Exact solutions for mass-dependent irreversible aggregations.

PubMed

Son, Seung-Woo; Christensen, Claire; Bizhani, Golnoosh; Grassberger, Peter; Paczuski, Maya

2011-10-01

We consider the mass-dependent aggregation process (k+1)X→X, given a fixed number of unit mass particles in the initial state. One cluster is chosen proportional to its mass and is merged into one, either with k neighbors in one dimension, or--in the well-mixed case--with k other clusters picked randomly. We find the same combinatorial exact solutions for the probability to find any given configuration of particles on a ring or line, and in the well-mixed case. The mass distribution of a single cluster exhibits scaling laws and the finite-size scaling form is given. The relation to the classical sum kernel of irreversible aggregation is discussed.

Position-dependent effective masses in semiconductor theory. II

NASA Technical Reports Server (NTRS)

Von Roos, O.; Mavromatis, H.

1985-01-01

A compound semiconductor possessing a slowly varying position-dependent chemical composition is considered. An effective-mass equation governing the dynamics of electron (or hole) motion using the Kohn-Luttinger representation and canonical transformations is derived. It is shown that, as long as the variation in chemical composition may be treated as a perturbation, the effective masses become constant, position-independent quantities. The effective-mass equation derived here is identical to the effective-mass equation derived previously by von Roos (1983), using a Wannier representation.

Bargmann's theorem and position-dependent effective mass

NASA Astrophysics Data System (ADS)

Kawamura, Kiyoshi; Brown, Ronald A.

1988-03-01

The physical significance of Galilean transformations applied to effective-mass (EM) equations for Bloch electrons in Wannier representation is discussed and contrasted with that of Galilean coordinate transformations applied to the free-particle Schrödinger equation. Mass constraints imposed on the latter by Bargmann's (1954) superselection rule do not extend to the EM, and criticisms of the position-dependent EM concept which have invoked Bargmann's theorem are shown to be without foundation. Other criticisms concerning the nonuniqueness and non-Hermiticity of effective Hamiltonians which employ this concept to describe crystals of graded composition are discussed, and it is argued that the problems are associated with the heuristic nature of the virtual-crystal model which is adopted rather than with the position-dependent EM.

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

ERIC Educational Resources Information Center

Stephenson, Michael T.

2003-01-01

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

Dependence of Microlensing on Source Size and Lens Mass

NASA Astrophysics Data System (ADS)

Congdon, A. B.; Keeton, C. R.

2007-11-01

In gravitational lensed quasars, the magnification of an image depends on the configuration of stars in the lensing galaxy. We study the statistics of the magnification distribution for random star fields. The width of the distribution characterizes the amount by which the observed magnification is likely to differ from models in which the mass is smoothly distributed. We use numerical simulations to explore how the width of the magnification distribution depends on the mass function of stars, and on the size of the source quasar. We then propose a semi-analytic model to describe the distribution width for different source sizes and stellar mass functions.

Spatial frequency dependence of target signature for infrared performance modeling

NASA Astrophysics Data System (ADS)

Du Bosq, Todd; Olson, Jeffrey

2011-05-01

The standard model used to describe the performance of infrared imagers is the U.S. Army imaging system target acquisition model, based on the targeting task performance metric. The model is characterized by the resolution and sensitivity of the sensor as well as the contrast and task difficulty of the target set. The contrast of the target is defined as a spatial average contrast. The model treats the contrast of the target set as spatially white, or constant, over the bandlimit of the sensor. Previous experiments have shown that this assumption is valid under normal conditions and typical target sets. However, outside of these conditions, the treatment of target signature can become the limiting factor affecting model performance accuracy. This paper examines target signature more carefully. The spatial frequency dependence of the standard U.S. Army RDECOM CERDEC Night Vision 12 and 8 tracked vehicle target sets is described. The results of human perception experiments are modeled and evaluated using both frequency dependent and independent target signature definitions. Finally the function of task difficulty and its relationship to a target set is discussed.

Landau problem with time dependent mass in time dependent electric and harmonic background fields

NASA Astrophysics Data System (ADS)

Lawson, Latévi M.; Avossevou, Gabriel Y. H.

2018-04-01

The spectrum of a Hamiltonian describing the dynamics of a Landau particle with time-dependent mass and frequency undergoing the influence of a uniform time-dependent electric field is obtained. The configuration space wave function of the model is expressed in terms of the generalised Laguerre polynomials. To diagonalize the time-dependent Hamiltonian, we employ the Lewis-Riesenfeld method of invariants. To this end, we introduce a unitary transformation in the framework of the algebraic formalism to construct the invariant operator of the system and then to obtain the exact solution of the Hamiltonian. We recover the solutions of the ordinary Landau problem in the absence of the electric and harmonic fields for a constant particle mass.

Targeted mass treatment for syphilis with oral azithromycin.

PubMed

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

2003-01-25

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

Maximizing in vivo target clearance by design of pH-dependent target binding antibodies with altered affinity to FcRn.

PubMed

Yang, Danlin; Giragossian, Craig; Castellano, Steven; Lasaro, Marcio; Xiao, Haiguang; Saraf, Himanshu; Hess Kenny, Cynthia; Rybina, Irina; Huang, Zhong-Fu; Ahlberg, Jennifer; Bigwarfe, Tammy; Myzithras, Maria; Waltz, Erica; Roberts, Simon; Kroe-Barrett, Rachel; Singh, Sanjaya

2017-10-01

Antibodies with pH-dependent binding to both target antigens and neonatal Fc receptor (FcRn) provide an alternative tool to conventional neutralizing antibodies, particularly for therapies where reduction in antigen level is challenging due to high target burden. However, the requirements for optimal binding kinetic framework and extent of pH dependence for these antibodies to maximize target clearance from circulation are not well understood. We have identified a series of naturally-occurring high affinity antibodies with pH-dependent target binding properties. By in vivo studies in cynomolgus monkeys, we show that pH-dependent binding to the target alone is not sufficient for effective target removal from circulation, but requires Fc mutations that increase antibody binding to FcRn. Affinity-enhanced pH-dependent FcRn binding that is double-digit nM at pH 7.4 and single-digit nM at pH 6 achieved maximal target reduction when combined with similar target binding affinities in reverse pH directions. Sustained target clearance below the baseline level was achieved 3 weeks after single-dose administration at 1.5 mg/kg. Using the experimentally derived mechanistic model, we demonstrate the essential kinetic interplay between target turnover and antibody pH-dependent binding during the FcRn recycling, and identify the key components for achieving maximal target clearance. These results bridge the demand for improved patient dosing convenience with the "know-how" of therapeutic modality by design.

Age, state, environment, and season dependence of senescence in body mass.

PubMed

Kroeger, Svenja B; Blumstein, Daniel T; Armitage, Kenneth B; Reid, Jane M; Martin, Julien G A

2018-02-01

Senescence is a highly variable process that comprises both age-dependent and state-dependent components and can be greatly affected by environmental conditions. However, few studies have quantified the magnitude of age-dependent and state-dependent senescence in key life-history traits across individuals inhabiting different spatially structured and seasonal environments. We used longitudinal data from wild female yellow-bellied marmots ( Marmota flaviventer ), living in two adjacent environments that differ in elevation and associated phenology, to quantify how age and individual state, measured as "time to death," affect body mass senescence in different environments. Further, we quantified how patterns of senescence differed between two biologically distinct seasons, spring, and late summer. Body mass senescence had an age-dependent component, expressed as a decrease in mass in old age. Overall, estimated age-dependent senescence was greater in females living in the more favorable lower elevation environment, than in the harsher higher elevation environment, and greater in late summer than in spring. Body mass senescence also had a state-dependent component, captured by effects of time to death, but only in the more favorable lower elevation environment. In spring, body mass gradually decreased from 2 years before death, whereas in late summer, state-dependent effects were expressed as a terminal decrease in body mass in the last year of life. Contrary to expectations, we found that senescence was more likely to be observed under more favorable environmental conditions, rather than under harsher conditions. By further demonstrating that senescence patterns differ among seasons, our results imply that within-year temporal environmental variation must be considered alongside spatial environmental variation in order to characterize and understand the pattern and magnitude of senescence in wild populations.

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

Characterisation of an ion source on the Helix MC Plus noble gas mass spectrometer - pressure dependent mass discrimination

NASA Astrophysics Data System (ADS)

Zhang, X.

2017-12-01

Characterisation of an ion source on the Helix MC Plusnoble gas mass spectrometer - pressure dependent mass discrimination Xiaodong Zhang* dong.zhang@anu.edu.au Masahiko Honda Masahiko.honda@anu.edu.au Research School of Earth Sciences, The Australian National University, Canberra, Australia To obtain reliable measurements of noble gas elemental and isotopic abundances in a geological sample it is essential that the mass discrimination (instrument-induced isotope fractionation) of the mass spectrometer remain constant over the working range of noble gas partial pressures. It is known, however, that there are pressure-dependent variations in sensitivity and mass discrimination in conventional noble gas mass spectrometers [1, 2, 3]. In this study, we discuss a practical approach to ensuring that the pressure effect in the Helix MC Plus high resolution, multi-collector noble gas mass spectrometer is minimised. The isotopic composition of atmospheric Ar was measured under a range of operating conditions to test the effects of different parameters on Ar mass discrimination. It was found that the optimised ion source conditions for pressure independent mass discrimination for Ar were different from those for maximised Ar sensitivity. The optimisation can be achieved by mainly adjusting the repeller voltage. It is likely that different ion source settings will be required to minimise pressure-dependent mass discrimination for different noble gases. A recommended procedure for tuning an ion source to reduce pressure dependent mass discrimination will be presented. References: Honda M., et al., Geochim. Cosmochim. Acta, 57, 859 -874, 1993. Burnard P. G., and Farley K. A., Geochemistry Geophysics Geosystems, Volume 1, 2000GC00038, 2000. Mabry J., et al., Journal of Analytical Atomic Spectrometry, 27, 1012 - 1017, 2012.

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.

Exact analytic solution of position-dependent mass Schrödinger equation

NASA Astrophysics Data System (ADS)

Rajbongshi, Hangshadhar

2018-03-01

Exact analytic solution of position-dependent mass Schrödinger equation is generated by using extended transformation, a method of mapping a known system into a new system equipped with energy eigenvalues and corresponding wave functions. First order transformation is performed on D-dimensional radial Schrödinger equation with constant mass by taking trigonometric Pöschl-Teller potential as known system. The exactly solvable potentials with position-dependent mass generated for different choices of mass functions through first order transformation are also taken as known systems in the second order transformation performed on D-dimensional radial position-dependent mass Schrödinger equation. The solutions are fitted for "Zhu and Kroemer" ordering of ambiguity. All the wave functions corresponding to nonzero energy eigenvalues are normalizable. The new findings are that the normalizability condition of the wave functions remains independent of mass functions, and some of the generated potentials show a family relationship among themselves where power law potentials also get related to non-power law potentials and vice versa through the transformation.

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

NASA Astrophysics Data System (ADS)

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

2015-06-01

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

Time-Dependent Damage Investigation of Rock Mass in an In Situ Experimental Tunnel

PubMed Central

Jiang, Quan; Cui, Jie; Chen, Jing

2012-01-01

In underground tunnels or caverns, time-dependent deformation or failure of rock mass, such as extending cracks, gradual rock falls, etc., are a costly irritant and a major safety concern if the time-dependent damage of surrounding rock is serious. To understand the damage evolution of rock mass in underground engineering, an in situ experimental testing was carried out in a large belowground tunnel with a scale of 28.5 m in width, 21 m in height and 352 m in length. The time-dependent damage of rock mass was detected in succession by an ultrasonic wave test after excavation. The testing results showed that the time-dependent damage of rock mass could last a long time, i.e., nearly 30 days. Regression analysis of damage factors defined by wave velocity, resulted in the time-dependent evolutional damage equation of rock mass, which corresponded with logarithmic format. A damage viscoelastic-plastic model was developed to describe the exposed time-dependent deterioration of rock mass by field test, such as convergence of time-dependent damage, deterioration of elastic modules and logarithmic format of damage factor. Furthermore, the remedial measures for damaged surrounding rock were discussed based on the measured results and the conception of damage compensation, which provides new clues for underground engineering design.

Neutrino masses, scale-dependent growth, and redshift-space distortions

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

Hernández, Oscar F., E-mail: oscarh@physics.mcgill.ca

2017-06-01

Massive neutrinos leave a unique signature in the large scale clustering of matter. We investigate the wavenumber dependence of the growth factor arising from neutrino masses and use a Fisher analysis to determine the aspects of a galaxy survey needed to measure this scale dependence.

Prospects for detection of target-dependent annual modulation in direct dark matter searches

DOE PAGES

Nobile, Eugenio Del; Gelmini, Graciela B.; Witte, Samuel J.

2016-02-03

Earth's rotation about the Sun produces an annual modulation in the expected scattering rate at direct dark matter detection experiments. The annual modulation as a function of the recoil energy E R imparted by the dark matter particle to a target nucleus is expected to vary depending on the detector material. However, for most interactions a change of variables from E R to v min, the minimum speed a dark matter particle must have to impart a fixed E R to a target nucleus, produces an annual modulation independent of the target element. We recently showed that if the darkmore » matter-nucleus cross section contains a non-factorizable target and dark matter velocity dependence, the annual modulation as a function of v min can be target dependent. Here we examine more extensively the necessary conditions for target-dependent modulation, its observability in present-day experiments, and the extent to which putative signals could identify a dark matter-nucleus differential cross section with a non-factorizable dependence on the dark matter velocity.« less

A position-dependent mass harmonic oscillator and deformed space

NASA Astrophysics Data System (ADS)

da Costa, Bruno G.; Borges, Ernesto P.

2018-04-01

We consider canonically conjugated generalized space and linear momentum operators x^ q and p^ q in quantum mechanics, associated with a generalized translation operator which produces infinitesimal deformed displacements controlled by a deformation parameter q. A canonical transformation (x ^ ,p ^ ) →(x^ q,p^ q ) leads the Hamiltonian of a position-dependent mass particle in usual space to another Hamiltonian of a particle with constant mass in a conservative force field of the deformed space. The equation of motion for the classical phase space (x, p) may be expressed in terms of the deformed (dual) q-derivative. We revisit the problem of a q-deformed oscillator in both classical and quantum formalisms. Particularly, this canonical transformation leads a particle with position-dependent mass in a harmonic potential to a particle with constant mass in a Morse potential. The trajectories in phase spaces (x, p) and (xq, pq) are analyzed for different values of the deformation parameter. Finally, we compare the results of the problem in classical and quantum formalisms through the principle of correspondence and the WKB approximation.

Algebraic solutions of shape-invariant position-dependent effective mass systems

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

Amir, Naila, E-mail: naila.amir@live.com, E-mail: naila.amir@seecs.edu.pk; Iqbal, Shahid, E-mail: sic80@hotmail.com, E-mail: siqbal@sns.nust.edu.pk

2016-06-15

Keeping in view the ordering ambiguity that arises due to the presence of position-dependent effective mass in the kinetic energy term of the Hamiltonian, a general scheme for obtaining algebraic solutions of quantum mechanical systems with position-dependent effective mass is discussed. We quantize the Hamiltonian of the pertaining system by using symmetric ordering of the operators concerning momentum and the spatially varying mass, initially proposed by von Roos and Lévy-Leblond. The algebraic method, used to obtain the solutions, is based on the concepts of supersymmetric quantum mechanics and shape invariance. In order to exemplify the general formalism a class ofmore » non-linear oscillators has been considered. This class includes the particular example of a one-dimensional oscillator with different position-dependent effective mass profiles. Explicit expressions for the eigenenergies and eigenfunctions in terms of generalized Hermite polynomials are presented. Moreover, properties of these modified Hermite polynomials, like existence of generating function and recurrence relations among the polynomials have also been studied. Furthermore, it has been shown that in the harmonic limit, all the results for the linear harmonic oscillator are recovered.« less

Mass dependence of calcium isotope fractionations in crown-ether resin chromatography.

PubMed

Fujii, Yasuhiko; Nomura, Masao; Kaneshiki, Tositaka; Sakuma, Yoichi; Suzuki, Tatsuya; Umehara, Saori; Kishimoto, Tadahumi

2010-06-01

Benzo 18-crown-6-ether resin was synthesised by the phenol condensation polymerisation process in porous silica beads, of which particle diameter was ca 60micro Calcium adsorption chromatography was performed with the synthesised resin packed in a glass column. The effluent was sampled in fractions, and the isotopic abundance ratios of (42)Ca, (43)Ca, (44)Ca, and (48)Ca against (40)Ca were measured by a thermo-ionisation mass spectrometer. The enrichment of heavier calcium isotopes was observed at the front boundary of calcium adsorption chromatogram. The mass dependence of mutual separation of calcium isotopes was analysed by using the three-isotope-plots method. The slopes of three-isotope-plots indicate the relative values of mutual separation coefficients for concerned isotopic pairs. The results have shown the normal mass dependence; isotope fractionation is proportional to the reduced mass difference, (M - M')/MM', where M and M' are masses of heavy and light isotope, respectively. The mass dependence clarifies that the isotope fractionations are originated from molecular vibration. The observed separation coefficient epsilon is 3.1x10(-3) for the pair of (40)Ca and (48)Ca. Productivity of enriched (48)Ca by crown-ether-resin was discussed as the function of the separation coefficient and the height equivalent to the theoretical plate.

The dependence of cosmic ray-driven galactic winds on halo mass

NASA Astrophysics Data System (ADS)

Jacob, Svenja; Pakmor, Rüdiger; Simpson, Christine M.; Springel, Volker; Pfrommer, Christoph

2018-03-01

Galactic winds regulate star formation in disc galaxies and help to enrich the circum-galactic medium. They are therefore crucial for galaxy formation, but their driving mechanism is still poorly understood. Recent studies have demonstrated that cosmic rays (CRs) can drive outflows if active CR transport is taken into account. Using hydrodynamical simulations of isolated galaxies with virial masses between 1010 and 1013 M⊙, we study how the properties of CR-driven winds depend on halo mass. CRs are treated in a two-fluid approximation and their transport is modelled through isotropic or anisotropic diffusion. We find that CRs are only able to drive mass-loaded winds beyond the virial radius in haloes with masses below 1012 M⊙. For our lowest examined halo mass, the wind is roughly spherical and has velocities of ˜20 km s-1. With increasing halo mass, the wind becomes biconical and can reach 10 times higher velocities. The mass loading factor drops rapidly with virial mass, a dependence that approximately follows a power law with a slope between -1 and -2. This scaling is slightly steeper than observational inferences, and also steeper than commonly used prescriptions for wind feedback in cosmological simulations. The slope is quite robust to variations of the CR injection efficiency or the CR diffusion coefficient. In contrast to the mass loading, the energy loading shows no significant dependence on halo mass. While these scalings are close to successful heuristic models of wind feedback, the CR-driven winds in our present models are not yet powerful enough to fully account for the required feedback strength.

Galaxy and Mass Assembly (GAMA): the star formation rate dependence of the stellar initial mass function

NASA Astrophysics Data System (ADS)

Gunawardhana, M. L. P.; Hopkins, A. M.; Sharp, R. G.; Brough, S.; Taylor, E.; Bland-Hawthorn, J.; Maraston, C.; Tuffs, R. J.; Popescu, C. C.; Wijesinghe, D.; Jones, D. H.; Croom, S.; Sadler, E.; Wilkins, S.; Driver, S. P.; Liske, J.; Norberg, P.; Baldry, I. K.; Bamford, S. P.; Loveday, J.; Peacock, J. A.; Robotham, A. S. G.; Zucker, D. B.; Parker, Q. A.; Conselice, C. J.; Cameron, E.; Frenk, C. S.; Hill, D. T.; Kelvin, L. S.; Kuijken, K.; Madore, B. F.; Nichol, B.; Parkinson, H. R.; Pimbblet, K. A.; Prescott, M.; Sutherland, W. J.; Thomas, D.; van Kampen, E.

2011-08-01

The stellar initial mass function (IMF) describes the distribution in stellar masses produced from a burst of star formation. For more than 50 yr, the implicit assumption underpinning most areas of research involving the IMF has been that it is universal, regardless of time and environment. We measure the high-mass IMF slope for a sample of low-to-moderate redshift galaxies from the Galaxy and Mass Assembly survey. The large range in luminosities and galaxy masses of the sample permits the exploration of underlying IMF dependencies. A strong IMF-star formation rate dependency is discovered, which shows that highly star-forming galaxies form proportionally more massive stars (they have IMFs with flatter power-law slopes) than galaxies with low star formation rates. This has a significant impact on a wide variety of galaxy evolution studies, all of which rely on assumptions about the slope of the IMF. Our result is supported by, and provides an explanation for, the results of numerous recent explorations suggesting a variation of or evolution in the IMF.

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.

Halo Intrinsic Alignment: Dependence on Mass, Formation Time, and Environment

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

Xia, Qianli; Kang, Xi; Wang, Peng

In this paper we use high-resolution cosmological simulations to study halo intrinsic alignment and its dependence on mass, formation time, and large-scale environment. In agreement with previous studies using N -body simulations, it is found that massive halos have stronger alignment. For the first time, we find that for a given halo mass older halos have stronger alignment and halos in cluster regions also have stronger alignment than those in filaments. To model these dependencies, we extend the linear alignment model with inclusion of halo bias and find that the halo alignment with its mass and formation time dependence canmore » be explained by halo bias. However, the model cannot account for the environment dependence, as it is found that halo bias is lower in clusters and higher in filaments. Our results suggest that halo bias and environment are independent factors in determining halo alignment. We also study the halo alignment correlation function and find that halos are strongly clustered along their major axes and less clustered along the minor axes. The correlated halo alignment can extend to scales as large as 100 h {sup −1} Mpc, where its feature is mainly driven by the baryon acoustic oscillation effect.« less

Experimental Characterization of Stress- and Strain-Dependent Stiffness in Grouted Rock Masses.

PubMed

Kim, Ji-Won; Chong, Song-Hun; Cho, Gye-Chun

2018-03-29

Grouting of fractured rock mass prior to excavation results in grout-filled discontinuities that govern the deformation characteristics of a site. The influence of joint characteristics on the properties of grouted rocks is important in assessing the effects of grouting on jointed rock mass. However, grouting remains a predominantly empirical practice and the effects of grouting on rock joint behavior and material properties have yet to be accurately assessed. Granular materials, including jointed rocks, typically display nonlinear strain-dependent responses that can be characterized by the shear modulus degradation curve. In this study, the effects of grouting on the strain-dependent shear stiffness of jointed rock mass were investigated at the small-strain (below 10 -5 ) and mid-strain (10 -5 to 10 -3 ) ranges using the quasi-static resonant column test and rock mass dynamic test devices. The effects of curing time, axial stress, initial joint roughness, and grouted joint thickness were examined. The results show that (1) grouting of rock joints leads to decreased stress sensitivity and increased small-strain shear stiffness for all tested samples; (2) the grouted rock samples display similar modulus degradation characteristics as the applied grout material; (3) the initial joint roughness determines the stress-dependent behaviors and general stiffness range of the jointed and grouted rocks, but the strain-dependent behaviors are dependent on the properties of the grout material; (4) increased grouted joint thickness results in larger contribution of the grout properties in the overall grouted rock mass.

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.

Body mass index trends of military dependents: a cross-sectional study.

PubMed

Winegarner, James

2015-03-01

Obesity is an epidemic affecting many people in the United States, to include military beneficiaries, with immediate and long-term implications on health care utilization and costs. We compared the body mass index (BMI) of officer vs. enlisted military-dependent spouses. Retrospective chart review of 7,226 random dependent spouses cared for at Madigan Army Medical Center. Statistical analysis of BMI was performed comparing the spouses of commissioned officers and enlisted soldiers. There are a higher percentage of overweight and obese enlisted spouses when compared to officer spouses. In all age groups, BMI was 2.6 to 4.8 points higher in enlisted spouses, in both all-inclusive and female-specific analyses (p < 0.001). Male spouse BMI was not statistically different. BMI generally increased with age, with a statistically significant difference in BMI between age groups (p < 0.001). Our study shows that the average BMI of enlisted soldier's female spouses is significantly higher than officer spouses of similar age groups. A much larger proportion of enlisted spouses are obese. This analysis provides public health information for military primary care doctors and identifies at-risk individuals for targeted education and interventions. Reprint & Copyright © 2015 Association of Military Surgeons of the U.S.

Evaluation of species-dependent detection efficiencies in the aerosol mass spectrometer

USDA-ARS?s Scientific Manuscript database

Mass concentrations of chemical species calculated from the aerosol mass spectrometer (AMS) depend on two factors: particle collection efficiency (CE) and relative ionization efficiency (RIE, relative to the primary calibrant ammonium nitrate). While previous studies have characterized CE, RIE is re...

Experimental Characterization of Stress- and Strain-Dependent Stiffness in Grouted Rock Masses

PubMed Central

Cho, Gye-Chun

2018-01-01

Grouting of fractured rock mass prior to excavation results in grout-filled discontinuities that govern the deformation characteristics of a site. The influence of joint characteristics on the properties of grouted rocks is important in assessing the effects of grouting on jointed rock mass. However, grouting remains a predominantly empirical practice and the effects of grouting on rock joint behavior and material properties have yet to be accurately assessed. Granular materials, including jointed rocks, typically display nonlinear strain-dependent responses that can be characterized by the shear modulus degradation curve. In this study, the effects of grouting on the strain-dependent shear stiffness of jointed rock mass were investigated at the small-strain (below 10−5) and mid-strain (10−5 to 10−3) ranges using the quasi-static resonant column test and rock mass dynamic test devices. The effects of curing time, axial stress, initial joint roughness, and grouted joint thickness were examined. The results show that (1) grouting of rock joints leads to decreased stress sensitivity and increased small-strain shear stiffness for all tested samples; (2) the grouted rock samples display similar modulus degradation characteristics as the applied grout material; (3) the initial joint roughness determines the stress-dependent behaviors and general stiffness range of the jointed and grouted rocks, but the strain-dependent behaviors are dependent on the properties of the grout material; (4) increased grouted joint thickness results in larger contribution of the grout properties in the overall grouted rock mass. PMID:29596371

Temperature dependence of yields from multi-foil SPES target

NASA Astrophysics Data System (ADS)

Corradetti, S.; Biasetto, L.; Manzolaro, M.; Scarpa, D.; Andrighetto, A.; Carturan, S.; Prete, G.; Zanonato, P.; Stracener, D. W.

2011-10-01

The temperature dependence of neutron-rich isotope yields was studied within the framework of the HRIBF-SPES Radioactive Ion Beams (RIB) project. On-line release measurements of fission fragments from a uranium carbide target at ensuremath 1600 {}^{circ}C , ensuremath 1800 {}^{circ}C and ensuremath 2000 {}^{circ}C were performed at ORNL (USA). The fission reactions were induced by a 40MeV proton beam accelerated into a uranium carbide target coupled to a plasma ion source. The experiments allowed for tests of performance of the SPES multi-foil target prototype loaded with seven UC2/graphite discs (ratio C/ U = 4 with density about 4g/cm3.

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.

Targeting glutaminase-mediated glutamine dependence in papillary thyroid cancer.

PubMed

Yu, Yang; Yu, Xiaohui; Fan, Chenling; Wang, Hong; Wang, Renee; Feng, Chen; Guan, Haixia

2018-06-25

Papillary thyroid cancer is a prevalent endocrine malignancy. Although alterations in glutamine metabolism have been reported in several types of hematological and solid tumors, little is known about the functions of glutamine and glutaminolysis-associated proteins in papillary thyroid cancer. Here, we demonstrated the glutamine dependence of papillary thyroid cancer cells, and with the use of RT 2 -PCR arrays, we screened for the aberrant overexpression of glutaminase in human papillary thyroid cancer tissues and cells. These results were later confirmed via real-time PCR, Western blots, and immunohistochemical staining. We found that the levels of glutaminase were significantly correlated with extrathyroidal extension. Inhibition of GLS suppressed glutaminolysis and reduced mitochondrial respiration. The proliferative, viable, migratory, and invasive abilities of papillary thyroid cancer cells were impaired by both the pharmacological inhibition and the genetic knockdown of glutaminase. Additionally, the inhibition of glutaminase deactivated the mechanistic target of the rapamycin complex 1 (mTORC1) signaling pathway, promoting autophagy and apoptosis. Collectively, these findings show that glutaminase-mediated glutamine dependence may be a potential therapeutic target for papillary thyroid cancer. PTC cells are glutamine-dependent, and GLS is aberrantly overexpressed in PTC. Inhibition of GLS suppressed glutaminolysis and reduced mitochondrial respiration. Inhibition of GLS impairs the viability of PTC cells. GLS blockade causes deactivation of mTORC1 and induction of autophagy and apoptosis. GLS may be a potential therapeutic target for PTC.

Position dependent mass Schroedinger equation and isospectral potentials: Intertwining operator approach

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

Midya, Bikashkali; Roy, B.; Roychoudhury, R.

2010-02-15

Here, we have studied first- and second-order intertwining approaches to generate isospectral partner potentials of position dependent (effective) mass Schroedinger equation. The second-order intertwiner is constructed directly by taking it as second-order linear differential operator with position dependent coefficients, and the system of equations arising from the intertwining relationship is solved for the coefficients by taking an ansatz. A complete scheme for obtaining general solution is obtained, which is valid for any arbitrary potential and mass function. The proposed technique allows us to generate isospectral potentials with the following spectral modifications: (i) to add new bound state(s), (ii) to removemore » bound state(s), and (iii) to leave the spectrum unaffected. To explain our findings with the help of an illustration, we have used point canonical transformation to obtain the general solution of the position dependent mass Schrodinger equation corresponding to a potential and mass function. It is shown that our results are consistent with the formulation of type A N-fold supersymmetry [T. Tanaka, J. Phys. A 39, 219 (2006); A. Gonzalez-Lopez and T. Tanaka, J. Phys. A 39, 3715 (2006)] for the particular cases N=1 and N=2, respectively.« less

The mass dependence of dark matter halo alignments with large-scale structure

NASA Astrophysics Data System (ADS)

Piras, Davide; Joachimi, Benjamin; Schäfer, Björn Malte; Bonamigo, Mario; Hilbert, Stefan; van Uitert, Edo

2018-02-01

Tidal gravitational forces can modify the shape of galaxies and clusters of galaxies, thus correlating their orientation with the surrounding matter density field. We study the dependence of this phenomenon, known as intrinsic alignment (IA), on the mass of the dark matter haloes that host these bright structures, analysing the Millennium and Millennium-XXL N-body simulations. We closely follow the observational approach, measuring the halo position-halo shape alignment and subsequently dividing out the dependence on halo bias. We derive a theoretical scaling of the IA amplitude with mass in a dark matter universe, and predict a power law with slope βM in the range 1/3 to 1/2, depending on mass scale. We find that the simulation data agree with each other and with the theoretical prediction remarkably well over three orders of magnitude in mass, with the joint analysis yielding an estimate of β M = 0.36^{+0.01}_{-0.01}. This result does not depend on redshift or on the details of the halo shape measurement. The analysis is repeated on observational data, obtaining a significantly higher value, β M = 0.56^{+0.05}_{-0.05}. There are also small but significant deviations from our simple model in the simulation signals at both the high- and low-mass end. We discuss possible reasons for these discrepancies, and argue that they can be attributed to physical processes not captured in the model or in the dark matter-only simulations.

Slotted rotatable target assembly and systematic error analysis for a search for long range spin dependent interactions from exotic vector boson exchange using neutron spin rotation

NASA Astrophysics Data System (ADS)

Haddock, C.; Crawford, B.; Fox, W.; Francis, I.; Holley, A.; Magers, S.; Sarsour, M.; Snow, W. M.; Vanderwerp, J.

2018-03-01

We discuss the design and construction of a novel target array of nonmagnetic test masses used in a neutron polarimetry measurement made in search for new possible exotic spin dependent neutron-atominteractions of Nature at sub-mm length scales. This target was designed to accept and efficiently transmit a transversely polarized slow neutron beam through a series of long open parallel slots bounded by flat rectangular plates. These openings possessed equal atom density gradients normal to the slots from the flat test masses with dimensions optimized to achieve maximum sensitivity to an exotic spin-dependent interaction from vector boson exchanges with ranges in the mm - μm regime. The parallel slots were oriented differently in four quadrants that can be rotated about the neutron beam axis in discrete 90°increments using a Geneva drive. The spin rotation signals from the 4 quadrants were measured using a segmented neutron ion chamber to suppress possible systematic errors from stray magnetic fields in the target region. We discuss the per-neutron sensitivity of the target to the exotic interaction, the design constraints, the potential sources of systematic errors which could be present in this design, and our estimate of the achievable sensitivity using this method.

Energy dependence of effective electron mass and laser-induced ionization of wide band-gap solids

NASA Astrophysics Data System (ADS)

Gruzdev, V. E.

2008-10-01

Most of the traditional theoretical models of laser-induced ionization were developed under the assumption of constant effective electron mass or weak dependence of the effective mass on electron energy. Those assumptions exclude from consideration all the effects resulting from significant increase of the effective mass with increasing of electron energy in real the conduction band. Promotion of electrons to the states with high effective mass can be done either via laserinduced electron oscillations or via electron-particle collisions. Increase of the effective mass during laser-material interactions can result in specific regimes of ionization. Performing a simple qualitative analysis by comparison of the constant-mass approximation vs realistic dependences of the effective mass on electron energy, we demonstrate that the traditional ionization models provide reliable estimation of the ionization rate in a very limited domain of laser intensity and wavelength. By taking into account increase of the effective mass with electron energy, we demonstrate that special regimes of high-intensity photo-ionization are possible depending on laser and material parameters. Qualitative analysis of the energy dependence of the effective mass also leads to conclusion that the avalanche ionization can be stopped by the effect of electron trapping in the states with large values of the effective mass.

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...

Modelling non-adiabatic effects in H_3^+: Solution of the rovibrational Schrödinger equation with motion-dependent masses and mass surfaces

NASA Astrophysics Data System (ADS)

Mátyus, Edit; Szidarovszky, Tamás; Császár, Attila G.

2014-10-01

Introducing different rotational and vibrational masses in the nuclear-motion Hamiltonian is a simple phenomenological way to model rovibrational non-adiabaticity. It is shown on the example of the molecular ion H_3^+, for which a global adiabatic potential energy surface accurate to better than 0.1 cm-1 exists [M. Pavanello, L. Adamowicz, A. Alijah, N. F. Zobov, I. I. Mizus, O. L. Polyansky, J. Tennyson, T. Szidarovszky, A. G. Császár, M. Berg et al., Phys. Rev. Lett. 108, 023002 (2012)], that the motion-dependent mass concept yields much more accurate rovibrational energy levels but, unusually, the results are dependent upon the choice of the embedding of the molecule-fixed frame. Correct degeneracies and an improved agreement with experimental data are obtained if an Eckart embedding corresponding to a reference structure of D3h point-group symmetry is employed. The vibrational mass of the proton in H_3^+ is optimized by minimizing the root-mean-square (rms) deviation between the computed and recent high-accuracy experimental transitions. The best vibrational mass obtained is larger than the nuclear mass of the proton by approximately one third of an electron mass, m^(v)_opt,p=m_nuc,p+0.31224 m_e. This optimized vibrational mass, along with a nuclear rotational mass, reduces the rms deviation of the experimental and computed rovibrational transitions by an order of magnitude. Finally, it is shown that an extension of the algorithm allowing the use of motion-dependent masses can deal with coordinate-dependent mass surfaces in the rovibrational Hamiltonian, as well.

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.

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.

Probing the Jet Turnover Frequency Dependence on Mass and Mass Accretion Rate

NASA Astrophysics Data System (ADS)

Hammerstein, Erica; Gültekin, Kayhan; King, Ashley

2018-01-01

We have examined a sample of 15 sub-Eddington supermassive black holes (SMBHs) in a variety of galaxy classifications to further understand the proposed fundamental plane of black hole activity and scaling relations between black hole masses and their radio and X-ray luminosities. This plane describes black holes from stellar-mass to supermassive. The physics probed by these sub-Eddington systems is thought to be a radiatively inefficient, jet-dominated accretion flow. By studying black holes in this regime, we can learn important information on the disk-jet connection for accreting black holes.A key factor in studying the fundamental plane is the turnover frequency — the frequency at which emission transitions from optically thick at lower frequencies to optically thin at higher frequencies. This turnover point can be measured by observing the source in both radio and X-ray. Our project aims to test the dependence of the turnover frequency on mass and mass accretion rate.Radio observations of the sample were obtained using the Karl G. Jansky Very Large Array (VLA) in the range of 5-40 GHz across four different frequency bands in A configuration to give the highest spatial resolution to focus on the core emission. Our carefully chosen sample of SMBHs with dynamically measured masses consists of two sub-samples: those with approximately constant mass accretion rate (LX/LEdd ~ 10‑7) and those with approximately constant mass (MBH ~ 108 Msun). X-ray data were obtained from archival Chandra observations. To find the turnover frequency, we used Markov Chain Monte Carlo methods to fit two power laws to the radio data and the archival X-ray data. The intersection of the radio and X-ray fits is the turnover frequency.We present the results for both subsamples of SMBHs and their relationship between the turnover frequency and X-ray luminosity, which we take to scale with mass accretion rate, and jet power derived from both radio and X-ray properties.

Incorporating signal-dependent noise for hyperspectral target detection

NASA Astrophysics Data System (ADS)

Morman, Christopher J.; Meola, Joseph

2015-05-01

The majority of hyperspectral target detection algorithms are developed from statistical data models employing stationary background statistics or white Gaussian noise models. Stationary background models are inaccurate as a result of two separate physical processes. First, varying background classes often exist in the imagery that possess different clutter statistics. Many algorithms can account for this variability through the use of subspaces or clustering techniques. The second physical process, which is often ignored, is a signal-dependent sensor noise term. For photon counting sensors that are often used in hyperspectral imaging systems, sensor noise increases as the measured signal level increases as a result of Poisson random processes. This work investigates the impact of this sensor noise on target detection performance. A linear noise model is developed describing sensor noise variance as a linear function of signal level. The linear noise model is then incorporated for detection of targets using data collected at Wright Patterson Air Force Base.

Origins of mass-dependent and mass-independent Ca isotope variations in meteoritic components and meteorites

NASA Astrophysics Data System (ADS)

Bermingham, K. R.; Gussone, N.; Mezger, K.; Krause, J.

2018-04-01

The Ca isotope composition of meteorites and their components may vary due to mass-dependent and/or -independent isotope effects. In order to evaluate the origin of these effects, five amoeboid olivine aggregates (AOAs), three calcium aluminum inclusions (CAIs), five chondrules (C), a dark inclusion from Allende (CV3), two dark fragments from North West Africa 753 (NWA 753; R3.9), and a whole rock sample of Orgueil (CI1) were analyzed. This is the first coupled mass-dependent and -independent Ca isotope dataset to include AOAs, a dark inclusion, and dark fragments. Where sample masses permit, Ca isotope data are reported with corresponding petrographic analyses and rare earth element (REE) relative abundance patterns. The CAIs and AOAs are enriched in light Ca isotopes (δ44/40Ca -5.32 to +0.72, where δ44/40Ca is reported relative to SRM 915a). Samples CAI 5 and AOA 1 have anomalous Group II REE patterns. These REE and δ44/40Ca data suggest that the CAI 5 and AOA 1 compositions were set via kinetic isotope fractionation during condensation and evaporation. The remaining samples show mass-dependent Ca isotope variations which cluster between δ44/40Ca +0.53 and +1.59, some of which are coupled with unfractionated REE abundance patterns. These meteoritic components likely formed through the coaccretion of the evaporative residue and condensate following Group II CAI formation or their chemical and isotopic signatures were decoupled (e.g., via nebular or parent-body alteration). The whole rock sample of Orgueil has a δ44/40Ca +0.67 ± 0.18 which is in agreement with most published data. Parent-body alteration, terrestrial alteration, and variable sampling of Ca-rich meteoritic components can have an effect on δ44/40Ca compositions in whole rock meteorites. Samples AOA 1, CAI 5, C 2, and C 4 display mass-independent 48/44Ca anomalies (ε48/44Ca +6 to +12) which are resolved from the standard composition. Other samples measured for these effects (AOA 5, CAI 1, CAI 2

On the scatter in the relation between stellar mass and halo mass: random or halo formation time dependent?

NASA Astrophysics Data System (ADS)

Wang, Lan; De Lucia, Gabriella; Weinmann, Simone M.

2013-05-01

The empirical traditional halo occupation distribution (HOD) model of Wang et al. fits, by construction, both the stellar mass function and correlation function of galaxies in the local Universe. In contrast, the semi-analytical models of De Lucia & Blazoit (hereafter DLB07) and Guo et al. (hereafter Guo11), built on the same dark matter halo merger trees than the empirical model, still have difficulties in reproducing these observational data simultaneously. We compare the relations between the stellar mass of galaxies and their host halo mass in the three models, and find that they are different. When the relations are rescaled to have the same median values and the same scatter as in Wang et al., the rescaled DLB07 model can fit both the measured galaxy stellar mass function and the correlation function measured in different galaxy stellar mass bins. In contrast, the rescaled Guo11 model still overpredicts the clustering of low-mass galaxies. This indicates that the detail of how galaxies populate the scatter in the stellar mass-halo mass relation does play an important role in determining the correlation functions of galaxies. While the stellar mass of galaxies in the Wang et al. model depends only on halo mass and is randomly distributed within the scatter, galaxy stellar mass depends also on the halo formation time in semi-analytical models. At fixed value of infall mass, galaxies that lie above the median stellar mass-halo mass relation reside in haloes that formed earlier, while galaxies that lie below the median relation reside in haloes that formed later. This effect is much stronger in Guo11 than in DLB07, which explains the overclustering of low mass galaxies in Guo11. Assembly bias in Guo11 model might be overly strong. Nevertheless, in case that a significant assembly bias indeed exists in the real Universe, one needs to use caution when applying current HOD and abundance matching models that employ the assumption of random scatter in the relation

The mass and speed dependence of meteor air plasma temperatures

NASA Technical Reports Server (NTRS)

Jenniskens, Peter; Laux, Christophe O.; Wilson, Michael A.; Schaller, Emily L.

2004-01-01

The speed and mass dependence of meteor air plasma temperatures is perhaps the most important data needed to understand how small meteoroids chemically change the ambient atmosphere in their path and enrich the ablated meteoric organic matter with oxygen. Such chemistry can play an important role in creating prebiotic compounds. The excitation conditions in various air plasma emissions were measured from high-resolution optical spectra of Leonid storm meteors during NASA's Leonid Multi-Instrument Aircraft Campaign. This was the first time a sufficient number and range of temperature measurements were obtained to search for meteoroid mass and speed dependencies. We found slight increases in temperature with decreasing altitude, but otherwise nearly constant values for meteoroids with speeds between 35 and 72 km/s and masses between 10(-5) g and 1 g. We conclude that faster and more massive meteoroids produce a larger emission volume, but not a higher air plasma temperature. We speculate that the meteoric plasma may be in multiphase equilibrium with the ambient atmosphere, which could mean lower plasma temperatures in a CO(2)-rich early Earth atmosphere.

The mass and speed dependence of meteor air plasma temperatures.

PubMed

Jenniskens, Peter; Laux, Christophe O; Wilson, Michael A; Schaller, Emily L

2004-01-01

The speed and mass dependence of meteor air plasma temperatures is perhaps the most important data needed to understand how small meteoroids chemically change the ambient atmosphere in their path and enrich the ablated meteoric organic matter with oxygen. Such chemistry can play an important role in creating prebiotic compounds. The excitation conditions in various air plasma emissions were measured from high-resolution optical spectra of Leonid storm meteors during NASA's Leonid Multi-Instrument Aircraft Campaign. This was the first time a sufficient number and range of temperature measurements were obtained to search for meteoroid mass and speed dependencies. We found slight increases in temperature with decreasing altitude, but otherwise nearly constant values for meteoroids with speeds between 35 and 72 km/s and masses between 10(-5) g and 1 g. We conclude that faster and more massive meteoroids produce a larger emission volume, but not a higher air plasma temperature. We speculate that the meteoric plasma may be in multiphase equilibrium with the ambient atmosphere, which could mean lower plasma temperatures in a CO(2)-rich early Earth atmosphere.

Neutron-proton effective mass splitting in neutron-rich matter at normal density from analyzing nucleon-nucleus scattering data within an isospin dependent optical model

NASA Astrophysics Data System (ADS)

Li, Xiao-Hua; Guo, Wen-Jun; Li, Bao-An; Chen, Lie-Wen; Fattoyev, Farrukh J.; Newton, William G.

2015-04-01

The neutron-proton effective mass splitting in asymmetric nucleonic matter of isospin asymmetry δ and normal density is found to be mn-p* ≡ (mn* - mp*) / m = (0.41 ± 0.15) δ from analyzing globally 1088 sets of reaction and angular differential cross sections of proton elastic scattering on 130 targets with beam energies from 0.783 MeV to 200 MeV, and 1161 sets of data of neutron elastic scattering on 104 targets with beam energies from 0.05 MeV to 200 MeV within an isospin dependent non-relativistic optical potential model. It sets a useful reference for testing model predictions on the momentum dependence of the nucleon isovector potential necessary for understanding novel structures and reactions of rare isotopes.

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

Inclination Dependence of Estimated Galaxy Masses and Star Formation Rates

NASA Astrophysics Data System (ADS)

Hernandez, Betsy; Maller, Ariyeh; McKernan, Barry; Ford, Saavik

2016-01-01

We examine the inclination dependence of inferred star formation rates and galaxy mass estimates in the Sloan Digital Sky Survey by combining the disk/bulge de-convolved catalog of Simard et al 2011 with stellar mass estimates catalog of Mendel et al 2014 and star formation rates measured from spectra by Brinchmann et al 2004. We know that optical star formation indicators are reddened by dust, but calculated star formation rates and stellar mass estimates should account for this. However, we find that face-on galaxies have a higher calculated average star formation rates than edge-on galaxies. We also find edge-on galaxies have ,on average, slightly smaller but similar estimated masses to face-on galaxies, suggesting that there are issues with the applied dust corrections for both models.

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.

Quark-mass dependence of the H dibaryon in Λ Λ scattering

NASA Astrophysics Data System (ADS)

Yamaguchi, Yasuhiro; Hyodo, Tetsuo

2016-12-01

We study the quark mass dependence of the H dibaryon in the strangeness S =-2 baryon-baryon scattering. A low-energy effective field theory is used to describe the coupled-channel scattering, in which the quark mass dependence is incorporated so as to reproduce the lattice QCD data by the HAL QCD collaboration in the SU(3) limit. We point out the existence of the Castillejo-Dalitz-Dyson pole in the Λ Λ scattering amplitude below the threshold in the SU(3) limit, which may cause the Ramsauer-Townsend effect near the N Ξ threshold at the physical point. The H dibaryon is unbound at the physical point, and a resonance appears just below the N Ξ threshold. As a consequence of the coupled-channel dynamics, the pole associated with the resonance is not continuously connected to the bound state in the SU(3) limit. Through the extrapolation in quark masses, we show that the unitary limit of the Λ Λ scattering is achieved between the physical point and the SU(3) limit. We discuss the possible realization of the "H matter" in the unphysical quark mass region.

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.

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

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

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

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

Z dependence of thick-target β-ray backscattering

NASA Astrophysics Data System (ADS)

Sharma, K. K.; Singh, M.

1980-04-01

Variation of β-ray backscattering with the atomic number of target material has been studied using thick targets of polythene, aluminum, iron, copper, zinc, tin, silver, tungsten, and lead for five β emitters, viz., 35S, 147Pm, 204Tl, 32P, and 90Sr-90Y. Effects of geometry and β-ray end-point energy have been investigated using a reflection geometry in which the geometry factors were varied by more than 40 and β-ray energy varied over a range 0.167-2.27 MeV. It is found that the mean value of the index of Z dependence of β-ray backscattering is 1.840.05 over these regions of geometry and energy. Deviations for soft β emitters have been confirmed as due to air absorption. The importance of these results in studies of two-component systems is emphasized.

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

Modelling non-adiabatic effects in H{sub 3}{sup +}: Solution of the rovibrational Schrödinger equation with motion-dependent masses and mass surfaces

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

Mátyus, Edit, E-mail: matyus@chem.elte.hu; Szidarovszky, Tamás; Császár, Attila G., E-mail: csaszar@chem.elte.hu

2014-10-21

Introducing different rotational and vibrational masses in the nuclear-motion Hamiltonian is a simple phenomenological way to model rovibrational non-adiabaticity. It is shown on the example of the molecular ion H{sub 3}{sup +}, for which a global adiabatic potential energy surface accurate to better than 0.1 cm{sup −1} exists [M. Pavanello, L. Adamowicz, A. Alijah, N. F. Zobov, I. I. Mizus, O. L. Polyansky, J. Tennyson, T. Szidarovszky, A. G. Császár, M. Berg et al., Phys. Rev. Lett. 108, 023002 (2012)], that the motion-dependent mass concept yields much more accurate rovibrational energy levels but, unusually, the results are dependent upon themore » choice of the embedding of the molecule-fixed frame. Correct degeneracies and an improved agreement with experimental data are obtained if an Eckart embedding corresponding to a reference structure of D{sub 3h} point-group symmetry is employed. The vibrational mass of the proton in H{sub 3}{sup +} is optimized by minimizing the root-mean-square (rms) deviation between the computed and recent high-accuracy experimental transitions. The best vibrational mass obtained is larger than the nuclear mass of the proton by approximately one third of an electron mass, m{sub opt,p}{sup (v)}=m{sub nuc,p}+0.31224 m{sub e}. This optimized vibrational mass, along with a nuclear rotational mass, reduces the rms deviation of the experimental and computed rovibrational transitions by an order of magnitude. Finally, it is shown that an extension of the algorithm allowing the use of motion-dependent masses can deal with coordinate-dependent mass surfaces in the rovibrational Hamiltonian, as well.« less

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.

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

Color priming in pop-out search depends on the relative color of the target

PubMed Central

Becker, Stefanie I.; Valuch, Christian; Ansorge, Ulrich

2014-01-01

In visual search for pop-out targets, search times are shorter when the target and non-target colors from the previous trial are repeated than when they change. This priming effect was originally attributed to a feature weighting mechanism that biases attention toward the target features, and away from the non-target features. However, more recent studies have shown that visual selection is strongly context-dependent: according to a relational account of feature priming, the target color is always encoded relative to the non-target color (e.g., as redder or greener). The present study provides a critical test of this hypothesis, by varying the colors of the search items such that either the relative color or the absolute color of the target always remained constant (or both). The results clearly show that color priming depends on the relative color of a target with respect to the non-targets but not on its absolute color value. Moreover, the observed priming effects did not change over the course of the experiment, suggesting that the visual system encodes colors in a relative manner from the start of the experiment. Taken together, these results strongly support a relational account of feature priming in visual search, and are inconsistent with the dominant feature-based views. PMID:24782795

RESOLVE and ECO: The Halo Mass-dependent Shape of Galaxy Stellar and Baryonic Mass Functions

NASA Astrophysics Data System (ADS)

Eckert, Kathleen D.; Kannappan, Sheila J.; Stark, David V.; Moffett, Amanda J.; Berlind, Andreas A.; Norris, Mark A.

2016-06-01

In this work, we present galaxy stellar and baryonic (stars plus cold gas) mass functions (SMF and BMF) and their halo mass dependence for two volume-limited data sets. The first, RESOLVE-B, coincides with the Stripe 82 footprint and is extremely complete down to baryonic mass M bary ˜ 109.1 M ⊙, probing the gas-rich dwarf regime below M bary ˜ 1010 M ⊙. The second, ECO, covers a ˜40× larger volume (containing RESOLVE-A) and is complete to M bary ˜ 109.4 M ⊙. To construct the SMF and BMF we implement a new “cross-bin sampling” technique with Monte Carlo sampling from the full likelihood distributions of stellar or baryonic mass. Our SMFs exhibit the “plateau” feature starting below M star ˜ 1010 M ⊙ that has been described in prior work. However, the BMF fills in this feature and rises as a straight power law below ˜1010 M ⊙, as gas-dominated galaxies become the majority of the population. Nonetheless, the low-mass slope of the BMF is not as steep as that of the theoretical dark matter halo MF. Moreover, we assign group halo masses by abundance matching, finding that the SMF and BMF, separated into four physically motivated halo mass regimes, reveal complex structure underlying the simple shape of the overall MFs. In particular, the satellite MFs are depressed below the central galaxy MF “humps” in groups with mass <1013.5 M ⊙ yet rise steeply in clusters. Our results suggest that satellite destruction and stripping are active from the point of nascent group formation. We show that the key role of groups in shaping MFs enables reconstruction of a given survey’s SMF or BMF based on its group halo mass distribution.

Klein-Gordon oscillator with position-dependent mass in the rotating cosmic string spacetime

NASA Astrophysics Data System (ADS)

Wang, Bing-Qian; Long, Zheng-Wen; Long, Chao-Yun; Wu, Shu-Rui

2018-02-01

A spinless particle coupled covariantly to a uniform magnetic field parallel to the string in the background of the rotating cosmic string is studied. The energy levels of the electrically charged particle subject to the Klein-Gordon oscillator are analyzed. Afterwards, we consider the case of the position-dependent mass and show how these energy levels depend on the parameters in the problem. Remarkably, it shows that for the special case, the Klein-Gordon oscillator coupled covariantly to a homogeneous magnetic field with the position-dependent mass in the rotating cosmic string background has the similar behaviors to the Klein-Gordon equation with a Coulomb-type configuration in a rotating cosmic string background in the presence of an external magnetic field.

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

PubMed

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

2017-02-17

Physical activity, a balanced diet, avoidance of tobacco exposure, and limited alcohol consumption may reduce morbidity and mortality from non-communicable diseases (NCDs). Mass media interventions are commonly used to encourage healthier behaviours in population groups. It is unclear whether targeted mass media interventions for ethnic minority groups are more or less effective in changing behaviours than those developed for the general population. To determine the effects of mass media interventions targeting adult ethnic minorities with messages about physical activity, dietary patterns, tobacco use or alcohol consumption to reduce the risk of NCDs. We searched CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, ERIC, SweMed+, and ISI Web of Science until August 2016. We also searched for grey literature in OpenGrey, Grey Literature Report, Eldis, and two relevant websites until October 2016. The searches were not restricted by language. We searched for individual and cluster-randomised controlled trials, controlled before-and-after studies (CBA) and interrupted time series studies (ITS). Relevant interventions promoted healthier behaviours related to physical activity, dietary patterns, tobacco use or alcohol consumption; were disseminated via mass media channels; and targeted ethnic minority groups. The population of interest comprised adults (≥ 18 years) from ethnic minority groups in the focal countries. Primary outcomes included indicators of behavioural change, self-reported behavioural change and knowledge and attitudes towards change. Secondary outcomes were the use of health promotion services and costs related to the project. Two authors independently reviewed the references to identify studies for inclusion. We extracted data and assessed the risk of bias in all included studies. We did not pool the results due to heterogeneity in comparisons made, outcomes, and study designs. We describe the results narratively and present them in 'Summary of findings

Relationship Between Integro-Differential Schrodinger Equation with a Symmetric Kernel and Position-Dependent Effective Mass

NASA Astrophysics Data System (ADS)

Khosropour, B.; Moayedi, S. K.; Sabzali, R.

2018-07-01

The solution of integro-differential Schrodinger equation (IDSE) which was introduced by physicists has a great role in the fields of science. The purpose of this paper comes in two parts. First, studying the relationship between integro-differential Schrodinger equation with a symmetric non-local potential and one-dimensional Schrodinger equation with a position-dependent effective mass. Second, we show that the quantum Hamiltonian for a particle with position-dependent mass after applying Liouville-Green transformations will be converted to a quantum Hamiltonian for a particle with constant mass.

Absolute and Mass-Dependent Titanium Isotope Compositions of Solar System Materials

NASA Astrophysics Data System (ADS)

Williams, N. H.; Fehr, M. A.; Akram, W. M.; Parkinson, I. J.; Schönbächler, M.

2013-09-01

Mass dependent Ti isotope data for various solar system material will be presented. This data has been obtained via double spike technique using ^47 Ti and ^49Ti as spikes. Absolute nucleosynthetic anomalie data for Ti will be presented also.

Anomalous pressure dependence of thermal conductivities of large mass ratio compounds

DOE PAGES

Lindsay, Lucas R; Broido, David A.; Carrete, Jesus; ...

2015-03-27

The lattice thermal conductivities (k) of binary compound materials are examined as a function of hydrostatic pressure P using a first-principles approach. Compound materials with relatively small mass ratios, such as MgO, show an increase in k with P, consistent with measurements. Conversely, compounds with large mass ratios (e.g., BSb, BAs, BeTe, BeSe) exhibit decreasing with increasing P, a behavior that cannot be understood using simple theories of k. This anomalous P dependence of k arises from the fundamentally different nature of the intrinsic scattering processes for heat-carrying acoustic phonons in large mass ratio compounds compared to those with smallmore » mass ratios. We find this work demonstrates the power of first principles methods for thermal properties and advances the understanding of thermal transport in non-metals.« less

Acoustic basis for recognition of aspect-dependent three-dimensional targets by an echolocating bottlenose dolphin.

PubMed

Helweg, D A; Au, W W; Roitblat, H L; Nachtigall, P E

1996-04-01

The relationships between acoustic features of target echoes and the cognitive representations of the target formed by an echolocating dolphin will influence the ease with which the dolphin can recognize a target. A blindfolded Atlantic bottlenose dolphin (Tursiops truncatus) learned to match aspect-dependent three-dimensional targets (such as a cube) at haphazard orientations, although with some difficulty. This task may have been difficult because aspect-dependent targets produce different echoes at different orientations, which required the dolphin to have some capability for object constancy across changes in echo characteristics. Significant target-related differences in echo amplitude, rms bandwidth, and distributions of interhighlight intervals were observed among echoes collected when the dolphin was performing the task. Targets could be classified using a combination of energy flux density and rms bandwidth by a linear discriminant analysis and a nearest centroid classifier. Neither statistical model could classify targets without amplitude information, but the highest accuracy required spectral information as well. This suggests that the dolphin recognized the targets using a multidimensional representation containing amplitude and spectral information and that dolphins can form stable representations of targets regardless of orientation based on varying sensory properties.

Hadron mass corrections in semi-inclusive deep-inelastic scattering

DOE PAGES

Guerrero Teran, Juan Vicente; Ethier, James J.; Accardi, Alberto; ...

2015-09-24

We found that the spin-dependent cross sections for semi-inclusive lepton-nucleon scattering are derived in the framework of collinear factorization, including the effects of masses of the target and produced hadron at finite Q 2. At leading order the cross sections factorize into products of parton distribution and fragmentation functions evaluated in terms of new, mass-dependent scaling variables. Furthermore, the size of the hadron mass corrections is estimated at kinematics relevant for current and future experiments, and the implications for the extraction of parton distributions from semi-inclusive measurements are discussed.

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.

Mutant p53 establishes targetable tumor dependency by promoting unscheduled replication

PubMed Central

Singh, Shilpa; Vaughan, Catherine A.; Frum, Rebecca A.; Grossman, Steven R.; Deb, Sumitra

2017-01-01

Gain-of-function (GOF) p53 mutations are observed frequently in most intractable human cancers and establish dependency for tumor maintenance and progression. While some of the genes induced by GOF p53 have been implicated in more rapid cell proliferation compared with p53-null cancer cells, the mechanism for dependency of tumor growth on mutant p53 is unknown. This report reveals a therapeutically targetable mechanism for GOF p53 dependency. We have shown that GOF p53 increases DNA replication origin firing, stabilizes replication forks, and promotes micronuclei formation, thus facilitating the proliferation of cells with genomic abnormalities. In contrast, absence or depletion of GOF p53 leads to decreased origin firing and a higher frequency of fork collapse in isogenic cells, explaining their poorer proliferation rate. Following genome-wide analyses utilizing ChIP-Seq and RNA-Seq, GOF p53–induced origin firing, micronuclei formation, and fork protection were traced to the ability of GOF p53 to transactivate cyclin A and CHK1. Highlighting the therapeutic potential of CHK1’s role in GOF p53 dependency, experiments in cell culture and mouse xenografts demonstrated that inhibition of CHK1 selectively blocked proliferation of cells and tumors expressing GOF p53. Our data suggest the possibility that checkpoint inhibitors could efficiently and selectively target cancers expressing GOF p53 alleles. PMID:28394262

Age dependent regulation of bone-mass and renal function by the MEPE ASARM-motif

PubMed Central

Zelenchuk, Lesya V; Hedge, Anne-Marie; Rowe, Peter S N

2015-01-01

renal function. Free ASARM-peptide also effects renal mineral phosphate handling by influencing FGF23 expression. These findings have implications for understanding age-dependent osteoporosis, unraveling drug-targets and developing treatments. PMID:26051469

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.

RESOLVE AND ECO: THE HALO MASS-DEPENDENT SHAPE OF GALAXY STELLAR AND BARYONIC MASS FUNCTIONS

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

Eckert, Kathleen D.; Kannappan, Sheila J.; Stark, David V.

2016-06-20

In this work, we present galaxy stellar and baryonic (stars plus cold gas) mass functions (SMF and BMF) and their halo mass dependence for two volume-limited data sets. The first, RESOLVE-B, coincides with the Stripe 82 footprint and is extremely complete down to baryonic mass M {sub bary} ∼ 10{sup 9.1} M {sub ⊙}, probing the gas-rich dwarf regime below M {sub bary} ∼ 10{sup 10} M {sub ⊙}. The second, ECO, covers a ∼40× larger volume (containing RESOLVE-A) and is complete to M {sub bary} ∼ 10{sup 9.4} M {sub ⊙}. To construct the SMF and BMF we implementmore » a new “cross-bin sampling” technique with Monte Carlo sampling from the full likelihood distributions of stellar or baryonic mass. Our SMFs exhibit the “plateau” feature starting below M {sub star} ∼ 10{sup 10} M {sub ⊙} that has been described in prior work. However, the BMF fills in this feature and rises as a straight power law below ∼10{sup 10} M {sub ⊙}, as gas-dominated galaxies become the majority of the population. Nonetheless, the low-mass slope of the BMF is not as steep as that of the theoretical dark matter halo MF. Moreover, we assign group halo masses by abundance matching, finding that the SMF and BMF, separated into four physically motivated halo mass regimes, reveal complex structure underlying the simple shape of the overall MFs. In particular, the satellite MFs are depressed below the central galaxy MF “humps” in groups with mass <10{sup 13.5} M {sub ⊙} yet rise steeply in clusters. Our results suggest that satellite destruction and stripping are active from the point of nascent group formation. We show that the key role of groups in shaping MFs enables reconstruction of a given survey’s SMF or BMF based on its group halo mass distribution.« less

Efficient protein targeting to the inner nuclear membrane requires Atlastin-dependent maintenance of ER topology

PubMed Central

Pawar, Sumit; Ungricht, Rosemarie; Tiefenboeck, Peter; Leroux, Jean-Christophe

2017-01-01

Newly synthesized membrane proteins are targeted to the inner nuclear membrane (INM) by diffusion within the membrane system of the endoplasmic reticulum (ER), translocation through nuclear pore complexes (NPCs) and retention on nuclear partners. Using a visual in vitro assay we previously showed that efficient protein targeting to the INM depends on nucleotide hydrolysis. We now reveal that INM targeting is GTP-dependent. Exploiting in vitro reconstitution and in vivo analysis of INM targeting, we establish that Atlastins, membrane-bound GTPases of the ER, sustain the efficient targeting of proteins to the INM by their continued activity in preserving ER topology. When ER topology is altered, the long-range diffusional exchange of proteins in the ER network and targeting efficiency to the INM are diminished. Highlighting the general importance of proper ER topology, we show that Atlastins also influence NPC biogenesis and timely exit of secretory cargo from the ER. PMID:28826471

Vitamin B12–dependent taurine synthesis regulates growth and bone mass

PubMed Central

Roman-Garcia, Pablo; Quiros-Gonzalez, Isabel; Mottram, Lynda; Lieben, Liesbet; Sharan, Kunal; Wangwiwatsin, Arporn; Tubio, Jose; Lewis, Kirsty; Wilkinson, Debbie; Santhanam, Balaji; Sarper, Nazan; Clare, Simon; Vassiliou, George S.; Velagapudi, Vidya R.; Dougan, Gordon; Yadav, Vijay K.

2014-01-01

Both maternal and offspring-derived factors contribute to lifelong growth and bone mass accrual, although the specific role of maternal deficiencies in the growth and bone mass of offspring is poorly understood. In the present study, we have shown that vitamin B12 (B12) deficiency in a murine genetic model results in severe postweaning growth retardation and osteoporosis, and the severity and time of onset of this phenotype in the offspring depends on the maternal genotype. Using integrated physiological and metabolomic analysis, we determined that B12 deficiency in the offspring decreases liver taurine production and associates with abrogation of a growth hormone/insulin-like growth factor 1 (GH/IGF1) axis. Taurine increased GH-dependent IGF1 synthesis in the liver, which subsequently enhanced osteoblast function, and in B12-deficient offspring, oral administration of taurine rescued their growth retardation and osteoporosis phenotypes. These results identify B12 as an essential vitamin that positively regulates postweaning growth and bone formation through taurine synthesis and suggests potential therapies to increase bone mass. PMID:24911144

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.

Strong orientation dependence of surface mass density profiles of dark haloes at large scales

NASA Astrophysics Data System (ADS)

Osato, Ken; Nishimichi, Takahiro; Oguri, Masamune; Takada, Masahiro; Okumura, Teppei

2018-06-01

We study the dependence of surface mass density profiles, which can be directly measured by weak gravitational lensing, on the orientation of haloes with respect to the line-of-sight direction, using a suite of N-body simulations. We find that, when major axes of haloes are aligned with the line-of-sight direction, surface mass density profiles have higher amplitudes than those averaged over all halo orientations, over all scales from 0.1 to 100 Mpc h-1 we studied. While the orientation dependence at small scales is ascribed to the halo triaxiality, our results indicate even stronger orientation dependence in the so-called two-halo regime, up to 100 Mpc h-1. The orientation dependence for the two-halo term is well approximated by a multiplicative shift of the amplitude and therefore a shift in the halo bias parameter value. The halo bias from the two-halo term can be overestimated or underestimated by up to ˜ 30 per cent depending on the viewing angle, which translates into the bias in estimated halo masses by up to a factor of 2 from halo bias measurements. The orientation dependence at large scales originates from the anisotropic halo-matter correlation function, which has an elliptical shape with the axis ratio of ˜0.55 up to 100 Mpc h-1. We discuss potential impacts of halo orientation bias on other observables such as optically selected cluster samples and a clustering analysis of large-scale structure tracers such as quasars.

The mass dependence of satellite quenching in Milky Way-like haloes

NASA Astrophysics Data System (ADS)

Phillips, John I.; Wheeler, Coral; Cooper, Michael C.; Boylan-Kolchin, Michael; Bullock, James S.; Tollerud, Erik

2015-02-01

Using the Sloan Digital Sky Survey, we examine the quenching of satellite galaxies around isolated Milky Way-like hosts in the local Universe. We find that the efficiency of satellite quenching around isolated galaxies is low and roughly constant over two orders of magnitude in satellite stellar mass (M⋆ = 108.5-1010.5 M⊙), with only ˜20 per cent of systems quenched as a result of environmental processes. While largely independent of satellite stellar mass, satellite quenching does exhibit clear dependence on the properties of the host. We show that satellites of passive hosts are substantially more likely to be quenched than those of star-forming hosts, and we present evidence that more massive haloes quench their satellites more efficiently. These results extend trends seen previously in more massive host haloes and for higher satellite masses. Taken together, it appears that galaxies with stellar masses larger than about 108 M⊙ are uniformly resistant to environmental quenching, with the relative harshness of the host environment likely serving as the primary driver of satellite quenching. At lower stellar masses (<108 M⊙), however, observations of the Local Group suggest that the vast majority of satellite galaxies are quenched, potentially pointing towards a characteristic satellite mass scale below which quenching efficiency increases dramatically.

Endothelial microparticle uptake in target cells is annexin I/phosphatidylserine receptor dependent and prevents apoptosis.

PubMed

Jansen, Felix; Yang, Xiaoyan; Hoyer, Friedrich Felix; Paul, Kathrin; Heiermann, Nadine; Becher, Marc Ulrich; Abu Hussein, Nebal; Kebschull, Moritz; Bedorf, Jörg; Franklin, Bernardo S; Latz, Eicke; Nickenig, Georg; Werner, Nikos

2012-08-01

Endothelial microparticles (EMP) are released from activated or apoptotic cells, but their effect on target cells and the exact way of incorporation are largely unknown. We sought to determine the uptake mechanism and the biological effect of EMP on endothelial and endothelial-regenerating cells. EMP were generated from starved endothelial cells and isolated by ultracentrifugation. Caspase 3 activity assay and terminal deoxynucleotidyl transferase dUTP nick end labeling assay showed that EMP protect target endothelial cells against apoptosis in a dose-dependent manner. Proteomic analysis was performed to identify molecules contained in EMP, which might be involved in EMP uptake. Expression of annexin I in EMP was found and confirmed by Western blot, whereas the corresponding receptor phosphatidylserine receptor was present on endothelial target cells. Silencing either annexin I on EMP or phosphatidylserine receptor on target cells using small interfering RNA showed that the uptake of EMP by human coronary artery endothelial cells is annexin I/phosphatidylserine receptor dependent. Annexin I-downregulated EMP abrogated the EMP-mediated protection against apoptosis of endothelial target cells. p38 activation was found to mediate camptothecin-induced apoptosis. Finally, human coronary artery endothelial cells pretreated with EMP inhibited camptothecin-induced p38 activation. EMP are incorporated by endothelial cells in an annexin I/phosphatidylserine receptor-dependent manner and protect target cells against apoptosis. Inhibition of p38 activity is involved in EMP-mediated protection against apoptosis.

The Quest for Targets Executing MYC-Dependent Cell Transformation.

PubMed

Hartl, Markus

2016-01-01

MYC represents a transcription factor with oncogenic potential converting multiple cellular signals into a broad transcriptional response, thereby controlling the expression of numerous protein-coding and non-coding RNAs important for cell proliferation, metabolism, differentiation, and apoptosis. Constitutive activation of MYC leads to neoplastic cell transformation, and deregulated MYC alleles are frequently observed in many human cancer cell types. Multiple approaches have been performed to isolate genes differentially expressed in cells containing aberrantly activated MYC proteins leading to the identification of thousands of putative targets. Functional analyses of genes differentially expressed in MYC-transformed cells had revealed that so far more than 40 upregulated or downregulated MYC targets are actively involved in cell transformation or tumorigenesis. However, further systematic and selective approaches are required for determination of the known or yet unidentified targets responsible for processing the oncogenic MYC program. The search for critical targets in MYC-dependent tumor cells is exacerbated by the fact that during tumor development, cancer cells progressively evolve in a multistep process, thereby acquiring their characteristic features in an additive manner. Functional expression cloning, combinatorial gene expression, and appropriate in vivo tests could represent adequate tools for dissecting the complex scenario of MYC-specified cell transformation. In this context, the central goal is to identify a minimal set of targets that suffices to phenocopy oncogenic MYC. Recently developed genomic editing tools could be employed to confirm the requirement of crucial transformation-associated targets. Knowledge about essential MYC-regulated genes is beneficial to expedite the development of specific inhibitors to interfere with growth and viability of human tumor cells in which MYC is aberrantly activated. Approaches based on the principle of

The Quest for Targets Executing MYC-Dependent Cell Transformation

PubMed Central

Hartl, Markus

2016-01-01

MYC represents a transcription factor with oncogenic potential converting multiple cellular signals into a broad transcriptional response, thereby controlling the expression of numerous protein-coding and non-coding RNAs important for cell proliferation, metabolism, differentiation, and apoptosis. Constitutive activation of MYC leads to neoplastic cell transformation, and deregulated MYC alleles are frequently observed in many human cancer cell types. Multiple approaches have been performed to isolate genes differentially expressed in cells containing aberrantly activated MYC proteins leading to the identification of thousands of putative targets. Functional analyses of genes differentially expressed in MYC-transformed cells had revealed that so far more than 40 upregulated or downregulated MYC targets are actively involved in cell transformation or tumorigenesis. However, further systematic and selective approaches are required for determination of the known or yet unidentified targets responsible for processing the oncogenic MYC program. The search for critical targets in MYC-dependent tumor cells is exacerbated by the fact that during tumor development, cancer cells progressively evolve in a multistep process, thereby acquiring their characteristic features in an additive manner. Functional expression cloning, combinatorial gene expression, and appropriate in vivo tests could represent adequate tools for dissecting the complex scenario of MYC-specified cell transformation. In this context, the central goal is to identify a minimal set of targets that suffices to phenocopy oncogenic MYC. Recently developed genomic editing tools could be employed to confirm the requirement of crucial transformation-associated targets. Knowledge about essential MYC-regulated genes is beneficial to expedite the development of specific inhibitors to interfere with growth and viability of human tumor cells in which MYC is aberrantly activated. Approaches based on the principle of

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.

Position-Dependent Mass Schrödinger Equation for the Morse Potential

NASA Astrophysics Data System (ADS)

Ovando, G.; Peña, J. J.; Morales, J.; López-Bonilla, J.

2017-01-01

The position dependent mass Schrödinger equation (PDMSE) has a wide range of quantum applications such as the study of semiconductors, quantum wells, quantum dots and impurities in crystals, among many others. On the other hand, the Morse potential is one of the most important potential models used to study the electronic properties of diatomic molecules. In this work, the solution of the effective mass one-dimensional Schrödinger equation for the Morse potential is presented. This is done by means of the canonical transformation method in algebraic form. The PDMSE is solved for any model of the proposed kinetic energy operators as for example the BenDaniel-Duke, Gora-Williams, Zhu-Kroemer or Li-Kuhn. Also, in order to solve the PDMSE with Morse potential, we consider a superpotential leading to a special form of the exactly solvable Schrödinger equation of constant mass for a class of multiparameter exponential-type potential along with a proper mass distribution. The proposed approach is general and can be applied in the search of new potentials suitable on science of materials by looking into the viable choices of the mass function.

The harmonic oscillator and the position dependent mass Schroedinger equation: isospectral partners and factorization operators

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

Morales, J.; Ovando, G.; Pena, J. J.

2010-12-23

One of the most important scientific contributions of Professor Marcos Moshinsky has been his study on the harmonic oscillator in quantum theory vis a vis the standard Schroedinger equation with constant mass [1]. However, a simple description of the motion of a particle interacting with an external environment such as happen in compositionally graded alloys consist of replacing the mass by the so-called effective mass that is in general variable and dependent on position. Therefore, honoring in memoriam Marcos Moshinsky, in this work we consider the position-dependent mass Schrodinger equations (PDMSE) for the harmonic oscillator potential model as former potentialmore » as well as with equi-spaced spectrum solutions, i.e. harmonic oscillator isospectral partners. To that purpose, the point canonical transformation method to convert a general second order differential equation (DE), of Sturm-Liouville type, into a Schroedinger-like standard equation is applied to the PDMSE. In that case, the former potential associated to the PDMSE and the potential involved in the Schroedinger-like standard equation are related through a Riccati-type relationship that includes the equivalent of the Witten superpotential to determine the exactly solvable positions-dependent mass distribution (PDMD)m(x). Even though the proposed approach is exemplified with the harmonic oscillator potential, the procedure is general and can be straightforwardly applied to other DEs.« less

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/

Model prediction for temperature dependence of meson pole masses from lattice QCD results on meson screening masses

NASA Astrophysics Data System (ADS)

Ishii, Masahiro; Kouno, Hiroaki; Yahiro, Masanobu

2017-06-01

We propose a practical effective model by introducing temperature (T ) dependence to the coupling strengths of four-quark and six-quark Kobayashi-Maskawa-'t Hooft interactions in the 2 +1 flavor Polyakov-loop extended Nambu-Jona-Lasinio model. The T dependence is determined from lattice QCD (LQCD) data on the renormalized chiral condensate around the pseudocritical temperature Tcχ of chiral crossover and the screening-mass difference between π and a0 mesons in T >1.1 Tcχ where only the U (1 )A-symmetry breaking survives. The model well reproduces LQCD data on screening masses Mξscr(T ) for both pseudoscalar mesons (ξ =π ,K ,η ,η' ) and scalar ones (ξ =a0,κ ,σ ,f0 ), particularly in T ≳Tcχ . Using this effective model, we predict meson pole masses Mξpole(T ) for scalar and pseudoscalar mesons. For η' meson, the prediction is consistent with the experimental value at finite T measured in heavy-ion collisions. We point out that the relation Mξscr(T )-Mξpole(T )≈Mξ' scr(T )-Mξ' pole(T ) is pretty good when ξ and ξ' are the scalar mesons, and show that the relation Mξscr(T )/Mξ' scr(T )≈Mξpole(T )/Mξ' pole(T ) is well satisfied within 20% error when ξ and ξ' are the pseudoscalar mesons and also when ξ and ξ' are the scalar mesons.

Analyzing fragment production in mass-asymmetric reactions as a function of density dependent part of symmetry energy

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

Kaur, Amandeep; Deepshikha; Vinayak, Karan Singh

2016-07-15

We performed a theoretical investigation of different mass-asymmetric reactions to access the direct impact of the density-dependent part of symmetry energy on multifragmentation. The simulations are performed for a specific set of reactions having same system mass and N/Z content, using isospin-dependent quantum molecular dynamics model to estimate the quantitative dependence of fragment production on themass-asymmetry factor (τ) for various symmetry energy forms. The dynamics associated with different mass-asymmetric reactions is explored and the direct role of symmetry energy is checked. Also a comparison with the experimental data (asymmetric reaction) is presented for a different equation of states (symmetry energymore » forms).« less

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.

Insulin Resistance Negatively Influences the Muscle-Dependent IGF-1-Bone Mass Relationship in Premenarcheal Girls.

PubMed

Kindler, J M; Pollock, N K; Laing, E M; Jenkins, N T; Oshri, A; Isales, C; Hamrick, M; Lewis, R D

2016-01-01

IGF-1 promotes bone growth directly and indirectly through its effects on skeletal muscle. Insulin and IGF-1 share a common cellular signaling process; thus, insulin resistance may influence the IGF-1-muscle-bone relationship. We sought to determine the effect of insulin resistance on the muscle-dependent relationship between IGF-1 and bone mass in premenarcheal girls. This was a cross-sectional study conducted at a university research center involving 147 girls ages 9 to 11 years. Glucose, insulin, and IGF-1 were measured from fasting blood samples. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated from glucose and insulin. Fat-free soft tissue (FFST) mass and bone mineral content (BMC) were measured by dual-energy x-ray absorptiometry. Our primary outcome was BMC/height. In our path model, IGF-1 predicted FFST mass (b = 0.018; P = .001), which in turn predicted BMC/height (b = 0.960; P < .001). IGF-1 predicted BMC/height (b = 0.001; P = .002), but not after accounting for the mediator of this relationship, FFST mass. The HOMA-IR by IGF-1 interaction negatively predicted FFST mass (b = -0.044; P = .034). HOMA-IR had a significant and negative effect on the muscle-dependent relationship between IGF-1 and BMC/height (b = -0.151; P = .047). Lean body mass is an important intermediary factor in the IGF-1-bone relationship. For this reason, bone development may be compromised indirectly via suboptimal IGF-1-dependent muscle development in insulin-resistant children.

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.

RNAi revised--target mRNA-dependent enhancement of gene silencing.

PubMed

Dornseifer, Simon; Willkomm, Sarah; Far, Rosel Kretschmer-Kazemi; Liebschwager, Janine; Beltsiou, Foteini; Frank, Kirsten; Laufer, Sandra D; Martinetz, Thomas; Sczakiel, Georg; Claussen, Jens Christian; Restle, Tobias

2015-12-15

The discovery of RNA interference (RNAi) gave rise to the development of new nucleic acid-based technologies as powerful investigational tools and potential therapeutics. Mechanistic key details of RNAi in humans need to be deciphered yet, before such approaches take root in biomedicine and molecular therapy. We developed and validated an in silico-based model of siRNA-mediated RNAi in human cells in order to link in vitro-derived pre-steady state kinetic data with a quantitative and time-resolved understanding of RNAi on the cellular level. The observation that product release by Argonaute 2 is accelerated in the presence of an excess of target RNA in vitro inspired us to suggest an associative mechanism for the RNA slicer reaction where incoming target mRNAs actively promote dissociation of cleaved mRNA fragments. This novel associative model is compatible with high multiple turnover rates of RNAi-based gene silencing in living cells and accounts for target mRNA concentration-dependent enhancement of the RNAi machinery. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Mass dependence of HBT correlations in e+e- annihilation

NASA Astrophysics Data System (ADS)

Bialas, A.; Kucharczyk, M.; Palka, H.; Zalewski, K.

2000-12-01

The mass dependence of the effective source radii, observed in hadronic Z0 decays by several CERN LEP I experiments, is analyzed in a model which assumes proportionality between the four-momentum of a produced particle and the four-vector describing its space-time position at freeze-out. It is shown that this relation (commonly accepted in the description of high-energy collisions) can explain the data, provided all particles are emitted from a ``tube'' of ~1 fm in diameter at a constant proper time ~1.5 fm.

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.

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.

Electron mass in dilute nitrides and its anomalous dependence on hydrostatic pressure.

PubMed

Pettinari, G; Polimeni, A; Masia, F; Trotta, R; Felici, M; Capizzi, M; Niebling, T; Stolz, W; Klar, P J

2007-04-06

The dependence of the electron mass on hydrostatic pressure P in N-diluted GaAs1-xNx (x=0.10% and 0.21%) is investigated by magnetophotoluminescence. Exceedingly large fluctuations (up to 60%/kbar) in the electron mass with increasing P are found. These originate from a pressure-driven tuning of the hybridization degree between the conduction band minimum and specific nitrogen-related states. Present results suggest a hierarchy between different nitrogen complexes as regards the extent of the perturbation these complexes exert on the electronic properties of the GaAs host.

Context-dependent sequential effects of target selection for action.

PubMed

Moher, Jeff; Song, Joo-Hyun

2013-07-11

Humans exhibit variation in behavior from moment to moment even when performing a simple, repetitive task. Errors are typically followed by cautious responses, minimizing subsequent distractor interference. However, less is known about how variation in the execution of an ultimately correct response affects subsequent behavior. We asked participants to reach toward a uniquely colored target presented among distractors and created two categories to describe participants' responses in correct trials based on analyses of movement trajectories; partial errors referred to trials in which observers initially selected a nontarget for action before redirecting the movement and accurately pointing to the target, and direct movements referred to trials in which the target was directly selected for action. We found that latency to initiate a hand movement was shorter in trials following partial errors compared to trials following direct movements. Furthermore, when the target and distractor colors were repeated, movement time and reach movement curvature toward distractors were greater following partial errors compared to direct movements. Finally, when the colors were repeated, partial errors were more frequent than direct movements following partial-error trials, and direct movements were more frequent following direct-movement trials. The dependence of these latter effects on repeated-task context indicates the involvement of higher-level cognitive mechanisms in an integrated attention-action system in which execution of a partial-error or direct-movement response affects memory representations that bias performance in subsequent trials. Altogether, these results demonstrate that whether a nontarget is selected for action or not has a measurable impact on subsequent behavior.

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

An Update on the Non-Mass-Dependent Isotope Fractionation under Thermal Gradient

NASA Technical Reports Server (NTRS)

Sun, Tao; Niles, Paul; Bao, Huiming; Socki, Richard; Liu, Yun

2013-01-01

Mass flow and compositional gradient (elemental and isotope separation) occurs when flu-id(s) or gas(es) in an enclosure is subjected to a thermal gradient, and the phenomenon is named thermal diffusion. Gas phase thermal diffusion has been theoretically and experimentally studied for more than a century, although there has not been a satisfactory theory to date. Nevertheless, for isotopic system, the Chapman-Enskog theory predicts that the mass difference is the only term in the thermal diffusion separation factors that differs one isotope pair to another,with the assumptions that the molecules are spherical and systematic (monoatomic-like structure) and the particle collision is elastic. Our previous report indicates factors may be playing a role because the Non-Mass Dependent (NMD) effect is found for both symmetric and asymmetric, linear and spherical polyatomic molecules over a wide range of temperature (-196C to +237C). The observed NMD phenomenon in the simple thermal-diffusion experiments demands quantitative validation and theoretical explanation. Besides the pressure and temperature dependency illustrated in our previous reports, efforts are made in this study to address issues such as the role of convection or molecular structure and whether it is a transient, non-equilibrium effect only.

Distance-dependent magnetic resonance tuning as a versatile MRI sensing platform for biological targets

NASA Astrophysics Data System (ADS)

Choi, Jin-Sil; Kim, Soojin; Yoo, Dongwon; Shin, Tae-Hyun; Kim, Hoyoung; Gomes, Muller D.; Kim, Sun Hee; Pines, Alexander; Cheon, Jinwoo

2017-05-01

Nanoscale distance-dependent phenomena, such as Förster resonance energy transfer, are important interactions for use in sensing and imaging, but their versatility for bioimaging can be limited by undesirable photon interactions with the surrounding biological matrix, especially in in vivo systems. Here, we report a new type of magnetism-based nanoscale distance-dependent phenomenon that can quantitatively and reversibly sense and image intra-/intermolecular interactions of biologically important targets. We introduce distance-dependent magnetic resonance tuning (MRET), which occurs between a paramagnetic `enhancer' and a superparamagnetic `quencher', where the T1 magnetic resonance imaging (MRI) signal is tuned ON or OFF depending on the separation distance between the quencher and the enhancer. With MRET, we demonstrate the principle of an MRI-based ruler for nanometre-scale distance measurement and the successful detection of both molecular interactions (for example, cleavage, binding, folding and unfolding) and biological targets in in vitro and in vivo systems. MRET can serve as a novel sensing principle to augment the exploration of a wide range of biological systems.

Mass-imbalanced Hubbard model in optical lattice with site-dependent interactions

NASA Astrophysics Data System (ADS)

Le, Duc-Anh; Tran, Thi-Thu-Trang; Hoang, Anh-Tuan; Nguyen, Toan-Thang; Tran, Minh-Tien

2018-03-01

We study the half-filled mass-imbalanced Hubbard model with spatially alternating interactions on an optical bipartite lattice by means of the dynamical mean-field theory. The Mott transition is investigated via the spin-dependent density of states and double occupancies. The phase diagrams for the homogeneous phases at zero temperature are constructed numerically. The boundary between metallic and insulating phases at zero temperature is analytically derived within the dynamical mean field theory using the equation of motion approach as the impurity solver. We found that the metallic region is reduced with increasing interaction anisotropy or mass imbalance. Our results are closely relevant to current researches in ultracold fermion experiments and can be verified through experimental observations.

Rapid profiling of polymeric phenolic acids in Salvia miltiorrhiza by hybrid data-dependent/targeted multistage mass spectrometry acquisition based on expected compounds prediction and fragment ion searching.

PubMed

Shen, Yao; Feng, Zijin; Yang, Min; Zhou, Zhe; Han, Sumei; Hou, Jinjun; Li, Zhenwei; Wu, Wanying; Guo, De-An

2018-04-01

Phenolic acids are the major water-soluble components in Salvia miltiorrhiza (>5%). According to previous studies, many of them contribute to the cardiovascular effects and antioxidant effects of S. miltiorrhiza. Polymeric phenolic acids can be considered as the tanshinol derived metabolites, e.g., dimmers, trimers, and tetramers. A strategy combined with tanshinol-based expected compounds prediction, total ion chromatogram filtering, fragment ion searching, and parent list-based multistage mass spectrometry acquisition by linear trap quadropole-orbitrap Velos mass spectrometry was proposed to rapid profile polymeric phenolic acids in S. miltiorrhiza. More than 480 potential polymeric phenolic acids could be screened out by this strategy. Based on the fragment information obtained by parent list-activated data dependent multistage mass spectrometry acquisition, 190 polymeric phenolic acids were characterized by comparing their mass information with literature data, and 18 of them were firstly detected from S. miltiorrhiza. Seven potential compounds were tentatively characterized as new polymeric phenolic acids from S. miltiorrhiza. This strategy facilitates identification of polymeric phenolic acids in complex matrix with both selectivity and sensitivity, which could be expanded for rapid discovery and identification of compounds from complex matrix. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

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.

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.

HGG-22. TARGETING NEURONAL ACTIVITY-REGULATED NEUROLIGIN-3 DEPENDENCY FOR HIGH-GRADE GLIOMA THERAPY

PubMed Central

Venkatesh, Humsa S; Tam, Lydia T; Woo, Pamelyn J; Monje, Michelle

2017-01-01

Abstract Neuronal activity promotes high-grade glioma (HGG) growth. An important mechanism mediating this neural regulation of brain cancer is activity-dependent cleavage and secretion of the synaptic molecule and glioma mitogen neuroligin-3 (Nlgn3), but the therapeutic potential of targeting Nlgn3 in glioma remains to be defined. Here, we demonstrate a striking dependence of HGG growth on microenvironmental Nlgn3 and determine a targetable mechanism of secretion. Patient-derived orthotopic xenografts of pediatric glioblastoma (pGBM) and diffuse intrinsic pontine glioma (DIPG) fail to grow in Nlgn3 knockout mice. Using genetic mouse models, we illustrate that Nlgn3 is cleaved from both neurons and oligodendrocyte precursor cells via the ADAM10 sheddase. Administration of an ADAM10 inhibitor robustly blocks pGBM and DIPG xenograft growth via modulation of the tumor microenvironment. This work defines the therapeutic potential of and a promising strategy for targeting Nlgn3 secretion in the glioma microenvironment, which could prove transformative for treatment of HGG.

NEW CONSTRAINTS ON MASS-DEPENDENT DISRUPTION OF STAR CLUSTERS IN M51

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

Chandar, Rupali; Whitmore, Bradley C.; Regan, Michael

2011-02-01

We use UBVI H{alpha} images of the Whirlpool galaxy, M51, taken with the Advanced Camera for Surveys and WFPC2 cameras on the Hubble Space Telescope (HST) to select star clusters, and to estimate their masses and ages by comparing their observed colors with predictions from population synthesis models. We construct the mass function of intermediate-age (1-4 x 10{sup 8} yr) clusters, and find that it is well described by a power law, {psi}(M) {proportional_to} M{sup {beta}}, with {beta} = -2.1 {+-} 0.2, for clusters more massive than M {approx} 6 x 10{sup 3} M{sub sun}. This extends the mass functionmore » of intermediate-age clusters in M51 to masses lower by nearly a factor of five over previous determinations. The mass function does not show evidence for curvature at either the high or low mass end. This shape indicates that there is no evidence for the earlier disruption of lower mass clusters compared with their higher mass counterparts (i.e., no mass-dependent disruption) over the observed range of masses and ages, or for a physical upper mass limit M{sub C} with which clusters in M51 can form. These conclusions differ from previous suggestions based on poorer-quality HST observations. We discuss their implications for the formation and disruption of the clusters. Ages of clusters in two 'feathers', stellar features extending from the outer portion of a spiral arm, show that the feather with a larger pitch angle formed earlier, and over a longer period, than the other.« less

Neutron–proton effective mass splitting in neutron-rich matter at normal density from analyzing nucleon–nucleus scattering data within an isospin dependent optical model

DOE PAGES

Li, Xiao -Hua; Guo, Wen -Jun; Li, Bao -An; ...

2015-04-01

The neutron–proton effective mass splitting in asymmetric nucleonic matter of isospin asymmetry δ and normal density is found to be m* n-p≡(m* n – m* p)/m = (0.41 ± 0.15)δ from analyzing globally 1088 sets of reaction and angular differential cross sections of proton elastic scattering on 130 targets with beam energies from 0.783 MeV to 200 MeV, and 1161 sets of data of neutron elastic scattering on 104 targets with beam energies from 0.05 MeV to 200 MeV within an isospin dependent non-relativistic optical potential model. It sets a useful reference for testing model predictions on the momentum dependencemore » of the nucleon isovector potential necessary for understanding novel structures and reactions of rare isotopes.« less

Using Generalizability Theory to Examine the Dependability of Scores from the Learning Target Rating Scale

ERIC Educational Resources Information Center

McLaughlin, Tara W.; Snyder, Patricia A.; Algina, James

2017-01-01

The Learning Target Rating Scale (LTRS) is a measure designed to evaluate the quality of teacher-developed learning targets for embedded instruction for early learning. In the present study, we examined the measurement dependability of LTRS scores by conducting a generalizability study (G-study). We used a partially nested, three-facet model to…

Delineating neurotrophin-3 dependent signaling pathways underlying sympathetic axon growth along intermediate targets.

PubMed

Keeler, Austin B; Suo, Dong; Park, Juyeon; Deppmann, Christopher D

2017-07-01

Postganglionic sympathetic neurons detect vascular derived neurotrophin 3 (NT3) via the axonally expressed receptor tyrosine kinase, TrkA, to promote chemo-attraction along intermediate targets. Once axons arrive to their final target, a structurally related neurotrophic factor, nerve growth factor (NGF), also acts through TrkA to promote final target innervation. Does TrkA signal differently at these different locales? We previously found that Coronin-1 is upregulated in sympathetic neurons upon exposure to NGF, thereby endowing the NGF-TrkA complex with new signaling capabilities (i.e. calcium signaling), which dampens axon growth and branching. Based on the notion that axons do not express functional levels of Coronin-1 prior to final target innervation, we developed an in vitro model for axon growth and branching along intermediate targets using Coro1a -/- neurons grown in NT3. We found that, similar to NGF-TrkA, NT3-TrkA is capable of inducing MAPK and PI3K in the presence or absence of Coronin-1. However, unlike NGF, NT3 does not induce calcium release from intracellular stores. Using a combination of pharmacology, knockout neurons and in vitro functional assays, we suggest that the NT3-TrkA complex uses Ras/MAPK and/or PI3K-AKT signaling to induce axon growth and inhibit axon branching along intermediate targets. However, in the presence of Coronin-1, these signaling pathways lose their ability to impact NT3 dependent axon growth or branching. This is consistent with a role for Coronin-1 as a molecular switch for axon behavior and suggests that Coronin-1 suppresses NT3 dependent axon behavior. Copyright © 2017 Elsevier Inc. All rights reserved.

The Dependence of Galaxy Clustering on Stellar-mass Assembly History for LRGs

NASA Astrophysics Data System (ADS)

Montero-Dorta, Antonio D.; Pérez, Enrique; Prada, Francisco; Rodríguez-Torres, Sergio; Favole, Ginevra; Klypin, Anatoly; Cid Fernandes, Roberto; González Delgado, Rosa M.; Domínguez, Alberto; Bolton, Adam S.; García-Benito, Rubén; Jullo, Eric; Niemiec, Anna

2017-10-01

We analyze the spectra of 300,000 luminous red galaxies (LRGs) with stellar masses {M}* ≳ {10}11 {M}⊙ from the SDSS-III Baryon Oscillation Spectroscopic Survey (BOSS). By studying their star formation histories, we find two main evolutionary paths converging into the same quiescent galaxy population at z˜ 0.55. Fast-growing LRGs assemble 80% of their stellar mass very early on (z˜ 5), whereas slow-growing LRGs reach the same evolutionary state at z˜ 1.5. Further investigation reveals that their clustering properties on scales of ˜1-30 Mpc are, at a high level of significance, also different. Fast-growing LRGs are found to be more strongly clustered and reside in overall denser large-scale structure environments than slow-growing systems, for a given stellar-mass threshold. Our results show a dependence of clustering on a property that is directly related to the evolution of galaxies, I.e., the stellar-mass assembly history, for a homogeneous population of similar mass and color. In a forthcoming work, we will address the halo connection in the context of galaxy assembly bias.

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

PubMed Central

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

2016-01-01

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

DISE: A Seed-Dependent RNAi Off-Target Effect That Kills Cancer Cells.

PubMed

Putzbach, William; Gao, Quan Q; Patel, Monal; Haluck-Kangas, Ashley; Murmann, Andrea E; Peter, Marcus E

2018-01-01

Off-target effects (OTEs) represent a significant caveat for RNAi caused by substantial complementarity between siRNAs and unintended mRNAs. We now discuss the existence of three types of seed-dependent OTEs (sOTEs). Type I involves unintended targeting through the guide strand seed of an siRNA. Type II is caused by the activity of the seed on the designated siRNA passenger strand when loaded into the RNA-induced silencing complex (RISC). Both type I and II sOTEs will elicit unpredictable cellular responses. By contrast, in sOTE type III the guide strand seed preferentially targets essential survival genes resulting in death induced by survival gene elimination (DISE). In this Opinion article, we discuss DISE as a consequence of RNAi that may preferentially affect cancer cells. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

[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.

Generation dependent cancer targeting potential of poly(propyleneimine) dendrimer.

PubMed

Kesharwani, Prashant; Tekade, Rakesh K; Jain, Narendra K

2014-07-01

Dendrimer-mediated delivery of bioactive is a successful and widely explored concept. This paper desribes comparative data pertaining to generation dependent cancer targeting propensity of Poly(propyleneimine) (PPI) dendrimers. This debut report reportsthe drug targeting and antciancer potential of different dendrimer generations. PPI dendrimers of different generations (3.0G, 4.0G and 5.0G) were synthesized and loaded with Melphalan. Results from loading, hemolysis, hematologic, cytotoxicty and flow cytometry assay depicted that as the generation of dendrimer increased from fourth to fifth, the only parameter i.e. toxicty is increased exponentionally. However, others parameters, i.e. loading, sustained release behavior, and targeting efficacy increased negligibly. Kaplan-Meier survival curves clearly depicted comparable therapeutic potential of PPI4M with PPI5M. In vivo investigations in Balb/c mice again favored 4.0G PPI dendrimer to be preferable nanocarrier for anticancer drug delivery owing to analogous anticancer potential. The outcomes of the investigation evidently projects 4.0G PPI dendrimer over 3.0G and 5.0G dendrimer in respect of its drug delivery benefit as well as superior biocompatibility. Thus, much against the common belief, 4.0G PPI dendrimers may be considered to be optimum in respect of drug delivery precluding the use of much more toxic 5.0G PPI dendrimer, which offers no benefit over 4.0G. Copyright © 2014 Elsevier Ltd. All rights reserved.

The kinetic energy operator for distance-dependent effective nuclear masses: Derivation for a triatomic molecule.

PubMed

Khoma, Mykhaylo; Jaquet, Ralph

2017-09-21

The kinetic energy operator for triatomic molecules with coordinate or distance-dependent nuclear masses has been derived. By combination of the chain rule method and the analysis of infinitesimal variations of molecular coordinates, a simple and general technique for the construction of the kinetic energy operator has been proposed. The asymptotic properties of the Hamiltonian have been investigated with respect to the ratio of the electron and proton mass. We have demonstrated that an ad hoc introduction of distance (and direction) dependent nuclear masses in Cartesian coordinates preserves the total rotational invariance of the problem. With the help of Wigner rotation functions, an effective Hamiltonian for nuclear motion can be derived. In the derivation, we have focused on the effective trinuclear Hamiltonian. All necessary matrix elements are given in closed analytical form. Preliminary results for the influence of non-adiabaticity on vibrational band origins are presented for H 3 + .

Mass-dependent Mo isotope variations in oceanic basalts - a new tracer for mantle recycling processes

NASA Astrophysics Data System (ADS)

Willbold, M.; Freymuth, H.; Hibbert, K.; Lai, Y. J.; Elliott, T.

2016-12-01

How and to what extent crustal material is recycled into the deeper mantle as a result of plate tectonic processes is a long-standing but still not fully understood question in Earth Sciences. Indirect evidence from chemical as well as radiogenic isotope data in oceanic basalts suggest that such a process may indeed have operated over much of Earth's history. Yet, uncertainties in characterising the age of the presumed recycled crustal components as well as the wide range in their chemical composition do not allow us to verify the mantle recycling hypothesis. Technological advances now enable us to explore new isotopic tracers that could shed light on this question. One of these new tools are mass-dependent isotope variation of molybdenum (Mo). Mass-dependent Mo isotope data in clastic and chemical sediments are a well-established geochemical tool to study redox conditions in the Earth's water masses over the geological past [1, 2, 3]. Being an intrinsic property of rocks exposed to the hydrosphere (see Anbar [4] for an overview), mass-dependent Mo isotope variation in mantle-derived rocks from oceanic settings could therefore be used a tracer of recycled crustal material in the Earth's mantle. In this contribution we provide a current overview over how different geological and magmatic processes - such as seawater alteration of oceanic crust, slab dehydration during plate subduction as well as magmatic emplacement - could affect the Mo isotopic composition of crustal components being transferred into the deeper mantle, as well as that of mantle melts that may contain such a recycled component. With this in mind, we explore the use of mass-dependent Mo isotope variations in mantle-derived rocks as a tracer of recycled crust in the mantle. [1] Archer & Vance (2008) Nature Geoscience 1, 597-600. [2] Barling et al. (2001) EPSL 193, 447-457. [3] Siebert et al. (2003) EPSL 211, 159-171. [4] Anbar (2004) Rev. Min. Geochem. 55, 429-454.

The VIMOS Ultra Deep Survey. Luminosity and stellar mass dependence of galaxy clustering at z 3

NASA Astrophysics Data System (ADS)

Durkalec, A.; Le Fèvre, O.; Pollo, A.; Zamorani, G.; Lemaux, B. C.; Garilli, B.; Bardelli, S.; Hathi, N.; Koekemoer, A.; Pforr, J.; Zucca, E.

2018-04-01

We present a study of the dependence of galaxy clustering on luminosity and stellar mass in the redshift range 2 < z < 3.5 using 3236 galaxies with robust spectroscopic redshifts from the VIMOS Ultra Deep Survey (VUDS), covering a total area of 0.92 deg2. We measured the two-point real-space correlation function wp(rp) for four volume-limited subsamples selected by stellar mass and four volume-limited subsamples selected by MUV absolute magnitude. We find that the scale-dependent clustering amplitude r0 significantly increases with increasing luminosity and stellar mass. For the least luminous galaxies (MUV < -19.0), we measured a correlation length r0 = 2.87 ± 0.22 h-1 Mpc and slope γ = 1.59 ± 0.07, while for the most luminous (MUV < -20.2) r0 = 5.35 ± 0.50 h-1 Mpc and γ = 1.92 ± 0.25. These measurements correspond to a strong relative bias between these two subsamples of Δb/b* = 0.43. Fitting a five-parameter halo occupation distribution (HOD) model, we find that the most luminous (MUV < -20.2) and massive (M⋆ > 1010 h-1 M⊙) galaxies occupy the most massive dark matter haloes with ⟨Mh⟩ = 1012.30 h-1 M⊙. Similar to the trends observed at lower redshift, the minimum halo mass Mmin depends on the luminosity and stellar mass of galaxies and grows from Mmin = 109.73 h-1 M⊙ to Mmin = 1011.58 h-1 M⊙ from the faintest to the brightest among our galaxy sample, respectively. We find the difference between these halo masses to be much more pronounced than is observed for local galaxies of similar properties. Moreover, at z 3, we observe that the masses at which a halo hosts, on average, one satellite and one central galaxy is M1 ≈ 4Mmin over all luminosity ranges, which is significantly lower than observed at z 0; this indicates that the halo satellite occupation increases with redshift. The luminosity and stellar mass dependence is also reflected in the measurements of the large-scale galaxy bias, which we model as bg,HOD (>L) = 1.92 + 25.36(L/L*)7

Sodium dependent multivitamin transporter (SMVT): a potential target for drug delivery.

PubMed

Vadlapudi, Aswani Dutt; Vadlapatla, Ramya Krishna; Mitra, Ashim K

2012-06-01

Sodium dependent multivitamin transporter (SMVT; product of the SLC5A6 gene) is an important transmembrane protein responsible for translocation of vitamins and other essential cofactors such as biotin, pantothenic acid and lipoic acid. Hydropathy plot (Kyte-Dolittle algorithm) revealed that human SMVT protein consists of 635 amino acids and 12 transmembrane domains with both amino and carboxyl termini oriented towards the cytoplasm. SMVT is expressed in various tissues such as placenta, intestine, brain, liver, lung, kidney, cornea, retina and heart. This transporter displays broad substrate specificity and excellent capacity for utilization in drug delivery. Drug absorption is often limited by the presence of physiological (epithelial tight junctions), biochemical (efflux transporters and enzymatic degradation) and chemical (size, lipophilicity, molecular weight, charge etc.) barriers. These barriers may cause many potential therapeutics to be dropped from the preliminary screening portfolio and subsequent entry into the market. Transporter targeted delivery has become a powerful approach to deliver drugs to target tissues because of the ability of the transporter to translocate the drug to intracellular organelles at a higher rate. This review highlights studies employing SMVT transporter as a target for drug delivery to improve bioavailability and investigate the feasibility of developing SMVT targeted drug delivery systems.

Targeted presurgical decompensation in patients with yaw-dependent facial asymmetry

PubMed Central

Kim, Kyung-A; Lee, Ji-Won; Park, Jeong-Ho; Kim, Byoung-Ho; Ahn, Hyo-Won

2017-01-01

Facial asymmetry can be classified into the rolling-dominant type (R-type), translation-dominant type (T-type), yawing-dominant type (Y-type), and atypical type (A-type) based on the distorted skeletal components that cause canting, translation, and yawing of the maxilla and/or mandible. Each facial asymmetry type represents dentoalveolar compensations in three dimensions that correspond to the main skeletal discrepancies. To obtain sufficient surgical correction, it is necessary to analyze the main skeletal discrepancies contributing to the facial asymmetry and then the skeletal-dental relationships in the maxilla and mandible separately. Particularly in cases of facial asymmetry accompanied by mandibular yawing, it is not simple to establish pre-surgical goals of tooth movement since chin deviation and posterior gonial prominence can be either aggravated or compromised according to the direction of mandibular yawing. Thus, strategic dentoalveolar decompensations targeting the real basal skeletal discrepancies should be performed during presurgical orthodontic treatment to allow for sufficient skeletal correction with stability. In this report, we document targeted decompensation of two asymmetry patients focusing on more complicated yaw-dependent types than others: Y-type and A-type. This may suggest a clinical guideline on the targeted decompensation in patient with different types of facial asymmetries. PMID:28523246

Targeted presurgical decompensation in patients with yaw-dependent facial asymmetry.

PubMed

Kim, Kyung-A; Lee, Ji-Won; Park, Jeong-Ho; Kim, Byoung-Ho; Ahn, Hyo-Won; Kim, Su-Jung

2017-05-01

Facial asymmetry can be classified into the rolling-dominant type (R-type), translation-dominant type (T-type), yawing-dominant type (Y-type), and atypical type (A-type) based on the distorted skeletal components that cause canting, translation, and yawing of the maxilla and/or mandible. Each facial asymmetry type represents dentoalveolar compensations in three dimensions that correspond to the main skeletal discrepancies. To obtain sufficient surgical correction, it is necessary to analyze the main skeletal discrepancies contributing to the facial asymmetry and then the skeletal-dental relationships in the maxilla and mandible separately. Particularly in cases of facial asymmetry accompanied by mandibular yawing, it is not simple to establish pre-surgical goals of tooth movement since chin deviation and posterior gonial prominence can be either aggravated or compromised according to the direction of mandibular yawing. Thus, strategic dentoalveolar decompensations targeting the real basal skeletal discrepancies should be performed during presurgical orthodontic treatment to allow for sufficient skeletal correction with stability. In this report, we document targeted decompensation of two asymmetry patients focusing on more complicated yaw-dependent types than others: Y-type and A-type. This may suggest a clinical guideline on the targeted decompensation in patient with different types of facial asymmetries.

The tree balance signature of mass extinction is erased by continued evolution in clades of constrained size with trait-dependent speciation

PubMed Central

Yang, Guan-Dong; Agapow, Paul-Michael

2017-01-01

The kind and duration of phylogenetic topological “signatures” left in the wake of macroevolutionary events remain poorly understood. To this end, we examined a broad range of simulated phylogenies generated using trait-biased, heritable speciation probabilities and mass extinction that could be either random or selective on trait value, but also using background extinction and diversity-dependence to constrain clade sizes. In keeping with prior results, random mass extinction increased imbalance of clades that recovered to pre-extinction size, but was a relatively weak effect. Mass extinction that was selective on trait values tended to produce clades of similar or greater balance compared to random extinction or controls. Allowing evolution to continue past the point of clade-size recovery resulted in erosion and eventual erasure of this signal, with all treatments converging on similar values of imbalance, except for very intense extinction regimes targeted at taxa with high speciation rates. Return to a more balanced state with extended post-extinction evolution was also associated with loss of the previous phylogenetic root in most treatments. These results further demonstrate that while a mass extinction event can produce a recognizable phylogenetic signal, its effects become increasingly obscured the further an evolving clade gets from that event, with any sharp imbalance due to unrelated evolutionary factors. PMID:28644846

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.

FBW7 targets KLF10 for ubiquitin-dependent degradation.

PubMed

Yu, Su; Wang, Feng; Tan, Xiao; Gao, Guo-Li; Pan, Wei-Juan; Luan, Yi; Ge, Xin

2018-01-08

FBW7, a key component of SCF FBW7 E3 ubiquitin ligase, targets various proteins for degradation via the conserved Cdc4 phosphodegron (CPD) in substrates. In this study, we report that KLF10 is degraded by FBW7 via a conserved CPD. Through systematic analysis of the degradation of KLF transcription factors by FBW7, we identified KLF10 as a novel degradation target of FBW7. Ectopic expression of FBW7 markedly promoted the degradation of KLF10 while knockdown of endogenous FBW7 increased the protein levels of KLF10. In addition, simultaneous mutations of both threonine 82 (T82) and serine 86 (S86) significantly reduced the FBW7-mediated KLF10 degradation. Moreover, KLF10 containing a conserved putative CPD (TPPXSP) from amino acids 82 to 87, directly interacted with WD40 domain of FBW7 in a phosphorylation-dependent manner. Importantly, FBW7 could reverse the KLF10-mediated inhibition of Smad7 activity. Thus, our study uncovers a novel regulatory mechanism underlying which KLF10 stability and its biological function are mediated by FBW7. Copyright © 2017 Elsevier Inc. All rights reserved.

Hα Equivalent Widths from the 3D-HST Survey: Evolution with Redshift and Dependence on Stellar Mass

NASA Astrophysics Data System (ADS)

Fumagalli, Mattia; Patel, Shannon G.; Franx, Marijn; Brammer, Gabriel; van Dokkum, Pieter; da Cunha, Elisabete; Kriek, Mariska; Lundgren, Britt; Momcheva, Ivelina; Rix, Hans-Walter; Schmidt, Kasper B.; Skelton, Rosalind E.; Whitaker, Katherine E.; Labbe, Ivo; Nelson, Erica

2012-10-01

We investigate the evolution of the Hα equivalent width, EW(Hα), with redshift and its dependence on stellar mass, using the first data from the 3D-HST survey, a large spectroscopic Treasury program with the Hubble Space Telescope Wide Field Camera 3. Combining our Hα measurements of 854 galaxies at 0.8 < z < 1.5 with those of ground-based surveys at lower and higher redshift, we can consistently determine the evolution of the EW(Hα) distribution from z = 0 to z = 2.2. We find that at all masses the characteristic EW(Hα) is decreasing toward the present epoch, and that at each redshift the EW(Hα) is lower for high-mass galaxies. We find EW(Hα) ~(1 + z)1.8 with little mass dependence. Qualitatively, this measurement is a model-independent confirmation of the evolution of star-forming galaxies with redshift. A quantitative conversion of EW(Hα) to specific star formation rate (sSFR) is model dependent because of differential reddening corrections between the continuum and the Balmer lines. The observed EW(Hα) can be reproduced with the characteristic evolutionary history for galaxies, whose star formation rises with cosmic time to z ~ 2.5 and then decreases to z = 0. This implies that EW(Hα) rises to 400 Å at z = 8. The sSFR evolves faster than EW(Hα), as the mass-to-light ratio also evolves with redshift. We find that the sSFR evolves as (1 + z)3.2, nearly independent of mass, consistent with previous reddening insensitive estimates. We confirm previous results that the observed slope of the sSFR-z relation is steeper than the one predicted by models, but models and observations agree in finding little mass dependence. Based on observations made with the NASA/ESA Hubble Space Telescope, obtained at the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., under NASA contract NAS 5-26555. These observations are associated with programs 12177, 12328.

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.

The turbulent mean-flow, Reynolds-stress, and heat flux equations in mass-averaged dependent variables

NASA Technical Reports Server (NTRS)

Rubesin, M. W.; Rose, W. C.

1973-01-01

The time-dependent, turbulent mean-flow, Reynolds stress, and heat flux equations in mass-averaged dependent variables are presented. These equations are given in conservative form for both generalized orthogonal and axisymmetric coordinates. For the case of small viscosity and thermal conductivity fluctuations, these equations are considerably simpler than the general Reynolds system of dependent variables for a compressible fluid and permit a more direct extension of low speed turbulence modeling to computer codes describing high speed turbulence fields.

First-principles X-ray absorption dose calculation for time-dependent mass and optical density.

PubMed

Berejnov, Viatcheslav; Rubinstein, Boris; Melo, Lis G A; Hitchcock, Adam P

2018-05-01

A dose integral of time-dependent X-ray absorption under conditions of variable photon energy and changing sample mass is derived from first principles starting with the Beer-Lambert (BL) absorption model. For a given photon energy the BL dose integral D(e, t) reduces to the product of an effective time integral T(t) and a dose rate R(e). Two approximations of the time-dependent optical density, i.e. exponential A(t) = c + aexp(-bt) for first-order kinetics and hyperbolic A(t) = c + a/(b + t) for second-order kinetics, were considered for BL dose evaluation. For both models three methods of evaluating the effective time integral are considered: analytical integration, approximation by a function, and calculation of the asymptotic behaviour at large times. Data for poly(methyl methacrylate) and perfluorosulfonic acid polymers measured by scanning transmission soft X-ray microscopy were used to test the BL dose calculation. It was found that a previous method to calculate time-dependent dose underestimates the dose in mass loss situations, depending on the applied exposure time. All these methods here show that the BL dose is proportional to the exposure time D(e, t) ≃ K(e)t.

Lysosomal enzyme delivery by ICAM-1-targeted nanocarriers bypassing glycosylation- and clathrin-dependent endocytosis.

PubMed

Muro, Silvia; Schuchman, Edward H; Muzykantov, Vladimir R

2006-01-01

Enzyme replacement therapy, a state-of-the-art treatment for many lysosomal storage disorders, relies on carbohydrate-mediated binding of recombinant enzymes to receptors that mediate lysosomal delivery via clathrin-dependent endocytosis. Suboptimal glycosylation of recombinant enzymes and deficiency of clathrin-mediated endocytosis in some lysosomal enzyme-deficient cells limit delivery and efficacy of enzyme replacement therapy for lysosomal disorders. We explored a novel delivery strategy utilizing nanocarriers targeted to a glycosylation- and clathrin-independent receptor, intercellular adhesion molecule (ICAM)-1, a glycoprotein expressed on diverse cell types, up-regulated and functionally involved in inflammation, a hallmark of many lysosomal disorders. We targeted recombinant human acid sphingomyelinase (ASM), deficient in types A and B Niemann-Pick disease, to ICAM-1 by loading this enzyme to nanocarriers coated with anti-ICAM. Anti-ICAM/ASM nanocarriers, but not control ASM or ASM nanocarriers, bound to ICAM-1-positive cells (activated endothelial cells and Niemann-Pick disease patient fibroblasts) via ICAM-1, in a glycosylation-independent manner. Anti-ICAM/ASM nanocarriers entered cells via CAM-mediated endocytosis, bypassing the clathrin-dependent pathway, and trafficked to lysosomes, where delivered ASM displayed stable activity and alleviated lysosomal lipid accumulation. Therefore, lysosomal enzyme targeting using nanocarriers targeted to ICAM-1 bypasses defunct pathways and may improve the efficacy of enzyme replacement therapy for lysosomal disorders, such as Niemann-Pick disease.

Mass Dependence of the HBT Radii Observed in e+e- Annihilation

NASA Astrophysics Data System (ADS)

Bialas, A.; Zalewski, K.

1999-02-01

It is shown that the recently established strong mass-dependence of the radii of the hadron sources, as observed in HBT analyses of the e+e- annihilation, can be explained by assuming a generalized inside--outside cascade, i.e. that (i) the four-momenta and the space-time position four-vectors of the produced particles are approximately proportional to each other and (ii) the ``freeze-out'' times are distributed along the hyperbola t2-z2= τ02.

Subcellular targeting of nine calcium-dependent protein kinase isoforms from Arabidopsis

NASA Technical Reports Server (NTRS)

Dammann, Christian; Ichida, Audrey; Hong, Bimei; Romanowsky, Shawn M.; Hrabak, Estelle M.; Harmon, Alice C.; Pickard, Barbara G.; Harper, Jeffrey F.; Evans, M. L. (Principal Investigator)

2003-01-01

Calcium-dependent protein kinases (CDPKs) are specific to plants and some protists. Their activation by calcium makes them important switches for the transduction of intracellular calcium signals. Here, we identify the subcellular targeting potentials for nine CDPK isoforms from Arabidopsis, as determined by expression of green fluorescent protein (GFP) fusions in transgenic plants. Subcellular locations were determined by fluorescence microscopy in cells near the root tip. Isoforms AtCPK3-GFP and AtCPK4-GFP showed a nuclear and cytosolic distribution similar to that of free GFP. Membrane fractionation experiments confirmed that these isoforms were primarily soluble. A membrane association was observed for AtCPKs 1, 7, 8, 9, 16, 21, and 28, based on imaging and membrane fractionation experiments. This correlates with the presence of potential N-terminal acylation sites, consistent with acylation as an important factor in membrane association. All but one of the membrane-associated isoforms targeted exclusively to the plasma membrane. The exception was AtCPK1-GFP, which targeted to peroxisomes, as determined by covisualization with a peroxisome marker. Peroxisome targeting of AtCPK1-GFP was disrupted by a deletion of two potential N-terminal acylation sites. The observation of a peroxisome-located CDPK suggests a mechanism for calcium regulation of peroxisomal functions involved in oxidative stress and lipid metabolism.

Targeting neuronal activity-regulated neuroligin-3 dependency in high-grade glioma.

PubMed

Venkatesh, Humsa S; Tam, Lydia T; Woo, Pamelyn J; Lennon, James; Nagaraja, Surya; Gillespie, Shawn M; Ni, Jing; Duveau, Damien Y; Morris, Patrick J; Zhao, Jean J; Thomas, Craig J; Monje, Michelle

2017-09-28

High-grade gliomas (HGG) are a devastating group of cancers, and represent the leading cause of brain tumour-related death in both children and adults. Therapies aimed at mechanisms intrinsic to glioma cells have translated to only limited success; effective therapeutic strategies will need also to target elements of the tumour microenvironment that promote glioma progression. Neuronal activity promotes the growth of a range of molecularly and clinically distinct HGG types, including adult and paediatric glioblastoma (GBM), anaplastic oligodendroglioma, and diffuse intrinsic pontine glioma (DIPG). An important mechanism that mediates this neural regulation of brain cancer is activity-dependent cleavage and secretion of the synaptic adhesion molecule neuroligin-3 (NLGN3), which promotes glioma proliferation through the PI3K-mTOR pathway. However, the necessity of NLGN3 for glioma growth, the proteolytic mechanism of NLGN3 secretion, and the further molecular consequences of NLGN3 secretion in glioma cells remain unknown. Here we show that HGG growth depends on microenvironmental NLGN3, identify signalling cascades downstream of NLGN3 binding in glioma, and determine a therapeutically targetable mechanism of secretion. Patient-derived orthotopic xenografts of paediatric GBM, DIPG and adult GBM fail to grow in Nlgn3 knockout mice. NLGN3 stimulates several oncogenic pathways, such as early focal adhesion kinase activation upstream of PI3K-mTOR, and induces transcriptional changes that include upregulation of several synapse-related genes in glioma cells. NLGN3 is cleaved from both neurons and oligodendrocyte precursor cells via the ADAM10 sheddase. ADAM10 inhibitors prevent the release of NLGN3 into the tumour microenvironment and robustly block HGG xenograft growth. This work defines a promising strategy for targeting NLGN3 secretion, which could prove transformative for HGG therapy.

Targeting neuronal activity-regulated neuroligin-3 dependency in high-grade glioma

PubMed Central

Venkatesh, Humsa S.; Tam, Lydia T.; Woo, Pamelyn J.; Lennon, James; Nagaraja, Surya; Gillespie, Shawn M.; Ni, Jing; Duveau, Damien Y.; Morris, Patrick J.; Zhao, Jean J.; Thomas, Craig J.; Monje, Michelle

2017-01-01

Summary High-grade gliomas (HGG) are a devastating group of cancers, representing the leading cause of brain tumor-related death in both children and adults. Therapies aimed at mechanisms intrinsic to the glioma cell have translated to only limited success; effective therapeutic strategies will need to also target elements of the tumor microenvironment that promote glioma progression. We recently demonstrated that neuronal activity robustly promotes the growth of a range of molecularly and clinically distinct HGG types, including adult glioblastoma (GBM), anaplastic oligodendroglioma, pediatric GBM, and diffuse intrinsic pontine glioma (DIPG)1. An important mechanism mediating this neural regulation of brain cancer is activity-dependent cleavage and secretion of the synaptic molecule neuroligin-3 (NLGN3), which promotes glioma proliferation through the PI3K-mTOR pathway1. However, neuroligin-3 necessity to glioma growth, proteolytic mechanism of secretion and further molecular consequences in glioma remain to be clarified. Here, we demonstrate a striking dependence of HGG growth on microenvironmental neuroligin-3, elucidate signaling cascades downstream of neuroligin-3 binding in glioma and determine a therapeutically targetable mechanism of secretion. Patient-derived orthotopic xenografts of pediatric GBM, DIPG and adult GBM fail to grow in Nlgn3 knockout mice. Neuroligin-3 stimulates numerous oncogenic pathways, including early focal adhesion kinase activation upstream of PI3K-mTOR, and induces transcriptional changes including upregulation of numerous synapse-related genes in glioma cells. Neuroligin-3 is cleaved from both neurons and oligodendrocyte precursor cells via the ADAM10 sheddase. ADAM10 inhibitors prevent release of neuroligin-3 into the tumor microenvironment and robustly block HGG xenograft growth. This work defines a promising strategy for targeting neuroligin-3 secretion, which could prove transformative for HGG therapy. PMID:28959975

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.

Evaluating the potential for secondary mass savings in vehicle lightweighting.

PubMed

Alonso, Elisa; Lee, Theresa M; Bjelkengren, Catarina; Roth, Richard; Kirchain, Randolph E

2012-03-06

Secondary mass savings are mass reductions that may be achieved in supporting (load-bearing) vehicle parts when the gross vehicle mass (GVM) is reduced. Mass decompounding is the process by which it is possible to identify further reductions when secondary mass savings result in further reduction of GVM. Maximizing secondary mass savings (SMS) is a key tool for maximizing vehicle fuel economy. In today's industry, the most complex parts, which require significant design detail (and cost), are designed first and frozen while the rest of the development process progresses. This paper presents a tool for estimating SMS potential early in the design process and shows how use of the tool to set SMS targets early, before subsystems become locked in, maximizes mass savings. The potential for SMS in current passenger vehicles is estimated with an empirical model using engineering analysis of vehicle components to determine mass-dependency. Identified mass-dependent components are grouped into subsystems, and linear regression is performed on subsystem mass as a function of GVM. A Monte Carlo simulation is performed to determine the mean and 5th and 95th percentiles for the SMS potential per kilogram of primary mass saved. The model projects that the mean theoretical secondary mass savings potential is 0.95 kg for every 1 kg of primary mass saved, with the 5th percentile at 0.77 kg/kg when all components are available for redesign. The model was used to explore an alternative scenario where realistic manufacturing and design limitations were implemented. In this case study, four key subsystems (of 13 total) were locked-in and this reduced the SMS potential to a mean of 0.12 kg/kg with a 5th percentile of 0.1 kg/kg. Clearly, to maximize the impact of mass reduction, targets need to be established before subsystems become locked in.

Target distance-dependent variation of hearing sensitivity during echolocation in a false killer whale.

PubMed

Supin, Alexander Ya; Nachtigall, Paul E; Breese, Marlee

2010-06-01

Evidence of varying hearing sensitivity according to the target distance was obtained in a false killer whale Pseudorca crassidens during echolocation. Auditory evoked potentials (AEPs) triggered by echolocation clicks were recorded. The target distance varied from 1 to 6 m. The records contained AEPs to the self-heard emitted click and AEPs to the echoes. Mean level of echolocation clicks depended on distance (the longer the distance, the higher the click level), however, the effect of click level on AEP amplitude was eliminated by extracting AEPs to clicks of certain particular levels. The amplitude of the echo-provoked AEP was almost independent of distance, however, the amplitude of the AEP to the emitted click, did depend on distance within a range from 1 to 4 m: the longer the distance, the higher the amplitude. The latter result is interpreted as confirmational evidence that the animal is capable of varying hearing sensitivity according to target distance. The variation of hearing sensitivity may help to compensate for the echo attenuation with distance; as a secondary effect, this variation manifested itself in a variation of the amplitude of the AEP to emitted clicks.

Higgs Boson Pair Production in Gluon Fusion at Next-to-Leading Order with Full Top-Quark Mass Dependence.

PubMed

Borowka, S; Greiner, N; Heinrich, G; Jones, S P; Kerner, M; Schlenk, J; Schubert, U; Zirke, T

2016-07-01

We present the calculation of the cross section and invariant mass distribution for Higgs boson pair production in gluon fusion at next-to-leading order (NLO) in QCD. Top-quark masses are fully taken into account throughout the calculation. The virtual two-loop amplitude has been generated using an extension of the program GoSam supplemented with an interface to Reduze for the integral reduction. The occurring integrals have been calculated numerically using the program SecDec. Our results, including the full top-quark mass dependence for the first time, allow us to assess the validity of various approximations proposed in the literature, which we also recalculate. We find substantial deviations between the NLO result and the different approximations, which emphasizes the importance of including the full top-quark mass dependence at NLO.

The 6dF Galaxy Survey: dependence of halo occupation on stellar mass

NASA Astrophysics Data System (ADS)

Beutler, Florian; Blake, Chris; Colless, Matthew; Jones, D. Heath; Staveley-Smith, Lister; Campbell, Lachlan; Parker, Quentin; Saunders, Will; Watson, Fred

2013-03-01

In this paper we study the stellar mass dependence of galaxy clustering in the 6dF Galaxy Survey (6dFGS). The near-infrared selection of 6dFGS allows more reliable stellar mass estimates compared to optical bands used in other galaxy surveys. Using the halo occupation distribution model, we investigate the trend of dark matter halo mass and satellite fraction with stellar mass by measuring the projected correlation function, wp(rp). We find that the typical halo mass (M1) as well as the satellite power-law index (α) increases with stellar mass. This indicates (1) that galaxies with higher stellar mass sit in more massive dark matter haloes and (2) that these more massive dark matter haloes accumulate satellites faster with growing mass compared to haloes occupied by low stellar mass galaxies. Furthermore, we find a relation between M1 and the minimum dark matter halo mass (Mmin) of M1 ≈ 22 Mmin, in agreement with similar findings for Sloan Digital Sky Survey galaxies. The satellite fraction of 6dFGS galaxies declines with increasing stellar mass from 21 per cent at Mstellar = 2.6 × 1010 h-2 M⊙ to 12 per cent at Mstellar = 5.4 × 1010 h-2 M⊙ indicating that high stellar mass galaxies are more likely to be central galaxies. We compare our results to two different semi-analytic models derived from the Millennium Simulation, finding some disagreement. Our results can be used for placing new constraints on semi-analytic models in the future, particularly the behaviour of luminous red satellites. Finally, we compare our results to studies of halo occupation using galaxy-galaxy weak lensing. We find good overall agreement, representing a valuable cross-check for these two different tools of studying the matter distribution in the Universe.

Radiatively induced neutrino mass model with flavor dependent gauge symmetry

NASA Astrophysics Data System (ADS)

Lee, SangJong; Nomura, Takaaki; Okada, Hiroshi

2018-06-01

We study a radiative seesaw model at one-loop level with a flavor dependent gauge symmetry U(1) μ - τ, in which we consider bosonic dark matter. We also analyze the constraints from lepton flavor violations, muon g - 2, relic density of dark matter, and collider physics, and carry out numerical analysis to search for allowed parameter region which satisfy all the constraints and to investigate some predictions. Furthermore we find that a simple but adhoc hypothesis induces specific two zero texture with inverse mass matrix, which provides us several predictions such as a specific pattern of Dirac CP phase.

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...

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.

Tumor cell membrane-targeting pH-dependent electron donor-acceptor fluorescence systems with low background signals.

PubMed

Han, Liang; Liu, Mingming; Ye, Deyong; Zhang, Ning; Lim, Ed; Lu, Jing; Jiang, Chen

2014-03-01

Minimizing the background signal is crucial for developing tumor-imaging techniques with sufficient specificity and sensitivity. Here we use pH difference between healthy tissues and tumor and tumor targeting delivery to achieve this goal. We synthesize fluorophore-dopamine conjugate as pH-dependent electron donor-acceptor fluorescence system. Fluorophores are highly sensitive to electron-transfer processes, which can alter their optical properties. The intrinsic redox properties of dopamine are oxidation of hydroquinone to quinone at basic pH and reduction of quinone to hydroquinone at acidic pH. Quinone can accept electron then quench fluorescence. We design tumor cell membrane-targeting carrier for delivery. We demonstrate quenched fluorophore-quinone can be specially transferred to tumor extracellular environment and tumor-accumulated fluorophore can be activated by acidic pH. These tumor-targeting pH-dependent electron donor-acceptor fluorescence systems may offer new opportunity for developing tumor-imaging techniques. Copyright © 2014 Elsevier Ltd. All rights reserved.

The dependence of galaxy clustering on stellar mass, star-formation rate and redshift at z = 0.8-2.2, with HiZELS

NASA Astrophysics Data System (ADS)

Cochrane, R. K.; Best, P. N.; Sobral, D.; Smail, I.; Geach, J. E.; Stott, J. P.; Wake, D. A.

2018-04-01

The deep, near-infrared narrow-band survey HiZELS has yielded robust samples of H α-emitting star-forming galaxies within narrow redshift slices at z = 0.8, 1.47 and 2.23. In this paper, we distinguish the stellar mass and star-formation rate (SFR) dependence of the clustering of these galaxies. At high stellar masses (M*/M⊙ ≳ 2 × 1010), where HiZELS selects galaxies close to the so-called star-forming main sequence, the clustering strength is observed to increase strongly with stellar mass (in line with the results of previous studies of mass-selected galaxy samples) and also with SFR. These two dependencies are shown to hold independently. At lower stellar masses, however, where HiZELS probes high specific SFR galaxies, there is little or no dependence of the clustering strength on stellar mass, but the dependence on SFR remains: high-SFR low-mass galaxies are found in more massive dark matter haloes than their lower SFR counterparts. We argue that this is due to environmentally driven star formation in these systems. We apply the same selection criteria to the EAGLE cosmological hydrodynamical simulations. We find that, in EAGLE, the high-SFR low-mass galaxies are central galaxies in more massive dark matter haloes, in which the high SFRs are driven by a (halo-driven) increased gas content.

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

Parkin loss leads to PARIS-dependent declines in mitochondrial mass and respiration

PubMed Central

Stevens, Daniel A.; Lee, Yunjong; Kang, Ho Chul; Lee, Byoung Dae; Lee, Yun-Il; Bower, Aaron; Jiang, Haisong; Kang, Sung-Ung; Andrabi, Shaida A.; Dawson, Valina L.; Shin, Joo-Ho; Dawson, Ted M.

2015-01-01

Mutations in parkin lead to early-onset autosomal recessive Parkinson’s disease (PD) and inactivation of parkin is thought to contribute to sporadic PD. Adult knockout of parkin in the ventral midbrain of mice leads to an age-dependent loss of dopamine neurons that is dependent on the accumulation of parkin interacting substrate (PARIS), zinc finger protein 746 (ZNF746), and its transcriptional repression of PGC-1α. Here we show that adult knockout of parkin in mouse ventral midbrain leads to decreases in mitochondrial size, number, and protein markers consistent with a defect in mitochondrial biogenesis. This decrease in mitochondrial mass is prevented by short hairpin RNA knockdown of PARIS. PARIS overexpression in mouse ventral midbrain leads to decreases in mitochondrial number and protein markers and PGC-1α–dependent deficits in mitochondrial respiration. Taken together, these results suggest that parkin loss impairs mitochondrial biogenesis, leading to declining function of the mitochondrial pool and cell death. PMID:26324925

An inclusive SUSY approach to position dependent mass systems

NASA Astrophysics Data System (ADS)

Karthiga, S.; Chithiika Ruby, V.; Senthilvelan, M.

2018-06-01

The supersymmetry (SUSY) formalism for a position dependent mass problem with a more general ordering is yet to be formulated. In this paper, we present an unified SUSY approach for PDM problems of any ordering. Highlighting all non-Hermitian Hamiltonians of PDM problems are of quasi-Hermitian nature, the SUSY operators of these problems are constructed using similarity transformation. The methodology that we propose here is applicable for even more general cases where the kinetic energy term is represented by linear combination of infinite number of possible orderings. We illustrate the method with an example, namely Mathews-Lakshmanan (ML) oscillator. Our results show that the latter system is shape invariant for all possible orderings. We derive eigenvalues and eigenvectors of this nonlinear oscillator for all possible orderings including Hermitian and non-Hermitian ones.

Mass dependence of Higgs boson production at large transverse momentum through a bottom-quark loop

NASA Astrophysics Data System (ADS)

Braaten, Eric; Zhang, Hong; Zhang, Jia-Wei

2018-05-01

In the production of the Higgs through a bottom-quark loop, the transverse momentum distribution of the Higgs at large PT is complicated by its dependence on two other important scales: the bottom quark mass mb and the Higgs mass mH. A strategy for simplifying the calculation of the cross section at large PT is to calculate only the leading terms in its expansion in mb2/PT2. In this paper, we consider the bottom-quark-loop contribution to the parton process q q ¯→H +g at leading order in αs. We show that the leading power of 1 /PT2 can be expressed in the form of a factorization formula that separates the large scale PT from the scale of the masses. All the dependence on mb and mH can be factorized into a distribution amplitude for b b ¯ in the Higgs, a distribution amplitude for b b ¯ in a real gluon, and an end point contribution. The factorization formula can be used to organize the calculation of the leading terms in the expansion in mb2/PT2 so that every calculation involves at most two scales.

Mitochondria-targeted ubiquinone (MitoQ) decreases ethanol-dependent micro and macro hepatosteatosis.

PubMed

Chacko, Balu K; Srivastava, Anup; Johnson, Michelle S; Benavides, Gloria A; Chang, Mi Jung; Ye, Yaozu; Jhala, Nirag; Murphy, Michael P; Kalyanaraman, Balaraman; Darley-Usmar, Victor M

2011-07-01

Chronic alcohol-induced liver disease results in inflammation, steatosis, and increased oxidative and nitrosative damage to the mitochondrion. We hypothesized that targeting an antioxidant to the mitochondria would prevent oxidative damage and attenuate the steatosis associated with alcoholic liver disease. To test this we investigated the effects of mitochondria-targeted ubiquinone (MitoQ) (5 and 25 mg/kg/day for 4 weeks) in male Sprague-Dawley rats consuming ethanol using the Lieber-DeCarli diet with pair-fed controls. Hepatic steatosis, 3-nitrotyrosine (3-NT), 4-hydroxynonenal (4-HNE), hypoxia inducible factor α (HIF1α), and the activity of the mitochondrial respiratory chain complexes were assessed. As reported previously, ethanol consumption resulted in hepatocyte ballooning, increased lipid accumulation in the form of micro and macrovesicular steatosis, and induction of cytochrome P450 2E1 (CYP2E1). MitoQ had a minor effect on the ethanol-dependent decrease in mitochondrial respiratory chain proteins and their activities; however, it did decrease hepatic steatosis in ethanol-consuming animals and prevented the ethanol-induced formation of 3-NT and 4-HNE. Interestingly, MitoQ completely blocked the increase in HIF1α in all ethanol-fed groups, which has previously been demonstrated in cell culture models and shown to be essential in ethanol-dependent hepatosteatosis. These results demonstrate the antioxidant capacity of MitoQ in alleviating alcohol-associated mitochondrial reactive oxygen species (ROS) and several downstream effects of ROS/RNS (reactive nitrogen species) production such as inhibiting protein nitration and protein aldehyde formation and specifically ROS-dependent HIF1α stabilization. Copyright © 2011 American Association for the Study of Liver Diseases.

Equation of state for nucleonic matter and its quark mass dependence from the nuclear force in lattice QCD.

PubMed

Inoue, Takashi; Aoki, Sinya; Doi, Takumi; Hatsuda, Tetsuo; Ikeda, Yoichi; Ishii, Noriyoshi; Murano, Keiko; Nemura, Hidekatsu; Sasaki, Kenji

2013-09-13

Quark mass dependence of the equation of state (EOS) for nucleonic matter is investigated, on the basis of the Brueckner-Hartree-Fock method with the nucleon-nucleon interaction extracted from lattice QCD simulations. We observe saturation of nuclear matter at the lightest available quark mass corresponding to the pseudoscalar meson mass ≃469  MeV. Mass-radius relation of the neutron stars is also studied with the EOS for neutron-star matter from the same nuclear force in lattice QCD. We observe that the EOS becomes stiffer and thus the maximum mass of neutron star increases as the quark mass decreases toward the physical point.

Improvement of Characteristics of Laser Source of Ions Using Two-Element Targets

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

Khaydarov, R. T.

2006-12-04

Two-element plasma ions generated from porous (Ho2O3) and solid (PbMg) targets were studied depending on the target density {rho} and on the fraction of light (Mg) component of the target, using a mass-spectrometer. Oxygen ions with maximal charge is observed for small values of {rho}, while the heavy component of the target Ho has maximal charge for larger values of {rho}. The influence of {rho} to the energy spectra and intensity of plasma ions is also investigated. In the case of solid (PbMg) target the increase of the fraction of Mg leads to the widening of the energy spectra ofmore » Pb ions by more than a factor of two, while the intensity of Pb ions of all charge states does not depend on the Mg fraction. These effects are explained by the friction existing between light and heavy ions during their expansion away from the target.« less

Comprehensive Analyses of Ventricular Myocyte Models Identify Targets Exhibiting Favorable Rate Dependence

PubMed Central

Bugana, Marco; Severi, Stefano; Sobie, Eric A.

2014-01-01

Reverse rate dependence is a problematic property of antiarrhythmic drugs that prolong the cardiac action potential (AP). The prolongation caused by reverse rate dependent agents is greater at slow heart rates, resulting in both reduced arrhythmia suppression at fast rates and increased arrhythmia risk at slow rates. The opposite property, forward rate dependence, would theoretically overcome these parallel problems, yet forward rate dependent (FRD) antiarrhythmics remain elusive. Moreover, there is evidence that reverse rate dependence is an intrinsic property of perturbations to the AP. We have addressed the possibility of forward rate dependence by performing a comprehensive analysis of 13 ventricular myocyte models. By simulating populations of myocytes with varying properties and analyzing population results statistically, we simultaneously predicted the rate-dependent effects of changes in multiple model parameters. An average of 40 parameters were tested in each model, and effects on AP duration were assessed at slow (0.2 Hz) and fast (2 Hz) rates. The analysis identified a variety of FRD ionic current perturbations and generated specific predictions regarding their mechanisms. For instance, an increase in L-type calcium current is FRD when this is accompanied by indirect, rate-dependent changes in slow delayed rectifier potassium current. A comparison of predictions across models identified inward rectifier potassium current and the sodium-potassium pump as the two targets most likely to produce FRD AP prolongation. Finally, a statistical analysis of results from the 13 models demonstrated that models displaying minimal rate-dependent changes in AP shape have little capacity for FRD perturbations, whereas models with large shape changes have considerable FRD potential. This can explain differences between species and between ventricular cell types. Overall, this study provides new insights, both specific and general, into the determinants of AP duration

Comprehensive analyses of ventricular myocyte models identify targets exhibiting favorable rate dependence.

PubMed

Cummins, Megan A; Dalal, Pavan J; Bugana, Marco; Severi, Stefano; Sobie, Eric A

2014-03-01

Reverse rate dependence is a problematic property of antiarrhythmic drugs that prolong the cardiac action potential (AP). The prolongation caused by reverse rate dependent agents is greater at slow heart rates, resulting in both reduced arrhythmia suppression at fast rates and increased arrhythmia risk at slow rates. The opposite property, forward rate dependence, would theoretically overcome these parallel problems, yet forward rate dependent (FRD) antiarrhythmics remain elusive. Moreover, there is evidence that reverse rate dependence is an intrinsic property of perturbations to the AP. We have addressed the possibility of forward rate dependence by performing a comprehensive analysis of 13 ventricular myocyte models. By simulating populations of myocytes with varying properties and analyzing population results statistically, we simultaneously predicted the rate-dependent effects of changes in multiple model parameters. An average of 40 parameters were tested in each model, and effects on AP duration were assessed at slow (0.2 Hz) and fast (2 Hz) rates. The analysis identified a variety of FRD ionic current perturbations and generated specific predictions regarding their mechanisms. For instance, an increase in L-type calcium current is FRD when this is accompanied by indirect, rate-dependent changes in slow delayed rectifier potassium current. A comparison of predictions across models identified inward rectifier potassium current and the sodium-potassium pump as the two targets most likely to produce FRD AP prolongation. Finally, a statistical analysis of results from the 13 models demonstrated that models displaying minimal rate-dependent changes in AP shape have little capacity for FRD perturbations, whereas models with large shape changes have considerable FRD potential. This can explain differences between species and between ventricular cell types. Overall, this study provides new insights, both specific and general, into the determinants of AP duration

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

NASA Astrophysics Data System (ADS)

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

2018-04-01

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

Quantum solvability of a general ordered position dependent mass system: Mathews-Lakshmanan oscillator

NASA Astrophysics Data System (ADS)

Karthiga, S.; Chithiika Ruby, V.; Senthilvelan, M.; Lakshmanan, M.

2017-10-01

In position dependent mass (PDM) problems, the quantum dynamics of the associated systems have been understood well in the literature for particular orderings. However, no efforts seem to have been made to solve such PDM problems for general orderings to obtain a global picture. In this connection, we here consider the general ordered quantum Hamiltonian of an interesting position dependent mass problem, namely, the Mathews-Lakshmanan oscillator, and try to solve the quantum problem for all possible orderings including Hermitian and non-Hermitian ones. The other interesting point in our study is that for all possible orderings, although the Schrödinger equation of this Mathews-Lakshmanan oscillator is uniquely reduced to the associated Legendre differential equation, their eigenfunctions cannot be represented in terms of the associated Legendre polynomials with integral degree and order. Rather the eigenfunctions are represented in terms of associated Legendre polynomials with non-integral degree and order. We here explore such polynomials and represent the discrete and continuum states of the system. We also exploit the connection between associated Legendre polynomials with non-integral degree with other orthogonal polynomials such as Jacobi and Gegenbauer polynomials.

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

Targeted, activity-dependent spinal stimulation produces long-lasting motor recovery in chronic cervical spinal cord injury

PubMed Central

McPherson, Jacob G.; Miller, Robert R.; Perlmutter, Steve I.

2015-01-01

Use-dependent movement therapies can lead to partial recovery of motor function after neurological injury. We attempted to improve recovery by developing a neuroprosthetic intervention that enhances movement therapy by directing spike timing-dependent plasticity in spared motor pathways. Using a recurrent neural–computer interface in rats with a cervical contusion of the spinal cord, we synchronized intraspinal microstimulation below the injury with the arrival of functionally related volitional motor commands signaled by muscle activity in the impaired forelimb. Stimulation was delivered during physical retraining of a forelimb behavior and throughout the day for 3 mo. Rats receiving this targeted, activity-dependent spinal stimulation (TADSS) exhibited markedly enhanced recovery compared with animals receiving targeted but open-loop spinal stimulation and rats receiving physical retraining alone. On a forelimb reach and grasp task, TADSS animals recovered 63% of their preinjury ability, more than two times the performance level achieved by the other therapy groups. Therapeutic gains were maintained for 3 additional wk without stimulation. The results suggest that activity-dependent spinal stimulation can induce neural plasticity that improves behavioral recovery after spinal cord injury. PMID:26371306

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

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.

Unbiased Inference of the Masses of Transiting Planets from Radial Velocity Follow-up

NASA Astrophysics Data System (ADS)

Montet, Benjamin T.

2018-05-01

Data from the TESS mission will be used to discover hundreds of small planets amenable to radial velocity (RV) followup. Often, RV observations are obtained until a particular fractional precision on the inferred mass is achieved. I show that when the decision to stop collecting RV observations depends on the mass inferred from already-collected data, this will bias mass measurements upward, particularly when the fixed length of RV observing campaigns is considered. I suggest that observing teams should determine their observing strategy for each star before any data are collected, and all stopping criteria should not directly depend on the inferred mass. Observing teams should explicitly publish both their criteria for observing targets and deciding to end their observations, as well as their mass non-detections to avoid introducing biases into the masses---and thus inferences on the densities, compositions, and atmospheres---of transiting planets.

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.

THE EVOLUTION OF THE STELLAR MASS FUNCTION OF GALAXIES FROM z = 4.0 AND THE FIRST COMPREHENSIVE ANALYSIS OF ITS UNCERTAINTIES: EVIDENCE FOR MASS-DEPENDENT EVOLUTION

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

Marchesini, Danilo; Van Dokkum, Pieter G.; Foerster Schreiber, Natascha M.

2009-08-20

We present the evolution of the stellar mass function (SMF) of galaxies from z = 4.0 to z = 1.3 measured from a sample constructed from the deep near-infrared Multi-wavelength Survey by Yale-Chile, the Faint Infrared Extragalactic Survey, and the Great Observatories Origins Deep Survey-Chandra Deep Field South surveys, all having very high-quality optical to mid-infrared data. This sample, unique in that it combines data from surveys with a large range of depths and areas in a self-consistent way, allowed us to (1) minimize the uncertainty due to cosmic variance and empirically quantify its contribution to the total error budget;more » (2) simultaneously probe the high-mass end and the low-mass end (down to {approx}0.05 times the characteristic stellar mass) of the SMF with good statistics; and (3) empirically derive the redshift-dependent completeness limits in stellar mass. We provide, for the first time, a comprehensive analysis of random and systematic uncertainties affecting the derived SMFs, including the effect of metallicity, extinction law, stellar population synthesis model, and initial mass function. We find that the mass density evolves by a factor of {approx}17{sup +7}{sub -10} since z = 4.0, mostly driven by a change in the normalization {phi}*. If only random errors are taken into account, we find evidence for mass-dependent evolution, with the low-mass end evolving more rapidly than the high-mass end. However, we show that this result is no longer robust when systematic uncertainties due to the SED-modeling assumptions are taken into account. Another significant uncertainty is the contribution to the overall stellar mass density of galaxies below our mass limit; future studies with WFC3 will provide better constraints on the SMF at masses below 10{sup 10} M{sub sun} at z>2. Taking our results at face value, we find that they are in conflict with semianalytic models of galaxy formation. The models predict SMFs that are in general too steep, with

mTOR target NDRG1 confers MGMT-dependent resistance to alkylating chemotherapy.

PubMed

Weiler, Markus; Blaes, Jonas; Pusch, Stefan; Sahm, Felix; Czabanka, Marcus; Luger, Sebastian; Bunse, Lukas; Solecki, Gergely; Eichwald, Viktoria; Jugold, Manfred; Hodecker, Sibylle; Osswald, Matthias; Meisner, Christoph; Hielscher, Thomas; Rübmann, Petra; Pfenning, Philipp-Niklas; Ronellenfitsch, Michael; Kempf, Tore; Schnölzer, Martina; Abdollahi, Amir; Lang, Florian; Bendszus, Martin; von Deimling, Andreas; Winkler, Frank; Weller, Michael; Vajkoczy, Peter; Platten, Michael; Wick, Wolfgang

2014-01-07

A hypoxic microenvironment induces resistance to alkylating agents by activating targets in the mammalian target of rapamycin (mTOR) pathway. The molecular mechanisms involved in this mTOR-mediated hypoxia-induced chemoresistance, however, are unclear. Here we identify the mTOR target N-myc downstream regulated gene 1 (NDRG1) as a key determinant of resistance toward alkylating chemotherapy, driven by hypoxia but also by therapeutic measures such as irradiation, corticosteroids, and chronic exposure to alkylating agents via distinct molecular routes involving hypoxia-inducible factor (HIF)-1alpha, p53, and the mTOR complex 2 (mTORC2)/serum glucocorticoid-induced protein kinase 1 (SGK1) pathway. Resistance toward alkylating chemotherapy but not radiotherapy was dependent on NDRG1 expression and activity. In posttreatment tumor tissue of patients with malignant gliomas, NDRG1 was induced and predictive of poor response to alkylating chemotherapy. On a molecular level, NDRG1 bound and stabilized methyltransferases, chiefly O(6)-methylguanine-DNA methyltransferase (MGMT), a key enzyme for resistance to alkylating agents in glioblastoma patients. In patients with glioblastoma, MGMT promoter methylation in tumor tissue was not more predictive for response to alkylating chemotherapy in patients who received concomitant corticosteroids.

mTOR target NDRG1 confers MGMT-dependent resistance to alkylating chemotherapy

PubMed Central

Weiler, Markus; Blaes, Jonas; Pusch, Stefan; Sahm, Felix; Czabanka, Marcus; Luger, Sebastian; Bunse, Lukas; Solecki, Gergely; Eichwald, Viktoria; Jugold, Manfred; Hodecker, Sibylle; Osswald, Matthias; Meisner, Christoph; Hielscher, Thomas; Rübmann, Petra; Pfenning, Philipp-Niklas; Ronellenfitsch, Michael; Kempf, Tore; Schnölzer, Martina; Abdollahi, Amir; Lang, Florian; Bendszus, Martin; von Deimling, Andreas; Winkler, Frank; Weller, Michael; Vajkoczy, Peter; Platten, Michael; Wick, Wolfgang

2014-01-01

A hypoxic microenvironment induces resistance to alkylating agents by activating targets in the mammalian target of rapamycin (mTOR) pathway. The molecular mechanisms involved in this mTOR-mediated hypoxia-induced chemoresistance, however, are unclear. Here we identify the mTOR target N-myc downstream regulated gene 1 (NDRG1) as a key determinant of resistance toward alkylating chemotherapy, driven by hypoxia but also by therapeutic measures such as irradiation, corticosteroids, and chronic exposure to alkylating agents via distinct molecular routes involving hypoxia-inducible factor (HIF)-1alpha, p53, and the mTOR complex 2 (mTORC2)/serum glucocorticoid-induced protein kinase 1 (SGK1) pathway. Resistance toward alkylating chemotherapy but not radiotherapy was dependent on NDRG1 expression and activity. In posttreatment tumor tissue of patients with malignant gliomas, NDRG1 was induced and predictive of poor response to alkylating chemotherapy. On a molecular level, NDRG1 bound and stabilized methyltransferases, chiefly O6-methylguanine-DNA methyltransferase (MGMT), a key enzyme for resistance to alkylating agents in glioblastoma patients. In patients with glioblastoma, MGMT promoter methylation in tumor tissue was not more predictive for response to alkylating chemotherapy in patients who received concomitant corticosteroids. PMID:24367102

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

Superconductivity in an almost localized Fermi liquid of quasiparticles with spin-dependent masses and effective-field induced by electron correlations

NASA Astrophysics Data System (ADS)

Kaczmarczyk, Jan; Spałek, Jozef

2009-06-01

Paired state of nonstandard quasiparticles is analyzed in detail in two model situations. Namely, we consider the Cooper-pair bound state and the condensed phase of an almost localized Fermi liquid composed of quasiparticles in a narrow band with the spin-dependent masses and an effective field, both introduced earlier and induced by strong electronic correlations. Each of these novel characteristics is calculated in a self-consistent manner. We analyze the bound states as a function of Cooper-pair momentum |Q| in applied magnetic field in the strongly Pauli limiting case (i.e., when the orbital effects of applied magnetic field are disregarded). The spin-direction dependence of the effective mass makes the quasiparticles comprising Cooper-pair spin distinguishable in the quantum-mechanical sense, whereas the condensed gas of pairs may still be regarded as composed of identical entities. The Fulde-Ferrell-Larkin-Ovchinnikov (FFLO) condensed phase of moving pairs is by far more robust in the applied field for the case with spin-dependent masses than in the situation with equal masses of quasiparticles. Relative stability of the Bardeen-Cooper-Schrieffer vs FFLO phase is analyzed in detail on temperature-applied field plane. Although our calculations are carried out for a model situation, we can conclude that the spin-dependent masses should play an important role in stabilizing high-field low-temperature unconventional superconducting phases (FFLO, for instance) in systems such as CeCoIn5 , organic metals, and possibly others.

Mass and Magnetic Field Dependence of Electrostatic Particle Transport and Turbulence in LAPD-U

NASA Astrophysics Data System (ADS)

Crocker, N. A.; Gilmore, M.; Peebles, W. A.; Will, S.; Nguyen, X. V.; Carter, T. A.

2003-10-01

The scaling of particle transport with ion mass and magnetic field strength remains an open question in plasma research. Direct comparison of experiment with theory is often complicated by inability to significantly vary critical parameters such as ion mass, pressure gradient, ion gyro-radius, etc. The LAPD-U magnetized, linear plasma at UCLA provides the ideal platform for such studies, allowing large parameter variation. The magnetic field in LAPD-U can be varied over a range of 500 - 1500 G, while ion species can be varied to change mass by a factor of at least 10. In addition, ion gyro-radii are small compared to the plasma diameter ( 1 m). Cross-field transport in LAPD-U is thought to be caused by electrostatic turbulence, also a leading candidate for transport in fusion plasmas. It is planned, therefore, to investigate turbulence and transport characteristics as a function of parameter space. In particular, measurement of the mass and magnetic field dependence of electrostatic particle transport and turbulence characteristics in LAPD-U will be presented.

Position-dependent mass, finite-gap systems, and supersymmetry

NASA Astrophysics Data System (ADS)

Bravo, Rafael; Plyushchay, Mikhail S.

2016-05-01

The ordering problem in quantum systems with position-dependent mass (PDM) is treated by inclusion of the classically fictitious similarity transformation into the kinetic term. This provides a generation of supersymmetry with the first-order supercharges from the kinetic term alone, while inclusion of the potential term allows us also to generate nonlinear supersymmetry with higher-order supercharges. A broad class of finite-gap systems with PDM is obtained by different reduction procedures, and general results on supersymmetry generation are applied to them. We show that elliptic finite-gap systems of Lamé and Darboux-Treibich-Verdier types can be obtained by reduction to Seiffert's spherical spiral and Bernoulli lemniscate in the presence of Calogero-like or harmonic oscillator potentials, or by angular momentum reduction of a free motion on some AdS2 -related surfaces in the presence of Aharonov-Bohm flux. The limiting cases include the Higgs and Mathews-Lakshmanan oscillator models as well as a reflectionless model with PDM exploited recently in the discussion of cosmological inflationary scenarios.

(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.

The Mitochondria-targeted ubiquinone MitoQ decreases ethanol-dependent micro and macro hepatosteatosis

PubMed Central

Chacko, Balu K; Srivastava, Anup; Johnson, Michelle; Benavides, Gloria A.; Chang, Mi Jung; Ye, Yaozu; Jhala, Nirag; Murphy, Michael P; Kalyanaraman, Balaraman; Darley-Usmar, Victor M.

2011-01-01

Chronic alcohol-induced liver disease results in inflammation, steatosis and increased oxidative and nitrosative damage to the mitochondrion. We hypothesized that targeting an antioxidant to the mitochondria would prevent oxidative damage and attenuate the steatosis associated with alcoholic liver disease. To test this we investigated the effects of mitochondria-targeted ubiquinone, MitoQ, (5 & 25 mg/kg/d for 4 weeks) in male Sprague-Dawley rats consuming ethanol using the Lieber-DeCarli diet with pair-fed controls. Hepatic steatosis, 3-nitrotyosine (3-NT), 4-hydroxynonenal (4-HNE), hypoxia inducible factor α (HIF1α) and the activity of the mitochondrial respiratory chain complexes were assessed. As reported previously, ethanol consumption resulted in hepatocyte ballooning, increased lipid accumulation in the form of micro and macrovesicular steatosis and induction of CYP2E1. MitoQ had a minor on the ethanol-dependent decrease in mitochondrial respiratory chain proteins and their activities, it did however decrease hepatic steatosis in ethanol consuming animals and prevented the ethanol-induced formation of 3-NT and 4-HNE. Interestingly, MitoQ completely blocks the increase in HIF1α in all ethanol-fed groups which has previously been demonstrated in cell culture models and shown to be essential in ethanol-dependent hepatosteatosis. These results demonstrate the antioxidant capacity of MitoQ in alleviating alcohol associated mitochondrial ROS and several downstream effects of ROS/RNS production such as inhibiting protein nitration and protein aldehyde formation and specifically ROS-dependant HIF1α stabilization. PMID:21520201

A position-dependent mass model for the Thomas–Fermi potential: Exact solvability and relation to δ-doped semiconductors

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

Schulze-Halberg, Axel, E-mail: xbataxel@gmail.com; García-Ravelo, Jesús; Pacheco-García, Christian

We consider the Schrödinger equation in the Thomas–Fermi field, a model that has been used for describing electron systems in δ-doped semiconductors. It is shown that the problem becomes exactly-solvable if a particular effective (position-dependent) mass distribution is incorporated. Orthogonal sets of normalizable bound state solutions are constructed in explicit form, and the associated energies are determined. We compare our results with the corresponding findings on the constant-mass problem discussed by Ioriatti (1990) [13]. -- Highlights: ► We introduce an exactly solvable, position-dependent mass model for the Thomas–Fermi potential. ► Orthogonal sets of solutions to our model are constructed inmore » closed form. ► Relation to delta-doped semiconductors is discussed. ► Explicit subband bottom energies are calculated and compared to results obtained in a previous study.« less

Conservation of σ28-Dependent Non-Coding RNA Paralogs and Predicted σ54-Dependent Targets in Thermophilic Campylobacter Species

PubMed Central

Le, My Thanh; van Veldhuizen, Mart; Porcelli, Ida; Bongaerts, Roy J.; Gaskin, Duncan J. H.; Pearson, Bruce M.; van Vliet, Arnoud H. M.

2015-01-01

Assembly of flagella requires strict hierarchical and temporal control via flagellar sigma and anti-sigma factors, regulatory proteins and the assembly complex itself, but to date non-coding RNAs (ncRNAs) have not been described to regulate genes directly involved in flagellar assembly. In this study we have investigated the possible role of two ncRNA paralogs (CjNC1, CjNC4) in flagellar assembly and gene regulation of the diarrhoeal pathogen Campylobacter jejuni. CjNC1 and CjNC4 are 37/44 nt identical and predicted to target the 5' untranslated region (5' UTR) of genes transcribed from the flagellar sigma factor σ54. Orthologs of the σ54-dependent 5' UTRs and ncRNAs are present in the genomes of other thermophilic Campylobacter species, and transcription of CjNC1 and CNC4 is dependent on the flagellar sigma factor σ28. Surprisingly, inactivation and overexpression of CjNC1 and CjNC4 did not affect growth, motility or flagella-associated phenotypes such as autoagglutination. However, CjNC1 and CjNC4 were able to mediate sequence-dependent, but Hfq-independent, partial repression of fluorescence of predicted target 5' UTRs in an Escherichia coli-based GFP reporter gene system. This hints towards a subtle role for the CjNC1 and CjNC4 ncRNAs in post-transcriptional gene regulation in thermophilic Campylobacter species, and suggests that the currently used phenotypic methodologies are insufficiently sensitive to detect such subtle phenotypes. The lack of a role of Hfq in the E. coli GFP-based system indicates that the CjNC1 and CjNC4 ncRNAs may mediate post-transcriptional gene regulation in ways that do not conform to the paradigms obtained from the Enterobacteriaceae. PMID:26512728

Galaxy And Mass Assembly (GAMA): gas fuelling of spiral galaxies in the local Universe II. - direct measurement of the dependencies on redshift and host halo mass of stellar mass growth in central disc galaxies

NASA Astrophysics Data System (ADS)

Grootes, M. W.; Dvornik, A.; Laureijs, R. J.; Tuffs, R. J.; Popescu, C. C.; Robotham, A. S. G.; Liske, J.; Brown, M. J. I.; Holwerda, B. W.; Wang, L.

2018-06-01

We present a detailed analysis of the specific star formation rate-stellar mass (sSFR-M*) of z ≤ 0.13 disc central galaxies using a morphologically selected mass-complete sample (M* ≥ 109.5 M⊙). Considering samples of grouped and ungrouped galaxies, we find the sSFR-M* relations of disc-dominated central galaxies to have no detectable dependence on host dark-matter halo (DMH) mass, even where weak-lensing measurements indicate a difference in halo mass of a factor ≳ 5. We further detect a gradual evolution of the sSFR-M* relation of non-grouped (field) central disc galaxies with redshift, even over a Δz ≈ 0.04 (≈5 × 108 yr) interval, while the scatter remains constant. This evolution is consistent with extrapolation of the `main sequence of star-forming-galaxies' from previous literature that uses larger redshift baselines and coarser sampling. Taken together, our results present new constraints on the paradigm under which the SFR of galaxies is determined by a self-regulated balance between gas inflows and outflows, and consumption of gas by star formation in discs, with the inflow being determined by the product of the cosmological accretion rate and a fuelling efficiency - \\dot{M}_{b,halo}ζ. In particular, maintaining the paradigm requires \\dot{M}_{b,halo}ζ to be independent of the mass Mhalo of the host DMH. Furthermore, it requires the fuelling efficiency ζ to have a strong redshift dependence (∝(1 + z)2.7 for M* = 1010.3 M⊙ over z = 0-0.13), even though no morphological transformation to spheroids can be invoked to explain this in our disc-dominated sample. The physical mechanisms capable of giving rise to such dependencies of ζ on Mhalo and z for discs are unclear.

Integrated Targeting and Guidance for Powered Planetary Descent

NASA Astrophysics Data System (ADS)

Azimov, Dilmurat M.; Bishop, Robert H.

2018-02-01

This paper presents an on-board guidance and targeting design that enables explicit state and thrust vector control and on-board targeting for planetary descent and landing. These capabilities are developed utilizing a new closed-form solution for the constant thrust arc of the braking phase of the powered descent trajectory. The key elements of proven targeting and guidance architectures, including braking and approach phase quartics, are employed. It is demonstrated that implementation of the proposed solution avoids numerical simulation iterations, thereby facilitating on-board execution of targeting procedures during the descent. It is shown that the shape of the braking phase constant thrust arc is highly dependent on initial mass and propulsion system parameters. The analytic solution process is explicit in terms of targeting and guidance parameters, while remaining generic with respect to planetary body and descent trajectory design. These features increase the feasibility of extending the proposed integrated targeting and guidance design to future cargo and robotic landing missions.

Integrated Targeting and Guidance for Powered Planetary Descent

NASA Astrophysics Data System (ADS)

Azimov, Dilmurat M.; Bishop, Robert H.

2018-06-01

This paper presents an on-board guidance and targeting design that enables explicit state and thrust vector control and on-board targeting for planetary descent and landing. These capabilities are developed utilizing a new closed-form solution for the constant thrust arc of the braking phase of the powered descent trajectory. The key elements of proven targeting and guidance architectures, including braking and approach phase quartics, are employed. It is demonstrated that implementation of the proposed solution avoids numerical simulation iterations, thereby facilitating on-board execution of targeting procedures during the descent. It is shown that the shape of the braking phase constant thrust arc is highly dependent on initial mass and propulsion system parameters. The analytic solution process is explicit in terms of targeting and guidance parameters, while remaining generic with respect to planetary body and descent trajectory design. These features increase the feasibility of extending the proposed integrated targeting and guidance design to future cargo and robotic landing missions.

Targeted BikDD expression kills androgen-dependent and castration-resistant prostate cancer cells

PubMed Central

Xie, Xiaoming; Kong, Yanan; Tang, Hailin; Yang, Lu; Hsu, Jennifer L; Hung, Mien-Chie

2014-01-01

Targeted gene therapy is a promising approach for treating prostate cancer after the discovery of prostate cancer-specific promoters such as prostate-specific antigen, rat probasin, and human glandular kallikrein. However, these promoters are androgen-dependent, and after castration or androgen ablation therapy, they become much less active or sometimes inactive. Importantly, the disease will inevitably progress from androgen-dependent (ADPC) to castration-resistant prostate cancer (CRPC) at which treatments fail and high mortality ensues. Therefore, it is critical to develop a targeted gene therapy strategy that is effective in both ADPC and CRPC to eradicate recurrent prostate tumors. The human telomerase reverse transcriptase-VP16-Gal4-WPRE integrated systemic amplifier composite (T-VISA) vector we previously developed which targets transgene expression in ovarian and breast cancer is also active in prostate cancer. To further improve its effectiveness based on androgen response in ADPC progression, the ARR2 element (two copies of androgen response region from rat probasin promoter) was incorporated into T-VISA to produce AT-VISA. Under androgen analog (R1881) stimulation, the activity of AT-VISA was increased to a level greater than or comparable to the cytomegalovirus (CMV) promoter in ADPC and CRPC cells, respectively. Importantly, AT-VISA demonstrated little or no expression in normal cells. Systemic administration of AT-VISA-BikDD encapsulated in liposomes repressed prostate tumor growth and prolonged mouse survival in orthotopic animal models as well as in the transgenic adenocarcinoma mouse prostate model, indicating that AT-VISA-BikDD has therapeutic potential to treat ADPC and CRPC safely and effectively in preclinical setting. PMID:24785255

Mass spectral chemical fingerprints reveal the molecular dependence of exhaust particulate matters on engine speeds.

PubMed

Li, Yi; Zhang, Hua; Zhao, Zongshan; Tian, Yong; Liu, Kun; Jie, Feifan; Zhu, Liang; Chen, Huanwen

2018-05-01

Particulate matters (PMs) emitted by automobile exhaust contribute to a significant fraction of the global PMs. Extractive atmospheric pressure chemical ionization mass spectrometry (EAPCI-MS) was developed to explore the molecular dependence of PMs collected from exhaust gases produced at different vehicle engine speeds. The mass spectral fingerprints of the organic compounds embedded in differentially sized PMs (e.g., 0.22-0.45, 0.45-1.00, 1.00-2.00, 2.00-3.00, 3.00-5.00, and 5.00-10.00μm) generated at different engine speeds (e.g., 1000, 1500, 2000, 2500, and 3000r/min) were chemically profiled in the mass range of mass to charge ratio (m/z) 50-800. Organic compounds, including alcohols, aldehydes, and esters, were detected in all the PMs tested, with varied concentration levels for each individual PM sample. At relatively low engine speeds (≤1500r/min), the total amount of organic species embedded in PMs of 0.22-1.00μm was greater than in PMs of other sizes, while more organic species were found in PMs of 5.00-10.00μm at high engine speeds (≥3000r/min), indicating that the organic compounds distributed in different sizes of PMs strongly correlated with the engine speed. The experimental data showed that the EAPCI-MS technique enables molecular characterization of PMs in exhaust, revealing the chemical dependence of PMs on the engine speeds (i.e., the combustion conditions) of automobiles. Copyright © 2017. Published by Elsevier B.V.

Quark matter at high density based on an extended confined isospin-density-dependent mass model

NASA Astrophysics Data System (ADS)

Qauli, A. I.; Sulaksono, A.

2016-01-01

We investigate the effect of the inclusion of relativistic Coulomb terms in a confined-isospin-density-dependent-mass (CIDDM) model of strange quark matter (SQM). We found that if we include the Coulomb term in scalar density form, the SQM equation of state (EOS) at high densities is stiffer but if we include the Coulomb term in vector density form it is softer than that of the standard CIDDM model. We also investigate systematically the role of each term of the extended CIDDM model. Compared with what was reported by Chu and Chen [Astrophys. J. 780, 135 (2014)], we found the stiffness of SQM EOS is controlled by the interplay among the oscillator harmonic, isospin asymmetry and Coulomb contributions depending on the parameter's range of these terms. We have found that the absolute stable condition of SQM and the mass of 2 M⊙ pulsars can constrain the parameter of oscillator harmonic κ1≈0.53 in the case the Coulomb term is excluded. If the Coulomb term is included, for the models with their parameters are consistent with SQM absolute stability condition, the 2.0 M⊙ constraint more prefers the maximum mass prediction of the model with the scalar Coulomb term than that of the model with the vector Coulomb term. On the contrary, the high densities EOS predicted by the model with the vector Coulomb is more compatible with the recent perturbative quantum chromodynamics result [1] than that predicted by the model with the scalar Coulomb. Furthermore, we also observed the quark composition in a very high density region depends quite sensitively on the kind of Coulomb term used.

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.

Nitric Oxide Is an Activity-Dependent Regulator of Target Neuron Intrinsic Excitability

PubMed Central

Steinert, Joern R.; Robinson, Susan W.; Tong, Huaxia; Haustein, Martin D.; Kopp-Scheinpflug, Cornelia; Forsythe, Ian D.

2011-01-01

Summary Activity-dependent changes in synaptic strength are well established as mediating long-term plasticity underlying learning and memory, but modulation of target neuron excitability could complement changes in synaptic strength and regulate network activity. It is thought that homeostatic mechanisms match intrinsic excitability to the incoming synaptic drive, but evidence for involvement of voltage-gated conductances is sparse. Here, we show that glutamatergic synaptic activity modulates target neuron excitability and switches the basis of action potential repolarization from Kv3 to Kv2 potassium channel dominance, thereby adjusting neuronal signaling between low and high activity states, respectively. This nitric oxide-mediated signaling dramatically increases Kv2 currents in both the auditory brain stem and hippocampus (>3-fold) transforming synaptic integration and information transmission but with only modest changes in action potential waveform. We conclude that nitric oxide is a homeostatic regulator, tuning neuronal excitability to the recent history of excitatory synaptic inputs over intervals of minutes to hours. PMID:21791288

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

Transgenic rescue of adipocyte glucose-dependent insulinotropic polypeptide receptor expression restores high fat diet-induced body weight gain.

PubMed

Ugleholdt, Randi; Pedersen, Jens; Bassi, Maria Rosaria; Füchtbauer, Ernst-Martin; Jørgensen, Signe Marie; Kissow, Hanne-Louise; Nytofte, Nikolaj; Poulsen, Steen Seier; Rosenkilde, Mette Marie; Seino, Yutaka; Thams, Peter; Holst, Peter Johannes; Holst, Jens Juul

2011-12-30

The glucose-dependent insulinotropic polypeptide receptor (GIPr) has been implicated in high fat diet-induced obesity and is proposed as an anti-obesity target despite an uncertainty regarding the mechanism of action. To independently investigate the contribution of the insulinotropic effects and the direct effects on adipose tissue, we generated transgenic mice with targeted expression of the human GIPr to white adipose tissue or beta-cells, respectively. These mice were then cross-bred with the GIPr knock-out strain. The central findings of the study are that mice with GIPr expression targeted to adipose tissue have a similar high fat diet -induced body weight gain as control mice, significantly greater than the weight gain in mice with a general ablation of the receptor. Surprisingly, this difference was due to an increase in total lean body mass rather than a gain in total fat mass that was similar between the groups. In contrast, glucose-dependent insulinotropic polypeptide-mediated insulin secretion does not seem to be important for regulation of body weight after high fat feeding. The study supports a role of the adipocyte GIPr in nutrient-dependent regulation of body weight and lean mass, but it does not support a direct and independent role for the adipocyte or beta-cell GIPr in promoting adipogenesis.

DNA-PKcs, a novel functional target of acriflavine, mediates acriflavine's p53-dependent synergistic anti-tumor efficiency with melphalan.

PubMed

Cao, Ji; Lin, Guanyu; Gong, Yanling; Pan, Peichen; Ma, Yaxi; Huang, Ping; Ying, Meidan; Hou, Tingjun; He, Qiaojun; Yang, Bo

2016-12-01

Acriflavine (ACF), a known antibacterial drug, has recently been recognized as a suitable candidate for cancer chemotherapy. However, the molecular target of ACF is not fully understood, which limits its application in cancer therapy. In this study, we established a structure-specific probe-based pull-down approach to comprehensively profile the potential target of ACF, and we identified DNA dependent protein kinase catalytic subunit (DNA-PKcs) as the direct target of ACF. Since DNA-PKcs facilitates the repair process following DNA double-strand breaks, we further developed a drug combination strategy that combined ACF with the bifunctional alkylating agent melphalan, which exerted a p53-dependent synergistic efficacy against human cancer cells both in vitro and in vivo. With these findings, our study demonstrated that structure-specific probe-based pull-down approaches can be used to identify new functional target of drug, and provided novel opportunities for the development of ACF-based antitumor chemotherapies. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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.

Directional detection of dark matter with two-dimensional targets

NASA Astrophysics Data System (ADS)

Hochberg, Yonit; Kahn, Yonatan; Lisanti, Mariangela; Tully, Christopher G.; Zurek, Kathryn M.

2017-09-01

We propose two-dimensional materials as targets for direct detection of dark matter. Using graphene as an example, we focus on the case where dark matter scattering deposits sufficient energy on a valence-band electron to eject it from the target. We show that the sensitivity of graphene to dark matter of MeV to GeV mass can be comparable, for similar exposure and background levels, to that of semiconductor targets such as silicon and germanium. Moreover, a two-dimensional target is an excellent directional detector, as the ejected electron retains information about the angular dependence of the incident dark matter particle. This proposal can be implemented by the PTOLEMY experiment, presenting for the first time an opportunity for directional detection of sub-GeV dark matter.

Directional detection of dark matter with two-dimensional targets

DOE PAGES

Hochberg, Yonit; Kahn, Yonatan; Lisanti, Mariangela; ...

2017-09-01

We propose two-dimensional materials as targets for direct detection of dark matter. Using graphene as an example, we focus on the case where dark matter scattering deposits sufficient energy on a valence-band electron to eject it from the target. Here, we show that the sensitivity of graphene to dark matter of MeV to GeV mass can be comparable, for similar exposure and background levels, to that of semiconductor targets such as silicon and germanium. Moreover, a two-dimensional target is an excellent directional detector, as the ejected electron retains information about the angular dependence of the incident dark matter particle. Ourmore » proposal can be implemented by the PTOLEMY experiment, presenting for the first time an opportunity for directional detection of sub-GeV dark matter.« less

Directional detection of dark matter with two-dimensional targets

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

Hochberg, Yonit; Kahn, Yonatan; Lisanti, Mariangela

We propose two-dimensional materials as targets for direct detection of dark matter. Using graphene as an example, we focus on the case where dark matter scattering deposits sufficient energy on a valence-band electron to eject it from the target. Here, we show that the sensitivity of graphene to dark matter of MeV to GeV mass can be comparable, for similar exposure and background levels, to that of semiconductor targets such as silicon and germanium. Moreover, a two-dimensional target is an excellent directional detector, as the ejected electron retains information about the angular dependence of the incident dark matter particle. Ourmore » proposal can be implemented by the PTOLEMY experiment, presenting for the first time an opportunity for directional detection of sub-GeV dark matter.« less

MAJOR-MERGER GALAXY PAIRS IN THE COSMOS FIELD-MASS-DEPENDENT MERGER RATE EVOLUTION SINCE z = 1

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

Xu, C. Kevin; Zhao, Yinghe; Gao, Y.

2012-03-10

We present results of a statistical study of the cosmic evolution of the mass-dependent major-merger rate since z = 1. A stellar mass limited sample of close major-merger pairs (the CPAIR sample) was selected from the archive of the COSMOS survey. Pair fractions at different redshifts derived using the CPAIR sample and a local K-band-selected pair sample show no significant variations with stellar mass. The pair fraction exhibits moderately strong cosmic evolution, with the best-fitting function of f{sub pair} = 10{sup -1.88({+-}0.03)}(1 + z){sup 2.2({+-}0.2)}. The best-fitting function for the merger rate is R{sub mg} (Gyr{sup -1}) = 0.053 Multiplication-Signmore » (M{sub star}/10{sup 10.7} M{sub Sun} ){sup 0.3}(1 + z){sup 2.2}/(1 + z/8). This rate implies that galaxies of M{sub star} {approx} 10{sup 10}-10{sup 11.5} M{sub Sun} have undergone {approx}0.5-1.5 major mergers since z = 1. Our results show that, for massive galaxies (M{sub star} {>=} 10{sup 10.5} M{sub Sun }) at z {<=} 1, major mergers involving star-forming galaxies (i.e., wet and mixed mergers) can account for the formation of both ellipticals and red quiescent galaxies (RQGs). On the other hand, major mergers cannot be responsible for the formation of most low mass ellipticals and RQGs of M{sub star} {approx}< 10{sup 10.3} M{sub Sun }. Our quantitative estimates indicate that major mergers have significant impact on the stellar mass assembly of the most massive galaxies (M{sub star} {>=} 10{sup 11.3} M{sub Sun }), but for less massive galaxies the stellar mass assembly is dominated by the star formation. Comparison with the mass-dependent (ultra)luminous infrared galaxies ((U)LIRG) rates suggests that the frequency of major-merger events is comparable to or higher than that of (U)LIRGs.« less

Imaging of β-cell mass and insulitis in insulin-dependent (Type 1) diabetes mellitus.

PubMed

Di Gialleonardo, Valentina; de Vries, Erik F J; Di Girolamo, Marco; Quintero, Ana M; Dierckx, Rudi A J O; Signore, Alberto

2012-12-01

Insulin-dependent (type 1) diabetes mellitus is a metabolic disease with a complex multifactorial etiology and a poorly understood pathogenesis. Genetic and environmental factors cause an autoimmune reaction against pancreatic β-cells, called insulitis, confirmed in pancreatic samples obtained at autopsy. The possibility to noninvasively quantify β-cell mass in vivo would provide important biological insights and facilitate aspects of diagnosis and therapy, including follow-up of islet cell transplantation. Moreover, the availability of a noninvasive tool to quantify the extent and severity of pancreatic insulitis could be useful for understanding the natural history of human insulin-dependent (type 1) diabetes mellitus, to early diagnose children at risk to develop overt diabetes, and to select patients to be treated with immunotherapies aimed at blocking the insulitis and monitoring the efficacy of these therapies. In this review, we outline the imaging techniques currently available for in vivo, noninvasive detection of β-cell mass and insulitis. These imaging techniques include magnetic resonance imaging, ultrasound, computed tomography, bioluminescence and fluorescence imaging, and the nuclear medicine techniques positron emission tomography and single-photon emission computed tomography. Several approaches and radiopharmaceuticals for imaging β-cells and lymphocytic insulitis are reviewed in detail.

Prevalence of low bone mass among adolescents with nontransfusion-dependent hemoglobin E/β-thalassemia and its relationship with anemia severity.

PubMed

Nakavachara, Pairunyar; Petchkul, Jaturat; Jeerawongpanich, Krittha; Kiattisakthavee, Pornpimol; Manpayak, Teerarat; Netsakulnee, Parichat; Chaichanwattanakul, Katharee; Pooliam, Julaporn; Srichairatanakool, Somdet; Viprakasit, Vip

2018-01-01

Low bone mass is common among adolescents with transfusion-dependent β-thalassemia despite adequate transfusion and iron chelation. However, there are few reports regarding bone mineral density (BMD) among adolescents with nontransfusion-dependent thalassemia (NTDT). Indeed, only BMD data in patients with nontransfusion-dependent (NTD) β-thalassemia intermedia have been reported. No previous study has investigated BMD among adolescents with NTD hemoglobin (Hb) E/β-thalassemia. To determine the prevalence of low bone mass among adolescents with NTD Hb E/β-thalassemia and factors relating to low bone mass. We investigated BMD of lumbar spine (L2-L4; BMDLS) and total body (BMDTB), as measured by dual-energy X-ray absorptiometry, in 22 adolescents (aged 13.2-20 years) with NTD Hb E/β-thalassemia. Low bone mass was found to be 18.2% and 22.7% at the lumbar spine (BMDLS Z-score adjusted for bone age and height age) and 13.6% and 9.1% at the total body (BMDTB Z-score adjusted for bone age and height age). Patients with mean Hb level <8 g/dl were more likely to have low bone mass (BMDLS and BMDTB Z-scores adjusted for bone age) compared to those with Hb level ≥ 8 g/dl. Mean Hb level correlated with BMDLS and BMDTB Z-scores adjusted for bone age. We demonstrated that a low Hb level was associated with low bone mass among adolescents with NTD Hb E/β-thalassemia. A significant proportion of low bone mass among these patients highlights the importance of appropriate management, including red cell transfusion, vitamin D and calcium supplementation for improved long-term bone health. © 2017 Wiley Periodicals, Inc.

The dependence of halo mass on galaxy size at fixed stellar mass using weak lensing

NASA Astrophysics Data System (ADS)

Charlton, Paul J. L.; Hudson, Michael J.; Balogh, Michael L.; Khatri, Sumeet

2017-12-01

Stellar mass has been shown to correlate with halo mass, with non-negligible scatter. The stellar mass-size and luminosity-size relationships of galaxies also show significant scatter in galaxy size at fixed stellar mass. It is possible that, at fixed stellar mass and galaxy colour, the halo mass is correlated with galaxy size. Galaxy-galaxy lensing allows us to measure the mean masses of dark matter haloes for stacked samples of galaxies. We extend the analysis of the galaxies in the CFHTLenS catalogue by fitting single Sérsic surface brightness profiles to the lens galaxies in order to recover half-light radius values, allowing us to determine halo masses for lenses according to their size. Comparing our halo masses and sizes to baselines for that stellar mass yields a differential measurement of the halo mass-galaxy size relationship at fixed stellar mass, defined as Mh(M_{*}) ∝ r_{eff}^{η }(M_{*}). We find that, on average, our lens galaxies have an η = 0.42 ± 0.12, i.e. larger galaxies live in more massive dark matter haloes. The η is strongest for high-mass luminous red galaxies. Investigation of this relationship in hydrodynamical simulations suggests that, at a fixed M*, satellite galaxies have a larger η and greater scatter in the Mh and reff relationship compared to central galaxies.

Dscam1-mediated self-avoidance counters Netrin-dependent targeting of dendrites in Drosophila

PubMed Central

Matthews, Benjamin J.; Grueber, Wesley B.

2011-01-01

SUMMARY Dendrites and axons show precise targeting and spacing patterns for proper reception and transmission of information in the nervous system. Self-avoidance promotes complete territory coverage and non-overlapping spacing between processes from the same cell [1, 2]. Neurons that lack Drosophila Down syndrome cell adhesion molecule 1 (Dscam1) show aberrant overlap, fasciculation, and accumulation of dendrites and axons, demonstrating a role in self-recognition and repulsion leading to self-avoidance [3–11]. Fasciculation and accumulation of processes suggested that Dscam1 might promote process spacing by counterbalancing developmental signals that otherwise promote self-association [9, 12]. Here we show that Dscam1 functions to counter sensory neuron dendritic targeting signals provided by secreted Netrin-B and Frazzled, a netrin receptor. Loss of Dscam1 function resulted in aberrant dendrite accumulation at a Netrin-B expressing target, whereas concomitant loss of Frazzled prevented accumulation and caused severe deficits in dendritic territory coverage. Netrin misexpression was sufficient to induce ectopic dendritic targeting in a Frazzled-dependent manner, whereas Dscam1 was required to prevent ectopic accumulation, consistent with separable roles for these receptors. Our results suggest that Dscam1-mediated self-avoidance counter extrinsic signals that are required for normal dendritic patterning, but whose action would otherwise favor neurite accumulation. Counterbalancing roles for Dscam1 may be deployed in diverse contexts during neural circuit formation. PMID:21871804

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

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.

Halo mass dependence of H I and O VI absorption: evidence for differential kinematics

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

Mathes, Nigel L.; Churchill, Christopher W.; Nielsen, Nikole M.

2014-09-10

We studied a sample of 14 galaxies (0.1 < z < 0.7) using HST/WFPC2 imaging and high-resolution HST/COS or HST/STIS quasar spectroscopy of Lyα, Lyβ, and O VI λλ1031, 1037 absorption. The galaxies, having 10.8 ≤ log (M {sub h}/M {sub ☉}) ≤ 12.2, lie within D = 300 kpc of quasar sightlines, probing out to D/R {sub vir} = 3. When the full range of M {sub h} and D/R {sub vir} of the sample are examined, ∼40% of the H I absorbing clouds can be inferred to be escaping their host halo. The fraction of bound clouds decreasesmore » as D/R {sub vir} increases such that the escaping fraction is ∼15% for D/R {sub vir} < 1, ∼45% for 1 ≤ D/R {sub vir} < 2, and ∼90% for 2 ≤ D/R {sub vir} < 3. Adopting the median mass log M {sub h}/M {sub ☉} = 11.5 to divide the sample into 'higher' and 'lower' mass galaxies, we find a mass dependency for the hot circumgalactic medium kinematics. To our survey limits, O VI absorption is found in only ∼40% of the H I clouds in and around lower mass halos as compared to ∼85% around higher mass halos. For D/R {sub vir} < 1, lower mass halos have an escape fraction of ∼65%, whereas higher mass halos have an escape fraction of ∼5%. For 1 ≤ D/R {sub vir} < 2, the escape fractions are ∼55% and ∼35% for lower mass and higher mass halos, respectively. For 2 ≤ D/R {sub vir} < 3, the escape fraction for lower mass halos is ∼90%. We show that it is highly likely that the absorbing clouds reside within 4R {sub vir} of their host galaxies and that the kinematics are dominated by outflows. Our finding of 'differential kinematics' is consistent with the scenario of 'differential wind recycling' proposed by Oppenheimer et al. We discuss the implications for galaxy evolution, the stellar to halo mass function, and the mass-metallicity relationship of galaxies.« less

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

Concentration Dependence of Solution Shear Viscosity and Solute Mass Diffusivity in Crystal Growth from Solutions

NASA Technical Reports Server (NTRS)

Izmailov, Alexander F.; Myerson, Allan S.

1995-01-01

The physical properties of a supersaturated binary solution such as its density rho, shear viscosity eta, and solute mass diffusivity D are dependent on the solute concentration c: rho = rho(c), eta = eta(c), and D = D(c). The diffusion boundary layer equations related to crystal growth from solution are derived for the case of natural convection with a solution density, a shear viscosity, and a solute diffusivity that are all depen- dent on solute concentration. The solution of these equations has demonstrated the following. (1) At the vicinity of the saturation concentration c(sub s) the solution shear viscosity eta depends on rho as eta(sub s) = eta(rho(sub s))varies as square root of rho(c(sub s)). This theoretically derived result has been verified in experiments with several aqueous solutions of inorganic and organic salts. (2) The maximum solute mass transfer towards the growing crystal surface can be achieved for values of c where the ratio of d ln(D(c)/dc) to d ln(eta(c)/dc) is a maximum.

MEASURING THE LUMINOSITY AND VIRIAL BLACK HOLE MASS DEPENDENCE OF QUASAR–GALAXY CLUSTERING AT z ∼ 0.8

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

Krolewski, Alex G.; Eisenstein, Daniel J., E-mail: akrolewski@college.harvard.edu

2015-04-10

We study the dependence of quasar clustering on quasar luminosity and black hole mass by measuring the angular overdensity of photometrically selected galaxies imaged by the Wide-field Infrared Survey Explorer (WISE) about z ∼ 0.8 quasars from SDSS. By measuring the quasar–galaxy cross-correlation function and using photometrically selected galaxies, we achieve a higher density of tracer objects and a more sensitive detection of clustering than measurements of the quasar autocorrelation function. We test models of quasar formation and evolution by measuring the luminosity dependence of clustering amplitude. We find a significant overdensity of WISE galaxies about z ∼ 0.8 quasarsmore » at 0.2–6.4 h{sup −1} Mpc in projected comoving separation. We find no appreciable increase in clustering amplitude with quasar luminosity across a decade in luminosity, and a power-law fit between luminosity and clustering amplitude gives an exponent of −0.01 ± 0.06 (1 σ error). We also fail to find a significant relationship between clustering amplitude and black hole mass, although our dynamic range in true mass is suppressed due to the large uncertainties in virial black hole mass estimates. Our results indicate that a small range in host dark matter halo mass maps to a large range in quasar luminosity.« less

Preferential Targeting of a Signal Recognition Particle-dependent Precursor to the Ssh1p Translocon in Yeast♦

PubMed Central

Spiller, Michael P.; Stirling, Colin J.

2011-01-01

Protein translocation across the endoplasmic reticulum membrane occurs via a “translocon” channel formed by the Sec61p complex. In yeast, two channels exist: the canonical Sec61p channel and a homolog called Ssh1p. Here, we used trapped translocation intermediates to demonstrate that a specific signal recognition particle-dependent substrate, Sec71p, is targeted exclusively to Ssh1p. Strikingly, we found that, in the absence of Ssh1p, precursor could be successfully redirected to canonical Sec61p, demonstrating that the normal targeting reaction must involve preferential sorting to Ssh1p. Our data therefore demonstrate that Ssh1p is the primary translocon for Sec71p and reveal a novel sorting mechanism at the level of the endoplasmic reticulum membrane enabling precursors to be directed to distinct translocons. Interestingly, the Ssh1p-dependent translocation of Sec71p was found to be dependent upon Sec63p, demonstrating a previously unappreciated functional interaction between Sec63p and the Ssh1p translocon. PMID:21454595

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

Delivery of CdiA Nuclease Toxins into Target Cells during Contact-Dependent Growth Inhibition

PubMed Central

Webb, Julia S.; Nikolakakis, Kiel C.; Willett, Julia L. E.; Aoki, Stephanie K.

2013-01-01

Bacterial contact-dependent growth inhibition (CDI) is mediated by the CdiB/CdiA family of two-partner secretion proteins. CDI systems deploy a variety of distinct toxins, which are contained within the polymorphic C-terminal region (CdiA-CT) of CdiA proteins. Several CdiA-CTs are nucleases, suggesting that the toxins are transported into the target cell cytoplasm to interact with their substrates. To analyze CdiA transfer to target bacteria, we used the CDI system of uropathogenic Escherichia coli 536 (UPEC536) as a model. Antibodies recognizing the amino- and carboxyl-termini of CdiAUPEC536 were used to visualize transfer of CdiA from CDIUPEC536+ inhibitor cells to target cells using fluorescence microscopy. The results indicate that the entire CdiAUPEC536 protein is deposited onto the surface of target bacteria. CdiAUPEC536 transfer to bamA101 mutants is reduced, consistent with low expression of the CDI receptor BamA on these cells. Notably, our results indicate that the C-terminal CdiA-CT toxin region of CdiAUPEC536 is translocated into target cells, but the N-terminal region remains at the cell surface based on protease sensitivity. These results suggest that the CdiA-CT toxin domain is cleaved from CdiAUPEC536 prior to translocation. Delivery of a heterologous Dickeya dadantii CdiA-CT toxin, which has DNase activity, was also visualized. Following incubation with CDI+ inhibitor cells targets became anucleate, showing that the D.dadantii CdiA-CT was delivered intracellularly. Together, these results demonstrate that diverse CDI toxins are efficiently translocated across target cell envelopes. PMID:23469034

Connexin-Dependent Neuroglial Networking as a New Therapeutic Target.

PubMed

Charvériat, Mathieu; Naus, Christian C; Leybaert, Luc; Sáez, Juan C; Giaume, Christian

2017-01-01

Astrocytes and neurons dynamically interact during physiological processes, and it is now widely accepted that they are both organized in plastic and tightly regulated networks. Astrocytes are connected through connexin-based gap junction channels, with brain region specificities, and those networks modulate neuronal activities, such as those involved in sleep-wake cycle, cognitive, or sensory functions. Additionally, astrocyte domains have been involved in neurogenesis and neuronal differentiation during development; they participate in the "tripartite synapse" with both pre-synaptic and post-synaptic neurons by tuning down or up neuronal activities through the control of neuronal synaptic strength. Connexin-based hemichannels are also involved in those regulations of neuronal activities, however, this feature will not be considered in the present review. Furthermore, neuronal processes, transmitting electrical signals to chemical synapses, stringently control astroglial connexin expression, and channel functions. Long-range energy trafficking toward neurons through connexin-coupled astrocytes and plasticity of those networks are hence largely dependent on neuronal activity. Such reciprocal interactions between neurons and astrocyte networks involve neurotransmitters, cytokines, endogenous lipids, and peptides released by neurons but also other brain cell types, including microglial and endothelial cells. Over the past 10 years, knowledge about neuroglial interactions has widened and now includes effects of CNS-targeting drugs such as antidepressants, antipsychotics, psychostimulants, or sedatives drugs as potential modulators of connexin function and thus astrocyte networking activity. In physiological situations, neuroglial networking is consequently resulting from a two-way interaction between astrocyte gap junction-mediated networks and those made by neurons. As both cell types are modulated by CNS drugs we postulate that neuroglial networking may emerge as

Evidence for a mass-dependent AGN Eddington ratio distribution via the flat relationship between SFR and AGN luminosity

NASA Astrophysics Data System (ADS)

Bernhard, E.; Mullaney, J. R.; Aird, J.; Hickox, R. C.; Jones, M. L.; Stanley, F.; Grimmett, L. P.; Daddi, E.

2018-05-01

The lack of a strong correlation between AGN X-ray luminosity (LX; a proxy for AGN power) and the star formation rate (SFR) of their host galaxies has recently been attributed to stochastic AGN variability. Studies using population synthesis models have incorporated this by assuming a broad, universal (i.e. does not depend on the host galaxy properties) probability distribution for AGN specific X-ray luminosities (i.e. the ratio of LX to host stellar mass; a common proxy for Eddington ratio). However, recent studies have demonstrated that this universal Eddington ratio distribution fails to reproduce the observed X-ray luminosity functions beyond z ˜ 1.2. Furthermore, empirical studies have recently shown that the Eddington ratio distribution may instead depend upon host galaxy properties, such as SFR and/or stellar mass. To investigate this further, we develop a population synthesis model in which the Eddington ratio distribution is different for star-forming and quiescent host galaxies. We show that, although this model is able to reproduce the observed X-ray luminosity functions out to z ˜ 2, it fails to simultaneously reproduce the observed flat relationship between SFR and X-ray luminosity. We can solve this, however, by incorporating a mass dependency in the AGN Eddington ratio distribution for star-forming host galaxies. Overall, our models indicate that a relative suppression of low Eddington ratios (λEdd ≲ 0.1) in lower mass galaxies (M* ≲ 1010 - 11 M⊙) is required to reproduce both the observed X-ray luminosity functions and the observed flat SFR/X-ray relationship.

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...

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.

Active debris removal of multiple priority targets

NASA Astrophysics Data System (ADS)

Braun, Vitali; Lüpken, A.; Flegel, S.; Gelhaus, J.; Möckel, M.; Kebschull, C.; Wiedemann, C.; Vörsmann, P.

2013-05-01

is possible to remove up to five high priority targets per year using a chemical propulsion system, however, missions may result in too high ΔV and/or mission duration depending on the orbital distribution of the targets. When using an electric propulsion system, the required fuel mass is significantly reduced when compared to the chemical propulsion system, but it was shown that mission duration strongly depends on the mass of the selected targets. More powerful engines as well as out-of-plane thrust are thus required to achieve the defined mission goals.

The Mass-dependent Star Formation Histories of Disk Galaxies: Infall Model Versus Observations

NASA Astrophysics Data System (ADS)

Chang, R. X.; Hou, J. L.; Shen, S. Y.; Shu, C. G.

2010-10-01

We introduce a simple model to explore the star formation histories of disk galaxies. We assume that the disk originate and grows by continuous gas infall. The gas infall rate is parameterized by the Gaussian formula with one free parameter: the infall-peak time tp . The Kennicutt star formation law is adopted to describe how much cold gas turns into stars. The gas outflow process is also considered in our model. We find that, at a given galactic stellar mass M *, the model adopting a late infall-peak time tp results in blue colors, low-metallicity, high specific star formation rate (SFR), and high gas fraction, while the gas outflow rate mainly influences the gas-phase metallicity and star formation efficiency mainly influences the gas fraction. Motivated by the local observed scaling relations, we "construct" a mass-dependent model by assuming that the low-mass galaxy has a later infall-peak time tp and a larger gas outflow rate than massive systems. It is shown that this model can be in agreement with not only the local observations, but also with the observed correlations between specific SFR and galactic stellar mass SFR/M * ~ M * at intermediate redshifts z < 1. Comparison between the Gaussian-infall model and the exponential-infall model is also presented. It shows that the exponential-infall model predicts a higher SFR at early stage and a lower SFR later than that of Gaussian infall. Our results suggest that the Gaussian infall rate may be more reasonable in describing the gas cooling process than the exponential infall rate, especially for low-mass systems.

Time-dependent mass of cosmological perturbations in the hybrid and dressed metric approaches to loop quantum cosmology

NASA Astrophysics Data System (ADS)

Elizaga Navascués, Beatriz; Martín de Blas, Daniel; Mena Marugán, Guillermo A.

2018-02-01

Loop quantum cosmology has recently been applied in order to extend the analysis of primordial perturbations to the Planck era and discuss the possible effects of quantum geometry on the cosmic microwave background. Two approaches to loop quantum cosmology with admissible ultraviolet behavior leading to predictions that are compatible with observations are the so-called hybrid and dressed metric approaches. In spite of their similarities and relations, we show in this work that the effective equations that they provide for the evolution of the tensor and scalar perturbations are somewhat different. When backreaction is neglected, the discrepancy appears only in the time-dependent mass term of the corresponding field equations. We explain the origin of this difference, arising from the distinct quantization procedures. Besides, given the privileged role that the big bounce plays in loop quantum cosmology, e.g. as a natural instant of time to set initial conditions for the perturbations, we also analyze the positivity of the time-dependent mass when this bounce occurs. We prove that the mass of the tensor perturbations is positive in the hybrid approach when the kinetic contribution to the energy density of the inflaton dominates over its potential, as well as for a considerably large sector of backgrounds around that situation, while this mass is always nonpositive in the dressed metric approach. Similar results are demonstrated for the scalar perturbations in a sector of background solutions that includes the kinetically dominated ones; namely, the mass then is positive for the hybrid approach, whereas it typically becomes negative in the dressed metric case. More precisely, this last statement is strictly valid when the potential is quadratic for values of the inflaton mass that are phenomenologically favored.

The Evolution of the Stellar Mass Function of Galaxies from z = 4.0 and the First Comprehensive Analysis of its Uncertainties: Evidence for Mass-Dependent Evolution

NASA Astrophysics Data System (ADS)

Marchesini, Danilo; van Dokkum, Pieter G.; Förster Schreiber, Natascha M.; Franx, Marijn; Labbé, Ivo; Wuyts, Stijn

2009-08-01

We present the evolution of the stellar mass function (SMF) of galaxies from z = 4.0 to z = 1.3 measured from a sample constructed from the deep near-infrared Multi-wavelength Survey by Yale-Chile, the Faint Infrared Extragalactic Survey, and the Great Observatories Origins Deep Survey-Chandra Deep Field South surveys, all having very high-quality optical to mid-infrared data. This sample, unique in that it combines data from surveys with a large range of depths and areas in a self-consistent way, allowed us to (1) minimize the uncertainty due to cosmic variance and empirically quantify its contribution to the total error budget; (2) simultaneously probe the high-mass end and the low-mass end (down to ~0.05 times the characteristic stellar mass) of the SMF with good statistics; and (3) empirically derive the redshift-dependent completeness limits in stellar mass. We provide, for the first time, a comprehensive analysis of random and systematic uncertainties affecting the derived SMFs, including the effect of metallicity, extinction law, stellar population synthesis model, and initial mass function. We find that the mass density evolves by a factor of ~17+7 -10 since z = 4.0, mostly driven by a change in the normalization Φsstarf. If only random errors are taken into account, we find evidence for mass-dependent evolution, with the low-mass end evolving more rapidly than the high-mass end. However, we show that this result is no longer robust when systematic uncertainties due to the SED-modeling assumptions are taken into account. Another significant uncertainty is the contribution to the overall stellar mass density of galaxies below our mass limit; future studies with WFC3 will provide better constraints on the SMF at masses below 1010 M sun at z>2. Taking our results at face value, we find that they are in conflict with semianalytic models of galaxy formation. The models predict SMFs that are in general too steep, with too many low-mass galaxies and too few high-mass

Dscam1-mediated self-avoidance counters netrin-dependent targeting of dendrites in Drosophila.

PubMed

Matthews, Benjamin J; Grueber, Wesley B

2011-09-13

Dendrites and axons show precise targeting and spacing patterns for proper reception and transmission of information in the nervous system. Self-avoidance promotes complete territory coverage and nonoverlapping spacing between processes from the same cell [1, 2]. Neurons that lack Drosophila Down syndrome cell adhesion molecule 1 (Dscam1) show aberrant overlap, fasciculation, and accumulation of dendrites and axons, demonstrating a role in self-recognition and repulsion leading to self-avoidance [3-11]. Fasciculation and accumulation of processes suggested that Dscam1 might promote process spacing by counterbalancing developmental signals that otherwise promote self-association [9, 12]. Here we show that Dscam1 functions to counter Drosophila sensory neuron dendritic targeting signals provided by secreted Netrin-B and Frazzled, a netrin receptor. Loss of Dscam1 function resulted in aberrant dendrite accumulation at a Netrin-B-expressing target, whereas concomitant loss of Frazzled prevented accumulation and caused severe deficits in dendritic territory coverage. Netrin misexpression was sufficient to induce ectopic dendritic targeting in a Frazzled-dependent manner, whereas Dscam1 was required to prevent ectopic accumulation, consistent with separable roles for these receptors. Our results suggest that Dscam1-mediated self-avoidance counters extrinsic signals that are required for normal dendritic patterning, but whose action would otherwise favor neurite accumulation. Counterbalancing roles for Dscam1 may be deployed in diverse contexts during neural circuit formation. Copyright © 2011 Elsevier Ltd. All rights reserved.

TBK1-targeted suppression of TRIF-dependent signaling pathway of Toll-like receptors by 6-shogaol, an active component of ginger.

PubMed

Park, Se-Jeong; Lee, Mi-Young; Son, Bu-Soon; Youn, Hyung-Sun

2009-07-01

Toll-like receptors (TLRs) are primary sensors that detect a wide variety of microbial components involving induction of innate immune responses. After recognition of microbial components, TLRs trigger the activation of myeloid differential factor 88 (MyD88) and Toll-interleukin-1 (IL-1) receptor domain-containing adapter inducing interferon-beta (TRIF)-dependent downstream signaling pathways. 6-Shoagol, an active ingredient of ginger, inhibits the MyD88-dependent signaling pathway by inhibiting inhibitor-kappaB kinase activity. Inhibitor-kappaB kinase is a key kinase in nuclear factor kappaB (NF-kappaB) activation. However, it is not known whether 6-shogaol inhibits the TRIF-dependent signaling pathway. Our goal was to identify the molecular target of 6-shogaol in the TRIF-dependent pathway of TLRs. 6-Shogaol inhibited the activation of interferon-regulatory factor 3 (IRF3) induced by lipopolysaccharide (LPS) and by polyriboinosinic polyribocytidylic acid (poly[I:C]), overexpression of TRIF, TANK-binding kinase1 (TBK1), and IRF3. Furthermore, 6-shogaol inhibited TBK1 activity in vitro. Together, these results suggest that 6-shogaol inhibits the TRIF-dependent signaling pathway of TLRs by targeting TBK1, and, they imply that 6-shogaol can modulate TLR-derived immune/inflammatory target gene expression induced by microbial infection.

Dependence of X-Ray Burst Models on Nuclear Masses

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

Schatz, H.; Ong, W.-J.

X-ray burst model predictions of light curves and the final composition of the nuclear ashes are affected by uncertain nuclear masses. However, not all of these masses are determined experimentally with sufficient accuracy. Here we identify the remaining nuclear mass uncertainties in X-ray burst models using a one-zone model that takes into account the changes in temperature and density evolution caused by changes in the nuclear physics. Two types of bursts are investigated—a typical mixed H/He burst with a limited rapid proton capture process (rp-process) and an extreme mixed H/He burst with an extended rp-process. When allowing for a 3more » σ variation, only three remaining nuclear mass uncertainties affect the light-curve predictions of a typical H/He burst ({sup 27}P, {sup 61}Ga, and {sup 65}As), and only three additional masses affect the composition strongly ({sup 80}Zr, {sup 81}Zr, and {sup 82}Nb). A larger number of mass uncertainties remain to be addressed for the extreme H/He burst, with the most important being {sup 58}Zn, {sup 61}Ga, {sup 62}Ge, {sup 65}As, {sup 66}Se, {sup 78}Y, {sup 79}Y, {sup 79}Zr, {sup 80}Zr, {sup 81}Zr, {sup 82}Zr, {sup 82}Nb, {sup 83}Nb, {sup 86}Tc, {sup 91}Rh, {sup 95}Ag, {sup 98}Cd, {sup 99}In, {sup 100}In, and {sup 101}In. The smallest mass uncertainty that still impacts composition significantly when varied by 3 σ is {sup 85}Mo with 16 keV uncertainty. For one of the identified masses, {sup 27}P, we use the isobaric mass multiplet equation to improve the mass uncertainty, obtaining an atomic mass excess of −716(7) keV. The results provide a roadmap for future experiments at advanced rare isotope beam facilities, where all the identified nuclides are expected to be within reach for precision mass measurements.« less

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...

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

Is vacuum ultraviolet detector a concentration or a mass dependent detector?

PubMed

Liu, Huian; Raffin, Guy; Trutt, Guillaume; Randon, Jérôme

2017-12-29

The vacuum ultraviolet detector (VUV) is a very effective tool for chromatogram deconvolution and peak identification, and can also be used for quantification. To avoid quantitative issues in relation to time drift, such as variation of peak area or peak height, the detector response type has to be well defined. Due to the make-up flow and pressure regulation of make-up, the detector response (height of the peak) and peak area appeared to be dependent on experimental conditions such as inlet pressure and make-up pressure. Even if for some experimental conditions, VUV looks like mass-flow sensitive detector, it has been demonstrated that VUV is a concentration sensitive detector. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

Mass dependent galaxy transformation mechanisms in the complex environment of SuperGroup Abell 1882

NASA Astrophysics Data System (ADS)

Sengupta, Aparajita

We present our data and results from panchromatic photometry and optical spectrometry of the nearest (extremely rich) filamentary large scale structure, SuperGroup Abell 1882. It is a precursor of a cluster and is an inevitable part of the narrative in the study of galaxy transformations. There has been strong empirical evidence over the past three decades that galaxy environment affects galaxy properties. Blue disky galaxies transform into red bulge-like galaxies as they traverse into the deeper recesses of a cluster. However, we have little insight into the story of galaxy evolution in the early stages of cluster formation. Besides, in relaxed clusters that have been studied extensively, several evolutionary mechanisms take effect on similar spatial and temporal scales, making it almost impossible to disentangle different local and global mechanisms. A SuperGroup on the other hand, has a shallower dark-matter potential. Here, the accreting galaxies are subjected to evolutionary mechanisms over larger time and spatial scales. This separates processes that are otherwise superimposed in rich cluster-filament interfaces. As has been found from cluster studies, galaxy color and morphology tie very strongly with local galaxy density even in a complex and nascent structure like Abell 1882. Our major results indicate that there is a strong dependence of galaxy transformations on the galaxy masses themselves. Mass- dependent evolutionary mechanisms affect galaxies at different spatial scales. The galaxy color also varies with radial projected distance from the assumed center of the structure for a constant local galaxy density, indicating the underlying large scale structure as a second order evolutionary driver. We have looked for clues to the types of mechanisms that might cause the transformations at various mass regimes. We have found the thoroughly quenched low mass galaxies confined to the groups, whereas there are evidences of intermediate-mass quenched galaxies

Akt mediated ROS-dependent selective targeting of mutant KRAS tumors.

PubMed

Iskandar, Kartini; Rezlan, Majidah; Pervaiz, Shazib

2014-10-01

Reactive oxygen species (ROS) play a critical role in a variety of cellular processes, ranging from cell survival and proliferation to cell death. Previously, we reported the ability of a small molecule compound, C1, to induce ROS dependent autophagy associated apoptosis in human cancer cell lines and primary tumor cells (Wong C. et al. 2010). Our ongoing investigations have unraveled a hitherto undefined novel signaling network involving hyper-phosphorylation of Akt and Akt-mediated ROS production in cancer cell lines. Interestingly, drug-induced Akt activation is selectively seen in cell lines that carry mutant KRAS; HCT116 cells that carry the V13D KRAS mutation respond favorably to C1 while HT29 cells expressing wild type KRAS are relatively resistant. Of note, not only does the compound target mutant KRAS expressing cells but also induces RAS activation as evidenced by the PAK pull down assay. Corroborating this, pharmacological inhibition as well as siRNA mediated silencing of KRAS or Akt, blocked C1-induced ROS production and rescued tumor colony forming ability in HCT116 cells. To further confirm the involvement of KRAS, we made use of mutant KRAS transformed RWPE-1 prostate epithelial cells. Notably, drug-induced ROS generation and death sensitivity was significantly higher in RWPE-1-KRAS cells than the RWPE-1-vector cells, thus confirming the results obtained with mutant KRAS colorectal carcinoma cell line. Lastly, we made use of HCT116 mutant KRAS knockout cells (KO) where the mutant KRAS allele had been deleted, thus expressing a single wild-type KRAS allele. Exposure of the KO cells to C1 failed to induce Akt activation and mitochondrial ROS production. Taken together, results show the involvement of activated Akt in ROS-mediated selective targeting of mutant KRAS expressing tumors, which could have therapeutic implications given the paucity of chemotherapeutic strategies specifically targeting KRAS mutant cancers. Copyright © 2014. Published by

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...

Evaluation of Mass Filtered, Time Dilated, Time-of-Flight Mass Spectrometry

DTIC Science & Technology

2010-01-01

Figure 4.4: Mass resolution dependence on field for selected actinides and surrogates...45 Figure 4.7: Mass resolution dependence on field for selected actinides and actinide surrogates, modeled with no initial...system. A somewhat better mass resolution would need to be achieved in order to separate hydride molecules in the actinide region. However, the

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.

DeMix Workflow for Efficient Identification of Cofragmented Peptides in High Resolution Data-dependent Tandem Mass Spectrometry*

PubMed Central

Zhang, Bo; Pirmoradian, Mohammad; Chernobrovkin, Alexey; Zubarev, Roman A.

2014-01-01

Based on conventional data-dependent acquisition strategy of shotgun proteomics, we present a new workflow DeMix, which significantly increases the efficiency of peptide identification for in-depth shotgun analysis of complex proteomes. Capitalizing on the high resolution and mass accuracy of Orbitrap-based tandem mass spectrometry, we developed a simple deconvolution method of “cloning” chimeric tandem spectra for cofragmented peptides. Additional to a database search, a simple rescoring scheme utilizes mass accuracy and converts the unwanted cofragmenting events into a surprising advantage of multiplexing. With the combination of cloning and rescoring, we obtained on average nine peptide-spectrum matches per second on a Q-Exactive workbench, whereas the actual MS/MS acquisition rate was close to seven spectra per second. This efficiency boost to 1.24 identified peptides per MS/MS spectrum enabled analysis of over 5000 human proteins in single-dimensional LC-MS/MS shotgun experiments with an only two-hour gradient. These findings suggest a change in the dominant “one MS/MS spectrum - one peptide” paradigm for data acquisition and analysis in shotgun data-dependent proteomics. DeMix also demonstrated higher robustness than conventional approaches in terms of lower variation among the results of consecutive LC-MS/MS runs. PMID:25100859

Dependency of human target detection performance on clutter and quality of supporting image analysis algorithms in a video surveillance task

NASA Astrophysics Data System (ADS)

Huber, Samuel; Dunau, Patrick; Wellig, Peter; Stein, Karin

2017-10-01

Background: In target detection, the success rates depend strongly on human observer performances. Two prior studies tested the contributions of target detection algorithms and prior training sessions. The aim of this Swiss-German cooperation study was to evaluate the dependency of human observer performance on the quality of supporting image analysis algorithms. Methods: The participants were presented 15 different video sequences. Their task was to detect all targets in the shortest possible time. Each video sequence showed a heavily cluttered simulated public area from a different viewing angle. In each video sequence, the number of avatars in the area was altered to 100, 150 and 200 subjects. The number of targets appearing was kept at 10%. The number of marked targets varied from 0, 5, 10, 20 up to 40 marked subjects while keeping the positive predictive value of the detection algorithm at 20%. During the task, workload level was assessed by applying an acoustic secondary task. Detection rates and detection times for the targets were analyzed using inferential statistics. Results: The study found Target Detection Time to increase and Target Detection Rates to decrease with increasing numbers of avatars. The same is true for the Secondary Task Reaction Time while there was no effect on Secondary Task Hit Rate. Furthermore, we found a trend for a u-shaped correlation between the numbers of markings and RTST indicating increased workload. Conclusion: The trial results may indicate useful criteria for the design of training and support of observers in observational tasks.

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.

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.

Renormalization scheme dependence of the two-loop QCD corrections to the neutral Higgs-boson masses in the MSSM.

PubMed

Borowka, S; Hahn, T; Heinemeyer, S; Heinrich, G; Hollik, W

Reaching a theoretical accuracy in the prediction of the lightest MSSM Higgs-boson mass, [Formula: see text], at the level of the current experimental precision requires the inclusion of momentum-dependent contributions at the two-loop level. Recently two groups presented the two-loop QCD momentum-dependent corrections to [Formula: see text] (Borowka et al., Eur Phys J C 74(8):2994, 2014; Degrassi et al., Eur Phys J C 75(2):61, 2015), using a hybrid on-shell-[Formula: see text] scheme, with apparently different results. We show that the differences can be traced back to a different renormalization of the top-quark mass, and that the claim in Ref. Degrassi et al. (Eur Phys J C 75(2):61, 2015) of an inconsistency in Ref. Borowka et al. (Eur Phys J C 74(8):2994, 2014) is incorrect. We furthermore compare consistently the results for [Formula: see text] obtained with the top-quark mass renormalized on-shell and [Formula: see text]. The latter calculation has been added to the FeynHiggs package and can be used to estimate missing higher-order corrections beyond the two-loop level.

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

Size-dependent lymphatic uptake of nanoscale-tailored particles as tumor mass increases.

PubMed

Kjellman, Pontus; Fredriksson, Sarah; Kjellman, Christian; Strand, Sven-Erik; Zandt, René In 't

2015-11-01

To investigate the size-dependent lymphatic uptake of nanoparticles in mice with rapidly growing syngeneic tumors. Mice were inoculated subcutaneously with EL4 lymphoma cells and on day 5 or day 6 of tumor growth, injected peritumorally with either 29 nm or 58 nm of ultra-small superparamagnetic iron oxide nanoparticles. Twenty-four hours later the animals were imaged using MRI. The larger of the two particles can only be detected in the lymph node when injected in animals with 6-day-old tumors while the 29 nm ultra-small superparamagnetic iron oxide nanoparticle is observed on both time points. Tumor mass greatly impacts the size of particles that are transported to the lymph nodes.

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.

Temporally dependent pollinator competition and facilitation with mass flowering crops affects yield in co-blooming crops

PubMed Central

Grab, Heather; Blitzer, Eleanor J.; Danforth, Bryan; Loeb, Greg; Poveda, Katja

2017-01-01

One of the greatest challenges in sustainable agricultural production is managing ecosystem services, such as pollination, in ways that maximize crop yields. Most efforts to increase services by wild pollinators focus on management of natural habitats surrounding farms or non-crop habitats within farms. However, mass flowering crops create resource pulses that may be important determinants of pollinator dynamics. Mass bloom attracts pollinators and it is unclear how this affects the pollination and yields of other co-blooming crops. We investigated the effects of mass flowering apple on the pollinator community and yield of co-blooming strawberry on farms spanning a gradient in cover of apple orchards in the landscape. The effect of mass flowering apple on strawberry was dependent on the stage of apple bloom. During early and peak apple bloom, pollinator abundance and yield were reduced in landscapes with high cover of apple orchards. Following peak apple bloom, pollinator abundance was greater on farms with high apple cover and corresponded with increased yields on these farms. Spatial and temporal overlap between mass flowering and co-blooming crops alters the strength and direction of these dynamics and suggests that yields can be optimized by designing agricultural systems that avoid competition while maximizing facilitation. PMID:28345653

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

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.

Genomic profiling of a Hepatocyte growth factor-dependent signature for MET-targeted therapy in glioblastoma.

PubMed

Johnson, Jennifer; Ascierto, Maria Libera; Mittal, Sandeep; Newsome, David; Kang, Liang; Briggs, Michael; Tanner, Kirk; Marincola, Francesco M; Berens, Michael E; Vande Woude, George F; Xie, Qian

2015-09-17

Constitutive MET signaling promotes invasiveness in most primary and recurrent GBM. However, deployment of available MET-targeting agents is confounded by lack of effective biomarkers for selecting suitable patients for treatment. Because endogenous HGF overexpression often causes autocrine MET activation, and also indicates sensitivity to MET inhibitors, we investigated whether it drives the expression of distinct genes which could serve as a signature indicating vulnerability to MET-targeted therapy in GBM. Interrogation of genomic data from TCGA GBM (Student's t test, GBM patients with high and low HGF expression, p ≤ 0.00001) referenced against patient-derived xenograft (PDX) models (Student's t test, sensitive vs. insensitive models, p ≤ 0.005) was used to identify the HGF-dependent signature. Genomic analysis of GBM xenograft models using both human and mouse gene expression microarrays (Student's t test, treated vs. vehicle tumors, p ≤ 0.01) were performed to elucidate the tumor and microenvironment cross talk. A PDX model with EGFR(amp) was tested for MET activation as a mechanism of erlotinib resistance. We identified a group of 20 genes highly associated with HGF overexpression in GBM and were up- or down-regulated only in tumors sensitive to MET inhibitor. The MET inhibitors regulate tumor (human) and host (mouse) cells within the tumor via distinct molecular processes, but overall impede tumor growth by inhibiting cell cycle progression. EGFR (amp) tumors undergo erlotinib resistance responded to a combination of MET and EGFR inhibitors. Combining TCGA primary tumor datasets (human) and xenograft tumor model datasets (human tumor grown in mice) using therapeutic efficacy as an endpoint may serve as a useful approach to discover and develop molecular signatures as therapeutic biomarkers for targeted therapy. The HGF dependent signature may serve as a candidate predictive signature for patient enrollment in clinical trials using MET inhibitors

NAD-dependent isocitrate dehydrogenase as a novel target of tributyltin in human embryonic carcinoma cells

PubMed Central

Yamada, Shigeru; Kotake, Yaichiro; Demizu, Yosuke; Kurihara, Masaaki; Sekino, Yuko; Kanda, Yasunari

2014-01-01

Tributyltin (TBT) is known to cause developmental defects as endocrine disruptive chemicals (EDCs). At nanomoler concentrations, TBT actions were mediated by genomic pathways via PPAR/RXR. However, non-genomic target of TBT has not been elucidated. To investigate non-genomic TBT targets, we performed comprehensive metabolomic analyses using human embryonic carcinoma NT2/D1 cells. We found that 100 nM TBT reduced the amounts of α-ketoglutarate, succinate and malate. We further found that TBT decreased the activity of NAD-dependent isocitrate dehydrogenase (NAD-IDH), which catalyzes the conversion of isocitrate to α-ketoglutarate in the TCA cycle. In addition, TBT inhibited cell growth and enhanced neuronal differentiation through NAD-IDH inhibition. Furthermore, studies using bacterially expressed human NAD-IDH and in silico simulations suggest that TBT inhibits NAD-IDH due to a possible interaction. These results suggest that NAD-IDH is a novel non-genomic target of TBT at nanomolar levels. Thus, a metabolomic approach may provide new insights into the mechanism of EDC action. PMID:25092173

NAD-dependent isocitrate dehydrogenase as a novel target of tributyltin in human embryonic carcinoma cells

NASA Astrophysics Data System (ADS)

Yamada, Shigeru; Kotake, Yaichiro; Demizu, Yosuke; Kurihara, Masaaki; Sekino, Yuko; Kanda, Yasunari

2014-08-01

Tributyltin (TBT) is known to cause developmental defects as endocrine disruptive chemicals (EDCs). At nanomoler concentrations, TBT actions were mediated by genomic pathways via PPAR/RXR. However, non-genomic target of TBT has not been elucidated. To investigate non-genomic TBT targets, we performed comprehensive metabolomic analyses using human embryonic carcinoma NT2/D1 cells. We found that 100 nM TBT reduced the amounts of α-ketoglutarate, succinate and malate. We further found that TBT decreased the activity of NAD-dependent isocitrate dehydrogenase (NAD-IDH), which catalyzes the conversion of isocitrate to α-ketoglutarate in the TCA cycle. In addition, TBT inhibited cell growth and enhanced neuronal differentiation through NAD-IDH inhibition. Furthermore, studies using bacterially expressed human NAD-IDH and in silico simulations suggest that TBT inhibits NAD-IDH due to a possible interaction. These results suggest that NAD-IDH is a novel non-genomic target of TBT at nanomolar levels. Thus, a metabolomic approach may provide new insights into the mechanism of EDC action.

NAD-dependent isocitrate dehydrogenase as a novel target of tributyltin in human embryonic carcinoma cells.

PubMed

Yamada, Shigeru; Kotake, Yaichiro; Demizu, Yosuke; Kurihara, Masaaki; Sekino, Yuko; Kanda, Yasunari

2014-08-05

Tributyltin (TBT) is known to cause developmental defects as endocrine disruptive chemicals (EDCs). At nanomoler concentrations, TBT actions were mediated by genomic pathways via PPAR/RXR. However, non-genomic target of TBT has not been elucidated. To investigate non-genomic TBT targets, we performed comprehensive metabolomic analyses using human embryonic carcinoma NT2/D1 cells. We found that 100 nM TBT reduced the amounts of α-ketoglutarate, succinate and malate. We further found that TBT decreased the activity of NAD-dependent isocitrate dehydrogenase (NAD-IDH), which catalyzes the conversion of isocitrate to α-ketoglutarate in the TCA cycle. In addition, TBT inhibited cell growth and enhanced neuronal differentiation through NAD-IDH inhibition. Furthermore, studies using bacterially expressed human NAD-IDH and in silico simulations suggest that TBT inhibits NAD-IDH due to a possible interaction. These results suggest that NAD-IDH is a novel non-genomic target of TBT at nanomolar levels. Thus, a metabolomic approach may provide new insights into the mechanism of EDC action.

Segmented beryllium target for a 2 MW super beam facility

DOE PAGES

Davenne, T.; Caretta, O.; Densham, C.; ...

2015-09-14

The Long Baseline Neutrino Facility (LBNF, formerly the Long Baseline Neutrino Experiment) is under design as a next generation neutrino oscillation experiment, with primary objectives to search for CP violation in the leptonic sector, to determine the neutrino mass hierarchy and to provide a precise measurement of θ 23. The facility will generate a neutrino beam at Fermilab by the interaction of a proton beam with a target material. At the ultimate anticipated proton beam power of 2.3 MW the target material must dissipate a heat load of between 10 and 25 kW depending on the target size. This paper presents amore » target concept based on an array of spheres and compares it to a cylindrical monolithic target such as that which currently operates at the T2K facility. Thus simulation results show that the proposed technology offers efficient cooling and lower stresses whilst delivering a neutrino production comparable with that of a conventional solid cylindrical target.« less

Next-to-Leading-Order QCD Corrections to Higgs Boson Plus Jet Production with Full Top-Quark Mass Dependence

NASA Astrophysics Data System (ADS)

Jones, S. P.; Kerner, M.; Luisoni, G.

2018-04-01

We present the next-to-leading-order QCD corrections to the production of a Higgs boson in association with one jet at the LHC including the full top-quark mass dependence. The mass of the bottom quark is neglected. The two-loop integrals appearing in the virtual contribution are calculated numerically using the method of sector decomposition. We study the Higgs boson transverse momentum distribution, focusing on the high pt ,H region, where the top-quark loop is resolved. We find that the next-to-leading-order QCD corrections are large but that the ratio of the next-to-leading-order to leading-order result is similar to that obtained by computing in the limit of large top-quark mass.

Next-to-Leading-Order QCD Corrections to Higgs Boson Plus Jet Production with Full Top-Quark Mass Dependence.

PubMed

Jones, S P; Kerner, M; Luisoni, G

2018-04-20

We present the next-to-leading-order QCD corrections to the production of a Higgs boson in association with one jet at the LHC including the full top-quark mass dependence. The mass of the bottom quark is neglected. The two-loop integrals appearing in the virtual contribution are calculated numerically using the method of sector decomposition. We study the Higgs boson transverse momentum distribution, focusing on the high p_{t,H} region, where the top-quark loop is resolved. We find that the next-to-leading-order QCD corrections are large but that the ratio of the next-to-leading-order to leading-order result is similar to that obtained by computing in the limit of large top-quark mass.

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.

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.

Target and beam-target spin asymmetries in exclusive pion electroproduction for Q2>1 GeV2. II. e p →e π0p

NASA Astrophysics Data System (ADS)

Bosted, P. E.; Kim, A.; Adhikari, K. P.; Adikaram, D.; Akbar, Z.; Amaryan, M. J.; Anefalos Pereira, S.; Avakian, H.; Badui, R. A.; Ball, J.; Balossino, I.; Battaglieri, M.; Bedlinskiy, I.; Biselli, A. S.; Boiarinov, S.; Briscoe, W. J.; Brooks, W. K.; Bültmann, S.; Burkert, V. D.; Cao, T.; Carman, D. S.; Celentano, A.; Chandavar, S.; Charles, G.; Chetry, T.; Ciullo, G.; Clark, L.; Colaneri, L.; Cole, P. L.; Contalbrigo, M.; Cortes, O.; Crede, V.; D'Angelo, A.; Dashyan, N.; De Vita, R.; De Sanctis, E.; Deur, A.; Djalali, C.; Dupre, R.; Egiyan, H.; El Alaoui, A.; El Fassi, L.; Elouadrhiri, L.; Eugenio, P.; Fanchini, E.; Fedotov, G.; Fegan, S.; Fersch, R.; Filippi, A.; Fleming, J. A.; Forest, T. A.; Fradi, A.; Ghandilyan, Y.; Gilfoyle, G. P.; Girod, F. X.; Glazier, D. I.; Gohn, W.; Golovatch, E.; Gothe, R. W.; Griffioen, K. A.; Guidal, M.; Guler, N.; Hakobyan, H.; Guo, L.; Hafidi, K.; Hakobyan, H.; Hanretty, C.; Harrison, N.; Hattawy, M.; Heddle, D.; Hicks, K.; Hollis, G.; Holtrop, M.; Hughes, S. M.; Ireland, D. G.; Isupov, E. L.; Jenkins, D.; Jiang, H.; Jo, H. S.; Joo, K.; Keller, D.; Khachatryan, G.; Khandaker, M.; Kim, W.; Klei, A.; Klein, F. J.; Koirala, S.; Kubarovsky, V.; Kuhn, S. E.; Lanza, L.; Lenisa, P.; Livingston, K.; Lu, H. Y.; MacGregor, I. J. D.; Markov, N.; Mayer, M.; McCracken, M. E.; McKinnon, B.; Mineeva, T.; Mirazita, M.; Mokeev, V. I.; Montgomery, R. A.; Movsisyan, A.; Munoz Camacho, C.; Murdoch, G.; Nadel-Turonski, P.; Ni, A.; Niccolai, S.; Niculescu, G.; Osipenko, M.; Ostrovidov, A. I.; Paolone, M.; Paremuzyan, R.; Park, K.; Pasyuk, E.; Phelps, W.; Pisano, S.; Pogorelko, O.; Price, J. W.; Prok, Y.; Protopopescu, D.; Puckett, A. J. R.; Raue, B. A.; Ripani, M.; Rizzo, A.; Rosner, G.; Rossi, P.; Roy, P.; Sabatié, F.; Saini, M. S.; Schumacher, R. A.; Seder, E.; Sharabian, Y. G.; Skorodumina, Iu.; Smith, G. D.; Sokhan, D.; Sparveris, N.; Stankovic, I.; Stepanyan, S.; Stoler, P.; Strakovsky, I. I.; Strauch, S.; Taiuti, M.; Tian, Ye; Torayev, B.; Ungaro, M.; Voskanyan, H.; Voutier, E.; Walford, N. K.; Watts, D. P.; Wei, X.; Weinstein, L. B.; Zachariou, N.; Zhang, J.; Zhao, Z. W.; Zonta, I.; CLAS Collaboration

2017-03-01

Beam-target double-spin asymmetries and target single-spin asymmetries were measured for the exclusive π0 electroproduction reaction γ*p →p π0 , expanding an analysis of the γ*p →n π+ reaction from the same experiment. The results were obtained from scattering of 6-GeV longitudinally polarized electrons off longitudinally polarized protons using the CEBAF Large Acceptance Spectrometer at Jefferson Laboratory. The kinematic ranges covered are 1.1 target asymmetries were found to generally be greater than zero, with relatively modest ϕ* dependence. The target asymmetries exhibit very strong ϕ* dependence, with a change in sign occurring between results at low W and high W , in contrast to π+ electroproduction. Reasonable agreement is found with phenomenological fits to previous data for W <1.6 GeV, but significant differences are seen at higher W . When combined with cross-sectional measurements, as well as π+ observables, the present results will provide powerful constraints on nucleon resonance amplitudes at moderate and large values of Q2, for resonances with masses as high as 2.4 GeV.

Wave packet dynamics for a system with position and time-dependent effective mass in an infinite square well

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

Vubangsi, M.; Tchoffo, M.; Fai, L. C.

The problem of a particle with position and time-dependent effective mass in a one-dimensional infinite square well is treated by means of a quantum canonical formalism. The dynamics of a launched wave packet of the system reveals a peculiar revival pattern that is discussed. .

The Interplay Between Fat Mass and Fat Distribution as Determinants of the Metabolic Syndrome Is Sex-Dependent.

PubMed

Lind, Lars; Ärnlöv, Johan; Lampa, Erik

2017-09-01

Fat mass and fat distribution are major determinants of the metabolic syndrome (MetS), but the interplay between them has not been thoroughly investigated. In addition, fat mass and fat distribution are generally different in men than in women. We aimed to determine whether the interplay between fat mass and fat distribution regarding MetS and its components is sex-dependent using data from the large-scale population-based sample EpiHealth. Occurrence of MetS and its components was determined together with fat mass by bioimpedance in 19,094 participants in the EpiHealth sample [mean age 61 years (SD 8.5), 56% females]. MetS was defined by the NCEP/ATPIII-criteria. MetS prevalence was 23.0%. Fat mass (percent of body weight) was more strongly related to MetS (and the number of MetS components) in men than in women (P < 0.0001 for interaction term) and in those with a high compared with those with a low waist/hip ratio (WHR). This modulating effect of WHR on the fat mass versus MetS-relationship was more pronounced in women than in men (P < 0.0001 for interaction term). When analyzing the MetS components one by one, fat mass was more closely related to all the individual MetS criteria in men than in women, except for the glucose criteria. Fat mass is more closely related to prevalent MetS in men than in women, but the modulating effect of an abdominal type of fat distribution on the fat mass versus MetS-relationship is stronger in women.

Ion propagation in an aluminum hollow cylinder target laser ion source

NASA Astrophysics Data System (ADS)

Saquilayan, Glynnis Mae Q.; Wada, Motoi

2018-01-01

Experimental results for the laser produced plasma in an aluminum hollow cylinder target are presented. Observing the plasma formation inside the cylinder, a high-speed camera captured the images of the plasma expanding towards the adjacent walls of target. The optical emission spectrum is obtained for the plasma inside the hollow cylinder and positive singly charged aluminum ions and neutrals are identified from emission spectral lines. Time dependent current signals of the Faraday cup displayed an enlarged signal intensity as the laser power density is increased up to 6.5 GW/cm2. Signal arrival times corresponding to fast ions appeared at the onset of the current waveforms when the laser power density exceeded 4.7 GW/cm2. For the mass analysis of plasma, an accelerating electric field was applied to separate the ions and the time-of-flight measurements showed positive ion signals with an identified peak to have an estimated mass of 350 amu.

Time dependency of temperature of a laser-irradiated infrared target pixel as a low-pass filter

NASA Technical Reports Server (NTRS)

Scholl, Marija S.; Scholl, James W.

1990-01-01

The thermal response of a surface layer of a pixel on an infrared target simulator is discussed. This pixel is maintained at a constant temperature by a rapidly scanning laser beam. An analytical model has been developed to describe the exact temperature dependence of a pixel as a function of time for different pixel refresh rates. The top layer of the pixel surface that generates the gray-body radiation shows the temperature dependence on time that is characteristic of a low-pass filter. The experimental results agree with the analytical predictions. The application of a pulsed laser beam to a noncontact, nondestructive diagnostic technique of surface characterization for the presence of microdefects is discussed.

Functional characterization of IgA-targeted bacterial taxa from malnourished Malawian children that produce diet-dependent enteropathy

PubMed Central

Kau, Andrew L.; Planer, Joseph D.; Liu, Jie; Rao, Sindhuja; Yatsunenko, Tanya; Trehan, Indi; Manary, Mark J.; Liu, Ta-Chiang; Stappenbeck, Thaddeus S.; Maleta, Kenneth M.; Ashorn, Per; Dewey, Kathryn G.; Houpt, Eric R.; Hsieh, Chyi-Song; Gordon, Jeffrey I.

2015-01-01

To gain insights into the interrelationships among childhood undernutrition, the gut microbiota, and gut mucosal immune/barrier function, we purified bacterial strains targeted by IgA from the fecal microbiota of two cohorts of Malawian infants and children. IgA responses to several bacterial taxa, including Enterobacteriaceae, correlated with anthropometric measurements of nutritional status in longitudinal studies. The relationship between IgA responses and growth was further explained by enteropathogen burden. Gnotobiotic mouse recipients of an IgA+-bacterial consortium purified from the gut microbiota of undernourished children exhibited a diet-dependent enteropathy characterized by rapid disruption of the small intestinal and colonic epithelial barrier, weight loss and sepsis that could be prevented by administering two IgA-targeted bacterial species from a healthy microbiota. Dissection of a culture collection of 11 IgA-targeted strains from an undernourished donor, sufficient to transmit these phenotypes, disclosed that Enterobacteriaceae interacted with other consortium members to produce enteropathy. These findings indicate that bacterial targets of IgA responses have etiologic, diagnostic, and therapeutic implications for childhood undernutrition. PMID:25717097

RNA-dependent RNA targeting by CRISPR-Cas9

PubMed Central

Strutt, Steven C; Torrez, Rachel M; Kaya, Emine; Negrete, Oscar A

2018-01-01

Double-stranded DNA (dsDNA) binding and cleavage by Cas9 is a hallmark of type II CRISPR-Cas bacterial adaptive immunity. All known Cas9 enzymes are thought to recognize DNA exclusively as a natural substrate, providing protection against DNA phage and plasmids. Here, we show that Cas9 enzymes from both subtypes II-A and II-C can recognize and cleave single-stranded RNA (ssRNA) by an RNA-guided mechanism that is independent of a protospacer-adjacent motif (PAM) sequence in the target RNA. RNA-guided RNA cleavage is programmable and site-specific, and we find that this activity can be exploited to reduce infection by single-stranded RNA phage in vivo. We also demonstrate that Cas9 can direct PAM-independent repression of gene expression in bacteria. These results indicate that a subset of Cas9 enzymes have the ability to act on both DNA and RNA target sequences, and suggest the potential for use in programmable RNA targeting applications. PMID:29303478

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.

Redox-Dependent HMGB1 Isoforms as Pivotal Co-Ordinators of Drug-Induced Liver Injury: Mechanistic Biomarkers and Therapeutic Targets.

PubMed

Lea, Jonathan D; Clarke, Joanna I; McGuire, Niamh; Antoine, Daniel J

2016-04-20

High-mobility group box 1 (HMGB1) is a critical protein in the coordination of the inflammatory response in drug-induced liver injury (DILI). HMGB1 is released from necrotic hepatocytes and activated immune cells. The extracellular function of HMGB1 is dependent upon redox modification of cysteine residues that control chemoattractant and cytokine-inducing properties. Existing biomarkers of DILI such as alanine aminotransferase (ALT) have limitations such as lack of sensitivity and tissue specificity that can adversely affect clinical intervention. HMGB1 isoforms have been shown to be more sensitive biomarkers than ALT for predicting DILI development and the requirement for liver transplant following acetaminophen (APAP) overdose. Hepatocyte-specific conditional knockout of HMGB1 has demonstrated the pivotal role of HMGB1 in DILI and liver disease. Tandem mass spectrometry (MS/MS) enables the characterization and quantification of different mechanism-dependent post-translationally modified isoforms of HMGB1. HMGB1 shows great promise as a biomarker of DILI. However, current diagnostic assays are either too time-consuming to be clinically applicable (MS/MS) or are unable to distinguish between different redox and acetyl isoforms of HMGB1 (ELISA). Additionally, HMGB1 is not liver specific, so while it outperforms ALT (also not liver specific) as a biomarker for the prediction of DILI development, it should be used in a biomarker panel along with liver-specific markers such as miR-122. A point-of-care test for HMGB1 and the development of redox and acetyl isoform-targeting antibodies will advance clinical utility. Work is ongoing to validate baseline levels of circulating HMGB1 in healthy volunteers.

Dependence of GAMA galaxy halo masses on the cosmic web environment from 100 deg2 of KiDS weak lensing data

NASA Astrophysics Data System (ADS)

Brouwer, Margot M.; Cacciato, Marcello; Dvornik, Andrej; Eardley, Lizzie; Heymans, Catherine; Hoekstra, Henk; Kuijken, Konrad; McNaught-Roberts, Tamsyn; Sifón, Cristóbal; Viola, Massimo; Alpaslan, Mehmet; Bilicki, Maciej; Bland-Hawthorn, Joss; Brough, Sarah; Choi, Ami; Driver, Simon P.; Erben, Thomas; Grado, Aniello; Hildebrandt, Hendrik; Holwerda, Benne W.; Hopkins, Andrew M.; de Jong, Jelte T. A.; Liske, Jochen; McFarland, John; Nakajima, Reiko; Napolitano, Nicola R.; Norberg, Peder; Peacock, John A.; Radovich, Mario; Robotham, Aaron S. G.; Schneider, Peter; Sikkema, Gert; van Uitert, Edo; Verdoes Kleijn, Gijs; Valentijn, Edwin A.

2016-11-01

Galaxies and their dark matter haloes are part of a complex network of mass structures, collectively called the cosmic web. Using the tidal tensor prescription these structures can be classified into four cosmic environments: voids, sheets, filaments and knots. As the cosmic web may influence the formation and evolution of dark matter haloes and the galaxies they host, we aim to study the effect of these cosmic environments on the average mass of galactic haloes. To this end we measure the galaxy-galaxy lensing profile of 91 195 galaxies, within 0.039 < z < 0.263, from the spectroscopic Galaxy And Mass Assembly survey, using {˜ }100 ° ^2 of overlapping data from the Kilo-Degree Survey. In each of the four cosmic environments we model the contributions from group centrals, satellites and neighbouring groups to the stacked galaxy-galaxy lensing profiles. After correcting the lens samples for differences in the stellar mass distribution, we find no dependence of the average halo mass of central galaxies on their cosmic environment. We do find a significant increase in the average contribution of neighbouring groups to the lensing profile in increasingly dense cosmic environments. We show, however, that the observed effect can be entirely attributed to the galaxy density at much smaller scales (within 4 h-1 Mpc), which is correlated with the density of the cosmic environments. Within our current uncertainties we find no direct dependence of galaxy halo mass on their cosmic environment.

Targeted Proteomics-Driven Computational Modeling of Macrophage S1P Chemosensing*

PubMed Central

Manes, Nathan P.; Angermann, Bastian R.; Koppenol-Raab, Marijke; An, Eunkyung; Sjoelund, Virginie H.; Sun, Jing; Ishii, Masaru; Germain, Ronald N.; Meier-Schellersheim, Martin; Nita-Lazar, Aleksandra

2015-01-01

Osteoclasts are monocyte-derived multinuclear cells that directly attach to and resorb bone. Sphingosine-1-phosphate (S1P)1 regulates bone resorption by functioning as both a chemoattractant and chemorepellent of osteoclast precursors through two G-protein coupled receptors that antagonize each other in an S1P-concentration-dependent manner. To quantitatively explore the behavior of this chemosensing pathway, we applied targeted proteomics, transcriptomics, and rule-based pathway modeling using the Simmune toolset. RAW264.7 cells (a mouse monocyte/macrophage cell line) were used as model osteoclast precursors, RNA-seq was used to identify expressed target proteins, and selected reaction monitoring (SRM) mass spectrometry using internal peptide standards was used to perform absolute abundance measurements of pathway proteins. The resulting transcript and protein abundance values were strongly correlated. Measured protein abundance values, used as simulation input parameters, led to in silico pathway behavior matching in vitro measurements. Moreover, once model parameters were established, even simulated responses toward stimuli that were not used for parameterization were consistent with experimental findings. These findings demonstrate the feasibility and value of combining targeted mass spectrometry with pathway modeling for advancing biological insight. PMID:26199343

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.

Full mass dependence in Higgs boson production in association with jets at the LHC and FCC

DOE PAGES

Greiner, Nicolas; Höche, Stefan; Luisoni, Gionata; ...

2017-01-23

The first computation of Higgs production in association with three jets at NLO in QCD has recently been performed using the effective theory, where the top quark is treated as an infinitely heavy particle and integrated out. This approach is restricted to the regions in phase space where the typical scales are not larger than the top quark mass. Here we investigate this statement at a quantitative level by calculating the leading-order contributions to the production of a Standard Model Higgs boson in association with up to three jets taking full top-quark and bottom-quark mass dependence into account. We findmore » that the transverse momentum of the hardest particle or jet plays a key role in the breakdown of the effective theory predictions, and that discrepancies can easily reach an order of magnitude for transverse momenta of about 1 TeV. The impact of bottom-quark loops is found to be visible in the small transverse momentum region, leading to corrections of up to 5 percent. Lastly, we further study the impact of mass corrections when VBF selection cuts are applied and when the center-of-mass energy is increased to 100 TeV.« less

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.

Neutrino mass in flavor dependent gauged lepton model

NASA Astrophysics Data System (ADS)

Nomura, Takaaki; Okada, Hiroshi

2018-03-01

We study a neutrino model introducing an additional nontrivial gauged lepton symmetry where the neutrino masses are induced at two-loop level, while the first and second charged-leptons of the standard model are done at one-loop level. As a result of the model structure, we can predict one massless active neutrino, and there is a dark matter candidate. Then we discuss the neutrino mass matrix, muon anomalous magnetic moment, lepton flavor violations, oblique parameters, and relic density of dark matter, taking into account the experimental constraints.

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.

A multielement isotopic study of refractory FUN and F CAIs: Mass-dependent and mass-independent isotope effects

NASA Astrophysics Data System (ADS)

Kööp, Levke; Nakashima, Daisuke; Heck, Philipp R.; Kita, Noriko T.; Tenner, Travis J.; Krot, Alexander N.; Nagashima, Kazuhide; Park, Changkun; Davis, Andrew M.

2018-01-01

Calcium-aluminum-rich inclusions (CAIs) are the oldest dated objects that formed inside the Solar System. Among these are rare, enigmatic objects with large mass-dependent fractionation effects (F CAIs), which sometimes also have large nucleosynthetic anomalies and a low initial abundance of the short-lived radionuclide 26Al (FUN CAIs). We have studied seven refractory hibonite-rich CAIs and one grossite-rich CAI from the Murchison (CM2) meteorite for their oxygen, calcium, and titanium isotopic compositions. The 26Al-26Mg system was also studied in seven of these CAIs. We found mass-dependent heavy isotope enrichment in all measured elements, but never simultaneously in the same CAI. The data are hard to reconcile with a single-stage melt evaporation origin and may require reintroduction or reequilibration for magnesium, oxygen and titanium after evaporation for some of the studied CAIs. The initial 26Al/27Al ratios inferred from model isochrons span a range from <1 × 10-6 to canonical (∼5 × 10-5). The CAIs show a mutual exclusivity relationship between inferred incorporation of live 26Al and the presence of resolvable anomalies in 48Ca and 50Ti. Furthermore, a relationship exists between 26Al incorporation and Δ17O in the hibonite-rich CAIs (i.e., 26Al-free CAIs have resolved variations in Δ17O, while CAIs with resolved 26Mg excesses have Δ17O values close to -23‰). Only the grossite-rich CAI has a relatively enhanced Δ17O value (∼-17‰) in spite of a near-canonical 26Al/27Al. We interpret these data as indicating that fractionated hibonite-rich CAIs formed over an extended time period and sampled multiple stages in the isotopic evolution of the solar nebula, including: (1) an 26Al-poor nebula with large positive and negative anomalies in 48Ca and 50Ti and variable Δ17O; (2) a stage of 26Al-admixture, during which anomalies in 48Ca and 50Ti had been largely diluted and a Δ17O value of ∼-23‰ had been achieved in the CAI formation region; and (3

Identification of POMC exonic variants associated with substance dependence and body mass index.

PubMed

Wang, Fan; Gelernter, Joel; Kranzler, Henry R; Zhang, Huiping

2012-01-01

Risk of substance dependence (SD) and obesity has been linked to the function of melanocortin peptides encoded by the proopiomelanocortin gene (POMC). POMC exons were Sanger sequenced in 280 African Americans (AAs) and 308 European Americans (EAs). Among them, 311 (167 AAs and 114 EAs) were affected with substance (alcohol, cocaine, opioid and/or marijuana) dependence and 277 (113 AAs and164 EAs) were screened controls. We identified 23 variants, including two common polymorphisms (rs10654394 and rs1042571) and 21 rare variants; 12 of which were novel. We used logistic regression to analyze the association between the two common variants and SD or body mass index (BMI), with sex, age, and ancestry proportion as covariates. The common variant rs1042571 in the 3'UTR was significantly associated with BMI in EAs (Overweight: P(adj) = 0.005; Obese: P(adj) = 0.018; Overweight+Obese: P(adj) = 0.002) but not in AAs. The common variant, rs10654394, was not associated with BMI and neither common variant was associated with SD in either population. To evaluate the association between the rare variants and SD or BMI, we collapsed rare variants and tested their prevalence using Fisher's exact test. In AAs, rare variants were nominally associated with SD overall and with specific SD traits (SD: P(FET,1df) = 0.026; alcohol dependence: P(FET,1df) = 0.027; cocaine dependence: P(FET,1df) = 0.007; marijuana dependence: P(FET,1df) = 0.050) (the P-value from cocaine dependence analysis survived Bonferroni correction). There was no such effect in EAs. Although the frequency of the rare variants did not differ significantly between the normal-weight group and the overweight or obese group in either population, certain rare exonic variants occurred only in overweight or obese subjects without SD. These findings suggest that POMC exonic variants may influence risk for both SD and elevated BMI, in a population-specific manner. However, common and rare variants in this gene may exert

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.

A potent series targeting the malarial cGMP-dependent protein kinase clears infection and blocks transmission.

PubMed

Baker, David A; Stewart, Lindsay B; Large, Jonathan M; Bowyer, Paul W; Ansell, Keith H; Jiménez-Díaz, María B; El Bakkouri, Majida; Birchall, Kristian; Dechering, Koen J; Bouloc, Nathalie S; Coombs, Peter J; Whalley, David; Harding, Denise J; Smiljanic-Hurley, Ela; Wheldon, Mary C; Walker, Eloise M; Dessens, Johannes T; Lafuente, María José; Sanz, Laura M; Gamo, Francisco-Javier; Ferrer, Santiago B; Hui, Raymond; Bousema, Teun; Angulo-Barturén, Iñigo; Merritt, Andy T; Croft, Simon L; Gutteridge, Winston E; Kettleborough, Catherine A; Osborne, Simon A

2017-09-05

To combat drug resistance, new chemical entities are urgently required for use in next generation anti-malarial combinations. We report here the results of a medicinal chemistry programme focused on an imidazopyridine series targeting the Plasmodium falciparum cyclic GMP-dependent protein kinase (PfPKG). The most potent compound (ML10) has an IC 50 of 160 pM in a PfPKG kinase assay and inhibits P. falciparum blood stage proliferation in vitro with an EC 50 of 2.1 nM. Oral dosing renders blood stage parasitaemia undetectable in vivo using a P. falciparum SCID mouse model. The series targets both merozoite egress and erythrocyte invasion, but crucially, also blocks transmission of mature P. falciparum gametocytes to Anopheles stephensi mosquitoes. A co-crystal structure of PvPKG bound to ML10, reveals intimate molecular contacts that explain the high levels of potency and selectivity we have measured. The properties of this series warrant consideration for further development to produce an antimalarial drug.Protein kinases are promising drug targets for treatment of malaria. Here, starting with a medicinal chemistry approach, Baker et al. generate an imidazopyridine that selectively targets Plasmodium falciparum PKG, inhibits blood stage parasite growth in vitro and in mice and blocks transmission to mosquitoes.

RNA-dependent RNA targeting by CRISPR-Cas9

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

Strutt, Steven C.; Torrez, Rachel M.; Kaya, Emine

Double-stranded DNA (dsDNA) binding and cleavage by Cas9 is a hallmark of type II CRISPR-Cas bacterial adaptive immunity. All known Cas9 enzymes are thought to recognize DNA exclusively as a natural substrate, providing protection against DNA phage and plasmids. Here, we show that Cas9 enzymes from both subtypes II-A and II-C can recognize and cleave single-stranded RNA (ssRNA) by an RNA-guided mechanism that is independent of a protospacer-adjacent motif (PAM) sequence in the target RNA. RNA-guided RNA cleavage is programmable and site-specific, and we find that this activity can be exploited to reduce infection by single-stranded RNA phage in vivo.more » We also demonstrate that Cas9 can direct PAM-independent repression of gene expression in bacteria. In conclusion, these results indicate that a subset of Cas9 enzymes have the ability to act on both DNA and RNA target sequences, and suggest the potential for use in programmable RNA targeting applications.« less

RNA-dependent RNA targeting by CRISPR-Cas9

DOE PAGES

Strutt, Steven C.; Torrez, Rachel M.; Kaya, Emine; ...

2018-01-05

Double-stranded DNA (dsDNA) binding and cleavage by Cas9 is a hallmark of type II CRISPR-Cas bacterial adaptive immunity. All known Cas9 enzymes are thought to recognize DNA exclusively as a natural substrate, providing protection against DNA phage and plasmids. Here, we show that Cas9 enzymes from both subtypes II-A and II-C can recognize and cleave single-stranded RNA (ssRNA) by an RNA-guided mechanism that is independent of a protospacer-adjacent motif (PAM) sequence in the target RNA. RNA-guided RNA cleavage is programmable and site-specific, and we find that this activity can be exploited to reduce infection by single-stranded RNA phage in vivo.more » We also demonstrate that Cas9 can direct PAM-independent repression of gene expression in bacteria. In conclusion, these results indicate that a subset of Cas9 enzymes have the ability to act on both DNA and RNA target sequences, and suggest the potential for use in programmable RNA targeting applications.« less

Quasi-stationary states of an electron with linearly dependent effective mass in an open nanostructure within transmission coefficient and S-matrix methods

NASA Astrophysics Data System (ADS)

Seti, Julia; Tkach, Mykola; Voitsekhivska, Oxana

2018-03-01

The exact solutions of the Schrödinger equation for a double-barrier open semiconductor plane nanostructure are obtained by using two different approaches, within the model of the rectangular potential profile and the continuous position-dependent effective mass of the electron. The transmission coefficient and scattering matrix are calculated for the double-barrier nanostructure. The resonance energies and resonance widths of the electron quasi-stationary states are analyzed as a function of the size of the near-interface region between wells and barriers, where the effective mass linearly depends on the coordinate. It is established that, in both methods, the increasing size affects in a qualitatively similar way the spectral characteristics of the states, shifting the resonance energies into the low- or high-energy region and increasing the resonance widths. It is shown that the relative difference of resonance energies and widths of a certain state, obtained in the model of position-dependent effective mass and in the widespread abrupt model in physically correct range of near-interface sizes, does not exceed 0.5% and 5%, respectively, independently of the other geometrical characteristics of the structure.

Determination of synthetic lethal interactions in KRAS oncogene-dependent cancer cells reveals novel therapeutic targeting strategies

PubMed Central

Steckel, Michael; Molina-Arcas, Miriam; Weigelt, Britta; Marani, Michaela; Warne, Patricia H; Kuznetsov, Hanna; Kelly, Gavin; Saunders, Becky; Howell, Michael; Downward, Julian; Hancock, David C

2012-01-01

Oncogenic mutations in RAS genes are very common in human cancer, resulting in cells with well-characterized selective advantages, but also less well-understood vulnerabilities. We have carried out a large-scale loss-of-function screen to identify genes that are required by KRAS-transformed colon cancer cells, but not by derivatives lacking this oncogene. Top-scoring genes were then tested in a larger panel of KRAS mutant and wild-type cancer cells. Cancer cells expressing oncogenic KRAS were found to be highly dependent on the transcription factor GATA2 and the DNA replication initiation regulator CDC6. Extending this analysis using a collection of drugs with known targets, we found that cancer cells with mutant KRAS showed selective addiction to proteasome function, as well as synthetic lethality with topoisomerase inhibition. Combination targeting of these functions caused improved killing of KRAS mutant cells relative to wild-type cells. These observations suggest novel targets and new ways of combining existing therapies for optimal effect in RAS mutant cancers, which are traditionally seen as being highly refractory to therapy. PMID:22613949

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

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

Analysis of the Proteome of Hair-Cell Stereocilia by Mass Spectrometry

PubMed Central

Krey, Jocelyn F.; Wilmarth, Philip A.; David, Larry L.; Barr-Gillespie, Peter G.

2017-01-01

Characterization of proteins that mediate mechanotransduction by hair cells, the sensory cells of the inner ear, is hampered by the scarcity of these cells and their sensory organelle, the hair bundle. Mass spectrometry, with its high sensitivity and identification precision, is the ideal method for determining which proteins are present in bundles and what proteins they interact with. We describe here the isolation of mouse hair bundles, as well as preparation of bundle-protein samples for mass spectrometry. We also describe protocols for data-dependent (shotgun) and parallel-reaction-monitoring (targeted) mass spectrometry that allow us to identify and quantify proteins of the hair bundle. These sensitive methods are particularly useful for comparing proteomes of wild-type and mice with deafness mutations affecting hair-bundle proteins. (120 words; maximum 250) PMID:28109437

The β Pictoris association low-mass members: Membership assessment, rotation period distribution, and dependence on multiplicity

NASA Astrophysics Data System (ADS)

Messina, S.; Lanzafame, A. C.; Malo, L.; Desidera, S.; Buccino, A.; Zhang, L.; Artemenko, S.; Millward, M.; Hambsch, F.-J.

2017-10-01

Context. Low-mass members of young loose stellar associations and open clusters exhibit a wide spread of rotation periods. Such a spread originates from the distributions of masses and initial rotation periods. However, multiplicity can also play a significant role. Aims: We aim to investigate the role played by physical companions in multiple systems in shortening the primordial disk lifetime, anticipating the rotation spin up with respect to single stars. Methods: We have compiled the most extensive list to date of low-mass bona fide and candidate members of the young 25-Myr β Pictoris association. We have measured from our own photometric time series or from archival time series the rotation periods of almost all members. In a few cases the rotation periods were retrieved from the literature. We used updated UVWXYZ components to assess the membership of the whole stellar sample. Thanks to the known basic properties of most members we built the rotation period distribution distinguishing between bona fide members and candidate members and according to their multiplicity status. Results: We find that single stars and components of multiple systems in wide orbits (>80 AU) have rotation periods that exhibit a well defined sequence arising from mass distribution with some level of spread likely arising from initial rotation period distribution. All components of multiple systems in close orbits (<80 AU) have rotation periods that are significantly shorter than their equal-mass single counterparts. For these close components of multiple systems a linear dependence of rotation rate on separation is only barely detected. A comparison with the younger 13 Myr h Per cluster and with the older 40-Myr open clusters and stellar associations NGC 2547, IC 2391, Argus, and IC 2602 and the 130-Myr Pleiades shows that whereas the evolution of F-G stars is well reproduced by angular momentum evolution models, this is not the case for the slow K and early-M stars. Finally, we find

Gallic acid targets acute myeloid leukemia via Akt/mTOR-dependent mitochondrial respiration inhibition.

PubMed

Gu, Ruixin; Zhang, Minqin; Meng, Hu; Xu, Dandan; Xie, Yonghua

2018-06-05

Gallic acid is one of the many phenolic acids that can be found in dietary substances and traditional medicine herbs. The anti-cancer activities of gallic acid have been shown in various cancers but its underlying molecular mechanisms are not well understood. In this study, we show Akt/mammalian target of rapamycin (mTOR)-dependent inhibition of mitochondrial respiration as a mechanism of gallic acid's action in acute myeloid leukemia (AML). Gallic acid significantly induces apoptosis of AML cell lines, primary mononuclear cells (MNC) and CD34 stem/progenitors isolated form AML patients via caspase-dependent pathway. It also significantly enhances two standard AML chemotherapeutic agents' efficacy in vitro cell culture system and in vivo xenograft model. Gallic acid inhibits dose- and time-dependent mitochondrial respiration, leading to decreased ATP production and oxidative stress. Overexpression of constitutively active Akt restores gallic acid-mediated inhibition of mTOR signaling, mitochondrial dysfunction, energy crisis and apoptosis. Our results demonstrate that mitochondrial respiration inhibition by gallic acid is a consequence of Akt/mTOR signaling suppression. Our findings suggest that combination therapy with gallic acid may enhance antileukemic efficacy of standard chemotherapeutic agents in AML. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

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...

Target Z dependence of Xe L x-ray emission in heavy ion-atom collision near the Bohr velocity: influence of level matching

NASA Astrophysics Data System (ADS)

Ren, Jieru; Zhao, Yongtao; Zhou, Xianming; Cheng, Rui; Lei, Yu; Sun, Yuanbo; Wang, Xing; Xu, Ge; Wang, Yuyu; Liu, Shidong; Yu, Yang; Li, Yongfeng; Zhang, Xiaoan; Xu, Zhongfeng; Xiao, Guoqing

2013-09-01

X-ray yields for the projectile L-shell have been measured for collisions between Xe20+ and thick solid targets throughout the periodic table with incident energies near the Bohr velocity. The yields show a very pronounced cyclic dependence on the target atomic number. This result indicates that Xe L x-ray emission intensity is greatly enhanced either in near-symmetric collisions or if the binding energy of the Xe M-shell matches the L- or N-shell binding energy of the target.

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…

Functional characterization of IgA-targeted bacterial taxa from undernourished Malawian children that produce diet-dependent enteropathy.

PubMed

Kau, Andrew L; Planer, Joseph D; Liu, Jie; Rao, Sindhuja; Yatsunenko, Tanya; Trehan, Indi; Manary, Mark J; Liu, Ta-Chiang; Stappenbeck, Thaddeus S; Maleta, Kenneth M; Ashorn, Per; Dewey, Kathryn G; Houpt, Eric R; Hsieh, Chyi-Song; Gordon, Jeffrey I

2015-02-25

To gain insights into the interrelationships among childhood undernutrition, the gut microbiota, and gut mucosal immune/barrier function, we purified bacterial strains targeted by immunoglobulin A (IgA) from the fecal microbiota of two cohorts of Malawian infants and children. IgA responses to several bacterial taxa, including Enterobacteriaceae, correlated with anthropometric measurements of nutritional status in longitudinal studies. The relationship between IgA responses and growth was further explained by enteropathogen burden. Gnotobiotic mouse recipients of an IgA(+) bacterial consortium purified from the gut microbiota of undernourished children exhibited a diet-dependent enteropathy characterized by rapid disruption of the small intestinal and colonic epithelial barrier, weight loss, and sepsis that could be prevented by administering two IgA-targeted bacterial species from a healthy microbiota. Dissection of a culture collection of 11 IgA-targeted strains from an undernourished donor, sufficient to transmit these phenotypes, disclosed that Enterobacteriaceae interacted with other consortium members to produce enteropathy. These findings indicate that bacterial targets of IgA responses have etiologic, diagnostic, and therapeutic implications for childhood undernutrition. Copyright © 2015, American Association for the Advancement of Science.

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.

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.

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

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

Label-free integrative pharmacology on-target of drugs at the β2-adrenergic receptor

NASA Astrophysics Data System (ADS)

Ferrie, Ann M.; Sun, Haiyan; Fang, Ye

2011-07-01

We describe a label-free integrative pharmacology on-target (iPOT) method to assess the pharmacology of drugs at the β2-adrenergic receptor. This method combines dynamic mass redistribution (DMR) assays using an array of probe molecule-hijacked cells with similarity analysis. The whole cell DMR assays track cell system-based, ligand-directed, and kinetics-dependent biased activities of the drugs, and translates their on-target pharmacology into numerical descriptors which are subject to similarity analysis. We demonstrate that the approach establishes an effective link between the label-free pharmacology and in vivo therapeutic indications of drugs.

Environmental dependence of the galaxy stellar mass function in the Dark Energy Survey Science Verification Data

DOE PAGES

Etherington, J.; Thomas, D.; Maraston, C.; ...

2016-01-04

Measurements of the galaxy stellar mass function are crucial to understand the formation of galaxies in the Universe. In a hierarchical clustering paradigm it is plausible that there is a connection between the properties of galaxies and their environments. Evidence for environmental trends has been established in the local Universe. The Dark Energy Survey (DES) provides large photometric datasets that enable further investigation of the assembly of mass. In this study we use ~3.2 million galaxies from the (South Pole Telescope) SPT-East field in the DES science verification (SV) dataset. From grizY photometry we derive galaxy stellar masses and absolutemore » magnitudes, and determine the errors on these properties using Monte-Carlo simulations using the full photometric redshift probability distributions. We compute galaxy environments using a fixed conical aperture for a range of scales. We construct galaxy environment probability distribution functions and investigate the dependence of the environment errors on the aperture parameters. We compute the environment components of the galaxy stellar mass function for the redshift range 0.15 < z < 1.05. For z < 0.75 we find that the fraction of massive galaxies is larger in high density environment than in low density environments. We show that the low density and high density components converge with increasing redshift up to z ~ 1.0 where the shapes of the mass function components are indistinguishable. As a result, our study shows how high density structures build up around massive galaxies through cosmic time.« less

Understanding and Improving the Activity of Flavin Dependent Halogenases via Random and Targeted Mutagenesis

PubMed Central

Andorfer, Mary C.

2018-01-01

Flavin dependent halogenases (FDHs) catalyze the halogenation of organic substrates by coordinating reactions of reduced flavin, molecular oxygen, and chloride. Targeted and random mutagenesis of these enzymes has been used to both understand and alter their reactivity. These studies have led to insights into residues essential for catalysis and FDH variants with improved stability, expanded substrate scope, and altered site selectivity. Mutations throughout FDH structures have contributed to all of these advances. More recent studies have sought to rationalize the impact of these mutations on FDH function and to identify new FDHs to deepen our understanding of this enzyme class and to expand their utility for biocatalytic applications. PMID:29589959

XRN2 is required for the degradation of target RNAs by RNase H1-dependent antisense oligonucleotides

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

Hori, Shin-Ichiro; Yamamoto, Tsuyoshi; Obika, Satoshi, E-mail: obika@phs.osaka-u.ac.jp

Antisense oligonucleotides (ASOs) can suppress the expression of a target gene by cleaving pre-mRNA and/or mature mRNA via RNase H1. Following the initial endonucleolytic cleavage by RNase H1, the target RNAs are degraded by a mechanism that is poorly understood. To better understand this degradation pathway, we depleted the expression of two major 5′ to 3′ exoribonucleases (XRNs), named XRN1 and XRN2, and analyzed the levels of 3′ fragments of the target RNAs in vitro. We found that the 3′ fragments of target pre-mRNA generated by ASO were almost completely degraded from their 5′ ends by nuclear XRN2 after RNase H1-mediatedmore » cleavage, whereas the 3′ fragments of mature mRNA were partially degraded by XRN2. In contrast to ASO, small interference RNA (siRNA) could reduce the expression level of only mature mRNA, and the 3′ fragment was degraded by cytoplasmic XRN1. Our findings indicate that the RNAs targeted by RNase H1-dependent ASO are rapidly degraded in the nucleus, contrary to the cytoplasmic degradation pathway mediated by siRNA. - Highlights: • We compared the degradation mechanism of the transcript targeted by ASO and siRNA. • We focused on two 5′ to 3′ exoribonucleases, cytoplasmic XRN1, and nuclear XRN2. • The 3′ fragment of target pre-mRNA generated by ASO was degraded by XRN2. • The 3′ fragment of target mRNA generated by ASO was partially degraded by XRN2. • XRN1 depletion promoted accumulation of the 3′ fragment of mRNA generated by siRNA.« less

Enhanced lysis by bispecific oncolytic measles viruses simultaneously using HER2/neu or EpCAM as target receptors

PubMed Central

Hanauer, Jan RH; Gottschlich, Lisa; Riehl, Dennis; Rusch, Tillmann; Koch, Vivian; Friedrich, Katrin; Hutzler, Stefan; Prüfer, Steffen; Friedel, Thorsten; Hanschmann, Kay-Martin; Münch, Robert C; Jost, Christian; Plückthun, Andreas; Cichutek, Klaus; Buchholz, Christian J; Mühlebach, Michael D

2016-01-01

To target oncolytic measles viruses (MV) to tumors, we exploit the binding specificity of designed ankyrin repeat proteins (DARPins). These DARPin-MVs have high tumor selectivity while maintaining excellent oncolytic potency. Stability, small size, and efficacy of DARPins allowed the generation of MVs simultaneously targeted to tumor marker HER2/neu and cancer stem cell (CSC) marker EpCAM. For optimization, the linker connecting both DARPins was varied in flexibility and length. Flexibility had no impact on fusion helper activity whereas length had. MVs with bispecific MV-H are genetically stable and revealed the desired double-target specificity. In vitro, the cytolytic activity of bispecific MVs was superior or comparable to mono-targeted viruses depending on the target cells. In vivo, therapeutic efficacy of the bispecific viruses was validated in an orthotopic ovarian carcinoma model revealing an effective reduction of tumor mass. Finally, the power of bispecific targeting was demonstrated on cocultures of different tumor cells thereby mimicking tumor heterogeneity in vitro, more closely reflecting real tumors. Here, bispecific excelled monospecific viruses in efficacy. DARPin-based targeting domains thus allow the generation of efficacious oncolytic viruses with double specificity, with the potential to handle intratumoral variation of antigen expression and to simultaneously target CSCs and the bulk tumor mass. PMID:27119117

Mercury (Hg) in meteorites: Variations in abundance, thermal release profile, mass-dependent and mass-independent isotopic fractionation

NASA Astrophysics Data System (ADS)

Meier, Matthias M. M.; Cloquet, Christophe; Marty, Bernard

2016-06-01

We have measured the concentration, isotopic composition and thermal release profiles of Mercury (Hg) in a suite of meteorites, including both chondrites and achondrites. We find large variations in Hg concentration between different meteorites (ca. 10 ppb to 14,000 ppb), with the highest concentration orders of magnitude above the expected bulk solar system silicates value. From the presence of several different Hg carrier phases in thermal release profiles (150-650 °C), we argue that these variations are unlikely to be mainly due to terrestrial contamination. The Hg abundance of meteorites shows no correlation with petrographic type, or mass-dependent fractionation of Hg isotopes. Most carbonaceous chondrites show mass-independent enrichments in the odd-numbered isotopes 199Hg and 201Hg. We show that the enrichments are not nucleosynthetic, as we do not find corresponding nucleosynthetic deficits of 196Hg. Instead, they can partially be explained by Hg evaporation and redeposition during heating of asteroids from primordial radionuclides and late-stage impact heating. Non-carbonaceous chondrites, most achondrites and the Earth do not show these enrichments in vapor-phase Hg. All meteorites studied here have however isotopically light Hg (δ202Hg = ∼-7 to -1) relative to the Earth's average crustal values, which could suggest that the Earth has lost a significant fraction of its primordial Hg. However, the late accretion of carbonaceous chondritic material on the order of ∼2%, which has been suggested to account for the water, carbon, nitrogen and noble gas inventories of the Earth, can also contribute most or all of the Earth's current Hg budget. In this case, the isotopically heavy Hg of the Earth's crust would have to be the result of isotopic fractionation between surface and deep-Earth reservoirs.

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.

A-dependence of phi meson production at HERA-B

NASA Astrophysics Data System (ADS)

Ispiryan, Mikayel

In the HERA-B experiment at DESY, Germany, 920 GeV protons collide with nuclei of the targets. In the collisions many hadrons are produced and detected by the spectrometer, allowing the study of various issues of hadron-hadron and hadron-nucleus interactions. In this thesis the production dependence of the φ meson on the atomic weight A of the nuclei has been studied for several materials, with the goal of obtaining experimental information on proton-nucleus (p-A) interactions. For this, runs and events have been selected according to special criteria. The φ meson's signature---its decay into two charged kaons---has been used to detect the fact of the production of a φ meson in the collision. The RICH detector, the tracking system, and selection algorithms have been used for identification of kaons. The main result, obtaining of which does not depend on the knowledge of integrated luminosity and does not depend heavily on the Monte Carlo simulation of the spectrometer, is the exponent Deltaalpha of the power law of the φ meson production cross-section in an inelastic interaction: sigma ∝ ADeltaalpha, which was measured to be 0.14 .. 0.19 for tungsten, titanium and rhenium, with Deltaalpha = 0.141 +/- 0.012(stat) +/- 0.022(sys) being the most exact number obtained from the analysis of ˜108 events on carbon and tungsten targets. As a by-product, the mass of the φ meson is obtained to be 1.01957 GeV, which did not show dependence on the type of the target nucleus within statistical error of approximately +/-80 keV. The results show a clear experimental indication of A-dependence for φ meson production in proton-nucleon inelastic interactions.

Mass Dependent and Mass Independent Fractionation of Hg Isotopes and Estimation of Photochemical Loss of Hg in Aquatic Systems

NASA Astrophysics Data System (ADS)

Bergquist, B. A.; Blum, J. D.

2007-12-01

Mercury is a globally distributed and highly toxic pollutant, the mobility and bioaccumulation of which is dependent on its redox cycling. Hg isotope analysis is an important new tool for identifying Hg sources and tracking Hg transformations in the environment. Most natural samples analyzed for Hg isotopes display mass-dependent isotope fractionation (MDF), but a small body of data suggests that some natural samples also display mass- independent isotope fractionation (MIF) of the odd Hg isotopes. Here we document MIF of Hg isotopes during an important natural process, constrain the potential mechanism of isotope fractionation, and apply the MIF observed in natural samples to quantify the photochemical reduction of Hg species in the environment. Reduction of Hg species to Hg0 vapor is an important pathway for removal of Hg from aqueous systems into the atmosphere and occurs by abiotic and biotic mechanisms. In laboratory experiments, we find that photochemical reduction Hg species by natural sunlight leads to large MIF of the odd isotopes. Also, the relationship between MIF for the two odd isotopes of Hg is significantly different for different photo-reduction pathways. In contrast, both biological reduction (Kritee et al., 2006) and dark abiotic organically-mediated reduction follow MDF. Natural samples from aquatic ecosystems preserve both MDF and MIF. In fish, MDF increases with the size and Hg concentration of fish suggesting MDF may be useful in understanding Hg bioaccumulation. Fish also display a large range in MIF (4‰), and the relationship between the MIF of the two odd isotopes in fish has a similar slope to the slope found for photo-reduction of CH3Hg+. Since fish bioaccumulate CH3Hg+, fish may be recording the extent to which CH3Hg+ is lost via photochemical reduction in an aquatic ecosystem. Fish populations from different locations have different MIF values, but mostly display similar MIF within a given locale. This suggests that MIF is preserved

Mass dependent stable isotope fractionation of mercury during mer mediated microbial degradation of monomethylmercury

NASA Astrophysics Data System (ADS)

Kritee, K.; Barkay, Tamar; Blum, Joel D.

2009-03-01

Controlling bioaccumulation of toxic monomethylmercury (MMHg) in aquatic food chains requires differentiation between biotic and abiotic pathways that lead to its production and degradation. Recent mercury (Hg) stable isotope measurements of natural samples suggest that Hg isotope ratios can be a powerful proxy for tracing dominant Hg transforming pathways in aquatic ecosystems. Specifically, it has been shown that photo-degradation of MMHg causes both mass dependent (MDF) and mass independent fractionation (MIF) of Hg isotopes. Because the extent of MDF and MIF observed in natural samples (e.g., fish, soil and sediments) can potentially be used to determine the relative importance of pathways leading to MMHg accumulation, it is important to determine the potential role of microbial pathways in contributing to the fractionation, especially MIF, observed in these samples. This study reports the extent of fractionation of Hg stable isotopes during degradation of MMHg to volatile elemental Hg and methane via the microbial Hg resistance ( mer) pathway in Escherichia coli carrying a mercury resistance ( mer) genetic system on a multi-copy plasmid. During experimental microbial degradation of MMHg, MMHg remaining in reactors became progressively heavier (increasing δ202Hg) with time and underwent mass dependent Rayleigh fractionation with a fractionation factor α202/198 = 1.0004 ± 0.0002 (2SD). However, MIF was not observed in any of the microbial MMHg degradation experiments indicating that the isotopic signature left by mer mediated MMHg degradation is significantly different from fractionation observed during DOC mediated photo-degradation of MMHg. Additionally, a clear suppression of Hg isotope fractionation, both during reduction of Hg(II) and degradation of MMHg, was observed when the cell densities increased, possibly due to a reduction in substrate bioavailability. We propose a multi-step framework for understanding the extent of fractionation seen in our MMHg

Differential plasma membrane targeting of voltage-dependent calcium channel subunits expressed in a polarized epithelial cell line

PubMed Central

Brice, Nicola L; Dolphin, Annette C

1999-01-01

Voltage-dependent calcium channels (VDCCs) show a highly non-uniform distribution in many cell types, including neurons and other polarized secretory cells. We have examined whether this can be mimicked in a polarized epithelial cell line (Madin-Darby canine kidney), which has been used extensively to study the targeting of proteins. We expressed the VDCC α1A, α1B or α1C subunits either alone or in combination with accessory subunits α2-δ and the different β subunits, and examined their localization immunocytochemically. An α1 subunit was only targeted to the plasma membrane if co-expressed with the accessory subunits. The combination α1C/α2-δ and all β subunits was always localized predominantly to the basolateral membrane. It has been suggested that this is equivalent to somatodendritic targeting in neurons. In contrast, the α1B subunit was expressed at the apical membrane with all the accessory subunit combinations, by 24 h after microinjection. This membrane destination shows some parallels with axonal targeting in neurons. The α1A subunit was consistently observed at the apical membrane in the combinations α1A/α2-δ/β1b or β4. In contrast, when co-expressed with α2-δ/β2a, α1A was clearly targeted to the basolateral membrane. In conclusion, the VDCC α1 subunit appears to be the primary determinant for targeting the VDCC complex, but the β subunit can modify this destination, particularly for α1A. PMID:10066897

Using a laboratory-based growth model to estimate mass- and temperature-dependent growth parameters across populations of juvenile Chinook Salmon

USGS Publications Warehouse

Perry, Russell W.; Plumb, John M.; Huntington, Charles

2015-01-01

To estimate the parameters that govern mass- and temperature-dependent growth, we conducted a meta-analysis of existing growth data from juvenile Chinook Salmon Oncorhynchus tshawytscha that were fed an ad libitum ration of a pelleted diet. Although the growth of juvenile Chinook Salmon has been well studied, research has focused on a single population, a narrow range of fish sizes, or a narrow range of temperatures. Therefore, we incorporated the Ratkowsky model for temperature-dependent growth into an allometric growth model; this model was then fitted to growth data from 11 data sources representing nine populations of juvenile Chinook Salmon. The model fit the growth data well, explaining 98% of the variation in final mass. The estimated allometric mass exponent (b) was 0.338 (SE = 0.025), similar to estimates reported for other salmonids. This estimate of b will be particularly useful for estimating mass-standardized growth rates of juvenile Chinook Salmon. In addition, the lower thermal limit, optimal temperature, and upper thermal limit for growth were estimated to be 1.8°C (SE = 0.63°C), 19.0°C (SE = 0.27°C), and 24.9°C (SE = 0.02°C), respectively. By taking a meta-analytical approach, we were able to provide a growth model that is applicable across populations of juvenile Chinook Salmon receiving an ad libitum ration of a pelleted diet.

Loss of Cyclin-dependent Kinase 2 in the Pancreas Links Primary β-Cell Dysfunction to Progressive Depletion of β-Cell Mass and Diabetes*

PubMed Central

Kim, So Yoon; Lee, Ji-Hyeon; Merrins, Matthew J.; Gavrilova, Oksana; Bisteau, Xavier; Kaldis, Philipp; Satin, Leslie S.; Rane, Sushil G.

2017-01-01

The failure of pancreatic islet β-cells is a major contributor to the etiology of type 2 diabetes. β-Cell dysfunction and declining β-cell mass are two mechanisms that contribute to this failure, although it is unclear whether they are molecularly linked. Here, we show that the cell cycle regulator, cyclin-dependent kinase 2 (CDK2), couples primary β-cell dysfunction to the progressive deterioration of β-cell mass in diabetes. Mice with pancreas-specific deletion of Cdk2 are glucose-intolerant, primarily due to defects in glucose-stimulated insulin secretion. Accompanying this loss of secretion are defects in β-cell metabolism and perturbed mitochondrial structure. Persistent insulin secretion defects culminate in progressive deficits in β-cell proliferation, reduced β-cell mass, and diabetes. These outcomes may be mediated directly by the loss of CDK2, which binds to and phosphorylates the transcription factor FOXO1 in a glucose-dependent manner. Further, we identified a requirement for CDK2 in the compensatory increases in β-cell mass that occur in response to age- and diet-induced stress. Thus, CDK2 serves as an important nexus linking primary β-cell dysfunction to progressive β-cell mass deterioration in diabetes. PMID:28100774

Concentration Dependent Speciation and Mass Transport Properties of Switchable Polarity Solvents

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

Aaron D. Wilson; Christopher J. Orme

2014-12-01

Tertiary amine switchable polarity solvents (SPS) consisting of predominantly water, tertiary amine, and tertiary ammonium and bicarbonate ions were produced at various concentrations for three different amines: N,N-dimethylcyclohexylamine, N,N-dimethyloctylamine, and 1 cyclohexylpiperidine. For all concentrations, physical properties were measured including viscosity, molecular diffusion coefficients, freezing point depression, and density. Based on these measurements a variation on the Mark Houwink equation was developed to predict the viscosity of any tertiary amine SPS as a function of concentration using the amine’s molecular mass. The observed physical properties allowed the identification of solution state speciation of non-osmotic SPS, where the amine to carbonicmore » acid ratio is significantly greater than one. These results indicate that at most concentrations the stoichiometric excess amine is involved in solvating a proton with two amines. The physical properties of osmotic SPS have consistent concentration dependence behavior over a wide range of concentrations; this consistence suggests osmotic pressures based on low concentrations freezing point studies can be reliably extrapolated to higher concentrations.« less

LeCPK1, a Calcium-Dependent Protein Kinase from Tomato. Plasma Membrane Targeting and Biochemical Characterization1

PubMed Central

Rutschmann, Frank; Stalder, Urs; Piotrowski, Markus; Oecking, Claudia; Schaller, Andreas

2002-01-01

The cDNA of LeCPK1, a calcium-dependent protein kinase, was cloned from tomato (Lycopersicon esculentum Mill.). LeCPK1 was expressed in Escherichia coli and purified from bacterial extracts. The recombinant protein was shown to be a functional protein kinase using a synthetic peptide as the substrate (syntide-2, Km = 85 μm). Autophosphorylation of LeCPK1 was observed on threonine and serine residues, one of which was identified as serine-439. Kinase activity was shown to be Ca2+ dependent and required the C-terminal, calmodulin-like domain of LeCPK1. Two classes of high- and low-affinity Ca2+-binding sites were observed, exhibiting dissociation constants of 0.6 and 55 μm, respectively. LeCPK1 was found to phosphorylate the regulatory C-terminal domain of the plasma membrane H+-ATPase in vitro. A potential role in the regulation of proton pump activity is corroborated by the apparent colocalization of the plasma membrane H+-ATPase and LeCPK1 in vivo. Upon transient expression in suspension-cultured cells, a C-terminal fusion of LeCPK1 with the green fluorescent protein was targeted to the plasma membrane. Myristoylation of the LeCPK1 N terminus was found to be required for plasma membrane targeting. PMID:12011347

Targeting oxidant-dependent mechanisms for the treatment of respiratory diseases and their comorbidities.

PubMed

Thomson, Neil C

2018-06-01

Oxidative stress is implicated in the pathogenesis of respiratory diseases, such as COPD and its comorbidities, asthma, idiopathic pulmonary fibrosis and radiation pneumonitis. Antioxidants drugs, such as small molecule thiols, nuclear erythroid-2 related factor 2 activators and catalytic enzyme mimetics have been developed to target oxidant-dependent mechanisms. The therapeutic effects of antioxidants have been generally disappointing. A small number of antioxidants are approved for clinical use, such as the small molecule thiol N-acetyl-l-cysteine for chronic obstructive pulmonary disease, and in the United States, the superoxide dismutase mimetic AEOL 10150 for severe radiation pneumonitis. The future use of antioxidants for the treatment of chronic respiratory diseases may require a precision medicine approach to identify responsive patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Body Mass Index, Blood Pressure, and Fasting Blood Glucose in Patients With Methamphetamine Dependence.

PubMed

Lv, Dezhao; Zhang, Meijuan; Jin, Xuru; Zhao, Jiyun; Han, Bin; Su, Hang; Zhang, Jie; Zhang, Xiangyang; Ren, Wenwei; He, Jincai

2016-03-01

Methamphetamine (MA) is a prevalently abused psychostimulant in the world. Previously published studies and case reports indicated potential associations between MA and body mass index (BMI) and cardiovascular factors (eg, blood pressure and fasting blood glucose). However, these associations have not been studied clearly. This study aimed to investigate BMI and cardiovascular factors in the MA-dependent patients.A total of 1019 MA-dependent patients were recruited between February 2, 2008 and March 11, 2013. A case report was used to gather information on sociocharacteristics and drug-dependent history. Meanwhile, a number of 1019 age- and sex-matched controls' information were collected from the physical examination center. We measured BMI, blood pressure, and fasting blood glucose among the participants.MA-dependent patients had significantly lower BMI (20.4 ± 0.1 vs 23.9 ± 0.1 kg/m, P < 0.001), lower fasting blood glucose (5.0 ± 0.01 vs 5.2 ± 0.01 mmol/L, P < 0.001) and higher systolic blood pressure (122.1 ± 0.4 vs 114.8 ± 0.4 mmHg, P < 0.001) compared with the control group after adjustment of possible confounders. Additional, we only found the duration of MA use was independently associated with BMI (B = -0.08, P = 0.04).This study demonstrated that MA dependence was associated with BMI and cardiovascular factors. In addition, we found a negative association between duration of MA use and BMI.

Morphological and compositional study of 238U thin film targets for nuclear experiments

NASA Astrophysics Data System (ADS)

Sibbens, Goedele; Ernstberger, Markus; Gouder, Thomas; Marouli, Maria; Moens, André; Seibert, Alice; Vanleeuw, David; Zúñiga, Martin Vargas; Wiss, Thierry; Zampella, Mariavittoria; Zuleger, Evelyn

2018-05-01

The uncertainty in neutron cross section values strongly depends on the quality and characteristics of the deposited actinide films which are used as "targets" in the nuclear experiments. Until recently, at the Joint Research Centre in Geel (JRC-Geel), mass and areal densities of actinide layers were determined by measuring activity (using alpha-particle counting), isotopic composition (using thermal ionisation mass spectrometry) and diameter. In this study a series of 238U deposits, prepared by molecular plating and vacuum deposition on different substrates, were characterized with additional non-destructive and destructive analysis techniques. The quality of the deposits was investigated by autoradiography, high-resolution alpha-particle spectrometry, and scanning electron microscopy. The elemental composition was determined by x-ray photoelectron spectroscopy and inductively coupled plasma mass spectrometry. The latter technique was also applied on the U3O8 starting material and the converted UF4 powder. This paper compares the quality and morphology of deposited 238U films prepared by molecular plating and vacuum deposition on various backings, including their elemental composition determined by different characterization techniques. Also discussed are problems in target preparation and characterization.

Quiescent luminous red galaxies as cosmic chronometers: on the significance of mass and environmental dependence

NASA Astrophysics Data System (ADS)

Liu, G. C.; Lu, Y. J.; Xie, L. Z.; Chen, X. L.; Zhao, Y. H.

2016-01-01

Context. Massive luminous red galaxies (LRGs) are believed to be evolving passively and can be used as cosmic chronometers to estimate the Hubble constant (the differential age method). However, different LRGs may be located in different environments. The environmental effects, if any, on the mean ages of LRGs, and the ages of the oldest LRGs at different redshift, may limit the use of the LRGs as cosmic chronometers. Aims: We aim to investigate the environmental and mass dependence of the formation of "quiescent" LRGs, selected from the Sloan Digital Sky Survey (SDSS) data release 8, and to pave the way for using LRGs as cosmic chronometers. Methods: Using the population synthesis software STARLIGHT, we derive the stellar populations in each LRG through the full spectrum fitting and obtain the mean age distribution and the mean star formation history (SFH) of those LRGs. Results: We find that there is no apparent dependence of the mean age and the SFH of quiescent LRGs on their environment, while the ages of those quiescent LRGs depend weakly on their mass. We compare the SFHs of the SDSS LRGs with those obtained from a semi-analytical galaxy formation model and find that they are roughly consistent with each other if we consider the errors in the STARLIGHT-derived ages. We find that a small fraction of later star formation in LRGs leads to a systematical overestimation (~28%) of the Hubble constant by the differential age method, and the systematical errors in the STARLIGHT-derived ages may lead to an underestimation (~ 16%) of the Hubble constant. However, these errors can be corrected by a detailed study of the mean SFH of those LRGs and by calibrating the STARLIGHT-derived ages with those obtained independently by other methods. Conclusions: The environmental effects do not play a significant role in the age estimates of quiescent LRGs; and the quiescent LRGs as a population can be used securely as cosmic chronometers, and the Hubble constant can be measured

Body mass dependence of glycogen stores in the anoxia-tolerant crucian carp ( Carassius carassius L.)

NASA Astrophysics Data System (ADS)

Vornanen, Matti; Asikainen, Juha; Haverinen, Jaakko

2011-03-01

Glycogen is a vital energy substrate for anaerobic organisms, and the size of glycogen stores can be a limiting factor for anoxia tolerance of animals. To this end, glycogen stores in 12 different tissues of the crucian carp ( Carassius carassius L.), an anoxia-tolerant fish species, were examined. Glycogen content of different tissues was 2-10 times higher in winter (0.68-18.20% of tissue wet weight) than in summer (0.12-4.23%). In scale, bone and brain glycogen stores were strongly dependent on body mass (range between 0.6 and 785 g), small fish having significantly more glycogen than large fish ( p < 0.05). In fin and skin, size dependence was evident in winter, but not in summer, while in other tissues (ventricle, atrium, intestine, liver, muscle, and spleen), no size dependence was found. The liver was much bigger in small than large fish ( p < 0.001), and there was a prominent enlargement of the liver in winter irrespective of fish size. As a consequence, the whole body glycogen reserves, measured as a sum of glycogen from different tissues, varied from 6.1% of the body mass in the 1-g fish to 2.0% in the 800-g fish. Since anaerobic metabolic rate scales down with body size, the whole body glycogen reserves could provide energy for approximately 79 and 88 days of anoxia in small and large fish, respectively. There was, however, a drastic difference in tissue distribution of glycogen between large and small fish: in the small fish, the liver was the major glycogen store (68% of the stores), while in the large fish, the white myotomal muscle was the principal deposit of glycogen (57%). Since muscle glycogen is considered to be unavailable for blood glucose regulation, its usefulness in anoxia tolerance of the large crucian carp might be limited, although not excluded. Therefore, mobilization of muscle glycogen under anoxia needs to be rigorously tested.

The fermionic projector in a time-dependent external potential: Mass oscillation property and Hadamard states

NASA Astrophysics Data System (ADS)

Finster, Felix; Murro, Simone; Röken, Christian

2016-07-01

We give a non-perturbative construction of the fermionic projector in Minkowski space coupled to a time-dependent external potential which is smooth and decays faster than quadratically for large times. The weak and strong mass oscillation properties are proven. We show that the integral kernel of the fermionic projector is of the Hadamard form, provided that the time integral of the spatial sup-norm of the potential satisfies a suitable bound. This gives rise to an algebraic quantum field theory of Dirac fields in an external potential with a distinguished pure quasi-free Hadamard state.

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.

A generalizable platform for interrogating target- and signal-specific consequences of electrophilic modifications in redox-dependent cell signaling.

PubMed

Lin, Hong-Yu; Haegele, Joseph A; Disare, Michael T; Lin, Qishan; Aye, Yimon

2015-05-20

Despite the known propensity of small-molecule electrophiles to react with numerous cysteine-active proteins, biological actions of individual signal inducers have emerged to be chemotype-specific. To pinpoint and quantify the impacts of modifying one target out of the whole proteome, we develop a target-protein-personalized "electrophile toolbox" with which specific intracellular targets can be selectively modified at a precise time by specific reactive signals. This general methodology, T-REX (targetable reactive electrophiles and oxidants), is established by (1) constructing a platform that can deliver a range of electronic and sterically different bioactive lipid-derived signaling electrophiles to specific proteins in cells; (2) probing the kinetics of targeted delivery concept, which revealed that targeting efficiency in cells is largely driven by initial on-rate of alkylation; and (3) evaluating the consequences of protein-target- and small-molecule-signal-specific modifications on the strength of downstream signaling. These data show that T-REX allows quantitative interrogations into the extent to which the Nrf2 transcription factor-dependent antioxidant response element (ARE) signaling is activated by selective electrophilic modifications on Keap1 protein, one of several redox-sensitive regulators of the Nrf2-ARE axis. The results document Keap1 as a promiscuous electrophile-responsive sensor able to respond with similar efficiencies to discrete electrophilic signals, promoting comparable strength of Nrf2-ARE induction. T-REX is also able to elicit cell activation in cases in which whole-cell electrophile flooding fails to stimulate ARE induction prior to causing cytotoxicity. The platform presents a previously unavailable opportunity to elucidate the functional consequences of small-molecule-signal- and protein-target-specific electrophilic modifications in an otherwise unaffected cellular background.

PIK3CA dependence and sensitivity to therapeutic targeting in urothelial carcinoma.

PubMed

Ross, R L; McPherson, H R; Kettlewell, L; Shnyder, S D; Hurst, C D; Alder, O; Knowles, M A

2016-07-28

Many urothelial carcinomas (UC) contain activating PIK3CA mutations. In telomerase-immortalized normal urothelial cells (TERT-NHUC), ectopic expression of mutant PIK3CA induces PI3K pathway activation, cell proliferation and cell migration. However, it is not clear whether advanced UC tumors are PIK3CA-dependent and whether PI3K pathway inhibition is a good therapeutic option in such cases. We used retrovirus-mediated delivery of shRNA to knock down mutant PIK3CA in UC cell lines and assessed effects on pathway activation, cell proliferation, migration and tumorigenicity. The effect of the class I PI3K inhibitor GDC-0941 was assessed in a panel of UC cell lines with a range of known molecular alterations in the PI3K pathway. Specific knockdown of PIK3CA inhibited proliferation, migration, anchorage-independent growth and in vivo tumor growth of cells with PIK3CA mutations. Sensitivity to GDC-0941 was dependent on hotspot PIK3CA mutation status. Cells with rare PIK3CA mutations and co-occurring TSC1 or PTEN mutations were less sensitive. Furthermore, downstream PI3K pathway alterations in TSC1 or PTEN or co-occurring AKT1 and RAS gene mutations were associated with GDC-0941 resistance. Mutant PIK3CA is a potent oncogenic driver in many UC cell lines and may represent a valuable therapeutic target in advanced bladder cancer.

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.

CRISPR/Cas9 mutagenesis invalidates a putative cancer dependency targeted in on-going clinical trials.

PubMed

Lin, Ann; Giuliano, Christopher J; Sayles, Nicole M; Sheltzer, Jason M

2017-03-24

The Maternal Embryonic Leucine Zipper Kinase (MELK) has been reported to be a genetic dependency in several cancer types. MELK RNAi and small-molecule inhibitors of MELK block the proliferation of various cancer cell lines, and MELK knockdown has been described as particularly effective against the highly-aggressive basal/triple-negative subtype of breast cancer. Based on these preclinical results, the MELK inhibitor OTS167 is currently being tested as a novel chemotherapy agent in several clinical trials. Here, we report that mutagenizing MELK with CRISPR/Cas9 has no effect on the fitness of basal breast cancer cell lines or cell lines from six other cancer types. Cells that harbor null mutations in MELK exhibit wild-type doubling times, cytokinesis, and anchorage-independent growth. Furthermore, MELK-knockout lines remain sensitive to OTS167, suggesting that this drug blocks cell division through an off-target mechanism. In total, our results undermine the rationale for a series of current clinical trials and provide an experimental approach for the use of CRISPR/Cas9 in preclinical target validation that can be broadly applied.

Two-proton correlations in the target fragmentation region of nuclear collisions at 200 A GeV

NASA Astrophysics Data System (ADS)

Awes, T. C.; Barlag, C.; Berger, F.; Bloomer, M. A.; Blume, C.; Bock, D.; Bock, R.; Bohne, E.-M.; Bucher, D.; Claussen, A.; Clewing, G.; Dragon, L.; Eklund, A.; Garpman, S.; Glasow, R.; Gustafsson, H.; Gutbrod, H. H.; Hölker, G.; Idh, J.; Jacobs, P.; Kampert, K. H.; Kolb, B. W.; Löhner, H.; Lund, I.; Obenshain, F. E.; Oskarsson, A.; Otterlund, I.; Peitzmann, T.; Plasil, F.; Poskanzer, A. M.; Purschke, M.; Roters, B.; Saini, S.; Santo, R.; Schmidt, H. R.; Sørensen, S. P.; Steffens, K.; Steinhaeuser, P.; Stenlund, E.; Stüken, D.; Young, G. R.

1995-06-01

Correlations between protons are studied in the target fragmentation region of reactions of protons and16O with C, Cu, Ag, Au and of32S with Al and Au at 200 A GeV. The emitted protons were measured with the Plastic Ball detector in the WA80 experiment at the CERN SPS. The comparison of the correlation function with calculations, assuming a spherical, gaussian shaped source with a lifetime τ=0 fm/ c, allows the extraction of radius parameters. The values are very close to those expected from the geometry of the target nuclei and increase with the target mass as α A {Target/1/3}. Even in proton induced reactions the whole target nucleus is involved. The dependence of the radii on centrality, polar angle θ lab, and energy, and their relation to measured proton yields are presented.

Androgen receptor-dependent and -independent mechanisms driving prostate cancer progression: Opportunities for therapeutic targeting from multiple angles

PubMed Central

Hoang, David T; Iczkowski, Kenneth A; Kilari, Deepak; See, William; Nevalainen, Marja T

2017-01-01

Despite aggressive treatment for localized cancer, prostate cancer (PC) remains a leading cause of cancer-related death for American men due to a subset of patients progressing to lethal and incurable metastatic castrate-resistant prostate cancer (CRPC). Organ-confined PC is treated by surgery or radiation with or without androgen deprivation therapy (ADT), while options for locally advanced and disseminated PC include radiation combined with ADT, or systemic treatments including chemotherapy. Progression to CRPC results from failure of ADT, which targets the androgen receptor (AR) signaling axis and inhibits AR-driven proliferation and survival pathways. The exact mechanisms underlying the transition from androgen-dependent PC to CRPC remain incompletely understood. Reactivation of AR has been shown to occur in CRPC despite depletion of circulating androgens by ADT. At the same time, the presence of AR-negative cell populations in CRPC has also been identified. While AR signaling has been proposed as the primary driver of CRPC, AR-independent signaling pathways may represent additional mechanisms underlying CRPC progression. Identification of new therapeutic strategies to target both AR-positive and AR-negative PC cell populations and, thereby, AR-driven as well as non-AR-driven PC cell growth and survival mechanisms would provide a two-pronged approach to eliminate CRPC cells with potential for synthetic lethality. In this review, we provide an overview of AR-dependent and AR-independent molecular mechanisms which drive CRPC, with special emphasis on the role of the Jak2-Stat5a/b signaling pathway in promoting castrate-resistant growth of PC through both AR-dependent and AR-independent mechanisms. PMID:27741508

A targeted complement-dependent strategy to improve the outcome of mAb therapy, and characterization in a murine model of metastatic cancer

PubMed Central

Elvington, Michelle; Huang, Yuxiang; Morgan, B. Paul; Qiao, Fei; van Rooijen, Nico; Atkinson, Carl

2012-01-01

Complement inhibitors expressed on tumor cells provide an evasion mechanism against mAb therapy and may modulate the development of an acquired antitumor immune response. Here we investigate a strategy to amplify mAb-targeted complement activation on a tumor cell, independent of a requirement to target and block complement inhibitor expression or function, which is difficult to achieve in vivo. We constructed a murine fusion protein, CR2Fc, and demonstrated that the protein targets to C3 activation products deposited on a tumor cell by a specific mAb, and amplifies mAb-dependent complement activation and tumor cell lysis in vitro. In syngeneic models of metastatic lymphoma (EL4) and melanoma (B16), CR2Fc significantly enhanced the outcome of mAb therapy. Subsequent studies using the EL4 model with various genetically modified mice and macrophage-depleted mice revealed that CR2Fc enhanced the therapeutic effect of mAb therapy via both macrophage-dependent FcγR-mediated antibody-dependent cellular cytotoxicity, and by direct complement-mediated lysis. Complement activation products can also modulate adaptive immunity, but we found no evidence that either mAb or CR2Fc treatment had any effect on an antitumor humoral or cellular immune response. CR2Fc represents a potential adjuvant treatment to increase the effectiveness of mAb therapy of cancer. PMID:22442351

Confirming therapeutic target of protopine using immobilized β2 -adrenoceptor coupled with site-directed molecular docking and the target-drug interaction by frontal analysis and injection amount-dependent method.

PubMed

Liu, Guangxin; Wang, Pei; Li, Chan; Wang, Jing; Sun, Zhenyu; Zhao, Xinfeng; Zheng, Xiaohui

2017-07-01

Drug-protein interaction analysis is pregnant in designing new leads during drug discovery. We prepared the stationary phase containing immobilized β 2 -adrenoceptor (β 2 -AR) by linkage of the receptor on macroporous silica gel surface through N,N'-carbonyldiimidazole method. The stationary phase was applied in identifying antiasthmatic target of protopine guided by the prediction of site-directed molecular docking. Subsequent application of immobilized β 2 -AR in exploring the binding of protopine to the receptor was realized by frontal analysis and injection amount-dependent method. The association constants of protopine to β 2 -AR by the 2 methods were (1.00 ± 0.06) × 10 5 M -1 and (1.52 ± 0.14) × 10 4 M -1 . The numbers of binding sites were (1.23 ± 0.07) × 10 -7 M and (9.09 ± 0.06) × 10 -7 M, respectively. These results indicated that β 2 -AR is the specific target for therapeutic action of protopine in vivo. The target-drug binding occurred on Ser 169 in crystal structure of the receptor. Compared with frontal analysis, injection amount-dependent method is advantageous to drug saving, improvement of sampling efficiency, and performing speed. It has grave potential in high-throughput drug-receptor interaction analysis. Copyright © 2017 John Wiley & Sons, Ltd.

A Generalizable Platform for Interrogating Target- and Signal-Specific Consequences of Electrophilic Modifications in Redox-Dependent Cell Signaling

PubMed Central

Lin, Hong-Yu; Haegele, Joseph A.; Disare, Michael T.; Lin, Qishan; Aye, Yimon

2015-01-01

Despite the known propensity of small-molecule electrophiles to react with numerous cysteine-active proteins, biological actions of individual signal inducers have emerged to be chemotype-specific. To pinpoint and quantify the impacts of modifying one target out of the whole proteome, we develop a target-protein-personalized “electrophile toolbox” with which specific intracellular targets can be selectively modified at a precise time by specific reactive signals. This general methodology—T-REX (targetable reactive electrophiles & oxidants)—is established by: (1) constructing a platform that can deliver a range of electronic and sterically different bioactive lipid-derived signaling electrophiles to specific proteins in cells; (2) probing the kinetics of targeted delivery concept which revealed that targeting efficiency in cells is largely driven by initial on-rate of alkylation; and (3) evaluating the consequences of protein-target- and small-molecule-signal-specific modifications on the strength of downstream signaling. These data show that T-REX allows quantitative interrogations into the extent to which the Nrf2 transcription factor-dependent antioxidant response element (ARE) signaling is activated by selective electrophilic modifications on Keap1 protein—one of several redox-sensitive regulators of the Nrf2–ARE axis. The results document Keap1 as a promiscuous electrophile-responsive sensor able to respond with similar efficiencies to discrete electrophilic signals, promoting comparable strength of Nrf2–ARE induction. T-REX is also able to elicit cell activation in cases in which whole-cell electrophile flooding fails to stimulate ARE induction prior to causing cytotoxicity. The platform presents a previously unavailable opportunity to elucidate the functional consequences of small-molecule-signal- and protein-target-specific electrophilic modifications in an otherwise unaffected cellular background. PMID:25909755

Continuous movement decoding using a target-dependent model with EMG inputs.

PubMed

Sachs, Nicholas A; Corbett, Elaine A; Miller, Lee E; Perreault, Eric J

2011-01-01

Trajectory-based models that incorporate target position information have been shown to accurately decode reaching movements from bio-control signals, such as muscle (EMG) and cortical activity (neural spikes). One major hurdle in implementing such models for neuroprosthetic control is that they are inherently designed to decode single reaches from a position of origin to a specific target. Gaze direction can be used to identify appropriate targets, however information regarding movement intent is needed to determine when a reach is meant to begin and when it has been completed. We used linear discriminant analysis to classify limb states into movement classes based on recorded EMG from a sparse set of shoulder muscles. We then used the detected state transitions to update target information in a mixture of Kalman filters that incorporated target position explicitly in the state, and used EMG activity to decode arm movements. Updating the target position initiated movement along new trajectories, allowing a sequence of appropriately timed single reaches to be decoded in series and enabling highly accurate continuous control.

Investigation of mass dependence effects for the accurate determination of molybdenum isotope amount ratios by MC-ICP-MS using synthetic isotope mixtures.

PubMed

Malinovsky, Dmitry; Dunn, Philip J H; Petrov, Panayot; Goenaga-Infante, Heidi

2015-01-01

Methodology for absolute Mo isotope amount ratio measurements by multicollector inductively coupled plasma-mass spectrometry (MC-ICP-MS) using calibration with synthetic isotope mixtures (SIMs) is presented. For the first time, synthetic isotope mixtures prepared from seven commercially available isotopically enriched molybdenum metal powders ((92)Mo, (94)Mo, (95)Mo, (96)Mo, (97)Mo, (98)Mo, and (100)Mo) are used to investigate whether instrumental mass discrimination of Mo isotopes in MC-ICP-MS is consistent with mass-dependent isotope distribution. The parent materials were dissolved and mixed as solutions to obtain mixtures with accurately known isotope amount ratios. The level of elemental impurities in the isotopically enriched molybdenum metal powders was quantified by ICP-MS by using both high-resolution and reaction cell instruments to completely resolve spectral interferences. The Mo isotope amount ratio values with expanded uncertainty (k = 2), determined by MC-ICP-MS for a high-purity Mo rod from Johnson Matthey, were as follows: (92)Mo/(95)Mo = 0.9235(9), (94)Mo/(95)Mo = 0.5785(8), (96)Mo/(95)Mo = 1.0503(9), (97)Mo/(95)Mo = 0.6033(6), (98)Mo/(95)Mo = 1.5291(20), and (100)Mo/(95)Mo = 0.6130(7). A full uncertainty budget for the measurements is presented which shows that the largest contribution to the uncertainty budget comes from correction for elemental impurities (∼51%), followed by the contribution from weighing operations (∼26 %). The atomic weight of molybdenum was calculated to be 95.947(2); the uncertainty in parentheses is expanded uncertainty with the coverage factor of 2. A particular advantage of the developed method is that calibration factors for all six Mo isotope amount ratios, involving the (95)Mo isotope, were experimentally determined. This allows avoiding any assumption on mass-dependent isotope fractions in MC-ICP-MS, inherent to the method of double spike previously used for Mo isotope amount ratio

The mass function and dynamical mass of young star clusters: why their initial crossing-time matters crucially

NASA Astrophysics Data System (ADS)

Parmentier, Geneviève; Baumgardt, Holger

2012-12-01

We highlight the impact of cluster-mass-dependent evolutionary rates upon the evolution of the cluster mass function during violent relaxation, that is, while clusters dynamically respond to the expulsion of their residual star-forming gas. Mass-dependent evolutionary rates arise when the mean volume density of cluster-forming regions is mass-dependent. In that case, even if the initial conditions are such that the cluster mass function at the end of violent relaxation has the same shape as the embedded-cluster mass function (i.e. infant weight-loss is mass-independent), the shape of the cluster mass function does change transiently during violent relaxation. In contrast, for cluster-forming regions of constant mean volume density, the cluster mass function shape is preserved all through violent relaxation since all clusters then evolve at the same mass-independent rate. On the scale of individual clusters, we model the evolution of the ratio of the dynamical mass to luminous mass of a cluster after gas expulsion. Specifically, we map the radial dependence of the time-scale for a star cluster to return to equilibrium. We stress that fields of view a few pc in size only, typical of compact clusters with rapid evolutionary rates, are likely to reveal cluster regions which have returned to equilibrium even if the cluster experienced a major gas expulsion episode a few Myr earlier. We provide models with the aperture and time expressed in units of the initial half-mass radius and initial crossing-time, respectively, so that our results can be applied to clusters with initial densities, sizes, and apertures different from ours.

Target fragments in collisions of 1.8 GeV/nucleon Fe-56 nuclei with photoemulsion nuclei, and the cascade-evaporation model

NASA Technical Reports Server (NTRS)

Dudkin, V. E.; Kovalev, E. E.; Nefedov, N. A.; Antonchik, V. A.; Bogdanov, S. D.; Ostroumov, V. I.; Benton, E. V.; Crawford, H. J.

1995-01-01

Nuclear photographic emulsion is used to study the dependence of the characteristics of target-nucleus fragments on the masses and impact parameters of interacting nuclei. The data obtained are compared in all details with the calculation results made in terms of the Dubna version of the cascade-evaporation model (DCM).

Body-mass dependence of age-related deterioration in human muscular function.

PubMed

Meltzer, D E

1996-04-01

Maximal anaerobic power of human muscles declines with increasing chronological age and is correlated with body mass. This study investigated whether the rate of deterioration in human muscular function among trained weight lifters is also correlated with body mass. Cross-sectional analysis of performance data of over 1,100 Masters competitors in Olympic-style weight lifting was carried out; eight body-weight classes and six age groups were represented. Two-lift total data (sum of snatch and clean and jerk lifts) were analyzed. Mean deterioration rates in the performance of athletes of widely diverse body masses were compared over the following age ranges: 42-57, 42-62, and 42-67 yr. No statistically significant correlation (P < 0.05) was found between rate of performance decline and body mass. The relationship between body mass and the magnitude of age-related variation of deterioration rate was also studied; no significant correlation was found. Previous studies have demonstrated that performance in Olympic-style weight lifting is correlated with maximal anaerobic muscular power. This leads us to suggest that the age-related deterioration rate of anaerobic power in trained subjects may not be correlated with the body mass of the individual.

Scaling the Drosophila Wing: TOR-Dependent Target Gene Access by the Hippo Pathway Transducer Yorkie

PubMed Central

Parker, Joseph; Struhl, Gary

2015-01-01

Organ growth is controlled by patterning signals that operate locally (e.g., Wingless/Ints [Wnts], Bone Morphogenetic Proteins [BMPs], and Hedgehogs [Hhs]) and scaled by nutrient-dependent signals that act systemically (e.g., Insulin-like peptides [ILPs] transduced by the Target of Rapamycin [TOR] pathway). How cells integrate these distinct inputs to generate organs of the appropriate size and shape is largely unknown. The transcriptional coactivator Yorkie (Yki, a YES-Associated Protein, or YAP) acts downstream of patterning morphogens and other tissue-intrinsic signals to promote organ growth. Yki activity is regulated primarily by the Warts/Hippo (Wts/Hpo) tumour suppressor pathway, which impedes nuclear access of Yki by a cytoplasmic tethering mechanism. Here, we show that the TOR pathway regulates Yki by a separate and novel mechanism in the Drosophila wing. Instead of controlling Yki nuclear access, TOR signaling governs Yki action after it reaches the nucleus by allowing it to gain access to its target genes. When TOR activity is inhibited, Yki accumulates in the nucleus but is sequestered from its normal growth-promoting target genes—a phenomenon we term “nuclear seclusion.” Hence, we posit that in addition to its well-known role in stimulating cellular metabolism in response to nutrients, TOR also promotes wing growth by liberating Yki from nuclear seclusion, a parallel pathway that we propose contributes to the scaling of wing size with nutrient availability. PMID:26474042

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

CCL2 and CCL5 Are Novel Therapeutic Targets for Estrogen-Dependent Breast Cancer.

PubMed

Svensson, Susanne; Abrahamsson, Annelie; Rodriguez, Gabriela Vazquez; Olsson, Anna-Karin; Jensen, Lasse; Cao, Yihai; Dabrosin, Charlotta

2015-08-15

Novel therapeutic targets of estrogen receptor (ER)-positive breast cancers are urgently needed because current antiestrogen therapy causes severe adverse effects, nearly 50% of patients are intrinsically resistant, and the majority of recurrences have maintained ER expression. We investigated the role of estrogen-dependent chemokine expression and subsequent cancer growth in human tissues and experimental breast cancer models. For in vivo sampling of human chemokines, microdialysis was used in breast cancers of women or normal human breast tissue before and after tamoxifen therapy. Estrogen exposure and targeted therapies were assessed in immune competent PyMT murine breast cancer, orthotopic human breast cancers in nude mice, cell culture of cancer cells, and freshly isolated human macrophages. Cancer cell dissemination was investigated using zebrafish. ER(+) cancers in women produced high levels of extracellular CCL2 and CCL5 in vivo, which was associated with infiltration of tumor-associated macrophages. In experimental breast cancer, estradiol enhanced macrophage influx and angiogenesis through increased release of CCL2, CCL5, and vascular endothelial growth factor. These effects were inhibited by anti-CCL2 or anti-CCL5 therapy, which resulted in potent inhibition of cancer growth. In addition, estradiol induced a protumorigenic activation of the macrophages. In a zebrafish model, macrophages increased cancer cell dissemination via CCL2 and CCL5 in the presence of estradiol, which was inhibited with anti-CCL2 and anti-CCL5 treatment. Our findings shed new light on the mechanisms underlying the progression of ER(+) breast cancer and indicate the potential of novel therapies targeting CCL2 and CCL5 pathways. ©2015 American Association for Cancer Research.

Model Cortical Association Fields Account for the Time Course and Dependence on Target Complexity of Human Contour Perception

PubMed Central

Gintautas, Vadas; Ham, Michael I.; Kunsberg, Benjamin; Barr, Shawn; Brumby, Steven P.; Rasmussen, Craig; George, John S.; Nemenman, Ilya; Bettencourt, Luís M. A.; Kenyon, Garret T.

2011-01-01

Can lateral connectivity in the primary visual cortex account for the time dependence and intrinsic task difficulty of human contour detection? To answer this question, we created a synthetic image set that prevents sole reliance on either low-level visual features or high-level context for the detection of target objects. Rendered images consist of smoothly varying, globally aligned contour fragments (amoebas) distributed among groups of randomly rotated fragments (clutter). The time course and accuracy of amoeba detection by humans was measured using a two-alternative forced choice protocol with self-reported confidence and variable image presentation time (20-200 ms), followed by an image mask optimized so as to interrupt visual processing. Measured psychometric functions were well fit by sigmoidal functions with exponential time constants of 30-91 ms, depending on amoeba complexity. Key aspects of the psychophysical experiments were accounted for by a computational network model, in which simulated responses across retinotopic arrays of orientation-selective elements were modulated by cortical association fields, represented as multiplicative kernels computed from the differences in pairwise edge statistics between target and distractor images. Comparing the experimental and the computational results suggests that each iteration of the lateral interactions takes at least ms of cortical processing time. Our results provide evidence that cortical association fields between orientation selective elements in early visual areas can account for important temporal and task-dependent aspects of the psychometric curves characterizing human contour perception, with the remaining discrepancies postulated to arise from the influence of higher cortical areas. PMID:21998562

Pre- versus post-mass extinction divergence of Mesozoic marine reptiles dictated by time-scale dependence of evolutionary rates.

PubMed

Motani, Ryosuke; Jiang, Da-Yong; Tintori, Andrea; Ji, Cheng; Huang, Jian-Dong

2017-05-17

The fossil record of a major clade often starts after a mass extinction even though evolutionary rates, molecular or morphological, suggest its pre-extinction emergence (e.g. squamates, placentals and teleosts). The discrepancy is larger for older clades, and the presence of a time-scale-dependent methodological bias has been suggested, yet it has been difficult to avoid the bias using Bayesian phylogenetic methods. This paradox raises the question of whether ecological vacancies, such as those after mass extinctions, prompt the radiations. We addressed this problem by using a unique temporal characteristic of the morphological data and a high-resolution stratigraphic record, for the oldest clade of Mesozoic marine reptiles, Ichthyosauromorpha. The evolutionary rate was fastest during the first few million years of ichthyosauromorph evolution and became progressively slower over time, eventually becoming six times slower. Using the later slower rates, estimates of divergence time become excessively older. The fast, initial rate suggests the emergence of ichthyosauromorphs after the end-Permian mass extinction, matching an independent result from high-resolution stratigraphic confidence intervals. These reptiles probably invaded the sea as a new ecosystem was formed after the end-Permian mass extinction. Lack of information on early evolution biased Bayesian clock rates. © 2017 The Author(s).

Pre- versus post-mass extinction divergence of Mesozoic marine reptiles dictated by time-scale dependence of evolutionary rates

PubMed Central

Ji, Cheng; Huang, Jian-dong

2017-01-01

The fossil record of a major clade often starts after a mass extinction even though evolutionary rates, molecular or morphological, suggest its pre-extinction emergence (e.g. squamates, placentals and teleosts). The discrepancy is larger for older clades, and the presence of a time-scale-dependent methodological bias has been suggested, yet it has been difficult to avoid the bias using Bayesian phylogenetic methods. This paradox raises the question of whether ecological vacancies, such as those after mass extinctions, prompt the radiations. We addressed this problem by using a unique temporal characteristic of the morphological data and a high-resolution stratigraphic record, for the oldest clade of Mesozoic marine reptiles, Ichthyosauromorpha. The evolutionary rate was fastest during the first few million years of ichthyosauromorph evolution and became progressively slower over time, eventually becoming six times slower. Using the later slower rates, estimates of divergence time become excessively older. The fast, initial rate suggests the emergence of ichthyosauromorphs after the end-Permian mass extinction, matching an independent result from high-resolution stratigraphic confidence intervals. These reptiles probably invaded the sea as a new ecosystem was formed after the end-Permian mass extinction. Lack of information on early evolution biased Bayesian clock rates. PMID:28515201

Allergenicity of Gramineae bee-collected pollen is proportional to its mass but is highly variable and depends on the members of the Gramineae family.

PubMed

Nonotte-Varly, C

2016-01-01

Gramineae bee-collected pollen is identified as being at the origin of allergic accidents but the biological potency of Gramineae bee-collected pollen is not well known. Cereal grasses (e.g., Zea) and European wild forage grasses (FG) are contained in bee-collected pollen. In this experiment, Zea-mass and FG-mass were identified in bee pollen mass and the proportion of Zea and of FG was calculated using the bee pollen melissopalynology spectrum. Skin reactivity to Zea and to FG were assessed by measuring wheal diameters (W) from skin prick tests using three serial dilutions of bee-collected pollen on 10 allergic patients to Gramineae, in order to calculate the relationship between Zea mass (Masszea) or FG mass (MassFG) in bee pollen and skin reactivity. The linear function Log10(WFG)=0.24(Log10(MassFG))+0.33 (R=0.99) was established using a bee pollen sample with 0.168mg of FG pollen per mg. The linear function Log10(Wzea)=0.23(Log10(Masszea))+0.14 (R=0.99) was established using a bee pollen sample with 0.983mg of Zea pollen per mg. Gramineae allergens seem to be little altered by bee secretions. Gramineae bee pollen retains its allergenic capacity but it depends on the members of the Gramineae family. To our knowledge this is the first time it has been shown that skin reactivity to Gramineae is proportional to the absolute Gramineae mass contained in the bee-collected pollen and that it depends on the members of the Gramineae family. Copyright © 2015 SEICAP. Published by Elsevier Espana. All rights reserved.

The mass dependence of chromospheric activity evolution & implications for gyrochronology

NASA Astrophysics Data System (ADS)

Curtis, Jason

2018-01-01

We know chromospheric emission decays over time, and yet this empirical relation is still fundamentally an interpolation over 3.5 Gyr from the Hyades to the Sun despite 45 years of progress. Furthermore, its very existence was called into question by Pace et al. (2004, 2009, 2013), who argued that activity plummets and flatlines around 1-2 Gyr. I will present new Ca II H & K data for NGC 752 (1.5 Gyr) and Ruprecht 147 (3 Gyr), and ISM-corrected data for M67 (4 Gyr, Curtis 2017), and pair this with the Sun's re-calibrated history (Egeland et al. 2017) and data on field stars from the Keck exoplanet program. I calculated ages for the field star sample using the [Y/Mg] "chemical clock," which was discovered from studies of solar twins and is due to galactic chemical enrichment. I find a mass dependence that matches the prediction from the activity-rotation-age relation of Mamajek & Hillenbrand (2008), where F stars rapidly plummet at 1-2 Gyr in line with the observations of F stars in clusters of similar age by Pace et al., whereas activity continuously declines for G and K dwarfs to approximately 5 and 7 Gyr, respectively. I will show that comparing ages estimated from [Y/Mg] to activity--rotation ages reveals known hot Jupiter hosts and other potentially anomalous stars. Combining the empirical relation between activity and Rossby number with estimates of stellar mass from spectroscopy and age from [Y/Mg] yields a gyrochronology relationship for FG and early K dwarfs that is independent of the cluster age scale and appears consistent with models from Mamajek & Hillenbrand (2008) and Barnes (2010). However, I have separately measured rotation periods for mid to late K dwarfs in 3 Gyr Ruprecht 147 with K2 and I find that they are rotating too rapidly relative to these empirical models and the semi-physical model of Matt et al. (2015). Apparently, K dwarfs spin down more slowly than the Skumanich square-root Law. Determining the K dwarf spin-down law is critical for

Glutamate-dependent phosphorylation of the mammalian target of rapamycin (mTOR) in Bergmann glial cells.

PubMed

Zepeda, Rossana C; Barrera, Iliana; Castelán, Francisco; Suárez-Pozos, Edna; Melgarejo, Yaaziel; González-Mejia, Elba; Hernández-Kelly, Luisa C; López-Bayghen, Esther; Aguilera, José; Ortega, Arturo

2009-09-01

Glutamate, the major excitatory neurotransmitter in the mammalian central nervous system, plays an important role in neuronal development and synaptic plasticity. It activates a variety of signaling pathways that regulate gene expression at the transcriptional and translational levels. Within glial cells, besides transcription, glutamate also regulates translation initiation and elongation. The mammalian target of rapamycin (mTOR), a key participant in the translation process, represents an important regulatory locus for translational control. Therefore, in the present communication we sought to characterize the mTOR phosphorylation pattern after glutamate treatment in chick cerebellar Bergmann glia primary cultures. A time- and dose-dependent increase in mTOR Ser 2448 phosphorylation was found. Pharmacological tools established that the glutamate effect is mediated through ionotropic and metabotropic receptors and interestingly, the glutamate transporter system is also involved. The signaling cascade triggered by glutamate includes an increase in intracellular Ca2+ levels, and the activation of the p60(Src)/PI-3K/PKB pathway. These results suggest that glia cells participate in the activity-dependent change in the brain protein repertoire.

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 ⊕.

DNA-Dependent Protein Kinase As Molecular Target for Radiosensitization of Neuroblastoma Cells.

PubMed

Dolman, M Emmy M; van der Ploeg, Ida; Koster, Jan; Bate-Eya, Laurel Tabe; Versteeg, Rogier; Caron, Huib N; Molenaar, Jan J

2015-01-01

Tumor cells might resist therapy with ionizing radiation (IR) by non-homologous end-joining (NHEJ) of IR-induced double-strand breaks. One of the key players in NHEJ is DNA-dependent protein kinase (DNA-PK). The catalytic subunit of DNA-PK, i.e. DNA-PKcs, can be inhibited with the small-molecule inhibitor NU7026. In the current study, the in vitro potential of NU7026 to radiosensitize neuroblastoma cells was investigated. DNA-PKcs is encoded by the PRKDC (protein kinase, DNA-activated, catalytic polypeptide) gene. We showed that PRKDC levels were enhanced in neuroblastoma patients and correlated with a more advanced tumor stage and poor prognosis, making DNA-PKcs an interesting target for radiosensitization of neuroblastoma tumors. Optimal dose finding for combination treatment with NU7026 and IR was performed using NGP cells. One hour pre-treatment with 10 μM NU7026 synergistically sensitized NGP cells to 0.63 Gy IR. Radiosensitizing effects of NU7026 increased in time, with maximum effects observed from 96 h after IR-exposure on. Combined treatment of NGP cells with 10 μM NU7026 and 0.63 Gy IR resulted in apoptosis, while no apoptotic response was observed for either of the therapies alone. Inhibition of IR-induced DNA-PK activation by NU7026 confirmed the capability of NGP cells to, at least partially, resist IR by NHEJ. NU7026 also synergistically radiosensitized other neuroblastoma cell lines, while no synergistic effect was observed for low DNA-PKcs-expressing non-cancerous fibroblasts. Results obtained for NU7026 were confirmed by PRKDC knockdown in NGP cells. Taken together, the current study shows that DNA-PKcs is a promising target for neuroblastoma radiosensitization.

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.

Novel antibiofilm chemotherapies target nitrogen from glutamate and glutamine.

PubMed

Hassanov, Tal; Karunker, Iris; Steinberg, Nitai; Erez, Ayelet; Kolodkin-Gal, Ilana

2018-05-08

Bacteria in nature often reside in differentiated communities termed biofilms, which are an active interphase between uni-cellular and multicellular life states for bacteria. Here we demonstrate that the development of B. subtilis biofilms is dependent on the use of glutamine or glutamate as a nitrogen source. We show a differential metabolic requirement within the biofilm; while glutamine is necessary for the dividing cells at the edges, the inner cell mass utilizes lactic acid. Our results indicate that biofilm cells preserve a short-term memory of glutamate metabolism. Finally, we establish that drugs that target glutamine and glutamate utilization restrict biofilm development. Overall, our work reveals a spatial regulation of nitrogen and carbon metabolism within the biofilm, which contributes to the fitness of bacterial complex communities. This acquired metabolic division of labor within biofilm can serve as a target for novel anti-biofilm chemotherapies.

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.

Phosphorylation of Nlp by Plk1 negatively regulates its dynein-dynactin-dependent targeting to the centrosome.

PubMed

Casenghi, Martina; Barr, Francis A; Nigg, Erich A

2005-11-01

When cells enter mitosis the microtubule (MT) network undergoes a profound rearrangement, in part due to alterations in the MT nucleating and anchoring properties of the centrosome. Ninein and the ninein-like protein (Nlp) are centrosomal proteins involved in MT organisation in interphase cells. We show that the overexpression of these two proteins induces the fragmentation of the Golgi, and causes lysosomes to disperse toward the cell periphery. The ability of Nlp and ninein to perturb the cytoplasmic distribution of these organelles depends on their ability to interact with the dynein-dynactin motor complex. Our data also indicate that dynactin is required for the targeting of Nlp and ninein to the centrosome. Furthermore, phosphorylation of Nlp by the polo-like kinase 1 (Plk1) negatively regulates its association with dynactin. These findings uncover a mechanism through which Plk1 helps to coordinate changes in MT organisation with cell cycle progression, by controlling the dynein-dynactin-dependent transport of centrosomal proteins.

Synaptic Targeting and Function of SAPAPs Mediated by Phosphorylation-Dependent Binding to PSD-95 MAGUKs.

PubMed

Zhu, Jinwei; Zhou, Qingqing; Shang, Yuan; Li, Hao; Peng, Mengjuan; Ke, Xiao; Weng, Zhuangfeng; Zhang, Rongguang; Huang, Xuhui; Li, Shawn S C; Feng, Guoping; Lu, Youming; Zhang, Mingjie

2017-12-26

The PSD-95/SAPAP/Shank complex functions as the major scaffold in orchestrating the formation and plasticity of the post-synaptic densities (PSDs). We previously demonstrated that the exquisitely specific SAPAP/Shank interaction is critical for Shank synaptic targeting and Shank-mediated synaptogenesis. Here, we show that the PSD-95/SAPAP interaction, SAPAP synaptic targeting, and SAPAP-mediated synaptogenesis require phosphorylation of the N-terminal repeat sequences of SAPAPs. The atomic structure of the PSD-95 guanylate kinase (GK) in complex with a phosphor-SAPAP repeat peptide, together with biochemical studies, reveals the molecular mechanism underlying the phosphorylation-dependent PSD-95/SAPAP interaction, and it also provides an explanation of a PSD-95 mutation found in patients with intellectual disabilities. Guided by the structural data, we developed potent non-phosphorylated GK inhibitory peptides capable of blocking the PSD-95/SAPAP interaction and interfering with PSD-95/SAPAP-mediated synaptic maturation and strength. These peptides are genetically encodable for investigating the functions of the PSD-95/SAPAP interaction in vivo. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

CRISPR/Cas9 mutagenesis invalidates a putative cancer dependency targeted in on-going clinical trials

PubMed Central

Lin, Ann; Giuliano, Christopher J; Sayles, Nicole M; Sheltzer, Jason M

2017-01-01

The Maternal Embryonic Leucine Zipper Kinase (MELK) has been reported to be a genetic dependency in several cancer types. MELK RNAi and small-molecule inhibitors of MELK block the proliferation of various cancer cell lines, and MELK knockdown has been described as particularly effective against the highly-aggressive basal/triple-negative subtype of breast cancer. Based on these preclinical results, the MELK inhibitor OTS167 is currently being tested as a novel chemotherapy agent in several clinical trials. Here, we report that mutagenizing MELK with CRISPR/Cas9 has no effect on the fitness of basal breast cancer cell lines or cell lines from six other cancer types. Cells that harbor null mutations in MELK exhibit wild-type doubling times, cytokinesis, and anchorage-independent growth. Furthermore, MELK-knockout lines remain sensitive to OTS167, suggesting that this drug blocks cell division through an off-target mechanism. In total, our results undermine the rationale for a series of current clinical trials and provide an experimental approach for the use of CRISPR/Cas9 in preclinical target validation that can be broadly applied. DOI: http://dx.doi.org/10.7554/eLife.24179.001 PMID:28337968

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

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.

Electronic and software systems of an automated portable static mass spectrometer

NASA Astrophysics Data System (ADS)

Chichagov, Yu. V.; Bogdanov, A. A.; Lebedev, D. S.; Kogan, V. T.; Tubol'tsev, Yu. V.; Kozlenok, A. V.; Moroshkin, V. S.; Berezina, A. V.

2017-01-01

The electronic systems of a small high-sensitivity static mass spectrometer and software and hardware tools, which allow one to determine trace concentrations of gases and volatile compounds in air and water samples in real time, have been characterized. These systems and tools have been used to set up the device, control the process of measurement, synchronize this process with accompanying measurements, maintain reliable operation of the device, process the obtained results automatically, and visualize and store them. The developed software and hardware tools allow one to conduct continuous measurements for up to 100 h and provide an opportunity for personnel with no special training to perform maintenance on the device. The test results showed that mobile mass spectrometers for geophysical and medical research, which were fitted with these systems, had a determination limit for target compounds as low as several ppb(m) and a mass resolving power (depending on the current task) as high as 250.

The dependence of bar frequency on galaxy mass, colour, and gas content - and angular resolution - in the local universe

NASA Astrophysics Data System (ADS)

Erwin, Peter

2018-03-01

I use distance- and mass-limited subsamples of the Spitzer Survey of Stellar Structure in Galaxies (S4G) to investigate how the presence of bars in spiral galaxies depends on mass, colour, and gas content and whether large, Sloan Digital Sky Survey (SDSS)-based investigations of bar frequencies agree with local data. Bar frequency reaches a maximum of fbar ≈ 0.70 at M⋆ ˜ 109.7M⊙, declining to both lower and higher masses. It is roughly constant over a wide range of colours (g - r ≈ 0.1-0.8) and atomic gas fractions (log (M_{H I}/ M_{\\star }) ≈ -2.5 to 1). Bars are thus as common in blue, gas-rich galaxies are they are in red, gas-poor galaxies. This is in sharp contrast to many SDSS-based studies of z ˜ 0.01-0.1 galaxies, which report fbar increasing strongly to higher masses (from M⋆ ˜ 1010 to 1011M⊙), redder colours, and lower gas fractions. The contradiction can be explained if SDSS-based studies preferentially miss bars in, and underestimate the bar fraction for, lower mass (bluer, gas-rich) galaxies due to poor spatial resolution and the correlation between bar size and stellar mass. Simulations of SDSS-style observations using the S4G galaxies as a parent sample, and assuming that bars below a threshold angular size of twice the point spread function full width at half-maximum cannot be identified, successfully reproduce typical SDSS fbar trends for stellar mass and gas mass ratio. Similar considerations may affect high-redshift studies, especially if bars grow in length over cosmic time; simulations suggest that high-redshift bar fractions may thus be systematically underestimated.

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.

The VIMOS Public Extragalactic Redshift Survey (VIPERS) . Luminosity and stellar mass dependence of galaxy clustering at 0.5 < z < 1.1

NASA Astrophysics Data System (ADS)

Marulli, F.; Bolzonella, M.; Branchini, E.; Davidzon, I.; de la Torre, S.; Granett, B. R.; Guzzo, L.; Iovino, A.; Moscardini, L.; Pollo, A.; Abbas, U.; Adami, C.; Arnouts, S.; Bel, J.; Bottini, D.; Cappi, A.; Coupon, J.; Cucciati, O.; De Lucia, G.; Fritz, A.; Franzetti, P.; Fumana, M.; Garilli, B.; Ilbert, O.; Krywult, J.; Le Brun, V.; Le Fèvre, O.; Maccagni, D.; Małek, K.; McCracken, H. J.; Paioro, L.; Polletta, M.; Schlagenhaufer, H.; Scodeggio, M.; Tasca, L. A. M.; Tojeiro, R.; Vergani, D.; Zanichelli, A.; Burden, A.; Di Porto, C.; Marchetti, A.; Marinoni, C.; Mellier, Y.; Nichol, R. C.; Peacock, J. A.; Percival, W. J.; Phleps, S.; Wolk, M.; Zamorani, G.

2013-09-01

Aims: We investigate the dependence of galaxy clustering on luminosity and stellar mass in the redshift range 0.5 < z < 1.1, using the first ~ 55 000 redshifts from the VIMOS Public Extragalactic Redshift Survey (VIPERS). Methods: We measured the redshift-space two-point correlation functions (2PCF), ξ(s) and ξ(rp,π) , and the projected correlation function, wp(rp), in samples covering different ranges of B-band absolute magnitudes and stellar masses. We considered both threshold and binned galaxy samples, with median B-band absolute magnitudes - 21.6 ≲ MB - 5log (h) ≲ - 19.5 and median stellar masses 9.8 ≲ log (M⋆ [h-2 M⊙]) ≲ 10.7. We assessed the real-space clustering in the data from the projected correlation function, which we model as a power law in the range 0.2 < rp [h-1 Mpc ] < 20. Finally, we estimated the galaxy bias as a function of luminosity, stellar mass, and redshift, assuming a flat Λ cold dark matter model to derive the dark matter 2PCF. Results: We provide the best-fit parameters of the power-law model assumed for the real-space 2PCF - the correlation length, r0, and the slope, γ - as well as the linear bias parameter, as a function of the B-band absolute magnitude, stellar mass, and redshift. We confirm and provide the tightest constraints on the dependence of clustering on luminosity at 0.5 < z < 1.1. We prove the complexity of comparing the clustering dependence on stellar mass from samples that are originally flux-limited and discuss the possible origin of the observed discrepancies. Overall, our measurements provide stronger constraints on galaxy formation models, which are now required to match, in addition to local observations, the clustering evolution measured by VIPERS galaxies between z = 0.5 and z = 1.1 for a broad range of luminosities and stellar masses. Based on observations collected at the European Southern Observatory, Paranal, Chile, under programmes 182.A-0886 (LP) at the Very Large Telescope, and also based on

Dispersive liquid-liquid microextraction and gas chromatography accurate mass spectrometry for extraction and non-targeted profiling of volatile and semi-volatile compounds in grape marc distillates.

PubMed

Fontana, Ariel; Rodríguez, Isaac; Cela, Rafael

2018-04-20

The suitability of dispersive liquid-liquid microextraction (DLLME) and gas chromatography accurate mass spectrometry (GC-MS), based on a time-of-flight (TOF) MS analyzer and using electron ionization (EI), for the characterization of volatile and semi-volatile profiles of grape marc distillates (grappa) are evaluated. DLLME conditions are optimized with a selection of compounds, from different chemical families, present in the distillate spirit. Under final working conditions, 2.5 mL of sample and 0.5 mL of organic solvents are consumed in the sample preparation process. The absolute extraction efficiencies ranged from 30 to 100%, depending on the compound. For the same sample volume, DLLME provided higher responses than solid-phase microextraction (SPME) for most of the model compounds. The GC-EI-TOF-MS records of grappa samples were processed using a data mining non-targeted search algorithm. In this way, chromatographic peaks and accurate EI-MS spectra of sample components were linked. The identities of more than 140 of these components are proposed from comparison of their accurate spectra with those in a low resolution EI-MS database, accurate masses of most intense fragment ions of known structure, and available chromatographic retention index. The use of chromatographic and spectral data, associated to the set of components mined from different grappa samples, for multivariate analysis purposes is also illustrated in the study. Copyright © 2018 Elsevier B.V. All rights reserved.

Unique Features and Anti-microbial Targeting of Folate- and Flavin-Dependent Methyltransferases Required for Accurate Maintenance of Genetic Information.

PubMed

Myllykallio, Hannu; Sournia, Pierre; Heliou, Alice; Liebl, Ursula

2018-01-01

Comparative genome analyses have led to the discovery and characterization of novel flavin- and folate-dependent methyltransferases that mainly function in DNA precursor synthesis and post-transcriptional RNA modification by forming (ribo) thymidylate and its derivatives. Here we discuss the recent literature on the novel mechanistic features of these enzymes sometimes referred to as "uracil methyltransferases," albeit we prefer to refer to them as (ribo) thymidylate synthases. These enzyme families attest to the convergent evolution of nucleic acid methylation. Special focus is given to describing the unique characteristics of these flavin- and folate-dependent enzymes that have emerged as new models for studying the non-canonical roles of reduced flavin co-factors (FADH 2 ) in relaying carbon atoms between enzyme substrates. This ancient enzymatic methylation mechanism with a very wide phylogenetic distribution may be more commonly used for biological methylation reactions than previously anticipated. This notion is exemplified by the recent discovery of additional substrates for these enzymes. Moreover, similar reaction mechanisms can be reversed by demethylases, which remove methyl groups e.g., from human histones. Future work is now required to address whether the use of different methyl donors facilitates the regulation of distinct methylation reactions in the cell. It will also be of great interest to address whether the low activity flavin-dependent thymidylate synthases ThyX represent ancestral enzymes that were eventually replaced by the more active thymidylate synthases of the ThyA family to facilitate the maintenance of larger genomes in fast-growing microbes. Moreover, we discuss the recent efforts from several laboratories to identify selective anti-microbial compounds that target flavin-dependent thymidylate synthase ThyX. Altogether we underline how the discovery of the alternative flavoproteins required for methylation of DNA and/or RNA nucleotides

Implications of the change in confinement status of a heterogeneous aquifer for scale-dependent dispersion and mass-transfer processes

NASA Astrophysics Data System (ADS)

Pedretti, D.; Molinari, A.; Fallico, C.; Guzzi, S.

2016-10-01

A series of experimental tracer tests were performed to explore the implications of the change in the pressure status of a heterogeneous bimodal aquifer for scale-dependent dispersion and mass-transfer processes. The sandbox was filled with sands and gravel channels and patches to form an alluvial-like bimodal aquifer. We performed multiple injections of a conservative tracer from 26 different locations of the sandbox and interpreted the resulting depth-integrated breakthrough curves (BTCs) at the central pumping well to obtain a scale-dependent distribution of local and field-integrated apparent longitudinal dispersivity (respectively, αLloc and αLapp). We repeated the experiments under confined (CS) and unconfined (UNS) pressure status, keeping the same heterogeneous configuration. Results showed that αLloc(associated with transport through gravel zones) was poorly influenced by the change in aquifer pressure and the presence of channels. Instead, αLapp(i.e. macrodispersion) strongly increased when changing from CS to UNS. In specific, we found αLapp ≈ 0.03 r for the CS and αLapp ≈ 0.15 r for the UNS (being r the distance from the well). Second-to-fourth-order temporal moments showed strong spatial dependence in the UNS and no spatial dependence in the CS. These results seem consistent with a ;vadose-zone-driven; kinetic mass-transfer process occurring in the UNS but not in the CS. The vadose zone enhances vertical flow due to the presence of free surface and large contrasts in hydraulic conductivity triggered by the desaturation of gravel channels nearby the pumping well. The vadose zone enhances vertical mixing between gravel and sands and generates BTC tailing. In the CS vertical mixing is negligible and anomalous transport is not observed.

Genetically Targeted All-Optical Electrophysiology with a Transgenic Cre-Dependent Optopatch Mouse

PubMed Central

Lou, Shan; Adam, Yoav; Weinstein, Eli N.; Williams, Erika; Williams, Katherine; Parot, Vicente; Kavokine, Nikita; Liberles, Stephen; Madisen, Linda; Zeng, Hongkui

2016-01-01

Recent advances in optogenetics have enabled simultaneous optical perturbation and optical readout of membrane potential in diverse cell types. Here, we develop and characterize a Cre-dependent transgenic Optopatch2 mouse line that we call Floxopatch. The animals expressed a blue-shifted channelrhodopsin, CheRiff, and a near infrared Archaerhodopsin-derived voltage indicator, QuasAr2, via targeted knock-in at the rosa26 locus. In Optopatch-expressing animals, we tested for overall health, genetically targeted expression, and function of the optogenetic components. In offspring of Floxopatch mice crossed with a variety of Cre driver lines, we observed spontaneous and optically evoked activity in vitro in acute brain slices and in vivo in somatosensory ganglia. Cell-type-specific expression allowed classification and characterization of neuronal subtypes based on their firing patterns. The Floxopatch mouse line is a useful tool for fast and sensitive characterization of neural activity in genetically specified cell types in intact tissue. SIGNIFICANCE STATEMENT Optical recordings of neural activity offer the promise of rapid and spatially resolved mapping of neural function. Calcium imaging has been widely applied in this mode, but is insensitive to the details of action potential waveforms and subthreshold events. Simultaneous optical perturbation and optical readout of single-cell electrical activity (“Optopatch”) has been demonstrated in cultured neurons and in organotypic brain slices, but not in acute brain slices or in vivo. Here, we describe a transgenic mouse in which expression of Optopatch constructs is controlled by the Cre-recombinase enzyme. This animal enables fast and robust optical measurements of single-cell electrical excitability in acute brain slices and in somatosensory ganglia in vivo, opening the door to rapid optical mapping of neuronal excitability. PMID:27798186

DNA-Dependent Protein Kinase As Molecular Target for Radiosensitization of Neuroblastoma Cells

PubMed Central

Dolman, M. Emmy M.; van der Ploeg, Ida; Koster, Jan; Bate-Eya, Laurel Tabe; Versteeg, Rogier; Caron, Huib N.; Molenaar, Jan J.

2015-01-01

Tumor cells might resist therapy with ionizing radiation (IR) by non-homologous end-joining (NHEJ) of IR-induced double-strand breaks. One of the key players in NHEJ is DNA-dependent protein kinase (DNA-PK). The catalytic subunit of DNA-PK, i.e. DNA-PKcs, can be inhibited with the small-molecule inhibitor NU7026. In the current study, the in vitro potential of NU7026 to radiosensitize neuroblastoma cells was investigated. DNA-PKcs is encoded by the PRKDC (protein kinase, DNA-activated, catalytic polypeptide) gene. We showed that PRKDC levels were enhanced in neuroblastoma patients and correlated with a more advanced tumor stage and poor prognosis, making DNA-PKcs an interesting target for radiosensitization of neuroblastoma tumors. Optimal dose finding for combination treatment with NU7026 and IR was performed using NGP cells. One hour pre-treatment with 10 μM NU7026 synergistically sensitized NGP cells to 0.63 Gy IR. Radiosensitizing effects of NU7026 increased in time, with maximum effects observed from 96 h after IR-exposure on. Combined treatment of NGP cells with 10 μM NU7026 and 0.63 Gy IR resulted in apoptosis, while no apoptotic response was observed for either of the therapies alone. Inhibition of IR-induced DNA-PK activation by NU7026 confirmed the capability of NGP cells to, at least partially, resist IR by NHEJ. NU7026 also synergistically radiosensitized other neuroblastoma cell lines, while no synergistic effect was observed for low DNA-PKcs-expressing non-cancerous fibroblasts. Results obtained for NU7026 were confirmed by PRKDC knockdown in NGP cells. Taken together, the current study shows that DNA-PKcs is a promising target for neuroblastoma radiosensitization. PMID:26716839

A precision oncology approach to the pharmacological targeting of mechanistic dependencies in neuroendocrine tumors. | Office of Cancer Genomics

Cancer.gov

We introduce and validate a new precision oncology framework for the systematic prioritization of drugs targeting mechanistic tumor dependencies in individual patients. Compounds are prioritized on the basis of their ability to invert the concerted activity of master regulator proteins that mechanistically regulate tumor cell state, as assessed from systematic drug perturbation assays. We validated the approach on a cohort of 212 gastroenteropancreatic neuroendocrine tumors (GEP-NETs), a rare malignancy originating in the pancreas and gastrointestinal tract.

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

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...

CAK-Cyclin-dependent Activating Kinase: a key kinase in cell cycle control and a target for drugs?

PubMed

Lolli, Graziano; Johnson, Louise N

2005-04-01

The Cyclin-dependent kinase (CDK) Activating Kinase (CAK) is responsible for the activating phosphorylation of CDK1, CDK2, CDK4 and CDK6 and regulation of the cell cycle. The kinase is composed of three subunits: CDK7, Cyclin H and MAT1 (ménage a trois). Together with six other subunits, CAK is also part of the general transcription factor TFIIH where it is involved in promoter clearance and progression of transcription from the preinitiation to the initiation stage. CAK is required for cell cycle progression, which suggests that CDK7 could be a target for cancer therapy. However its role in transcription and its ubiquitous presence raise sensible concerns about possible toxicity of its inhibitors. The recently determined structure of CDK7 allows the design of inhibitors with differential specificity for the different CDKs. We review the role of CAK in different biological processes and evaluate the biological evidence for CDK7 as a possible pharmacological target.

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.

Systemic SMAD7 Gene Therapy Increases Striated Muscle Mass and Enhances Exercise Capacity in a Dose-Dependent Manner.

PubMed

Maricelli, Joseph W; Bishaw, Yemeserach M; Wang, Bo; Du, Min; Rodgers, Buel D

2018-03-01

Striated muscle wasting occurs with a variety of disease indications, contributing to mortality and compromising life quality. Recent studies indicate that the recombinant adeno-associated virus (serotype 6) Smad7 gene therapeutic, AVGN7, enhances skeletal and cardiac muscle mass and prevents cancer-induced wasting of both tissues. This is accomplished by attenuating ActRIIb intracellular signaling and, as a result, the physiological actions of myostatin and other ActRIIb ligands. AVGN7 also enhances isolated skeletal muscle twitch force, but is unknown to improve systemic muscle function similarly, especially exercise capacity. A 2-month-long dose-escalation study was therefore conducted using 5 × 10 11 , 1 × 10 12 , and 5 × 10 12 vg/mouse and different tests of systemic muscle function. Body mass, skeletal muscle mass, heart mass, and forelimb grip strength were all increased in a dose-dependent manner, as was the fiber cross-sectional area of tibialis anterior muscles. Maximal oxygen consumption (VO 2 max), a measure of metabolic rate, was similarly enhanced during forced treadmill running, and although the total distance traveled was only elevated by the highest dose, all doses reduced the energy expenditure rate compared to control mice injected with an empty vector. Such improvements in VO 2 max are consistent with physiological cardiac hypertrophy, which is highly beneficial and a normal adaptive response to exercise. This was particularly evident at the lowest dose tested, which had minimal significant effects on skeletal muscle mass and/or function, but increased heart weight and exercise capacity. These results together suggest that AVGN7 enhances striated muscle mass and systemic muscle function. They also define minimally effective and optimal doses for future preclinical trials and toxicology studies and in turn will aid in establishing dose ranges for clinical trials.

Ejecta velocity distribution for impact cratering experiments on porous and low strength targets

NASA Astrophysics Data System (ADS)

Michikami, Tatsuhiro; Moriguchi, Kouichi; Hasegawa, Sunao; Fujiwara, Akira

2007-01-01

Impact cratering experiments on porous targets with various compressive strength ranging from ˜0.5 to ˜250 MPa were carried out in order to investigate the relationship between the ejecta velocity, and material strength or porosity of the target. A spherical alumina projectile (diameter ˜1 mm) was shot perpendicularly into the target surface with velocity ranging from 1.2 to 4.5 km/s (nominal 4 km/s), using a two-stage light-gas gun. The ejecta velocity was estimated from the fall point distance of ejecta. The results show that there are in fact a large fraction of ejecta with very low velocities when the material strength of the target is small and the porosity is high. As an example, in the case of one specific target (compressive strength ˜0.5 MPa and porosity 43%), the amount of ejecta with velocities lower than 1 m/s is about 40% of the total mass. The average velocity of the ejecta decreases with decreasing material strength or increasing the porosity of the target. Moreover, in our experiments, the ejecta velocity distributions normalized to total ejecta mass seem to be mainly dependent on the material strength of the target, and not so greatly on the porosity. We also compare our experimental results with those of Gault et al. [1963. Spray ejected from the lunar surface by meteoroid impact. NASA Technical Note D-1767] and Housen [1992. Crater ejecta velocities for impacts on rocky bodies. LPSC XXIII, 555-556] for the ejecta velocity distribution using Housen's nondimensional scaling parameter. The ejecta velocity distributions of our experiments are lower than those of Gault et al. [1963. Spray ejected from the lunar surface by meteoroid impact. NASA Technical Note D-1767] and Housen [1992. Crater ejecta velocities for impacts on rocky bodies. LPSC XIII, 555-556].

Boundaries of mass resolution in native mass spectrometry.

PubMed

Lössl, Philip; Snijder, Joost; Heck, Albert J R

2014-06-01

Over the last two decades, native mass spectrometry (MS) has emerged as a valuable tool to study intact proteins and noncovalent protein complexes. Studied experimental systems range from small-molecule (drug)-protein interactions, to nanomachineries such as the proteasome and ribosome, to even virus assembly. In native MS, ions attain high m/z values, requiring special mass analyzers for their detection. Depending on the particular mass analyzer used, instrumental mass resolution does often decrease at higher m/z but can still be above a couple of thousand at m/z 5000. However, the mass resolving power obtained on charge states of protein complexes in this m/z region is experimentally found to remain well below the inherent instrument resolution of the mass analyzers employed. Here, we inquire into reasons for this discrepancy and ask how native MS would benefit from higher instrumental mass resolution. To answer this question, we discuss advantages and shortcomings of mass analyzers used to study intact biomolecules and biomolecular complexes in their native state, and we review which other factors determine mass resolving power in native MS analyses. Recent examples from the literature are given to illustrate the current status and limitations.

Evolution of wavelength-dependent mass absorption cross sections of carbonaceous aerosols during the 2010 DOE CARES campaign

NASA Astrophysics Data System (ADS)

Flowers, B. A.; Dubey, M. K.; Subramanian, R.; Sedlacek, A. J.; Kelley, P.; Luke, W. T.; Jobson, B. T.; Zaveri, R. A.

2011-12-01

Predictions of aerosol radiative forcing require process level optical property models that are built on precise and accurate field observations. Evolution of aerosol optical properties for urban influenced carbonaceous aerosol undergoing transport and mixing with rural air masses was a focal point of the DOE Carbonaceous Aerosol and Radiative Effects (CARES) campaign near Sacramento, CA in summer 2010. Urban aerosol was transported from Sacramento, CA (T0) to the foothills of the Sierra Nevada Mountains to a rural site located near Cool, CA (T1). Aerosol absorption and scattering coefficients were measured at the T0 and T1 sites using integrated photoacoustic acoustic/nephelometer instruments (PASS-3 and PASS-UV) at 781, 532, 405, and 375 nm. Single particle soot photometry (SP2) instrumentation was used to monitor black carbon (BC) mass at both sites. Combining data from these sensors allows estimate of the wavelength-dependent mass absorption coefficient (MAC(λ)) and partitioning of MAC(λ) into contributions from the BC core and from enhancements from coating of BC cores. MAC(λ) measured in this way is free of artifacts associated with filter-based aerosol absorption measurements and takes advantage of the single particle sensitivity of the SP2 instrument, allowing observation of MAC(λ) on 10 minute and faster time scales. Coating was observed to enhance MAC(λ) by 20 - 30 % and different wavelength dependence for MAC(λ) was observed for urban and biomass burning aerosol. Further, T0 - T1 evolution of MAC(λ) was correlated with separately measured NO/NOy ratios and CO/CO2 ratios to understand the effects of aging & transport on MAC(λ) and the implications of aerosol processing that links air quality to radiative forcing on a regional scale. Aircraft observations made from the Gulfstream-1 during CARES are also analyzed to enhance process level understanding of the optical properties of fresh and aged carbonaceous aerosol in the urban-rural interface.

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.

Electrospray Ionization with High-Resolution Mass Spectrometry as a Tool for Lignomics: Lignin Mass Spectrum Deconvolution

NASA Astrophysics Data System (ADS)

Andrianova, Anastasia A.; DiProspero, Thomas; Geib, Clayton; Smoliakova, Irina P.; Kozliak, Evguenii I.; Kubátová, Alena

2018-05-01

The capability to characterize lignin, lignocellulose, and their degradation products is essential for the development of new renewable feedstocks. Electrospray ionization high-resolution time-of-flight mass spectrometry (ESI-HR TOF-MS) method was developed expanding the lignomics toolkit while targeting the simultaneous detection of low and high molecular weight (MW) lignin species. The effect of a broad range of electrolytes and various ionization conditions on ion formation and ionization effectiveness was studied using a suite of mono-, di-, and triarene lignin model compounds as well as kraft alkali lignin. Contrary to the previous studies, the positive ionization mode was found to be more effective for methoxy-substituted arenes and polyphenols, i.e., species of a broadly varied MW structurally similar to the native lignin. For the first time, we report an effective formation of multiply charged species of lignin with the subsequent mass spectrum deconvolution in the presence of 100 mmol L-1 formic acid in the positive ESI mode. The developed method enabled the detection of lignin species with an MW between 150 and 9000 Da or higher, depending on the mass analyzer. The obtained M n and M w values of 1500 and 2500 Da, respectively, were in good agreement with those determined by gel permeation chromatography. Furthermore, the deconvoluted ESI mass spectrum was similar to that obtained with matrix-assisted laser desorption/ionization (MALDI)-HR TOF-MS, yet featuring a higher signal-to-noise ratio. The formation of multiply charged species was confirmed with ion mobility ESI-HR Q-TOF-MS. [Figure not available: see fulltext.

Electrospray Ionization with High-Resolution Mass Spectrometry as a Tool for Lignomics: Lignin Mass Spectrum Deconvolution

NASA Astrophysics Data System (ADS)

Andrianova, Anastasia A.; DiProspero, Thomas; Geib, Clayton; Smoliakova, Irina P.; Kozliak, Evguenii I.; Kubátová, Alena

2018-03-01

The capability to characterize lignin, lignocellulose, and their degradation products is essential for the development of new renewable feedstocks. Electrospray ionization high-resolution time-of-flight mass spectrometry (ESI-HR TOF-MS) method was developed expanding the lignomics toolkit while targeting the simultaneous detection of low and high molecular weight (MW) lignin species. The effect of a broad range of electrolytes and various ionization conditions on ion formation and ionization effectiveness was studied using a suite of mono-, di-, and triarene lignin model compounds as well as kraft alkali lignin. Contrary to the previous studies, the positive ionization mode was found to be more effective for methoxy-substituted arenes and polyphenols, i.e., species of a broadly varied MW structurally similar to the native lignin. For the first time, we report an effective formation of multiply charged species of lignin with the subsequent mass spectrum deconvolution in the presence of 100 mmol L-1 formic acid in the positive ESI mode. The developed method enabled the detection of lignin species with an MW between 150 and 9000 Da or higher, depending on the mass analyzer. The obtained M n and M w values of 1500 and 2500 Da, respectively, were in good agreement with those determined by gel permeation chromatography. Furthermore, the deconvoluted ESI mass spectrum was similar to that obtained with matrix-assisted laser desorption/ionization (MALDI)-HR TOF-MS, yet featuring a higher signal-to-noise ratio. The formation of multiply charged species was confirmed with ion mobility ESI-HR Q-TOF-MS. [Figure not available: see fulltext.

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.

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.

The dependence of crowding on flanker complexity and target-flanker similarity

PubMed Central

Bernard, Jean-Baptiste; Chung, Susana T.L.

2013-01-01

We examined the effects of the spatial complexity of flankers and target-flanker similarity on the performance of identifying crowded letters. On each trial, observers identified the middle character of random strings of three characters (“trigrams”) briefly presented at 10° below fixation. We tested the 26 lowercase letters of the Times-Roman and Courier fonts, a set of 79 characters (letters and non-letters) of the Times-Roman font, and the uppercase letters of two highly complex ornamental fonts, Edwardian and Aristocrat. Spatial complexity of characters was quantified by the length of the morphological skeleton of each character, and target-flanker similarity was defined based on a psychometric similarity matrix. Our results showed that (1) letter identification error rate increases with flanker complexity up to a certain value, beyond which error rate becomes independent of flanker complexity; (2) the increase of error rate is slower for high-complexity target letters; (3) error rate increases with target-flanker similarity; and (4) mislocation error rate increases with target-flanker similarity. These findings, combined with the current understanding of the faulty feature integration account of crowding, provide some constraints of how the feature integration process could cause perceptual errors. PMID:21730225

Isospectral Hamiltonian for position-dependent mass for an arbitrary quantum system and coherent states

NASA Astrophysics Data System (ADS)

Yahiaoui, Sid-Ahmed; Bentaiba, Mustapha

2017-06-01

By means of the unitary transformation, a new way for discussing the ordering prescription of the Schrödinger equation with a position-dependent mass (PDM) for isospectral Hamiltonian operators is presented. We show that the ambiguity parameter choices in the kinetic part of the Hamiltonian can be explained through an exact SUSY QM symmetry as well as a consequence of an accidental symmetry under the Z2 action. By making use of the unitary transformation, we construct coherent states for a family of PDM isospectral Hamiltonians from a suitable choice of ladder operators. We show that these states preserve the usual structure of Klauder-Perelomov's states and thus saturate and minimize the position-momentum uncertainty relation (PMUR) under some special restrictions. We show that PMUR properties can be used to determine the sign of the superpotential.

How to Explain the Non-Zero Mass of Electromagnetic Radiation Consisting of Zero-Mass Photons

ERIC Educational Resources Information Center

Gabovich, Alexander M.; Gabovich, Nadezhda A.

2007-01-01

The mass of electromagnetic radiation in a cavity is considered using the correct relativistic approach based on the concept of a scalar mass not dependent on the particle (system) velocity. It is shown that due to the non-additivity of mass in the special theory of relativity the ensemble of chaotically propagating mass-less photons in the cavity…

Galaxy And Mass Assembly (GAMA): spectroscopic analysis

NASA Astrophysics Data System (ADS)

Hopkins, A. M.; Driver, S. P.; Brough, S.; Owers, M. S.; Bauer, A. E.; Gunawardhana, M. L. P.; Cluver, M. E.; Colless, M.; Foster, C.; Lara-López, M. A.; Roseboom, I.; Sharp, R.; Steele, O.; Thomas, D.; Baldry, I. K.; Brown, M. J. I.; Liske, J.; Norberg, P.; Robotham, A. S. G.; Bamford, S.; Bland-Hawthorn, J.; Drinkwater, M. J.; Loveday, J.; Meyer, M.; Peacock, J. A.; Tuffs, R.; Agius, N.; Alpaslan, M.; Andrae, E.; Cameron, E.; Cole, S.; Ching, J. H. Y.; Christodoulou, L.; Conselice, C.; Croom, S.; Cross, N. J. G.; De Propris, R.; Delhaize, J.; Dunne, L.; Eales, S.; Ellis, S.; Frenk, C. S.; Graham, Alister W.; Grootes, M. W.; Häußler, B.; Heymans, C.; Hill, D.; Hoyle, B.; Hudson, M.; Jarvis, M.; Johansson, J.; Jones, D. H.; van Kampen, E.; Kelvin, L.; Kuijken, K.; López-Sánchez, Á.; Maddox, S.; Madore, B.; Maraston, C.; McNaught-Roberts, T.; Nichol, R. C.; Oliver, S.; Parkinson, H.; Penny, S.; Phillipps, S.; Pimbblet, K. A.; Ponman, T.; Popescu, C. C.; Prescott, M.; Proctor, R.; Sadler, E. M.; Sansom, A. E.; Seibert, M.; Staveley-Smith, L.; Sutherland, W.; Taylor, E.; Van Waerbeke, L.; Vázquez-Mata, J. A.; Warren, S.; Wijesinghe, D. B.; Wild, V.; Wilkins, S.

2013-04-01

The Galaxy And Mass Assembly (GAMA) survey is a multiwavelength photometric and spectroscopic survey, using the AAOmega spectrograph on the Anglo-Australian Telescope to obtain spectra for up to ˜300 000 galaxies over 280 deg2, to a limiting magnitude of rpet < 19.8 mag. The target galaxies are distributed over 0 < z ≲ 0.5 with a median redshift of z ≈ 0.2, although the redshift distribution includes a small number of systems, primarily quasars, at higher redshifts, up to and beyond z = 1. The redshift accuracy ranges from σv ≈ 50 km s-1 to σv ≈ 100 km s-1 depending on the signal-to-noise ratio of the spectrum. Here we describe the GAMA spectroscopic reduction and analysis pipeline. We present the steps involved in taking the raw two-dimensional spectroscopic images through to flux-calibrated one-dimensional spectra. The resulting GAMA spectra cover an observed wavelength range of 3750 ≲ λ ≲ 8850 Å at a resolution of R ≈ 1300. The final flux calibration is typically accurate to 10-20 per cent, although the reliability is worse at the extreme wavelength ends, and poorer in the blue than the red. We present details of the measurement of emission and absorption features in the GAMA spectra. These measurements are characterized through a variety of quality control analyses detailing the robustness and reliability of the measurements. We illustrate the quality of the measurements with a brief exploration of elementary emission line properties of the galaxies in the GAMA sample. We demonstrate the luminosity dependence of the Balmer decrement, consistent with previously published results, and explore further how Balmer decrement varies with galaxy mass and redshift. We also investigate the mass and redshift dependencies of the [N II]/Hα versus [O III]/Hβ spectral diagnostic diagram, commonly used to discriminate between star forming and nuclear activity in galaxies.

Selectivity and Efficiency of Late Transgene Expression by Transcriptionally Targeted Oncolytic Adenoviruses Are Dependent on the Transgene Insertion Strategy

PubMed Central

Quirin, Christina; Rohmer, Stanimira; Fernández-Ulibarri, Inés; Behr, Michael; Hesse, Andrea; Engelhardt, Sarah; Erbs, Philippe; Enk, Alexander H.

2011-01-01

Abstract Key challenges facing cancer therapy are the development of tumor-specific drugs and potent multimodal regimens. Oncolytic adenoviruses possess the potential to realize both aims by restricting virus replication to tumors and inserting therapeutic genes into the virus genome, respectively. A major effort in this regard is to express transgenes in a tumor-specific manner without affecting virus replication. Using both luciferase as a sensitive reporter and genetic prodrug activation, we show that promoter control of E1A facilitates highly selective expression of transgenes inserted into the late transcription unit. This, however, required multistep optimization of late transgene expression. Transgene insertion via internal ribosome entry site (IRES), splice acceptor (SA), or viral 2A sequences resulted in replication-dependent expression. Unexpectedly, analyses in appropriate substrates and with matching control viruses revealed that IRES and SA, but not 2A, facilitated indirect transgene targeting via tyrosinase promoter control of E1A. Transgene expression via SA was more selective (up to 1,500-fold) but less effective than via IRES. Notably, we also revealed transgene-dependent interference with splicing. Hence, the prodrug convertase FCU1 (a cytosine deaminase–uracil phosphoribosyltransferase fusion protein) was expressed only after optimizing the sequence surrounding the SA site and mutating a cryptic splice site within the transgene. The resulting tyrosinase promoter-regulated and FCU1-encoding adenovirus combined effective oncolysis with targeted prodrug activation therapy of melanoma. Thus, prodrug activation showed potent bystander killing and increased cytotoxicity of the virus up to 10-fold. We conclude that armed oncolytic viruses can be improved substantially by comparing and optimizing strategies for targeted transgene expression, thereby implementing selective and multimodal cancer therapies. PMID:20939692

Toward a Micro Gas Chromatograph/Mass Spectrometer (GC/MS) System

NASA Technical Reports Server (NTRS)

Wiberg, D. V.; Eyre, F. B.; Orient, O.; Chutjian, A.; Garkarian, V.

2001-01-01

Miniature mass filters (e.g., quadrupoles, ion traps) have been the subject of several miniaturization efforts. A project is currently in progress at JPL to develop a miniaturized Gas Chromatograph/Mass Spectrometer (GC/MS) system, incorporating and/or developing miniature system components including turbomolecular pumps, scroll type roughing pump, quadrupole mass filter, gas chromatograph, precision power supply and other electronic components. The preponderance of the system elements will be fabricated using microelectromechanical systems (MEMS) techniques. The quadrupole mass filter will be fabricated using an X-ray lithography technique producing high precision, 5x5 arrays of quadrupoles with pole lengths of about 3 mm and a total volume of 27 cubic mm. The miniature scroll pump will also be fabricated using X-ray lithography producing arrays of scroll stages about 3 mm in diameter. The target detection range for the mass spectrometer is 1 to 300 atomic mass units (AMU) with are solution of 0.5 AMU. This resolution will allow isotopic characterization for geochronology, atmospheric studies and other science efforts dependant on the understanding of isotope ratios of chemical species. This paper will discuss the design approach, the current state-of-the art regarding the system components and the progress toward development of key elements. The full system is anticipated to be small enough in mass, volume and power consumption to allow in situ chemical analysis on highly miniaturized science craft for geochronology, atmospheric characterization and detection of life experiments applicable to outer planet roadmap missions.

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.

Mapping the core mass function to the initial mass function

NASA Astrophysics Data System (ADS)

Guszejnov, Dávid; Hopkins, Philip F.

2015-07-01

It has been shown that fragmentation within self-gravitating, turbulent molecular clouds (`turbulent fragmentation') can naturally explain the observed properties of protostellar cores, including the core mass function (CMF). Here, we extend recently developed analytic models for turbulent fragmentation to follow the time-dependent hierarchical fragmentation of self-gravitating cores, until they reach effectively infinite density (and form stars). We show that turbulent fragmentation robustly predicts two key features of the initial mass function (IMF). First, a high-mass power-law scaling very close to the Salpeter slope, which is a generic consequence of the scale-free nature of turbulence and self-gravity. We predict the IMF slope (-2.3) is slightly steeper than the CMF slope (-2.1), owing to the slower collapse and easier fragmentation of large cores. Secondly, a turnover mass, which is set by a combination of the CMF turnover mass (a couple solar masses, determined by the `sonic scale' of galactic turbulence, and so weakly dependent on galaxy properties), and the equation of state (EOS). A `soft' EOS with polytropic index γ < 1.0 predicts that the IMF slope becomes `shallow' below the sonic scale, but fails to produce the full turnover observed. An EOS, which becomes `stiff' at sufficiently low surface densities Σgas ˜ 5000 M⊙ pc-2, and/or models, where each collapsing core is able to heat and effectively stiffen the EOS of a modest mass (˜0.02 M⊙) of surrounding gas, are able to reproduce the observed turnover. Such features are likely a consequence of more detailed chemistry and radiative feedback.

Development of a transgenic Plasmodium berghei line (Pb pfpkg) expressing the P. falciparum cGMP-dependent protein kinase, a novel antimalarial drug target.

PubMed

Tewari, Rita; Patzewitz, Eva-Maria; Poulin, Benoit; Stewart, Lindsay; Baker, David A

2014-01-01

With the inevitable selection of resistance to antimalarial drugs in treated populations, there is a need for new medicines to enter the clinic and new targets to progress through the drug discovery pipeline. In this study we set out to develop a transgenic rodent model for testing inhibitors of the Plasmodium falciparum cyclic GMP-dependent kinase in vivo. A model was needed that would allow us to investigate whether differences in amino acid sequence of this enzyme between species influences in vivo efficacy. Here we report the successful development of a transgenic P. berghei line in which the cyclic GMP-dependent protein kinase (PKG) was replaced by the P. falciparum orthologue. We demonstrate that the P. falciparum orthologue was able to functionally complement the endogenous P. berghei pkg gene throughout blood stage development and early sexual development. However, subsequent development in the mosquito was severely compromised. We show that this is due to a defect in the female lineage of the transgenic by using genetic crosses with both male and female deficient P. berghei lines. This defect could be due to expression of a female-specific target in the mosquito stages of P. berghei that cannot be phosphorylated by the P. falciparum kinase. Using a previously reported anti-coccidial inhibitor of the cyclic GMP-dependent protein kinase, we show no difference in in vivo efficacy between the transgenic and control P. berghei lines. This in vivo model will be useful for screening future generations of cyclic GMP-dependent protein kinase inhibitors and allowing us to overcome any species-specific differences in the enzyme primary sequence that would influence in vivo efficacy in the rodent model. The approach will also be applicable to in vivo testing of other antimalarial compounds where the target is known.

Smurf2 negatively modulates RIG-I-dependent antiviral response by targeting VISA/MAVS for ubiquitination and degradation.

PubMed

Pan, Yu; Li, Rui; Meng, Jun-Ling; Mao, He-Ting; Zhang, Yu; Zhang, Jun

2014-05-15

VISA (also known as MAVS, Cardif, IPS-1) is the essential adaptor protein for virus-induced activation of IFN regulatory factors 3 and 7 and production of type I IFNs. Understanding the regulatory mechanisms for VISA will provide detailed insights into the positive or negative regulation of innate immune responses. In this study, we identified Smad ubiquitin regulatory factor (Smurf) 2, one of the Smad ubiquitin regulator factor proteins, as an important negative regulator of virus-triggered type I IFN signaling, which targets at the VISA level. Overexpression of Smurf2 inhibits virus-induced IFN-β and IFN-stimulated response element activation. The E3 ligase defective mutant Smurf2/C716A loses the ability to suppress virus-induced type I IFN signaling, suggesting that the negative regulation is dependent on the ubiquitin E3 ligase activity of Smurf2. Further studies demonstrated that Smurf2 interacted with VISA and targeted VISA for K48-linked ubiquitination, which promoted the degradation of VISA. Consistently, knockout or knockdown of Smurf2 expression therefore promoted antiviral signaling, which was correlated with the increase in protein stability of VISA. Our findings suggest that Smurf2 is an important nonredundant negative regulator of virus-triggered type I IFN signaling by targeting VISA for K48-linked ubiquitination and degradation.

Revealing kinetics and state-dependent binding properties of IKur-targeting drugs that maximize atrial fibrillation selectivity

NASA Astrophysics Data System (ADS)

Ellinwood, Nicholas; Dobrev, Dobromir; Morotti, Stefano; Grandi, Eleonora

2017-09-01

The KV1.5 potassium channel, which underlies the ultra-rapid delayed-rectifier current (IKur) and is predominantly expressed in atria vs. ventricles, has emerged as a promising target to treat atrial fibrillation (AF). However, while numerous KV1.5-selective compounds have been screened, characterized, and tested in various animal models of AF, evidence of antiarrhythmic efficacy in humans is still lacking. Moreover, current guidelines for pre-clinical assessment of candidate drugs heavily rely on steady-state concentration-response curves or IC50 values, which can overlook adverse cardiotoxic effects. We sought to investigate the effects of kinetics and state-dependent binding of IKur-targeting drugs on atrial electrophysiology in silico and reveal the ideal properties of IKur blockers that maximize anti-AF efficacy and minimize pro-arrhythmic risk. To this aim, we developed a new Markov model of IKur that describes KV1.5 gating based on experimental voltage-clamp data in atrial myocytes from patient right-atrial samples in normal sinus rhythm. We extended the IKur formulation to account for state-specificity and kinetics of KV1.5-drug interactions and incorporated it into our human atrial cell model. We simulated 1- and 3-Hz pacing protocols in drug-free conditions and with a [drug] equal to the IC50 value. The effects of binding and unbinding kinetics were determined by examining permutations of the forward (kon) and reverse (koff) binding rates to the closed, open, and inactivated states of the KV1.5 channel. We identified a subset of ideal drugs exhibiting anti-AF electrophysiological parameter changes at fast pacing rates (effective refractory period prolongation), while having little effect on normal sinus rhythm (limited action potential prolongation). Our results highlight that accurately accounting for channel interactions with drugs, including kinetics and state-dependent binding, is critical for developing safer and more effective pharmacological anti

Effects of functional group mass variance on vibrational properties and thermal transport in graphene

DOE PAGES

Lindsay, L.; Kuang, Y.

2017-03-13

Intrinsic thermal resistivity critically depends on features of phonon dispersions dictated by harmonic interatomic forces and masses. We present the effects of functional group mass variance on vibrational properties and thermal conductivity (κ ) of functionalized graphene from first principles calculations. We also use graphane, a buckled graphene backbone with covalently bonded Hydrogen atoms on both sides, as the base material and vary the mass of the Hydrogen atoms to simulate the effect of mass variance from other functional groups. We find non-monotonic behavior of κ with increasing mass of the functional group and an unusual cross-over from acoustic-dominated tomore » optic-dominated thermal transport behavior. We connect this cross-over to changes in the phonon dispersion with varying mass which suppress acoustic phonon velocities, but also give unusually high velocity optic modes. Further, we show that out-of-plane acoustic vibrations contribute significantly more to thermal transport than in-plane acoustic modes despite breaking of a reflection symmetry based scattering selection rule responsible for their large contributions in graphene. Our work demonstrates the potential for manipulation and engineering of thermal transport properties in two dimensional materials toward targeted applications.« less

Effects of functional group mass variance on vibrational properties and thermal transport in graphene

NASA Astrophysics Data System (ADS)

Lindsay, L.; Kuang, Y.

2017-03-01

Intrinsic thermal resistivity critically depends on features of phonon dispersions dictated by harmonic interatomic forces and masses. Here we present the effects of functional group mass variance on vibrational properties and thermal conductivity (κ ) of functionalized graphene from first-principles calculations. We use graphane, a buckled graphene backbone with covalently bonded hydrogen atoms on both sides, as the base material and vary the mass of the hydrogen atoms to simulate the effect of mass variance from other functional groups. We find nonmonotonic behavior of κ with increasing mass of the functional group and an unusual crossover from acoustic-dominated to optic-dominated thermal transport behavior. We connect this crossover to changes in the phonon dispersion with varying mass which suppress acoustic phonon velocities, but also give unusually high velocity optic modes. Further, we show that out-of-plane acoustic vibrations contribute significantly more to thermal transport than in-plane acoustic modes despite breaking of a reflection-symmetry-based scattering selection rule responsible for their large contributions in graphene. This work demonstrates the potential for manipulation and engineering of thermal transport properties in two-dimensional materials toward targeted applications.

Effects of functional group mass variance on vibrational properties and thermal transport in graphene

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

Lindsay, L.; Kuang, Y.

Intrinsic thermal resistivity critically depends on features of phonon dispersions dictated by harmonic interatomic forces and masses. We present the effects of functional group mass variance on vibrational properties and thermal conductivity (κ ) of functionalized graphene from first principles calculations. We also use graphane, a buckled graphene backbone with covalently bonded Hydrogen atoms on both sides, as the base material and vary the mass of the Hydrogen atoms to simulate the effect of mass variance from other functional groups. We find non-monotonic behavior of κ with increasing mass of the functional group and an unusual cross-over from acoustic-dominated tomore » optic-dominated thermal transport behavior. We connect this cross-over to changes in the phonon dispersion with varying mass which suppress acoustic phonon velocities, but also give unusually high velocity optic modes. Further, we show that out-of-plane acoustic vibrations contribute significantly more to thermal transport than in-plane acoustic modes despite breaking of a reflection symmetry based scattering selection rule responsible for their large contributions in graphene. Our work demonstrates the potential for manipulation and engineering of thermal transport properties in two dimensional materials toward targeted applications.« less

The Mass Dependence between Protoplanetary Disks and their Stellar Hosts

NASA Astrophysics Data System (ADS)

Andrews, Sean M.; Rosenfeld, Katherine A.; Kraus, Adam L.; Wilner, David J.

2013-07-01

We present a substantial extension of the millimeter (mm) wave continuum photometry catalog for circumstellar dust disks in the Taurus star-forming region, based on a new "snapshot" λ = 1.3 mm survey with the Submillimeter Array. Combining these new data with measurements in the literature, we construct a mm-wave luminosity distribution, f(L mm), for Class II disks that is statistically complete for stellar hosts with spectral types earlier than M8.5 and has a 3σ depth of roughly 3 mJy. The resulting census eliminates a longstanding selection bias against disks with late-type hosts, and thereby demonstrates that there is a strong correlation between L mm and the host spectral type. By translating the locations of individual stars in the Hertzsprung-Russell diagram into masses and ages, and adopting a simple conversion between L mm and the disk mass, Md , we confirm that this correlation corresponds to a statistically robust relationship between the masses of dust disks and the stars that host them. A Bayesian regression technique is used to characterize these relationships in the presence of measurement errors, data censoring, and significant intrinsic scatter: the best-fit results indicate a typical 1.3 mm flux density of ~25 mJy for 1 M ⊙ hosts and a power-law scaling L_mm ∝ M_{\\ast}^{1.5-2.0}. We suggest that a reasonable treatment of dust temperature in the conversion from L mm to Md favors an inherently linear Md vpropM * scaling, with a typical disk-to-star mass ratio of ~0.2%-0.6%. The measured rms dispersion around this regression curve is ±0.7 dex, suggesting that the combined effects of diverse evolutionary states, dust opacities, and temperatures in these disks imprint a full width at half-maximum range of a factor of ~40 on the inferred Md (or L mm) at any given host mass. We argue that this relationship between Md and M * likely represents the origin of the inferred correlation between giant planet frequency and host star mass in the exoplanet

Evolution of a mass spectrometry-grade protease with PTM-directed specificity.

PubMed

Tran, Duc T; Cavett, Valerie J; Dang, Vuong Q; Torres, Héctor L; Paegel, Brian M

2016-12-20

Mapping posttranslational modifications (PTMs), which diversely modulate biological functions, represents a significant analytical challenge. The centerpiece technology for PTM site identification, mass spectrometry (MS), requires proteolytic cleavage in the vicinity of a PTM to yield peptides for sequencing. This requirement catalyzed our efforts to evolve MS-grade mutant PTM-directed proteases. Citrulline, a PTM implicated in epigenetic and immunological function, made an ideal first target, because citrullination eliminates arginyl tryptic sites. Bead-displayed trypsin mutant genes were translated in droplets, the mutant proteases were challenged to cleave bead-bound fluorogenic probes of citrulline-dependent proteolysis, and the resultant beads (1.3 million) were screened. The most promising mutant efficiently catalyzed citrulline-dependent peptide bond cleavage (k cat /K M = 6.9 × 10 5 M -1 ⋅s -1 ). The resulting C-terminally citrullinated peptides generated characteristic isotopic patterns in MALDI-TOF MS, and both a fragmentation product y 1 ion corresponding to citrulline (176.1030 m/z) and diagnostic peak pairs in the extracted ion chromatograms of LC-MS/MS analysis. Using these signatures, we identified citrullination sites in protein arginine deiminase 4 (12 sites) and in fibrinogen (25 sites, two previously unknown). The unique mass spectral features of PTM-dependent proteolytic digest products promise a generalized PTM site-mapping strategy based on a toolbox of such mutant proteases, which are now accessible by laboratory evolution.

Mass properties measurement system dynamics

NASA Technical Reports Server (NTRS)

Doty, Keith L.

1993-01-01

The MPMS mechanism possess two revolute degrees-of-freedom and allows the user to measure the mass, center of gravity, and the inertia tensor of an unknown mass. The dynamics of the Mass Properties Measurement System (MPMS) from the Lagrangian approach to illustrate the dependency of the motion on the unknown parameters.

Dual targeting of HER3 and MEK may overcome HER3-dependent drug-resistance of colon cancers

PubMed Central

Bon, Giulia; Loria, Rossella; Amoreo, Carla Azzurra; Verdina, Alessandra; Sperduti, Isabella; Mastrofrancesco, Arianna; Soddu, Silvia; Diodoro, Maria Grazia; Mottolese, Marcella; Todaro, Matilde; Stassi, Giorgio; Milella, Michele; De Maria, Ruggero; Falcioni, Rita

2017-01-01

Although the medical treatment of colorectal cancer has evolved greatly in the last years, a significant portion of early-stage patients develops recurrence after therapies. The current clinical trials are directed to evaluate new drug combinations and treatment schedules. By the use of patient-derived or established colon cancer cell lines, we found that the tyrosine kinase receptor HER3 is involved in the mechanisms of resistance to therapies. In agreement, the immunohistochemical analysis of total and phospho-HER3 expression in 185 colorectal cancer specimens revealed a significant correlation with lower disease-free survival. Targeting HER3 by the use of the monoclonal antibody patritumab we found induction of growth arrest in all cell lines. Despite the high efficiency of patritumab in abrogating the HER3-dependent activation of PI3K pathway, the HER2 and EGFR-dependent MAPK pathway is activated as a compensatory mechanism. Interestingly, we found that the MEK-inhibitor trametinib inhibits, as expected, the MAPK pathway but induces the HER3-dependent activation of PI3K pathway. The combined treatment results in the abrogation of both PI3K and MAPK pathways and in a significant reduction of cell proliferation and survival. These data suggest a new strategy of therapy for HER3-overexpressing colon cancers. PMID:29312543

The dependence of oxygen and nitrogen abundances on stellar mass from the CALIFA survey

NASA Astrophysics Data System (ADS)

Pérez-Montero, E.; García-Benito, R.; Vílchez, J. M.; Sánchez, S. F.; Kehrig, C.; Husemann, B.; Duarte Puertas, S.; Iglesias-Páramo, J.; Galbany, L.; Mollá, M.; Walcher, C. J.; Ascasíbar, Y.; González Delgado, R. M.; Marino, R. A.; Masegosa, J.; Pérez, E.; Rosales-Ortega, F. F.; Sánchez-Blázquez, P.; Bland-Hawthorn, J.; Bomans, D.; López-Sánchez, Á. R.; Ziegler, B.; Califa Collaboration

2016-10-01

Context. The study of the integrated properties of star-forming galaxies is central to understand their formation and evolution. Some of these properties are extensive and therefore their analysis require totally covering and spatially resolved observations. Among these properties, metallicity can be defined in spiral discs by means of integral field spectroscopy (IFS) of individual H II regions. The simultaneous analysis of the abundances of primary elements, as oxygen, and secondary, as nitrogen, also provides clues about the star formation history and the processes that shape the build-up of spiral discs. Aims: Our main aim is to analyse simultaneously O/H and N/O abundance ratios in H II regions in different radial positions of the discs in a large sample of spiral galaxies to obtain the slopes and the characteristic abundance ratios that can be related to their integrated properties. Methods: We analysed the optical spectra of individual selected H II regions extracted from a sample of 350 spiral galaxies of the CALIFA survey. We calculated total O/H abundances and, for the first time, N/O ratios using the semi-empirical routine Hii-Chi-mistry, which, according to Pérez-Montero (2014, MNRAS, 441, 2663), is consistent with the direct method and reduces the uncertainty in the O/H derivation using [N II] lines owing to the dispersion in the O/H-N/O relation. Then we performed linear fittings to the abundances as a function of the de-projected galactocentric distances. Results: The analysis of the radial distribution both for O/H and N/O in the non-interacting galaxies reveals that both average slopes are negative, but a non-negligible fraction of objects have a flat or even a positive gradient (at least 10% for O/H and 4% for N/O). The slopes normalised to the effective radius appear to have a slight dependence on the total stellar mass and the morphological type, as late low-mass objects tend to have flatter slopes. No clear relation is found, however, to

Sex- and concentration-dependent effects of predator feces on seasonal regulation of body mass in the bank vole Clethrionomys glareolus.

PubMed

Tidhar, Wendy L; Bonier, Frances; Speakman, John R

2007-11-01

Increased perception of predation risk can cause changes in activity, feeding and reproductive behavior in a wide range of taxa. Many small mammals in the temperate zone exhibit fluctuations in body mass in response to changing photoperiod. Bank voles lose body mass in winter which they regain when photoperiod increases in the spring. To determine if predation risk affects seasonal changes in body mass (BM), bank voles were exposed to two concentrations (low: LC and high: HC) of weasel feces. Food intake (FI) and daily energy expenditure (DEE) were measured to establish if differences in body mass were due to adjustment in energy intake or expenditure. Fecal corticosterone (CORT) was measured to assess whether the voles had detected and responded to predator feces as a physiological stressor. Voles of both sexes had higher levels of fecal CORT in the groups exposed to weasel feces compared to controls. Voles responded to the predator feces in a sex- and concentration-dependent manner. Males responded to LC feces by gaining less mass following the change in photoperiod. This was mediated by reduced FI and higher DEE. Female voles also gained less BM in response to HC feces, but increased both FI and DEE. We hypothesize that males may gain a short-term advantage by lowering BM in response to predation risk, which may be regained without affecting reproductive success. The consequences of mass loss in females may be more significant as this may delay the onset of breeding or reduce the size or number of young, thereby negatively affecting breeding success.

The Influence of Attention and Target Identification on Saccadic Eye Movements Depends on Prior Target Location