yang, Li-Sing

2016-07-08

Information on the effect of open-field burning of agricultural residues on ambient black carbon (BC) mass and size-resolved particle number concentrations is scarce. In this study, to understand the effect of such open-field burning on short-term air quality, real-time variations of the BC mass and size-resolved particle number concentrations were monitored before and during a corn straw open-field burning episode at a rural site. Correlations between the BC mass and size-resolved particle number concentrations during the episode were investigated. Moreover, the particle number size distribution and absorption Ångström exponent were determined for obtaining the characteristics of aerosol emissions from the corn straw open-field burning. The results can be used to address public health concerns and as a reference for managing similar episodes of open-field burning of agricultural residues.

X-ray constraints on the number of stellar mass black holes in the inner parsec

NASA Astrophysics Data System (ADS)

Deegan, Patrick; Nayakshin, Sergei

2006-12-01

Due to dynamical friction stellar mass black holes should form a cusp in the inner parsec. Calculations [5, 6] show that approximately 20 thousand black holes would be present in a sphere with radius of about a parsec around Sgr A*. The presence of these objects opens up the possibility that they might be accreting ''cool'' gas (i.e. the Minispiral) as discussed by Morris [6]. Here we calculate the X-ray emission expected from these black holes as a method to constrain their population. We find that the data limits the total number of such black holes to around 10 - 20 thousand. Even a much smaller number of such black holes, i.e. 5 thousand, is sufficient to produce several sources with X-ray luminosity above Lx ~ 1033 erg s-1 at any one time. We suggest that some of the discrete X-ray sources observed by Muno [7] with Chandra in the inner parsec may be such ''fake X-ray binaries''.

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.

Animal cognition. Number-space mapping in the newborn chick resembles humans' mental number line.

PubMed

Rugani, Rosa; Vallortigara, Giorgio; Priftis, Konstantinos; Regolin, Lucia

2015-01-30

Humans represent numbers along a mental number line (MNL), where smaller values are located on the left and larger on the right. The origin of the MNL and its connections with cultural experience are unclear: Pre-verbal infants and nonhuman species master a variety of numerical abilities, supporting the existence of evolutionary ancient precursor systems. In our experiments, 3-day-old domestic chicks, once familiarized with a target number (5), spontaneously associated a smaller number (2) with the left space and a larger number (8) with the right space. The same number (8), though, was associated with the left space when the target number was 20. Similarly to humans, chicks associate smaller numbers with the left space and larger numbers with the right space. Copyright © 2015, American Association for the Advancement of Science.

Extended Glauber Model of Antiproton-Nucleus Annihilation for All Energies and Mass Numbers

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

Lee, Teck-Ghee; Wong, Cheuk-Yin

2014-01-01

Previous analytical formulas in the Glauber model for high-energy nucleus-nucleus collisions developed by Wong are utilized and extended to study Antiproton-nucleus annihilations for both high and low energies, after taking into account the effects of Coulomb and nuclear interactions, and the change of the antiproton momentum inside a nucleus. The extended analytical formulas capture the main features of the experimental antiproton-nucleus annihilation cross sections for all energies and mass numbers. At high antiproton energies, they exhibit the granular property for the lightest nuclei and the black-disk limit for the heavy nuclei. At low antiproton energies, they display the effect ofmore » the antiproton momentum increase due to the nuclear interaction for the light nuclei, and the effect of the magnification due to the attractive Coulomb interaction for the heavy nuclei.« less

Multi-Target Tracking Using an Improved Gaussian Mixture CPHD Filter.

PubMed

Si, Weijian; Wang, Liwei; Qu, Zhiyu

2016-11-23

The cardinalized probability hypothesis density (CPHD) filter is an alternative approximation to the full multi-target Bayesian filter for tracking multiple targets. However, although the joint propagation of the posterior intensity and cardinality distribution in its recursion allows more reliable estimates of the target number than the PHD filter, the CPHD filter suffers from the spooky effect where there exists arbitrary PHD mass shifting in the presence of missed detections. To address this issue in the Gaussian mixture (GM) implementation of the CPHD filter, this paper presents an improved GM-CPHD filter, which incorporates a weight redistribution scheme into the filtering process to modify the updated weights of the Gaussian components when missed detections occur. In addition, an efficient gating strategy that can adaptively adjust the gate sizes according to the number of missed detections of each Gaussian component is also presented to further improve the computational efficiency of the proposed filter. Simulation results demonstrate that the proposed method offers favorable performance in terms of both estimation accuracy and robustness to clutter and detection uncertainty over the existing methods.

Clinical Validation of Copy Number Variant Detection from Targeted Next-Generation Sequencing Panels.

PubMed

Kerkhof, Jennifer; Schenkel, Laila C; Reilly, Jack; McRobbie, Sheri; Aref-Eshghi, Erfan; Stuart, Alan; Rupar, C Anthony; Adams, Paul; Hegele, Robert A; Lin, Hanxin; Rodenhiser, David; Knoll, Joan; Ainsworth, Peter J; Sadikovic, Bekim

2017-11-01

Next-generation sequencing (NGS) technology has rapidly replaced Sanger sequencing in the assessment of sequence variations in clinical genetics laboratories. One major limitation of current NGS approaches is the ability to detect copy number variations (CNVs) approximately >50 bp. Because these represent a major mutational burden in many genetic disorders, parallel CNV assessment using alternate supplemental methods, along with the NGS analysis, is normally required, resulting in increased labor, costs, and turnaround times. The objective of this study was to clinically validate a novel CNV detection algorithm using targeted clinical NGS gene panel data. We have applied this approach in a retrospective cohort of 391 samples and a prospective cohort of 2375 samples and found a 100% sensitivity (95% CI, 89%-100%) for 37 unique events and a high degree of specificity to detect CNVs across nine distinct targeted NGS gene panels. This NGS CNV pipeline enables stand-alone first-tier assessment for CNV and sequence variants in a clinical laboratory setting, dispensing with the need for parallel CNV analysis using classic techniques, such as microarray, long-range PCR, or multiplex ligation-dependent probe amplification. This NGS CNV pipeline can also be applied to the assessment of complex genomic regions, including pseudogenic DNA sequences, such as the PMS2CL gene, and to mitochondrial genome heteroplasmy detection. Copyright © 2017 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Technical Note: Using k-means clustering to determine the number and position of isocenters in MLC-based multiple target intracranial radiosurgery.

PubMed

Yock, Adam D; Kim, Gwe-Ya

2017-09-01

To present the k-means clustering algorithm as a tool to address treatment planning considerations characteristic of stereotactic radiosurgery using a single isocenter for multiple targets. For 30 patients treated with stereotactic radiosurgery for multiple brain metastases, the geometric centroids and radii of each met were determined from the treatment planning system. In-house software used this as well as weighted and unweighted versions of the k-means clustering algorithm to group the targets to be treated with a single isocenter, and to position each isocenter. The algorithm results were evaluated using within-cluster sum of squares as well as a minimum target coverage metric that considered the effect of target size. Both versions of the algorithm were applied to an example patient to demonstrate the prospective determination of the appropriate number and location of isocenters. Both weighted and unweighted versions of the k-means algorithm were applied successfully to determine the number and position of isocenters. Comparing the two, both the within-cluster sum of squares metric and the minimum target coverage metric resulting from the unweighted version were less than those from the weighted version. The average magnitudes of the differences were small (-0.2 cm 2 and 0.1% for the within cluster sum of squares and minimum target coverage, respectively) but statistically significant (Wilcoxon signed-rank test, P < 0.01). The differences between the versions of the k-means clustering algorithm represented an advantage of the unweighted version for the within-cluster sum of squares metric, and an advantage of the weighted version for the minimum target coverage metric. While additional treatment planning considerations have a large influence on the final treatment plan quality, both versions of the k-means algorithm provide automatic, consistent, quantitative, and objective solutions to the tasks associated with SRS treatment planning using a single isocenter

Fragmentation analysis of water-soluble atmospheric organic matter using ultrahigh-resolution FT-ICR mass spectrometry.

PubMed

Leclair, Jeffrey P; Collett, Jeffrey L; Mazzoleni, Lynn R

2012-04-17

Isolated water-soluble atmospheric organic matter (AOM) analytes extracted from radiation fogwater samples were analyzed using collision induced dissociation with ultrahigh-resolution Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). Tandem mass analysis was performed on several mass ranges between 100 and 400 Da to characterize the functional groups of AOM species. Compounds containing nitrogen and/or sulfur were targeted because of the high number of oxygen atoms contained in their molecular formulas. Due to the large number of isobaric ions in the precursor isolation ranges, large numbers of product ions resulted from collision induced dissociation. Common neutral losses were assigned by matching the molecular formulas of the expected product ions with the detected product ions within the appropriate mass spectra. Since polar functional groups are expected to affect the hygroscopic properties of aerosols, the losses of H(2)O, CO(2), CH(3)OH, HNO(3), CH(3)NO(3), SO(3), SO(4) and combinations of these were specifically targeted. Among the 421 compounds studied, the most frequently observed neutral losses were CO(2) (54%), H(2)O (43%) and CH(3)OH (40%). HNO(3) losses were observed for 63% of the studied nitrogen containing compounds and 33% of the studied compounds containing both nitrogen and sulfur. SO(3) losses were observed for 85% of the studied sulfur containing compounds and 42% of studied compounds containing both nitrogen and sulfur. A number of molecular formulas matching those of monoterpene ozonolysis SOA were observed; they include organonitrates, organosulfates, and nitroxy-organosulfates. Overall, the results of fragmentation analysis of 400+ individual molecular precursors elucidate the complexity and multifunctional nature of the isolated water-soluble AOM.

Quantitative comparison of tumor delivery for multiple targeted nanoparticles simultaneously by multiplex ICP-MS.

PubMed

Elias, Andrew; Crayton, Samuel H; Warden-Rothman, Robert; Tsourkas, Andrew

2014-07-28

Given the rapidly expanding library of disease biomarkers and targeting agents, the number of unique targeted nanoparticles is growing exponentially. The high variability and expense of animal testing often makes it unfeasible to examine this large number of nanoparticles in vivo. This often leads to the investigation of a single formulation that performed best in vitro. However, nanoparticle performance in vivo depends on many variables, many of which cannot be adequately assessed with cell-based assays. To address this issue, we developed a lanthanide-doped nanoparticle method that allows quantitative comparison of multiple targeted nanoparticles simultaneously. Specifically, superparamagnetic iron oxide (SPIO) nanoparticles with different targeting ligands were created, each with a unique lanthanide dopant. Following the simultaneous injection of the various SPIO compositions into tumor-bearing mice, inductively coupled plasma mass spectroscopy was used to quantitatively and orthogonally assess the concentration of each SPIO composition in serial blood and resected tumor samples.

Quantitative Comparison of Tumor Delivery for Multiple Targeted Nanoparticles Simultaneously by Multiplex ICP-MS

PubMed Central

Elias, Andrew; Crayton, Samuel H.; Warden-Rothman, Robert; Tsourkas, Andrew

2014-01-01

Given the rapidly expanding library of disease biomarkers and targeting agents, the number of unique targeted nanoparticles is growing exponentially. The high variability and expense of animal testing often makes it unfeasible to examine this large number of nanoparticles in vivo. This often leads to the investigation of a single formulation that performed best in vitro. However, nanoparticle performance in vivo depends on many variables, many of which cannot be adequately assessed with cell-based assays. To address this issue, we developed a lanthanide-doped nanoparticle method that allows quantitative comparison of multiple targeted nanoparticles simultaneously. Specifically, superparamagnetic iron oxide (SPIO) nanoparticles with different targeting ligands were created, each with a unique lanthanide dopant. Following the simultaneous injection of the various SPIO compositions into tumor-bearing mice, inductively coupled plasma mass spectroscopy was used to quantitatively and orthogonally assess the concentration of each SPIO composition in serial blood and resected tumor samples. PMID:25068300

Photon mass attenuation coefficients, effective atomic numbers and electron densities of some thermoluminescent dosimetric compounds

NASA Astrophysics Data System (ADS)

Gowda, Shivalinge; Krishnaveni, S.; Yashoda, T.; Umesh, T. K.; Gowda, Ramakrishna

2004-09-01

Photon mass attenuation coefficients of some thermoluminescent dosimetric (TLD) compounds, such as LiF, CaCO_3, CaSO_4, CaSO_4\\cdot2H_2O, SrSO_4, CdSO_4, BaSO_4, C_4H_6BaO_4 and 3CdSO_4\\cdot8H_2O were determined at 279.2, 320.07, 514.0, 661.6, 1115.5, 1173.2 and 1332.5 keV in a well-collimated narrow beam good geometry set-up using a high resolution, hyper pure germanium detector. The attenuation coefficient data were then used to compute the effective atomic number and the electron density of TLD compounds. The interpolation of total attenuation cross-sections of photons of energy E in elements of atomic number Z was performed using the logarithmic regression analysis of the data measured by the authors and reported earlier. The best-fit coefficients so obtained in the photon energy range of 279.2 to 320.07 keV, 514.0 to 661.6 keV and 1115.5 to 1332.5 keV by a piece-wise interpolation method were then used to find the effective atomic number and electron density of the compounds. These values are found to be in agreement with other available published values.

Application of targeted quantitative proteomics analysis in human cerebrospinal fluid using a liquid chromatography matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometer (LC MALDI TOF/TOF) platform.

PubMed

Pan, Sheng; Rush, John; Peskind, Elaine R; Galasko, Douglas; Chung, Kathryn; Quinn, Joseph; Jankovic, Joseph; Leverenz, James B; Zabetian, Cyrus; Pan, Catherine; Wang, Yan; Oh, Jung Hun; Gao, Jean; Zhang, Jianpeng; Montine, Thomas; Zhang, Jing

2008-02-01

Targeted quantitative proteomics by mass spectrometry aims to selectively detect one or a panel of peptides/proteins in a complex sample and is particularly appealing for novel biomarker verification/validation because it does not require specific antibodies. Here, we demonstrated the application of targeted quantitative proteomics in searching, identifying, and quantifying selected peptides in human cerebrospinal spinal fluid (CSF) using a matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometer (MALDI TOF/TOF)-based platform. The approach involved two major components: the use of isotopic-labeled synthetic peptides as references for targeted identification and quantification and a highly selective mass spectrometric analysis based on the unique characteristics of the MALDI instrument. The platform provides high confidence for targeted peptide detection in a complex system and can potentially be developed into a high-throughput system. Using the liquid chromatography (LC) MALDI TOF/TOF platform and the complementary identification strategy, we were able to selectively identify and quantify a panel of targeted peptides in the whole proteome of CSF without prior depletion of abundant proteins. The effectiveness and robustness of the approach associated with different sample complexity, sample preparation strategies, as well as mass spectrometric quantification were evaluated. Other issues related to chromatography separation and the feasibility for high-throughput analysis were also discussed. Finally, we applied targeted quantitative proteomics to analyze a subset of previously identified candidate markers in CSF samples of patients with Parkinson's disease (PD) at different stages and Alzheimer's disease (AD) along with normal controls.

Fast tandem mass spectra-based protein identification regardless of the number of spectra or potential modifications examined.

PubMed

Falkner, Jayson; Andrews, Philip

2005-05-15

Comparing tandem mass spectra (MSMS) against a known dataset of protein sequences is a common method for identifying unknown proteins; however, the processing of MSMS by current software often limits certain applications, including comprehensive coverage of post-translational modifications, non-specific searches and real-time searches to allow result-dependent instrument control. This problem deserves attention as new mass spectrometers provide the ability for higher throughput and as known protein datasets rapidly grow in size. New software algorithms need to be devised in order to address the performance issues of conventional MSMS protein dataset-based protein identification. This paper describes a novel algorithm based on converting a collection of monoisotopic, centroided spectra to a new data structure, named 'peptide finite state machine' (PFSM), which may be used to rapidly search a known dataset of protein sequences, regardless of the number of spectra searched or the number of potential modifications examined. The algorithm is verified using a set of commercially available tryptic digest protein standards analyzed using an ABI 4700 MALDI TOFTOF mass spectrometer, and a free, open source PFSM implementation. It is illustrated that a PFSM can accurately search large collections of spectra against large datasets of protein sequences (e.g. NCBI nr) using a regular desktop PC; however, this paper only details the method for identifying peptide and subsequently protein candidates from a dataset of known protein sequences. The concept of using a PFSM as a peptide pre-screening technique for MSMS-based search engines is validated by using PFSM with Mascot and XTandem. Complete source code, documentation and examples for the reference PFSM implementation are freely available at the Proteome Commons, http://www.proteomecommons.org and source code may be used both commercially and non-commercially as long as the original authors are credited for their work.

Attentional Control via Parallel Target-Templates in Dual-Target Search

PubMed Central

Barrett, Doug J. K.; Zobay, Oliver

2014-01-01

Simultaneous search for two targets has been shown to be slower and less accurate than independent searches for the same two targets. Recent research suggests this ‘dual-target cost’ may be attributable to a limit in the number of target-templates than can guide search at any one time. The current study investigated this possibility by comparing behavioural responses during single- and dual-target searches for targets defined by their orientation. The results revealed an increase in reaction times for dual- compared to single-target searches that was largely independent of the number of items in the display. Response accuracy also decreased on dual- compared to single-target searches: dual-target accuracy was higher than predicted by a model restricting search guidance to a single target-template and lower than predicted by a model simulating two independent single-target searches. These results are consistent with a parallel model of dual-target search in which attentional control is exerted by more than one target-template at a time. The requirement to maintain two target-templates simultaneously, however, appears to impose a reduction in the specificity of the memory representation that guides search for each target. PMID:24489793

Breakup and fusion cross sections of the 6Li nucleus with targets of mass A = 58, 144 and 208

NASA Astrophysics Data System (ADS)

Mukeru, B.; Rampho, G. J.; Lekala, M. L.

2018-04-01

We use the continuum discretized coupled channels method to investigate the effects of continuum-continuum coupling on the breakup and fusion cross sections of the weakly bound 6Li nucleus with the 58Ni, 144Sm and 208Pb nuclear targets. The cross sections were analyzed at incident energies E cm below, close to and above the Coulomb barrier V B. We found that for the medium and heavy targets, the breakup cross sections are enhanced at energies below the Coulomb barrier (E cm/V B ≤ 0.8) owing to these couplings. For the lighter target, relatively small enhancement of the breakup cross sections appear at energies well below the barrier (E cm/V B ≤ 0.6). At energies E cm/V B > 0.8 for medium and heavy targets, and E cm/V B > 0.6 for the light target, the continuum-continuum couplings substantially suppress the breakup cross sections. On the other hand, the fusion cross sections are enhanced at energies E cm/V B < 1.4, E cm/V B < 1.2 and E cm/V B < 0.8 for the light, medium and heavy target, respectively. The enhancement decreases as the target mass increases. Above the indicated respective energies, these couplings suppress the fusion cross sections. We also compared the breakup and fusion cross sections, and found that below the barrier, the breakup cross sections are more dominant regardless of whether continuum-continuum couplings are included.

Simultaneous quantification of protein phosphorylation sites using liquid chromatography-tandem mass spectrometry-based targeted proteomics: a linear algebra approach for isobaric phosphopeptides.

PubMed

Xu, Feifei; Yang, Ting; Sheng, Yuan; Zhong, Ting; Yang, Mi; Chen, Yun

2014-12-05

As one of the most studied post-translational modifications (PTM), protein phosphorylation plays an essential role in almost all cellular processes. Current methods are able to predict and determine thousands of phosphorylation sites, whereas stoichiometric quantification of these sites is still challenging. Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS)-based targeted proteomics is emerging as a promising technique for site-specific quantification of protein phosphorylation using proteolytic peptides as surrogates of proteins. However, several issues may limit its application, one of which relates to the phosphopeptides with different phosphorylation sites and the same mass (i.e., isobaric phosphopeptides). While employment of site-specific product ions allows for these isobaric phosphopeptides to be distinguished and quantified, site-specific product ions are often absent or weak in tandem mass spectra. In this study, linear algebra algorithms were employed as an add-on to targeted proteomics to retrieve information on individual phosphopeptides from their common spectra. To achieve this simultaneous quantification, a LC-MS/MS-based targeted proteomics assay was first developed and validated for each phosphopeptide. Given the slope and intercept of calibration curves of phosphopeptides in each transition, linear algebraic equations were developed. Using a series of mock mixtures prepared with varying concentrations of each phosphopeptide, the reliability of the approach to quantify isobaric phosphopeptides containing multiple phosphorylation sites (≥ 2) was discussed. Finally, we applied this approach to determine the phosphorylation stoichiometry of heat shock protein 27 (HSP27) at Ser78 and Ser82 in breast cancer cells and tissue samples.

Specter: linear deconvolution for targeted analysis of data-independent acquisition mass spectrometry proteomics.

PubMed

Peckner, Ryan; Myers, Samuel A; Jacome, Alvaro Sebastian Vaca; Egertson, Jarrett D; Abelin, Jennifer G; MacCoss, Michael J; Carr, Steven A; Jaffe, Jacob D

2018-05-01

Mass spectrometry with data-independent acquisition (DIA) is a promising method to improve the comprehensiveness and reproducibility of targeted and discovery proteomics, in theory by systematically measuring all peptide precursors in a biological sample. However, the analytical challenges involved in discriminating between peptides with similar sequences in convoluted spectra have limited its applicability in important cases, such as the detection of single-nucleotide polymorphisms (SNPs) and alternative site localizations in phosphoproteomics data. We report Specter (https://github.com/rpeckner-broad/Specter), an open-source software tool that uses linear algebra to deconvolute DIA mixture spectra directly through comparison to a spectral library, thus circumventing the problems associated with typical fragment-correlation-based approaches. We validate the sensitivity of Specter and its performance relative to that of other methods, and show that Specter is able to successfully analyze cases involving highly similar peptides that are typically challenging for DIA analysis methods.

WE-G-BRE-03: Dose Painting by Numbers Using Targeted Gold Nanoparticles

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

Altundal, Y; Sajo, E; Korideck, H

Purpose: Homogeneous dose enhancement in tumor cells of lung cancer patients treated with conventional dose of 60–66 Gy in five fractions is limited due to increased risk of toxicity to normal structures. Dose painting by numbers (DPBN) is the prescription of a non-uniform radiation dose distribution in the tumor for each voxel based on the intensity level of that voxel obtained from the tumor image. The purpose of this study is to show that DPBN using targeted gold nanoparticles (GNPs) could enhance conventional doses in the more resistant tumor areas. Methods: Cone beam computed tomography (CBCT) images of GNPs aftermore » intratumoral injection into human tumor were taken at 0, 48, 144 and 160 hours. The dose enhancement in the tumor voxels by secondary electrons from the GNPs was calculated based on analytical microdosimetry methods. The dose enhancement factor (DEF) is the ratio of the doses to the tumor with and without the presence of GNPs. The DEF was calculated for each voxel of the images based on the GNP concentration in the tumor sub-volumes using 6-MV photon spectra obtained using Monte Carlo simulations at 5 cm depth (10×10 cm2 field). Results: The results revealed DEF values of 1.05–2.38 for GNPs concentrations of 1–30 mg/g which corresponds to 12.60 – 28.56 Gy per fraction for delivering 12 Gy per fraction homogenously to lung tumor region. Conclusion: Our preliminary results verify that DPBN could be achieved using GNPs to enhance conventional doses to high risk tumor sub-volumes. In practice, DPBN using GNPs could be achieved due to diffusion of targeted GNPs sustainably released in-situ from radiotherapy biomaterials (e.g. fiducials) coated with polymer film containing the GNPs.« less

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

Targeted next-generation sequencing at copy-number breakpoints for personalized analysis of rearranged ends in solid tumors.

PubMed

Kim, Hyun-Kyoung; Park, Won Cheol; Lee, Kwang Man; Hwang, Hai-Li; Park, Seong-Yeol; Sorn, Sungbin; Chandra, Vishal; Kim, Kwang Gi; Yoon, Woong-Bae; Bae, Joon Seol; Shin, Hyoung Doo; Shin, Jong-Yeon; Seoh, Ju-Young; Kim, Jong-Il; Hong, Kyeong-Man

2014-01-01

The concept of the utilization of rearranged ends for development of personalized biomarkers has attracted much attention owing to its clinical applicability. Although targeted next-generation sequencing (NGS) for recurrent rearrangements has been successful in hematologic malignancies, its application to solid tumors is problematic due to the paucity of recurrent translocations. However, copy-number breakpoints (CNBs), which are abundant in solid tumors, can be utilized for identification of rearranged ends. As a proof of concept, we performed targeted next-generation sequencing at copy-number breakpoints (TNGS-CNB) in nine colon cancer cases including seven primary cancers and two cell lines, COLO205 and SW620. For deduction of CNBs, we developed a novel competitive single-nucleotide polymorphism (cSNP) microarray method entailing CNB-region refinement by competitor DNA. Using TNGS-CNB, 19 specific rearrangements out of 91 CNBs (20.9%) were identified, and two polymerase chain reaction (PCR)-amplifiable rearrangements were obtained in six cases (66.7%). And significantly, TNGS-CNB, with its high positive identification rate (82.6%) of PCR-amplifiable rearrangements at candidate sites (19/23), just from filtering of aligned sequences, requires little effort for validation. Our results indicate that TNGS-CNB, with its utility for identification of rearrangements in solid tumors, can be successfully applied in the clinical laboratory for cancer-relapse and therapy-response monitoring.

Analysis of Method TO-14 target analytes using a cryofocusing high-speed gas chromatograph interfaced to a high-speed time-of-flight mass spectrometer

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

Berkley, R.E.; Gardner, B.D.; Holland, J.F.

1997-12-31

A high-speed gas chromatograph coupled with a high-speed time-of-flight mass spectrometer was used to gain a six-fold increase in overall rate of analytical throughput for analysis of EPA Method TO-14 target compounds. Duration of chromatograms was 180 seconds. One hundred mass spectra per second, ranging from 35 to 270 mass units, were collected. Single ion chromatograms were searched at appropriate retention times for chromatographic peaks, which were integrated. Thirty-eight of the forty-one TO-14 target compounds were calibrated using standards at five concentrations from 2.5 to 40 ppb. Four grab samples of ambient air were collected at four different locations atmore » an automobile repair facility, and two grab samples were collected less than one minute apart at a site near a chemical plant, just before and just after passage of three large diesel trucks. All samples were analyzed on the same day they were collected. Most of the duplicate analyses were in close agreement. Ability of the high-speed TOF/GC/MS system to perform analyses of TO-14 target compounds rapidly and precisely was demonstrated. This paper has been reviewed according to US Environmental Protection Agency peer and administrative review policies and approved for presentation and publication. Mention of trade names or commercial products does not constitute endorsement or recommendation for use.« less

Changes in the number of eggs loaded in Pantala flavescens females with age from mass flights (Odonata: Libellulidae).

PubMed

Ichikawa, Yuta; Watanabe, Mamoru

2014-11-01

The wandering glider dragonfly Pantala flavescens migrates to Japan every spring, where the population increases until autumn, in which mass flights often occur, followed by death in the winter. There have been no reports to date on the maturation process of this species throughout its lifespan in Japan. We collected females from mass flights when the flight height was low, and classified them into seven age stages by examining their wing condition. Very few females of the older stage were collected from the mass flights. The wing condition corresponded with the change in body color and with the egg production process in the ovaries. While pre-reproductive-stage females did not release eggs when treated with our artificial oviposition technique, each reproductive-stage female released about 640 eggs. Nearly all eggs released were fertilized. The ovaries developed with the stage, and reproductive-stage females had about 1100 ovarioles. The estimated maximum fecundity was about 29,000 eggs. The lifetime number of eggs laid of P. flavescens should be revealed by dissection.

A novel approach for copy number variation analysis by combining multiplex PCR with matrix-assisted laser desorption ionization time-of-flight mass spectrometry.

PubMed

Gao, Yonghui; Chen, Xiaoli; Wang, Jianhua; Shangguan, Shaofang; Dai, Yaohua; Zhang, Ting; Liu, Junling

2013-06-20

With the increasing interest in copy number variation as it pertains to human genomic variation, common phenotypes, and disease susceptibility, there is a pressing need for methods to accurately identify copy number. In this study, we developed a simple approach that combines multiplex PCR with matrix-assisted laser desorption ionization time-of-flight mass spectrometry for submicroscopic copy number variation detection. Two pairs of primers were used to simultaneously amplify query and endogenous control regions in the same reaction. Using a base extension reaction, the two amplicons were then distinguished and quantified in a mass spectrometry map. The peak ratio between the test region and the endogenous control region was manually calculated. The relative copy number could be determined by comparing the peak ratio between the test and control samples. This method generated a copy number measurement comparable to those produced by two other commonly used methods - multiplex ligation-dependent probe amplification and quantitative real-time PCR. Furthermore, it can discriminate a wide range of copy numbers. With a typical 384-format SpectroCHIP, at least six loci on 384 samples can be analyzed simultaneously in a hexaplex assay, making this assay adaptable for high throughput, and potentially applicable for large-scale association studies. Copyright © 2013 Elsevier B.V. All rights reserved.

Target Characterization and Follow-Up Observations in Support of the Kepler Mission

NASA Technical Reports Server (NTRS)

Latham, David W.

2003-01-01

A variety of experiments were carried out to investigate the number and characteristics of the stars to be included in the Kepler Input Catalog. One result of this work was the proposal that the 2MASS Catalog of astrometry and photometry in the infrared be used as the primary source for the initial selection of candidate target stars, because this would naturally decrease the number of unsuitable hot blue stars and would also increase the number of desirable solar-type dwarf stars. Another advantage of the 2MASS catalogue is that the stellar positions have more than adequate astrometric accuracy for the Kepler target selection. The original plan reported in the Concept Study Report was to use the parallaxes and multi-band photometry from the FAME mission to provide the information needed for reliable separation of giants and dwarfs. As a result of NASA's withdrawal of support for FAME an alternate approach was needed. In November 2002 we proposed to the Kepler Science Team that a ground-based multi-band photometric survey could help alleviate the loss of the FAME data. The Science Team supported this proposal strongly, and we undertook a survey of possible facilities for such a survey. We concluded that the SAO's 4Shooter CCD camera on the 1.2-m telescope at the Whipple Observatory on Mount Hopkins, Arizona, showed promise for this work.

LipidPioneer: A Comprehensive User-Generated Exact Mass Template for Lipidomics

PubMed Central

Ulmer, Candice Z.; Koelmel, Jeremy P.; Ragland, Jared M.; Garrett, Timothy J.

2017-01-01

Lipidomics, the comprehensive measurement of lipid species in a biological system, has promising potential in biomarker discovery and disease etiology elucidation. Advances in chromatographic separation, mass spectrometric techniques, and novel substrate applications continue to expand the number of lipid species observed. The total number and type of lipid species detected in a given sample are generally indicative of the sample matrix examined (e.g. serum, plasma, cells, bacteria, tissue, etc.). Current exact mass lipid libraries are static and represent the most commonly analyzed matrices. It is common practice for users to manually curate their own lists of lipid species and adduct masses; however, this process is time-consuming. LipidPioneer, an interactive template, can be used to generate exact masses and molecular formulas of lipid species that may be encountered in the mass spectrometric analysis of lipid profiles. Over 60 lipid classes are present in the LipidPioneer template, and include several unique lipid species, such as ether-linked lipids and lipid oxidation products. In the template, users can add any fatty acyl constituents without limitation in the number of carbons or degrees of unsaturation. LipidPioneer accepts naming using the lipid class level (sum composition) and the LIPID MAPS notation for fatty acyl structure level. In addition to lipid identification, user generated lipid m/z values can be used to develop inclusion lists for targeted fragmentation experiments. Resulting lipid names and m/z values can be imported into software such as MZmine or Compound Discoverer to automate exact mass searching and isotopic pattern matching across experimental data. PMID:28074328

Distribution of volumes of individual glomeruli in kidneys at autopsy: association with age, nephron number, birth weight and body mass index.

PubMed

Hoy, W E; Hughson, M D; Zimanyi, M; Samuel, T; Douglas-Denton, R; Holden, L; Mott, S; Bertram, J F

2010-11-01

Glomerular hypertrophy occurs in a number of normal and pathological states. Glomerular volume in kidneys at autopsy is usually indirectly derived from estimates of total glomerular mass and nephron number, and provides only a single value per kidney, with no indication of the range of volumes of glomeruli within the kidney of any given subject. We review findings of the distribution of volumes of different glomeruli within subjects without kidney disease, and their correlations with age, nephron number, birth weight and body mass index (BMI). The study describes findings from autopsy kidneys of selected adult white males from the Southeast USA who had unexpected deaths, and who did not have renal scarring or renal disease. Total glomerular (nephron) number and total glomerular volume were estimated using the disector/fractionator combination, and mean glomerular volume (Vglom) was derived. The volumes of 30 individual glomeruli (IGV) in each subject were determined using the disector/Cavalieri method. IGV values were compared by categories of age, nephron number, birth weight and BMI. There was substantial variation in IGV within subjects. Older age, lower nephron number, lower birth weight and gross obesity were associated with higher mean IGV and with greater IGV heterogeneity. High Vglom and high IGVs were associated with more glomerulosclerosis. However, amongst the generally modest numbers of sclerosed glomeruli, the pattern was uniformly of ischemic collapse of the glomerular tuft. There was no detectable focal segmental glomerular tuft injury. In this series of people without overt renal disease, greater age, nephron deficit, lower birth weight and obesity were marked by glomerular enlargement and greater glomerular volume heterogeneity within individuals.

Seedling root targets

Treesearch

Diane L. Haase

2011-01-01

Roots are critical to seedling performance after outplanting. Although root quality is not as quick and simple to measure as shoot quality, target root characteristics should be included in any seedling quality assessment program. This paper provides a brief review of root characteristics most commonly targeted for operational seedling production. These are: root mass...

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…

Differential response to targeted recruitment strategies to fitness promotion research by African-American women of varying body mass index.

PubMed

Yancey, A K; Miles, O L; McCarthy, W J; Sandoval, G; Hill, J; Leslie, J J; Harrison, G G

2001-01-01

To assess patterns of recruitment into a community-based NCI-funded physical activity and dietary lifestyle change program targeting African-American women. Acquisition of a convenience sample to be screened for participation in a randomized, controlled prevention intervention. African-American-owned and -operated health club located in an area of Los Angeles in which African Americans are concentrated. 893 African-American women. RECRUITMENT STRATEGIES: Social networking/word-of-mouth, staff presentations, mass and targeted media, and physician referral. Completion of screening questionnaire indicating a desire to enroll in the study. Screening questionnaire domains included self-reported height and weight, recent participation in organized weight loss programs, ability to walk one mile unassisted, current medication use, smoking status, personal medical history of cancer, sociodemographic variables, and recruitment source. Sociodemographic and anthropometric characteristics distinguished between respondents obtained through different recruitment strategies. In particular, women with a higher body mass index (BMI) were more likely than those with lower BMIs (P = .014) to be recruited through more personalized methods (eg, social networking). Culturally tailored recruitment strategies are critical in securing the participation of members of "hard-to-reach" populations, who are both under-represented in health promotion research and at high risk for chronic diseases.

Studies on mass attenuation coefficient, effective atomic number and electron density of some thermoluminescent dosimetric compounds

NASA Astrophysics Data System (ADS)

Önder, P.; Turşucu, A.; Demir, D.; Gürol, A.

2012-12-01

Mass attenuation coefficient, μm , effective atomic number, Zeff, and effective electron density, Nel, were determined experimentally and theoretically for some thermoluminescent dosimetric (TLD) compounds such as MgSO4, CdSO4, Al2O3, Mg2SiO4, ZnSO4, CaSO4, CaF2, NaSO4, Na4P2O7, Ca5F(PO4)3, SiO2, CaCO3 and BaSO4 at 8.04, 8.91, 13.37, 14.97, 17.44, 19.63, 22.10, 24.90, 30.82, 32.06, 35.40, 36.39, 37.26, 43.74, 44.48, 50.38, 51.70, 53.16, 80.99, 276.40, 302.85, 356.01, 383.85 and 661.66 keV photon energies by using an HPGe detector with a resolution of 182 eV at 5.9 keV. The theoretical mass attenuation coefficients were estimated using mixture rule. The calculated values were compared with the experimental values for all compounds. Good agreement has been observed between experimental and theoretical values within experimental uncertainties.

A novel approach to transforming a non-targeted metabolic profiling method to a pseudo-targeted method using the retention time locking gas chromatography/mass spectrometry-selected ions monitoring.

PubMed

Li, Yong; Ruan, Qiang; Li, Yanli; Ye, Guozhu; Lu, Xin; Lin, Xiaohui; Xu, Guowang

2012-09-14

Non-targeted metabolic profiling is the most widely used method for metabolomics. In this paper, a novel approach was established to transform a non-targeted metabolic profiling method to a pseudo-targeted method using the retention time locking gas chromatography/mass spectrometry-selected ion monitoring (RTL-GC/MS-SIM). To achieve this transformation, an algorithm based on the automated mass spectral deconvolution and identification system (AMDIS), GC/MS raw data and a bi-Gaussian chromatographic peak model was developed. The established GC/MS-SIM method was compared with GC/MS-full scan (the total ion current and extracted ion current, TIC and EIC) methods, it was found that for a typical tobacco leaf extract, 93% components had their relative standard deviations (RSDs) of relative peak areas less than 20% by the SIM method, while 88% by the EIC method and 81% by the TIC method. 47.3% components had their linear correlation coefficient higher than 0.99, compared with 5.0% by the EIC and 6.2% by TIC methods. Multivariate analysis showed the pooled quality control samples clustered more tightly using the developed method than using GC/MS-full scan methods, indicating a better data quality. With the analysis of the variance of the tobacco samples from three different planting regions, 167 differential components (p<0.05) were screened out using the RTL-GC/MS-SIM method, but 151 and 131 by the EIC and TIC methods, respectively. The results show that the developed method not only has a higher sensitivity, better linearity and data quality, but also does not need complicated peak alignment among different samples. It is especially suitable for the screening of differential components in the metabolic profiling investigation. Copyright © 2012 Elsevier B.V. All rights reserved.

Effects of a Televised Two-City Safer Sex Mass Media Campaign Targeting High-Sensation-Seeking and Impulsive-Decision-Making Young Adults

PubMed Central

Zimmerman, Rick S.; Palmgreen, Philip M.; Noar, Seth M.; Lustria, Mia Liza A.; Lu, Hung-Yi; Horosewski, Mary Lee

2015-01-01

This study evaluates the ability of a safer sex televised public service announcement (PSA) campaign to increase safer sexual behavior among at-risk young adults. Independent, monthly random samples of 100 individuals were surveyed in each city for 21 months as part of an interrupted-time-series design with a control community. The 3-month high-audience-saturation campaign took place in Lexington, KY, with Knoxville, TN, as a comparison city. Messages were especially designed and selected for the target audience (those above the median on a composite sensation-seeking/impulsive-decision-making scale). Data indicate high campaign exposure among the target audience, with 85%–96% reporting viewing one or more PSAs. Analyses indicate significant 5-month increases in condom use, condom-use self-efficacy, and behavioral intentions among the target group in the campaign city with no changes in the comparison city. The results suggest that a carefully targeted, intensive mass media campaign using televised PSAs can change safer sexual behaviors. PMID:17602097

Decision-level fusion of SAR and IR sensor information for automatic target detection

NASA Astrophysics Data System (ADS)

Cho, Young-Rae; Yim, Sung-Hyuk; Cho, Hyun-Woong; Won, Jin-Ju; Song, Woo-Jin; Kim, So-Hyeon

2017-05-01

We propose a decision-level architecture that combines synthetic aperture radar (SAR) and an infrared (IR) sensor for automatic target detection. We present a new size-based feature, called target-silhouette to reduce the number of false alarms produced by the conventional target-detection algorithm. Boolean Map Visual Theory is used to combine a pair of SAR and IR images to generate the target-enhanced map. Then basic belief assignment is used to transform this map into a belief map. The detection results of sensors are combined to build the target-silhouette map. We integrate the fusion mass and the target-silhouette map on the decision level to exclude false alarms. The proposed algorithm is evaluated using a SAR and IR synthetic database generated by SE-WORKBENCH simulator, and compared with conventional algorithms. The proposed fusion scheme achieves higher detection rate and lower false alarm rate than the conventional algorithms.

The gut microbiota regulates bone mass in mice

PubMed Central

Sjögren, Klara; Engdahl, Cecilia; Henning, Petra; Lerner, Ulf H; Tremaroli, Valentina; Lagerquist, Marie K; Bäckhed, Fredrik; Ohlsson, Claes

2012-01-01

The gut microbiota modulates host metabolism and development of immune status. Here we show that the gut microbiota is also a major regulator of bone mass in mice. Germ-free (GF) mice exhibit increased bone mass associated with reduced number of osteoclasts per bone surface compared with conventionally raised (CONV-R) mice. Colonization of GF mice with a normal gut microbiota normalizes bone mass. Furthermore, GF mice have decreased frequency of CD4+ T cells and CD11b+/GR 1 osteoclast precursor cells in bone marrow, which could be normalized by colonization. GF mice exhibited reduced expression of inflammatory cytokines in bone and bone marrow compared with CONV-R mice. In summary, the gut microbiota regulates bone mass in mice, and we provide evidence for a mechanism involving altered immune status in bone and thereby affected osteoclast-mediated bone resorption. Further studies are required to evaluate the gut microbiota as a novel therapeutic target for osteoporosis. © 2012 American Society for Bone and Mineral Research. PMID:22407806

Effect of added mass on the interaction of bubbles in a low-Reynolds-number shear flow.

PubMed

Lavrenteva, Olga; Prakash, Jai; Nir, Avinoam

2016-02-01

Equal size air bubbles that are entrapped by a Taylor vortex of the secondary flow in a Couette device, thereby defying buoyancy, slowly form a stable ordered ring with equal separation distances between all neighbors. We present two models of the process dynamics based on force balance on a bubble in the presence of other bubbles positioned on the same streamline in a simple shear flow. The forces taken into account are the viscous resistance, the added mass force, and the inertia-induced repulsing force between two bubbles in a low-Reynolds-number shear flow obtained in Prakash et al. [J. Prakash et al., Phys. Rev. E 87, 043002 (2013)]. The first model of the process assumes that each bubble interacts solely with its nearest neighbors. The second model takes into account pairwise interactions among all the bubbles in the ring. The performed dynamic simulations were compared to the experimental results reported in Prakash et al. [J. Prakash et al., Phys. Rev. E 87, 043002 (2013)] and to the results of quasistationary models (ignoring the added mass effect) suggested in that paper. It is demonstrated that taking into account the effect of added mass, the models describe the major effect of the bubbles' ordering, provide good estimation of the relaxation time, and also predict nonmonotonic behavior of the separation distance between the bubbles, which exhibit over- and undershooting of equilibrium separations. The latter effects were observed in experiments, but are not predicted by the quasistationary models.

Counterforce Targeting Capabilities and Challenges

DTIC Science & Technology

2004-08-01

COUNTERFORCE TARGETING CAPABILITIES AND CHALLENGES by Barry R. Schneider The Counterproliferation Papers Future Warfare Series No. 22 USAF...TITLE AND SUBTITLE Counterforce Targeting Capabilities and Challenges 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d...Rev. 8-98) Prescribed by ANSI Std Z39-18 Counterforce Targeting Capabilities and Challenges Barry R. Schneider August 2004 The Counterproliferation

CRISPR/Cas9-mediated gene knockout is insensitive to target copy number but is dependent on guide RNA potency and Cas9/sgRNA threshold expression level

PubMed Central

Yuen, Garmen; Khan, Fehad J.; Gao, Shaojian; Stommel, Jayne M.; Batchelor, Eric; Wu, Xiaolin

2017-01-01

Abstract CRISPR/Cas9 is a powerful gene editing tool for gene knockout studies and functional genomic screens. Successful implementation of CRISPR often requires Cas9 to elicit efficient target knockout in a population of cells. In this study, we investigated the role of several key factors, including variation in target copy number, inherent potency of sgRNA guides, and expression level of Cas9 and sgRNA, in determining CRISPR knockout efficiency. Using isogenic, clonal cell lines with variable copy numbers of an EGFP transgene, we discovered that CRISPR knockout is relatively insensitive to target copy number, but is highly dependent on the potency of the sgRNA guide sequence. Kinetic analysis revealed that most target mutation occurs between 5 and 10 days following Cas9/sgRNA transduction, while sgRNAs with different potencies differ by their knockout time course and by their terminal-phase knockout efficiency. We showed that prolonged, low level expression of Cas9 and sgRNA often fails to elicit target mutation, particularly if the potency of the sgRNA is also low. Our findings provide new insights into the behavior of CRISPR/Cas9 in mammalian cells that could be used for future improvement of this platform. PMID:29036671

CRISPR/Cas9-mediated gene knockout is insensitive to target copy number but is dependent on guide RNA potency and Cas9/sgRNA threshold expression level.

PubMed

Yuen, Garmen; Khan, Fehad J; Gao, Shaojian; Stommel, Jayne M; Batchelor, Eric; Wu, Xiaolin; Luo, Ji

2017-11-16

CRISPR/Cas9 is a powerful gene editing tool for gene knockout studies and functional genomic screens. Successful implementation of CRISPR often requires Cas9 to elicit efficient target knockout in a population of cells. In this study, we investigated the role of several key factors, including variation in target copy number, inherent potency of sgRNA guides, and expression level of Cas9 and sgRNA, in determining CRISPR knockout efficiency. Using isogenic, clonal cell lines with variable copy numbers of an EGFP transgene, we discovered that CRISPR knockout is relatively insensitive to target copy number, but is highly dependent on the potency of the sgRNA guide sequence. Kinetic analysis revealed that most target mutation occurs between 5 and 10 days following Cas9/sgRNA transduction, while sgRNAs with different potencies differ by their knockout time course and by their terminal-phase knockout efficiency. We showed that prolonged, low level expression of Cas9 and sgRNA often fails to elicit target mutation, particularly if the potency of the sgRNA is also low. Our findings provide new insights into the behavior of CRISPR/Cas9 in mammalian cells that could be used for future improvement of this platform. Published by Oxford University Press on behalf of Nucleic Acids Research 2017.

Mapping the Substellar Mass-Luminosity Relation Down to the L/T Transition

NASA Astrophysics Data System (ADS)

Dupuy, Trent

2016-10-01

Substellar models underpin our theoretical understanding of brown dwarfs and gas-giant exoplanets, so assessing their accuracy is paramount. The past several years have seen progress in testing models thanks to a growing number of dynamical (total) masses for brown dwarf binaries determined via (relative) orbit monitoring from ground-based AO. However, the strongest tests of models require individual masses, particularly for calibrating the mass-luminosity relation. This is poorly constrained over the range of spectral types most influenced by clouds (mid-L to early-T). Given the observed prevalence of clouds in the atmospheres of directly imaged planets, testing models at such temperatures is crucial.We propose a 3-year program to obtain individual masses for a sample of 11 substellar binaries. Our proposal builds on nearly a decade of orbital monitoring from the ground to measure dynamical total masses. Our goal is thus to measure precise mass ratios, utilizing HST's unique wide-field, high-angular resolution astrometric capabilities. We will obtain WFC3-UVIS images capturing our targets and numerous reference stars so that we can measure the relative amount of orbital motion in each component to determine mass ratios. Three of our targets have I-band photocenter orbits measured at USNO and VLT and thus only require one epoch of resolved I-band imaging to unlock individual masses. We will use this first large sample of substellar individual masses to map out the mass-luminosity relation over a wide range of temperatures (1000-2000 K) including the L/T transition. This will become a touchstone sample for tests of ultracool atmospheric models in the era of JWST.

Mapping the Substellar Mass-Luminosity Relation Down to the L/T Transition

NASA Astrophysics Data System (ADS)

Dupuy, Trent

2017-08-01

Substellar models underpin our theoretical understanding of brown dwarfs and gas-giant exoplanets, so assessing their accuracy is paramount. The past several years have seen progress in testing models thanks to a growing number of dynamical (total) masses for brown dwarf binaries determined via (relative) orbit monitoring from ground-based AO. However, the strongest tests of models require individual masses, particularly for calibrating the mass-luminosity relation. This is poorly constrained over the range of spectral types most influenced by clouds (mid-L to early-T). Given the observed prevalence of clouds in the atmospheres of directly imaged planets, testing models at such temperatures is crucial.We propose a 3-year program to obtain individual masses for a sample of 11 substellar binaries. Our proposal builds on nearly a decade of orbital monitoring from the ground to measure dynamical total masses. Our goal is thus to measure precise mass ratios, utilizing HST's unique wide-field, high-angular resolution astrometric capabilities. We will obtain WFC3-UVIS images capturing our targets and numerous reference stars so that we can measure the relative amount of orbital motion in each component to determine mass ratios. Three of our targets have I-band photocenter orbits measured at USNO and VLT and thus only require one epoch of resolved I-band imaging to unlock individual masses. We will use this first large sample of substellar individual masses to map out the mass-luminosity relation over a wide range of temperatures (1000-2000 K) including the L/T transition. This will become a touchstone sample for tests of ultracool atmospheric models in the era of JWST.

The Effect of Stiffness Parameter on Mass Distribution in Heavy-Ion Induced Fission

NASA Astrophysics Data System (ADS)

Soheyli, Saeed; Khalil Khalili, Morteza; Ashrafi, Ghazaaleh

2018-06-01

The stiffness parameter of the composite system has been studied for several heavy-ion induced fission reactions without the contribution of non-compound nucleus fission events. In this research, determination of the stiffness parameter is based on the comparison between the experimental data on the mass widths of fission fragments and those predicted by the statistical model treatments at the saddle and scission points. Analysis of the results shows that for the induced fission reactions of different targets by the same projectile, the stiffness parameter of the composite system decreases with increasing the fissility parameter, as well as with increasing the mass number of the compound nucleus. This parameter also exhibits a similar behavior for the reactions of a given target induced by different projectiles. As expected, nearly same stiffness values are obtained for different reactions leading to the same compound nucleus.

Target productions in forward and backward hemispheres in the interactions of 28Si-EM at 14.6A GeV

NASA Astrophysics Data System (ADS)

Abdelsalam, A.; El-Nagdy, M. S.; Abdalla, A. M.; Saber, A.

2015-11-01

This paper search for the results and properties of slow particle productions, appear as a gray and black tracks in nuclear emulsions, producing secondary charged particles which are emitted from 28Si interactions with emulsion nuclei at 14.6A GeV. The forward particles emission of interactions, (θlab<90∘) as well as the backward ones (θlab≥90∘), have been investigated. It includes the effect of both projectile mass number and energy on the production and multiplicities of these particles. The results compared with other experiments for the same target but with different projectiles and energies. The experimental data show that there are two different mechanisms responsible for the production of gray particles for the chosen channels of emission angles and each are energy dependence. This dependence is weakly on the projectile mass number. The same investigations are applied for black tracks producing particles. The experimental results show the production of these particles is purely target fragments independent on both projectile mass number and its energy. The anisotropy ratio of angular distribution (F/B) is applied for both kinds of particles which are found the value for gray particle production depends on the direction of emissions while it is unchanged for black particles.

Revised Stellar Properties of Kepler Targets for the Q1-17 (DR25) Transit Detection Run

NASA Astrophysics Data System (ADS)

Mathur, Savita; Huber, Daniel; Batalha, Natalie M.; Ciardi, David R.; Bastien, Fabienne A.; Bieryla, Allyson; Buchhave, Lars A.; Cochran, William D.; Endl, Michael; Esquerdo, Gilbert A.; Furlan, Elise; Howard, Andrew; Howell, Steve B.; Isaacson, Howard; Latham, David W.; MacQueen, Phillip J.; Silva, David R.

2017-04-01

The determination of exoplanet properties and occurrence rates using Kepler data critically depends on our knowledge of the fundamental properties (such as temperature, radius, and mass) of the observed stars. We present revised stellar properties for 197,096 Kepler targets observed between Quarters 1–17 (Q1-17), which were used for the final transiting planet search run by the Kepler Mission (Data Release 25, DR25). Similar to the Q1–16 catalog by Huber et al., the classifications are based on conditioning published atmospheric parameters on a grid of Dartmouth isochrones, with significant improvements in the adopted method and over 29,000 new sources for temperatures, surface gravities, or metallicities. In addition to fundamental stellar properties, the new catalog also includes distances and extinctions, and we provide posterior samples for each stellar parameter of each star. Typical uncertainties are ∼27% in radius, ∼17% in mass, and ∼51% in density, which is somewhat smaller than previous catalogs because of the larger number of improved {log}g constraints and the inclusion of isochrone weighting when deriving stellar posterior distributions. On average, the catalog includes a significantly larger number of evolved solar-type stars, with an increase of 43.5% in the number of subgiants. We discuss the overall changes of radii and masses of Kepler targets as a function of spectral type, with a particular focus on exoplanet host stars.

Validation of highly sensitive simultaneous targeted and untargeted analysis of keto-steroids by Girard P derivatization and stable isotope dilution-liquid chromatography-high resolution mass spectrometry.

PubMed

Frey, Alexander J; Wang, Qingqing; Busch, Christine; Feldman, Daniel; Bottalico, Lisa; Mesaros, Clementina A; Blair, Ian A; Vachani, Anil; Snyder, Nathaniel W

2016-12-01

A multiplexed quantitative method for the analysis of three major unconjugated steroids in human serum by stable isotope dilution liquid chromatography-high resolution mass spectrometry (LC-HRMS) was developed and validated on a Q Exactive Plus hybrid quadrupole/Orbitrap mass spectrometer. This quantification utilized isotope dilution and Girard P derivatization on the keto-groups of testosterone (T), androstenedione (AD) and dehydroepiandrosterone (DHEA) to improve ionization efficiency using electrospray ionization. Major isomeric compounds to T and DHEA; the inactive epimer of testosterone (epiT), and the metabolite of AD, 5α-androstanedione (5α-AD) were completely resolved on a biphenyl column within an 18min method. Inter- and intra-day method validation using LC-HRMS with qualifying product ions was performed and acceptable analytical performance was achieved. The method was further validated by comparing steroid levels from 100μL of serum from young vs older subjects. Since this approach provides high-dimensional HRMS data, untargeted analysis by age group was performed. DHEA and T were detected among the top analytes most significantly different across the two groups after untargeted LC-HRMS analysis, as well as a number of other still unknown metabolites, indicating the potential for combined targeted/untargeted analysis in steroid analysis. Copyright © 2016 Elsevier Inc. All rights reserved.

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

Nonlinear excitation of the ablative Rayleigh-Taylor instability for all wave numbers

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

Zhang, H.; Betti, R.; Gopalaswamy, V.

Small-scale perturbations in the ablative Rayleigh-Taylor instability (ARTI) are often neglected because they are linearly stable when their wavelength is shorter than a linear cutoff. Using 2D and 3D numerical simulations, it is shown that linearly stable modes of any wavelength can be destabilized. This instability regime requires finite amplitude initial perturbations and linearly stable ARTI modes are more easily destabilized in 3D than in 2D. In conclusion, it is shown that for conditions found in laser fusion targets, short wavelength ARTI modes are more efficient at driving mixing of ablated material throughout the target since the nonlinear bubble densitymore » increases with the wave number and small scale bubbles carry a larger mass flux of mixed material.« less

Nonlinear excitation of the ablative Rayleigh-Taylor instability for all wave numbers

DOE PAGES

Zhang, H.; Betti, R.; Gopalaswamy, V.; ...

2018-01-16

Small-scale perturbations in the ablative Rayleigh-Taylor instability (ARTI) are often neglected because they are linearly stable when their wavelength is shorter than a linear cutoff. Using 2D and 3D numerical simulations, it is shown that linearly stable modes of any wavelength can be destabilized. This instability regime requires finite amplitude initial perturbations and linearly stable ARTI modes are more easily destabilized in 3D than in 2D. In conclusion, it is shown that for conditions found in laser fusion targets, short wavelength ARTI modes are more efficient at driving mixing of ablated material throughout the target since the nonlinear bubble densitymore » increases with the wave number and small scale bubbles carry a larger mass flux of mixed material.« less

Measurements of mass attenuation coefficient, effective atomic number and electron density of some amino acids

NASA Astrophysics Data System (ADS)

Kore, Prashant S.; Pawar, Pravina P.

2014-05-01

The mass attenuation coefficients of some amino acids, such as DL-aspartic acid-LR(C4H7NO4), L-glutamine (C4H10N2O3), creatine monohydrate LR(C4H9N3O2H2O), creatinine hydrochloride (C4H7N3O·HCl) L-asparagine monohydrate(C4H9N3O2H2O), L-methionine LR(C5H11NO2S), were measured at 122, 356, 511, 662, 1170, 1275 and 1330 keV photon energies using a well-collimated narrow beam good geometry set-up. The gamma-rays were detected using NaI (Tl) scintillation detection system with a resolution of 0.101785 at 662 keV. The attenuation coefficient data were then used to obtain the effective atomic numbers (Zeff), and effective electron densities (Neff) of amino acids. It was observed that the effective atomic number (Zeff) and effective electron densities (Neff) initially decrease and tend to be almost constant as a function of gamma-ray energy. Zeff and Neff experimental values showed good agreement with the theoretical values with less than 1% error for amino acids.

Discriminating quantum-optical beam-splitter channels with number-diagonal signal states: Applications to quantum reading and target detection

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

Nair, Ranjith

2011-09-15

We consider the problem of distinguishing, with minimum probability of error, two optical beam-splitter channels with unequal complex-valued reflectivities using general quantum probe states entangled over M signal and M' idler mode pairs of which the signal modes are bounced off the beam splitter while the idler modes are retained losslessly. We obtain a lower bound on the output state fidelity valid for any pure input state. We define number-diagonal signal (NDS) states to be input states whose density operator in the signal modes is diagonal in the multimode number basis. For such input states, we derive series formulas formore » the optimal error probability, the output state fidelity, and the Chernoff-type upper bounds on the error probability. For the special cases of quantum reading of a classical digital memory and target detection (for which the reflectivities are real valued), we show that for a given input signal photon probability distribution, the fidelity is minimized by the NDS states with that distribution and that for a given average total signal energy N{sub s}, the fidelity is minimized by any multimode Fock state with N{sub s} total signal photons. For reading of an ideal memory, it is shown that Fock state inputs minimize the Chernoff bound. For target detection under high-loss conditions, a no-go result showing the lack of appreciable quantum advantage over coherent state transmitters is derived. A comparison of the error probability performance for quantum reading of number state and two-mode squeezed vacuum state (or EPR state) transmitters relative to coherent state transmitters is presented for various values of the reflectances. While the nonclassical states in general perform better than the coherent state, the quantitative performance gains differ depending on the values of the reflectances. The experimental outlook for realizing nonclassical gains from number state transmitters with current technology at moderate to high values of

Preparation and Immunoaffinity Depletion of Fresh Frozen Tissue Homogenates for Mass Spectrometry-Based Proteomics in the Context of Drug Target/Biomarker Discovery.

PubMed

Prieto, DaRue A; Chan, King C; Johann, Donald J; Ye, Xiaoying; Whitely, Gordon; Blonder, Josip

2017-01-01

The discovery of novel drug targets and biomarkers via mass spectrometry (MS)-based proteomic analysis of clinical specimens has proven to be challenging. The wide dynamic range of protein concentration in clinical specimens and the high background/noise originating from highly abundant proteins in tissue homogenates and serum/plasma encompass two major analytical obstacles. Immunoaffinity depletion of highly abundant blood-derived proteins from serum/plasma is a well-established approach adopted by numerous researchers; however, the utilization of this technique for immunodepletion of tissue homogenates obtained from fresh frozen clinical specimens is lacking. We first developed immunoaffinity depletion of highly abundant blood-derived proteins from tissue homogenates, using renal cell carcinoma as a model disease, and followed this study by applying it to different tissue types. Tissue homogenate immunoaffinity depletion of highly abundant proteins may be equally important as is the recognized need for depletion of serum/plasma, enabling more sensitive MS-based discovery of novel drug targets, and/or clinical biomarkers from complex clinical samples. Provided is a detailed protocol designed to guide the researcher through the preparation and immunoaffinity depletion of fresh frozen tissue homogenates for two-dimensional liquid chromatography, tandem mass spectrometry (2D-LC-MS/MS)-based molecular profiling of tissue specimens in the context of drug target and/or biomarker discovery.

Development of vacuum ultraviolet absorption spectroscopy system for wide measurement range of number density using a dual-tube inductively coupled plasma light source

NASA Astrophysics Data System (ADS)

Kuwahara, Akira; Matsui, Makoto; Yamagiwa, Yoshiki

2012-12-01

A vacuum ultraviolet absorption spectroscopy system for a wide measurement range of atomic number densities is developed. Dual-tube inductively coupled plasma was used as a light source. The probe beam profile was optimized for the target number density range by changing the mass flow rate of the inner and outer tubes. This system was verified using cold xenon gas. As a result, the measurement number density range was extended from the conventional two orders to five orders of magnitude.

Widely-targeted quantitative lipidomics methodology by supercritical fluid chromatography coupled with fast-scanning triple quadrupole mass spectrometry.

PubMed

Takeda, Hiroaki; Izumi, Yoshihiro; Takahashi, Masatomo; Paxton, Thanai; Tamura, Shohei; Koike, Tomonari; Yu, Ying; Kato, Noriko; Nagase, Katsutoshi; Shiomi, Masashi; Bamba, Takeshi

2018-05-03

Lipidomics, the mass spectrometry-based comprehensive analysis of lipids, has attracted attention as an analytical approach to provide novel insight into lipid metabolism and to search for biomarkers. However, an ideal method for both comprehensive and quantitative analysis of lipids has not been fully developed. Herein, we have proposed a practical methodology for widely-targeted quantitative lipidome analysis using supercritical fluid chromatography fast-scanning triple-quadrupole mass spectrometry (SFC/QqQMS) and theoretically calculated a comprehensive lipid multiple reaction monitoring (MRM) library. Lipid classes can be separated by SFC with a normal phase diethylamine-bonded silica column with high-resolution, high-throughput, and good repeatability. Structural isomers of phospholipids can be monitored by mass spectrometric separation with fatty acyl-based MRM transitions. SFC/QqQMS analysis with an internal standard-dilution method offers quantitative information for both lipid class and individual lipid molecular species in the same lipid class. Additionally, data acquired using this method has advantages including reduction of misidentification and acceleration of data analysis. Using the SFC/QqQMS system, alteration of plasma lipid levels in myocardial infarction-prone rabbits to the supplementation of eicosapentaenoic acid was first observed. Our developed SFC/QqQMS method represents a potentially useful tool for in-depth studies focused on complex lipid metabolism and biomarker discovery. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

Competing features influence children's attention to number.

PubMed

Chan, Jenny Yun-Chen; Mazzocco, Michèle M M

2017-04-01

Spontaneous focus on numerosity (SFON), an attentional process that some consider distinct from number knowledge, predicts later mathematical skills. Here we assessed the "spontaneity" and malleability of SFON using a picture-matching task. We asked children to view a target picture and to choose which of four other pictures matched the target. We tested whether attention to number (defined as number-based matches) was affected by (a) age, (b) the presence of very noticeable (or salient) features among alternative match choices, and (c) the examiner's use of motor actions to emphasize numerosity. Although adults attended to number more frequently than did preschoolers, the salience of competing features affected responses to number in both age groups. Specifically, number-based matches were more likely when alternative choices matched the target on features of low versus high salience (e.g., the relative location within a picture frame vs. color). In addition, adults' attention to number was more frequent if their first exposure to number-based matches occurred with alternative choices that matched the target on low salience features. This order by salience interaction was not observed among children. Simply observing motor actions that emphasized number (i.e., tapping stimuli) did not enhance children's attention to number. The results extend previous findings on SFON and provide evidence for the contextual influences on, and malleability of, attention to number. Copyright © 2016 Elsevier Inc. All rights reserved.

Elliptic flow of ϕ mesons at intermediate pT: Influence of mass versus quark number

NASA Astrophysics Data System (ADS)

Choudhury, Subikash; Sarkar, Debojit; Chattopadhyay, Subhasis

2017-02-01

We have studied elliptic flow (v2) of ϕ mesons in the framework of a multiphase transport (AMPT) model at CERN Large Hadron Collider (LHC) energy. In the realms of AMPT model we observe that ϕ mesons at intermediate transverse momentum (pT) deviate from the previously observed [at the BNL Relativistic Heavy Ion Collider (RHIC)] particle type grouping of v2 according to the number of quark content, i.e, baryons and mesons. Recent results from the ALICE Collaboration have shown that ϕ meson and proton v2 has a similar trend, possibly indicating that particle type grouping might be due to the mass of the particles and not the quark content. A stronger radial boost at LHC compared to RHIC seems to offer a consistent explanation to such observation. However, recalling that ϕ mesons decouple from the hadronic medium before additional radial flow is built up in the hadronic phase, a similar pattern in ϕ meson and proton v2 may not be due to radial flow alone. Our study reveals that models incorporating ϕ -meson production from K K ¯ fusion in the hadronic rescattering phase also predict a comparable magnitude of ϕ meson and proton v2 particularly in the intermediate region of pT. Whereas, v2 of ϕ mesons created in the partonic phase is in agreement with quark-coalescence motivated baryon-meson grouping of hadron v2. This observation seems to provide a plausible alternative interpretation for the apparent mass-like behavior of ϕ -meson v2. We have also observed a violation of hydrodynamical mass ordering between proton and ϕ meson v2 further supporting that ϕ mesons are negligibly affected by the collective radial flow in the hadronic phase due to the small in-medium hadronic interaction cross sections.

Assessment of targeted automated messages on herpes zoster immunization numbers in an independent community pharmacy.

PubMed

Bedwick, Brian W; Garofoli, Gretchen K; Elswick, Betsy M

To evaluate the impact of an automated phone call by a pharmacy owner on the number of herpes zoster vaccinations given in the independent community pharmacy setting, compare herpes zoster immunization numbers in the 3 months during the previous year to the 3 months during the intervention, and assess patient satisfaction with the automated phone call service. This prospective study took place in an independent community pharmacy. A message was recorded by the pharmacy owner using a telephone-message program that notified patients aged 60 and older that the herpes zoster vaccine is recommended for them. This message was sent out monthly for a total of 3 months. Patients who received this vaccine in the 3 months following the initial phone call were surveyed to determine their reason for receiving the vaccine, and to assess satisfaction with the phone call. The total number of herpes zoster immunizations given at the pharmacy during the study period was compared to the total given at the pharmacy during the same period of the previous year. A total of 25 participants received the herpes zoster vaccine at the pharmacy during the study period, compared to 16 during the control period. Receiving the phone call was the most commonly cited reason for receiving the vaccine, followed by doctor recommendation. Of the 18 participants who received the call, 12 stated that they would be very likely to respond to similar phone calls in the future. These results demonstrate that using a targeted, automated phone call directed at eligible patients appears to have a positive effect on their willingness to receive the herpes zoster vaccine and may lead to an increase in vaccination numbers among eligible patients. Various factors must be considered before implementation of this service, including cost and added call volume. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Absolute Quantification of Middle- to High-Abundant Plasma Proteins via Targeted Proteomics.

PubMed

Dittrich, Julia; Ceglarek, Uta

2017-01-01

The increasing number of peptide and protein biomarker candidates requires expeditious and reliable quantification strategies. The utilization of liquid chromatography coupled to quadrupole tandem mass spectrometry (LC-MS/MS) for the absolute quantitation of plasma proteins and peptides facilitates the multiplexed verification of tens to hundreds of biomarkers from smallest sample quantities. Targeted proteomics assays derived from bottom-up proteomics principles rely on the identification and analysis of proteotypic peptides formed in an enzymatic digestion of the target protein. This protocol proposes a procedure for the establishment of a targeted absolute quantitation method for middle- to high-abundant plasma proteins waiving depletion or enrichment steps. Essential topics as proteotypic peptide identification and LC-MS/MS method development as well as sample preparation and calibration strategies are described in detail.

Halobacterium salinarum NRC-1 PeptideAtlas: toward strategies for targeted proteomics and improved proteome coverage.

PubMed

Van, Phu T; Schmid, Amy K; King, Nichole L; Kaur, Amardeep; Pan, Min; Whitehead, Kenia; Koide, Tie; Facciotti, Marc T; Goo, Young Ah; Deutsch, Eric W; Reiss, David J; Mallick, Parag; Baliga, Nitin S

2008-09-01

The relatively small numbers of proteins and fewer possible post-translational modifications in microbes provide a unique opportunity to comprehensively characterize their dynamic proteomes. We have constructed a PeptideAtlas (PA) covering 62.7% of the predicted proteome of the extremely halophilic archaeon Halobacterium salinarum NRC-1 by compiling approximately 636 000 tandem mass spectra from 497 mass spectrometry runs in 88 experiments. Analysis of the PA with respect to biophysical properties of constituent peptides, functional properties of parent proteins of detected peptides, and performance of different mass spectrometry approaches has highlighted plausible strategies for improving proteome coverage and selecting signature peptides for targeted proteomics. Notably, discovery of a significant correlation between absolute abundances of mRNAs and proteins has helped identify low abundance of proteins as the major limitation in peptide detection. Furthermore, we have discovered that iTRAQ labeling for quantitative proteomic analysis introduces a significant bias in peptide detection by mass spectrometry. Therefore, despite identifying at least one proteotypic peptide for almost all proteins in the PA, a context-dependent selection of proteotypic peptides appears to be the most effective approach for targeted proteomics.

Study of mass attenuation coefficients and effective atomic numbers of bismuth-ground granulated blast furnace slag concretes

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

Kumar, Sandeep, E-mail: sandeep0078monu@gmail.com; Singh, Sukhpal, E-mail: sukhpal-78@rediffmail.com

2016-05-06

Five samples of Bismuth-Ground granulated blast furnace slag (Bi-GGBFS) concretes were prepared using composition (0.6 cement + x Bi{sub 2}O{sub 3} + (0.4-x) GGBFS, x = 0.05, 0.10, 0.15, 0.20 and 0.25) by keeping constant water (W) cement (C) ratio. Mass attenuation coefficients (μ{sub m}) of these prepared samples were calculated using a computer program winXCOM at different gamma ray energies, whereas effective atomic numbers (Z{sub eff}) is calculated using mathematical formulas. The radiation shielding properties of Bi-GGBFS concrete has been compared with standard radiation shielding concretes.

Cuban Mass Media: Organization, Control and Functions. Journalism Monographs Number Seventy-Eight.

ERIC Educational Resources Information Center

Nichols, John Spicer

The mass media as interdependent parts of a larger social system both control and are controlled by other subsystems. The various combinations of control, in turn, determine the functions the media system will serve. In the 1960's, the Cuban mass media underwent frequent change that reflected the volatility of the revolutionary process. Today,…

Specific targeting of TGF-β family ligands demonstrates distinct roles in the regulation of muscle mass in health and disease.

PubMed

Chen, Justin L; Walton, Kelly L; Hagg, Adam; Colgan, Timothy D; Johnson, Katharine; Qian, Hongwei; Gregorevic, Paul; Harrison, Craig A

2017-06-27

The transforming growth factor-β (TGF-β) network of ligands and intracellular signaling proteins is a subject of intense interest within the field of skeletal muscle biology. To define the relative contribution of endogenous TGF-β proteins to the negative regulation of muscle mass via their activation of the Smad2/3 signaling axis, we used local injection of adeno-associated viral vectors (AAVs) encoding ligand-specific antagonists into the tibialis anterior (TA) muscles of C57BL/6 mice. Eight weeks after AAV injection, inhibition of activin A and activin B signaling produced moderate (∼20%), but significant, increases in TA mass, indicating that endogenous activins repress muscle growth. Inhibiting myostatin induced a more profound increase in muscle mass (∼45%), demonstrating a more prominent role for this ligand as a negative regulator of adult muscle mass. Remarkably, codelivery of activin and myostatin inhibitors induced a synergistic response, resulting in muscle mass increasing by as much as 150%. Transcription and protein analysis indicated that this substantial hypertrophy was associated with both the complete inhibition of the Smad2/3 pathway and activation of the parallel bone morphogenetic protein (BMP)/Smad1/5 axis (recently identified as a positive regulator of muscle mass). Analyses indicated that hypertrophy was primarily driven by an increase in protein synthesis, but a reduction in ubiquitin-dependent protein degradation pathways was also observed. In models of muscular dystrophy and cancer cachexia, combined inhibition of activins and myostatin increased mass or prevented muscle wasting, respectively, highlighting the potential therapeutic advantages of specifically targeting multiple Smad2/3-activating ligands in skeletal muscle.

Specific targeting of TGF-β family ligands demonstrates distinct roles in the regulation of muscle mass in health and disease

PubMed Central

Chen, Justin L.; Walton, Kelly L.; Hagg, Adam; Colgan, Timothy D.; Johnson, Katharine; Qian, Hongwei; Gregorevic, Paul; Harrison, Craig A.

2017-01-01

The transforming growth factor-β (TGF-β) network of ligands and intracellular signaling proteins is a subject of intense interest within the field of skeletal muscle biology. To define the relative contribution of endogenous TGF-β proteins to the negative regulation of muscle mass via their activation of the Smad2/3 signaling axis, we used local injection of adeno-associated viral vectors (AAVs) encoding ligand-specific antagonists into the tibialis anterior (TA) muscles of C57BL/6 mice. Eight weeks after AAV injection, inhibition of activin A and activin B signaling produced moderate (∼20%), but significant, increases in TA mass, indicating that endogenous activins repress muscle growth. Inhibiting myostatin induced a more profound increase in muscle mass (∼45%), demonstrating a more prominent role for this ligand as a negative regulator of adult muscle mass. Remarkably, codelivery of activin and myostatin inhibitors induced a synergistic response, resulting in muscle mass increasing by as much as 150%. Transcription and protein analysis indicated that this substantial hypertrophy was associated with both the complete inhibition of the Smad2/3 pathway and activation of the parallel bone morphogenetic protein (BMP)/Smad1/5 axis (recently identified as a positive regulator of muscle mass). Analyses indicated that hypertrophy was primarily driven by an increase in protein synthesis, but a reduction in ubiquitin-dependent protein degradation pathways was also observed. In models of muscular dystrophy and cancer cachexia, combined inhibition of activins and myostatin increased mass or prevented muscle wasting, respectively, highlighting the potential therapeutic advantages of specifically targeting multiple Smad2/3-activating ligands in skeletal muscle. PMID:28607086

Insights into neutrino decoupling gleaned from considerations of the role of electron mass

NASA Astrophysics Data System (ADS)

Grohs, E.; Fuller, George M.

2017-10-01

We present calculations showing how electron rest mass influences entropy flow, neutrino decoupling, and Big Bang Nucleosynthesis (BBN) in the early universe. To elucidate this physics and especially the sensitivity of BBN and related epochs to electron mass, we consider a parameter space of rest mass values larger and smaller than the accepted vacuum value. Electromagnetic equilibrium, coupled with the high entropy of the early universe, guarantees that significant numbers of electron-positron pairs are present, and dominate over the number of ionization electrons to temperatures much lower than the vacuum electron rest mass. Scattering between the electrons-positrons and the neutrinos largely controls the flow of entropy from the plasma into the neutrino seas. Moreover, the number density of electron-positron-pair targets can be exponentially sensitive to the effective in-medium electron mass. This entropy flow influences the phasing of scale factor and temperature, the charged current weak-interaction-determined neutron-to-proton ratio, and the spectral distortions in the relic neutrino energy spectra. Our calculations show the sensitivity of the physics of this epoch to three separate effects: finite electron mass, finite-temperature quantum electrodynamic (QED) effects on the plasma equation of state, and Boltzmann neutrino energy transport. The ratio of neutrino to plasma-component energy scales manifests in Cosmic Microwave Background (CMB) observables, namely the baryon density and the radiation energy density, along with the primordial helium and deuterium abundances. Our results demonstrate how the treatment of in-medium electron mass (i.e., QED effects) could translate into an important source of uncertainty in extracting neutrino and beyond-standard-model physics limits from future high-precision CMB data.

Increased Body Mass Index Associated with Increased Risky Sexual Behaviors

PubMed Central

Gordon, Lonna P.; Diaz, Angela; Soghomonian, Christine; Nucci-Sack, Anne T.; Weiss, Jocelyn M.; Strickler, Howard D.; Burk, Robert D.; Schlecht, Nicolas F.; Ochner, Christopher N.

2015-01-01

Study Objective The increasing prevalence of adolescent obesity has led to consideration of the potential effect of obesity on risky sexual behaviors. The current study examined whether body mass index (BMI) was related to age at sexual debut, type of sexual behavior, partner number, and condom use in a population of adolescent women at high risk for obesity and risky sexual behaviors. Study Design Cross-sectional examination of 860 sexually active, predominantly minority, adolescent women who received medical care at an urban health center from 2007 – 2013. Intervention Self-reported age at sexual debut, types of sexual intercourse, number of partners and condom use was compared to clinically – assessed BMI. Results Body mass index was positively associated with number of sexual partners (p = 0.001) and history of attempted anal intercourse (p = 0.002). An inverse association was observed with age at first anal intercourse (p = 0.040). Conclusions In this sample of adolescent women, increased BMI was associated with riskier sexual practices at a younger age. This study suggests that overweight and obese adolescents are a vulnerable population who may need targeted sexual health counseling. PMID:26358938

The Mass Distribution of Stellar-mass Black Holes

NASA Astrophysics Data System (ADS)

Farr, Will M.; Sravan, Niharika; Cantrell, Andrew; Kreidberg, Laura; Bailyn, Charles D.; Mandel, Ilya; Kalogera, Vicky

2011-11-01

We perform a Bayesian analysis of the mass distribution of stellar-mass black holes using the observed masses of 15 low-mass X-ray binary systems undergoing Roche lobe overflow and 5 high-mass, wind-fed X-ray binary systems. Using Markov Chain Monte Carlo calculations, we model the mass distribution both parametrically—as a power law, exponential, Gaussian, combination of two Gaussians, or log-normal distribution—and non-parametrically—as histograms with varying numbers of bins. We provide confidence bounds on the shape of the mass distribution in the context of each model and compare the models with each other by calculating their relative Bayesian evidence as supported by the measurements, taking into account the number of degrees of freedom of each model. The mass distribution of the low-mass systems is best fit by a power law, while the distribution of the combined sample is best fit by the exponential model. This difference indicates that the low-mass subsample is not consistent with being drawn from the distribution of the combined population. We examine the existence of a "gap" between the most massive neutron stars and the least massive black holes by considering the value, M 1%, of the 1% quantile from each black hole mass distribution as the lower bound of black hole masses. Our analysis generates posterior distributions for M 1%; the best model (the power law) fitted to the low-mass systems has a distribution of lower bounds with M 1%>4.3 M sun with 90% confidence, while the best model (the exponential) fitted to all 20 systems has M 1%>4.5 M sun with 90% confidence. We conclude that our sample of black hole masses provides strong evidence of a gap between the maximum neutron star mass and the lower bound on black hole masses. Our results on the low-mass sample are in qualitative agreement with those of Ozel et al., although our broad model selection analysis more reliably reveals the best-fit quantitative description of the underlying mass

A Method to Estimate the Atomic Number and Mass Thickness of Intervening Materials in Uranium and Plutonium Gamma-Ray Spectroscopy Measurements

NASA Astrophysics Data System (ADS)

Streicher, Michael; Brown, Steven; Zhu, Yuefeng; Goodman, David; He, Zhong

2016-10-01

To accurately characterize shielded special nuclear materials (SNM) using passive gamma-ray spectroscopy measurement techniques, the effective atomic number and the thickness of shielding materials must be measured. Intervening materials between the source and detector may affect the estimated source isotopics (uranium enrichment and plutonium grade) for techniques which rely on raw count rates or photopeak ratios of gamma-ray lines separated in energy. Furthermore, knowledge of the surrounding materials can provide insight regarding the configuration of a device containing SNM. The described method was developed using spectra recorded using high energy resolution CdZnTe detectors, but can be expanded to any gamma-ray spectrometers with energy resolution of better than 1% FWHM at 662 keV. The effective atomic number, Z, and mass thickness of the intervening shielding material are identified by comparing the relative attenuation of different gamma-ray lines and estimating the proportion of Compton scattering interactions to photoelectric absorptions within the shield. While characteristic Kα x-rays can be used to identify shielding materials made of high Z elements, this method can be applied to all shielding materials. This algorithm has adequately estimated the effective atomic number for shields made of iron, aluminum, and polyethylene surrounding uranium samples using experimental data. The mass thicknesses of shielding materials have been estimated with a standard error of less than 1.3 g/cm2 for iron shields up to 2.5 cm thick. The effective atomic number was accurately estimated to 26 ± 5 for all iron thicknesses.

Copy number variations of obesity relevant loci associated with body mass index in young Chinese.

PubMed

Sun, Chen; Cao, Min; Shi, Juan; Li, Lijuan; Miao, Lin; Hong, Jie; Cui, Bin; Ning, Guang

2013-03-10

Obesity is one of the most complex human diseases that are widely concerned and studied. More recently, copy number variations (CNVs) emerge as another important genetic marker to influence various human diseases. To elucidate the relationship between obesity and CNVs, this current study selected obesity-related candidate CNVs and analyzed their association with body mass index (BMI). Results showed that a CNV locus, 8q24.3, was significantly different (P=0.0070) in CNV frequency between the obese and healthy controls in a young eastern Chinese cohort, while no statistical significance was observed in other seven candidate loci including well reported 10q11.22 and 16p11.2 loci. The association of 8q24.3 CNVs with BMI of the subjects only showed marginal significance, while the copy number (CN) of 5p15.33 had a significant correlation with the BMI of the subject. These results suggested that 8q24.3 CN gains was associated with obesity, and 5p15.33 might also contribute to obesity pathogenesis, highlighting the importance of these CNVs for obesity risks, as well as providing new evidence for CNVs in the pathology of common diseases. Copyright © 2012 Elsevier B.V. All rights reserved.

Determination of the number density of excited and ground Zn atoms during rf magnetron sputtering of ZnO target

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

Maaloul, L.; Gangwar, R. K.; Stafford, L., E-mail: luc.stafford@umontreal.ca

2015-07-15

A combination of optical absorption spectroscopy (OAS) and optical emission spectroscopy measurements was used to monitor the number density of Zn atoms in excited 4s4p ({sup 3}P{sub 2} and {sup 3}P{sub 0}) metastable states as well as in ground 4s{sup 2} ({sup 1}S{sub 0}) state in a 5 mTorr Ar radio-frequency (RF) magnetron sputtering plasma used for the deposition of ZnO-based thin films. OAS measurements revealed an increase by about one order of magnitude of Zn {sup 3}P{sub 2} and {sup 3}P{sub 0} metastable atoms by varying the self-bias voltage on the ZnO target from −115 to −300 V. Over themore » whole range of experimental conditions investigated, the triplet-to-singlet metastable density ratio was 5 ± 1, which matches the statistical weight ratio of these states in Boltzmann equilibrium. Construction of a Boltzmann plot using all Zn I emission lines in the 200–500 nm revealed a constant excitation temperature of 0.33 ± 0.04 eV. In combination with measured populations of Zn {sup 3}P{sub 2} and {sup 3}P{sub 0} metastable atoms, this temperature was used to extrapolate the absolute number density of ground state Zn atoms. The results were found to be in excellent agreement with those obtained previously by actinometry on Zn atoms using Ar as the actinometer gas [L. Maaloul and L. Stafford, J. Vac. Sci. Technol., A 31, 061306 (2013)]. This set of data was then correlated to spectroscopic ellipsometry measurements of the deposition rate of Zn atoms on a Si substrate positioned at 12 cm away from the ZnO target. The deposition rate scaled linearly with the number density of Zn atoms. In sharp contrast with previous studies on RF magnetron sputtering of Cu targets, these findings indicate that metastable atoms play a negligible role on the plasma deposition dynamics of Zn-based coatings.« less

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

Mass media campaign improves cervical screening across all socio-economic groups.

PubMed

Anderson, Jenny O; Mullins, Robyn M; Siahpush, Mohammad; Spittal, Matthew J; Wakefield, Melanie

2009-10-01

Low socio-economic status (SES) has been associated with lower cervical screening rates. Mass media is one known strategy that can increase cervical screening participation. This study sought to determine whether a mass media campaign conducted in Victoria, Australia, in 2005 was effective in encouraging women across all SES groups to screen. Data were obtained from the Victorian Cervical Cytology Registry for each Pap test registered during 2005 and categorized into SES quintiles using the Index of Socio-Economic Advantage/Disadvantage. Negative binomial regression was used to determine the impact of the campaign on the weekly number of Pap tests and whether the media campaign had a differential effect by SES, after adjusting for the number of workdays per week, age group and time since previous test. Cervical screening increased 27% during the campaign period and was equally effective in encouraging screening across all SES groups, including low-SES women. Mass media campaigns can prompt increased rates of cervical screening among all women, not just those from more advantaged areas. Combining media with additional strategies targeted at low-SES women may help lessen the underlying differences in screening rates across SES.

The Frequency of Low-Mass Exoplanets

NASA Astrophysics Data System (ADS)

O'Toole, S. J.; Jones, H. R. A.; Tinney, C. G.; Butler, R. P.; Marcy, G. W.; Carter, B.; Bailey, J.; Wittenmyer, R. A.

2009-08-01

We report first results from the Anglo-Australian Telescope Rocky Planet Search—an intensive, high-precision Doppler planet search targeting low-mass exoplanets in contiguous 48 night observing blocks. On this run, we targeted 24 bright, nearby and intrinsically stable Sun-like stars selected from the Anglo-Australian Planet Search's main sample. These observations have already detected one low-mass planet reported elsewhere (HD 16417b), and here we reconfirm the detection of HD 4308b. Further, we have Monte Carlo simulated data from this run on a star-by-star basis to produce robust detection constraints. These simulations demonstrate clear differences in the exoplanet detectability functions from star to star due to differences in sampling, data quality and intrinsic stellar stability. They reinforce the importance of star-by-star simulation when interpreting the data from Doppler planet searches. These simulations indicate that for some of our target stars we are sensitive to close-orbiting planets as small as a few Earth masses. The two low-mass planets present in our 24-star sample indicate that the exoplanet minimum mass function at low masses is likely to be a flat α ~ -1 (for dN/dM vprop M α) and that between 15% ± 10% (at α = -0.3) and 48% ± 34% (at α = -1.3) of stars host planets with orbital periods of less than 16 days and minimum masses greater than 3 M ⊕.

Cosmological baryon and lepton number in the presence of electroweak fermion-number violation

NASA Technical Reports Server (NTRS)

Harvey, Jeffrey A.; Turner, Michael S.

1990-01-01

In the presence of rapid fermion-number violation due to nonperturbative electroweak effects certain relations between the baryon number of the Universe and the lepton numbers of the Universe are predicted. In some cases the electron-neutrino asymmetry is exactly specified in terms of the baryon asymmetry. Without introducing new particles, beyond the usual quarks and leptons, it is necessary that the Universe possess a nonzero value of B - L prior to the epoch of fermion-number violation if baryon and lepton asymmetries are to survive. Contrary to intuition, even though electroweak processes violate B + L, a nonzero value of B + L persists after the epoch of rapid fermion-number violation. If the standard model is extended to include lepton-number violation, for example through Majorana neutrino masses, then electroweak processes will reduce the baryon number to zero even in the presence of an initial B - L unless 20 M(sub L) approximately greater than the square root of (T(sub B - L) m(sub P1)) where M(sub L) sets the scale of lepton number violation and T(sub B - L) is the temperature at which a B - L asymmetry is produced. In many models this implies that neutrinos must be so light that they cannot contribute appreciably to the mass density of the Universe.

Gold nanoparticle-enhanced target (AuNPET) as universal solution for laser desorption/ionization mass spectrometry analysis and imaging of low molecular weight compounds.

PubMed

Sekuła, Justyna; Nizioł, Joanna; Rode, Wojciech; Ruman, Tomasz

2015-05-22

Preparation is described of a durable surface of cationic gold nanoparticles (AuNPs), covering commercial and custom-made MALDI targets, along with characterization of the nanoparticle surface properties and examples of the use in MS analyses and MS imaging (IMS) of low molecular weight (LMW) organic compounds. Tested compounds include nucleosides, saccharides, amino acids, glycosides, and nucleic bases for MS measurements, as well as over one hundred endogenous compounds in imaging experiment. The nanoparticles covering target plate were enriched in sodium in order to promote sodium-adduct formation. The new surface allows fast analysis, high sensitivity of detection and high mass determination accuracy. Example of application of new Au nanoparticle-enhanced target for fast and simple MS imaging of a fingerprint is also presented. Copyright © 2015 Elsevier B.V. All rights reserved.

Mass spectrometry for biomarker development

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

Wu, Chaochao; Liu, Tao; Baker, Erin Shammel

2015-06-19

Biomarkers potentially play a crucial role in early disease diagnosis, prognosis and targeted therapy. In the past decade, mass spectrometry based proteomics has become increasingly important in biomarker development due to large advances in technology and associated methods. This chapter mainly focuses on the application of broad (e.g. shotgun) proteomics in biomarker discovery and the utility of targeted proteomics in biomarker verification and validation. A range of mass spectrometry methodologies are discussed emphasizing their efficacy in the different stages in biomarker development, with a particular emphasis on blood biomarker development.

Low-end mass function of the Quintuplet cluster

NASA Astrophysics Data System (ADS)

Shin, Jihye; Kim, Sungsoo S.

2016-08-01

The Quintuplet and Arches clusters, which were formed in the harsh environment of the Galactic Centre (GC) a few million years ago, have been excellent targets for studying the effects of a star-forming environment on the initial mass function (IMF). In order to estimate the shape of the low-end IMF of the Arches cluster, Shin & Kim devised a novel photometric method that utilizes pixel intensity histograms (PIHs) of the observed images. Here, we apply the PIH method to the Quintuplet cluster and estimate the shape of its low-end IMF below the magnitude of completeness limit as set by conventional photometry. We found that the low-end IMF of the Quintuplet is consistent with that found for the Arches cluster-Kroupa MF, with a significant number of low-mass stars below 1 M⊙. We conclude that the most likely IMFs of the Quintuplet and the Arches clusters are not too different from the IMFs found in the Galactic disc. We also find that the observed PIHs and stellar number density profiles of both clusters are best reproduced when the clusters are assumed to be at three-dimensional distances of approximately 100 pc from the GC.

Target-decoy Based False Discovery Rate Estimation for Large-scale Metabolite Identification.

PubMed

Wang, Xusheng; Jones, Drew R; Shaw, Timothy I; Cho, Ji-Hoon; Wang, Yuanyuan; Tan, Haiyan; Xie, Boer; Zhou, Suiping; Li, Yuxin; Peng, Junmin

2018-05-23

Metabolite identification is a crucial step in mass spectrometry (MS)-based metabolomics. However, it is still challenging to assess the confidence of assigned metabolites. In this study, we report a novel method for estimating false discovery rate (FDR) of metabolite assignment with a target-decoy strategy, in which the decoys are generated through violating the octet rule of chemistry by adding small odd numbers of hydrogen atoms. The target-decoy strategy was integrated into JUMPm, an automated metabolite identification pipeline for large-scale MS analysis, and was also evaluated with two other metabolomics tools, mzMatch and mzMine 2. The reliability of FDR calculation was examined by false datasets, which were simulated by altering MS1 or MS2 spectra. Finally, we used the JUMPm pipeline coupled with the target-decoy strategy to process unlabeled and stable-isotope labeled metabolomic datasets. The results demonstrate that the target-decoy strategy is a simple and effective method for evaluating the confidence of high-throughput metabolite identification.

Nonlinear Excitation of the Ablative Rayleigh-Taylor Instability for All Wave Numbers

NASA Astrophysics Data System (ADS)

Zhang, H.; Betti, R.; Gopalaswamy, V.; Aluie, H.; Yan, R.

2017-10-01

Small-scale modes of the ablative Rayleigh-Taylor instability (ARTI) are often neglected because they are linearly stable when their wavelength is shorter than a linear cutoff. Using 2-D and 3-D numerical simulations, it is shown that linearly stable modes of any wavelength can be destabilized. This instability regime requires finite amplitude initial perturbations. Compared to 2-D, linearly stable ARTI modes are more easily destabilized in 3-D and the penetrating bubbles have a higher density because of enhanced vorticity. It is shown that for conditions found in laser fusion targets, short-wavelength ARTI modes are more efficient at driving mixing of ablated material throughout the target since the nonlinear bubble density increases with the wave number and small-scale bubbles carry a larger mass flux of mixed material. This work was supported by the Office of Fusion Energy Sciences Nos. DE-FG02-04ER54789, DE-SC0014318, the Department of Energy National Nuclear Security Administration under Award No. DE-NA0001944, the Ministerio de Ciencia e Innovacion of Spain (Grant No. ENE2011-28489), and the NANL LDRD program through Project Number 20150568ER.

Mass spectrometer calibration standard

NASA Technical Reports Server (NTRS)

Ross, D. S.

1978-01-01

Inert perfluorinated alkane and alkyl ethers mixture is used to calibrate mass spectrometer. Noncontaminating, commercially-available liquid provides series of reproducible reference peaks over broad mass spectrum that ranges over mass numbers from 1 to 200.

Mo100 to Mo99 Target Cooling Enhancements Report

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

Woloshun, Keith Albert; Dale, Gregory E.; Olivas, Eric Richard

2016-02-16

Target design requirements changed significantly over the past year to a much higher beam current on larger diameter disks, and with a beam impingement on both ends of the target. Scaling from the previous design, that required significantly more mass flow rate of helium coolant, and also thinner disks. A new Aerzen GM12.4 blower was selected that can deliver up to 400 g/s at 400 psi, compared to about 100 g/s possible with the Tuthill blower previously selected.Further, to accommodate the 42 MeV, 2.7 mA beam on each side of the target, the disk thickness and the coolant gaps weremore » halved to create the current baseline design: 0.5 mm disk thickness (at 29 mm diameter) and 0.25 mm coolant gap. Thermal-hydraulic analysis of this target, presented below for reference, gave very good results, suggesting that the target could be improved with fewer, thicker disks and with disk thickness increasing toward the target center. The total thickness of Mo100 in the target remaining the same, that reduces the number of coolant gaps. This allows for the gap width to be increased, increasing the mass flow in each gap and consequently increasing heat transfer. A preliminary geometry was selected and analyzed with variable disk thickness and wider coolant gaps. The result of analysis of this target shows that disk thickness increase near the window was too aggressive and further resizing of the disks is necessary, but it does illustrate the potential improvements that are possible. Experimental and analytical study of diffusers on the target exit has been done. This shows modest improvement in requcing pressure drop, as will be summarized below. However, the benefit is not significant, and implementation becomes problematic when disk thickness is varying. A bull nose at the entrance does offer significant benefit and is relatively easy to incorporate. A bull nose on both ends is now a feature of the baseline design, and will be a feature of any redesign or enhanced designs

Targeted Mass Spectrometric Approach for Biomarker Discovery and Validation with Nonglycosylated Tryptic Peptides from N-linked Glycoproteins in Human Plasma*

PubMed Central

Lee, Ju Yeon; Kim, Jin Young; Park, Gun Wook; Cheon, Mi Hee; Kwon, Kyung-Hoon; Ahn, Yeong Hee; Moon, Myeong Hee; Lee, Hyoung–Joo; Paik, Young Ki; Yoo, Jong Shin

2011-01-01

A simple mass spectrometric approach for the discovery and validation of biomarkers in human plasma was developed by targeting nonglycosylated tryptic peptides adjacent to glycosylation sites in an N-linked glycoprotein, one of the most important biomarkers for early detection, prognoses, and disease therapies. The discovery and validation of novel biomarkers requires complex sample pretreatment steps, such as depletion of highly abundant proteins, enrichment of desired proteins, or the development of new antibodies. The current study exploited the steric hindrance of glycan units in N-linked glycoproteins, which significantly affects the efficiency of proteolytic digestion if an enzymatically active amino acid is adjacent to the N-linked glycosylation site. Proteolytic digestion then results in quantitatively different peptide products in accordance with the degree of glycosylation. The effect of glycan steric hindrance on tryptic digestion was first demonstrated using alpha-1-acid glycoprotein (AGP) as a model compound versus deglycosylated alpha-1-acid glycoprotein. Second, nonglycosylated tryptic peptide biomarkers, which generally show much higher sensitivity in mass spectrometric analyses than their glycosylated counterparts, were quantified in human hepatocellular carcinoma plasma using a label-free method with no need for N-linked glycoprotein enrichment. Finally, the method was validated using a multiple reaction monitoring analysis, demonstrating that the newly discovered nonglycosylated tryptic peptide targets were present at different levels in normal and hepatocellular carcinoma plasmas. The area under the receiver operating characteristic curve generated through analyses of nonglycosylated tryptic peptide from vitronectin precursor protein was 0.978, the highest observed in a group of patients with hepatocellular carcinoma. This work provides a targeted means of discovering and validating nonglycosylated tryptic peptides as biomarkers in human plasma

Corra: Computational framework and tools for LC-MS discovery and targeted mass spectrometry-based proteomics

PubMed Central

Brusniak, Mi-Youn; Bodenmiller, Bernd; Campbell, David; Cooke, Kelly; Eddes, James; Garbutt, Andrew; Lau, Hollis; Letarte, Simon; Mueller, Lukas N; Sharma, Vagisha; Vitek, Olga; Zhang, Ning; Aebersold, Ruedi; Watts, Julian D

2008-01-01

Background Quantitative proteomics holds great promise for identifying proteins that are differentially abundant between populations representing different physiological or disease states. A range of computational tools is now available for both isotopically labeled and label-free liquid chromatography mass spectrometry (LC-MS) based quantitative proteomics. However, they are generally not comparable to each other in terms of functionality, user interfaces, information input/output, and do not readily facilitate appropriate statistical data analysis. These limitations, along with the array of choices, present a daunting prospect for biologists, and other researchers not trained in bioinformatics, who wish to use LC-MS-based quantitative proteomics. Results We have developed Corra, a computational framework and tools for discovery-based LC-MS proteomics. Corra extends and adapts existing algorithms used for LC-MS-based proteomics, and statistical algorithms, originally developed for microarray data analyses, appropriate for LC-MS data analysis. Corra also adapts software engineering technologies (e.g. Google Web Toolkit, distributed processing) so that computationally intense data processing and statistical analyses can run on a remote server, while the user controls and manages the process from their own computer via a simple web interface. Corra also allows the user to output significantly differentially abundant LC-MS-detected peptide features in a form compatible with subsequent sequence identification via tandem mass spectrometry (MS/MS). We present two case studies to illustrate the application of Corra to commonly performed LC-MS-based biological workflows: a pilot biomarker discovery study of glycoproteins isolated from human plasma samples relevant to type 2 diabetes, and a study in yeast to identify in vivo targets of the protein kinase Ark1 via phosphopeptide profiling. Conclusion The Corra computational framework leverages computational innovation to

Constraining the right-handed gauge boson mass from lepton number violating meson decays in a low scale left-right model

NASA Astrophysics Data System (ADS)

Mandal, Sanjoy; Mitra, Manimala; Sinha, Nita

2017-08-01

We analyze the lepton number violating (LNV) meson decays that arise in a TeV scale left-right symmetry model. The right-handed Majorana neutrino N along with the right-handed or Standard Model gauge bosons mediate the meson decays and provide a resonant enhancement of the rates if the mass of N (MN) lies in the range ˜(100 MeV - 5 GeV ) . Using the expected upper limits on the number of events for the LNV decay modes M1+→ℓ+ℓ+ π- (M1=B,D,Ds, K ), we derive constraints plausible on the mass of the right handed charged gauge boson by future searches at the ongoing NA62 and LHCb experiments at CERN, the upcoming Belle II at SuperKEK, as well as at the proposed future experiments, SHiP and FCC-ee. These bounds are complimentary to the limits from the same-sign dilepton search at the Large Hadron Collider (LHC). The very high intensity of charmed mesons expected to be produced at SHiP will result in a far more stringent bound, MW R>18.4 TeV (corresponding to MN=1.46 GeV ), than the other existing bounds from collider and neutrinoless double beta decay searches.

Gaussian mass optimization for kernel PCA parameters

NASA Astrophysics Data System (ADS)

Liu, Yong; Wang, Zulin

2011-10-01

This paper proposes a novel kernel parameter optimization method based on Gaussian mass, which aims to overcome the current brute force parameter optimization method in a heuristic way. Generally speaking, the choice of kernel parameter should be tightly related to the target objects while the variance between the samples, the most commonly used kernel parameter, doesn't possess much features of the target, which gives birth to Gaussian mass. Gaussian mass defined in this paper has the property of the invariance of rotation and translation and is capable of depicting the edge, topology and shape information. Simulation results show that Gaussian mass leads a promising heuristic optimization boost up for kernel method. In MNIST handwriting database, the recognition rate improves by 1.6% compared with common kernel method without Gaussian mass optimization. Several promising other directions which Gaussian mass might help are also proposed at the end of the paper.

PROPERTIES OF 42 SOLAR-TYPE KEPLER TARGETS FROM THE ASTEROSEISMIC MODELING PORTAL

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

Metcalfe, T. S.; Mathur, S.; Creevey, O. L.

2014-10-01

Recently the number of main-sequence and subgiant stars exhibiting solar-like oscillations that are resolved into individual mode frequencies has increased dramatically. While only a few such data sets were available for detailed modeling just a decade ago, the Kepler mission has produced suitable observations for hundreds of new targets. This rapid expansion in observational capacity has been accompanied by a shift in analysis and modeling strategies to yield uniform sets of derived stellar properties more quickly and easily. We use previously published asteroseismic and spectroscopic data sets to provide a uniform analysis of 42 solar-type Kepler targets from the Asteroseismicmore » Modeling Portal. We find that fitting the individual frequencies typically doubles the precision of the asteroseismic radius, mass, and age compared to grid-based modeling of the global oscillation properties, and improves the precision of the radius and mass by about a factor of three over empirical scaling relations. We demonstrate the utility of the derived properties with several applications.« less

Mass trapping for Anastrepha suspensa

USDA-ARS?s Scientific Manuscript database

Mass trapping has been found to be highly effective for control of pest fruit flies when populations are low and a highly effective lure is available for the target species. Successful population control through mass trapping is an indicator that attract-and-kill bait stations may be equally succes...

Performance evaluation of the multiple-image optical compression and encryption method by increasing the number of target images

NASA Astrophysics Data System (ADS)

Aldossari, M.; Alfalou, A.; Brosseau, C.

2017-08-01

In an earlier study [Opt. Express 22, 22349-22368 (2014)], a compression and encryption method that simultaneous compress and encrypt closely resembling images was proposed and validated. This multiple-image optical compression and encryption (MIOCE) method is based on a special fusion of the different target images spectra in the spectral domain. Now for the purpose of assessing the capacity of the MIOCE method, we would like to evaluate and determine the influence of the number of target images. This analysis allows us to evaluate the performance limitation of this method. To achieve this goal, we use a criterion based on the root-mean-square (RMS) [Opt. Lett. 35, 1914-1916 (2010)] and compression ratio to determine the spectral plane area. Then, the different spectral areas are merged in a single spectrum plane. By choosing specific areas, we can compress together 38 images instead of 26 using the classical MIOCE method. The quality of the reconstructed image is evaluated by making use of the mean-square-error criterion (MSE).

A liquid chromatography-tandem mass spectrometry-based targeted proteomics assay for monitoring P-glycoprotein levels in human breast tissue.

PubMed

Yang, Ting; Chen, Fei; Xu, Feifei; Wang, Fengliang; Xu, Qingqing; Chen, Yun

2014-09-25

P-glycoprotein (P-gp) can efflux drugs from cancer cells, and its overexpression is commonly associated with multi-drug resistance (MDR). Thus, the accurate quantification of P-gp would help predict the response to chemotherapy and for prognosis of breast cancer patients. An advanced liquid chromatography-tandem mass spectrometry (LC/MS/MS)-based targeted proteomics assay was developed and validated for monitoring P-gp levels in breast tissue. Tryptic peptide 368IIDNKPSIDSYSK380 was selected as a surrogate analyte for quantification, and immuno-depleted tissue extract was used as a surrogate matrix. Matched pairs of breast tissue samples from 60 patients who were suspected to have drug resistance were subject to analysis. The levels of P-gp were quantified. Using data from normal tissue, we suggested a P-gp reference interval. The experimental values of tumor tissue samples were compared with those obtained from Western blotting and immunohistochemistry (IHC). The result indicated that the targeted proteomics approach was comparable to IHC but provided a lower limit of quantification (LOQ) and could afford more reliable results at low concentrations than the other two methods. LC/MS/MS-based targeted proteomics may allow the quantification of P-gp in breast tissue in a more accurate manner. Copyright © 2014 Elsevier B.V. All rights reserved.

Overcoming biofluid protein complexity during targeted mass spectrometry detection and quantification of protein biomarkers by MRM cubed (MRM3).

PubMed

Jeudy, Jeremy; Salvador, Arnaud; Simon, Romain; Jaffuel, Aurore; Fonbonne, Catherine; Léonard, Jean-François; Gautier, Jean-Charles; Pasquier, Olivier; Lemoine, Jerome

2014-02-01

Targeted mass spectrometry in the so-called multiple reaction monitoring mode (MRM) is certainly a promising way for the precise, accurate, and multiplexed measurement of proteins and their genetic or posttranslationally modified isoforms. MRM carried out on a low-resolution triple quadrupole instrument faces a lack of specificity when addressing the quantification of weakly concentrated proteins. In this case, extensive sample fractionation or immunoenrichment alleviates signal contamination by interferences, but in turn decreases assay performance and throughput. Recently, MRM(3) was introduced as an alternative to MRM to improve the limit of quantification of weakly concentrated protein biomarkers. In the present work, we compare MRM and MRM(3) modes for the detection of biomarkers in plasma and urine. Calibration curves drawn with MRM and MRM(3) showed a similar range of linearity (R(2) > 0.99 for both methods) with protein concentrations above 1 μg/mL in plasma and a few nanogram per milliliter in urine. In contrast, optimized MRM(3) methods improve the limits of quantification by a factor of 2 to 4 depending on the targeted peptide. This gain arises from the additional MS(3) fragmentation step, which significantly removes or decreases interfering signals within the targeted transition channels.

Mass attenuation coefficients and effective atomic numbers of biological compounds for gamma ray interactions

NASA Astrophysics Data System (ADS)

Gaikwad, Dhammajyot Kundlik; Pawar, Pravina P.; Selvam, T. Palani

2017-09-01

The mass attenuation coefficients (μ/ρ) for some enzymes, proteins, amino acids and fatty acids were measured at 122, 356, 511, 662, 1170, 1275 and 1330 keV photon energies, by performing transmission experiments using 57Co, 133Ba, 137Cs, 60Co and 22Na sources collimated to produce 0.52 cm diameter beams. A NaI (Tl) scintillation detector with energy resolution 8.2% at 663 keV was used for detection. The experimental values of (μ/ρ) were then used to determine the atomic cross section (σa), electronic cross section (σe), effective atomic number (Zeff) and electron density (Neff). It was observed that (μ/ρ), σa and σe decrease initially and then tends to be almost constant at higher energies. Values of Zeff and Neff were observed roughly constant with energy. The deviations in experimental results of radiological parameters were believed to be affected by physical and chemical environments. Experimental results of radiological parameters were observed in good agreement with WinXCom values.

Advances in the Study of Aptamer-Protein Target Identification Using the Chromatographic Approach.

PubMed

Drabik, Anna; Ner-Kluza, Joanna; Mielczarek, Przemyslaw; Civit, Laia; Mayer, Günter; Silberring, Jerzy

2018-06-01

Ever since the development of the process known as the systematic evolution of ligands by exponential enrichment (SELEX), aptamers have been widely used in a variety of studies, including the exploration of new diagnostic tools and the discovery of new treatment methods. Aptamers' ability to bind to proteins with high affinity and specificity, often compared to that of antibodies, enables the search for potential cancer biomarkers and helps us understand the mechanisms of carcinogenesis. The blind spot of those investigations is usually the difficulty in the selective extraction of targets attached to the aptamer. There are many studies describing the cell SELEX for the prime choice of aptamers toward living cancer cells or even whole tumors in the animal models. However, a dilemma arises when a large number of proteins are being identified as potential targets, which is often the case. In this article, we present a new analytical approach designed to selectively target proteins bound to aptamers. During studies, we have focused on the unambiguous identification of the molecular targets of aptamers characterized by high specificity to the prostate cancer cells. We have compared four assay approaches using electrophoretic and chromatographic methods for "fishing out" aptamer protein targets followed by mass spectrometry identification. We have established a new methodology, based on the fluorescent-tagged oligonucleotides commonly used for flow-cytometry experiments or as optic aptasensors, that allowed the detection of specific aptamer-protein interactions by mass spectrometry. The use of atto488-labeled aptamers for the tracking of the formation of specific aptamer-target complexes provides the possibility of studying putative protein counterparts without needing to apply enrichment techniques. Significantly, changes in the hydrophobic properties of atto488-labeled aptamer-protein complexes facilitate their separation by reverse-phase chromatography combined with

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

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.

Mass analyzer ``MASHA'' high temperature target and plasma ion source

NASA Astrophysics Data System (ADS)

Semchenkov, A. G.; Rassadov, D. N.; Bekhterev, V. V.; Bystrov, V. A.; Chizov, A. Yu.; Dmitriev, S. N.; Efremov, A. A.; Guljaev, A. V.; Kozulin, E. M.; Oganessian, Yu. Ts.; Starodub, G. Ya.; Voskresensky, V. M.; Bogomolov, S. L.; Paschenko, S. V.; Zelenak, A.; Tikhonov, V. I.

2004-05-01

A new separator and mass analyzer of super heavy atoms (MASHA) has been created at the FLNR JINR Dubna to separate and measure masses of nuclei and molecules with precision better than 10-3. First experiments with the FEBIAD plasma ion source have been done and give an efficiency of ionization of up to 20% for Kr with a low flow test leak (6 particle μA). We suppose a magnetic field optimization, using the additional electrode (einzel lens type) in the extracting system, and an improving of the vacuum conditions in order to increase the ion source efficiency.

Advanced Automation for Ion Trap Mass Spectrometry-New Opportunities for Real-Time Autonomous Analysis

NASA Technical Reports Server (NTRS)

Palmer, Peter T.; Wong, C. M.; Salmonson, J. D.; Yost, R. A.; Griffin, T. P.; Yates, N. A.; Lawless, James G. (Technical Monitor)

1994-01-01

The utility of MS/MS for both target compound analysis and the structure elucidation of unknowns has been described in a number of references. A broader acceptance of this technique has not yet been realized as it requires large, complex, and costly instrumentation which has not been competitive with more conventional techniques. Recent advancements in ion trap mass spectrometry promise to change this situation. Although the ion trap's small size, sensitivity, and ability to perform multiple stages of mass spectrometry have made it eminently suitable for on-line, real-time monitoring applications, advance automation techniques are required to make these capabilities more accessible to non-experts. Towards this end we have developed custom software for the design and implementation of MS/MS experiments. This software allows the user to take full advantage of the ion trap's versatility with respect to ionization techniques, scan proxies, and ion accumulation/ejection methods. Additionally, expert system software has been developed for autonomous target compound analysis. This software has been linked to ion trap control software and a commercial data system to bring all of the steps in the analysis cycle under control of the expert system. These software development efforts and their utilization for a number of trace analysis applications will be described.

Estimation of surface area concentration of workplace incidental nanoparticles based on number and mass concentrations

NASA Astrophysics Data System (ADS)

Park, J. Y.; Ramachandran, G.; Raynor, P. C.; Kim, S. W.

2011-10-01

Surface area was estimated by three different methods using number and/or mass concentrations obtained from either two or three instruments that are commonly used in the field. The estimated surface area concentrations were compared with reference surface area concentrations (SAREF) calculated from the particle size distributions obtained from a scanning mobility particle sizer and an optical particle counter (OPC). The first estimation method (SAPSD) used particle size distribution measured by a condensation particle counter (CPC) and an OPC. The second method (SAINV1) used an inversion routine based on PM1.0, PM2.5, and number concentrations to reconstruct assumed lognormal size distributions by minimizing the difference between measurements and calculated values. The third method (SAINV2) utilized a simpler inversion method that used PM1.0 and number concentrations to construct a lognormal size distribution with an assumed value of geometric standard deviation. All estimated surface area concentrations were calculated from the reconstructed size distributions. These methods were evaluated using particle measurements obtained in a restaurant, an aluminum die-casting factory, and a diesel engine laboratory. SAPSD was 0.7-1.8 times higher and SAINV1 and SAINV2 were 2.2-8 times higher than SAREF in the restaurant and diesel engine laboratory. In the die casting facility, all estimated surface area concentrations were lower than SAREF. However, the estimated surface area concentration using all three methods had qualitatively similar exposure trends and rankings to those using SAREF within a workplace. This study suggests that surface area concentration estimation based on particle size distribution (SAPSD) is a more accurate and convenient method to estimate surface area concentrations than estimation methods using inversion routines and may be feasible to use for classifying exposure groups and identifying exposure trends.

A systematic correlation analysis of carotenoids, chlorophyll, non-pigmented cell mass, and cell number for the blueprint of Dunaliella salina culture in a photobioreactor.

PubMed

Song, Hyeon Gi; Byeon, Seon Yeong; Chung, Goo Yong; Jung, Sang-Myung; Choi, Jung Il; Shin, Hwa Sung

2018-05-28

Microalgal carotenoids are attractive health ingredients, but their production should be optimized to improve cost-effectiveness. Understanding cellular physiology centered on carotenoid synthesis is the prerequisite for this work. Therefore, systematic correlation analyses were conducted among chlorophyll, carotenoids, non-pigmented cell mass, and cell number of Dunaliella salina in a specified condition over a relatively long culture time. First, an integrated correlation was performed: a temporal profile of the carotenoids was correlated with those of other factors, including chlorophyll, non-pigmented cell mass, and cell number. Pearson and Spearman correlation analyses were performed to identify linearity and monotonicity of the correlation, respectively, and then cross-correlation was executed to determine if the correlation had a time lag. Second, to understand the cellular potential of metabolism, the procedure was repeated to provide a data set composed of the specific synthesis rates of the factors or growth rate, which additionally provided kinetic correlations among the constituting components of the cell, excluding the effect of cell number. This systematic approach could generate a blueprint model that is composed of only what it needs, which could make it possible to efficiently control and optimize the process.

A method for determination mass absorption coefficient of gamma rays by Compton scattering.

PubMed

El Abd, A

2014-12-01

A method was proposed for determination mass absorption coefficient of gamma rays for compounds, alloys and mixtures. It is based on simulating interaction processes of gamma rays with target elements having atomic numbers from Z=1 to Z=92 using the MCSHAPE software. Intensities of Compton scattered gamma rays at saturation thicknesses and at a scattering angle of 90° were calculated for incident gamma rays of different energies. The obtained results showed that the intensity of Compton scattered gamma rays at saturations and mass absorption coefficients can be described by mathematical formulas. These were used to determine mass absorption coefficients for compound, alloys and mixtures with the knowledge of their Compton scattered intensities. The method was tested by calculating mass absorption coefficients for some compounds, alloys and mixtures. There is a good agreement between obtained results and calculated ones using WinXom software. The advantages and limitations of the method were discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

The Assessment of Selectivity in Different Quadrupole-Orbitrap Mass Spectrometry Acquisition Modes

NASA Astrophysics Data System (ADS)

Berendsen, Bjorn J. A.; Wegh, Robin S.; Meijer, Thijs; Nielen, Michel W. F.

2015-02-01

Selectivity of the confirmation of identity in liquid chromatography (tandem) mass spectrometry using Q-Orbitrap instrumentation was assessed using different acquisition modes based on a representative experimental data set constructed from 108 samples, including six different matrix extracts and containing over 100 analytes each. Single stage full scan, all ion fragmentation, and product ion scanning were applied. By generating reconstructed ion chromatograms using unit mass window in targeted MS2, selected reaction monitoring (SRM), regularly applied using triple-quadrupole instruments, was mimicked. This facilitated the comparison of single stage full scan, all ion fragmentation, (mimicked) SRM, and product ion scanning applying a mass window down to 1 ppm. Single factor Analysis of Variance was carried out on the variance (s2) of the mass error to determine which factors and interactions are significant parameters with respect to selectivity. We conclude that selectivity is related to the target compound (mainly the mass defect), the matrix, sample clean-up, concentration, and mass resolution. Selectivity of the different instrumental configurations was quantified by counting the number of interfering peaks observed in the chromatograms. We conclude that precursor ion selection significantly contributes to selectivity: monitoring of a single product ion at high mass accuracy with a 1 Da precursor ion window proved to be equally selective or better to monitoring two transition products in mimicked SRM. In contrast, monitoring a single fragment in all ion fragmentation mode results in significantly lower selectivity versus mimicked SRM. After a thorough inter-laboratory evaluation study, the results of this study can be used for a critical reassessment of the current identification points system and contribute to the next generation of evidence-based and robust performance criteria in residue analysis and sports doping.

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, �

New Targets for New Accelerators

NASA Astrophysics Data System (ADS)

Frentz, Bryce; Manukyan, Khachatur; Aprahamian, Ani

2013-10-01

New accelerators, such as the 5 MV Sta Ana accelerator at the University of Notre Dame, will produce more powerful beams up to 100's of μAmps. These accelerators require a complete rethinking of target preparation since the high intensity of such beams would melt conventional targets. Traditionally, accelerator targets are made with a tantalum backing because of its high atomic mass. However, tantalum is brittle, a poor conductor, and, if produced commercially, often contains impurities (e.g. fluorine) that produce undesirable background and reaction products. Tungsten, despite its brittle structure and poor conductivity, has a high atomic mass and lacks impurities, making it a more desirable backing. In conjunction with tungsten's properties, copper is robust and a far superior thermal conductor. We describe a new method of reactive joining that we developed for creating targets that use the advantageous properties of both tungsten and copper. This process involved placing a reactive mixture between tungsten and copper and applying a load force. The mixture is then ignited, and while under pressure, the system produces conditions to join the materials. We present our investigation to optimize the process of reactive joining, as well as some of the final target's properties. This work was supported by the National Science Foundation under Grant PHY-1068192.

Maternal pre-pregnancy body mass index and circulating microRNAs in pregnancy.

PubMed

Enquobahrie, Daniel A; Wander, Pandora L; Tadesse, Mahlet G; Qiu, Chunfang; Holzman, Claudia; Williams, Michelle A

Maternal pre-pregnancy overweight and obese status has been associated with a number of pregnancy complications and adverse offspring outcomes. Mechanisms for observed associations, however, are largely unknown. We investigated associations of pre-pregnancy body mass index with early-mid pregnancy epigenetic biomarkers, circulating microRNAs. Peripheral blood was collected from participants (16-27 weeks gestation) of two multi-racial pregnancy cohorts, the Omega Study and the Pregnancy Outcomes and Community Health Study. Plasma miRNA expression was characterised using epigenome-wide (319 miRNAs) profiling among 20 pregnant women in each cohort. Cohort-specific linear regression models that included the predictor (pre-pregnancy body mass index), the outcome (microRNA expression), and adjustment factors (maternal age, gestational age at blood collection, and race) were fit. Expression of 27 miRNAs was positively associated with pre-pregnancy body mass index in both cohorts (p-values <0.05). A number of these differentially expressed miRNAs have previously been associated with adipogenesis (e.g. let-7d*, miR-103-2*, -130b, -146b-5-p, -29c, and -26b). Identified miRNAs as well as their experimentally validated targets participate in pathways that involve organismal injury, reproductive system disease, connective tissue disorders, cancer, cellular development, growth and proliferation. Pre-pregnancy body mass index is associated with circulating miRNAs in early-mid pregnancy. Published by Elsevier Ltd.

Interaction between numbers and size during visual search.

PubMed

Krause, Florian; Bekkering, Harold; Pratt, Jay; Lindemann, Oliver

2017-05-01

The current study investigates an interaction between numbers and physical size (i.e. size congruity) in visual search. In three experiments, participants had to detect a physically large (or small) target item among physically small (or large) distractors in a search task comprising single-digit numbers. The relative numerical size of the digits was varied, such that the target item was either among the numerically large or small numbers in the search display and the relation between numerical and physical size was either congruent or incongruent. Perceptual differences of the stimuli were controlled by a condition in which participants had to search for a differently coloured target item with the same physical size and by the usage of LCD-style numbers that were matched in visual similarity by shape transformations. The results of all three experiments consistently revealed that detecting a physically large target item is significantly faster when the numerical size of the target item is large as well (congruent), compared to when it is small (incongruent). This novel finding of a size congruity effect in visual search demonstrates an interaction between numerical and physical size in an experimental setting beyond typically used binary comparison tasks, and provides important new evidence for the notion of shared cognitive codes for numbers and sensorimotor magnitudes. Theoretical consequences for recent models on attention, magnitude representation and their interactions are discussed.

Target identification for small bioactive molecules: finding the needle in the haystack.

PubMed

Ziegler, Slava; Pries, Verena; Hedberg, Christian; Waldmann, Herbert

2013-03-04

Identification and confirmation of bioactive small-molecule targets is a crucial, often decisive step both in academic and pharmaceutical research. Through the development and availability of several new experimental techniques, target identification is, in principle, feasible, and the number of successful examples steadily grows. However, a generic methodology that can successfully be applied in the majority of the cases has not yet been established. Herein we summarize current methods for target identification of small molecules, primarily for a chemistry audience but also the biological community, for example, the chemist or biologist attempting to identify the target of a given bioactive compound. We describe the most frequently employed experimental approaches for target identification and provide several representative examples illustrating the state-of-the-art. Among the techniques currently available, protein affinity isolation using suitable small-molecule probes (pulldown) and subsequent mass spectrometric analysis of the isolated proteins appears to be most powerful and most frequently applied. To provide guidance for rapid entry into the field and based on our own experience we propose a typical workflow for target identification, which centers on the application of chemical proteomics as the key step to generate hypotheses for potential target proteins. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

Protein turnover measurement using selected reaction monitoring-mass spectrometry (SRM-MS)

PubMed Central

Holman, Stephen W.; Hammond, Dean E.; Simpson, Deborah M.; Waters, John; Hurst, Jane L.

2016-01-01

Protein turnover represents an important mechanism in the functioning of cells, with deregulated synthesis and degradation of proteins implicated in many diseased states. Therefore, proteomics strategies to measure turnover rates with high confidence are of vital importance to understanding many biological processes. In this study, the more widely used approach of non-targeted precursor ion signal intensity (MS1) quantification is compared with selected reaction monitoring (SRM), a data acquisition strategy that records data for specific peptides, to determine if improved quantitative data would be obtained using a targeted quantification approach. Using mouse liver as a model system, turnover measurement of four tricarboxylic acid cycle proteins was performed using both MS1 and SRM quantification strategies. SRM outperformed MS1 in terms of sensitivity and selectivity of measurement, allowing more confident determination of protein turnover rates. SRM data are acquired using cheaper and more widely available tandem quadrupole mass spectrometers, making the approach accessible to a larger number of researchers than MS1 quantification, which is best performed on high mass resolution instruments. SRM acquisition is ideally suited to focused studies where the turnover of tens of proteins is measured, making it applicable in determining the dynamics of proteins complexes and complete metabolic pathways. This article is part of the themed issue ‘Quantitative mass spectrometry’. PMID:27644981

Validated multiclass targeted determination of antibiotics in fish with high performance liquid chromatography-benchtop quadrupole orbitrap hybrid mass spectrometry.

PubMed

Chiesa, Luca; Panseri, Sara; Pasquale, Elisa; Malandra, Renato; Pavlovic, Radmila; Arioli, Francesco

2018-08-30

High performance liquid chromatography, coupled with a benchtop Q-Exactive Orbitrap high-resolution mass spectrometer, was successfully applied for the determination of 24 target antibiotics (selected beta-lactams, tetracyclines, fluoroquinolones, sulfonamids, phenicols, macrolides, cephalosporins, lincosamides, diaminopyrimidine) in fish matrices. The Q-Exactive parameters were carefully studied to accomplish the best compromise between a suitable scan speed and selectivity, considering the restrictions associated with generic sample preparation methodology. Retention time, an exact mass with tolerance of 2 ppm and data-dependent MS 2 spectra were the main identifiers. The method was validated through specificity, linearity, recovery, intra- and inter-day repeatability, decision limit (CCα) and detection capability (CCβ), according to 2002/657/EC. The values of CCα and CCβ ranged from 29.2 to 36.8 and 32.5 to 48.9, respectively, while overall recovery ranged from 91.1 to 105.6%. Fifty fish samples were analysed, showing the sporadic incidence of enrofloxacin, chlortetracycline, oxytetracycline, amoxicillin and trimethoprim, albeit below the maximum residual levels. Copyright © 2018 Elsevier Ltd. All rights reserved.

Non-targeted glycosidic profiling of international wines using neutral loss-high resolution mass spectrometry.

PubMed

Barnaba, C; Dellacassa, E; Nicolini, G; Nardin, T; Serra, M; Larcher, R

2018-07-06

Many metabolites naturally occur as glycosides, since sugar moieties can be crucial for their biological activity and increase their water solubility. In the plant kingdom they may occur as glycosides or sugar esters, depending on precursor chemical structure, and in wine they have traditionally attracted attention due to their organoleptic properties, such as astringency and bitterness, and because they affect the colour and aroma of wines. A new approach directed at detailed description of glycosides in a large selection of monovarietal wines (8 samples each of Pinot Blanc, Muller Thurgau, Riesling, Traminer, Merlot, Pinot Noir and Cabernet Sauvignon) was developed by combining high performance liquid chromatography with high resolution tandem mass spectrometry. Analytical separation was performed on an Accucore™ Polar Premium LC column, while mass analysis was performed in negative ion mode with an non-targeted screening approach, using a Full MS/AIF/NL dd-MS 2 experiment at a resolving power of 140,000 FWHM. Over 280 glycoside-like compounds were detected, of which 133 (including low-molecular weight phenols, flavonoids and monoterpenols) were tentatively identified in the form of pentose (6), deoxyhexose (17), hexose (73), hexose-pentose (16), hexose-deoxyhexose (7), dihexose (5) and hexose ester (9) derivatives. It was not possible to univocally define the corresponding chemical structure for the remaining 149 glycosides. Non-parametric statistical analysis showed it was possible to well characterise the glycosylated profile of all red and Traminer wines, while the identified glycosides were almost entirely lacking in Pinot Blanc, Riesling and Muller Thurgau wines. Also Tukey's Honestly Significant Difference test (p < 0.05) and Principal Component Analysis confirmed that it was possible to almost entirely distinguish the selected red wines from each other according to their glycosylated profile. Copyright © 2018 Elsevier B.V. All rights reserved.

Novel Therapeutic Targets for Chronic Migraine

DTIC Science & Technology

2014-11-01

Award Number: W81XWH-11-1-0647 TITLE: Novel Therapeutic Targets for Chronic Migraine PRINCIPAL INVESTIGATORS: Peter Goadsby CONTRACTING...Therapeutic Targets for Chronic Migraine 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-11-1-0647 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Peter Goadsby, M.D...ABSTRACT Chronic migraine is a disabling disorder that affects millions of individuals worldwide, and may result from traumatic brain injury. The purpose of

Characteristics of compound multiplicity in 84Kr36 with various light and heavy targets at 1 GeV per nucleon

NASA Astrophysics Data System (ADS)

Chouhan, N. S.; Singh, M. K.; Singh, V.; Pathak, R.

2013-12-01

Interactions of 84Kr36 having kinetic energy around 1 GeV per nucleon with NIKFI BR-2 nuclear emulsion detector's target reveal some of the important features of compound multiplicity. Present article shows that width of compound multiplicity distributions and value of mean compound multiplicity have linear relationship with mass number of the projectile colliding system.

Number concentration, size distribution and horizontal mass flux of Asian dust particles collected over free troposphere of Chinese desert region in calm weather condition using balloon borne measurements.

NASA Astrophysics Data System (ADS)

Habib, A.; Chen, B.

2017-12-01

Balloon borne measurements were carried out during calm weather conditions in Taklamakan Desert, which is considered as one of the major source areas of Asian dust (KOSA) particles. Vertical distribution of aerosols number concentration, size distribution, mass concentration and horizontal mass flux due to westerly wind was investigated .Vertical distribution of aerosol number concentration and size distribution at Dunhuang (40 °00'N, 94°30'E) China were observed by optical particle counter (OPC) on August 17, 2001, October 17, 2011, January 11, 2002, April 30, 2002. Five channels (0.3, 0.5, 0.8, 1.2 and 3.6 µm) were used in OPC for particle sizing measurements. Aerosol number concentration in winter season (January 11, 2002) at 3-5 km was very high. Variation of free tropospheric aerosols in April 30, 2002 was noticeable. Many inversions of temperature and aerosol concentration change are found at these inversion points. Super micron range was noticeable in size distribution of all balloon borne measurements. High values of estimated mass concentration of aerosols were observed at the ground atmosphere (1-2 km), and interestingly relatively high concentrations were frequently detected above about 2 km. Wind pattern observed by ERA-interim data sets at 500 and 850 hPa, shows that westerly winds were dominated in Taklamakan Desert during balloon borne observation period. Average horizontal mass flux of background Asian dust due to westerly wind was about in the range of 1219-58.5 μg/m³ tons/km2/day. Most of the profiles showed active transport of aerosols in the westerly dominated region, while, fluxes were found to be very low on January 11, 2002, compared with the other seasons. Vertical profiles of aerosols number concentration showed that significant transport of aerosols was dominated in westerly region (4-7 km). Low horizontal mass flux of aerosols was found in winter season

Mercury target R&D for the Oak Ridge spallation neutron source

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

Haines, J.R.; DiStefano, J.; Farrell, K.

1996-06-01

The conceptual design for the Oak Ridge Spallation Neutron Source (ORSNS) incorporates liquid mercury as its reference target material. A flowing liquid target was selected mainly because of the increased power handling capability possible with the convective transport process. The major reasons for choosing mercury as the liquid target material are because it: (1) is a liquid at room temperature, (2) has good heat transport properties, and (3) has a high atomic number and mass density resulting in high neutron yield and source brightness. Since liquid targets are not widely utilized in presently operating accelerator targets and because of themore » challenges posed by the intense, pulsed thermal energy deposition ({approximately}20-100 kJ deposited during each 1-10 {mu}s pulse), considerable R&D is planned for the mercury target concept. The key feasibility issue that will be addressed in early R&D efforts are the effects of the thermal shock environment, which will include development and testing of approaches to mitigate these effects. Materials compatiblity and ES&H issues associated with the use of liquid mercury are also of major importance in early R&D efforts. A brief description of the mercury target design concept, results of initial evaluations of its performance characteristics, identification of its critical issues, and an outline of the R&D program aimed at addressing these issues will be presented.« less

Shock-induced perturbation evolution in planar laser targets

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.

2013-10-01

Experimental studies of hydrodynamic perturbation evolution triggered by a laser-driven shock wave in a planar target done on the KrF Nike laser facility are reported. The targets were made of solid plastic and/or plastic foam with single mode sinusoidal perturbation on the front or back surface or plastic/foam interface. Two specific cases are discussed. When a planar solid plastic target rippled at the front side is irradiated with a 350 ps long laser pulse, ablative Richtmyer-Meshkov (RM) oscillation of its areal mass modulation amplitude is detected while the laser is on, followed by observed strong oscillations of the areal mass in the unsupported shock flow after the laser pulse ends. When the target is rippled at the rear side, the nature of the perturbation evolution after the shock breakout is determined by the strength of the laser-driven shock wave. At pressure below 1 Mbar shock interaction with rear-surface ripples produces planar collimated jets manifesting the development of a classical RM instability in a weakly compressible shocked fluid. At shock pressure ~ 8 Mbar sufficient for vaporizing the shocked target material we observed instead the strong areal mass oscillations characteristic of a rippled centered rarefaction wave. Work supported by US DOE, Defense Programs.

Measurement of total acid number (TAN) and TAN boiling point distribution in petroleum products by electrospray ionization mass spectrometry.

PubMed

Qian, Kuangnan; Edwards, Kathleen E; Dechert, Gary J; Jaffe, Stephen B; Green, Larry A; Olmstead, William N

2008-02-01

We report a new method for rapid measurement of total acid number (TAN) and TAN boiling point (BP) distribution for petroleum crude and products. The technology is based on negative ion electrospray ionization mass spectrometry (ESI-MS) for selective ionization of petroleum acid and quantification of acid structures and molecular weight distributions. A chip-based nanoelectrospray system enables microscale (<200 mg) and higher throughput (20 samples/h) measurement. Naphthenic acid structures were assigned based on nominal masses of a set of predefined acid structures. Stearic acid is used as an internal standard to calibrate ESI-MS response factors for quantification purposes. With the use of structure-property correlations, boiling point distributions of TAN values can be calculated from the composition. The rapid measurement of TAN BP distributions by ESI is demonstrated for a series of high-TAN crudes and distillation cuts. TAN values determined by the technique agree well with those by the titration method. The distributed properties compare favorably with those measured by distillation and measurement of TAN of corresponding cuts.

ANALYSIS OF RESPIRATORY DEPOSITION OF INHALED PARTICLES FOR DIFFERENT DOSE METRICS: COMPARISON OF NUMBER, SURFACE AREA AND MASS DOSE OF TYPICAL AMBIENT BI-MODAL AEROSOLS

EPA Science Inventory

ANALYSIS OF RESPIRATORY DEPOSITION OF INHALED PARTICLES FOR DIFFERENT DOSE METRICS: COMPARISON OF NUMBER, SURFACE AREA AND MASS DOSE OF TYPICAL AMBIENT BI-MODAL AEROSOLS.
Chong S. Kim, SC. Hu*, PA Jaques*, US EPA, National Health and Environmental Effects Research Laboratory, ...

Targeted Nanoparticles for Kidney Cancer Therapy

DTIC Science & Technology

2013-10-01

AD_________________ Award Number: W81XWH-10-1-0434 TITLE: Targeted Nanoparticles for Kidney Cancer Therapy PRINCIPAL...Targeted Nanoparticles for Kidney Cancer Therapy 5b. GRANT NUMBER W81XWH-10-1-0434 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT...lines following treatment with D5 nanotubes. Tthermoablation will be studied initially. Human kidney cancer cells will be injected into the kidney

Optimal Target Stars in the Search for Life

NASA Astrophysics Data System (ADS)

Lingam, Manasvi; Loeb, Abraham

2018-04-01

The selection of optimal targets in the search for life represents a highly important strategic issue. In this Letter, we evaluate the benefits of searching for life around a potentially habitable planet orbiting a star of arbitrary mass relative to a similar planet around a Sun-like star. If recent physical arguments implying that the habitability of planets orbiting low-mass stars is selectively suppressed are correct, we find that planets around solar-type stars may represent the optimal targets.

A Systematic Analysis of Caustic Methods for Galaxy Cluster Masses

NASA Astrophysics Data System (ADS)

Gifford, Daniel; Miller, Christopher; Kern, Nicholas

2013-08-01

We quantify the expected observed statistical and systematic uncertainties of the escape velocity as a measure of the gravitational potential and total mass of galaxy clusters. We focus our attention on low redshift (z <=0.15) clusters, where large and deep spectroscopic datasets currently exist. Utilizing a suite of Millennium Simulation semi-analytic galaxy catalogs, we find that the dynamical mass, as traced by either the virial relation or the escape velocity, is robust to variations in how dynamical friction is applied to "orphan" galaxies in the mock catalogs (i.e., those galaxies whose dark matter halos have fallen below the resolution limit). We find that the caustic technique recovers the known halo masses (M 200) with a third less scatter compared to the virial masses. The bias we measure increases quickly as the number of galaxies used decreases. For N gal > 25, the scatter in the escape velocity mass is dominated by projections along the line-of-sight. Algorithmic uncertainties from the determination of the projected escape velocity profile are negligible. We quantify how target selection based on magnitude, color, and projected radial separation can induce small additional biases into the escape velocity masses. Using N gal = 150 (25), the caustic technique has a per cluster scatter in ln (M|M 200) of 0.3 (0.5) and bias 1% ± 3} (16% ± 5}) for clusters with masses >1014 M ⊙ at z < 0.15.

Experimental study on ablative stabilization of Rayleigh-Taylor instability of laser-irradiated targets

NASA Astrophysics Data System (ADS)

Shigemori, Keisuke; Sakaiya, Tatsuhiko; Otani, Kazuto; Fujioka, Shinsuke; Nakai, Mitsuo; Azechi, Hiroshi; Shiraga, Hiroyuki; Tamari, Yohei; Okuno, Kazuki; Sunahara, Atsushi; Nagatomo, Hideo; Murakami, Masakatsu; Nishihara, Katsunobu; Izawa, Yasukazu

2004-09-01

Hydrodynamic instabilities are key issues of the physics of inertial confinement fusion (ICF) targets. Among the instabilities, Rayleigh-Taylor (RT) instability is the most important because it gives the largest growth factor in the ICF targets. Perturbations on the laser irradiated surface grow exponentially, but the growth rate is reduced by ablation flow. The growth rate γ is written as Takabe-Betti formula: γ = [kg/(1+kL)]1/2-βkm/pa, where k is wave number of the perturbation, g is acceleration, L is density scale-length, β is a coefficient, m is mass ablation rate per unit surface, and ρa is density at the ablation front. We experimentally measured all the parameters in the formula for polystyrene (CH) targets. Experiments were done on the HIPER laser facility at Institute of Laser Engineering, Osaka University. We found that the β value in the formula is ~ 1.7, which is in good agreements with the theoretical prediction, whereas the β for certain perturbation wavelengths are larger than the prediction. This disagreement between the experiment and the theory is mainly due to the deformation of the cutoff surface, which is created by non-uniform ablation flow from the ablation surface. We also found that high-Z doped plastic targets have multiablation structure, which can reduce the RT growth rate. When a low-Z target with high-Z dopant is irradiated by laser, radiation due to the high-Z dopant creates secondary ablation front deep inside the target. Since, the secondary ablation front is ablated by x-rays, the mass ablation rate is larger than the laser-irradiated ablation surface, that is, further reduction of the RT growth is expected. We measured the RT growth rate of Br-doped polystyrene targets. The experimental results indicate that of the CHBr targets show significantly small growth rate, which is very good news for the design of the ICF targets.

Influence of trans-boundary biomass burning impacted air masses on submicron particle number concentrations and size distributions

NASA Astrophysics Data System (ADS)

Betha, Raghu; Zhang, Zhe; Balasubramanian, Rajasekhar

2014-08-01

Submicron particle number concentration (PNC) and particle size distribution (PSD) in the size range of 5.6-560 nm were investigated in Singapore from 27 June 2009 through 6 September 2009. Slightly hazy conditions lasted in Singapore from 6 to 10 August. Backward air trajectories indicated that the haze was due to the transport of biomass burning impacted air masses originating from wild forest and peat fires in Sumatra, Indonesia. Three distinct peaks in the morning (08:00-10:00), afternoon (13:00-15:00) and evening (16:00-20:00) were observed on a typical normal day. However, during the haze period no distinct morning and afternoon peaks were observed and the PNC (39,775 ± 3741 cm-3) increased by 1.5 times when compared to that during non-haze periods (26,462 ± 6017). The morning and afternoon peaks on the normal day were associated with the local rush hour traffic while the afternoon peak was induced by new particle formation (NPF). Diurnal profiles of PNCs and PSDs showed that primary particle peak diameters were large during the haze (60 nm) period when compared to that during the non-haze period (45.3 nm). NPF events observed in the afternoon period on normal days were suppressed during the haze periods due to heavy particle loading in atmosphere caused by biomass burning impacted air masses.

Characterisation of particle mass and number concentration on the east coast of the Malaysian Peninsula during the northeast monsoon

NASA Astrophysics Data System (ADS)

Dominick, Doreena; Latif, Mohd Talib; Juneng, Liew; Khan, Md Firoz; Amil, Norhaniza; Mead, Mohammed Iqbal; Nadzir, Mohd Shahrul Mohd; Moi, Phang Siew; Samah, Azizan Abu; Ashfold, Matthew J.; Sturges, William T.; Harris, Neil R. P.; Robinson, Andrew D.; Pyle, John A.

2015-09-01

Particle mass concentrations (PM10, PM2.5 and PM1) and particle number concentration ((PNC); 0.27 μm ≤ Dp ≤ 34.00 μm) were measured in the tropical coastal environment of Bachok, Kelantan on the Malaysian Peninsula bordering the southern edge of the South China Sea. Statistical methods were applied on a three-month hourly data set (9th January to 24th March 2014) to study the influence of north-easterly winds on the patterns of particle mass and PNC size distributions. The 24-h concentrations of particle mass obtained in this study were below the standard values detailed by the Recommended Malaysian Air Quality Guideline (RMAQG), United States Environmental Protection Agency (US EPA) and European Union (EU) except for PM2.5, which recorded a 24-h average of 30 ± 18 μg m-3 and exceeded the World Health Organisation (WHO) threshold value (25 μg m-3). Principal component analysis (PCA) revealed that PNC with smaller diameter sizes (0.27-4.50 μm) showed a stronger influence, accounting for 57.6% of the variability in PNC data set. Concentrations of both particle mass and PNC increased steadily in the morning with a distinct peak observed at around 8.00 h, related to a combination of dispersion of accumulated particles overnight and local traffic. In addition to local anthropogenic, agricultural burning and forest fire activities, long-range transport also affects the study area. Hotspot and backward wind trajectory observations illustrated that the biomass burning episode (around February-March) significantly influenced PNC. Meteorological parameters influenced smaller size particles (i.e. PM1 and Dp (0.27-0.43 μm)) the most.

Targeted peptide measurements in biology and medicine: best practices for mass spectrometry-based assay development using a fit-for-purpose approach.

PubMed

Carr, Steven A; Abbatiello, Susan E; Ackermann, Bradley L; Borchers, Christoph; Domon, Bruno; Deutsch, Eric W; Grant, Russell P; Hoofnagle, Andrew N; Hüttenhain, Ruth; Koomen, John M; Liebler, Daniel C; Liu, Tao; MacLean, Brendan; Mani, D R; Mansfield, Elizabeth; Neubert, Hendrik; Paulovich, Amanda G; Reiter, Lukas; Vitek, Olga; Aebersold, Ruedi; Anderson, Leigh; Bethem, Robert; Blonder, Josip; Boja, Emily; Botelho, Julianne; Boyne, Michael; Bradshaw, Ralph A; Burlingame, Alma L; Chan, Daniel; Keshishian, Hasmik; Kuhn, Eric; Kinsinger, Christopher; Lee, Jerry S H; Lee, Sang-Won; Moritz, Robert; Oses-Prieto, Juan; Rifai, Nader; Ritchie, James; Rodriguez, Henry; Srinivas, Pothur R; Townsend, R Reid; Van Eyk, Jennifer; Whiteley, Gordon; Wiita, Arun; Weintraub, Susan

2014-03-01

Adoption of targeted mass spectrometry (MS) approaches such as multiple reaction monitoring (MRM) to study biological and biomedical questions is well underway in the proteomics community. Successful application depends on the ability to generate reliable assays that uniquely and confidently identify target peptides in a sample. Unfortunately, there is a wide range of criteria being applied to say that an assay has been successfully developed. There is no consensus on what criteria are acceptable and little understanding of the impact of variable criteria on the quality of the results generated. Publications describing targeted MS assays for peptides frequently do not contain sufficient information for readers to establish confidence that the tests work as intended or to be able to apply the tests described in their own labs. Guidance must be developed so that targeted MS assays with established performance can be made widely distributed and applied by many labs worldwide. To begin to address the problems and their solutions, a workshop was held at the National Institutes of Health with representatives from the multiple communities developing and employing targeted MS assays. Participants discussed the analytical goals of their experiments and the experimental evidence needed to establish that the assays they develop work as intended and are achieving the required levels of performance. Using this "fit-for-purpose" approach, the group defined three tiers of assays distinguished by their performance and extent of analytical characterization. Computational and statistical tools useful for the analysis of targeted MS results were described. Participants also detailed the information that authors need to provide in their manuscripts to enable reviewers and readers to clearly understand what procedures were performed and to evaluate the reliability of the peptide or protein quantification measurements reported. This paper presents a summary of the meeting and

Targeted Peptide Measurements in Biology and Medicine: Best Practices for Mass Spectrometry-based Assay Development Using a Fit-for-Purpose Approach*

PubMed Central

Carr, Steven A.; Abbatiello, Susan E.; Ackermann, Bradley L.; Borchers, Christoph; Domon, Bruno; Deutsch, Eric W.; Grant, Russell P.; Hoofnagle, Andrew N.; Hüttenhain, Ruth; Koomen, John M.; Liebler, Daniel C.; Liu, Tao; MacLean, Brendan; Mani, DR; Mansfield, Elizabeth; Neubert, Hendrik; Paulovich, Amanda G.; Reiter, Lukas; Vitek, Olga; Aebersold, Ruedi; Anderson, Leigh; Bethem, Robert; Blonder, Josip; Boja, Emily; Botelho, Julianne; Boyne, Michael; Bradshaw, Ralph A.; Burlingame, Alma L.; Chan, Daniel; Keshishian, Hasmik; Kuhn, Eric; Kinsinger, Christopher; Lee, Jerry S.H.; Lee, Sang-Won; Moritz, Robert; Oses-Prieto, Juan; Rifai, Nader; Ritchie, James; Rodriguez, Henry; Srinivas, Pothur R.; Townsend, R. Reid; Van Eyk, Jennifer; Whiteley, Gordon; Wiita, Arun; Weintraub, Susan

2014-01-01

Adoption of targeted mass spectrometry (MS) approaches such as multiple reaction monitoring (MRM) to study biological and biomedical questions is well underway in the proteomics community. Successful application depends on the ability to generate reliable assays that uniquely and confidently identify target peptides in a sample. Unfortunately, there is a wide range of criteria being applied to say that an assay has been successfully developed. There is no consensus on what criteria are acceptable and little understanding of the impact of variable criteria on the quality of the results generated. Publications describing targeted MS assays for peptides frequently do not contain sufficient information for readers to establish confidence that the tests work as intended or to be able to apply the tests described in their own labs. Guidance must be developed so that targeted MS assays with established performance can be made widely distributed and applied by many labs worldwide. To begin to address the problems and their solutions, a workshop was held at the National Institutes of Health with representatives from the multiple communities developing and employing targeted MS assays. Participants discussed the analytical goals of their experiments and the experimental evidence needed to establish that the assays they develop work as intended and are achieving the required levels of performance. Using this “fit-for-purpose” approach, the group defined three tiers of assays distinguished by their performance and extent of analytical characterization. Computational and statistical tools useful for the analysis of targeted MS results were described. Participants also detailed the information that authors need to provide in their manuscripts to enable reviewers and readers to clearly understand what procedures were performed and to evaluate the reliability of the peptide or protein quantification measurements reported. This paper presents a summary of the meeting and

Sustainability of algae derived biodiesel: a mass balance approach.

PubMed

Pfromm, Peter H; Amanor-Boadu, Vincent; Nelson, Richard

2011-01-01

A rigorous chemical engineering mass balance/unit operations approach is applied here to bio-diesel from algae mass culture. An equivalent of 50,000,000 gallons per year (0.006002 m3/s) of petroleum-based Number 2 fuel oil (US, diesel for compression-ignition engines, about 0.1% of annual US consumption) from oleaginous algae is the target. Methyl algaeate and ethyl algaeate diesel can according to this analysis conceptually be produced largely in a technologically sustainable way albeit at a lower available diesel yield. About 11 square miles of algae ponds would be needed with optimistic assumptions of 50 g biomass yield per day and m2 pond area. CO2 to foster algae growth should be supplied from a sustainable source such as a biomass-based ethanol production. Reliance on fossil-based CO2 from power plants or fertilizer production renders algae diesel non-sustainable in the long term. Copyright © 2010 Elsevier Ltd. All rights reserved.

Parameterizing by the Number of Numbers

NASA Astrophysics Data System (ADS)

Fellows, Michael R.; Gaspers, Serge; Rosamond, Frances A.

The usefulness of parameterized algorithmics has often depended on what Niedermeier has called "the art of problem parameterization". In this paper we introduce and explore a novel but general form of parameterization: the number of numbers. Several classic numerical problems, such as Subset Sum, Partition, 3-Partition, Numerical 3-Dimensional Matching, and Numerical Matching with Target Sums, have multisets of integers as input. We initiate the study of parameterizing these problems by the number of distinct integers in the input. We rely on an FPT result for Integer Linear Programming Feasibility to show that all the above-mentioned problems are fixed-parameter tractable when parameterized in this way. In various applied settings, problem inputs often consist in part of multisets of integers or multisets of weighted objects (such as edges in a graph, or jobs to be scheduled). Such number-of-numbers parameterized problems often reduce to subproblems about transition systems of various kinds, parameterized by the size of the system description. We consider several core problems of this kind relevant to number-of-numbers parameterization. Our main hardness result considers the problem: given a non-deterministic Mealy machine M (a finite state automaton outputting a letter on each transition), an input word x, and a census requirement c for the output word specifying how many times each letter of the output alphabet should be written, decide whether there exists a computation of M reading x that outputs a word y that meets the requirement c. We show that this problem is hard for W[1]. If the question is whether there exists an input word x such that a computation of M on x outputs a word that meets c, the problem becomes fixed-parameter tractable.

Low frequency of broadly neutralizing HIV antibodies during chronic infection even in quaternary epitope targeting antibodies containing large numbers of somatic mutations.

PubMed

Hicar, Mark D; Chen, Xuemin; Kalams, Spyros A; Sojar, Hakimuddin; Landucci, Gary; Forthal, Donald N; Spearman, Paul; Crowe, James E

2016-02-01

Neutralizing antibodies (Abs) are thought to be a critical component of an appropriate HIV vaccine response. It has been proposed that Abs recognizing conformationally dependent quaternary epitopes on the HIV envelope (Env) trimer may be necessary to neutralize diverse HIV strains. A number of recently described broadly neutralizing monoclonal Abs (mAbs) recognize complex and quaternary epitopes. Generally, many such Abs exhibit extensive numbers of somatic mutations and unique structural characteristics. We sought to characterize the native antibody (Ab) response against circulating HIV focusing on such conformational responses, without a prior selection based on neutralization. Using a capture system based on VLPs incorporating cleaved envelope protein, we identified a selection of B cells that produce quaternary epitope targeting Abs (QtAbs). Similar to a number of broadly neutralizing Abs, the Ab genes encoding these QtAbs showed extensive numbers of somatic mutations. However, when expressed as recombinant molecules, these Abs failed to neutralize virus or mediate ADCVI activity. Molecular analysis showed unusually high numbers of mutations in the Ab heavy chain framework 3 region of the variable genes. The analysis suggests that large numbers of somatic mutations occur in Ab genes encoding HIV Abs in chronically infected individuals in a non-directed, stochastic, manner. Copyright © 2015 Elsevier Ltd. All rights reserved.

Pharmacological therapeutics targeting the secondary defects and downstream pathology of Duchenne muscular dystrophy

PubMed Central

Spinazzola, Janelle M.; Kunkel, Louis M.

2016-01-01

Introduction Since the identification of the dystrophin gene in 1986, a cure for Duchenne muscular dystrophy (DMD) has yet to be discovered. Presently, there are a number of genetic-based therapies in development aimed at restoration and/or repair of the primary defect. However, growing understanding of the pathophysiological consequences of dystrophin absence has revealed several promising downstream targets for the development of therapeutics. Areas covered In this review, we discuss various strategies for DMD therapy targeting downstream consequences of dystrophin absence including loss of muscle mass, inflammation, fibrosis, calcium overload, oxidative stress, and ischemia. The rationale of each approach and the efficacy of drugs in preclinical and clinical studies are discussed. Expert opinion For the last 30 years, effective DMD drug therapy has been limited to corticosteroids, which are associated with a number of negative side effects. Our knowledge of the consequences of dystrophin absence that contribute to DMD pathology has revealed several potential therapeutic targets. Some of these approaches may have potential to improve or slow disease progression independently or in combination with genetic-based approaches. The applicability of these pharmacological therapies to DMD patients irrespective of their genetic mutation, as well as the potential benefits even for advanced stage patients warrants their continued investigation. PMID:28670506

Direct antigen detection from immunoprecipitated beads using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry; a new method for immunobeads-mass spectrometry (iMS).

PubMed

Shimada, Takashi; Toyama, Atsuhiko; Aoki, Chikage; Aoki, Yutaka; Tanaka, Koichi; Sato, Taka-Aki

2011-12-15

One-step detection of biological molecules is one of the principal techniques for clinical diagnosis, and the potential of mass spectrometry for biomarker detection has been a promising new approach in the field of medical sciences. We demonstrate here a new and high-sensitivity method that we termed immunobeads-mass spectrometry (iMS), which combines conventional immunoprecipitation and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The key feature of iMS is the MS-compatible condition of immunoprecipitation using detergents with a monosaccaride-C8 alkyl chain or a disaccharide-C10 alkyl chain, and the minimized number of steps required for high-sensitivity detection of target peptides in serum or biological fluid. This was achieved by optimizing the wash buffer and subjecting the immunobeads directly to MALDI-TOF MS analysis. Using this method, we showed that 1 fmol of amyloid beta peptide spiked in serum was readily detectable, demonstrating the powerful tool of iMS as a biomarker detection method. Copyright © 2011 John Wiley & Sons, Ltd.

Planning schistosomiasis control: investigation of alternative sampling strategies for Schistosoma mansoni to target mass drug administration of praziquantel in East Africa.

PubMed

Sturrock, Hugh J W; Gething, Pete W; Ashton, Ruth A; Kolaczinski, Jan H; Kabatereine, Narcis B; Brooker, Simon

2011-09-01

In schistosomiasis control, there is a need to geographically target treatment to populations at high risk of morbidity. This paper evaluates alternative sampling strategies for surveys of Schistosoma mansoni to target mass drug administration in Kenya and Ethiopia. Two main designs are considered: lot quality assurance sampling (LQAS) of children from all schools; and a geostatistical design that samples a subset of schools and uses semi-variogram analysis and spatial interpolation to predict prevalence in the remaining unsurveyed schools. Computerized simulations are used to investigate the performance of sampling strategies in correctly classifying schools according to treatment needs and their cost-effectiveness in identifying high prevalence schools. LQAS performs better than geostatistical sampling in correctly classifying schools, but at a cost with a higher cost per high prevalence school correctly classified. It is suggested that the optimal surveying strategy for S. mansoni needs to take into account the goals of the control programme and the financial and drug resources available.

Trypsin and MALDI matrix pre-coated targets simplify sample preparation for mapping proteomic distributions within biological tissues by imaging mass spectrometry

PubMed Central

Zubair, Faizan; Laibinis, Paul E.; Swisher, William G.; Yang, Junhai; Spraggins, Jeffrey M.; Norris, Jeremy L.; Caprioli, Richard M.

2017-01-01

Prefabricated surfaces containing α-cyano-4-hydroxycinnamic acid and trypsin have been developed to facilitate enzymatic digestion of endogenous tissue proteins prior to matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS). Tissue sections are placed onto slides that were previously coated with α-cyano-4-hydroxycinnamic acid and trypsin. After incubation to promote enzymatic digestion, the tissue is analyzed by MALDI IMS to determine the spatial distribution of the tryptic fragments. The peptides detected in the MALDI IMS dataset were identified by Liquid chromatography-tandem mass spectrometry/mass spectrometry. Protein identification was further confirmed by correlating the localization of unique tryptic fragments originating from common parent proteins. Using this procedure, proteins with molecular weights as large as 300 kDa were identified and their distributions were imaged in sections of rat brain. In particular, large proteins such as myristoylated alanine-rich C-kinase substrate (29.8 kDa) and spectrin alpha chain, non-erythrocytic 1 (284 kDa) were detected that are not observed without trypsin. The pre-coated targets simplify workflow and increase sample throughput by decreasing the sample preparation time. Further, the approach allows imaging at higher spatial resolution compared with robotic spotters that apply one drop at a time. PMID:27676701

Targeting ESR1-Mutant Breast Cancer

DTIC Science & Technology

2015-09-01

AWARD NUMBER: W81XWH-14-1-0359 TITLE: Targeting ESR1 -Mutant Breast Cancer PRINCIPAL INVESTIGATOR: Dr. Sarat Chandarlapaty CONTRACTING...31 Aug 2015 4. TITLE AND SUBTITLE Targeting ESR1 -Mutant Breast Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-14-1-0359 5c. PROGRAM ELEMENT...Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT The hypothesis of this proposal is that LBD mutations in ESR1 promote resistance to

Geographic variation in left ventricular mass and mass index: a systematic review.

PubMed

Poppe, K K; Bachmann, M Edgerton; Triggs, C M; Doughty, R N; Whalley, G A

2012-07-01

Left ventricular (LV) hypertrophy, defined as an abnormal increase in LV mass (LVM), is an important prognostic indicator and therapeutic target. LVM is often divided by body surface area to derive indexed mass; however, this does not correctly identify pathological LV hypertrophy in all people, especially when body composition is altered, or in different ethnic groups. We evaluated published ranges of echocardiographic LVM in healthy adult populations from different countries, excluding control groups, and compared them with the American Society of Echocardiography reference ranges. A total of 33 studies met the inclusion criteria. In men and women, there was wide variation in the ranges of LVM with a tendency for the upper limit to increase geographically westward; this variation remained for indexed mass. Several ranges fell outside the upper reference limits: in men, 13 of the mass ranges and 16 of indexed mass; and in women, 8 mass and 16 indexed mass. This review has shown that current guidelines may need revision as some published series suggest that greater LV mass should be considered normal. This may be explained by ethnic differences and supports the need for widely applicable and ethnically diverse reference ranges to be established.

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.

Identification of the Geographic Origin of Parmigiano Reggiano (P.D.O.) Cheeses Deploying Non-Targeted Mass Spectrometry and Chemometrics.

PubMed

Popping, Bert; De Dominicis, Emiliano; Dante, Mario; Nocetti, Marco

2017-02-16

Parmigiano Reggiano is an Italian product with a protected designation of origin (P.D.O.). It is an aged hard cheese made from raw milk. P.D.O. products are protected by European regulations. Approximately 3 million wheels are produced each year, and the product attracts a relevant premium price due to its quality and all around the world well known typicity. Due to the high demand that exceeds the production, several fraudulent products can be found on the market. The rate of fraud is estimated between 20% and 40%, the latter predominantly in the grated form. We have developed a non-target method based on Liquid Chomatography-High Resolution Mass Spectrometry (LC-HRMS) that allows the discrimination of Parmigiano Reggiano from non-authentic products with milk from different geographical origins or products, where other aspects of the production process do not comply with the rules laid down in the production specifications for Parmeggiano Reggiano. Based on a database created with authentic samples provided by the Consortium of Parmigiano Reggiano Cheese, a reliable classification model was built. The overall classification capabilities of this non-targeted method was verified on 32 grated cheese samples. The classification was 87.5% accurate.

Extension of the analytical window for characterizing aromatic compounds in oils using a comprehensive suite of high-resolution mass spectrometry techniques and double bond equivalence versus carbon number plot

USGS Publications Warehouse

Cho, Yunju; Birdwell, Justin E.; Hur, Manhoi; Lee, Joonhee; Kim, Byungjoo; Kim, Sunghwan

2017-01-01

In this study, comprehensive two-dimensional (2D) gas chromatography–mass spectrometry (GC–MS), atmospheric pressure photoionization (APPI) quadrupole-Orbitrap mass spectrometry (MS), and Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) were used to study the aromatic fractions of crude oil and oil shale pyrolysates (shale oils). The collected data were compared and combined in the double bond equivalence (DBE) versus carbon number plot to obtain a more complete understanding of the composition of the oil fractions. The numbers of peaks observed by each technique followed the order 2D GC–MS < Orbitrap MS < FT-ICR MS. The class distributions observed by Orbitrap MS and FT-ICR MS were similar to each other but different from that observed by 2D GC–MS. The DBE and carbon number distributions of the 2D GC–MS and Orbitrap MS data were similar for crude oil aromatics. The FT-ICR MS plots of DBE and carbon number showed an extended range of higher values relative to the other methods. For the aromatic fraction of an oil shale pyrolysate generated by the Fischer assay, only a few nitrogen-containing compounds were observed by 2D GC–MS but a large number of these compounds were detected by Orbitrap MS and FT-ICR MS. This comparison clearly shows that the data obtained from these three techniques can be combined to more completely characterize oil composition. The data obtained by Orbitrap MS and FT-ICR MS agreed well with one another, and the combined DBE versus carbon number plot provided more complete coverage of compounds present in the fractions. In addition, the chemical structure information provided by 2D GC–MS could be matched with the chemical formulas in the DBE versus carbon number plots, providing information not available in ultrahigh-resolution MS results. It was therefore concluded that the combination of 2D GC–MS, Orbitrap MS, and FT-ICR MS in the DBE versus carbon number space facilitates structural assignment of heavy

A general method for targeted quantitative cross-linking mass spectrometry

USDA-ARS?s Scientific Manuscript database

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, NM...

Novel Targeted Therapies for Inflammatory Breast Cancer

DTIC Science & Technology

2017-10-01

AWARD NUMBER: W81XWH-16-1-0461 TITLE: Novel Targeted Therapies for Inflammatory Breast Cancer PRINCIPAL INVESTIGATOR: Jose Silva CONTRACTING...CONTRACT NUMBER Novel Targeted Therapies for Inflammatory Breast Cancer 5b. GRANT NUMBER W81XWH-16-1-0461 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) l 5d...NOTES 14. ABSTRACT Inflammatory breast cancer (IBC, ~5% of all breast cancers ) is the most lethal form of breast cancer , presenting a 5- year

Development and application of a channelized Hotelling observer for DBT optimization on structured background test images with mass simulating targets

NASA Astrophysics Data System (ADS)

Petrov, Dimitar; Michielsen, Koen; Cockmartin, Lesley; Zhang, Gouzhi; Young, Kenneth; Marshall, Nicholas; Bosmans, Hilde

2016-03-01

Digital breast tomosynthesis (DBT) is a 3D mammography technique that promises better visualization of low contrast lesions than conventional 2D mammography. A wide range of parameters influence the diagnostic information in DBT images and a systematic means of DBT system optimization is needed. The gold standard for image quality assessment is to perform a human observer experiment with experienced readers. Using human observers for optimization is time consuming and not feasible for the large parameter space of DBT. Our goal was to develop a model observer (MO) that can predict human reading performance for standard detection tasks of target objects within a structured phantom and subsequently apply it in a first comparative study. The phantom consists of an acrylic semi-cylindrical container with acrylic spheres of different sizes and the remaining space filled with water. Three types of lesions were included: 3D printed spiculated and non-spiculated mass lesions along with calcification groups. The images of the two mass lesion types were reconstructed with 3 different reconstruction methods (FBP, FBP with SRSAR, MLTRpr) and read by human readers. A Channelized Hotelling model observer was created for the non-spiculated lesion detection task using five Laguerre-Gauss channels, tuned for better performance. For the non-spiculated mass lesions a linear relation between the MO and human observer results was found, with correlation coefficients of 0.956 for standard FBP, 0.998 for FBP with SRSAR and 0.940 for MLTRpr. Both the MO and human observer percentage correct results for the spiculated masses were close to 100%, and showed no difference from each other for every reconstruction algorithm.

Mass Spectrometry Strategies for Clinical Metabolomics and Lipidomics in Psychiatry, Neurology, and Neuro-Oncology

PubMed Central

Wood, Paul L

2014-01-01

Metabolomics research has the potential to provide biomarkers for the detection of disease, for subtyping complex disease populations, for monitoring disease progression and therapy, and for defining new molecular targets for therapeutic intervention. These potentials are far from being realized because of a number of technical, conceptual, financial, and bioinformatics issues. Mass spectrometry provides analytical platforms that address the technical barriers to success in metabolomics research; however, the limited commercial availability of analytical and stable isotope standards has created a bottleneck for the absolute quantitation of a number of metabolites. Conceptual and financial factors contribute to the generation of statistically under-powered clinical studies, whereas bioinformatics issues result in the publication of a large number of unidentified metabolites. The path forward in this field involves targeted metabolomics analyses of large control and patient populations to define both the normal range of a defined metabolite and the potential heterogeneity (eg, bimodal) in complex patient populations. This approach requires that metabolomics research groups, in addition to developing a number of analytical platforms, build sufficient chemistry resources to supply the analytical standards required for absolute metabolite quantitation. Examples of metabolomics evaluations of sulfur amino-acid metabolism in psychiatry, neurology, and neuro-oncology and of lipidomics in neurology will be reviewed. PMID:23842599

Mass spectrometry strategies for clinical metabolomics and lipidomics in psychiatry, neurology, and neuro-oncology.

PubMed

Wood, Paul L

2014-01-01

Metabolomics research has the potential to provide biomarkers for the detection of disease, for subtyping complex disease populations, for monitoring disease progression and therapy, and for defining new molecular targets for therapeutic intervention. These potentials are far from being realized because of a number of technical, conceptual, financial, and bioinformatics issues. Mass spectrometry provides analytical platforms that address the technical barriers to success in metabolomics research; however, the limited commercial availability of analytical and stable isotope standards has created a bottleneck for the absolute quantitation of a number of metabolites. Conceptual and financial factors contribute to the generation of statistically under-powered clinical studies, whereas bioinformatics issues result in the publication of a large number of unidentified metabolites. The path forward in this field involves targeted metabolomics analyses of large control and patient populations to define both the normal range of a defined metabolite and the potential heterogeneity (eg, bimodal) in complex patient populations. This approach requires that metabolomics research groups, in addition to developing a number of analytical platforms, build sufficient chemistry resources to supply the analytical standards required for absolute metabolite quantitation. Examples of metabolomics evaluations of sulfur amino-acid metabolism in psychiatry, neurology, and neuro-oncology and of lipidomics in neurology will be reviewed.

Mass selective separation applied to radioisotopes of cesium: Mass selective applied to radioisotopes

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

Dion, Michael; Eiden, Greg; Farmer, Orville

2016-07-22

A developed technique that uses the intrinsic mass-based separation capability of a quadrupole mass spectrometer has been used to resolve spectral radiometric interference of two isotopes of the same element. In this work the starting sample was a combination of 137Cs and 134Cs and was (activity) dominated by 137Cs and this methodology separated and “implanted” 134Cs that was later quantified for spectral features and ac- tivity with traditional radiometric techniques. This work demonstrated a 134Cs/137Cs activity ratio enhancement of >4 orders of magnitude and complete removal of 137Cs spectral features from the implanted target mass (i.e., 134).

Assessing the impact of mass rape on the incidence of HIV in conflict-affected countries

PubMed Central

Virginie, Supervie; Yasmin, Halima; Sally, Blower

2010-01-01

Objectives To quantify the potential impact of mass rape on HIV incidence in seven conflict-afflicted-countries (CACs), with severe HIV epidemics, in Sub-Saharan Africa. Design Uncertainty analysis of a risk equation model. Methods A mathematical model was used to evaluate the potential impact of mass rape on increasing HIV incidence in women and girls in: Burundi, Democratic Republic of Congo (DRC), Rwanda, Sierra Leone, Somalia, southern Sudan and Uganda. The model was parameterized with data from UNAIDS/WHO and the US Census Bureau’s International Data Base. Incidence data from UNAIDS/WHO were used for calibration. Results Mass rape could cause ~five HIV infections per 100,000 females per year in the DRC, Sudan, Somalia and Sierra Leone, double that in Burundi and Rwanda, and quadruple that in Uganda. The number of females infected per year due to mass rape is likely to be relatively low in Somalia and Sierra Leone, 127 (median: Inter-Quartile-Range (IQR) 55–254) and 156 (median: IQR 69–305), respectively. Numbers could be high in the DRC and Uganda: 1,120 (median: IQR 527–2,360) and 2,172 (median: IQR 1,031–4,668), respectively. In Burundi, Rwanda and Sudan numbers are likely to be intermediate. Under extreme conditions 10,000 women and girls could be infected per year in the DRC, and 20,000 women and girls in Uganda. Mass rape could increase annual incidence by ~ 7% (median: IQR 3–15). Conclusions Interventions and treatment targeted to rape survivors during armed conflicts could reduce HIV incidence. Support should be provided both on the basis of human rights and public health. PMID:20859191

Prostate Cancer Clinical Consortium Clinical Research Site:Targeted Therapies

DTIC Science & Technology

2015-10-01

AWARD NUMBER: W81XWH-14-2-0159 TITLE: Prostate Cancer Clinical Consortium Clinical Research Site: Targeted Therapies PRINCIPAL INVESTIGATOR...Sep 2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Prostate Cancer Clinical Consortium Clinical Research Site: Targeted Therapies 5b. GRANT NUMBER... therapy resistance/sensitivity, identification of new therapeutic targets through high quality genomic analyses, providing access to the highest quality

Mass amplifying probe for sensitive fluorescence anisotropy detection of small molecules in complex biological samples.

PubMed

Cui, Liang; Zou, Yuan; Lin, Ninghang; Zhu, Zhi; Jenkins, Gareth; Yang, Chaoyong James

2012-07-03

Fluorescence anisotropy (FA) is a reliable and excellent choice for fluorescence sensing. One of the key factors influencing the FA value for any molecule is the molar mass of the molecule being measured. As a result, the FA method with functional nucleic acid aptamers has been limited to macromolecules such as proteins and is generally not applicable for the analysis of small molecules because their molecular masses are relatively too small to produce observable FA value changes. We report here a molecular mass amplifying strategy to construct anisotropy aptamer probes for small molecules. The probe is designed in such a way that only when a target molecule binds to the probe does it activate its binding ability to an anisotropy amplifier (a high molecular mass molecule such as protein), thus significantly increasing the molecular mass and FA value of the probe/target complex. Specifically, a mass amplifying probe (MAP) consists of a targeting aptamer domain against a target molecule and molecular mass amplifying aptamer domain for the amplifier protein. The probe is initially rendered inactive by a small blocking strand partially complementary to both target aptamer and amplifier protein aptamer so that the mass amplifying aptamer domain would not bind to the amplifier protein unless the probe has been activated by the target. In this way, we prepared two probes that constitute a target (ATP and cocaine respectively) aptamer, a thrombin (as the mass amplifier) aptamer, and a fluorophore. Both probes worked well against their corresponding small molecule targets, and the detection limits for ATP and cocaine were 0.5 μM and 0.8 μM, respectively. More importantly, because FA is less affected by environmental interferences, ATP in cell media and cocaine in urine were directly detected without any tedious sample pretreatment. Our results established that our molecular mass amplifying strategy can be used to design aptamer probes for rapid, sensitive, and selective

[Imaging Mass Spectrometry in Histopathologic Analysis].

PubMed

Yamazaki, Fumiyoshi; Seto, Mitsutoshi

2015-04-01

Matrix-assisted laser desorption/ionization (MALDI)-imaging mass spectrometry (IMS) enables visualization of the distribution of a range of biomolecules by integrating biochemical information from mass spectrometry with positional information from microscopy. IMS identifies a target molecule. In addition, IMS enables global analysis of biomolecules containing unknown molecules by detecting the ratio of the molecular weight to electric charge without any target, which makes it possible to identify novel molecules. IMS generates data on the distribution of lipids and small molecules in tissues, which is difficult to visualize with either conventional counter-staining or immunohistochemistry. In this review, we firstly introduce the principle of imaging mass spectrometry and recent advances in the sample preparation method. Secondly, we present findings regarding biological samples, especially pathological ones. Finally, we discuss the limitations and problems of the IMS technique and clinical application, such as in drug development.

Choosing a therapy electron accelerator target.

PubMed

Hutcheon, R M; Schriber, S O; Funk, L W; Sherman, N K

1979-01-01

Angular distributions of photon depth dose produced by 25-MeV electrons incident on several fully stopping single-element targets (C, Al, Cu, Mo, Ta, Pb) and two composite layered targets (Ni-Al, W-Al) were studied. Depth-dose curves measured using TLD-700 (thermoluminescent dosimeter) chips embedded in lucite phantoms. Several useful therapy electron accelerator design curves were determined, including relative flattener thickness as a function of target atomic number, "effective" bremsstrahlung endpoint energy or beam "hardness" as a function of target atomic number and photon emission angle, and estimates of shielding thickness as a function of angle required to reduce the radiation outside the treatment cone to required levels.

MassTRIX: mass translator into pathways.

PubMed

Suhre, Karsten; Schmitt-Kopplin, Philippe

2008-07-01

Recent technical advances in mass spectrometry (MS) have brought the field of metabolomics to a point where large numbers of metabolites from numerous prokaryotic and eukaryotic organisms can now be easily and precisely detected. The challenge today lies in the correct annotation of these metabolites on the basis of their accurate measured masses. Assignment of bulk chemical formula is generally possible, but without consideration of the biological and genomic context, concrete metabolite annotations remain difficult and uncertain. MassTRIX responds to this challenge by providing a hypothesis-driven approach to high precision MS data annotation. It presents the identified chemical compounds in their genomic context as differentially colored objects on KEGG pathway maps. Information on gene transcription or differences in the gene complement (e.g. samples from different bacterial strains) can be easily added. The user can thus interpret the metabolic state of the organism in the context of its potential and, in the case of submitted transcriptomics data, real enzymatic capacities. The MassTRIX web server is freely accessible at http://masstrix.org.

Automated Validation of Results and Removal of Fragment Ion Interferences in Targeted Analysis of Data-independent Acquisition Mass Spectrometry (MS) using SWATHProphet*

PubMed Central

Keller, Andrew; Bader, Samuel L.; Shteynberg, David; Hood, Leroy; Moritz, Robert L.

2015-01-01

Proteomics by mass spectrometry technology is widely used for identifying and quantifying peptides and proteins. The breadth and sensitivity of peptide detection have been advanced by the advent of data-independent acquisition mass spectrometry. Analysis of such data, however, is challenging due to the complexity of fragment ion spectra that have contributions from multiple co-eluting precursor ions. We present SWATHProphet software that identifies and quantifies peptide fragment ion traces in data-independent acquisition data, provides accurate probabilities to ensure results are correct, and automatically detects and removes contributions to quantitation originating from interfering precursor ions. Integration in the widely used open source Trans-Proteomic Pipeline facilitates subsequent analyses such as combining results of multiple data sets together for improved discrimination using iProphet and inferring sample proteins using ProteinProphet. This novel development should greatly help make data-independent acquisition mass spectrometry accessible to large numbers of users. PMID:25713123

A SYSTEMATIC ANALYSIS OF CAUSTIC METHODS FOR GALAXY CLUSTER MASSES

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

Gifford, Daniel; Miller, Christopher; Kern, Nicholas

We quantify the expected observed statistical and systematic uncertainties of the escape velocity as a measure of the gravitational potential and total mass of galaxy clusters. We focus our attention on low redshift (z {<=}0.15) clusters, where large and deep spectroscopic datasets currently exist. Utilizing a suite of Millennium Simulation semi-analytic galaxy catalogs, we find that the dynamical mass, as traced by either the virial relation or the escape velocity, is robust to variations in how dynamical friction is applied to ''orphan'' galaxies in the mock catalogs (i.e., those galaxies whose dark matter halos have fallen below the resolution limit).more » We find that the caustic technique recovers the known halo masses (M{sub 200}) with a third less scatter compared to the virial masses. The bias we measure increases quickly as the number of galaxies used decreases. For N{sub gal} > 25, the scatter in the escape velocity mass is dominated by projections along the line-of-sight. Algorithmic uncertainties from the determination of the projected escape velocity profile are negligible. We quantify how target selection based on magnitude, color, and projected radial separation can induce small additional biases into the escape velocity masses. Using N{sub gal} = 150 (25), the caustic technique has a per cluster scatter in ln (M|M{sub 200}) of 0.3 (0.5) and bias 1% {+-} 3{r_brace} (16% {+-} 5{r_brace}) for clusters with masses >10{sup 14} M{sub Sun} at z < 0.15.« less

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.

Soft-Rotator Coupled Channels Global Optical Potential for A=24-122 Mass Region Nuclides up to 200-MeV Incident Nucleon Energies

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

Soukhovitski, Efrem Sh.; Chiba, Satoshi; Lee, Jeong-Yeon

2005-05-24

A coupled-channels optical model with a coupling scheme based on nuclear wave functions of the soft-rotator model was applied to analyze experimental nucleon-nucleus interaction data for even-even nuclides with mass number A=24-122. We found that all the available data (total cross sections, angular distributions of elastically and inelastically scattered nucleons, and reaction cross sections) for these nuclides can be described to a good accuracy using an optical potential having smooth dependencies of potential values, radii, and diffuseness on the mass number. The individual properties of the target nuclides are accounted for by individuality of the nuclear Hamiltonian parameters, adjusted tomore » reproduce the low-lying collective level structure, Fermi energies, and deformation parameters.« less

Novel Therapeutic Target for the Treatment of Lupus

DTIC Science & Technology

2014-09-01

AWARD NUMBER: W81XWH-12-1-0205 TITLE: Novel Therapeutic Target for the Treatment of Lupus PRINCIPAL INVESTIGATOR: Lisa Laury-Kleintop...SUBTITLE 5a. CONTRACT NUMBER Novel Therapeutic Target for the Treatment of Lupus 5b. GRANT NUMBER W81XWH-12-1-0205 5c. PROGRAM ELEMENT NUMBER 6...Systemic lupus erythematosus, autoantibodies. 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 7 19a. NAME OF

miR-24-2 controls H2AFX expression regardless of gene copy number alteration and induces apoptosis by targeting antiapoptotic gene BCL-2: a potential for therapeutic intervention.

PubMed

Srivastava, Niloo; Manvati, Siddharth; Srivastava, Archita; Pal, Ranjana; Kalaiarasan, Ponnusamy; Chattopadhyay, Shilpi; Gochhait, Sailesh; Dua, Raina; Bamezai, Rameshwar N K

2011-04-04

New levels of gene regulation with microRNA (miR) and gene copy number alterations (CNAs) have been identified as playing a role in various cancers. We have previously reported that sporadic breast cancer tissues exhibit significant alteration in H2AX gene copy number. However, how CNA affects gene expression and what is the role of miR, miR-24-2, known to regulate H2AX expression, in the background of the change in copy number, are not known. Further, many miRs, including miR-24-2, are implicated as playing a role in cell proliferation and apoptosis, but their specific target genes and the pathways contributing to them remain unexplored. Changes in gene copy number and mRNA/miR expression were estimated using real-time polymerase chain reaction assays in two mammalian cell lines, MCF-7 and HeLa, and in a set of sporadic breast cancer tissues. In silico analysis was performed to find the putative target for miR-24-2. MCF-7 cells were transfected with precursor miR-24-2 oligonucleotides, and the gene expression levels of BRCA1, BRCA2, ATM, MDM2, TP53, CHEK2, CYT-C, BCL-2, H2AFX and P21 were examined using TaqMan gene expression assays. Apoptosis was measured by flow cytometric detection using annexin V dye. A luciferase assay was performed to confirm BCL-2 as a valid cellular target of miR-24-2. It was observed that H2AX gene expression was negatively correlated with miR-24-2 expression and not in accordance with the gene copy number status, both in cell lines and in sporadic breast tumor tissues. Further, the cells overexpressing miR-24-2 were observed to be hypersensitive to DNA damaging drugs, undergoing apoptotic cell death, suggesting the potentiating effect of mir-24-2-mediated apoptotic induction in human cancer cell lines treated with anticancer drugs. BCL-2 was identified as a novel cellular target of miR-24-2. mir-24-2 is capable of inducing apoptosis by modulating different apoptotic pathways and targeting BCL-2, an antiapoptotic gene. The study suggests

Mass discharge assessment at a brominated DNAPL site: Effects of known DNAPL source mass removal

NASA Astrophysics Data System (ADS)

Johnston, C. D.; Davis, G. B.; Bastow, T. P.; Woodbury, R. J.; Rao, P. S. C.; Annable, M. D.; Rhodes, S.

2014-08-01

Management and closure of contaminated sites is increasingly being proposed on the basis of mass flux of dissolved contaminants in groundwater. Better understanding of the links between source mass removal and contaminant mass fluxes in groundwater would allow greater acceptance of this metric in dealing with contaminated sites. Our objectives here were to show how measurements of the distribution of contaminant mass flux and the overall mass discharge emanating from the source under undisturbed groundwater conditions could be related to the processes and extent of source mass depletion. In addition, these estimates of mass discharge were sought in the application of agreed remediation targets set in terms of pumped groundwater quality from offsite wells. Results are reported from field studies conducted over a 5-year period at a brominated DNAPL (tetrabromoethane, TBA; and tribromoethene, TriBE) site located in suburban Perth, Western Australia. Groundwater fluxes (qw; L3/L2/T) and mass fluxes (Jc; M/L2/T) of dissolved brominated compounds were simultaneously estimated by deploying Passive Flux Meters (PFMs) in wells in a heterogeneous layered aquifer. PFMs were deployed in control plane (CP) wells immediately down-gradient of the source zone, before (2006) and after (2011) 69-85% of the source mass was removed, mainly by groundwater pumping from the source zone. The high-resolution (26-cm depth interval) measures of qw and Jc along the source CP allowed investigation of the DNAPL source-zone architecture and impacts of source mass removal. Comparable estimates of total mass discharge (MD; M/T) across the source zone CP reduced from 104 g day- 1 to 24-31 g day- 1 (70-77% reductions). Importantly, this mass discharge reduction was consistent with the estimated proportion of source mass remaining at the site (15-31%). That is, a linear relationship between mass discharge and source mass is suggested. The spatial detail of groundwater and mass flux distributions also

Mass discharge assessment at a brominated DNAPL site: Effects of known DNAPL source mass removal.

PubMed

Johnston, C D; Davis, G B; Bastow, T P; Woodbury, R J; Rao, P S C; Annable, M D; Rhodes, S

2014-08-01

Management and closure of contaminated sites is increasingly being proposed on the basis of mass flux of dissolved contaminants in groundwater. Better understanding of the links between source mass removal and contaminant mass fluxes in groundwater would allow greater acceptance of this metric in dealing with contaminated sites. Our objectives here were to show how measurements of the distribution of contaminant mass flux and the overall mass discharge emanating from the source under undisturbed groundwater conditions could be related to the processes and extent of source mass depletion. In addition, these estimates of mass discharge were sought in the application of agreed remediation targets set in terms of pumped groundwater quality from offsite wells. Results are reported from field studies conducted over a 5-year period at a brominated DNAPL (tetrabromoethane, TBA; and tribromoethene, TriBE) site located in suburban Perth, Western Australia. Groundwater fluxes (qw; L(3)/L(2)/T) and mass fluxes (Jc; M/L(2)/T) of dissolved brominated compounds were simultaneously estimated by deploying Passive Flux Meters (PFMs) in wells in a heterogeneous layered aquifer. PFMs were deployed in control plane (CP) wells immediately down-gradient of the source zone, before (2006) and after (2011) 69-85% of the source mass was removed, mainly by groundwater pumping from the source zone. The high-resolution (26-cm depth interval) measures of qw and Jc along the source CP allowed investigation of the DNAPL source-zone architecture and impacts of source mass removal. Comparable estimates of total mass discharge (MD; M/T) across the source zone CP reduced from 104gday(-1) to 24-31gday(-1) (70-77% reductions). Importantly, this mass discharge reduction was consistent with the estimated proportion of source mass remaining at the site (15-31%). That is, a linear relationship between mass discharge and source mass is suggested. The spatial detail of groundwater and mass flux distributions

Effect of Name Change of Schizophrenia on Mass Media Between 1985 and 2013 in Japan: A Text Data Mining Analysis

PubMed Central

Koike, Shinsuke; Yamaguchi, Sosei; Ojio, Yasutaka; Ohta, Kazusa; Ando, Shuntaro

2016-01-01

Background: Mass media such as newspapers and TV news affect mental health-related stigma. In Japan, the name of schizophrenia was changed in 2002 for the purposes of stigma reduction; however, little has been known about the effect of name change of schizophrenia on mass media. Method: Articles including old and new names of schizophrenia, depressive disorder, and diabetes mellitus (DM) in headlines and/or text were extracted from 23169092 articles in 4 major Japanese newspapers and 1 TV news program (1985–2013). The trajectory of the number of articles including each term was determined across years. Then, all text in news headlines was segmented as per part-of-speech level using text data mining. Segmented words were classified into 6 categories and in each category of extracted words by target term and period were also tested. Results: Total 51789 and 1106 articles including target terms in newspaper articles and TV news segments were obtained, respectively. The number of articles including the target terms increased across years. Relative increase was observed in the articles published on schizophrenia since 2003 compared with those on DM and between 2000 and 2005 compared with those on depressive disorder. Word tendency used in headlines was equivalent before and after 2002 for the articles including each target term. Articles for schizophrenia contained more negative words than depressive disorder and DM (31.5%, 16.0%, and 8.2%, respectively). Conclusions: Name change of schizophrenia had a limited effect on the articles published and little effect on its contents. PMID:26614786

Targeted Analyte Detection by Standard Addition Improves Detection Limits in MALDI Mass Spectrometry

PubMed Central

Eshghi, Shadi Toghi; Li, Xingde; Zhang, Hui

2014-01-01

Matrix-assisted laser desorption/ionization has proven an effective tool for fast and accurate determination of many molecules. However, the detector sensitivity and chemical noise compromise the detection of many invaluable low-abundance molecules from biological and clinical samples. To challenge this limitation, we developed a targeted analyte detection (TAD) technique. In TAD, the target analyte is selectively elevated by spiking a known amount of that analyte into the sample, thereby raising its concentration above the noise level, where we take advantage of the improved sensitivity to detect the presence of the endogenous analyte in the sample. We assessed TAD on three peptides in simple and complex background solutions with various exogenous analyte concentrations in two MALDI matrices. TAD successfully improved the limit of detection (LOD) of target analytes when the target peptides were added to the sample in a concentration close to optimum concentration. The optimum exogenous concentration was estimated through a quantitative method to be approximately equal to the original LOD for each target. Also, we showed that TAD could achieve LOD improvements on an average of 3-fold in a simple and 2-fold in a complex sample. TAD provides a straightforward assay to improve the LOD of generic target analytes without the need for costly hardware modifications. PMID:22877355

Digital imaging mass spectrometry.

PubMed

Bamberger, Casimir; Renz, Uwe; Bamberger, Andreas

2011-06-01

Methods to visualize the two-dimensional (2D) distribution of molecules by mass spectrometric imaging evolve rapidly and yield novel applications in biology, medicine, and material surface sciences. Most mass spectrometric imagers acquire high mass resolution spectra spot-by-spot and thereby scan the object's surface. Thus, imaging is slow and image reconstruction remains cumbersome. Here we describe an imaging mass spectrometer that exploits the true imaging capabilities by ion optical means for the time of flight mass separation. The mass spectrometer is equipped with the ASIC Timepix chip as an array detector to acquire the position, mass, and intensity of ions that are imaged by matrix-assisted laser desorption/ionization (MALDI) directly from the target sample onto the detector. This imaging mass spectrometer has a spatial resolving power at the specimen of (84 ± 35) μm with a mass resolution of 45 and locates atoms or organic compounds on a surface area up to ~2 cm(2). Extended laser spots of ~5 mm(2) on structured specimens allows parallel imaging of selected masses. The digital imaging mass spectrometer proves high hit-multiplicity, straightforward image reconstruction, and potential for high-speed readout at 4 kHz or more. This device demonstrates a simple way of true image acquisition like a digital photographic camera. The technology may enable a fast analysis of biomolecular samples in near future.

AdA Compiler Validation Summary Report: Certificate Number: 910920W1. 11211 Verdix Corporation, VADS Sun4 SunOS= 68020/30 ARTX, VAda-110-40120, Version 6.0, SPAECstation 2 (Host) to Motorola MVME147 (Target)

DTIC Science & Technology

1991-09-20

SunOS Release 4.1.1) Target Computer System: Motorola MVME147 (Motorola 68030 Bare Board) Customer Agreement Number: 91-07-16- VRX See section 3.1 for...AVF-VSR-504.0292 18 February 1992 91-07-1 6- VRX Ada COMPILER VALIDATION SUMMARY REPORT: Certificate Number: 910920W1.11211 VERDIX Corporation VADS...SunOS Release 4.1.1) Target Computer System: Motorola MVME147 (Motorola 68030 Bare Board) Customer Agreement Number: 91-07-16- VRX See section 3.1 for

Stable isotope labelling methods in mass spectrometry-based quantitative proteomics.

PubMed

Chahrour, Osama; Cobice, Diego; Malone, John

2015-09-10

Mass-spectrometry based proteomics has evolved as a promising technology over the last decade and is undergoing a dramatic development in a number of different areas, such as; mass spectrometric instrumentation, peptide identification algorithms and bioinformatic computational data analysis. The improved methodology allows quantitative measurement of relative or absolute protein amounts, which is essential for gaining insights into their functions and dynamics in biological systems. Several different strategies involving stable isotopes label (ICAT, ICPL, IDBEST, iTRAQ, TMT, IPTL, SILAC), label-free statistical assessment approaches (MRM, SWATH) and absolute quantification methods (AQUA) are possible, each having specific strengths and weaknesses. Inductively coupled plasma mass spectrometry (ICP-MS), which is still widely recognised as elemental detector, has recently emerged as a complementary technique to the previous methods. The new application area for ICP-MS is targeting the fast growing field of proteomics related research, allowing absolute protein quantification using suitable elemental based tags. This document describes the different stable isotope labelling methods which incorporate metabolic labelling in live cells, ICP-MS based detection and post-harvest chemical label tagging for protein quantification, in addition to summarising their pros and cons. Copyright © 2015 Elsevier B.V. All rights reserved.

Extension to Higher Mass Numbers of an Improved Knockout-Ablation-Coalescence Model for Secondary Neutron and Light Ion Production in Cosmic Ray Interactions

NASA Astrophysics Data System (ADS)

Indi Sriprisan, Sirikul; Townsend, Lawrence; Cucinotta, Francis A.; Miller, Thomas M.

Purpose: An analytical knockout-ablation-coalescence model capable of making quantitative predictions of the neutron spectra from high-energy nucleon-nucleus and nucleus-nucleus collisions is being developed for use in space radiation protection studies. The FORTRAN computer code that implements this model is called UBERNSPEC. The knockout or abrasion stage of the model is based on Glauber multiple scattering theory. The ablation part of the model uses the classical evaporation model of Weisskopf-Ewing. In earlier work, the knockout-ablation model has been extended to incorporate important coalescence effects into the formalism. Recently, alpha coalescence has been incorporated, and the ability to predict light ion spectra with the coalescence model added. The earlier versions were limited to nuclei with mass numbers less than 69. In this work, the UBERNSPEC code has been extended to make predictions of secondary neutrons and light ion production from the interactions of heavy charged particles with higher mass numbers (as large as 238). The predictions are compared with published measurements of neutron spectra and light ion energy for a variety of collision pairs. Furthermore, the predicted spectra from this work are compared with the predictions from the recently-developed heavy ion event generator incorporated in the Monte Carlo radiation transport code HETC-HEDS.

Broad screening of illicit ingredients in cosmetics using ultra-high-performance liquid chromatography-hybrid quadrupole-Orbitrap mass spectrometry with customized accurate-mass database and mass spectral library.

PubMed

Meng, Xianshuang; Bai, Hua; Guo, Teng; Niu, Zengyuan; Ma, Qiang

2017-12-15

Comprehensive identification and quantitation of 100 multi-class regulated ingredients in cosmetics was achieved using ultra-high-performance liquid chromatography (UHPLC) coupled with hybrid quadrupole-Orbitrap high-resolution mass spectrometry (Q-Orbitrap HRMS). A simple, efficient, and inexpensive sample pretreatment protocol was developed using ultrasound-assisted extraction (UAE), followed by dispersive solid-phase extraction (dSPE). The cosmetic samples were analyzed by UHPLC-Q-Orbitrap HRMS under synchronous full-scan MS and data-dependent MS/MS (full-scan MS 1 /dd-MS 2 ) acquisition mode. The mass resolution was set to 70,000 FWHM (full width at half maximum) for full-scan MS 1 and 17,500 FWHM for dd-MS 2 stage with the experimentally measured mass deviations of less than 2ppm (parts per million) for quasi-molecular ions and 5ppm for characteristic fragment ions for each individual analyte. An accurate-mass database and a mass spectral library were built in house for searching the 100 target compounds. Broad screening was conducted by comparing the experimentally measured exact mass of precursor and fragment ions, retention time, isotopic pattern, and ionic ratio with the accurate-mass database and by matching the acquired MS/MS spectra against the mass spectral library. The developed methodology was evaluated and validated in terms of limits of detection (LODs), limits of quantitation (LOQs), linearity, stability, accuracy, and matrix effect. The UHPLC-Q-Orbitrap HRMS approach was applied for the analysis of 100 target illicit ingredients in 123 genuine cosmetic samples, and exhibited great potential for high-throughput, sensitive, and reliable screening of multi-class illicit compounds in cosmetics. Copyright © 2017 Elsevier B.V. All rights reserved.

Using thresholds based on risk of cardiovascular disease to target treatment for hypertension: modelling events averted and number treated

PubMed Central

Baker, Simon; Priest, Patricia; Jackson, Rod

2000-01-01

Objective To estimate the impact of using thresholds based on absolute risk of cardiovascular disease to target drug treatment to lower blood pressure in the community. Design Modelling of three thresholds of treatment for hypertension based on the absolute risk of cardiovascular disease. 5 year risk of disease was estimated for each participant using an equation to predict risk. Net predicted impact of the thresholds on the number of people treated and the number of disease events averted over 5 years was calculated assuming a relative treatment benefit of one quarter. Setting Auckland, New Zealand. Participants 2158 men and women aged 35-79 years randomly sampled from the general electoral rolls. Main outcome measures Predicted 5 year risk of cardiovascular disease event, estimated number of people for whom treatment would be recommended, and disease events averted over 5 years at different treatment thresholds. Results 46 374 (12%) Auckland residents aged 35-79 receive drug treatment to lower their blood pressure, averting an estimated 1689 disease events over 5 years. Restricting treatment to individuals with blood pressure ⩾170/100 mm Hg and those with blood pressure between 150/90-169/99 mm Hg who have a predicted 5 year risk of disease ⩾10% would increase the net number for whom treatment would be recommended by 19 401. This 42% relative increase is predicted to avert 1139/1689 (68%) additional disease events overall over 5 years compared with current treatment. If the threshold for 5 year risk of disease is set at 15% the number recommended for treatment increases by <10% but about 620/1689 (37%) additional events can be averted. A 20% threshold decreases the net number of patients recommended for treatment by about 10% but averts 204/1689 (12%) more disease events than current treatment. Conclusions Implementing treatment guidelines that use treatment thresholds based on absolute risk could significantly improve the efficiency of drug treatment to

Effective atomic numbers and electron density of dosimetric material

PubMed Central

Kaginelli, S. B.; Rajeshwari, T.; Sharanabasappa; Kerur, B. R.; Kumar, Anil S.

2009-01-01

A novel method for determination of mass attenuation coefficient of x-rays employing NaI (Tl) detector system and radioactive sources is described.in this paper. A rigid geometry arrangement and gating of the spectrometer at FWHM position and selection of absorber foils are all done following detailed investigation, to minimize the effect of small angle scattering and multiple scattering on the mass attenuation coefficient, μ/ρ, value. Firstly, for standardization purposes the mass attenuation coefficients of elemental foils such as Aluminum, Copper, Molybdenum, Tantalum and Lead are measured and then, this method is utilized for dosimetric interested material (sulfates). The experimental mass attenuation coefficient values are compared with the theoretical values to find good agreement between the theory and experiment within one to two per cent. The effective atomic numbers of the biological substitute material are calculated by sum rule and from the graph. The electron density of dosimetric material is calculated using the effective atomic number. The study has discussed in detail the attenuation coefficient, effective atomic number and electron density of dosimetric material/biological substitutes. PMID:20098566

Targeted Peptide Measurements in Biology and Medicine: Best Practices for Mass Spectrometry-based Assay Development Using a Fit-for-Purpose Approach

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

Carr, Steven A.; Abbateillo, Susan E.; Ackermann, Bradley L.

2014-01-14

Adoption of targeted mass spectrometry (MS) approaches such as multiple reaction monitoring (MRM) to study biological and biomedical questions is well underway in the proteomics community. Successful application depends on the ability to generate reliable assays that uniquely and confidently identify target peptides in a sample. Unfortunately, there is a wide range of criteria being applied to say that an assay has been successfully developed. There is no consensus on what criteria are acceptable and little understanding of the impact of variable criteria on the quality of the results generated. Publications describing targeted MS assays for peptides frequently do notmore » contain sufficient information for readers to establish confidence that the tests work as intended or to be able to apply the tests described in their own labs. Guidance must be developed so that targeted MS assays with established performance can be made widely distributed and applied by many labs worldwide. To begin to address the problems and their solutions, a workshop was held at the National Institutes of Health with representatives from the multiple communities developing and employing targeted MS assays. Participants discussed the analytical goals of their experiments and the experimental evidence needed to establish that the assays they develop work as intended and are achieving the required levels of performance. Using this “fit-for-purpose” approach, the group defined three tiers of assays distinguished by their performance and extent of analytical characterization. Computational and statistical tools useful for the analysis of targeted MS results were described. Participants also detailed the information that authors need to provide in their manuscripts to enable reviewers and readers to clearly understand what procedures were performed and to evaluate the reliability of the peptide or protein quantification measurements reported. This paper presents a summary of the meeting

Determination of thiol metabolites in human urine by stable isotope labeling in combination with pseudo-targeted mass spectrometry analysis

NASA Astrophysics Data System (ADS)

Liu, Ping; Qi, Chu-Bo; Zhu, Quan-Fei; Yuan, Bi-Feng; Feng, Yu-Qi

2016-02-01

Precursor ion scan and multiple reaction monitoring scan (MRM) are two typical scan modes in mass spectrometry analysis. Here, we developed a strategy by combining stable isotope labeling (IL) with liquid chromatography-mass spectrometry (LC-MS) under double precursor ion scan (DPI) and MRM for analysis of thiols in 5 types of human cancer urine. Firstly, the IL-LC-DPI-MS method was applied for non-targeted profiling of thiols from cancer samples. Compared to traditional full scan mode, the DPI method significantly improved identification selectivity and accuracy. 103 thiol candidates were discovered in all cancers and 6 thiols were identified by their standards. It is worth noting that pantetheine, for the first time, was identified in human urine. Secondly, the IL-LC-MRM-MS method was developed for relative quantification of thiols in cancers compared to healthy controls. All the MRM transitions of light and heavy labeled thiols were acquired from urines by using DPI method. Compared to DPI method, the sensitivity of MRM improved by 2.1-11.3 folds. In addition, the concentration of homocysteine, γ-glutamylcysteine and pantetheine enhanced more than two folds in cancer patients compared to healthy controls. Taken together, the method demonstrated to be a promising strategy for identification and comprehensive quantification of thiols in human urines.

The remote ischemic preconditioning algorithm: effect of number of cycles, cycle duration and effector organ mass on efficacy of protection.

PubMed

Johnsen, Jacob; Pryds, Kasper; Salman, Rasha; Løfgren, Bo; Kristiansen, Steen Buus; Bøtker, Hans Erik

2016-03-01

Remote ischemic preconditioning (rIPC), induced by cycles of transient limb ischemia and reperfusion (IR), is cardioprotective. The optimal rIPC-algorithm is not established. We investigated the effect of cycle numbers and ischemia duration within each rIPC-cycle and the influence of effector organ mass on the efficacy of cardioprotection. Furthermore, the duration of the early phase of protection by rIPC was investigated. Using a tourniquet tightened at the inguinal level, we subjected C57Bl/6NTac mice to intermittent hind-limb ischemia and reperfusion. The rIPC-protocols consisted of (I) two, four, six or eight cycles, (II) 2, 5 or 10 min of ischemia in each cycle, (III) single or two hind-limb occlusions and (IV) 0.5, 1.5, 2.0 or 2.5 h intervals from rIPC to index cardiac ischemia. All rIPC algorithms were followed by 5 min of reperfusion. The hearts were subsequently exposed to 25 min of global ischemia and 60 min of reperfusion in an ex vivo Langendorff model. Cardioprotection was evaluated by infarct size and post-ischemic hemodynamic recovery. Four to six rIPC cycles yielded significant cardioprotection with no further protection by eight cycles. Ischemic cycles lasting 2 min offered the same protection as cycles of 5 min ischemia, whereas prolonged cycles lasting 10 min abrogated protection. One and two hind-limb preconditioning were equally protective. In our mouse model, the duration of protection by rIPC was 1.5 h. These findings indicate that the number and duration of cycles rather than the tissue mass exposed to rIPC determines the efficacy of rIPC.

Categorization and identification of simultaneous targets.

PubMed

Theeuwes, J

1991-02-01

Early and late selection theories of visual attention disagree about whether identification occurs before or after selection. Studies showing the category effect, i.e., the time to detect a letter is hardly affected by the number of digits present in the display, are taken as evidence for late selection theories since these studies suggest parallel identification of all items in the display. As an extension of previous studies, in the present study two categorically different targets were presented simultaneously among a variable number of nontargets. Subjects were shown brief displays of two target letters among either 2, 4 or 6 nontarget digits. Subjects responded 'same' when the two letters were identical and 'different' otherwise. Since the 'same-different' response reflects the combined outcome of the simultaneous targets, late-selection theory predicts that the time to match the target letters is independent of the number of nontarget digits. Alternatively, early-selection theory predicts a linear increase of reaction time with display size since the presence of more than one target disrupts parallel preattentive processing, leading to a serial search through all items in the display. The results provide evidence for the early-selection view since reaction time increased linearly with the number of categorically different nontargets. A control experiment revealed that none of the alternative explanations could account for the display size effect.

Estimation of the emission factors of particle number and mass fractions from traffic at a site where mean vehicle speeds vary over short distances

NASA Astrophysics Data System (ADS)

Jones, Alan M.; Harrison, Roy M.

Emission factors for particle number in three size ranges (11-30; 30-100 and >100 nm) as well as for PM 2.5, PM 2.5-10 and PM 10 mass have been estimated separately for heavy and light-duty vehicles in a heavily trafficked street canyon in London where traffic speeds vary considerably over short distances. Emissions of NO x were estimated from published emission factors, and emissions of other pollutants estimated from their ratio to NO x in the roadside concentration after subtraction of the simultaneously measured urban background. The estimated emission factors are compared with other published data. Despite many differences in the design and implementation of the various studies, the results for particulate matter are broadly similar. Estimates of particle number emissions in this study for light-duty vehicles are very close to other published data, whilst those for heavy-duty vehicles are lower than in the more comparable studies. It is suggested that a contributory factor may be the introduction of diesel particle oxidation traps on some of the bus fleet in London. Estimates of emission factors for particle mass (PM 2.5 and PM 2.5-10) are within the range of other published data, and total mass emissions estimated from the ratio of concentration to NO x are tolerably close to those estimated using emission factors from the National Atmospheric Emissions Inventory (NAEI). However, the method leads to an estimate of carbon monoxide emissions 3-6 times larger than that derived using the NAEI factors.

An exploratory review of HIV prevention mass media campaigns targeting men who have sex with men

PubMed Central

2014-01-01

Background Men who have sex with men (MSM) are at increased risk of HIV infection in both high- and low-income settings. Mass media campaigns have been used as a means of communicating HIV health promotion messages to large audiences of MSM. There is no consensus on which designs are most appropriate to evaluate the process and outcomes of such interventions. Methods An exploratory review was conducted to assess research examining awareness, acceptability, effects on HIV testing, disclosure and sexual risk, and cost-effectiveness of HIV mass media campaigns targeting MSM. We searched for quantitative and qualitative studies published between 1990 and May 2011 via the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, Psych Info, ISI Web of Science, OpenGrey and COPAC, and contacting experts. No exclusions were made on the basis of study design or methods because our primary aim was to map evidence. We appraised study quality and present a narrative synthesis of findings. Results Sixteen reports from 12 studies were included. All were from high-income countries and most examined multi-media interventions. Half of the studies were single cross-sectional surveys. Three repeat cross-sectional studies collected data pre and post the campaign launch. The remaining three studies monitored routine data. Three studies included a nested qualitative component. Campaign coverage was the most commonly reported outcome (9 studies). Imagery, tone of language, content and relevance were identified in the qualitative research as factors influencing campaign acceptability. HIV testing rates (or intention to test) were reported by five studies. Two studies reported that testing rates were higher among men who had seen the campaigns compared to men who had not, but this may reflect confounding. Findings were less consistent regarding reductions in sexual risk behaviours (4 studies). None of the studies examined cost-effectiveness. Conclusions Campaigns aim to provide MSM

An exploratory review of HIV prevention mass media campaigns targeting men who have sex with men.

PubMed

French, Rebecca S; Bonell, Chris; Wellings, Kaye; Weatherburn, Peter

2014-06-18

Men who have sex with men (MSM) are at increased risk of HIV infection in both high- and low-income settings. Mass media campaigns have been used as a means of communicating HIV health promotion messages to large audiences of MSM. There is no consensus on which designs are most appropriate to evaluate the process and outcomes of such interventions. An exploratory review was conducted to assess research examining awareness, acceptability, effects on HIV testing, disclosure and sexual risk, and cost-effectiveness of HIV mass media campaigns targeting MSM. We searched for quantitative and qualitative studies published between 1990 and May 2011 via the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, Psych Info, ISI Web of Science, OpenGrey and COPAC, and contacting experts. No exclusions were made on the basis of study design or methods because our primary aim was to map evidence. We appraised study quality and present a narrative synthesis of findings. Sixteen reports from 12 studies were included. All were from high-income countries and most examined multi-media interventions. Half of the studies were single cross-sectional surveys. Three repeat cross-sectional studies collected data pre and post the campaign launch. The remaining three studies monitored routine data. Three studies included a nested qualitative component. Campaign coverage was the most commonly reported outcome (9 studies). Imagery, tone of language, content and relevance were identified in the qualitative research as factors influencing campaign acceptability. HIV testing rates (or intention to test) were reported by five studies. Two studies reported that testing rates were higher among men who had seen the campaigns compared to men who had not, but this may reflect confounding. Findings were less consistent regarding reductions in sexual risk behaviours (4 studies). None of the studies examined cost-effectiveness. Campaigns aim to provide MSM with information to help prevent

Comparison of Quantitative Mass Spectrometry Platforms for Monitoring Kinase ATP Probe Uptake in Lung Cancer.

PubMed

Hoffman, Melissa A; Fang, Bin; Haura, Eric B; Rix, Uwe; Koomen, John M

2018-01-05

Recent developments in instrumentation and bioinformatics have led to new quantitative mass spectrometry platforms including LC-MS/MS with data-independent acquisition (DIA) and targeted analysis using parallel reaction monitoring mass spectrometry (LC-PRM), which provide alternatives to well-established methods, such as LC-MS/MS with data-dependent acquisition (DDA) and targeted analysis using multiple reaction monitoring mass spectrometry (LC-MRM). These tools have been used to identify signaling perturbations in lung cancers and other malignancies, supporting the development of effective kinase inhibitors and, more recently, providing insights into therapeutic resistance mechanisms and drug repurposing opportunities. However, detection of kinases in biological matrices can be challenging; therefore, activity-based protein profiling enrichment of ATP-utilizing proteins was selected as a test case for exploring the limits of detection of low-abundance analytes in complex biological samples. To examine the impact of different MS acquisition platforms, quantification of kinase ATP uptake following kinase inhibitor treatment was analyzed by four different methods: LC-MS/MS with DDA and DIA, LC-MRM, and LC-PRM. For discovery data sets, DIA increased the number of identified kinases by 21% and reduced missingness when compared with DDA. In this context, MRM and PRM were most effective at identifying global kinome responses to inhibitor treatment, highlighting the value of a priori target identification and manual evaluation of quantitative proteomics data sets. We compare results for a selected set of desthiobiotinylated peptides from PRM, MRM, and DIA and identify considerations for selecting a quantification method and postprocessing steps that should be used for each data acquisition strategy.

Mass synchronization: Occurrence and its control with possible applications to brain dynamics

NASA Astrophysics Data System (ADS)

Chandrasekar, V. K.; Sheeba, Jane H.; Lakshmanan, M.

2010-12-01

Occurrence of strong or mass synchronization of a large number of neuronal populations in the brain characterizes its pathological states. In order to establish an understanding of the mechanism underlying such pathological synchronization, we present a model of coupled populations of phase oscillators representing the interacting neuronal populations. Through numerical analysis, we discuss the occurrence of mass synchronization in the model, where a source population which gets strongly synchronized drives the target populations onto mass synchronization. We hypothesize and identify a possible cause for the occurrence of such a synchronization, which is so far unknown: Pathological synchronization is caused not just because of the increase in the strength of coupling between the populations but also because of the strength of the strong synchronization of the drive population. We propose a demand controlled method to control this pathological synchronization by providing a delayed feedback where the strength and frequency of the synchronization determine the strength and the time delay of the feedback. We provide an analytical explanation for the occurrence of pathological synchronization and its control in the thermodynamic limit.

Engineering and Design: Rock Mass Classification Data Requirements for Rippability

DTIC Science & Technology

1983-06-30

Engineering and Design ROCK MASS CLASSIFICATION DATA REQUIREMENTS FOR RIPPABILITY Distribution Restriction Statement Approved for public release...and Design: Rock Mass Classification Data Requirements for Rippability Contract Number Grant Number Program Element Number Author(s) Project...Technical Letter 1110-2-282 Engineering and Design ROCK MASS CLASSIFICATION DATA REQUIREMENTS FOR RIPPABILITY 1“ -“ This ETL contains information on data

Defining the wheat gluten peptide fingerprint via a discovery and targeted proteomics approach.

PubMed

Martínez-Esteso, María José; Nørgaard, Jørgen; Brohée, Marcel; Haraszi, Reka; Maquet, Alain; O'Connor, Gavin

2016-09-16

Accurate, reliable and sensitive detection methods for gluten are required to support current EU regulations. The enforcement of legislative levels requires that measurement results are comparable over time and between methods. This is not a trivial task for gluten which comprises a large number of protein targets. This paper describes a strategy for defining a set of specific analytical targets for wheat gluten. A comprehensive proteomic approach was applied by fractionating wheat gluten using RP-HPLC (reversed phase high performance liquid chromatography) followed by a multi-enzymatic digestion (LysC, trypsin and chymotrypsin) with subsequent mass spectrometric analysis. This approach identified 434 peptide sequences from gluten. Peptides were grouped based on two criteria: unique to a single gluten protein sequence; contained known immunogenic and toxic sequences in the context of coeliac disease. An LC-MS/MS method based on selected reaction monitoring (SRM) was developed on a triple quadrupole mass spectrometer for the specific detection of the target peptides. The SRM based screening approach was applied to gluten containing cereals (wheat, rye, barley and oats) and non-gluten containing flours (corn, soy and rice). A unique set of wheat gluten marker peptides were identified and are proposed as wheat specific markers. The measurement of gluten in processed food products in support of regulatory limits is performed routinely. Mass spectrometry is emerging as a viable alternative to ELISA based methods. Here we outline a set of peptide markers that are representative of gluten and consider the end user's needs in protecting those with coeliac disease. The approach taken has been applied to wheat but can be easily extended to include other species potentially enabling the MS quantification of different gluten containing species from the identified markers. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Small Business Innovations (Mass Microbalance)

NASA Technical Reports Server (NTRS)

1991-01-01

Femtometrics of Costa Mesa, CA, developed the Model 200-1 SAW Mass Microbalance under a NASA Small Business Innovation Research (SBIR) contract with Langley Research Center. The product is described as "the next generation of aerosol mass microbalance technology," because a new type of sensor, the Surface Acoustic Wave (SAW) piezoelectric crystal, offers mass resolution two orders of magnitude greater than the Quartz Crystal Microbalance cascade impactor (QCM) (used at Langley since 1979 for collection and measurement of aerosol particles in the upper atmosphere). The Model 200-1 SAW Mass Microbalance, which provides a 400-fold increase in mass sensitivity per unit area over the QCM, can be used for real-time particle monitoring in clean rooms, measuring chemical vapors in very low concentrations, measuring target chemicals in the stratosphere and in industry as a toxic vapor monitor.

Elemental mass spectroscopy of remote surfaces from laser-induced plasmas

NASA Technical Reports Server (NTRS)

Situ, W.; DeYoung, R. J.

1994-01-01

The elemental mass analysis of laser-produced ions from Al, Cu, Ge, Ag, and a lunar simulant target when irradiated by a 400-mJ, 8-ns, Nd: YAG laser at 1 x 10(exp 9) W/cm(exp 2), is reported. Ions traveled down a 11.1-m evacuated tube to an ion-trap 1-m time-of-flight (TOF) mass spectrometer where an elemental mass spectrum was recorded. The amount of target material removed per laser pulse and the ionization fraction were measured. The ion spatial distribution was measured at 11.1-m distance and found to be near a fourth-power cosine distribution. These results indicate the ability to mass analyze a surface over a distance of many kilometers for lunar and asteroid surface elemental mass analysis by a remote satellite or lunar rover.

Direct online extraction and determination by supercritical fluid extraction with chromatography and mass spectrometry of targeted carotenoids from red Habanero peppers (Capsicum chinense Jacq.).

PubMed

Zoccali, Mariosimone; Giuffrida, Daniele; Dugo, Paola; Mondello, Luigi

2017-10-01

Recently, supercritical fluid chromatography coupled to mass spectrometry has gained attention as a fast and useful technology applied to the carotenoids analysis. However, no reports are available in the literature on the direct online extraction and determination by supercritical fluid extraction with chromatography and mass spectrometry. The aim of this research was the development of an online method coupling supercritical fluid extraction and supercritical fluid chromatography for a detailed targeted native carotenoids characterization in red habanero peppers. The online nature of the system, compared to offline approaches, improves run-to-run precision, enables the setting of batch-type applications, and reduces the risks of sample contamination. The extraction has been optimized using different temperatures, starting from 40°C up to 80°C. Multiple extractions, until depletion, were performed on the same sample to evaluate the extraction yield. The range of the first extraction yield, carried out at 80°C, which was the best extraction temperature, was 37.4-65.4%, with a %CV range of 2-12. Twenty-one targeted analytes were extracted and identified by the developed methodology in less than 17 min, including free, monoesters, and diesters carotenoids, in a very fast and efficient way. Quantification of the β-carotene was carried out by using the optimized conditions. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Using System Mass (SM), Equivalent Mass (EM), Equivalent System Mass (ESM) or Life Cycle Mass (LCM) in Advanced Life Support (ALS) Reporting

NASA Technical Reports Server (NTRS)

Jones, Harry

2003-01-01

The Advanced Life Support (ALS) has used a single number, Equivalent System Mass (ESM), for both reporting progress and technology selection. ESM is the launch mass required to provide a space system. ESM indicates launch cost. ESM alone is inadequate for technology selection, which should include other metrics such as Technology Readiness Level (TRL) and Life Cycle Cost (LCC) and also consider perfom.arxe 2nd risk. ESM has proven difficult to implement as a reporting metric, partly because it includes non-mass technology selection factors. Since it will not be used exclusively for technology selection, a new reporting metric can be made easier to compute and explain. Systems design trades-off performance, cost, and risk, but a risk weighted cost/benefit metric would be too complex to report. Since life support has fixed requirements, different systems usually have roughly equal performance. Risk is important since failure can harm the crew, but it is difficult to treat simply. Cost is not easy to estimate, but preliminary space system cost estimates are usually based on mass, which is better estimated than cost. Amass-based cost estimate, similar to ESM, would be a good single reporting metric. The paper defines and compares four mass-based cost estimates, Equivalent Mass (EM), Equivalent System Mass (ESM), Life Cycle Mass (LCM), and System Mass (SM). EM is traditional in life support and includes mass, volume, power, cooling and logistics. ESM is the specifically defined ALS metric, which adds crew time and possibly other cost factors to EM. LCM is a new metric, a mass-based estimate of LCC measured in mass units. SM includes only the factors of EM that are originally measured in mass, the hardware and logistics mass. All four mass-based metrics usually give similar comparisons. SM is by far the simplest to compute and easiest to explain.

Application of Laser Mass Spectrometry to Art and Archaeology

NASA Technical Reports Server (NTRS)

Gulian, Lase Lisa E.; Callahan, Michael P.; Muliadi, Sarah; Owens, Shawn; McGovern, Patrick E.; Schmidt, Catherine M.; Trentelman, Karen A.; deVries, Mattanjah S.

2011-01-01

REMPI laser mass spectrometry is a combination of resonance enhanced multiphoton ionization spectroscopy and time of flight mass spectrometry, This technique enables the collection of mass specific optical spectra as well as of optically selected mass spectra. Analytes are jet-cooled by entrainment in a molecular beam, and this low temperature gas phase analysis has the benefit of excellent vibronic resolution. Utilizing this method, mass spectrometric analysis of historically relevant samples can be simplified and improved; Optical selection of targets eliminates the need for chromatography while knowledge of a target's gas phase spectroscopy allows for facile differentiation of molecules that are in the aqueous phase considered spectroscopically indistinguishable. These two factors allow smaller sample sizes than commercial MS instruments, which in turn will require less damage to objects of antiquity. We have explored methods to optimize REMPI laser mass spectrometry as an analytical tool to archaeology using theobromine and caffeine as molecular markers in Mesoamerican pottery, and are expanding this approach to the field of art to examine laccaic acid in shellacs.

(Un)targeted Scanning of Locks of Hair for Drugs of Abuse by Direct Analysis in Real Time-High-Resolution Mass Spectrometry.

PubMed

Duvivier, Wilco F; van Putten, Marc R; van Beek, Teris A; Nielen, Michel W F

2016-02-16

Forensic hair evidence can be used to obtain retrospective timelines of drug use by analysis of hair segments. However, this is a laborious and time-consuming process, and mass spectrometric (MS) imaging techniques, which show great potential for single-hair targeted analysis, are less useful due to differences in hair growth rate between individual hairs. As an alternative, a fast untargeted analysis method was developed that uses direct analysis in real time-high-resolution mass spectrometry (DART-HRMS) to longitudinally scan intact locks of hair without extensive sample preparation or segmentation. The hair scan method was validated for cocaine against an accredited liquid chromatography/tandem mass spectrometry (LC/MS/MS) method. The detection limit for cocaine in hair was found to comply with the cutoff value of 0.5 ng/mg recommended by the Society of Hair Testing; that is, the DART hair scan method is amenable to forensic cases. Under DART conditions, no significant thermal degradation of cocaine occurred. The standard DART spot size of 5.1 ± 1.1 mm could be improved to 3.3 ± 1.0 mm, corresponding to approximately 10 days of hair growth, by using a high spatial resolution exit cone. By use of data-dependent product ion scans, multiple drugs of abuse could be detected in a single drug user hair scan with confirmation of identity by both exact mass and MS/HRMS fragmentation patterns. Furthermore, full-scan high-resolution data were retrospectively interrogated versus a list of more than 100 compounds and revealed additional hits and temporal profiles in good correlation with reported drug use.

Sejong Open Cluster Survey (SOS). 0. Target Selection and Data Analysis

NASA Astrophysics Data System (ADS)

Sung, Hwankyung; Lim, Beomdu; Bessell, Michael S.; Kim, Jinyoung S.; Hur, Hyeonoh; Chun, Moo-Young; Park, Byeong-Gon

2013-06-01

Star clusters are superb astrophysical laboratories containing cospatial and coeval samples of stars with similar chemical composition. We initiate the Sejong Open cluster Survey (SOS) - a project dedicated to providing homogeneous photometry of a large number of open clusters in the SAAO Johnson-Cousins' UBVI system. To achieve our main goal, we pay much attention to the observation of standard stars in order to reproduce the SAAO standard system. Many of our targets are relatively small sparse clusters that escaped previous observations. As clusters are considered building blocks of the Galactic disk, their physical properties such as the initial mass function, the pattern of mass segregation, etc. give valuable information on the formation and evolution of the Galactic disk. The spatial distribution of young open clusters will be used to revise the local spiral arm structure of the Galaxy. In addition, the homogeneous data can also be used to test stellar evolutionary theory, especially concerning rare massive stars. In this paper we present the target selection criteria, the observational strategy for accurate photometry, and the adopted calibrations for data analysis such as color-color relations, zero-age main sequence relations, Sp - M_V relations, Sp - T_{eff} relations, Sp - color relations, and T_{eff} - BC relations. Finally we provide some data analysis such as the determination of the reddening law, the membership selection criteria, and distance determination.

Surveillance study of a number of synthetic and natural growth promoters in bovine muscle samples using liquid chromatography-tandem mass spectrometry.

PubMed

Malone, E; Elliott, C; Kennedy, G; Savage, D; Regan, L

2011-05-01

A simple, new method permitting the simultaneous determination and confirmation of trace residues of 24 different growth promoters and metabolites using liquid chromatography-mass spectrometry was developed and validated. The compounds were extracted from bovine tissue using acetonitrile; sodium sulphate was also added at this stage to aid with purification. The resulting mixture was then evaporated to approximately 1 ml and subsequently centrifuged at high speed and an aliquot injected onto the LC-MS/MS system. The calculated CCα values ranged between 0.11 and 0.46 µg kg(-1); calculated CCβ were in the range 0.19-0.79 µg kg(-1). Accuracy, measurement of uncertainty, repeatability and linearity were also determined for each analyte. The analytical method was applied to a number of bovine tissue samples imported into Ireland from third countries. Levels of progesterone were found in a number of samples at concentrations ranging between 0.28 and 30.30 µg kg(-1). Levels of alpha- and beta-testosterone were also found in a number of samples at concentrations ranging between 0.22 and 8.63 µg kg(-1) and between 0.16 and 2.08 µg kg(-1) respectively.

a Plutonium Ceramic Target for Masha

NASA Astrophysics Data System (ADS)

Wilk, P. A.; Shaughnessy, D. A.; Moody, K. J.; Kenneally, J. M.; Wild, J. F.; Stoyer, M. A.; Patin, J. B.; Lougheed, R. W.; Ebbinghaus, B. B.; Landingham, R. L.; Oganessian, Yu. Ts.; Yeremin, A. V.; Dmitriev, S. N.

2005-09-01

We are currently developing a plutonium ceramic target for the MASHA mass separator. The MASHA separator will use a thick plutonium ceramic target capable of tolerating temperatures up to 2000 °C. Promising candidates for the target include oxides and carbides, although more research into their thermodynamic properties will be required. Reaction products will diffuse out of the target into an ion source, where they will then be transported through the separator to a position-sensitive focal-plane detector array. Experiments on MASHA will allow us to make measurements that will cement our identification of element 114 and provide for future experiments where the chemical properties of the heaviest elements are studied.

A Plutonium Ceramic Target for MASHA

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

Wilk, P A; Shaughnessy, D A; Moody, K J

2004-07-06

We are currently developing a plutonium ceramic target for the MASHA mass separator. The MASHA separator will use a thick plutonium ceramic target capable of tolerating temperatures up to 2000 C. Promising candidates for the target include oxides and carbides, although more research into their thermodynamic properties will be required. Reaction products will diffuse out of the target into an ion source, where they will then be transported through the separator to a position-sensitive focal-plane detector array. Experiments on MASHA will allow us to make measurements that will cement our identification of element 114 and provide for future experiments wheremore » the chemical properties of the heaviest elements are studied.« less

Annual Enrollment Report Number of Students Studying Journalism and Mass Communication at All-time High.

ERIC Educational Resources Information Center

Becker, Lee B.; Vlad, Tudor; Huh, Jisu; Prine, Joelle

2001-01-01

Finds that journalism and mass communication programs appear to be entering another period of rapid enrollment growth, swept up by overall increases in enrollments at United States universities. Finds that only about four in ten of the journalism and mass communication programs report enrollments by race, suggesting many administrators are not…

Confidence level estimation in multi-target classification problems

NASA Astrophysics Data System (ADS)

Chang, Shi; Isaacs, Jason; Fu, Bo; Shin, Jaejeong; Zhu, Pingping; Ferrari, Silvia

2018-04-01

This paper presents an approach for estimating the confidence level in automatic multi-target classification performed by an imaging sensor on an unmanned vehicle. An automatic target recognition algorithm comprised of a deep convolutional neural network in series with a support vector machine classifier detects and classifies targets based on the image matrix. The joint posterior probability mass function of target class, features, and classification estimates is learned from labeled data, and recursively updated as additional images become available. Based on the learned joint probability mass function, the approach presented in this paper predicts the expected confidence level of future target classifications, prior to obtaining new images. The proposed approach is tested with a set of simulated sonar image data. The numerical results show that the estimated confidence level provides a close approximation to the actual confidence level value determined a posteriori, i.e. after the new image is obtained by the on-board sensor. Therefore, the expected confidence level function presented in this paper can be used to adaptively plan the path of the unmanned vehicle so as to optimize the expected confidence levels and ensure that all targets are classified with satisfactory confidence after the path is executed.

Combination of Mass Signal Amplification and Isotope-Labeled Alkanethiols for the Multiplexed Detection of miRNAs.

PubMed

Kang, Hyunook; Hong, Seol-Hye; Sung, Jiha; Yeo, Woon-Seok

2017-08-04

We report a fast and sensitive method for the multiplexed detection of miRNAs by combining mass signal amplification and isotope-labeled signal reporter molecules. In our strategy, target miRNAs are captured specifically by immobilized DNAs on gold nanoparticles (AuNPs), which carry a large number of small molecules, called amplification tags (Am-tags), as the reporter for the detection of target miRNAs. For multiplexed detection, we designed and synthesized four Am-tags containing 0, 4, 8, 12 isotopes so that they had same molecular properties but different molecular weights. By observing the mass signals of the Am-tags on AuNPs decorated along with different probe DNAs, four types of miRNAs in a sample could be easily discriminated, and the relative amounts of these miRNAs could be quantified. The practicability of our strategy was further verified by measuring the expression levels of two miRNAs in HUVECs in response to different CuSO 4 concentrations. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Targeted liquid chromatography–mass spectrometry analysis of serum acylcarnitines in acetaminophen toxicity in children

PubMed Central

Bhattacharyya, Sudeepa; Yan, Ke; Pence, Lisa; Simpson, Pippa M; Gill, Pritmohinder; Letzig, Lynda G; Beger, Richard D; Sullivan, Janice E; Kearns, Gregory L; Reed, Michael D; Marshall, James D; Van Den Anker, John N; James, Laura P

2014-01-01

Aim Long-chain acylcarnitines have been postulated to be sensitive biomarkers of acetaminophen (APAP)-induced hepatotoxicity in mouse models. In the following study, the relationship of acylcarnitines with other known indicators of APAP toxicity was examined in children receiving low-dose (therapeutic) and high-dose (‘overdose’ or toxic ingestion) exposure to APAP. Materials & methods The study included three subject groups: group A (therapeutic dose, n = 187); group B (healthy controls, n = 23); and group C (overdose, n = 62). Demographic, clinical and laboratory data were collected for each subject. Serum samples were used for measurement of APAP protein adducts, a biomarker of the oxidative metabolism of APAP and for targeted metabolomics analysis of serum acylcarnitines using ultra performance liquid chromatography–triple-quadrupole mass spectrometry. Results Significant increases in oleoyl- and palmitoyl-carnitines were observed with APAP exposure (low dose and overdose) compared with controls. Significant increases in serum ALT, APAP protein adducts and acylcarnitines were observed in overdose children that received delayed treatment (time to treatment from overdose >24 h) with the antidote N-acetylcysteine. Time to peak APAP protein adducts in serum was shorter than that of the acylcarnitines and serum ALT. Conclusion Perturbations in long-chain acylcarnitines in children with APAP toxicity suggest that mitochrondrial injury and associated impairment in the β-oxidation of fatty acids are clinically relevant as biomarkers of APAP toxicity. PMID:24521011

Targeted liquid chromatography-mass spectrometry analysis of serum acylcarnitines in acetaminophen toxicity in children.

PubMed

Bhattacharyya, Sudeepa; Yan, Ke; Pence, Lisa; Simpson, Pippa M; Gill, Pritmohinder; Letzig, Lynda G; Beger, Richard D; Sullivan, Janice E; Kearns, Gregory L; Reed, Michael D; Marshall, James D; Van Den Anker, John N; James, Laura P

2014-01-01

Long-chain acylcarnitines have been postulated to be sensitive biomarkers of acetaminophen (APAP)-induced hepatotoxicity in mouse models. In the following study, the relationship of acylcarnitines with other known indicators of APAP toxicity was examined in children receiving low-dose (therapeutic) and high-dose ('overdose' or toxic ingestion) exposure to APAP. The study included three subject groups: group A (therapeutic dose, n = 187); group B (healthy controls, n = 23); and group C (overdose, n = 62). Demographic, clinical and laboratory data were collected for each subject. Serum samples were used for measurement of APAP protein adducts, a biomarker of the oxidative metabolism of APAP and for targeted metabolomics analysis of serum acylcarnitines using ultra performance liquid chromatography-triple-quadrupole mass spectrometry. Significant increases in oleoyl- and palmitoyl-carnitines were observed with APAP exposure (low dose and overdose) compared with controls. Significant increases in serum ALT, APAP protein adducts and acylcarnitines were observed in overdose children that received delayed treatment (time to treatment from overdose >24 h) with the antidote N-acetylcysteine. Time to peak APAP protein adducts in serum was shorter than that of the acylcarnitines and serum ALT. Perturbations in long-chain acylcarnitines in children with APAP toxicity suggest that mitochrondrial injury and associated impairment in the β-oxidation of fatty acids are clinically relevant as biomarkers of APAP toxicity.

Rotation to a Partially Specified Target Matrix in Exploratory Factor Analysis: How Many Targets?

ERIC Educational Resources Information Center

Myers, Nicholas D.; Ahn, Soyeon; Jin, Ying

2013-01-01

The purpose of this study was to explore the influence of the number of targets specified on the quality of exploratory factor analysis solutions with a complex underlying structure and incomplete substantive measurement theory. Three Monte Carlo studies were performed based on the ratio of the number of observed variables to the number of…

Binaries among low-mass stars in nearby young moving groups

NASA Astrophysics Data System (ADS)

Janson, Markus; Durkan, Stephen; Hippler, Stefan; Dai, Xiaolin; Brandner, Wolfgang; Schlieder, Joshua; Bonnefoy, Mickaël; Henning, Thomas

2017-03-01

The solar galactic neighborhood contains a number of young co-moving associations of stars (known as young moving groups) with ages of 10-150 Myr, which are prime targets for a range of scientific studies, including direct imaging planet searches. The late-type stellar populations of such groups still remain in their pre-main sequence phase, and are thus well suited for purposes such as isochronal dating. Close binaries are particularly useful in this regard since they allow for a model-independent dynamical mass determination. Here we present a dedicated effort to identify new close binaries in nearby young moving groups, through high-resolution imaging with the AstraLux Sur Lucky Imaging camera. We surveyed 181 targets, resulting in the detection of 61 companions or candidates, of which 38 are new discoveries. An interesting example of such a case is 2MASS J00302572-6236015 AB, which is a high-probability member of the Tucana-Horologium moving group, and has an estimated orbital period of less than 10 yr. Among the previously known objects is a serendipitous detection of the deuterium burning boundary circumbinary companion 2MASS J01033563-5515561 (AB)b in the z' band, thereby extending the spectral coverage for this object down to near-visible wavelengths. Based on observations collected at the European Southern Observatory, Chile (Programs 096.C-0243 and 097.C-0135).Tables 1-3 are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (http://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/599/A70

Ionization enhancement in atmospheric pressure chemical ionization and suppression in electrospray ionization between target drugs and stable-isotope-labeled internal standards in quantitative liquid chromatography/tandem mass spectrometry.

PubMed

Liang, H R; Foltz, R L; Meng, M; Bennett, P

2003-01-01

The phenomena of ionization suppression in electrospray ionization (ESI) and enhancement in atmospheric pressure chemical ionization (APCI) were investigated in selected-ion monitoring and selected-reaction monitoring modes for nine drugs and their corresponding stable-isotope-labeled internal standards (IS). The results showed that all investigated target drugs and their co-eluting isotope-labeled IS suppress each other's ionization responses in ESI. The factors affecting the extent of suppression in ESI were investigated, including structures and concentrations of drugs, matrix effects, and flow rate. In contrast to the ESI results, APCI caused seven of the nine investigated target drugs and their co-eluting isotope-labeled IS to enhance each other's ionization responses. The mutual ionization suppression or enhancement between drugs and their isotope-labeled IS could possibly influence assay sensitivity, reproducibility, accuracy and linearity in quantitative liquid chromatography/mass spectrometry (LC/MS) and liquid chromatography/tandem mass spectrometry (LC/MS/MS). However, calibration curves were linear if an appropriate IS concentration was selected for a desired calibration range to keep the response factors constant. Copyright 2003 John Wiley & Sons, Ltd.

Self-assessing target with automatic feedback

DOEpatents

Larkin, Stephen W.; Kramer, Robert L.

2004-03-02

A self assessing target with four quadrants and a method of use thereof. Each quadrant containing possible causes for why shots are going into that particular quadrant rather than the center mass of the target. Each possible cause is followed by a solution intended to help the marksman correct the problem causing the marksman to shoot in that particular area. In addition, the self assessing target contains possible causes for general shooting errors and solutions to the causes of the general shooting error. The automatic feedback with instant suggestions and corrections enables the shooter to improve their marksmanship.

Evaluation of active and passive recruitment methods used in randomized controlled trials targeting pediatric obesity.

PubMed

Raynor, Hollie A; Osterholt, Kathrin M; Hart, Chantelle N; Jelalian, Elissa; Vivier, Patrick; Wing, Rena R

2009-01-01

Evaluate enrollment numbers, randomization rates, costs, and cost-effectiveness of active versus passive recruitment methods for parent-child dyads into two pediatric obesity intervention trials. Recruitment methods were categorized into active (pediatrician referral and targeted mailings, with participants identified by researcher/health care provider) versus passive methods (newspaper, bus, internet, television, and earning statements; fairs/community centers/schools; and word of mouth; with participants self-identified). Numbers of enrolled and randomized families and costs/recruitment method were monitored throughout the 22-month recruitment period. Costs (in USD) per recruitment method included staff time, mileage, and targeted costs of each method. A total of 940 families were referred or made contact, with 164 families randomized (child: 7.2+/-1.6 years, 2.27+/-0.61 standardized body mass index [zBMI], 86.6% obese, 61.7% female, 83.5% Caucasian; parent: 38.0+/-5.8 years, 32.9+/-8.4 BMI, 55.2% obese, 92.7% female, 89.6% caucasian). Pediatrician referral, followed by targeted mailings, produced the largest number of enrolled and randomized families (both methods combined producing 87.2% of randomized families). Passive recruitment methods yielded better retention from enrollment to randomization (p<0.05), but produced few families (21 in total). Approximately $91,000 was spent on recruitment, with cost per randomized family at $554.77. Pediatrician referral was the most cost-effective method, $145.95/randomized family, but yielded only 91 randomized families over 22-months of continuous recruitment. Pediatrician referral and targeted mailings, which are active recruitment methods, were the most successful strategies. However, recruitment demanded significant resources. Successful recruitment for pediatric trials should use several strategies. NCT00259324, NCT00200265.

Using iRT, a normalized retention time for more targeted measurement of peptides

PubMed Central

Escher, Claudia; Reiter, Lukas; MacLean, Brendan; Ossola, Reto; Herzog, Franz; Chilton, John; MacCoss, Michael J.; Rinner, Oliver

2014-01-01

Multiple reaction monitoring (MRM) has recently become the method of choice for targeted quantitative measurement of proteins using mass spectrometry. The method, however, is limited in the number of peptides that can be measured in one run. This number can be markedly increased by scheduling the acquisition if the accurate retention time (RT) of each peptide is known. Here we present iRT, an empirically derived dimensionless peptide-specific value that allows for highly accurate RT prediction. The iRT of a peptide is a fixed number relative to a standard set of reference iRT-peptides that can be transferred across laboratories and chromatographic systems. We show that iRT facilitates the setup of multiplexed experiments with acquisition windows more than 4 times smaller compared to in silico RT predictions resulting in improved quantification accuracy. iRTs can be determined by any laboratory and shared transparently. The iRT concept has been implemented in Skyline, the most widely used software for MRM experiments. PMID:22577012

Mass spectrometric profiling of flavonoid glycoconjugates possessing isomeric aglycones.

PubMed

Abrankó, László; Szilvássy, Blanka

2015-01-01

In fields such as food and nutrition science or plant physiology, interest in untargeted profiling of flavonoids continues to expand. The group of flavonoids encompasses several thousands of chemically distinguishable compounds, among which are a number of isobaric compounds with the same elemental composition. Thus, the mass spectrometric identification of these compounds is challenging, especially when reference standards are not available to support their identification. Many different types of isomers of flavonoid glycoconjugates are known, i.e. compounds that differ in their glycosylation position, glycan sequence or type of interglycosidic linkage. This work focuses on the mass spectrometric identification of flavonoid glycoconjugate isomers possessing the same glycan mass and differing only in their aglycone core. A non-targeted HPLC-ESI-MS/MS profiling method using a triple quadrupole MS is presented herein, which utilizes in-source fragmentation and a pseudo-MS(3) approach for the selective analysis of flavonoid glycoconjugates with isomeric/isobaric aglycones. A selective MRM-based identification of the in-source formed isobaric aglycone fragments was established. Additionally, utilizing the precursor scanning capability of the employed triple quadrupole instrument, the developed method enabled the determination of the molecular weight of the studied intact flavonoid glycoconjugate. The versatility of the method was proven with various types of flavonoid aglycones, i.e. anthocyanins, flavonols, flavones, flavanones and isoflavones, along with their representative glycoconjugates. The developed method was also successfully applied to a commercially available sour cherry sample, in which 16 different glycoconjugates of pelargonidin, genistein, cyanidin, kaempferol and quercetin could be tentatively identified, including a number of compounds containing isomeric/isobaric aglycones. Copyright © 2015 John Wiley & Sons, Ltd.

When increasing distraction helps learning: Distractor number and content interact in their effects on memory.

PubMed

Nussenbaum, Kate; Amso, Dima; Markant, Julie

2017-11-01

Previous work has demonstrated that increasing the number of distractors in a search array can reduce interference from distractor content during target processing. However, it is unclear how this reduced interference influences learning of target information. Here, we investigated how varying the amount and content of distraction present in a learning environment affects visual search and subsequent memory for target items. In two experiments, we demonstrate that the number and content of competing distractors interact in their influence on target selection and memory. Specifically, while increasing the number of distractors present in a search array made target detection more effortful, it did not impair learning and memory for target content. Instead, when the distractors contained category information that conflicted with the target, increasing the number of distractors from one to three actually benefitted learning and memory. These data suggest that increasing numbers of distractors may reduce interference from conflicting conceptual information during encoding.

Ultrahigh-Performance Liquid Chromatography (UHPLC)-Tandem Mass Spectrometry (MS/MS) Quantification of Nine Target Indoles in Sparkling Wines.

PubMed

Tudela, Rebeca; Ribas-Agustí, Albert; Buxaderas, Susana; Riu-Aumatell, Montserrat; Castellari, Massimo; López-Tamames, Elvira

2016-06-15

An ultrahigh-performance liquid chromatography (UHPLC)-tandem mass spectrometry (MS/MS) method was developed for the simultaneous determination of nine target indoles in sparkling wines. The proposed method requires minimal sample pretreatment, and its performance parameters (accuracy, repeatability, LOD, and matrix effect) indicate that it is suitable for routine analysis. Four indoles were found at detectable levels in commercial Cava samples: 5-methoxytryptophol (5MTL), tryptophan (TRP), tryptophan ethyl ester (TEE), and N-acetylserotonin (NSER). Two of them, NSER and 5MTL, are reported here for the first time in sparkling wines, with values of 0.3-2 and 0.29-29.2 μg/L, respectively. In the same samples, the contents of melatonin (MEL), serotonin (SER), 5-hydroxytryptophan (5-OHTRP), 5-hydroxyindole-3-acetic acid (5OHIA), and 5-methoxy-3-indoleacetic acid (5MIA) were all below the corresponding limits of detection.

Targeted profiling of hydrophilic constituents of royal jelly by hydrophilic interaction liquid chromatography-tandem mass spectrometry.

PubMed

Pina, Athanasia; Begou, Olga; Kanelis, Dimitris; Gika, Helen; Kalogiannis, Stavros; Tananaki, Chrysoula; Theodoridis, Georgios; Zotou, Anastasia

2018-01-05

In the present work a Hydrophilic Interaction Liquid Chromatography-tandem Mass Spectrometry (HILIC-MS/MS) method was developed for the efficient separation and quantification of a large number of small polar bioactive molecules in Royal Jelly. The method was validated and provided satisfactory detection sensitivity for 88 components. Quantification was proven to be precise for 64 components exhibiting good linearity, recoveries R% >90% for the majority of analytes and intra- and inter-day precision from 0.14 to 20% RSD. Analysis of 125 fresh royal jelly samples of Greek origin provided useful information on royal jelly's hydrophilic bioactive components revealing lysine, ribose, proline, melezitose and glutamic acid to be in high abundance. In addition the occurrence of 18 hydrophilic nutrients which have not been reported previously as royal jelly constituents is shown. Copyright © 2017 Elsevier B.V. All rights reserved.

Mass Spectrometric Immunoassay and Multiple Reaction Monitoring as Targeted MS-based Quantitative Approaches in Biomarker Development: Potential Applications to Cardiovascular Disease and Diabetes

PubMed Central

Yassine, Hussein; Borges, Chad R.; Schaab, Matthew R.; Billheimer, Dean; Stump, Craig; Reaven, Peter; Lau, Serrine S.; Nelson, Randall

2014-01-01

Type 2 diabetes (T2DM) is an important risk factor for cardiovascular disease (CVD)—the leading cause of death in the US. Yet not all subjects with T2DM are at equal risk for CVD complications; the challenge lies in identifying those at greatest risk. Therapies directed towards treating conventional risk factors have failed to significantly reduce this residual risk in T2DM patients. Thus newer targets and markers are needed for the development and testing of novel therapies. Herein we review two complementary mass spectrometry-based approaches—Mass Spectrometric Immunoassay (MSIA) and tandem mass spectrometry as multiple reaction monitoring (MRM)—for the analysis of plasma proteins and post translational modifications (PTMs) of relevance to T2DM and CVD. Together, these complementary approaches allow for high-throughput monitoring of many PTMs and the absolute quantification of proteins near the low picomolar range. In this review article, we discuss the clinical relevance of the HDL proteome and Apolipoprotein A-I PTMs to T2DM and CVD as well as provide illustrative MSIA and MRM data on high density lipoprotein (HDL) proteins from T2DM patients to provide examples of how these mass spectrometry approaches can be applied to gain new insight regarding cardiovascular risk factors. Also discussed are the reproducibility, interpretation and limitations of each technique with an emphasis on their capacities to facilitate the translation of new biomarkers into clinical practice. PMID:23696124

Literature evidence in open targets - a target validation platform.

PubMed

Kafkas, Şenay; Dunham, Ian; McEntyre, Johanna

2017-06-06

We present the Europe PMC literature component of Open Targets - a target validation platform that integrates various evidence to aid drug target identification and validation. The component identifies target-disease associations in documents and ranks the documents based on their confidence from the Europe PMC literature database, by using rules utilising expert-provided heuristic information. The confidence score of a given document represents how valuable the document is in the scope of target validation for a given target-disease association by taking into account the credibility of the association based on the properties of the text. The component serves the platform regularly with the up-to-date data since December, 2015. Currently, there are a total number of 1168365 distinct target-disease associations text mined from >26 million PubMed abstracts and >1.2 million Open Access full text articles. Our comparative analyses on the current available evidence data in the platform revealed that 850179 of these associations are exclusively identified by literature mining. This component helps the platform's users by providing the most relevant literature hits for a given target and disease. The text mining evidence along with the other types of evidence can be explored visually through https://www.targetvalidation.org and all the evidence data is available for download in json format from https://www.targetvalidation.org/downloads/data .

Lipid-Polymer Nanoparticles for Folate-Receptor Targeting Delivery of Doxorubicin.

PubMed

Zheng, Mingbin; Gong, Ping; Zheng, Cuifang; Zhao, Pengfei; Luo, Zhenyu; Ma, Yifan; Cai, Lintao

2015-07-01

A biocompatible PLGA-lipid hybrid nanoparticles (NPs) was developed for targeted delivery of anticancer drugs with doxorubicin (DOX). The hydrodynamic diameter and zeta potential of DOX-loaded PLGA-lipid NPs (DNPs) were affected by the mass ratio of Lipid/PLGA or DSPE-PEG-COOH/Lecithin. At the 1:20 drug/polymer mass ratio, the mean hydrodynamic diameter of DNPs was the lowest (99.2 1.83 nm) and the NPs presented the encapsulation efficiency of DOX with 42.69 1.30%. Due to the folate-receptor mediated endocytosis, the PLGA-lipid NPs with folic acid (FA) targeting ligand showed significant higher uptake by folate-receptor-positive MCF-7 cells as compared to PLGA-lipid NPs without folate. Confocal microscopic observation and flow cytometry analysis also supported the enhanced cellular uptake of the FA-targeted NPs. The results indicated that the FA-targeted DNPs exhibited higher cytotoxicity in MCF-7 cells compared with non-targeted NPs. The lipid-polymer nanoparticles provide a solution of biocompatible nanocarrier for cancer targeting therapy.

How may targeted proteomics complement genomic data in breast cancer?

PubMed

Guerin, Mathilde; Gonçalves, Anthony; Toiron, Yves; Baudelet, Emilie; Audebert, Stéphane; Boyer, Jean-Baptiste; Borg, Jean-Paul; Camoin, Luc

2017-01-01

Breast cancer (BC) is the most common female cancer in the world and was recently deconstructed in different molecular entities. Although most of the recent assays to characterize tumors at the molecular level are genomic-based, proteins are the actual executors of cellular functions and represent the vast majority of targets for anticancer drugs. Accumulated data has demonstrated an important level of quantitative and qualitative discrepancies between genomic/transcriptomic alterations and their protein counterparts, mostly related to the large number of post-translational modifications. Areas covered: This review will present novel proteomics technologies such as Reverse Phase Protein Array (RPPA) or mass-spectrometry (MS) based approaches that have emerged and that could progressively replace old-fashioned methods (e.g. immunohistochemistry, ELISA, etc.) to validate proteins as diagnostic, prognostic or predictive biomarkers, and eventually monitor them in the routine practice. Expert commentary: These different targeted proteomic approaches, able to complement genomic data in BC and characterize tumors more precisely, will permit to go through a more personalized treatment for each patient and tumor.

Liquid film target impingement scrubber

DOEpatents

McDowell, William J.; Coleman, Charles F.

1977-03-15

An improved liquid film impingement scrubber is provided wherein particulates suspended in a gas are removed by jetting the particle-containing gas onto a relatively small thin liquid layer impingement target surface. The impingement target is in the form of a porous material which allows a suitable contacting liquid from a pressurized chamber to exude therethrough to form a thin liquid film target surface. The gas-supported particles collected by impingement of the gas on the target are continuously removed and flushed from the system by the liquid flow through each of a number of pores in the target.

Suspect screening of maternal serum to identify new environmental chemical biomonitoring targets using liquid chromatography-quadrupole time-of-flight mass spectrometry.

PubMed

Gerona, Roy R; Schwartz, Jackie M; Pan, Janet; Friesen, Matthew M; Lin, Thomas; Woodruff, Tracey J

2018-03-01

The use and advantages of high-resolution mass spectrometry (MS) as a discovery tool for environmental chemical monitoring has been demonstrated for environmental samples but not for biological samples. We developed a method using liquid chromatography-quadrupole time-of-flight MS (LC-QTOF/MS) for discovery of previously unmeasured environmental chemicals in human serum. Using non-targeted data acquisition (full scan MS analysis) we were able to screen for environmental organic acids (EOAs) in 20 serum samples from second trimester pregnant women. We define EOAs as environmental organic compounds with at least one dissociable proton which are utilized in commerce. EOAs include environmental phenols, phthalate metabolites, perfluorinated compounds, phenolic metabolites of polybrominated diphenyl ethers and polychlorinated biphenyls, and acidic pesticides and/or predicted acidic pesticide metabolites. Our validated method used solid phase extraction, reversed-phase chromatography in a C18 column with gradient elution, electrospray ionization in negative polarity and automated tandem MS (MS/MS) data acquisition to maximize true positive rates. We identified "suspect EOAs" using Agilent MassHunter Qualitative Analysis software, to match chemical formulas generated from each sample run with molecular formulas in our unique database of 693 EOAs assembled from multiple environmental literature sources. We found potential matches for 282 (41%) of the EOAs in our database. Sixty-five of these suspect EOAs were detected in at least 75% of the samples; only 19 of these compounds are currently biomonitored in National Health and Nutrition Examination Survey. We confirmed two of three suspect EOAs by LC-QTOF/MS using a targeted method developed through LC-MS/MS, reporting the first confirmation of benzophenone-1 and bisphenol S in pregnant women's sera. Our suspect screening workflow provides an approach to comprehensively scan environmental chemical exposures in humans. This

Effect of Name Change of Schizophrenia on Mass Media Between 1985 and 2013 in Japan: A Text Data Mining Analysis.

PubMed

Koike, Shinsuke; Yamaguchi, Sosei; Ojio, Yasutaka; Ohta, Kazusa; Ando, Shuntaro

2016-05-01

Mass media such as newspapers and TV news affect mental health-related stigma. In Japan, the name of schizophrenia was changed in 2002 for the purposes of stigma reduction; however, little has been known about the effect of name change of schizophrenia on mass media. Articles including old and new names of schizophrenia, depressive disorder, and diabetes mellitus (DM) in headlines and/or text were extracted from 23169092 articles in 4 major Japanese newspapers and 1 TV news program (1985-2013). The trajectory of the number of articles including each term was determined across years. Then, all text in news headlines was segmented as per part-of-speech level using text data mining. Segmented words were classified into 6 categories and in each category of extracted words by target term and period were also tested. Total 51789 and 1106 articles including target terms in newspaper articles and TV news segments were obtained, respectively. The number of articles including the target terms increased across years. Relative increase was observed in the articles published on schizophrenia since 2003 compared with those on DM and between 2000 and 2005 compared with those on depressive disorder. Word tendency used in headlines was equivalent before and after 2002 for the articles including each target term. Articles for schizophrenia contained more negative words than depressive disorder and DM (31.5%, 16.0%, and 8.2%, respectively). Name change of schizophrenia had a limited effect on the articles published and little effect on its contents. © The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Collisional disruption of porous weak sintered targets at low impact velocity

NASA Astrophysics Data System (ADS)

Setoh, M.; Nakamura, A. M.; Hirata, N.; Hiraoka, K.; Arakawa, M.

Porous structure is common in asteroids and satellites of outer planets In order to study the relation between structure of the small bodies and their thermal and collisional evolution we prepared porous sintered targets measured the compressive strength and determined their impact strength Previous studies showed using sintered glass beads Love et al 1993 the targets with higher compressive strength have higher impact strength and the targets with higher porosity have higher impact strength However in these experiments the porosity of the targets were changed according to the compressive strength Therefore we fixed the porosity while the compressive strength was varied Our experiments were performed with low impact velocity condition because low impact velocities are common among icy bodies far from the Earth We sintered soda lime glass beads of 50 micron diameter and 2 5g cm -3 nominal density at various temperatures and durations to produce targets with similar porosity sim 40 and different compressive strength 0 2 sim 7 8MPa We performed impact disruption experiments using a low velocity light-gas gun at Kobe University sim 100m s We used cylindrical polycarbonate projectiles 1 5 cm in height and 1 0 cm in diameter We determined the specific energy J kg of projectile kinetic energy per kilo gram initial target mass for the condition that the largest fragment mass being the half of the initial target mass is the threshold energy for collisional disruption Q Fujiwara et al 1989 Holsapple et al

Study of odor recorder using Mass Spectrometry

NASA Astrophysics Data System (ADS)

Miura, Tomohiro; Nakamoto, Takamichi; Moriizumi, Toyosaka

It is necessary to determine the recipe of a target odor with sufficient accuracy to realize an odor recorder for recording and reproducing it. We studied the recipe measurement method of a target odor using a mass spectrometry. It was confirmed that the linear superposition was valid when the binary mixture of the apple-flavor components such as isobutyric acid and ethyl valerate was measured. The superposition of a mass spectrum pattern may enable the recipe determination of a multi-component odor easily. In this research, we succeeded in the recipe determinations of orange flavor made up of 14 component odors when its typical recipe, the equalized, the citral-enhanced and the citronellol-enhanced ones were measured.

Determination of thiol metabolites in human urine by stable isotope labeling in combination with pseudo-targeted mass spectrometry analysis

PubMed Central

Liu, Ping; Qi, Chu-Bo; Zhu, Quan-Fei; Yuan, Bi-Feng; Feng, Yu-Qi

2016-01-01

Precursor ion scan and multiple reaction monitoring scan (MRM) are two typical scan modes in mass spectrometry analysis. Here, we developed a strategy by combining stable isotope labeling (IL) with liquid chromatography-mass spectrometry (LC-MS) under double precursor ion scan (DPI) and MRM for analysis of thiols in 5 types of human cancer urine. Firstly, the IL-LC-DPI-MS method was applied for non-targeted profiling of thiols from cancer samples. Compared to traditional full scan mode, the DPI method significantly improved identification selectivity and accuracy. 103 thiol candidates were discovered in all cancers and 6 thiols were identified by their standards. It is worth noting that pantetheine, for the first time, was identified in human urine. Secondly, the IL-LC-MRM-MS method was developed for relative quantification of thiols in cancers compared to healthy controls. All the MRM transitions of light and heavy labeled thiols were acquired from urines by using DPI method. Compared to DPI method, the sensitivity of MRM improved by 2.1–11.3 folds. In addition, the concentration of homocysteine, γ-glutamylcysteine and pantetheine enhanced more than two folds in cancer patients compared to healthy controls. Taken together, the method demonstrated to be a promising strategy for identification and comprehensive quantification of thiols in human urines. PMID:26888486

Towards large scale multi-target tracking

NASA Astrophysics Data System (ADS)

Vo, Ba-Ngu; Vo, Ba-Tuong; Reuter, Stephan; Lam, Quang; Dietmayer, Klaus

2014-06-01

Multi-target tracking is intrinsically an NP-hard problem and the complexity of multi-target tracking solutions usually do not scale gracefully with problem size. Multi-target tracking for on-line applications involving a large number of targets is extremely challenging. This article demonstrates the capability of the random finite set approach to provide large scale multi-target tracking algorithms. In particular it is shown that an approximate filter known as the labeled multi-Bernoulli filter can simultaneously track one thousand five hundred targets in clutter on a standard laptop computer.

Galaxy growth from redshift 5 to 0 at fixed comoving number density

NASA Astrophysics Data System (ADS)

van de Voort, Freeke

2016-10-01

Studying the average properties of galaxies at a fixed comoving number density over a wide redshift range has become a popular observational method, because it may trace the evolution of galaxies statistically. We test this method by comparing the evolution of galaxies at fixed number density and by following individual galaxies through cosmic time (z = 0-5) in cosmological, hydrodynamical simulations from the OverWhelmingly Large Simulations project. Comparing progenitors, descendants, and galaxies selected at fixed number density at each redshift, we find differences of up to a factor of 3 for galaxy and interstellar medium (ISM) masses. The difference is somewhat larger for black hole masses. The scatter in ISM mass increases significantly towards low redshift with all selection techniques. We use the fixed number density technique to study the assembly of dark matter, gas, stars, and black holes and the evolution in accretion and star formation rates. We find three different regimes for massive galaxies, consistent with observations: at high redshift the gas accretion rate dominates, at intermediate redshifts the star formation rate is the highest, and at low redshift galaxies grow mostly through mergers. Quiescent galaxies have much lower ISM masses (by definition) and much higher black hole masses, but the stellar and halo masses are fairly similar. Without active galactic nucleus (AGN) feedback, massive galaxies are dominated by star formation down to z = 0 and most of their stellar mass growth occurs in the centre. With AGN feedback, stellar mass is only added to the outskirts of galaxies by mergers and they grow inside-out.

Antipodal fragment velocities for porous and weak targets at catastrophic impacts

NASA Technical Reports Server (NTRS)

Yanagisawa, M.; Itoi, T.

1993-01-01

Mortar, porous alumina, and sand targets, which were spherical in shape and from 11 to 15 cm in diameter, were impacted normally by plastic (polycarbonate) projectiles of nearly 1 g in mass at velocities about 6 km/s. Fragment velocity at the antipole of impact site (antipodal velocity, V(sub a)), for each experiment, was obtained from two Flash X-ray images recorded prior to and at predetermined delayed time after impact event. It has been revealed that the velocities for the same E/M(sub t) (impact energy divided by target mass) depend strongly on target material, and differ about an order of magnitude between the sand and basalt.

Antipodal fragment velocities for porous and weak targets at catastrophic impacts

NASA Astrophysics Data System (ADS)

Yanagisawa, M.; Itoi, T.

1993-03-01

Mortar, porous alumina, and sand targets, which were spherical in shape and from 11 to 15 cm in diameter, were impacted normally by plastic (polycarbonate) projectiles of nearly 1 g in mass at velocities about 6 km/s. Fragment velocity at the antipole of impact site (antipodal velocity, V(sub a)), for each experiment, was obtained from two Flash X-ray images recorded prior to and at predetermined delayed time after impact event. It has been revealed that the velocities for the same E/M(sub t) (impact energy divided by target mass) depend strongly on target material, and differ about an order of magnitude between the sand and basalt.

Galaxy And Mass Assembly (GAMA): bivariate functions of Hα star-forming galaxies

NASA Astrophysics Data System (ADS)

Gunawardhana, M. L. P.; Hopkins, A. M.; Taylor, E. N.; Bland-Hawthorn, J.; Norberg, P.; Baldry, I. K.; Loveday, J.; Owers, M. S.; Wilkins, S. M.; Colless, M.; Brown, M. J. I.; Driver, S. P.; Alpaslan, M.; Brough, S.; Cluver, M.; Croom, S.; Kelvin, L.; Lara-López, M. A.; Liske, J.; López-Sánchez, A. R.; Robotham, A. S. G.

2015-02-01

We present bivariate luminosity and stellar mass functions of Hα star-forming galaxies drawn from the Galaxy And Mass Assembly (GAMA) survey. While optically deep spectroscopic observations of GAMA over a wide sky area enable the detection of a large number of 0.001 < SFRHα (M⊙ yr-1) < 100 galaxies, the requirement for an Hα detection in targets selected from an r-band magnitude-limited survey leads to an incompleteness due to missing optically faint star-forming galaxies. Using z < 0.1 bivariate distributions as a reference we model the higher-z distributions, thereby approximating a correction for the missing optically faint star-forming galaxies to the local star formation rate (SFR) and M densities. Furthermore, we obtain the r-band luminosity functions (LFs) and stellar mass functions of Hα star-forming galaxies from the bivariate LFs. As our sample is selected on the basis of detected Hα emission, a direct tracer of ongoing star formation, this sample represents a true star-forming galaxy sample, and is drawn from both photometrically classified blue and red subpopulations, though mostly from the blue population. On average 20-30 per cent of red galaxies at all stellar masses are star forming, implying that these galaxies may be dusty star-forming systems.

Variation of high-power aluminum-wire array Z-pinch dynamics with wire number, load mass, and array radius

NASA Astrophysics Data System (ADS)

Sanford, T. W. L.; Mock, R. C.; Marder, B. M.; Nash, T. J.; Spielman, R. B.; Peterson, D. L.; Roderick, N. F.; Hammer, J. H.; De Groot, J. S.; Mosher, D.; Whitney, K. G.; Apruzese, J. P.

1997-05-01

A systematic study of annular aluminum-wire z-pinches on the Saturn accelerator shows that the quality of the implosion, (as measured by the radial convergence, the radiated energy, pulse width, and power), increases with wire number. Radiation magnetohydrodynamic (RMHC) xy simulations suggest that the implosion transitions from that of individual wire plasmas to that of a continuous plasma shell when the interwire spacing is reduced below ˜1.4 mm. In this "plasma-shell regime," many of the global radiation and plasma characteristics are in agreement with those simulated by 2D-RMHC rz simulations. In this regime, measured changes in the radiation pulse width with variations in load mass and array radius are consistent with the simulations and are explained by the development of 2D fluid motion in the rz plane. Associated variations in the K-shell yield are qualitatively explained by simple radiation-scaling models.

43 CFR 3106.4-3 - Mass transfers.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false Mass transfers. 3106.4-3 Section 3106.4-3... or Otherwise § 3106.4-3 Mass transfers. (a) A mass transfer may be utilized in lieu of the provisions... large number of Federal leases to the same transferee. (b) Three originally executed copies of the mass...

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.

Non-target evaluation of contaminants in honey bees and pollen samples by gas chromatography time-of-flight mass spectrometry.

PubMed

Hakme, E; Lozano, A; Gómez-Ramos, M M; Hernando, M D; Fernández-Alba, A R

2017-10-01

This work presents a non-targeted screening approach for the detection and quantitation of contaminants in bees and pollen, collected from the same hive, by GC-EI-ToF-MS. It consists of a spectral library datasets search using a compound database followed by a manual investigation and analytical standard confirmation together with semi-quantitation purposes. Over 20% of the compounds found automatically by the library search could not be confirmed manually. This number of false positive detections was mainly a consequence of an inadequate ion ratio criterion (±30%), not considered in the automatic searching procedure. Eight compounds were detected in bees and pollen. They include insecticides/acaricides (chlorpyrifos, coumaphos, fluvalinate-tau, chlorfenvinphos, pyridaben, and propyl cresol) at a concentration range of 1-1207 μg kg -1 , herbicides (oxyfluorfen) at a concentration range of 212-1773 μg kg -1 and a growth regulator hormone (methoprene). Some compounds were detected only in pollen; such as herbicides (clomazone), insecticides/acaricides and fungicides used to control Varroa mites as benzylbenzoate, bufencarb, allethrin, permethrin, eugenol and cyprodinil. Additional compounds were detected only in bees: flamprop-methyl, 2-methylphenol (2-49 μg kg -1 ) and naphthalene (1-23 μg kg -1 ). The proposed method presents important advantages as it can avoid the use of an unachievable number of analytical standards considered target compounds "a priori" but not present in the analyzed samples. Copyright © 2017 Elsevier Ltd. All rights reserved.

Quadrupole Ion Mass Spectrometer for Masses of 2 to 50 Da

NASA Technical Reports Server (NTRS)

Helms, William; Griffin, Timothy P.; Ottens, Andrew; Harrison, Willard

2005-01-01

A customized quadrupole ion-trap mass spectrometer (QITMS) has been built to satisfy a need for a compact, rugged instrument for measuring small concentrations of hydrogen, helium, oxygen, and argon in a nitrogen atmosphere. This QITMS can also be used to perform quantitative analyses of other gases within its molecular-mass range, which is 2 to 50 daltons (Da). (More precisely, it can be used to perform quantitative analysis of gases that, when ionized, are characterized by m/Z ratios between 2 and 50, where m is the mass of an ion in daltons and Z is the number of fundamental electric charges on the ion.

ISDD: A computational model of particle sedimentation, diffusion and target cell dosimetry for in vitro toxicity studies

PubMed Central

2010-01-01

Background The difficulty of directly measuring cellular dose is a significant obstacle to application of target tissue dosimetry for nanoparticle and microparticle toxicity assessment, particularly for in vitro systems. As a consequence, the target tissue paradigm for dosimetry and hazard assessment of nanoparticles has largely been ignored in favor of using metrics of exposure (e.g. μg particle/mL culture medium, particle surface area/mL, particle number/mL). We have developed a computational model of solution particokinetics (sedimentation, diffusion) and dosimetry for non-interacting spherical particles and their agglomerates in monolayer cell culture systems. Particle transport to cells is calculated by simultaneous solution of Stokes Law (sedimentation) and the Stokes-Einstein equation (diffusion). Results The In vitro Sedimentation, Diffusion and Dosimetry model (ISDD) was tested against measured transport rates or cellular doses for multiple sizes of polystyrene spheres (20-1100 nm), 35 nm amorphous silica, and large agglomerates of 30 nm iron oxide particles. Overall, without adjusting any parameters, model predicted cellular doses were in close agreement with the experimental data, differing from as little as 5% to as much as three-fold, but in most cases approximately two-fold, within the limits of the accuracy of the measurement systems. Applying the model, we generalize the effects of particle size, particle density, agglomeration state and agglomerate characteristics on target cell dosimetry in vitro. Conclusions Our results confirm our hypothesis that for liquid-based in vitro systems, the dose-rates and target cell doses for all particles are not equal; they can vary significantly, in direct contrast to the assumption of dose-equivalency implicit in the use of mass-based media concentrations as metrics of exposure for dose-response assessment. The difference between equivalent nominal media concentration exposures on a μg/mL basis and target cell

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

Compositional Analysis of Asymmetric and Symmetric Dimethylated H3R2 Using Liquid Chromatography-Tandem Mass Spectrometry-Based Targeted Proteomics.

PubMed

Xu, Qingqing; Xu, Feifei; Liu, Liang; Chen, Yun

2016-09-06

Protein arginine methylation is one of the common post-translational modifications in cellular processes. To date, two isomeric forms of dimethylated arginine have been identified: asymmetric N(G),N(G)-dimethylarginine (aDMA), and symmetric N(G),N'(G)-dimethylarginine (sDMA). Evidence indicated that these isomers can coexist and have different or even opposite functions, with aDMA and sDMA forms of arginine 2 on histone H3 (i.e., H3R2me2a and H3R2me2s) being an example. Thus, specific detection and quantification of each isomeric form is important. Current methods are capable of predicting and detecting thousands of methylarginine sites in proteins, whereas differentiation and stoichiometric measurement of dimethylated protein isomers are still challenging. Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS)-based targeted proteomics has emerged as a promising technique for site-specific quantification of protein methylation using enzymatic peptides as surrogates of target proteins. However, it should be pointed out that a routine targeted proteomics strategy cannot easily distinguish sDMA- and aDMA-containing surrogate peptides due to their common nature. The estimated amount should be considered as the sum of both arginine dimethylated isomers. In this study, compositional analysis based on a linear algebra algorithm as an add-on to targeted proteomics was employed to quantify H3R2me2a and H3R2me2s (i.e., surrogate peptides of AR(me2a)TK(me1/2)QT and AR(me2s)TK(me1/2)QT). To achieve this simultaneous quantification, a targeted proteomics assay was developed and validated for each isomer first. With the slope and intercept of their calibration curves for each multiple reaction monitoring (MRM) transition, linear algebraic equations were derived. Using a series of mock mixtures consisting of isomers in varying concentrations, the reliability of the method was confirmed. Finally, the H3R2 dimethylation status was analyzed in normal MCF-10A cells

Detecting drug-target binding in cells using fluorescence-activated cell sorting coupled with mass spectrometry analysis.

PubMed

Wilson, Kris; Webster, Scott P; Iredale, John P; Zheng, Xiaozhong; Homer, Natalie Z; Pham, Nhan T; Auer, Manfred; Mole, Damian J

2017-12-15

The assessment of drug-target engagement for determining the efficacy of a compound inside cells remains challenging, particularly for difficult target proteins. Existing techniques are more suited to soluble protein targets. Difficult target proteins include those with challenging in vitro solubility, stability or purification properties that preclude target isolation. Here, we report a novel technique that measures intracellular compound-target complex formation, as well as cellular permeability, specificity and cytotoxicity-the toxicity-affinity-permeability-selectivity (TAPS) technique. The TAPS assay is exemplified here using human kynurenine 3-monooxygenase (KMO), a challenging intracellular membrane protein target of significant current interest. TAPS confirmed target binding of known KMO inhibitors inside cells. We conclude that the TAPS assay can be used to facilitate intracellular hit validation on most, if not all intracellular drug targets.

Detecting drug-target binding in cells using fluorescence-activated cell sorting coupled with mass spectrometry analysis

NASA Astrophysics Data System (ADS)

Wilson, Kris; Webster, Scott P.; Iredale, John P.; Zheng, Xiaozhong; Homer, Natalie Z.; Pham, Nhan T.; Auer, Manfred; Mole, Damian J.

2018-01-01

The assessment of drug-target engagement for determining the efficacy of a compound inside cells remains challenging, particularly for difficult target proteins. Existing techniques are more suited to soluble protein targets. Difficult target proteins include those with challenging in vitro solubility, stability or purification properties that preclude target isolation. Here, we report a novel technique that measures intracellular compound-target complex formation, as well as cellular permeability, specificity and cytotoxicity-the toxicity-affinity-permeability-selectivity (TAPS) technique. The TAPS assay is exemplified here using human kynurenine 3-monooxygenase (KMO), a challenging intracellular membrane protein target of significant current interest. TAPS confirmed target binding of known KMO inhibitors inside cells. We conclude that the TAPS assay can be used to facilitate intracellular hit validation on most, if not all intracellular drug targets.

Menstruation disorders in adolescents with eating disorders-target body mass index percentiles for their resolution.

PubMed

Vale, Beatriz; Brito, Sara; Paulos, Lígia; Moleiro, Pascoal

2014-04-01

To analyse the progression of body mass index in eating disorders and to determine the percentile for establishment and resolution of the disease. A retrospective descriptive cross-sectional study. Review of clinical files of adolescents with eating disorders. Of the 62 female adolescents studied with eating disorders, 51 presented with eating disorder not otherwise specified, 10 anorexia nervosa, and 1 bulimia nervosa. Twenty-one of these adolescents had menstrual disorders; in that, 14 secondary amenorrhea and 7 menstrual irregularities (6 eating disorder not otherwise specified, and 1 bulimia nervosa). In average, in anorectic adolescents, the initial body mass index was in 75th percentile; secondary amenorrhea was established 1 month after onset of the disease; minimum weight was 76.6% of ideal body mass index (at 4th percentile) at 10.2 months of disease; and resolution of amenorrhea occurred at 24 months, with average weight recovery of 93.4% of the ideal. In eating disorder not otherwise specified with menstrual disorder (n=10), the mean initial body mass index was at 85th percentile; minimal weight was in average 97.7% of the ideal value (minimum body mass index was in 52nd percentile) at 14.9 months of disease; body mass index stabilization occurred at 1.6 year of disease; and mean body mass index was in 73rd percentile. Considering eating disorder not otherwise specified with secondary amenorrhea (n=4); secondary amenorrhea occurred at 4 months, with resolution at 12 months of disease (mean 65th percentile body mass index). One-third of the eating disorder group had menstrual disorder - two-thirds presented with amenorrhea. This study indicated that for the resolution of their menstrual disturbance the body mass index percentiles to be achieved by female adolescents with eating disorders was 25-50 in anorexia nervosa, and 50-75, in eating disorder not otherwise specified.

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.

Design challenges in nanoparticle-based platforms: Implications for targeted drug delivery systems

NASA Astrophysics Data System (ADS)

Mullen, Douglas Gurnett

Characterization and control of heterogeneous distributions of nanoparticle-ligand components are major design challenges for nanoparticle-based platforms. This dissertation begins with an examination of poly(amidoamine) (PAMAM) dendrimer-based targeted delivery platform. A folic acid targeted modular platform was developed to target human epithelial cancer cells. Although active targeting was observed in vitro, active targeting was not found in vivo using a mouse tumor model. A major flaw of this platform design was that it did not provide for characterization or control of the component distribution. Motivated by the problems experienced with the modular design, the actual composition of nanoparticle-ligand distributions were examined using a model dendrimer-ligand system. High Pressure Liquid Chromatography (HPLC) resolved the distribution of components in samples with mean ligand/dendrimer ratios ranging from 0.4 to 13. A peak fitting analysis enabled the quantification of the component distribution. Quantified distributions were found to be significantly more heterogeneous than commonly expected and standard analytical parameters, namely the mean ligand/nanoparticle ratio, failed to adequately represent the component heterogeneity. The distribution of components was also found to be sensitive to particle modifications that preceded the ligand conjugation. With the knowledge gained from this detailed distribution analysis, a new platform design was developed to provide a system with dramatically improved control over the number of components and with improved batch reproducibility. Using semi-preparative HPLC, individual dendrimer-ligand components were isolated. The isolated dendrimer with precise numbers of ligands were characterized by NMR and analytical HPLC. In total, nine different dendrimer-ligand components were obtained with degrees of purity ≥80%. This system has the potential to serve as a platform to which a precise number of functional molecules

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.

Open tubular lab-on-column/mass spectrometry for targeted proteomics of nanogram sample amounts.

PubMed

Hustoft, Hanne Kolsrud; Vehus, Tore; Brandtzaeg, Ole Kristian; Krauss, Stefan; Greibrokk, Tyge; Wilson, Steven Ray; Lundanes, Elsa

2014-01-01

A novel open tubular nanoproteomic platform featuring accelerated on-line protein digestion and high-resolution nano liquid chromatography mass spectrometry (LC-MS) has been developed. The platform features very narrow open tubular columns, and is hence particularly suited for limited sample amounts. For enzymatic digestion of proteins, samples are passed through a 20 µm inner diameter (ID) trypsin + endoproteinase Lys-C immobilized open tubular enzyme reactor (OTER). Resulting peptides are subsequently trapped on a monolithic pre-column and transferred on-line to a 10 µm ID porous layer open tubular (PLOT) liquid chromatography LC separation column. Wnt/ß-catenein signaling pathway (Wnt-pathway) proteins of potentially diagnostic value were digested+detected in targeted-MS/MS mode in small cell samples and tumor tissues within 120 minutes. For example, a potential biomarker Axin1 was identifiable in just 10 ng of sample (protein extract of ∼1,000 HCT15 colon cancer cells). In comprehensive mode, the current OTER-PLOT set-up could be used to identify approximately 1500 proteins in HCT15 cells using a relatively short digestion+detection cycle (240 minutes), outperforming previously reported on-line digestion/separation systems. The platform is fully automated utilizing common commercial instrumentation and parts, while the reactor and columns are simple to produce and have low carry-over. These initial results point to automated solutions for fast and very sensitive MS based proteomics, especially for samples of limited size.

Direct molecular mass determination of trehalose monomycolate from 11 species of mycobacteria by MALDI-TOF mass spectrometry.

PubMed

Fujita, Yukiko; Naka, Takashi; Doi, Takeshi; Yano, Ikuya

2005-05-01

Direct estimation of the molecular mass of single molecular species of trehalose 6-monomycolate (TMM), a ubiquitous cell-wall component of mycobacteria, was performed by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. When less than 1 microg TMM was analysed by MALDI-TOF mass spectrometry, quasimolecular ions [M+Na]+ of each molecular species were demonstrated and the numbers of carbons and double bonds (or cyclopropane rings) were determined. Since the introduction of oxygen atoms such as carbonyl, methoxy and ester groups yielded the appropriate shift of mass ions, the major subclasses of mycolic acid (alpha, methoxy, keto and wax ester) were identified without resorting to hydrolytic procedures. The results showed a marked difference in the molecular species composition of TMM among mycobacterial species. Unexpectedly, differing from other mycoloyl glycolipids, TMM from Mycobacterium tuberculosis showed a distinctive mass pattern, with abundant odd-carbon-numbered monocyclopropanoic (or monoenoic) alpha-mycolates besides dicyclopropanoic mycolate, ranging from C75 to C85, odd- and even-carbon-numbered methoxymycolates ranging from C83 to C94 and even- and odd-carbon-numbered ketomycolates ranging from C83 to C90. In contrast, TMM from Mycobacterium bovis (wild strain and BCG substrains) possessed even-carbon-numbered dicyclopropanoic alpha-mycolates. BCG Connaught strain lacked methoxymycolates almost completely. These results were confirmed by MALDI-TOF mass analysis of mycolic acid methyl esters liberated by alkaline hydrolysis and methylation of the original TMM. Wax ester-mycoloyl TMM molecular species were demonstrated for the first time as an intact form in the Mycobacterium avium-intracellulare group, M. phlei and M. flavescens. The M. avium-intracellulare group possessed predominantly C85 and C87 wax ester-mycoloyl TMM, while M. phlei and the rapid growers tested contained C80, C81, C82 and C83 wax ester

Targeting Histone Abnormality in Triple Negative Breast Cancer

DTIC Science & Technology

2015-08-01

Casero RA, Davidson NE. Molecular mechanisms of polyamine analogues in cancer cells. Anti - Cancer Drugs, 16(3): 229-241, 2005. PMID: 15711175 18 3...1 AWARD NUMBER: W81XWH-14-1-0237 TITLE: Targeting Histone Abnormality in Triple-Negative Breast Cancer PRINCIPAL INVESTIGATOR: Yi...TITLE AND SUBTITLE 5a. CONTRACT NUMBER Targeting Histone Abnormality in Triple-Negative Breast Cancer 5b. GRANT NUMBER W81XWH-14-1-0237 5c

Quantum Illumination-Based Target Detection and Discrimination

DTIC Science & Technology

2014-06-30

amplifier (EDFA) was combined with the signal to simulate a high-noise environment, with a noise photon number per mode NB in the range 40–300. The...Research Triangle Park, NC 27709-2211 quantum communication, target detection, entanglement , parametric downconversion, optical parametric amplifiers...laser system of the same average transmitted photon number, when the target return has random-amplitude behavior. Receiver operating characteristic

Mass Notification for Higher Education

ERIC Educational Resources Information Center

Schneider, Tod

2010-01-01

Mass notification is a high priority in educational institutions. As the number of electronic communication devices has diversified, so has the complexity of designing an effective mass notification system. Picking the right system, with the right features, support services and price, can be daunting. This publication, updated quarterly due to…

New cardioprotective agent flokalin and its supramolecular complexes with target amino acids: An integrated mass-spectrometry and quantum-chemical study

NASA Astrophysics Data System (ADS)

Pashynska, Vlada; Stepanian, Stepan; Gömöry, Ágnes; Vékey, Károly; Adamowicz, Ludwik

2017-10-01

This study is devoted to examining the molecular structure and molecular mechanisms of action of the recently developed cardioprotective agent flokalin (Fl), a fluorine containing analogue of pinacidil, which is known as an activator of ATP sensitive potassium membrane channels. A combined experimental and computational investigation of flokalin and its biologically relevant supramolecular complexes with selected amino acids involved in KATP-channels proteins is performed by electrospray ionization mass spectrometry (ESI MS) and by B3LYP/aug-cc-pVDZ quantum-mechanical calculations. First Fl solution is probed by ESI MS and a characteristic mass spectrum of the agent is obtained. Next the intermolecular interactions of Fl with the potentially targeted aminoacids (AA), Lys and Thr, are experimentally investigated. The spectra of the model Fl:AA systems (in 1:1 M ratio) contain information on the ions characteristic to the individual components of the mixtures; though the most interesting spectral results from the biophysical view point are related to the ions of stable molecular clusters formed by flokalin with AA. The peaks of such ions are quite prominent in the spectrum for the Fl:Lys system and less prominent for Fl:Thr. The equilibrium geometries and the corresponding interaction energies of the noncovalent supramolecular complexes registered in the mass spectra are determined in the quantum chemical calculations. The formation of the stable noncovalent complexes of Fl with Lyz and Thr revealed by the ESI MS probing and by the theoretical modelling testify to a possibility of interaction of flokalin with the KATP-channel domains enriched with the two amino acids in biological systems.

Prostate Cancer Clinical Consortium Clinical Research Site: Targeted Therapies

DTIC Science & Technology

2017-10-01

AWARD NUMBER: W81XWH-14-2-0159 TITLE: Prostate Cancer Clinical Consortium Clinical Research Site: Targeted Therapies PRINCIPAL INVESTIGATOR...Annual PREPARED FOR: U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 DISTRIBUTION STATEMENT: Approved for...AND SUBTITLE Prostate Cancer Clinical Consortium Clinical Research Site: Targeted Therapies 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT

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.

Multiple Auto-Adapting Color Balancing for Large Number of Images

NASA Astrophysics Data System (ADS)

Zhou, X.

2015-04-01

This paper presents a powerful technology of color balance between images. It does not only work for small number of images but also work for unlimited large number of images. Multiple adaptive methods are used. To obtain color seamless mosaic dataset, local color is adjusted adaptively towards the target color. Local statistics of the source images are computed based on the so-called adaptive dodging window. The adaptive target colors are statistically computed according to multiple target models. The gamma function is derived from the adaptive target and the adaptive source local stats. It is applied to the source images to obtain the color balanced output images. Five target color surface models are proposed. They are color point (or single color), color grid, 1st, 2nd and 3rd 2D polynomials. Least Square Fitting is used to obtain the polynomial target color surfaces. Target color surfaces are automatically computed based on all source images or based on an external target image. Some special objects such as water and snow are filtered by percentage cut or a given mask. Excellent results are achieved. The performance is extremely fast to support on-the-fly color balancing for large number of images (possible of hundreds of thousands images). Detailed algorithm and formulae are described. Rich examples including big mosaic datasets (e.g., contains 36,006 images) are given. Excellent results and performance are presented. The results show that this technology can be successfully used in various imagery to obtain color seamless mosaic. This algorithm has been successfully using in ESRI ArcGis.

Estimating Mass Parameters of Doubly Synchronous Binary Asteroids

NASA Astrophysics Data System (ADS)

Davis, Alex; Scheeres, Daniel J.

2017-10-01

The non-spherical mass distributions of binary asteroid systems lead to coupled mutual gravitational forces and torques. Observations of the coupled attitude and orbital dynamics can be leveraged to provide information about the mass parameters of the binary system. The full 3-dimensional motion has 9 degrees of freedom, and coupled dynamics require the use of numerical investigation only. In the current study we simplify the system to a planar ellipsoid-ellipsoid binary system in a doubly synchronous orbit. Three modes are identified for the system, which has 4 degrees of freedom, with one degree of freedom corresponding to an ignorable coordinate. The three modes correspond to the three major librational modes of the system when it is in a doubly synchronous orbit. The linearized periods of each mode are a function of the mass parameters of the two asteroids, enabling measurement of these parameters based on observations of the librational motion. Here we implement estimation techniques to evaluate the capabilities of this mass measurement method. We apply this methodology to the Trojan binary asteroid system 617 Patroclus and Menoetius (1906 VY), the final flyby target of the recently announced LUCY Discovery mission. This system is of interest because a stellar occultation campaign of the Patroclus and Menoetius system has suggested that the asteroids are similarly sized oblate ellipsoids moving in a doubly-synchronous orbit, making the system an ideal test for this investigation. A number of missed observations during the campaign also suggested the possibility of a crater on the southern limb of Menoetius, the presence of which could be evaluated by our mass estimation method. This presentation will review the methodology and potential accuracy of our approach in addition to evaluating how the dynamical coupling can be used to help understand light curve and stellar occultation observations for librating binary systems.

Clustering analysis of moving target signatures

NASA Astrophysics Data System (ADS)

Martone, Anthony; Ranney, Kenneth; Innocenti, Roberto

2010-04-01

Previously, we developed a moving target indication (MTI) processing approach to detect and track slow-moving targets inside buildings, which successfully detected moving targets (MTs) from data collected by a low-frequency, ultra-wideband radar. Our MTI algorithms include change detection, automatic target detection (ATD), clustering, and tracking. The MTI algorithms can be implemented in a real-time or near-real-time system; however, a person-in-the-loop is needed to select input parameters for the clustering algorithm. Specifically, the number of clusters to input into the cluster algorithm is unknown and requires manual selection. A critical need exists to automate all aspects of the MTI processing formulation. In this paper, we investigate two techniques that automatically determine the number of clusters: the adaptive knee-point (KP) algorithm and the recursive pixel finding (RPF) algorithm. The KP algorithm is based on a well-known heuristic approach for determining the number of clusters. The RPF algorithm is analogous to the image processing, pixel labeling procedure. Both algorithms are used to analyze the false alarm and detection rates of three operational scenarios of personnel walking inside wood and cinderblock buildings.

Evaluation of active and passive recruitment methods used in randomized controlled trials targeting pediatric obesity

PubMed Central

RAYNOR, HOLLIE A.; OSTERHOLT, KATHRIN M.; HART, CHANTELLE N.; JELALIAN, ELISSA; VIVIER, PATRICK; WING, RENA R.

2016-01-01

Objective Evaluate enrollment numbers, randomization rates, costs, and cost-effectiveness of active versus passive recruitment methods for parent-child dyads into two pediatric obesity intervention trials. Methods Recruitment methods were categorized into active (pediatrician referral and targeted mailings, with participants identified by researcher/health care provider) versus passive methods (newspaper, bus, internet, television, and earning statements; fairs/community centers/schools; and word of mouth; with participants self-identified). Numbers of enrolled and randomized families and costs/recruitment method were monitored throughout the 22-month recruitment period. Costs (in USD) per recruitment method included staff time, mileage, and targeted costs of each method. Results A total of 940 families were referred or made contact, with 164 families randomized (child: 7.2±1.6 years, 2.27±0.61 standardized body mass index [zBMI], 86.6% obese, 61.7% female, 83.5% white; parent: 38.0±5.8 years, 32.9±8.4 BMI, 55.2% obese, 92.7% female, 89.6% white). Pediatrician referral, followed by targeted mailings, produced the largest number of enrolled and randomized families (both methods combined producing 87.2% of randomized families). Passive recruitment methods yielded better retention from enrollment to randomization (p <0.05), but produced few families (21 in total). Approximately $91 000 was spent on recruitment, with cost per randomized family at $554.77. Pediatrician referral was the most cost-effective method, $145.95/randomized family, but yielded only 91 randomized families over 22-months of continuous recruitment. Conclusion Pediatrician referral and targeted mailings, which are active recruitment methods, were the most successful strategies. However, recruitment demanded significant resources. Successful recruitment for pediatric trials should use several strategies. Clinical Trials Registration: NCT00259324, NCT00200265 PMID:19922036

Targeted disruption of BMP signaling through type IA receptor (BMPR1A) in osteocyte suppresses SOST and RANKL, leading to dramatic increase in bone mass, bone mineral density and mechanical strength.

PubMed

Kamiya, Nobuhiro; Shuxian, Lin; Yamaguchi, Ryosuke; Phipps, Matthew; Aruwajoye, Olumide; Adapala, Naga Suresh; Yuan, Hui; Kim, Harry K W; Feng, Jian Q

2016-10-01

Recent studies suggest a critical role of osteocytes in controlling skeletal development and bone remodeling although the molecular mechanism is largely unknown. This study investigated BMP signaling in osteocytes by disrupting Bmpr1a under the Dmp1-promoter. The conditional knockout (cKO) mice displayed a striking osteosclerotic phenotype with increased trabecular bone volume, thickness, number, and mineral density as assessed by X-ray and micro-CT. The bone histomorphometry, H&E, and TRAP staining revealed a dramatic increase in trabecular and cortical bone masses but a sharp reduction in osteoclast number. Moreover, there was an increase in BrdU positive osteocytes (2-5-fold) and osteoid volume (~4-fold) but a decrease in the bone formation rate (~85%) in the cKO bones, indicating a defective mineralization. The SEM analysis revealed poorly formed osteocytes: a sharp increase in cell numbers, a great reduction in cell dendrites, and a remarkable change in the cell distribution pattern. Molecular studies demonstrated a significant decrease in the Sost mRNA levels in bone (>95%), and the SOST protein levels in serum (~85%) and bone matrices. There was a significant increase in the β-catenin (>3-fold) mRNA levels as well as its target genes Tcf1 (>6-fold) and Tcf3 (~2-fold) in the cKO bones. We also showed a significant decrease in the RANKL levels of serum proteins (~65%) and bone mRNA (~57%), and a significant increase in the Opg mRNA levels (>20-fold) together with a significant reduction in the Rankl/Opg ratio (>95%), which are responsible for a sharp reduction in the cKO osteoclasts. The values of mechanical strength were higher in cKO femora (i.e. max force, displacement, and work failure). These results suggest that loss of BMP signaling specifically in osteocytes dramatically increases bone mass presumably through simultaneous inhibition of RANKL and SOST, leading to osteoclast inhibition and Wnt activation together. Finally, a working hypothesis is

Mass media interventions for smoking cessation in adults.

PubMed

Bala, Malgorzata M; Strzeszynski, Lukasz; Topor-Madry, Roman; Cahill, Kate

2013-06-06

Mass media tobacco control campaigns can reach large numbers of people. Much of the literature is focused on the effects of tobacco control advertising on young people, but there are also a number of evaluations of campaigns targeting adult smokers, which show mixed results. Campaigns may be local, regional or national, and may be combined with other components of a comprehensive tobacco control policy. To assess the effectiveness of mass media interventions in reducing smoking among adults. The Cochrane Tobacco Addiction Group search strategy was combined with additional searches for any studies that referred to tobacco/smoking cessation, mass media and adults. We also searched the Cochrane Register of Controlled Trials (CENTRAL) and a number of electronic databases. The last search was carried out in February 2013. Controlled trials allocating communities, regions or states to intervention or control conditions; interrupted time series. Adults, 25 years or older, who regularly smoke cigarettes. Studies which cover all adults as defined in studies were included. Mass media are defined here as channels of communication such as television, radio, newspapers, billboards, posters, leaflets or booklets intended to reach large numbers of people, and which are not dependent on person-to-person contact. The purpose of the mass media campaign must be primarily to encourage smokers to quit. They could be carried out alone or in conjunction with tobacco control programmes. The primary outcome was change in smoking behaviour. This could be reported as changes in prevalence, changes in cigarette consumption, quit rates, odds of being a smoker. Two authors independently assessed all studies for inclusion criteria and for study quality. One author (MB) extracted data, and a second author (LS) checked them.Results were not pooled due to heterogeneity of the included studies and are presented narratively and in table form. Eleven campaigns met the inclusion criteria for this

Mass media interventions for smoking cessation in adults.

PubMed

Bala, Malgorzata M; Strzeszynski, Lukasz; Topor-Madry, Roman

2017-11-21

Mass media tobacco control campaigns can reach large numbers of people. Much of the literature is focused on the effects of tobacco control advertising on young people, but there are also a number of evaluations of campaigns targeting adult smokers, which show mixed results. Campaigns may be local, regional or national, and may be combined with other components of a comprehensive tobacco control policy. To assess the effectiveness of mass media interventions in reducing smoking among adults. The Cochrane Tobacco Addiction Group search strategy was combined with additional searches for any studies that referred to tobacco/smoking cessation, mass media and adults. We also searched the Cochrane Central Register of Controlled Trials (CENTRAL) and a number of electronic databases. The last search was carried out in November 2016. Controlled trials allocating communities, regions or states to intervention or control conditions; interrupted time series.Adults, 25 years or older, who regularly smoke cigarettes. Studies which cover all adults as defined in studies were included.Mass media are defined here as channels of communication such as television, radio, newspapers, billboards, posters, leaflets or booklets intended to reach large numbers of people, and which are not dependent on person-to-person contact. The purpose of the mass media campaign must be primarily to encourage smokers to quit. They could be carried out alone or in conjunction with tobacco control programmes.The primary outcome was change in smoking behaviour. This could be reported as changes in prevalence, changes in cigarette consumption, quit rates, or odds of being a smoker. Two authors independently assessed all studies for inclusion criteria and for study quality (MB, LS, RTM). One author (MB) extracted data, and a second author (LS) checked them.Results were not pooled due to heterogeneity of the included studies and are presented narratively and in table form. Eleven campaigns met the inclusion

Highly charged ion secondary ion mass spectroscopy

DOEpatents

Hamza, Alex V.; Schenkel, Thomas; Barnes, Alan V.; Schneider, Dieter H.

2001-01-01

A secondary ion mass spectrometer using slow, highly charged ions produced in an electron beam ion trap permits ultra-sensitive surface analysis and high spatial resolution simultaneously. The spectrometer comprises an ion source producing a primary ion beam of highly charged ions that are directed at a target surface, a mass analyzer, and a microchannel plate detector of secondary ions that are sputtered from the target surface after interaction with the primary beam. The unusually high secondary ion yield permits the use of coincidence counting, in which the secondary ion stops are detected in coincidence with a particular secondary ion. The association of specific molecular species can be correlated. The unique multiple secondary nature of the highly charged ion interaction enables this new analytical technique.

Multi-core and GPU accelerated simulation of a radial star target imaged with equivalent t-number circular and Gaussian pupils

NASA Astrophysics Data System (ADS)

Greynolds, Alan W.

2013-09-01

Results from the GelOE optical engineering software are presented for the through-focus, monochromatic coherent and polychromatic incoherent imaging of a radial "star" target for equivalent t-number circular and Gaussian pupils. The FFT-based simulations are carried out using OpenMP threading on a multi-core desktop computer, with and without the aid of a many-core NVIDIA GPU accessing its cuFFT library. It is found that a custom FFT optimized for the 12-core host has similar performance to a simply implemented 256-core GPU FFT. A more sophisticated version of the latter but tuned to reduce overhead on a 448-core GPU is 20 to 28 times faster than a basic FFT implementation running on one CPU core.

Shock Ignition Target Design for Inertial Fusion Energy

DTIC Science & Technology

2010-01-01

Shock ignition target design for inertial fusion energy Andrew J. Schmitt,1, a) Jason W. Bates,1 Steven P. Obenschain,1 Steven T. Zalesak,2 and David...2010 to 00-00-2010 4. TITLE AND SUBTITLE Shock ignition target design for inertial fusion energy 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM

Quantum partial search for uneven distribution of multiple target items

NASA Astrophysics Data System (ADS)

Zhang, Kun; Korepin, Vladimir

2018-06-01

Quantum partial search algorithm is an approximate search. It aims to find a target block (which has the target items). It runs a little faster than full Grover search. In this paper, we consider quantum partial search algorithm for multiple target items unevenly distributed in a database (target blocks have different number of target items). The algorithm we describe can locate one of the target blocks. Efficiency of the algorithm is measured by number of queries to the oracle. We optimize the algorithm in order to improve efficiency. By perturbation method, we find that the algorithm runs the fastest when target items are evenly distributed in database.

Muscle mass as a target to reduce fatigue in patients with advanced cancer.

PubMed

Neefjes, Elisabeth C W; van den Hurk, Renske M; Blauwhoff-Buskermolen, Susanne; van der Vorst, Maurice J D L; Becker-Commissaris, Annemarie; de van der Schueren, Marian A E; Buffart, Laurien M; Verheul, Henk M W

2017-08-01

Cancer-related fatigue (CRF) reduces quality of life and the activity level of patients with cancer. Cancer related fatigue can be reduced by exercise interventions that may concurrently increase muscle mass. We hypothesized that low muscle mass is directly related to higher CRF. A total of 233 patients with advanced cancer starting palliative chemotherapy for lung, colorectal, breast, or prostate cancer were studied. The skeletal muscle index (SMI) was calculated as the patient's muscle mass on level L3 or T4 of a computed tomography scan, adjusted for height. Fatigue was assessed with the Functional Assessment of Chronic Illness Therapy-fatigue questionnaire (cut-off for fatigue <34). Multiple linear regression analyses were conducted to study the association between SMI and CRF adjusting for relevant confounders. In this group of patients with advanced cancer, the median fatigue score was 36 (interquartile range 26-44). A higher SMI on level L3 was significantly associated with less CRF for men (B 0.447, P 0.004) but not for women (B - 0.401, P 0.090). No association between SMI on level T4 and the Functional Assessment of Chronic Illness Therapy-fatigue score was found (n = 82). The association between SMI and CRF may lead to the suggestion that male patients may be able to reduce fatigue by exercise interventions aiming at an increased muscle mass. In women with advanced cancer, CRF is more influenced by other causes, because it is not significantly related to muscle mass. To further reduce CRF in both men and women with cancer, multifactorial assessments need to be performed in order to develop effective treatment strategies. © 2017 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.

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…

Fabrication and characterization of carbon-backed thin 208Pb targets.

PubMed

Thakur, Meenu; Dubey, R; Abhilash, S R; Behera, B R; Mohanty, B P; Kabiraj, D; Ojha, Sunil; Duggal, Heena

2016-01-01

Thin carbon-backed isotopically enriched 208 Pb targets were required for our experiment aimed to study the reaction dynamics for 48 Ti +  208 Pb system, populating the near super-heavy nucleus 256 Rf, through mass-energy correlation of the fission fragments. Purity and thickness of the targets are of utmost importance in such studies as these factors have strong influence on the measurement accuracy of mass and energy distribution of fission fragments. 208 Pb targets with thickness ranging from 60 μg/cm 2 to 250 μg/cm 2 have been fabricated in high vacuum environment using physical vapor deposition method. Important points in the method are as follows: • 208 Pb was deposited using resistive heating method, whereas carbon (backing foil) deposition was performed by using the electron beam bombardment technique.•Different characterization techniques such as Particle Induced X-ray Emission (PIXE), Energy Dispersive X-Ray Fluorescence (EDXRF) and Rutherford Backscattering Spectrometry (RBS) were used to assert the purity and thickness of the targets.•These targets have successfully been used to accomplish our experimental objectives.