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Sample records for lines identifies molecular

  1. Comprehensive expression profiling of tumor cell lines identifies molecular signatures of melanoma progression.

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    Byungwoo Ryu

    Full Text Available BACKGROUND: Gene expression profiling has revolutionized our ability to molecularly classify primary human tumors and significantly enhanced the development of novel tumor markers and therapies; however, progress in the diagnosis and treatment of melanoma over the past 3 decades has been limited, and there is currently no approved therapy that significantly extends lifespan in patients with advanced disease. Profiling studies of melanoma to date have been inconsistent due to the heterogeneous nature of this malignancy and the limited availability of informative tissue specimens from early stages of disease. METHODOLOGY/PRINCIPLE FINDINGS: In order to gain an improved understanding of the molecular basis of melanoma progression, we have compared gene expression profiles from a series of melanoma cell lines representing discrete stages of malignant progression that recapitulate critical characteristics of the primary lesions from which they were derived. Here we describe the unsupervised hierarchical clustering of profiling data from melanoma cell lines and melanocytes. This clustering identifies two distinctive molecular subclasses of melanoma segregating aggressive metastatic tumor cell lines from less-aggressive primary tumor cell lines. Further analysis of expression signatures associated with melanoma progression using functional annotations categorized these transcripts into three classes of genes: 1 Upregulation of activators of cell cycle progression, DNA replication and repair (CDCA2, NCAPH, NCAPG, NCAPG2, PBK, NUSAP1, BIRC5, ESCO2, HELLS, MELK, GINS1, GINS4, RAD54L, TYMS, and DHFR, 2 Loss of genes associated with cellular adhesion and melanocyte differentiation (CDH3, CDH1, c-KIT, PAX3, CITED1/MSG-1, TYR, MELANA, MC1R, and OCA2, 3 Upregulation of genes associated with resistance to apoptosis (BIRC5/survivin. While these broad classes of transcripts have previously been implicated in the progression of melanoma and other malignancies, the

  2. Simplified molecular input-line entry system and International Chemical Identifier in the QSAR analysis of styrylquinoline derivatives as HIV-1 integrase inhibitors.

    Science.gov (United States)

    Toropova, Alla P; Toropov, Andrey A; Benfenati, Emilio; Gini, Giuseppina

    2011-05-01

    The simplified molecular input-line entry system (SMILES) and IUPAC International Chemical Identifier (InChI) were examined as representations of the molecular structure for quantitative structure-activity relationships (QSAR), which can be used to predict the inhibitory activity of styrylquinoline derivatives against the human immunodeficiency virus type 1 (HIV-1). Optimal SMILES-based descriptors give a best model with n = 26, r(2) = 0.6330, q(2) = 0.5812, s = 0.502, F = 41 for the training set and n = 10, r(2) = 0.7493, r(pred)(2) = 0.6235, R(m)(2) = 0.537, s = 0.541, F = 24 for the validation set. Optimal InChI-based descriptors give a best model with n = 26, r(2) = 0.8673, q(2) = 0.8456, s = 0.302, F = 157 for the training set and n = 10, r(2) = 0.8562, r(pred)(2) = 0.7715, R(m)(2) = 0.819, s = 0.329, F = 48 for the validation set. Thus, the InChI-based model is preferable. The described SMILES-based and InChI-based approaches have been checked with five random splits into the training and test sets. © 2011 John Wiley & Sons A/S.

  3. Newly Identified Rydberg Emission Lines in Novae

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    Lynch, David K.; Rudy, R. J.; Bernstein, L. S.

    2008-09-01

    Newly Identified Rydberg Emission Lines in Novae David K. Lynch, Richard. J. Rudy (The Aerospace Corporation) & Lawrence S. Bernstein (Spectral Sciences, Inc.) Novae spectra in the near infrared frequently show a set of six emission lines that have not been positively identified (Williams, Longmore, & Geballe 1996, MNRAS, 279, 804; Lynch et al. 2001, AJ, 122, 2013; Rudy et al. 2002 ApJ, 573, 794; Lynch et al. 2004 Astron. J. 127, 1089-1097). These lines are at 0.8926, 1.1114, 1.1901, 1.5545, 2.0996 and 2.425 µm ± 0.005 µm. Krautter et al. (1984 A&A 137, 304) suggested that three of the lines were due to rydberg (hydrogenic) transitions in an unspecified atomic species that was in the 4th or 5th ionization stage (core charge = 4 & 5). We believe that Krautter et al.'s explanation is correct based on 4 additional lines that we have identified in the visible and near infrared spectrum of V723 Cassiopeiae. The observed Rydberg lines appear to originate from high angular momentum states with negligible quantum defects. The species cannot be determined with any certainty because in rydberg states, the outer electron sees a nucleus shielded by the inner electrons and together the inner atom appears to have a charge of +1, like hydrogen. As a result, the atom looks hydrogenic and species such as CV, NV, OV, MgV, SiV, etc. have their rydberg transitions at very similar wavelengths. All the lines represent permitted transitions, most likely formed by recombination. Atoms with core charges 4, 5 & 6 are rarely seen in the astrophysical environment because an extremely hot radiation field is necessary to ionize them. Thermonuclear runaways on the surface of a white dwarf can reach millions of degrees K, and thus there are enough X-ray photons available to achieve the necessary high ionization levels.

  4. Identifying Fractions on a Number Line

    Science.gov (United States)

    Wong, Monica

    2013-01-01

    Fractions are generally introduced to students using the part--whole model. Yet the number line is another important representation which can be used to build fraction concepts (Australian Curriculum Assessment and Reporting Authority [ACARA], 2012). Number lines are recognised as key in students' number development not only of fractions, but…

  5. Magnetic Splitting of Molecular Lines in Sunspot

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    Berdyugina, S. V.; Frutiger, C.; Solanki, S. K.

    A study of molecular lines in sunspots is of particular interest because of their high temperature and pressure sensitivity. Many of them are also magnetically sensitive, but this was not yet widely investigated. With high-resolution, high signal-to-noise Fourier spectroscopy in four Stokes parameters now available, the use of molecular lines for studying the structure of sunspots brings real gains. One is the extension of spot models, including magnetic field, up to layers, where atomic lines suffer from NLTE effects but molecules can still be treated in the LTE approximation. Equally important is the fact that since molecular lines are extremely temperature sensitive they can be used to probe the thermal and magnetic structure of the coolest parts of sunspots. We present calculations of splitting and the Stokes parameters for a number of molecular lines in the visible and near-infrared regions. Our first selections are the green system of MgH A2Π-X2σ and the TiO triplet α, γ' and γ systems as the most studied band systems in the sunspot spectrum. The calculations involve different regimes of the molecular Zeeman effect, up to the complete Paschen-Back effect for individual lines. We look for molecular lines which can be used along with atomic lines to derive magnetic, thermal and dynamic properties of the umbra.

  6. Molecular analysis and anticancer properties of two identified isolates, Fusarium solani and Emericella nidulans isolated from Wady El-Natron soil in Egypt against Caco-2 (ATCC) cell line.

    Science.gov (United States)

    Mohamed, Hala F

    2012-11-01

    To characterize, identify and investigate the anticancer properties of two new soil fungal isolates, Emericella nidulans and Fusarium solani isolated from Wady El-Natron in Egypt against colon cancer Caco-2 (ATCC) cell line. Soil sample was cultured and two strains were chosen for morphological and phenotypical characterization. Partial sequences of the 18s rRNA gene and the internal transcribed spacer region ITS of the two isolates were amplified by PCR. Phylogenetic tree construction and analysis of the resulted multiple sequences from the two fugal isolates were also carried out. In vitro anticancer activity of the two strains was done against colon Caco-2 cancer cell line. Reverse transcription - PCR was carried out to detect level of expression of p53 in Caco-2 cell line. HF.1 displayed morphological and genotypic characteristics most similar to that of Fusarium solani while HF.2 was most similar to Emericella nidulans with high similarity of 99% and 97% respectively. The multiple sequence alignment of the two fungal isolates showed that, the maximum identical conserved domains in the 18s rRNA genes were identified with the nucleotide regions of 51st to 399th base pairs, 88th to 525th base pairs respectively. While those in the ITS genes were identified with the nucleotide regions of 88th to 463rd and 51st to 274th. The two isolates showed IC50 value with (6.24±5.21) and (9.84±0.36) µg/mL) concentrations respectively at 28h. Reverse transcription - PCR indicated that these cells showed high level of expression for p53 mRNA. The morphology and molecular analysis identified HF.1 and HF.2 to be Fusarium solani and Emericella nidulans; new isolates of anticancer producing fungi from Wady El-Natroon city in Egypt. Treatment with the two isolates caused P53 expression in Caco-2 cell line. These two isolates can be used as an anticancer agents.

  7. Molecular analysis and anticancer properties of two identified isolates, Fusarium solani and Emericella nidulans isolated from Wady El-Natron soil in Egypt against Caco-2 (ATCC) cell line

    Institute of Scientific and Technical Information of China (English)

    Hala F Mohamed

    2012-01-01

    Objective: To characterize, identify and investigate the anticancer properties of two new soil fungal isolates, Emericella nidulans and Fusarium solani isolated from Wady El-Natron in Egypt against colon cancer Caco-2 (ATCC) cell line. Methods: Soil sample was cultured and two strains were chosen for morphological and phenotypical characterization. Partial sequences of the 18s rRNA gene and the internal transcribed spacer region ITS of the two isolates were amplified by PCR. Phylogenetic tree construction and analysis of the resulted multiple sequences from the two fugal isolates were also carried out. In vitro anticancer activity of the two strains was done against colon Caco-2 cancer cell line. Reverse transcription – PCR was carried out to detect level of expression of p53 in Caco-2 cell line. Results: HF.1 displayed morphological and genotypic characteristics most similar to that of Fusarium solani while HF.2 was most similar to Emericella nidulans with high similarity of 99% and 97% respectively. The multiple sequence alignment of the two fungal isolates showed that, the maximum identical conserved domains in the 18s rRNA genes were identified with the nucleotide regions of 51st to 399th base pairs, 88th to 525th base pairs respectively. While those in the ITS genes were identified with the nucleotide regions of 88th to 463rdand 51st to 274th. The two isolates showed IC50 value with (6.24±5.21) and (9.84±0.36) μg/mL) concentrations respectively at 28h. Reverse transcription – PCR indicated that these cells showed high level of expression for p53 mRNA. Conclusions: The morphology and molecular analysis identified HF.1 and HF.2 to be Fusarium solani and Emericella nidulans; new isolates of anticancer producing fungi from Wady El-Natroon city in Egypt. Treatment with the two isolates caused P53 expression in Caco-2 cell line. These two isolates can be used as an anticancer agents.

  8. Modeling molecular hyperfine line emission

    CERN Document Server

    Keto, Eric

    2010-01-01

    In this paper we discuss two approximate methods previously suggested for modeling hyperfine spectral line emission for molecules whose collisional transitions rates between hyperfine levels are unknown. Hyperfine structure is seen in the rotational spectra of many commonly observed molecules such as HCN, HNC, NH3, N2H+, and C17O. The intensities of these spectral lines can be modeled by numerical techniques such as Lambda-iteration that alternately solve the equations of statistical equilibrium and the equation of radiative transfer. However, these calculations require knowledge of both the radiative and collisional rates for all transitions. For most commonly observed radio frequency spectral lines, only the net collisional rates between rotational levels are known. For such cases, two approximate methods have been suggested. The first method, hyperfine statistical equilibrium (HSE), distributes the hyperfine level populations according to their statistical weight, but allows the population of the rotationa...

  9. Molecular Fingerprints to Identify Candida Species

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    Claudia Spampinato

    2013-01-01

    Full Text Available A wide range of molecular techniques have been developed for genotyping Candida species. Among them, multilocus sequence typing (MLST and microsatellite length polymorphisms (MLP analysis have recently emerged. MLST relies on DNA sequences of internal regions of various independent housekeeping genes, while MLP identifies microsatellite instability. Both methods generate unambiguous and highly reproducible data. Here, we review the results achieved by using these two techniques and also provide a brief overview of a new method based on high-resolution DNA melting (HRM. This method identifies sequence differences by subtle deviations in sample melting profiles in the presence of saturating fluorescent DNA binding dyes.

  10. Molecular absorption in transition region spectral lines

    CERN Document Server

    Schmit, Donald; Ayres, Thomas; Peter, Hardi; Curdt, Werner; Jaeggli, Sarah

    2014-01-01

    Aims: We present observations from the Interface Region Imaging Spectrograph (IRIS) of absorption features from a multitude of cool atomic and molecular lines within the profiles of Si IV transition region lines. Many of these spectral lines have not previously been detected in solar spectra. Methods: We examined spectra taken from deep exposures of plage on 12 October 2013. We observed unique absorption spectra over a magnetic element which is bright in transition region line emission and the ultraviolet continuum. We compared the absorption spectra with emission spectra that is likely related to fluorescence. Results: The absorption features require a population of sub-5000 K plasma to exist above the transition region. This peculiar stratification is an extreme deviation from the canonical structure of the chromosphere-corona boundary . The cool material is not associated with a filament or discernible coronal rain. This suggests that molecules may form in the upper solar atmosphere on small spatial scales...

  11. Accuracy and Completeness of Molecular Line Lists

    Science.gov (United States)

    Polyansky, Oleg; Tennyson, Jonathan

    2017-06-01

    We review recent progress in the calculation of the global, high-temperature and accurate room-temperature linelists of various molecules relevant for the analysis of both Earth and exoplanet atmospheres and cool stars. These global line lists can be constructed based on progress in calculation of energy levels up to dissociation and the fitting of the molecular PESs to the experimental data close to dissociation. Sub-percent accuracy in the intensity of calculated absorption lines is achieved thanks to progress in ab initio electronic structure calculations which is aided by the possibility of characterizing their accuracy by the comparison with experimental intensities measured with sub-percent accuracy for some molecular lines. The advantage of variational calculations over experiment though is the ability to produce billions of lines covering all the isotopologues, which is clearly impossible for the experimental observations. Atmospherically and astrophysically important molecules such as H_2O, CO_2, CO and H_3^+ will be considered together with some examples of the other molecules.

  12. Hyperspectral imaging to identify salt-tolerant wheat lines

    Science.gov (United States)

    Moghimi, Ali; Yang, Ce; Miller, Marisa E.; Kianian, Shahryar; Marchetto, Peter

    2017-05-01

    In order to address the worldwide growing demand for food, agriculture is facing certain challenges and limitations. One of the important threats limiting crop productivity is salinity. Identifying salt tolerate varieties is crucial to mitigate the negative effects of this abiotic stress in agricultural production systems. Traditional measurement methods of this stress, such as biomass retention, are labor intensive, environmentally influenced, and often poorly correlated to salinity stress alone. In this study, hyperspectral imaging, as a non-destructive and rapid method, was utilized to expedite the process of identifying relatively the most salt tolerant line among four wheat lines including Triticum aestivum var. Kharchia, T. aestivum var. Chinese Spring, (Ae. columnaris) T. aestivum var. Chinese Spring, and (Ae. speltoides) T. aestivum var. Chinese Spring. To examine the possibility of early detection of a salt tolerant line, image acquisition was started one day after stress induction and continued on three, seven, and 12 days after adding salt. Simplex volume maximization (SiVM) method was deployed to detect superior wheat lines in response to salt stress. The results of analyzing images taken as soon as one day after salt induction revealed that Kharchia and (columnaris)Chinese Spring are the most tolerant wheat lines, while (speltoides) Chinese Spring was a moderately susceptible, and Chinese Spring was a relatively susceptible line to salt stress. These results were confirmed with the measuring biomass performed several weeks later.

  13. A molecular line scan in the Hubble deep field north

    Energy Technology Data Exchange (ETDEWEB)

    Decarli, R.; Walter, F.; Colombo, D.; Da Cunha, E.; Rix, H.-W. [Max-Planck Institut für Astronomie, Königstuhl 17, D-69117 Heidelberg (Germany); Carilli, C. [NRAO, Pete V. Domenici Array Science Center, P.O. Box O, Socorro, NM 87801 (United States); Riechers, D. [Cornell University, 220 Space Sciences Building, Ithaca, NY 14853 (United States); Cox, P.; Neri, R.; Downes, D. [IRAM, 300 rue de la Piscine, F-38406 Saint-Martin d' Hères (France); Aravena, M. [European Southern Observatory, Alonso de Cordova 3107, Casilla 19001, Vitacura Santiago (Chile); Bell, E. [Department of Astronomy, University of Michigan, 500 Church Street, Ann Arbor, MI 48109 (United States); Bertoldi, F. [Argelander Institute for Astronomy, University of Bonn, Auf dem Hügel 71, D-53121 Bonn (Germany); Daddi, E.; Sargent, M. [Laboratoire AIM, CEA/DSM-CNRS-Universite Paris Diderot, Irfu/Service d' Astrophysique, CEA Saclay, Orme des Merisiers, F-91191 Gif-sur-Yvette cedex (France); Dickinson, M. [National Optical Astronomy Observatory, 950 North Cherry Avenue, Tucson, AZ 85719 (United States); Ellis, R. [Astronomy Department, California Institute of Technology, MC105-24, Pasadena, CA 91125 (United States); Lentati, L.; Maiolino, R. [Cavendish Laboratory, University of Cambridge, 19 J. J. Thomson Avenue, Cambridge CB3 0HE (United Kingdom); Menten, K. M., E-mail: decarli@mpia.de [Max-Planck-Institut für Radioastronomie, Auf dem Hügel 69, D-53121 Bonn (Germany); and others

    2014-02-20

    We present a molecular line scan in the Hubble Deep Field North (HDF-N) that covers the entire 3 mm window (79-115 GHz) using the IRAM Plateau de Bure Interferometer. Our CO redshift coverage spans z ≲ 0.45, 1 ≲ z ≲ 1.9 and all z ≳ 2. We reach a CO detection limit that is deep enough to detect essentially all z > 1 CO lines reported in the literature so far. We have developed and applied different line-searching algorithms, resulting in the discovery of 17 line candidates. We estimate that the rate of false positive line detections is ∼2/17. We identify optical/NIR counterparts from the deep ancillary database of the HDF-N for seven of these candidates and investigate their available spectral energy distributions. Two secure CO detections in our scan are identified with star-forming galaxies at z = 1.784 and at z = 2.047. These galaxies have colors consistent with the 'BzK' color selection and they show relatively bright CO emission compared with galaxies of similar dust continuum luminosity. We also detect two spectral lines in the submillimeter galaxy HDF 850.1 at z = 5.183. We consider an additional nine line candidates as high quality. Our observations also provide a deep 3 mm continuum map (1σ noise level = 8.6 μJy beam{sup –1}). Via a stacking approach, we find that optical/MIR bright galaxies contribute only to <50% of the star formation rate density at 1 < z < 3, unless high dust temperatures are invoked. The present study represents a first, fundamental step toward an unbiased census of molecular gas in 'normal' galaxies at high-z, a crucial goal of extragalactic astronomy in the ALMA era.

  14. Identifying anti-growth factors for human cancer cell lines through genome-scale metabolic modeling

    DEFF Research Database (Denmark)

    Ghaffari, Pouyan; Mardinoglu, Adil; Asplund, Anna

    2015-01-01

    Human cancer cell lines are used as important model systems to study molecular mechanisms associated with tumor growth, hereunder how genomic and biological heterogeneity found in primary tumors affect cellular phenotypes. We reconstructed Genome scale metabolic models (GEMs) for eleven cell lines...... based on RNA-Seq data and validated the functionality of these models with data from metabolite profiling. We used cell line-specific GEMs to analyze the differences in the metabolism of cancer cell lines, and to explore the heterogeneous expression of the metabolic subsystems. Furthermore, we predicted...... antimetabolites using two cell lines with different phenotypic origins, and found that it is effective in inhibiting the growth of these cell lines. Using immunohistochemistry, we also showed high or moderate expression levels of proteins targeted by the validated antimetabolite. Identified anti-growth factors...

  15. Molecular clouds photoevaporation and FIR line emission

    Science.gov (United States)

    Vallini, L.; Ferrara, A.; Pallottini, A.; Gallerani, S.

    2017-01-01

    With the aim of improving predictions on far infrared (FIR) line emission from Giant Molecular Clouds (GMC), we study the effects of photoevaporation (PE) produced by external far-ultraviolet (FUV) and ionizing (extreme-ultraviolet, EUV) radiation on GMC structure. We consider three different GMCs with mass in the range M_GMC = 10^{3-6} {M_{⊙}}. Our model includes: (i) an observationally-based inhomogeneous GMC density field, and (ii) its time evolution during the PE process. In the fiducial case (MGMC ≈ 105M⊙), the photoevaporation time (tpe) increases from 1 Myr to 30 Myr for gas metallicity Z=0.05-1 Z_{⊙}, respectively. Next, we compute the time-dependent luminosity of key FIR lines tracing the neutral and ionized gas layers of the GMCs, ([C II] at 158 {μ m}, [O III] at 88 μ m) as a function of G0, and Z until complete photoevaporation at tpe. We find that the specific [C II] luminosity is almost independent on the GMC model within the survival time of the cloud. Stronger FUV fluxes produce higher [C II] and [O III] luminosities, however lasting for progressively shorter times. At Z = Z⊙ the [C II] emission is maximized (L_CII≈ 10^4 {L_{⊙}} for the fiducial model) for tpopulations.

  16. Molecular clouds photoevaporation and FIR line emission

    CERN Document Server

    Vallini, L; Pallottini, A; Gallerani, S

    2016-01-01

    With the aim of improving predictions on the far infrared (FIR) line emission from Giant Molecular Clouds (GMC), we have studied the effects of photoevaporation (PE) produced by external far-ultraviolet (FUV) and ionizing (extreme-ultraviolet, EUV) radiation on the GMC structure. Our model includes: (i) an observationally-based inhomogeneous GMC density field, and (ii) its time evolution during the PE process. We find that the photoevaporation timescale, $t_{pe}$, of a typical GMC ($M_{\\rm GMC}=9 \\times 10^{4}\\,\\rm{M_{\\odot}}$) is in the range $1-30$ Myr, for gas metallicity $Z=0.05-1\\,\\rm Z_{\\odot}$, respectively. At fixed metallicity, $t_{pe}$ decreases for higher FUV fluxes, $G_0$, due to the larger temperature of the photodissociation region (PDR). The presence of EUV radiation is important at $Z<0.2\\,\\rm{Z_{\\odot}}$, when the size of the HII layer becomes comparable to the cloud radius. We then compute the time-dependent luminosity (for which we give fitting formulae) of several key FIR lines ([CII], ...

  17. Molecular Line Observations of NGC 281

    Science.gov (United States)

    Lee, Youngung; Jung, Jae-Hoon

    1994-12-01

    We have mapped 110' times 40' region centered on NGC281 (S184, IC1590), an expanding HII region associated with molecular cloud, in (12) CO, (13) CO, HCO(+) J=1--0, C(18) O J=1--0, and CS J=2--1 using the 3 mm receiver on the Daeduk Radio Astronomy Observatory (DRAO) 14 m telescope. We also conducted coarse-sampled mapping (6') toward the northern part of NGC281 to detect any possible molecular emission associated. Molecular emission around NGC281 is found to be very extended and comprised of many pieces of clouds. The emission is all distributed toward the southern part of the NGC281 and no emission is detected toward northern part. The identified clouds are arbitrarily named as A to H depending on their morphology and radial velocity. All Clouds (A to F) are weakly connected one another and have almost the same radial velocities, thus it is likely that these are fragmented from a larger cloud. Clouds A, B, D, and E show that larger centroid velocity dispersion, which implys that larger bulk motions exist in these clouds. In fact, it is known that star formation is active in Clouds D and E. But Clouds A and B are also possible star-forming regions, as they show strong CO and CS emission and they are all associated with IRAS point sources. The masses are estimated in three independent ways for all the Clouds. As some of the Clouds are severely disturbed, thus the virial mass estimate is up to several times larger than the estimate using (12) CO luminosity to mass coversion factor. However, Cloud A is very bright and dense, and the two estimates give almost the same mass (CS emission is 1.3 K, which is the bright of all). Various physical parameters are also estimated. From their spatial-velocity map and spectra, a new bipolar outflow is identified within Cloud A. Cloud E, in which a large bipolar outflow was identified, is the largest and brightest molecular cloud. We detected significantly strong CS, and HCO(+) emission (1.8 K), which is the strong sign of shock.

  18. Identifying thermal cycling mechanisms in PWR branch line piping

    Energy Technology Data Exchange (ETDEWEB)

    Rosinski, S.T. [EPRI, Charlotte, NC (United States); Keller, J.D.; Bilanin, A.J. [Continuum Dynamics, Inc., Ewing, NJ (United States)

    2002-07-01

    Predicting the onset and the characteristics of thermal cycling in pressurized water reactor (PWR) branch line piping systems is critical to formulation of thermal fatigue screening tools. The complex nature of the underlying thermal-hydraulic phenomena, however, significantly complicates prediction using analytical models or direct numerical simulations. Instead, it is necessary to perform scaled experiments to identify the physical mechanisms and to gather data for formulation of semi-empirical models for the thermal cycling phenomena. Through the EPRI Materials Reliability Program a test program is underway to identify and develop semi-empirical correlations for the physical thermalhydraulic mechanisms that cause thermal cycling in dead-ended PWR branch line piping systems. Three series of tests are being performed in this test program: configuration tests on a representative up-horizontal (UH) branch line piping geometry, configuration tests on a representative down-horizontal (DH) branch line piping geometry, and high Reynolds number tests to assess penetration of secondary flow structures into a dead-ended branch line. Results from UH and DH configuration tests indicate that random turbulence penetration is not sufficient for thermal cycling to occur. Rather a swirling flow structure, representative of a large, 'corkscrew' vortical structure, is required for thermal cycling. Scale tests on the UH configuration have simulated cycling phenomena observed in full-scale plant data and have been used to determine parametric sensitivities in formulating a predictive model for the thermal cycling. Data indicate that the mechanism for thermal cycling in UH configurations is stochastic but scales with the leak rate from the valve. The critical dependent variables are reduced to several non-dimensional scaling curves, resulting in a semiempirical predictive model. This paper discusses the test program and the results obtained to date. Application of these

  19. Identifying power line harmonic radiation from an electrical network

    Directory of Open Access Journals (Sweden)

    S. M. Werner

    2005-09-01

    Full Text Available It has been suggested that the space environment is being polluted by power line harmonic radiation (PLHR, generated from harmonics of the electrical power transmission frequency (50 or 60 Hz and radiated into the ionosphere and magnetosphere by long power lines. While some in-situ satellite measurements of PLHR have been reported, it has proved difficult to confirm the source and overall significance. The electricity network of the city of Dunedin, New Zealand, is tiny compared to the many large industrial zones found outside New Zealand. However, the 1050Hz ripple control signal injected into the local electrical grid at regular intervals as a load-control mechanism provides an opportunity for identifying PLHR strengths radiated from a spatially well defined electrical network. In-situ observations by satellites should allow a greater understanding of PLHR and its significance as man-made pollution to near-Earth space. Calculations have been undertaken to estimate the strength of the radiation fields expected from the ripple control signal which is injected into the Dunedin city electrical network. We find that ground-based measurements will not be sensitive enough for detection of the ripple control radiation fields, even during the quietest winter night. While significant power penetrates the lower ionosphere, this is well below the reported threshold required for nonlinear triggering in the Van Allen radiation belts. Some radiated fields at satellite altitudes should be detectable, allowing in-situ measurements. At the altitude of the DEMETER mission, the radiated electric fields will not be detectable under any ionospheric conditions. However, we find that the radiated magnetic fields may be detectable by the DEMETER satellite at certain times, although this will be very difficult. Nonetheless, there is the possibility for future experimental campaigns.

    Keywords. Magnetospheric physics (Magnetosphereionosphere interactions; Plasma

  20. Morphological and molecular characterization of two G.Somalense monosomic alien addition lines(MAALs)

    Institute of Scientific and Technical Information of China (English)

    ZHOU Zhonghua; YU Ping; LIU Guanghui; HE Jianxing; CHEN Jinxiang; ZHANG Xinxue

    2004-01-01

    Two G. somalense monosomic alien addition lines were identified from the derived backcross progenies of allohexaploid between G. hirsutum and G. somalense through cytological and morphological observation. Furthermore, the alien addition chromosome was identified and distinguished by RAPD analysis. A total of 160 RAPD primers were used for PCR amplification. Primer SBSG11 could produce a specific molecular marker (600 bp) for monosomic alien addition line Ⅰ(MAAL Ⅰ). Primer SBSC03 could produce a specific molecular marker (700 bp) for monosomic alien addition line Ⅱ(MAAL Ⅱ). SBSE07 and SBSE08 could respectively produce common molecular marker for monosomic alien addition lines Ⅰ and Ⅱ. G . somalense alien addition lines could be important for cotton improvement.

  1. NEWLY IDENTIFIED EXTENDED GREEN OBJECTS (EGOs) FROM THE SPITZER GLIMPSE II SURVEY. II. MOLECULAR CLOUD ENVIRONMENTS

    Energy Technology Data Exchange (ETDEWEB)

    Chen Xi; Gan Conggui; Shen Zhiqiang [Key Laboratory for Research in Galaxies and Cosmology, Shanghai Astronomical Observatory, Chinese Academy of Sciences, Shanghai 200030 (China); Ellingsen, Simon P.; Titmarsh, Anita [School of Mathematics and Physics, University of Tasmania, Hobart, Tasmania (Australia); He Jinhua, E-mail: chenxi@shao.ac.cn [Key Laboratory for the Structure and Evolution of Celestial Objects, Yunnan Astronomical Observatory/National Astronomical Observatory, Chinese Academy of Sciences, P.O. Box 110, Kunming 650011, Yunnan Province (China)

    2013-06-01

    We have undertaken a survey of molecular lines in the 3 mm band toward 57 young stellar objects using the Australia Telescope National Facility Mopra 22 m radio telescope. The target sources were young stellar objects with active outflows (extended green objects (EGOs)) newly identified from the GLIMPSE II survey. We observe a high detection rate (50%) of broad line wing emission in the HNC and CS thermal lines, which combined with the high detection rate of class I methanol masers toward these sources (reported in Paper I) further demonstrates that the GLIMPSE II EGOs are associated with outflows. The physical and kinematic characteristics derived from the 3 mm molecular lines for these newly identified EGOs are consistent with these sources being massive young stellar objects with ongoing outflow activity and rapid accretion. These findings support our previous investigations of the mid-infrared properties of these sources and their association with other star formation tracers (e.g., infrared dark clouds, methanol masers and millimeter dust sources) presented in Paper I. The high detection rate (64%) of the hot core tracer CH{sub 3}CN reveals that the majority of these new EGOs have evolved to the hot molecular core stage. Comparison of the observed molecular column densities with predictions from hot core chemistry models reveals that the newly identified EGOs from the GLIMPSE II survey are members of the youngest hot core population, with an evolutionary time scale of the order of 10{sup 3} yr.

  2. A General Catalogue of Molecular Hydrogen Emission-Line Objects (MHOs) in Outflows from Young Stars

    CERN Document Server

    Davis, Christopher J; Khanzadyan, Tigran; Smith, Michael D; Jenness, Tim

    2009-01-01

    We present a catalogue of Molecular Hydrogen emission-line Objects (MHOs) in outflows from embedded young stars. All objects are identified in the near-infrared lines of molecular hydrogen, all reside in the Milky Way, and all are associated with jets or molecular outflows from young stars. Objects in both low and high-mass star forming regions are included. This catalogue complements the existing database of Herbig-Haro objects; indeed, for completeness, HH objects that are detected in H2 emission are included in the MHO catalogue.

  3. Identify Fractions and Decimals on a Number Line

    Science.gov (United States)

    Shaughnessy, Meghan M.

    2011-01-01

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

  4. Spectropolarimetry of the molecular hydrogen line emission from OMC-1

    Science.gov (United States)

    Burton, Michael G.; Hough, J. H.; Axon, David J.; Hasegawa, T.; Tamura, M.

    1988-01-01

    Observations of the H2 v = 1-0 S(1) line at 35 km/s velocity resolution were obtained at several locations within OMC-1, including the molecular hydrogen reflection nebula. All line profiles are smooth and show no evidence for being composed of discrete components. The data are discussed with respect to a model for the H2 line formation in which the emission originates in discrete clumps moving at different velocities. It is suggested that the extended blue wing may come from fast-moving clumps embedded in a wind.

  5. Spectropolarimetry of the molecular hydrogen line emission from OMC-1

    Science.gov (United States)

    Burton, Michael G.; Hough, J. H.; Axon, David J.; Hasegawa, T.; Tamura, M.

    1988-01-01

    Observations of the H2 v = 1-0 S(1) line at 35 km/s velocity resolution were obtained at several locations within OMC-1, including the molecular hydrogen reflection nebula. All line profiles are smooth and show no evidence for being composed of discrete components. The data are discussed with respect to a model for the H2 line formation in which the emission originates in discrete clumps moving at different velocities. It is suggested that the extended blue wing may come from fast-moving clumps embedded in a wind.

  6. Spectral Line Survey toward a Molecular Cloud in IC10

    CERN Document Server

    Nishimura, Yuri; Watanabe, Yoshimasa; Sakai, Nami; Aikawa, Yuri; Kawamura, Akiko; Yamamoto, Satoshi

    2016-01-01

    We have conducted a spectral line survey observation in the 3 mm band toward the low-metallicity dwarf galaxy IC10 with the 45 m radio telescope of Nobeyama Radio Observatory to explore its chemical composition at a molecular-cloud scale (~80 pc). The CS, SO, CCH, HCN, HCO+, and HNC lines are detected for the first time in this galaxy in addition to the CO and 13CO lines, while c-C3H2, CH3OH, CN, C18O, and N2H+ lines are not detected. The spectral intensity pattern is found to be similar to those observed toward molecular clouds in the Large Magellanic Cloud, whose metallicity is as low as IC10. Nitrogen-bearing species are deficient in comparison with the Galactic molecular clouds due to a lower elemental abundance of nitrogen. CCH is abundant in comparison with Galactic translucent clouds, whereas CH3OH may be deficient. These characteristic trends for CCH and CH3OH are also seen in the LMC, and seem to originate from photodissociation regions more extended in peripheries of molecular clouds due to the lowe...

  7. Molecular spectral line surveys and the organic molecules in the interstellar molecular clouds

    Science.gov (United States)

    Ohishi, Masatoshi

    2008-10-01

    It is known that more than 140 interstellar and circumstellar molecules have so far been detected, mainly by means of the radio astronomy observations. Many organic molecules are also detected, including alcohols, ketons, ethers, aldehydes, and others, that are distributed from dark clouds and hot cores in the giant molecular clouds. It is believed that most of the organic molecules in space are synthesized through the grain surface reactions, and are evaporated from the grain surface when they are heated up by the UV radiation from adjacent stars. On the other hand the recent claim on the detection of glycine have raised an important issue how difficult it is to confirm secure detection of weak spectra from less abundant organic molecules in the interstellar molecular cloud. I will review recent survey observations of organic molecules in the interstellar molecular clouds, including independent observations of glycine by the 45 m radio telescope in Japan, and will discuss the procedure to securely identify weak spectral lines from organic molecules and the importance of laboratory measurement of organic species.

  8. Cell Line Data Base: structure and recent improvements towards molecular authentication of human cell lines.

    Science.gov (United States)

    Romano, Paolo; Manniello, Assunta; Aresu, Ottavia; Armento, Massimiliano; Cesaro, Michela; Parodi, Barbara

    2009-01-01

    The Cell Line Data Base (CLDB) is a well-known reference information source on human and animal cell lines including information on more than 6000 cell lines. Main biological features are coded according to controlled vocabularies derived from international lists and taxonomies. HyperCLDB (http://bioinformatics.istge.it/hypercldb/) is a hypertext version of CLDB that improves data accessibility by also allowing information retrieval through web spiders. Access to HyperCLDB is provided through indexes of biological characteristics and navigation in the hypertext is granted by many internal links. HyperCLDB also includes links to external resources. Recently, an interest was raised for a reference nomenclature for cell lines and CLDB was seen as an authoritative system. Furthermore, to overcome the cell line misidentification problem, molecular authentication methods, such as fingerprinting, single-locus short tandem repeat (STR) profile and single nucleotide polymorphisms validation, were proposed. Since this data is distributed, a reference portal on authentication of human cell lines is needed. We present here the architecture and contents of CLDB, its recent enhancements and perspectives. We also present a new related database, the Cell Line Integrated Molecular Authentication (CLIMA) database (http://bioinformatics.istge.it/clima/), that allows to link authentication data to actual cell lines.

  9. Molecular signatures in response to Isoliquiritigenin in lymphoblastoid cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jae-Eun; Hong, Eun-Jung; Nam, Hye-Young [National Biobank of Korea, Center for Genome Science, Korea National Institute of Health, Korea Centers for Disease Control and Prevention (Korea, Republic of); Hwang, Meeyul [Research Center for Biomedical Resource of Oriental Medicine, Daegu Haany University (Korea, Republic of); Kim, Ji-Hyun [National Biobank of Korea, Center for Genome Science, Korea National Institute of Health, Korea Centers for Disease Control and Prevention (Korea, Republic of); Han, Bok-Ghee, E-mail: bokghee@nih.go.kr [National Biobank of Korea, Center for Genome Science, Korea National Institute of Health, Korea Centers for Disease Control and Prevention (Korea, Republic of); Jeon, Jae-Pil, E-mail: jpjeon@cdc.go.kr [National Biobank of Korea, Center for Genome Science, Korea National Institute of Health, Korea Centers for Disease Control and Prevention (Korea, Republic of)

    2012-10-19

    Highlights: Black-Right-Pointing-Pointer We identified the inhibitory effect of ISL on cell proliferation of LCLs. Black-Right-Pointing-Pointer We found ISL-induced genes and miRNAs through microarray approach. Black-Right-Pointing-Pointer ISL-treated LCLs represented gene expression changes in cell cycle and p53 pathway. Black-Right-Pointing-Pointer We revealed 12 putative mRNA-miRNA functional pairs associated with ISL effect. -- Abstract: Isoliquiritigenin (ISL) has been known to induce cell cycle arrest and apoptosis of various cancer cells. However, genetic factors regulating ISL effects remain unclear. The aim of this study was to identify the molecular signatures involved in ISL-induced cell death of EBV-transformed lymphoblastoid cell lines (LCLs) using microarray analyses. For gene expression and microRNA (miRNA) microarray experiments, each of 12 LCL strains was independently treated with ISL or DMSO as a vehicle control for a day prior to total RNA extraction. ISL treatment inhibited cell proliferation of LCLs in a dose-dependent manner. Microarray analysis showed that ISL-treated LCLs represented gene expression changes in cell cycle and p53 signaling pathway, having a potential as regulators in LCL survival and sensitivity to ISL-induced cytotoxicity. In addition, 36 miRNAs including five miRNAs with unknown functions were differentially expressed in ISL-treated LCLs. The integrative analysis of miRNA and gene expression profiles revealed 12 putative mRNA-miRNA functional pairs. Among them, miR-1207-5p and miR-575 were negatively correlated with p53 pathway- and cell cycle-associated genes, respectively. In conclusion, our study suggests that miRNAs play an important role in ISL-induced cytotoxicity in LCLs by targeting signaling pathways including p53 pathway and cell cycle.

  10. High accuracy molecular line lists for exoplanetary atmospheres

    Science.gov (United States)

    Barber, R. J.; Tennyson, J.

    2008-09-01

    Water, carbon monoxide, methane and ammonia are major constituents exoplanetary atmospheres. Measurements of the relative abundances of these species are capable of yielding information about physical conditions, including: temperature, pressure, thermal profile and metallicity. Modern observational techniques and instrumentation mean that in principle, we now have the capability to detect these molecules in the emission and absorption spectra of transiting exoplanets. However, in order to be able to interpret these data, robust atmospheric models and complete and accurate molecular line lists are required. Our team at UCL is a world leader in the computation of molecular spectroscopic line lists. The BT2 water line list [1], which contains over 500 million transitions, was used in the first secure detection of H2O in the atmosphere of a transiting exoplanet [2]. We are currently computing a line list for NH3, which is a considerably more difficult task as the molecule has nine degrees of internal freedom (H2O has six). In this paper, we will discuss the ab initio computation of ro-vibrational molecular spectra and their application in exoplanetary studies. References [1] Barber R. J., Tennyson J., Harris G. J., Tolchenov R., 2006, MNRAS, 368, 1087 [2] Tinetti G. et al., 2007, Nature, 448, 169

  11. Cosmology with intensity mapping techniques using atomic and molecular lines

    CERN Document Server

    Fonseca, José; Santos, Mário G; Cooray, Asantha

    2016-01-01

    We present a systematic study of the intensity mapping technique using updated models for the different emission lines from galaxies and identify which ones are more promising for cosmological studies of the post reionization epoch. We consider the emission of ${\\rm Ly\\alpha}$, ${\\rm H\\alpha}$, H$\\beta$, optical and infrared oxygen lines, nitrogen lines, CII and the CO rotational lines. We then identify that ${\\rm Ly\\alpha}$, ${\\rm H\\alpha}$, OII, CII and the lowest rotational CO lines are the best candidates to be used as IM probes. These lines form a complementary set of probes of the galaxies emission spectra. We then use reasonable experimental setups from current, planned or proposed experiments to access the detectability of the power spectrum of each emission line. Intensity mapping of ${\\rm Ly\\alpha}$ emission from $z=2$ to 3 will be possible in the near future with HETDEX, while far-infrared lines require new dedicated experiments. We also show that the proposed SPHEREx satellite can use OII and ${\\r...

  12. A Multi-molecular Line Study of an Entire Giant Molecular Cloud

    Science.gov (United States)

    Lo, Nadia

    2009-05-01

    A unified theory of star formation remains one of the major unsolved issues in astrophysics. Presented here are the results of multi-molecular lines mapping of the entire giant molecular cloud G333, comprised sites of low- and high-mass star forming regions in various evolution stages of star formation. The result shows the spatial distribution of CS, HCO+, HCN and HNC are similar on large scales, while N2H+ seems to trace preferentially the very densest regions, possibly due to the chemical difference, that N2H+ is sensitive to temperature and readily destroyed by CO. Two analysis methods were used to characterise this large set of data cubes: GAUSSCLUMPS and principal component analysis (PCA). We found the clumps are heavily fragmented with a beam filling factor of 0.2. We found no correlation between clump radius and line width, contradicts to Larson's Law. Possible explanation is the clumps are fragmented and unresolved with the resolution of Mopra beam, thus the decomposed clump radius is blended and no physical properties can be interpreted. PCA of the velocity dimension found no significant differences among CS, HCO+, HNC and C2H line emissions, suggesting these four molecules are `well-mixed' on large scale, possibly by turbulence. PCA of the integrated emission maps separates molecules into low (13CO and C18O) and high (the rest) density tracers, identifies anti-correlation between HCO+ and N2H+ (due to the depletion of CO). The possibility of removing the scanning patterns of the `on-the-fly' mapping with PCA was also explored. The detection of broad thermal SiO from the massive dense cold core G333.125-0.562, along with other collected transitions, suggesting the core will host massive star formation and the SiO emission arises from shocks associated with an outflow in the cold core. Result of the modelling infall with 3D radiative transfer code using the derived physical parameters have successfully reproduce the line profiles. Recent observation of the

  13. Cosmology with intensity mapping techniques using atomic and molecular lines

    Science.gov (United States)

    Fonseca, José; Silva, Marta B.; Santos, Mário G.; Cooray, Asantha

    2017-01-01

    We present a systematic study of the intensity mapping (IM) technique using updated models for the different emission lines from galaxies. We identify which ones are more promising for cosmological studies of the post-reionization epoch. We consider the emission of Lyα, Hα, Hβ, optical and infrared oxygen lines, nitrogen lines, C II and the CO rotational lines. We show that Lyα, Hα, O II, C II and the lowest rotational CO lines are the best candidates to be used as IM probes. These lines form a complementary set of probes of the galaxies' emission spectra. We then use reasonable experimental setups from current, planned or proposed experiments to assess the detectability of the power spectrum of each emission line. IM of Lyα emission from z = 2 to 3 will be possible in the near future with Hobby-Eberly Telescope Dark Energy Experiment, while far-infrared lines require new dedicated experiments. We also show that the proposed SPHEREx satellite can use O II and Hα IM to study the large-scale distribution of matter in intermediate redshifts of 1-4. We find that submillimetre experiments with bolometers can have similar performances at intermediate redshifts using C II and CO(3-2).

  14. Molecular Lines of 13 Glactic Infrared Bubble Regions

    CERN Document Server

    Yan, Q Z; Zhang, B; Lu, D R; Chen, X; Tang, Z H

    2016-01-01

    We investigated the physical properties of molecular clouds and star formation processes around infrared bubbles which are essentially expanding HII regions. We performed observations of 13 galactic infrared bubble fields containing 18 bubbles. Five molecular lines, 12CO (J=1-0), 13CO (J=1-0), C18O(J=1-0), HCN (J=1-0), and HCO+ (J=1-0), were observed, and several publicly available surveys, GLIMPSE, MIPSGAL, ATLASGAL, BGPS, VGPS, MAGPIS, and NVSS, were used for comparison. We find that these bubbles are generally connected with molecular clouds, most of which are giant. Several bubble regions display velocity gradients and broad shifted profiles, which could be due to the expansion of bubbles. The masses of molecular clouds within bubbles range from 100 to 19,000 solar mass, and their dynamic ages are about 0.3-3.7 Myr, which takes into account the internal turbulence pressure of surrounding molecular clouds. Clumps are found in the vicinity of all 18 bubbles, and molecular clouds near four of these bubbles w...

  15. Genomic analyses identify molecular subtypes of pancreatic cancer.

    Science.gov (United States)

    Bailey, Peter; Chang, David K; Nones, Katia; Johns, Amber L; Patch, Ann-Marie; Gingras, Marie-Claude; Miller, David K; Christ, Angelika N; Bruxner, Tim J C; Quinn, Michael C; Nourse, Craig; Murtaugh, L Charles; Harliwong, Ivon; Idrisoglu, Senel; Manning, Suzanne; Nourbakhsh, Ehsan; Wani, Shivangi; Fink, Lynn; Holmes, Oliver; Chin, Venessa; Anderson, Matthew J; Kazakoff, Stephen; Leonard, Conrad; Newell, Felicity; Waddell, Nick; Wood, Scott; Xu, Qinying; Wilson, Peter J; Cloonan, Nicole; Kassahn, Karin S; Taylor, Darrin; Quek, Kelly; Robertson, Alan; Pantano, Lorena; Mincarelli, Laura; Sanchez, Luis N; Evers, Lisa; Wu, Jianmin; Pinese, Mark; Cowley, Mark J; Jones, Marc D; Colvin, Emily K; Nagrial, Adnan M; Humphrey, Emily S; Chantrill, Lorraine A; Mawson, Amanda; Humphris, Jeremy; Chou, Angela; Pajic, Marina; Scarlett, Christopher J; Pinho, Andreia V; Giry-Laterriere, Marc; Rooman, Ilse; Samra, Jaswinder S; Kench, James G; Lovell, Jessica A; Merrett, Neil D; Toon, Christopher W; Epari, Krishna; Nguyen, Nam Q; Barbour, Andrew; Zeps, Nikolajs; Moran-Jones, Kim; Jamieson, Nigel B; Graham, Janet S; Duthie, Fraser; Oien, Karin; Hair, Jane; Grützmann, Robert; Maitra, Anirban; Iacobuzio-Donahue, Christine A; Wolfgang, Christopher L; Morgan, Richard A; Lawlor, Rita T; Corbo, Vincenzo; Bassi, Claudio; Rusev, Borislav; Capelli, Paola; Salvia, Roberto; Tortora, Giampaolo; Mukhopadhyay, Debabrata; Petersen, Gloria M; Munzy, Donna M; Fisher, William E; Karim, Saadia A; Eshleman, James R; Hruban, Ralph H; Pilarsky, Christian; Morton, Jennifer P; Sansom, Owen J; Scarpa, Aldo; Musgrove, Elizabeth A; Bailey, Ulla-Maja Hagbo; Hofmann, Oliver; Sutherland, Robert L; Wheeler, David A; Gill, Anthony J; Gibbs, Richard A; Pearson, John V; Waddell, Nicola; Biankin, Andrew V; Grimmond, Sean M

    2016-03-01

    Integrated genomic analysis of 456 pancreatic ductal adenocarcinomas identified 32 recurrently mutated genes that aggregate into 10 pathways: KRAS, TGF-β, WNT, NOTCH, ROBO/SLIT signalling, G1/S transition, SWI-SNF, chromatin modification, DNA repair and RNA processing. Expression analysis defined 4 subtypes: (1) squamous; (2) pancreatic progenitor; (3) immunogenic; and (4) aberrantly differentiated endocrine exocrine (ADEX) that correlate with histopathological characteristics. Squamous tumours are enriched for TP53 and KDM6A mutations, upregulation of the TP63∆N transcriptional network, hypermethylation of pancreatic endodermal cell-fate determining genes and have a poor prognosis. Pancreatic progenitor tumours preferentially express genes involved in early pancreatic development (FOXA2/3, PDX1 and MNX1). ADEX tumours displayed upregulation of genes that regulate networks involved in KRAS activation, exocrine (NR5A2 and RBPJL), and endocrine differentiation (NEUROD1 and NKX2-2). Immunogenic tumours contained upregulated immune networks including pathways involved in acquired immune suppression. These data infer differences in the molecular evolution of pancreatic cancer subtypes and identify opportunities for therapeutic development.

  16. A 6-gene signature identifies four molecular subgroups of neuroblastoma

    Directory of Open Access Journals (Sweden)

    Kogner Per

    2011-04-01

    Full Text Available Abstract Background There are currently three postulated genomic subtypes of the childhood tumour neuroblastoma (NB; Type 1, Type 2A, and Type 2B. The most aggressive forms of NB are characterized by amplification of the oncogene MYCN (MNA and low expression of the favourable marker NTRK1. Recently, mutations or high expression of the familial predisposition gene Anaplastic Lymphoma Kinase (ALK was associated to unfavourable biology of sporadic NB. Also, various other genes have been linked to NB pathogenesis. Results The present study explores subgroup discrimination by gene expression profiling using three published microarray studies on NB (47 samples. Four distinct clusters were identified by Principal Components Analysis (PCA in two separate data sets, which could be verified by an unsupervised hierarchical clustering in a third independent data set (101 NB samples using a set of 74 discriminative genes. The expression signature of six NB-associated genes ALK, BIRC5, CCND1, MYCN, NTRK1, and PHOX2B, significantly discriminated the four clusters (p ALK, BIRC5, and PHOX2B, and was significantly associated with higher tumour stage, poor outcome and poor survival compared to the Type 1-corresponding favourable group (INSS stage 4 and/or dead of disease, p Conclusions Based on expression profiling we have identified four molecular subgroups of neuroblastoma, which can be distinguished by a 6-gene signature. The fourth subgroup has not been described elsewhere, and efforts are currently made to further investigate this group's specific characteristics.

  17. Modeling of the continuum and molecular line emission from the Sagittarius B2 molecular cloud

    Energy Technology Data Exchange (ETDEWEB)

    Lis, D.C.; Goldsmith, P.F. (Massachusetts Univ., Amherst (USA))

    1990-06-01

    The continuum and molecular line emission from the Sagittarius B2 molecular cloud are modeled in order to determine the conditions in the core and the envelope of the cloud. The continuum models suggest that the total luminosity of the middle source Sgr B2(M) is an order of magnitude higher than that of the northern source Sgr B2(N). The microturbulent models of the molecular line emission predict the correct spatial intensity distribution of the J = 1 - 0 transitions of C(O-18) and (C-13)O. They have difficulties, however, reproducing the observed intensities of the higher transitions of these molecules. This may indicate that the envelope has a clumpy structure. Sgr B2 differs significantly from typical disk giant molecular clouds in that it has higher mass and luminosity of the continuum sources, much greater H2 column density and mean volume density, and different fractional abundances of many interstellar molecules. 43 refs.

  18. A general catalogue of molecular hydrogen emission-line objects (MHOs) in outflows from young stars

    Science.gov (United States)

    Davis, C. J.; Gell, R.; Khanzadyan, T.; Smith, M. D.; Jenness, T.

    2010-02-01

    We present a catalogue of Molecular Hydrogen emission-line Objects (MHOs) in outflows from young stars, most of which are deeply embedded. All objects are identified in the near-infrared lines of molecular hydrogen, all reside in the Milky Way, and all are associated with jets or molecular outflows. Objects in both low and high-mass star forming regions are included. This catalogue complements the existing database of Herbig-Haro objects; indeed, for completeness, HH objects that are detected in H2 emission are included in the MHO catalogue. http://www.jach.hawaii.edu/UKIRT/MHCat/ Tables A.1 to A.15 are also available in electronic form at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsweb.u-strasbg.fr/cgi-bin/qcat?J/A+A/511/A24

  19. Multigene mutational profiling of cholangiocarcinomas identifies actionable molecular subgroups

    Science.gov (United States)

    Mafficini, Andrea; Wood, Laura D.; Corbo, Vincenzo; Melisi, Davide; Malleo, Giuseppe; Vicentini, Caterina; Malpeli, Giorgio; Antonello, Davide; Sperandio, Nicola; Capelli, Paola; Tomezzoli, Anna; Iacono, Calogero; Lawlor, Rita T.; Bassi, Claudio; Hruban, Ralph H.; Guglielmi, Alfredo; Tortora, Giampaolo; de Braud, Filippo; Scarpa, Aldo

    2014-01-01

    One-hundred-fifty-three biliary cancers, including 70 intrahepatic cholangiocarcinomas (ICC), 57 extrahepatic cholangiocarcinomas (ECC) and 26 gallbladder carcinomas (GBC) were assessed for mutations in 56 genes using multigene next-generation sequencing. Expression of EGFR and mTOR pathway genes was investigated by immunohistochemistry. At least one mutated gene was observed in 118/153 (77%) cancers. The genes most frequently involved were KRAS (28%), TP53 (18%), ARID1A (12%), IDH1/2 (9%), PBRM1 (9%), BAP1 (7%), and PIK3CA (7%). IDH1/2 (p=0.0005) and BAP1 (p=0.0097) mutations were characteristic of ICC, while KRAS (p=0.0019) and TP53 (p=0.0019) were more frequent in ECC and GBC. Multivariate analysis identified tumour stage and TP53 mutations as independent predictors of survival. Alterations in chromatin remodeling genes (ARID1A, BAP1, PBRM1, SMARCB1) were seen in 31% of cases. Potentially actionable mutations were seen in 104/153 (68%) cancers: i) KRAS/NRAS/BRAF mutations were found in 34% of cancers; ii) mTOR pathway activation was documented by immunohistochemistry in 51% of cases and by mutations in mTOR pathway genes in 19% of cancers; iii) TGF-ß/Smad signaling was altered in 10.5% cancers; iv) mutations in tyrosine kinase receptors were found in 9% cases. Our study identified molecular subgroups of cholangiocarcinomas that can be explored for specific drug targeting in clinical trials. PMID:24867389

  20. Identifying molecular targets of lifestyle modifications in colon cancer prevention

    Directory of Open Access Journals (Sweden)

    Molly Marie Derry

    2013-05-01

    Full Text Available One in four deaths in the United States is cancer-related, and colorectal cancer (CRC is the second leading cause of cancer-associated deaths. Screening strategies are utilized but have not reduced disease incidence or mortality. In this regard, there is an interest in cancer preventive strategies focusing on lifestyle intervention, where specific etiologic factors involved in cancer initiation, promotion, and progression could be targeted. For example, exposure to dietary carcinogens, such as nitrosamines and polycyclic aromatic hydrocarbons influences colon carcinogenesis. Furthermore, dietary deficiencies could alter sensitivity to genetic damage and influence carcinogen metabolism contributing to CRC. High alcohol consumption increases the risk of mutations including the fact that acetaldehyde, an ethanol metabolite, is classified as a group 1 carcinogen. Tobacco smoke exposure is also a risk factor for cancer development; ~20% of CRCs are associated with smoking. Additionally, obese patients have a higher risk of cancer development, which is further supported by the fact that physical activity decreases CRC risk by 55%. Similarly, chronic inflammatory conditions also increase the risk of CRC development. Moreover, the circadian clock alters digestion and regulates other biochemical, physiological and behavioral processes that could positively influence CRC. Taken together, colon carcinogenesis involves a number of etiological factors, and therefore, to create effective preventive strategies, molecular targets need to be identified and beleaguered prior to disease progression. With this in mind, the following is a comprehensive review identifying downstream target proteins of the above lifestyle risk factors, which are modulated during colon carcinogenesis and could be targeted for CRC prevention by novel agents including phytochemicals.

  1. Molecular Surveillance Identifies Multiple Transmissions of Typhoid in West Africa

    Science.gov (United States)

    Wong, Vanessa K.; Holt, Kathryn E.; Okoro, Chinyere; Baker, Stephen; Pickard, Derek J.; Marks, Florian; Page, Andrew J.; Olanipekun, Grace; Munir, Huda; Alter, Roxanne; Fey, Paul D.; Feasey, Nicholas A.; Weill, Francois-Xavier; Le Hello, Simon; Hart, Peter J.; Kariuki, Samuel; Breiman, Robert F.; Gordon, Melita A.; Heyderman, Robert S.; Jacobs, Jan; Lunguya, Octavie; Msefula, Chisomo; MacLennan, Calman A.; Keddy, Karen H.; Smith, Anthony M.; Onsare, Robert S.; De Pinna, Elizabeth; Nair, Satheesh; Amos, Ben; Dougan, Gordon; Obaro, Stephen

    2016-01-01

    Background The burden of typhoid in sub-Saharan African (SSA) countries has been difficult to estimate, in part, due to suboptimal laboratory diagnostics. However, surveillance blood cultures at two sites in Nigeria have identified typhoid associated with Salmonella enterica serovar Typhi (S. Typhi) as an important cause of bacteremia in children. Methods A total of 128 S. Typhi isolates from these studies in Nigeria were whole-genome sequenced, and the resulting data was used to place these Nigerian isolates into a worldwide context based on their phylogeny and carriage of molecular determinants of antibiotic resistance. Results Several distinct S. Typhi genotypes were identified in Nigeria that were related to other clusters of S. Typhi isolates from north, west and central regions of Africa. The rapidly expanding S. Typhi clade 4.3.1 (H58) previously associated with multiple antimicrobial resistances in Asia and in east, central and southern Africa, was not detected in this study. However, antimicrobial resistance was common amongst the Nigerian isolates and was associated with several plasmids, including the IncHI1 plasmid commonly associated with S. Typhi. Conclusions These data indicate that typhoid in Nigeria was established through multiple independent introductions into the country, with evidence of regional spread. MDR typhoid appears to be evolving independently of the haplotype H58 found in other typhoid endemic countries. This study highlights an urgent need for routine surveillance to monitor the epidemiology of typhoid and evolution of antimicrobial resistance within the bacterial population as a means to facilitate public health interventions to reduce the substantial morbidity and mortality of typhoid. PMID:27657909

  2. A 6-gene signature identifies four molecular subgroups of neuroblastoma

    LENUS (Irish Health Repository)

    Abel, Frida

    2011-04-14

    Abstract Background There are currently three postulated genomic subtypes of the childhood tumour neuroblastoma (NB); Type 1, Type 2A, and Type 2B. The most aggressive forms of NB are characterized by amplification of the oncogene MYCN (MNA) and low expression of the favourable marker NTRK1. Recently, mutations or high expression of the familial predisposition gene Anaplastic Lymphoma Kinase (ALK) was associated to unfavourable biology of sporadic NB. Also, various other genes have been linked to NB pathogenesis. Results The present study explores subgroup discrimination by gene expression profiling using three published microarray studies on NB (47 samples). Four distinct clusters were identified by Principal Components Analysis (PCA) in two separate data sets, which could be verified by an unsupervised hierarchical clustering in a third independent data set (101 NB samples) using a set of 74 discriminative genes. The expression signature of six NB-associated genes ALK, BIRC5, CCND1, MYCN, NTRK1, and PHOX2B, significantly discriminated the four clusters (p < 0.05, one-way ANOVA test). PCA clusters p1, p2, and p3 were found to correspond well to the postulated subtypes 1, 2A, and 2B, respectively. Remarkably, a fourth novel cluster was detected in all three independent data sets. This cluster comprised mainly 11q-deleted MNA-negative tumours with low expression of ALK, BIRC5, and PHOX2B, and was significantly associated with higher tumour stage, poor outcome and poor survival compared to the Type 1-corresponding favourable group (INSS stage 4 and\\/or dead of disease, p < 0.05, Fisher\\'s exact test). Conclusions Based on expression profiling we have identified four molecular subgroups of neuroblastoma, which can be distinguished by a 6-gene signature. The fourth subgroup has not been described elsewhere, and efforts are currently made to further investigate this group\\'s specific characteristics.

  3. A consensus line search algorithm for molecular potential energy functions.

    Science.gov (United States)

    Rurainski, Alexander; Hildebrandt, Andreas; Lenhof, Hans-Peter

    2009-07-15

    Force field based energy minimization of molecular structures is a central task in computational chemistry and biology. Solving this problem usually requires efficient local minimization techniques, i.e., iterative two-step methods that search first for a descent direction and then try to estimate the step width. The second step, the so called line search, typically uses polynomial interpolation schemes to estimate the next trial step. However, dependent on local properties of the objective function alternative schemes may be more appropriate especially if the objective function shows singularities or exponential behavior. As the choice of the best interpolation scheme cannot be made a priori, we propose a new consensus line search approach that performs several different interpolation schemes at each step and then decides which one is the most reliable at the current position. Although a naive consensus approach would lead to severe performance impacts, our method does not require additional evaluations of the energy function, imposing only negligible computational overhead. Additionally, our method can be easily adapted to the local behavior of other objective functions by incorporating suitable interpolation schemes or omitting non-fitting schemes. The performance of our consensus line search approach has been evaluated and compared to established standard line search algorithms by minimizing the structures of a large set of molecules using different force fields. The proposed algorithm shows better performance in almost all test cases, i.e., it reduces the number of iterations and function and gradient evaluations, leading to significantly reduced run times.

  4. Molecularly imprinted polymers for on-line extraction techniques.

    Science.gov (United States)

    Moein, Mohammad M; Abdel-Rehim, Mohamed

    2015-01-01

    Recent years have seen an increasing interest in the use of molecularly imprinted polymers (MIPs) as a sorbent for different extraction methods and this is due to its high selectivity. The MIP is designed to show specificity for the analyte of interest. Moreover, MIPs show physical robustness, resistance to high temperatures and pressures, and stability in the presence of acids, bases and a wide range of organic solvents. In the present article, various novel sample preparation techniques which MIPs applied as sorbent and on-line connected with analytical instruments were highlighted and discussed. The future aspects of MIPs as well were described.

  5. Survey of Outer Galaxy Molecular Lines Associated with Water Masers

    Science.gov (United States)

    Mochizuki, N.; Hachisuka, K.; Umemoto, T.

    2009-08-01

    H_2O masers in Young stellar objects (YSOs) in our Galaxy are one of the targets of the VSOP-2 science. The advantage of VSOP-2 observation is the highest angular resolution which can detect a proper motion of H_2O masers for distant objects over short time intervals. To find candidate sources, we observed H2O maser sources in the outer Galaxy using the VLA, and we surveyed the molecular lines toward these sources to understand the environment of YSOs. Higher H2 column densities of YSOs were found for objects with active H2O masers.

  6. Extracellular matrix proteomics identifies molecular signature of symptomatic carotid plaques

    Science.gov (United States)

    Langley, Sarah R.; Willeit, Karin; Didangelos, Athanasios; Matic, Ljubica Perisic; Skroblin, Philipp; Barallobre-Barreiro, Javier; Lengquist, Mariette; Rungger, Gregor; Kapustin, Alexander; Kedenko, Ludmilla; Molenaar, Chris; Lu, Ruifang; Barwari, Temo; Suna, Gonca; Iglseder, Bernhard; Paulweber, Bernhard; Willeit, Peter; Pasterkamp, Gerard; Davies, Alun H.; Monaco, Claudia; Hedin, Ulf; Shanahan, Catherine M.; Willeit, Johann; Kiechl, Stefan

    2017-01-01

    BACKGROUND. The identification of patients with high-risk atherosclerotic plaques prior to the manifestation of clinical events remains challenging. Recent findings question histology- and imaging-based definitions of the “vulnerable plaque,” necessitating an improved approach for predicting onset of symptoms. METHODS. We performed a proteomics comparison of the vascular extracellular matrix and associated molecules in human carotid endarterectomy specimens from 6 symptomatic versus 6 asymptomatic patients to identify a protein signature for high-risk atherosclerotic plaques. Proteomics data were integrated with gene expression profiling of 121 carotid endarterectomies and an analysis of protein secretion by lipid-loaded human vascular smooth muscle cells. Finally, epidemiological validation of candidate biomarkers was performed in two community-based studies. RESULTS. Proteomics and at least one of the other two approaches identified a molecular signature of plaques from symptomatic patients that comprised matrix metalloproteinase 9, chitinase 3-like-1, S100 calcium binding protein A8 (S100A8), S100A9, cathepsin B, fibronectin, and galectin-3-binding protein. Biomarker candidates measured in 685 subjects in the Bruneck study were associated with progression to advanced atherosclerosis and incidence of cardiovascular disease over a 10-year follow-up period. A 4-biomarker signature (matrix metalloproteinase 9, S100A8/S100A9, cathepsin D, and galectin-3-binding protein) improved risk prediction and was successfully replicated in an independent cohort, the SAPHIR study. CONCLUSION. The identified 4-biomarker signature may improve risk prediction and diagnostics for the management of cardiovascular disease. Further, our study highlights the strength of tissue-based proteomics for biomarker discovery. FUNDING. UK: British Heart Foundation (BHF); King’s BHF Center; and the National Institute for Health Research Biomedical Research Center based at Guy’s and St

  7. Molecular Outflows Identified in the FCRAO CO Survey of the Taurus Molecular Cloud

    CERN Document Server

    Narayanan, Gopal; Bemis, Ashley

    2012-01-01

    The 100 square degree FCRAO CO survey of the Taurus molecular cloud provides an excellent opportunity to undertake an unbiased survey of a large, nearby, molecular cloud complex for molecular outflow activity. Our study provides information on the extent, energetics and frequency of outflows in this region, which are then used to assess the impact of outflows on the parent molecular cloud. The search identified 20 outflows in the Taurus region, 8 of which were previously unknown. Both $^{12}$CO and $^{13}$CO data cubes from the Taurus molecular map were used, and dynamical properties of the outflows are derived. Even for previously known outflows, our large-scale maps indicate that many of the outflows are much larger than previously suspected, with eight of the flows (40%) being more than a parsec long. The mass, momentum and kinetic energy from the 20 outflows are compared to the repository of turbulent energy in Taurus. Comparing the energy deposition rate from outflows to the dissipation rate of turbulenc...

  8. Modelling Alkali Line Absorption and Molecular Bands in Cool DAZs

    CERN Document Server

    Homeier, D; Allard, F; Hauschildt, P H; Schweitzer, A; Stancil, P C; Weck, P F; Homeier, Derek; Allard, Nicole F.; Allard, France; Hauschildt, Peter H.; Schweitzer, Andreas; Stancil, Phillip C.; Weck, Philippe F.

    2005-01-01

    Two peculiar stars showing an apparent extremely broadened and strong NaI D absorption have been discovered in surveys for cool white dwarfs by Oppenheimer et al. (2001) and Harris et al. (SDSS, 2003). We discuss the nature of these objects using PHOENIX atmosphere models for metal-poor brown dwarfs/very low mass stars, and new white dwarf LTE and NLTE models for hydrogen- and helium-dominated atmospheres with metals. These include complete molecular formation in chemical equilibrium and a model for the alkali resonance line broadening based on the damping profiles of Allard et al. (2003), as well as new molecular line opacities for metal hydrides. First results of our calculations indicate good agreement with a hydrogen-dominated WD atmosphere with a Na abundance roughly consistent with a state of high accretion. We analyse deviations of the abundances of Na, K, Mg and Ca from the cosmic pattern and comment on implications of these results for standard accretion scenarios.

  9. Molecular and phenotypic characterisation of paediatric glioma cell lines as models for preclinical drug development

    DEFF Research Database (Denmark)

    Bax, Dorine A; Little, Suzanne E; Gaspar, Nathalie;

    2009-01-01

    in comparison to routinely used adult lines. PRINCIPAL FINDINGS: All lines proliferate as adherent monolayers and express glial markers. Copy number profiling revealed complex genomes including amplification and deletions of genes known to be pivotal in core glioblastoma signalling pathways. Expression...... profiling identified 93 differentially expressed genes which were able to distinguish between the adult and paediatric high grade cell lines, including a number of kinases and co-ordinated sets of genes associated with DNA integrity and the immune response. SIGNIFICANCE: These data demonstrate that glioma...... cell lines derived from paediatric patients show key molecular differences to those from adults, some of which are well known, whilst others may provide novel targets for evaluation in primary tumours. We thus provide the rationale and demonstrate the practicability of using paediatric glioma cell...

  10. An EXES High-Resolution Molecular Line Survey towards Orion IRc2

    Science.gov (United States)

    Rangwala, Naseem

    High spectral resolution molecular line surveys provide a chemical inventory for star forming regions and are essential for studying their chemistry, kinematics and physical conditions. Previous surveys have been limited to radio, sub-mm and FIR wavelengths. In the mid-infrared (MIR), there has not been any line survey with high spectral resolution. MIR missions such as ISO and Spitzer had low to moderate resolving power that were only able to link broad features with particular molecular bands and could not resolve the individual rovibrational transitions needed to identify specific molecules with certainty. The EXES instrument is currently the only available (airborne or spaceborne) spectrograph that provides high spectral resolution in the MIR region. We propose to use EXES to conduct an unbiased molecular line survey towards Orion IRc2 from 6 - 28.5 microns with a S/N of better than 70 over 90% of the proposed bandpass. The survey (due to its higher resolving power; R = 50,000) will do 5 - 50 times better than ISO in detecting isolated, narrow lines. This will allow us to (a) resolve the rovibrational structure of the gas phase molecules in order to identify them, (b) resolve their kinematics, (c) detect new gas phase molecules that were missed by ISO, and (d) provide useful constraints on Orion's hot core chemistry as sampled by IRc2. The proposed observations will provide the best infrared measurements (to date) of molecular column densities and physical conditions - providing strong constraints on the current chemical network models for star forming regions. This survey will greatly enhance the inventory of resolved line features in the MIR, making it an invaluable reference to be used by the JWST and ALMA scientific communities. By waiving the proprietary period, this program will allow astronomers to exploit these data as soon as they become available.

  11. Millimeter-wave molecular line observations of the Tornado nebula

    Energy Technology Data Exchange (ETDEWEB)

    Sakai, D. [Department of Astronomy, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Oka, T.; Tanaka, K.; Matsumura, S.; Miura, K.; Takekawa, S., E-mail: sakai.daisuke@nao.ac.jp [Department of Physics, Institute of Science and Technology, Keio University, 3-14-1 Hiyoshi, Yokohama, Kanagawa 223-8522 (Japan)

    2014-08-10

    We report the results of millimeter-wave molecular line observations of the Tornado Nebula (G357.7-0.1), which is a bright radio source behind the Galactic center region. A 15' × 15' area was mapped in the J = 1-0 lines of CO, {sup 13}CO, and HCO{sup +} with the Nobeyama Radio Observatory 45 m telescope. The Very Large Array archival data of OH at 1720 MHz were also reanalyzed. We found two molecular clouds with separate velocities, V{sub LSR} = –14 km s{sup –1} and +5 km s{sup –1}. These clouds show rough spatial anti-correlation. Both clouds are associated with OH 1720 MHz emissions in the area overlapping with the Tornado Nebula. The spatial and velocity coincidence indicates violent interaction between the clouds and the Tornado Nebula. Modestly excited gas prefers the position of the Tornado 'head' in the –14 km s{sup –1} cloud, also suggesting the interaction. Virial analysis shows that the +5 km s{sup –1} cloud is more tightly bound by self-gravity than the –14 km s{sup –1} cloud. We propose a formation scenario for the Tornado Nebula; the +5 km s{sup –1} cloud collided into the –14 km s{sup –1} cloud, generating a high-density layer behind the shock front, which activates a putative compact object by Bondi-Hoyle-Lyttleton accretion to eject a pair of bipolar jets.

  12. Molecular predictors of 3D morphogenesis by breast cancer cell lines in 3D culture.

    Directory of Open Access Journals (Sweden)

    Ju Han

    2010-02-01

    Full Text Available Correlative analysis of molecular markers with phenotypic signatures is the simplest model for hypothesis generation. In this paper, a panel of 24 breast cell lines was grown in 3D culture, their morphology was imaged through phase contrast microscopy, and computational methods were developed to segment and represent each colony at multiple dimensions. Subsequently, subpopulations from these morphological responses were identified through consensus clustering to reveal three clusters of round, grape-like, and stellate phenotypes. In some cases, cell lines with particular pathobiological phenotypes clustered together (e.g., ERBB2 amplified cell lines sharing the same morphometric properties as the grape-like phenotype. Next, associations with molecular features were realized through (i differential analysis within each morphological cluster, and (ii regression analysis across the entire panel of cell lines. In both cases, the dominant genes that are predictive of the morphological signatures were identified. Specifically, PPARgamma has been associated with the invasive stellate morphological phenotype, which corresponds to triple-negative pathobiology. PPARgamma has been validated through two supporting biological assays.

  13. Molecular Predictors of 3D Morphogenesis by Breast Cancer Cell Lines in 3D Culture

    Energy Technology Data Exchange (ETDEWEB)

    Han, Ju; Chang, Hang; Giricz, Orsi; Lee, Genee; Baehner, Frederick; Gray, Joe; Bissell, Mina; Kenny, Paraic; Parvin, Bahram

    2010-02-01

    Correlative analysis of molecular markers with phenotypic signatures is the simplest model for hypothesis generation. In this paper, a panel of 24 breast cell lines was grown in 3D culture, their morphology was imaged through phase contrast microscopy, and computational methods were developed to segment and represent each colony at multiple dimensions. Subsequently, subpopulations from these morphological responses were identified through consensus clustering to reveal three clusters of round, grape-like, and stellate phenotypes. In some cases, cell lines with particular pathobiological phenotypes clustered together (e.g., ERBB2 amplified cell lines sharing the same morphometric properties as the grape-like phenotype). Next, associations with molecular features were realized through (i) differential analysis within each morphological cluster, and (ii) regression analysis across the entire panel of cell lines. In both cases, the dominant genes that are predictive of the morphological signatures were identified. Specifically, PPAR? has been associated with the invasive stellate morphological phenotype, which corresponds to triple-negative pathobiology. PPAR? has been validated through two supporting biological assays.

  14. Molecular cytogenetic characterization of a human thyroid cancercell line

    Energy Technology Data Exchange (ETDEWEB)

    Weier, Heinz-Ulrich G.; Tuton, Tiffany B.; Ito, Yuko; Chu, LisaW.; Lu, Chung-Mei; Baumgartner, Adolf; Zitzelsberger, Horst F.; Weier,Jingly F.

    2006-01-04

    The incidence of papillary thyroid carcinoma (PTC) increases significantly after exposure of the head and neck region to ionizing radiation, yet we know neither the steps involved in malignant transformation of thyroid epithelium nor the specific carcinogenic mode of action of radiation. Such increased tumor frequency became most evident in children after the 1986 nuclear accident in Chernobyl, Ukraine. In the twelve years following the accident, the average incidence of childhood PTCs (chPTC) increased over one hundred-fold compared to the rate of about 1 tumor incidence per 10{sup 6} children per year prior to 1986. To study the etiology of radiation-induced thyroid cancer, we formed an international consortium to investigate chromosomal changes and altered gene expression in cases of post-Chernobyl chPTC. Our approach is based on karyotyping of primary cultures established from chPTC specimens, establishment of cell lines and studies of genotype-phenotype relationships through high resolution chromosome analysis, DNA/cDNA micro-array studies, and mouse xenografts that test for tumorigenicity. Here, we report the application of fluorescence in situ hybridization (FISH)-based techniques for the molecular cytogenetic characterization of a highly tumorigenic chPTC cell line, S48TK, and its subclones. Using chromosome 9 rearrangements as an example, we describe a new approach termed ''BAC-FISH'' to rapidly delineate chromosomal breakpoints, an important step towards a better understanding of the formation of translocations and their functional consequences.

  15. High-resolution molecular line observations of active galaxies

    CERN Document Server

    García-Burillo, S; Usero, A; Gracia-Carpio, J

    2008-01-01

    The study of the content, distribution and kinematics of interstellar gas is a key to understand the origin and maintenance of both starburst and nuclear (AGN) activity in galaxies. The processes involved in AGN fueling encompass a wide range of scales, both spatial and temporal, which have to be studied. Probing the gas flow from the outer disk down to the central engine of an AGN host, requires the use of specific tracers of the interstellar medium adapted to follow the change of phase of the gas as a function of radius. Current mm-interferometers can provide a sharp view of the distribution and kinematics of molecular gas in the circumnuclear disks of galaxies through extensive CO line mapping. As such, CO maps are an essential tool to study AGN feeding mechanisms in the local universe. This is the scientific driver of the NUclei of GAlaxies (NUGA) survey, whose latest results are here reviewed. On the other hand, the use of specific molecular tracers of the dense gas phase can probe the feedback influence...

  16. Molecular outflows identified in the FCRAO CO survey of the Taurus Molecular Cloud

    Science.gov (United States)

    Narayanan, Gopal; Snell, Ronald; Bemis, Ashley

    2012-10-01

    Jets and outflows are an integral part of the star formation process. While there are many detailed studies of molecular outflows towards individual star-forming sites, few studies have surveyed an entire star-forming molecular cloud for this phenomenon. The 100-deg2 Five College Radio Astronomy Observatory CO survey of the Taurus Molecular Cloud provides an excellent opportunity to undertake an unbiased survey of a large, nearby, molecular cloud complex for molecular outflow activity. Our study provides information on the extent, energetics and frequency of outflows in this region, which are then used to assess the impact of outflows on the parent molecular cloud. The search identified 20 outflows in the Taurus region, eight of which were previously unknown. Both 12CO and 13CO data cubes from the Taurus molecular map were used, and dynamical properties of the outflows are derived. Even for previously known outflows, our large-scale maps indicate that many of the outflows are much larger than previously suspected, with eight of the outflows (40 per cent) being more than a parsec long. The mass, momentum and kinetic energy from the 20 outflows are compared to the repository of turbulent energy in Taurus. Comparing the energy deposition rate from outflows to the dissipation rate of turbulence, we conclude that outflows by themselves cannot sustain the observed turbulence seen in the entire cloud. However, when the impact of outflows is studied in selected regions of Taurus, it is seen that locally outflows can provide a significant source of turbulence and feedback. The L1551 dark cloud which is just south of the main Taurus complex was not covered by this survey, but the outflows in L1551 have much higher energies compared to the outflows in the main Taurus cloud. In the L1551 cloud, outflows can not only account for the turbulent energy present, but are probably also disrupting their parent cloud. We conclude that for a molecular cloud like Taurus, an L1551-like

  17. Molecular line study of evolution in protostellar cloud cores

    CERN Document Server

    Kontinen, S; Heikkilä, A; Haikala, L K

    2000-01-01

    Two dense dark cloud cores representing different stages of dynamical evolution were observed in a number of molecular spectral lines. One of the cores, Cha- MMS1 in the Chamaeleon cloud I contains a Class 0 protostar, whereas the other, CrA C in the R Coronae Australis cloud, is pre-stellar. We find that the cores have very different chemical compositions. Cha-MMS1 exhibits characteristics of so-called `early-type' chemistry with high abundan- ces of carbon-chain molecules such as HC3N, but it also has a large N2H+ abundance, which is expected only to build up at later stages. In contrast, none of the carbon-chain molecules were detected in CrA C. CrA C has a higher SO abundance than Cha-MMS1, which implies that it is chemically `older' than Cha- MMS1. The most striking difference between the two cores is seen in the HC3N/SO abundance ratio, which is at least three orders of magnitude higher in Cha-MMS than in CrA C. This result is surprising since starless cores are usually thought to be chemically younger ...

  18. Cancer in silico drug discovery: a systems biology tool for identifying candidate drugs to target specific molecular tumor subtypes.

    Science.gov (United States)

    San Lucas, F Anthony; Fowler, Jerry; Chang, Kyle; Kopetz, Scott; Vilar, Eduardo; Scheet, Paul

    2014-12-01

    Large-scale cancer datasets such as The Cancer Genome Atlas (TCGA) allow researchers to profile tumors based on a wide range of clinical and molecular characteristics. Subsequently, TCGA-derived gene expression profiles can be analyzed with the Connectivity Map (CMap) to find candidate drugs to target tumors with specific clinical phenotypes or molecular characteristics. This represents a powerful computational approach for candidate drug identification, but due to the complexity of TCGA and technology differences between CMap and TCGA experiments, such analyses are challenging to conduct and reproduce. We present Cancer in silico Drug Discovery (CiDD; scheet.org/software), a computational drug discovery platform that addresses these challenges. CiDD integrates data from TCGA, CMap, and Cancer Cell Line Encyclopedia (CCLE) to perform computational drug discovery experiments, generating hypotheses for the following three general problems: (i) determining whether specific clinical phenotypes or molecular characteristics are associated with unique gene expression signatures; (ii) finding candidate drugs to repress these expression signatures; and (iii) identifying cell lines that resemble the tumors being studied for subsequent in vitro experiments. The primary input to CiDD is a clinical or molecular characteristic. The output is a biologically annotated list of candidate drugs and a list of cell lines for in vitro experimentation. We applied CiDD to identify candidate drugs to treat colorectal cancers harboring mutations in BRAF. CiDD identified EGFR and proteasome inhibitors, while proposing five cell lines for in vitro testing. CiDD facilitates phenotype-driven, systematic drug discovery based on clinical and molecular data from TCGA.

  19. Understanding star formation in molecular clouds. III. Probability distribution functions of molecular lines in Cygnus X

    Science.gov (United States)

    Schneider, N.; Bontemps, S.; Motte, F.; Ossenkopf, V.; Klessen, R. S.; Simon, R.; Fechtenbaum, S.; Herpin, F.; Tremblin, P.; Csengeri, T.; Myers, P. C.; Hill, T.; Cunningham, M.; Federrath, C.

    2016-03-01

    The probability distribution function of column density (N-PDF) serves as a powerful tool to characterise the various physical processes that influence the structure of molecular clouds. Studies that use extinction maps or H2 column-density maps (N) that are derived from dust show that star-forming clouds can best be characterised by lognormal PDFs for the lower N range and a power-law tail for higher N, which is commonly attributed to turbulence and self-gravity and/or pressure, respectively. While PDFs from dust cover a large dynamic range (typically N ~ 1020-24 cm-2 or Av~ 0.1-1000), PDFs obtained from molecular lines - converted into H2 column density - potentially trace more selectively different regimes of (column) densities and temperatures. They also enable us to distinguish different clouds along the line of sight through using the velocity information. We report here on PDFs that were obtained from observations of 12CO, 13CO, C18O, CS, and N2H+ in the Cygnus X North region, and make a comparison to a PDF that was derived from dust observations with the Herschel satellite. The PDF of 12CO is lognormal for Av ~ 1-30, but is cut for higher Av because of optical depth effects. The PDFs of C18O and 13CO are mostly lognormal up to Av ~ 1-15, followed by excess up to Av ~ 40. Above that value, all CO PDFs drop, which is most likely due to depletion. The high density tracers CS and N2H+ exhibit only a power law distribution between Av ~ 15 and 400, respectively. The PDF from dust is lognormal for Av ~ 3-15 and has a power-law tail up to Av ~ 500. Absolute values for the molecular line column densities are, however, rather uncertain because of abundance and excitation temperature variations. If we take the dust PDF at face value, we "calibrate" the molecular line PDF of CS to that of the dust and determine an abundance [CS]/[H2] of 10-9. The slopes of the power-law tails of the CS, N2H+, and dust PDFs are -1.6, -1.4, and -2.3, respectively, and are thus consistent

  20. How to identify dislocations in molecular dynamics simulations?

    Science.gov (United States)

    Li, Duo; Wang, FengChao; Yang, ZhenYu; Zhao, YaPu

    2014-12-01

    Dislocations are of great importance in revealing the underlying mechanisms of deformed solid crystals. With the development of computational facilities and technologies, the observations of dislocations at atomic level through numerical simulations are permitted. Molecular dynamics (MD) simulation suggests itself as a powerful tool for understanding and visualizing the creation of dislocations as well as the evolution of crystal defects. However, the numerical results from the large-scale MD simulations are not very illuminating by themselves and there exist various techniques for analyzing dislocations and the deformed crystal structures. Thus, it is a big challenge for the beginners in this community to choose a proper method to start their investigations. In this review, we summarized and discussed up to twelve existing structure characterization methods in MD simulations of deformed crystal solids. A comprehensive comparison was made between the advantages and disadvantages of these typical techniques. We also examined some of the recent advances in the dynamics of dislocations related to the hydraulic fracturing. It was found that the dislocation emission has a significant effect on the propagation and bifurcation of the crack tip in the hydraulic fracturing.

  1. Phenotypic and Molecular Characterization of MCF10DCIS and SUM Breast Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Nandita Barnabas

    2013-01-01

    Full Text Available We reviewed the phenotypic and molecular characteristics of MCF10DCIS.com and the SUM cell lines based on numerous studies performed over the years. The major signaling pathways that give rise to the phenotype of these cells may serve as a good resource of information when researchers in drug discovery and development use these cells to identify novel targets and biomarkers. Major signaling pathways and mutations affecting the coding sequence are also described providing important information when using these cells as a model in a variety of studies.

  2. Molecular Line Parameters & VAMDC: An Atmospheric/Laboratory Physicist Point of View

    Science.gov (United States)

    Janssen, Christof

    2017-09-01

    "Molecular line parameters are used to interpret observational spectra and are an integral part in the data evaluation chain. Given from the perspective of a laboratory physicist, this talk provides an overview on molecular line parameters, how they are obtained and how they are made available to the user. Taking NH3 and O3 as two example molecules, the problem of measuring and modelling line parameters using current technologies from the UV to the mid-infrared are described and associated uncertainties are discussed. We also cover availability and access of molecular line data through the database infrastructure VAMDC (http://portal.vamdc.org/)."

  3. Molecular profiling of breast cancer cell lines defines relevant tumor models and provides a resource for cancer gene discovery.

    Directory of Open Access Journals (Sweden)

    Jessica Kao

    Full Text Available BACKGROUND: Breast cancer cell lines have been used widely to investigate breast cancer pathobiology and new therapies. Breast cancer is a molecularly heterogeneous disease, and it is important to understand how well and which cell lines best model that diversity. In particular, microarray studies have identified molecular subtypes-luminal A, luminal B, ERBB2-associated, basal-like and normal-like-with characteristic gene-expression patterns and underlying DNA copy number alterations (CNAs. Here, we studied a collection of breast cancer cell lines to catalog molecular profiles and to assess their relation to breast cancer subtypes. METHODS: Whole-genome DNA microarrays were used to profile gene expression and CNAs in a collection of 52 widely-used breast cancer cell lines, and comparisons were made to existing profiles of primary breast tumors. Hierarchical clustering was used to identify gene-expression subtypes, and Gene Set Enrichment Analysis (GSEA to discover biological features of those subtypes. Genomic and transcriptional profiles were integrated to discover within high-amplitude CNAs candidate cancer genes with coordinately altered gene copy number and expression. FINDINGS: Transcriptional profiling of breast cancer cell lines identified one luminal and two basal-like (A and B subtypes. Luminal lines displayed an estrogen receptor (ER signature and resembled luminal-A/B tumors, basal-A lines were associated with ETS-pathway and BRCA1 signatures and resembled basal-like tumors, and basal-B lines displayed mesenchymal and stem/progenitor-cell characteristics. Compared to tumors, cell lines exhibited similar patterns of CNA, but an overall higher complexity of CNA (genetically simple luminal-A tumors were not represented, and only partial conservation of subtype-specific CNAs. We identified 80 high-level DNA amplifications and 13 multi-copy deletions, and the resident genes with concomitantly altered gene-expression, highlighting known and

  4. Molecular line tracers of high-mass star forming regions

    NARCIS (Netherlands)

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

    2013-01-01

    High-mass stars influence their environment in different ways including feedback via their FUV radiation. The penetration of FUV photons into molecular clouds creates Photon Dominated Regions (PDRs) with different chemical layers where the mainly ionized medium changes into mainly molecular. Differe

  5. A CARMA Spectral Line and Continuum Survey of the Central Molecular Zone

    Science.gov (United States)

    Pound, Marc W.; Yusef-Zadeh, F.

    2014-01-01

    Because of its large angular extent, the Central Molecular Zone has to date only been mapped at millimeter wavelengths with singledish telescopes, with resolution about 1.2 pc (30"). We have completed a 3 mm continuum and spectral line interferometric maps made with CARMA of a 90 pc X 50 pc region of the CMZ (0.6 < l < -0.2; 0.15 < b < -0.2), with resolution of ~0.3 pc We present here the first results of this survey. One of the advantages of observing the Galactic Center at 3mm with CARMA iis that it allows identification of different classes of objects in this confusing region of the Galaxy. This is the first 3mm continuum survey showing a high concentration of HII complexes, and thermal and nonthermal sources distributed throughout the region. Our continuum survey identifies a number of infrared dark clouds, the most prominent of which is G0.253+0.016, part of a chain of clouds forming a ridge of molecular gas between G0.253+0.016 and Sgr B2. We also see emission from the magnetized filaments in the l = 0.2 Radio Arc. We combined our spectral line maps of SiO(2-1), HCO+(1-0), HCN(1-0), N2H+(1-0) with the MOPRA singledish survey so the final maps include all spatial frequencies down to 3". The combined CARMA plus MOPRA maps show a rich structure of both compact and filamentary clouds. We examine the relationship between the distribution of molecular line emission, the 6.4 keV Fe K-alpha emission, and the nonthermal radio emission and discuss preliminary results of the analysis.

  6. Measured-predicted molecular spectra at band-line resolution

    Science.gov (United States)

    Freeman, G. N.; Akagi, T.; Barton, P. B. C.

    2016-10-01

    Early ERIM measurements of hot-through-cold gas (CO2, H2O, N2) emission-absorption spectra are replicated by modern line-band computations that incorporate independent fundamental line strength-frequency information. Close agreement is achieved for all cases by empirical adjustment of the line broadening function. Line spectra for CO2 and H2O computed at 0.001 cm-1 resolution were integrated to 3.2 and 14 cm-1 using a triangular slit function consistent with ERIM measurements for the 4.3 and 2.7 μm spectral regions. Band spectra computed at 0.1 cm-1 resolution give close agreement with spectra generated at higher resolution. The findings demonstrate a merged line-band model for nonuniform path radiance and transmittance based on the line-sum spectral cross section for each piecewise-uniform path segment. The band-and-line transmittance become equivalent at high spectral resolution.

  7. Molecular Line Emission Towards High-Mass Clumps: The MALT90 Catalogue

    Science.gov (United States)

    Rathborne, J. M.; Whitaker, J. S.; Jackson, J. M.; Foster, J. B.; Contreras, Y.; Stephens, I. W.; Guzmán, A. E.; Longmore, S. N.; Sanhueza, P.; Schuller, F.; Wyrowski, F.; Urquhart, J. S.

    2016-07-01

    The Millimetre Astronomy Legacy Team 90 GHz survey aims to characterise the physical and chemical evolution of high-mass clumps. Recently completed, it mapped 90 GHz line emission towards 3 246 high-mass clumps identified from the ATLASGAL 870 μm Galactic plane survey. By utilising the broad frequency coverage of the Mopra telescope's spectrometer, maps in 16 different emission lines were simultaneously obtained. Here, we describe the first catalogue of the detected line emission, generated by Gaussian profile fitting to spectra extracted towards each clumps' 870 μm dust continuum peak. Synthetic spectra show that the catalogue has a completeness of > 95%, a probability of a false-positive detection of < 0.3%, and a relative uncertainty in the measured quantities of < 20% over the range of detection criteria. The detection rates are highest for the (1-0) transitions of HCO+, HNC, N2H+, and HCN (~77-89%). Almost all clumps (~95%) are detected in at least one of the molecular transitions, just over half of the clumps (~53%) are detected in four or more of the transitions, while only one clump is detected in 13 transitions. We find several striking trends in the ensemble of properties for the different molecular transitions when plotted as a function of the clumps' evolutionary state as estimated from Spitzer mid-IR images, including (1) HNC is relatively brighter in colder, less evolved clumps than those that show active star formation, (2) N2H+ is relatively brighter in the earlier stages, (3) that the observed optical depth decreases as the clumps evolve, and (4) the optically thickest HCO+ emission shows a `blue-red asymmetry' indicating overall collapse that monotonically decreases as the clumps evolve. This catalogue represents the largest compiled database of line emission towards high-mass clumps and is a valuable data set for detailed studies of these objects.

  8. Definitive molecular cytogenetic characterization of 15 colorectal cancer cell lines.

    Science.gov (United States)

    Knutsen, Turid; Padilla-Nash, Hesed M; Wangsa, Danny; Barenboim-Stapleton, Linda; Camps, Jordi; McNeil, Nicole; Difilippantonio, Michael J; Ried, Thomas

    2010-03-01

    In defining the genetic profiles in cancer, cytogenetically aberrant cell lines derived from primary tumors are important tools for the study of carcinogenesis. Here, we present the results of a comprehensive investigation of 15 established colorectal cancer cell lines using spectral karyotyping (SKY), fluorescence in situ hybridization, and comparative genomic hybridization (CGH). Detailed karyotypic analysis by SKY on five of the lines (P53HCT116, T84, NCI-H508, NCI-H716, and SK-CO-1) is described here for the first time. The five lines with karyotypes in the diploid range and that are characterized by defects in DNA mismatch repair had a mean of 4.8 chromosomal abnormalities per line, whereas the 10 aneuploid lines exhibited complex karyotypes and a mean of 30 chromosomal abnormalities. Of the 150 clonal translocations, only eight were balanced and none were recurrent among the lines. We also reviewed the karyotypes of 345 cases of adenocarcinoma of the large intestine listed in the Mitelman Database of Chromosome Aberrations in Cancer. The types of abnormalities observed in the cell lines reflected those seen in primary tumors: there were no recurrent translocations in either tumors or cell lines; isochromosomes were the most common recurrent abnormalities; and breakpoints occurred most frequently at the centromeric/pericentromeric and telomere regions. Of the genomic imbalances detected by array CGH, 87% correlated with chromosome aberrations observed in the SKY studies. The fact that chromosome abnormalities predominantly result in copy number changes rather than specific chromosome or gene fusions suggests that this may be the major mechanism leading to carcinogenesis in colorectal cancer.

  9. Multiple breast cancer cell-lines derived from a single tumor differ in their molecular characteristics and tumorigenic potential.

    Directory of Open Access Journals (Sweden)

    Goar Mosoyan

    Full Text Available BACKGROUND: Breast cancer cell lines are widely used tools to investigate breast cancer biology and to develop new therapies. Breast cancer tissue contains molecularly heterogeneous cell populations. Thus, it is important to understand which cell lines best represent the primary tumor and have similarly diverse phenotype. Here, we describe the development of five breast cancer cell lines from a single patient's breast cancer tissue. We characterize the molecular profiles, tumorigenicity and metastatic ability in vivo of all five cell lines and compare their responsiveness to 4-hydroxytamoxifen (4-OHT treatment. METHODS: Five breast cancer cell lines were derived from a single patient's primary breast cancer tissue. Expression of different antigens including HER2, estrogen receptor (ER, CK8/18, CD44 and CD24 was determined by flow cytometry, western blotting and immunohistochemistry (IHC. In addition, a Fluorescent In Situ Hybridization (FISH assay for HER2 gene amplification and p53 genotyping was performed on all cell lines. A xenograft model in nude mice was utilized to assess the tumorigenic and metastatic abilities of the breast cancer cells. RESULTS: We have isolated, cloned and established five new breast cancer cell lines with different tumorigenicity and metastatic abilities from a single primary breast cancer. Although all the cell lines expressed low levels of ER, their growth was estrogen-independent and all had high-levels of expression of mutated non-functional p53. The HER2 gene was rearranged in all cell lines. Low doses of 4-OHT induced proliferation of these breast cancer cell lines. CONCLUSIONS: All five breast cancer cell lines have different antigenic expression profiles, tumorigenicity and organ specific metastatic abilities although they derive from a single tumor. None of the studied markers correlated with tumorigenic potential. These new cell lines could serve as a model for detailed genomic and proteomic analyses to

  10. Identifying Ecological Red Lines: A Case Study of the Coast in Liaoning Province

    Directory of Open Access Journals (Sweden)

    Chuansheng Wang

    2015-07-01

    Full Text Available The global decline in estuarine and coastal ecosystems is affecting critical ecosystem services. The spatial agglomeration of population, industries and resources has led to the emergence of regionally-specific ecological problems. Therefore, identifying “ecological red lines”, based on specific natural and environmental features, could help to differentiate the economic development and ecological protection directions or potentials of different regions in future. The aim of this case study is to define the ecological red line in the coastal zone of Liaoning Province, China, by evaluating the ecological importance and environmental stress in its marine and terrestrial ecosystems. For this purpose, the ecological importance of this area was first classified into four conservation indices (species, wetland, water and coast and islands and assigned values of 5, 3 and 1 for indications of high, moderate and minor importance. In the meantime, environmental stress was also classified into four indices (water environment, salinization, soil erosion and erosion of coasts and islands and assigned values of 5, 3 and 1 for indications of high, moderate and low stress, respectively. Then, based on an overlay analysis and evaluation of the above results, we defined two grades of ecological red line zones. Grade I ecological red line zones contain the areas with critical and diverse ecosystem services, areas of high importance for species conservation and nature reserves, as well as ecologically-vulnerable and sensitive areas. It is important in these areas to maintain the biological diversity and to improve the quality of the ecological environment, which should be strictly protected and explicitly controlled. Grade II ecological red line zones display areas with minimum requirements for maintaining the basic needs of a livable environment and human health, moderate to minor levels of ecological importance and high to moderate levels of environmental

  11. A lambda = 1.3 mm and 2 mm molecular line survey towards M82

    CERN Document Server

    Aladro, Rebeca; Martín-Pintado, Jesús; Mauersberger, Rainer; Henkel, Christian; Ocaña, Breezy; Amo-Baladrón, Arancha

    2011-01-01

    We study the chemical complexity towards the central parts of the starburst galaxy M82, and investigate the role of certain molecules as tracers of the physical processes in the galaxy circumnuclear region. We carried out a spectral line survey with the IRAM-30m telescope towards the northeastern molecular lobe of M82. It covers the frequency range between 129.8 GHz and 175.0 GHz in the 2 mm atmospheric window, and between 241.0 GHz and 260.0 GHz in the 1.3 mm atmospheric window. Sixty-nine spectral features corresponding to 18 different molecular species are identified. In addition, three hydrogen recombination lines are detected. The species NO, H2S, H2CS, NH2CN, and CH3CN are detected for the first time in this galaxy. Assuming local thermodynamic equilibrium, we determine the column densities of all the detected molecules. We also calculated upper limits to the column densities of fourteen other important, but undetected, molecules, such as SiO, HNCO, or OCS. We compare the chemical composition of the two...

  12. Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH-Mutant Molecular Profiles

    DEFF Research Database (Denmark)

    Farshidfar, Farshad; Zheng, Siyuan; Gingras, Marie-Claude

    2017-01-01

    intrahepatic CCA cases and propose a molecular classification scheme. We identified an IDH mutant-enriched subtype with distinct molecular features including low expression of chromatin modifiers, elevated expression of mitochondrial genes, and increased mitochondrial DNA copy number. Leveraging the multi...

  13. A computational method to help identify and measure metal lines in high resolution QSO spectra

    Institute of Scientific and Technical Information of China (English)

    Xi-Heng Shi; David Tytler; Jin-Liang Hou; David Kirkman; Jeffery Lee; Benjamin Ou

    2011-01-01

    A computational code is developed to help identify metal absorption lines in high resolution QSO spectra,especially in the Lyα forest.The input to the code includes a list of line central wavelengths,column densities and Doppler widths.The code then searches for candidate metal absorption systems and assesses the probability that each system could be real.The framework of the strategy we employ is described in detail and we discuss how to estimate the errors in line profile fitting that are essential to identification.A series of artificial spectra is constructed to calibrate the performance of the code.Due to the effects of blending and noise on Voigt profile fitting,the completeness of the identification depends on the column density of absorbers.For intermediate and strong artificial metal absorbers,more than 90% could be confirmed by the code.The results of applying the code to the real spectra of QSOs HS0757+5218 and Q0100+1300 are also presented.

  14. Exploring Photometric Methods for Identifying Emission-Line B-Type Stars

    Science.gov (United States)

    Glazier, Amy; Whelan, David

    2017-06-01

    Emission-line B-type stars, or Be stars, are a mysterious class of stars defined by their unique behavior: These stars eject material from their surfaces, forming a disc of gas that surrounds them. Furthermore, the gaseous disc is not necessarily a permanent feature of its host star. Some Be stars’ discs vary in structure over time, and may even disappear only to be regenerated later. Other Be stars may never show appreciable changes in the natures of their discs once they have been formed. The disc’s existence causes the appearance of characteristic emission lines in Be stars’ spectra, making spectroscopy the traditional method for identifying Be stars. However, spectroscopy is an inefficient and time-consuming method of finding Be stars, because it allows for only a single star to be observed in each exposure, and each star may require multiple exposures for durations of many minutes. Photometry, on the other hand, can be used to observe many stars simultaneously, but at the cost of the greater detail afforded by spectroscopy. While photometry has been used to identify Be stars, its success has been limited. In this work, we present a novel photometric technique that enables efficient identification of Be stars.

  15. Notch reporter activity in breast cancer cell lines identifies a subset of cells with stem cell activity.

    Science.gov (United States)

    D'Angelo, Rosemarie C; Ouzounova, Maria; Davis, April; Choi, Daejin; Tchuenkam, Stevie M; Kim, Gwangil; Luther, Tahra; Quraishi, Ahmed A; Senbabaoglu, Yasin; Conley, Sarah J; Clouthier, Shawn G; Hassan, Khaled A; Wicha, Max S; Korkaya, Hasan

    2015-03-01

    Developmental pathways such as Notch play a pivotal role in tissue-specific stem cell self-renewal as well as in tumor development. However, the role of Notch signaling in breast cancer stem cells (CSC) remains to be determined. We utilized a lentiviral Notch reporter system to identify a subset of cells with a higher Notch activity (Notch(+)) or reduced activity (Notch(-)) in multiple breast cancer cell lines. Using in vitro and mouse xenotransplantation assays, we investigated the role of the Notch pathway in breast CSC regulation. Breast cancer cells with increased Notch activity displayed increased sphere formation as well as expression of breast CSC markers. Interestingly Notch(+) cells displayed higher Notch4 expression in both basal and luminal breast cancer cell lines. Moreover, Notch(+) cells demonstrated tumor initiation capacity at serial dilutions in mouse xenografts, whereas Notch(-) cells failed to generate tumors. γ-Secretase inhibitor (GSI), a Notch blocker but not a chemotherapeutic agent, effectively targets these Notch(+) cells in vitro and in mouse xenografts. Furthermore, elevated Notch4 and Hey1 expression in primary patient samples correlated with poor patient survival. Our study revealed a molecular mechanism for the role of Notch-mediated regulation of breast CSCs and provided a compelling rationale for CSC-targeted therapeutics.

  16. RNAi Screen Identifies Novel Regulators of RNP Granules in the Caenorhabditis elegans Germ Line

    Science.gov (United States)

    Wood, Megan P.; Hollis, Angela; Severance, Ashley L.; Karrick, Megan L.; Schisa, Jennifer A.

    2016-01-01

    Complexes of RNA and RNA binding proteins form large-scale supramolecular structures under many cellular contexts. In Caenorhabditis elegans, small germ granules are present in the germ line that share characteristics with liquid droplets that undergo phase transitions. In meiotically-arrested oocytes of middle-aged hermaphrodites, the germ granules appear to aggregate or condense into large assemblies of RNA-binding proteins and maternal mRNAs. Prior characterization of the assembly of large-scale RNP structures via candidate approaches has identified a small number of regulators of phase transitions in the C. elegans germ line; however, the assembly, function, and regulation of these large RNP assemblies remain incompletely understood. To identify genes that promote remodeling and assembly of large RNP granules in meiotically-arrested oocytes, we performed a targeted, functional RNAi screen and identified over 300 genes that regulate the assembly of the RNA-binding protein MEX-3 into large granules. Among the most common GO classes are several categories related to RNA biology, as well as novel categories such as cell cortex, ER, and chromosome segregation. We found that arrested oocytes that fail to localize MEX-3 into cortical granules display reduced oocyte quality, consistent with the idea that the larger RNP assemblies promote oocyte quality when fertilization is delayed. Interestingly, a relatively small number of genes overlap with the regulators of germ granule assembly during normal development, or with the regulators of solid RNP granules in cgh-1 oocytes, suggesting fundamental differences in the regulation of RNP granule phase transitions during meiotic arrest. PMID:27317775

  17. ExoMol molecular line lists XII: Line Lists for 8 isotopologues of CS

    CERN Document Server

    Paulose, Geethu; Yurchenko, Sergei N; Tennyson, Jonathan

    2015-01-01

    Comprehensive vibration-rotation line lists for eight isotopologues of carbon monosulphide (CS) ($^{12}$C$^{32}$S, $^{12}$C$^{33}$S, $^{12}$C$^{34}$S, $^{12}$C$^{36}$S, $^{13}$C$^{32}$S, $^{13}$C$^{33}$S, $^{13}$C$^{34}$S, $^{13}$C$^{36}$S) in their ground electronic states are calculated. These line lists are suitable for temperatures up to 3000 K. A spectroscopically-determined potential energy curve (PEC) and dipole moment curve (DMC) are taken from literature. This PEC is adapted to suit our method prior to the computation of ro-vibrational energies. The calculated energies are then substituted by experimental energies, where available, to improve the accuracy of the line lists. The {\\it ab initio} DMC is used without refinement to generate Einstein A coefficients. Full line lists of vibration-rotation transitions and partition functions are made available in an electronic form as supporting information to this paper and at \\url{www.exomol.com}.

  18. Venus. I - Carbon monoxide distribution and molecular-line searches

    Science.gov (United States)

    Wilson, W. J.; Klein, M. J.; Kahar, R. K.; Gulkis, S.; Olsen, E. T.; Ho, P. T. P.

    1981-01-01

    An observational program to study variations of the vertical distribution of CO in the Venus atmosphere is presented. Measurements of the J = 0 - 1 absorption line at 2.6 mm wavelength are reported for two phase angles in 1977, one near eastern elongation (February) and the other near inferior conjunction (April). The two spectra are significantly different, with the April absorption line being narrower and deeper. The results of numerical inversion calculations show that the CO mixing ratio increases by a factor of approximately 100 between 78 and 100 km and that the CO abundance above approximately 100 km is greatest on the night-side hemisphere. These conclusions are in qualitative agreement with theoretical models. In addition to the CO observations, a search for other molecules was made to provide further information on the composition of the Venus middle atmosphere. The J = 0 - 1 transition of (C-13)O was detected and upper limits were derived for nine other molecules.

  19. Exomol molecular line lists VI: A high temperature line list for Phosphorus Nitride

    CERN Document Server

    Yorke, Leo; Lodi, Lorenzo; Tennyson, Jonathan

    2015-01-01

    Accurate rotational-vibrational line lists for $^{31}$P$^{14}$N and $^{31}$P$^{15}$N in their ground electronic states are computed. The line lists are produced using an empirical potential energy curve obtained by fitting to the experimental transition frequencies available in the literature in conjunction with an accurate, high level \\textit{ab initio} dipole moment curve. In these calculations the programs DPotFit and LEVEL~8.0 were used. The new line lists reproduce the experimental wavenumbers with a root-mean-square error of 0.004~cm$^{-1}$. The line lists cover the frequency range 0--51000 cm$^{-1}$, contain almost 700~000 lines each and extend up to a maximum vibrational level of $v$=66 and a maximum rotational level of $J$=357. They should be applicable for a large range of temperature up to, at least, 5000~K. These new line lists are used to simulate spectra for PN at a range of temperatures and are deposited in the Strasbourg data centre. This work is performed as part of the ExoMol project.

  20. Identifying tools for comparing simulations and observations of spectral-line data cubes

    Science.gov (United States)

    Koch, Eric W.; Ward, Caleb G.; Offner, Stella; Loeppky, Jason L.; Rosolowsky, Erik W.

    2017-10-01

    We present a statistical framework to compare spectral-line data cubes of molecular clouds and use the framework to perform an analysis of various statistical tools developed from methods proposed in the literature. We test whether our methods are sensitive to changes in the underlying physical properties of the clouds or whether their behaviour is governed by random fluctuations. We perform a set of 32 self-gravitating magnetohydrodynamic simulations that test all combinations of five physical parameters - Mach number, plasma parameter, virial parameter, driving scales and solenoidal driving fraction - each of which can be set to a low or high value. We create mock observational data sets of 13CO(1-0) emission from each simulation. We compare these mock data to those generated from a set of baseline simulations using pseudo-distance metrics based on 18 different statistical techniques that have previously been used to study molecular clouds. We analyse these results using methods from the statistical field of experimental design and find that several of the statistics can reliably track changes in the underlying physics. Our analysis shows that the interactions between parameters are often among the most significant effects. A small fraction of statistics are also sensitive to changes in magnetic field properties. We use this framework to compare the set of simulations to observations of three nearby star-forming regions: NGC 1333, Oph A and IC 348. We find that no one simulation agrees significantly better with the observations, although there is evidence that the high Mach number simulations are more consistent with the observations.

  1. A Study of the Molecular Cloud S64 with Multiple Lines of CO Isotopes

    Institute of Scientific and Technical Information of China (English)

    Lei Zhu; Yue-Fang Wu; Yue Wei

    2006-01-01

    We report on a study of the molecular cloud S64 with observations at millimeter wavelengths of multiple molecular lines of CO isotopes. A weak outflow is found, and its physical parameters are estimated. The departure of the core of S64 from the S64 HⅡ region indicates that there are still other star formation activities in that region.

  2. NMD inhibition fails to identify tumour suppressor genes in microsatellite stable gastric cancer cell lines

    Directory of Open Access Journals (Sweden)

    Ylstra Bauke

    2009-06-01

    Full Text Available Abstract Background Gastric cancers frequently show chromosomal alterations which can cause activation of oncogenes, and/or inactivation of tumour suppressor genes. In gastric cancer several chromosomal regions are described to be frequently lost, but for most of the regions, no tumour suppressor genes have been identified yet. The present study aimed to identify tumour suppressor genes inactivated by nonsense mutation and deletion in gastric cancer by means of GINI (gene identification by nonsense mediated decay inhibition and whole genome copy number analysis. Methods Two non-commercial gastric cancer cell lines, GP202 and IPA220, were transfected with siRNA directed against UPF1, to specifically inhibit the nonsense mediated decay (NMD pathway, and with siRNA directed against non-specific siRNA duplexes (CVII as a control. Microarray expression experiments were performed in triplicate on 4 × 44 K Agilent arrays by hybridizing RNA from UPF1-transfected cells against non-specific CVII-transfected cells. In addition, array CGH of the two cell lines was performed on 4 × 44K agilent arrays to obtain the DNA copy number profiles. Mutation analysis of GINI candidates was performed by sequencing. Results UPF1 expression was reduced for >70% and >80% in the GP202 and IPA220 gastric cancer cell lines, respectively. Integration of array CGH and microarray expression data provided a list of 134 and 50 candidate genes inactivated by nonsense mutation and deletion for GP202 and IPA220, respectively. We selected 12 candidate genes for mutation analysis. Of these, sequence analysis was performed on 11 genes. One gene, PLA2G4A, showed a silent mutation, and in two genes, CTSA and PTPRJ, missense mutations were detected. No nonsense mutations were detected in any of the 11 genes tested. Conclusion Although UPF1 was substantially repressed, thus resulting in the inhibition of the NMD system, we did not find genes inactivated by nonsense mutations. Our results

  3. Study of Molecular Line Parameters down to Very Low Temperature

    Science.gov (United States)

    Mondelain, D.; Camy-Peyret, C.; Deng, W.; Payan, S.; Mantz, A. W.

    2008-01-01

    The impact of precise spectroscopic measurements on the P(9) multiplet in the v3 band of 12CH4, obtained using a newly developed cold Herriott cell coupled with a tunable diode laser spectrometer, is examined in the context of remote sensing of methane in the atmosphere. More specifically, the influence of the air-broadening temperature dependence, of line narrowing and of line-mixing effects is assessed when fitting high resolution atmospheric spectra recorded from a balloon in the solar occultation mode. This is achieved by considering residuals and retrieved methane volume mixing ratio profiles. By combining data from previous studies together with new measurements, the expression for the temperature dependence of the broadening coefficient has been revisited. It is shown that a correcting factor applied to the usual law gives better results, when considering all the available measurements from room temperature down to about 10-20 K, as compared to the usual expression of the width versus temperature. These results clearly demonstrate that collision broadening is more sensitive to long-range attractive forces when the temperature is decreased.

  4. Molecular lines and continuum from W51A (I)

    Institute of Scientific and Technical Information of China (English)

    PEI; Chunchuan

    2001-01-01

    ., Wampler, E. J., Gaskell, C. M., Emission-line properties of optically and radio-selected complete quasars samples, Astrophys. J., 1989, 338: 630.[13]Yong, P., Sargent, W. L. W. A., High-resolution study of the absorption spectra of three QSOs: evidence for cosmological evolution in the lyman-alpha lines, Astrophys. J., 1982, 252: 10.[14]Lawrence, J., Zucker, J. R., Readhead, A. C. S. et al., Optical spectra of a complete sample of radio sources I. The spectra, Astrophys. J. Suppl., 1996, 107: 541.[15]Junkkarinen, V. T. , Burbidge E. M. , Smith, H. E. , Spectrophyotometry of six broad absoption line QSOs, Astrophys. J. ,1987, 317, 460.[16]Laor, A., Babcall, J. N., Jannuzi, B. T. et al., The ultraviolet emission properties of 13 quasars, Astrophys. J. Suppl.,1995, 99: 1.[17]Baldwin, J. A., Rees, M. J., Longair, M. S. et al., QSOs with narrow emission lines, Astrophys. J., 1988, 327: 103.[18]Shaver, P. A. , Boksenberg A. , Robertson, J. G. , Spectroscopy of the QSO pair Q0028 + 003/Q0029 + 003, Astrophys.J., 1982, 261: L7.[19]Baldwin, J. A., Netzer, H., The emission-line regions of high-redshift QSOs, Astrophys. J., 1978, 226: 1.[20]Wills, B. J., Thompson, K. L., Han, M. et al. , The Hubble space telescope sample of radio-loud quasars: Ultraviolet spectra of the first 31 quasars, Astrophys. J., 1995, 447: 139.[21]Osmer, P. S., Smith, M. G. , Discovery and spectroscopic observations of 27 optical selected quasars with 1.4 < z < 2.5,Astrophys. J., 1977, 213: 607.[22]Storrie-Lombardi, L. J., McMabon, R. G., Irwin, M. J. et al., APM Z > = 4 QSO Survey: Spectra and Intervening Ab-sorption Systems, Astrophys. J., 1996, 468: 121.[23]Young, P. , Sargent, W. L. W. , Boksenberg, A. , Clv absorption in an unbiased sample of 33 QSOs: evidence for the inter-vening galaxy hypothesis, Astrophys. J. Suppl., 1982, 48: 455.[24]Zitelli, V., Mignoli, M., Zarano, B. et al., A spectroscopically complete sample of quasars with Bj ≤ 22

  5. Molecular and morphological evaluation of doubled-haploid lines in maize. 2. Comparison with single-seed-descent lines.

    Science.gov (United States)

    Murigneux, A; Baud, S; Beckert, M

    1993-10-01

    Doubled-haploid (DH) and single-seed-descent (SSD) lines in maize have been compared for quantitatively inherited traits and for RFLP markers. The comparisons of the distributions for agromorphological traits do not allow definite conclusions to be drawn on the similarity of the two reproductive systems. We have used more than 100 RFLP markers to provide a precise description of the parental allele frequency and the recombination fractions. A comparison of two DH populations shows that non-random meiotic reassortment is influenced by differences in the anther culture capacities of the two parental lines. For the DH lines derived from the cross DH5 x DH7, involving two responsive lines in anther culture, the distortion in segregation (P description of the material at the molecular level, it has not been possible to make a definite conclusion as to whether or not the differences in some morphological characters are the consequences of differences in the segregation ratio and/or the recombination frequency. However, the agromorphological evaluation shows a narrow range in differences between the two types of lines and suggests that the use of DH lines is possible in breeding programmes.

  6. Adaptive PSS using a simple on-line identifier and linear pole-shift controller

    Energy Technology Data Exchange (ETDEWEB)

    Ramakrishna, G. [Department of Electrical Engineering, University of Saskatchewan, Saskatoon SK S7N 5A9 (Canada); Malik, O.P. [Department of Electrical and Computer Engineering, The University of Calgary, Calgary AB T2N 1N4 (Canada)

    2010-04-15

    Implementation of an adaptive power system stabilizer (APSS) and experimental studies are presented in this paper. The APSS consists of an adaptive linear element (ADALINE) based identifier that identifies the power system as a third-order discrete auto-regressive moving average (ARMA) model and a pole-shift controller. The ADALINE is modeled so that its weights have a one-to-one relationship with the ARMA model parameters. The weights are updated at each sampling interval to track the dynamic characteristics of the actual system. The on-line updated ARMA parameters are used in the PS control algorithm to calculate the new closed-loop poles of the system that are always inside the unit circle in the z-plane. The calculated control is such that it achieves regulation of the system to a constant setpoint in the shortest interval of time. Experimental studies on a physical model of power system verify that the proposed adaptive PSS effectively damps the oscillations and improves power system stability. (author)

  7. Cross-contamination of a UROtsa stock with T24 cells--molecular comparison of different cell lines and stocks.

    Directory of Open Access Journals (Sweden)

    Georg Johnen

    Full Text Available BACKGROUND: UROtsa is an authentic, immortalized human urothelial cell line that is used to study the effects of metals and other toxic substances, mostly in the context of bladder cancer carcinogenesis. Unusual properties on the molecular level of a provided UROtsa cell line stock prompted us to verify its identity. METHODS: UROtsa cell line stocks from different sources were tested on several molecular levels and compared with other cell lines. MicroRNA and mRNA expression was determined by Real-Time PCR. Chromosome numbers were checked and PCR of different regions of the large T-antigen was performed. DNA methylation of RARB, PGR, RASSF1, CDH1, FHIT, ESR1, C1QTNF6, PTGS2, SOCS3, MGMT, and LINE1 was analyzed by pyrosequencing and compared with results from the cell lines RT4, T24, HeLa, BEAS-2B, and HepG2. Finally, short tandem repeat (STR profiling was applied. RESULTS: All tested UROtsa cell line stocks lacked large T-antigen. STR analysis unequivocally identified our main UROtsa stock as the bladder cancer cell line T24, which was different from two authentic UROtsa stocks that served as controls. Analysis of DNA methylation patterns and RNA expression confirmed their differences. Methylation pattern and mRNA expression of the contaminating T24 cell line showed moderate changes even after long-term culture of up to 56 weeks, whereas miRNAs and chromosome numbers varied markedly. CONCLUSIONS: It is important to check the identity of cell lines, especially those that are not distributed by major cell banks. However, for some cell lines STR profiles are not available. Therefore, new cell lines should either be submitted to cell banks or at least their STR profile determined and published as part of their initial characterization. Our results should help to improve the identification of UROtsa and other cells on different molecular levels and provide information on the use of urothelial cells for long-term experiments.

  8. [Analysis of software for identifying spectral line of laser-induced breakdown spectroscopy based on LabVIEW].

    Science.gov (United States)

    Hu, Zhi-yu; Zhang, Lei; Ma, Wei-guang; Yan, Xiao-juan; Li, Zhi-xin; Zhang, Yong-zhi; Wang, Le; Dong, Lei; Yin, Wang-bao; Jia, Suo-tang

    2012-03-01

    Self-designed identifying software for LIBS spectral line was introduced. Being integrated with LabVIEW, the soft ware can smooth spectral lines and pick peaks. The second difference and threshold methods were employed. Characteristic spectrum of several elements matches the NIST database, and realizes automatic spectral line identification and qualitative analysis of the basic composition of sample. This software can analyze spectrum handily and rapidly. It will be a useful tool for LIBS.

  9. Characterization of cell lines derived from breast cancers and normal mammary tissues for the study of the intrinsic molecular subtypes.

    Science.gov (United States)

    Prat, Aleix; Karginova, Olga; Parker, Joel S; Fan, Cheng; He, Xiaping; Bixby, Lisa; Harrell, J Chuck; Roman, Erick; Adamo, Barbara; Troester, Melissa; Perou, Charles M

    2013-11-01

    Five molecular subtypes (luminal A, luminal B, HER2-enriched, basal-like, and claudin-low) with clinical implications exist in breast cancer. Here, we evaluated the molecular and phenotypic relationships of (1) a large in vitro panel of human breast cancer cell lines (BCCLs), human mammary fibroblasts (HMFs), and human mammary epithelial cells (HMECs); (2) in vivo breast tumors; (3) normal breast cell subpopulations; (4) human embryonic stem cells (hESCs); and (5) bone marrow-derived mesenchymal stem cells (hMSC). First, by integrating genomic data of 337 breast tumor samples with 93 cell lines we were able to identify all the intrinsic tumor subtypes in the cell lines, except for luminal A. Secondly, we observed that the cell lines recapitulate the differentiation hierarchy detected in the normal mammary gland, with claudin-low BCCLs and HMFs cells showing a stromal phenotype, HMECs showing a mammary stem cell/bipotent progenitor phenotype, basal-like cells showing a luminal progenitor phenotype, and luminal B cell lines showing a mature luminal phenotype. Thirdly, we identified basal-like and highly migratory claudin-low subpopulations of cells within a subset of triple-negative BCCLs (SUM149PT, HCC1143, and HCC38). Interestingly, both subpopulations within SUM149PT were enriched for tumor-initiating cells, but the basal-like subpopulation grew tumors faster than the claudin-low subpopulation. Finally, claudin-low BCCLs resembled the phenotype of hMSCs, whereas hESCs cells showed an epithelial phenotype without basal or luminal differentiation. The results presented here help to improve our understanding of the wide range of breast cancer cell line models through the appropriate pairing of cell lines with relevant in vivo tumor and normal cell counterparts.

  10. Integrated Molecular Profiling of Human Gastric Cancer Identifies DDR2 as a Potential Regulator of Peritoneal Dissemination.

    Science.gov (United States)

    Kurashige, Junji; Hasegawa, Takanori; Niida, Atsushi; Sugimachi, Keishi; Deng, Niantao; Mima, Kosuke; Uchi, Ryutaro; Sawada, Genta; Takahashi, Yusuke; Eguchi, Hidetoshi; Inomata, Masashi; Kitano, Seigo; Fukagawa, Takeo; Sasako, Mitsuru; Sasaki, Hiroki; Sasaki, Shin; Mori, Masaki; Yanagihara, Kazuyoshi; Baba, Hideo; Miyano, Satoru; Tan, Patrick; Mimori, Koshi

    2016-03-03

    Peritoneal dissemination is the most frequent, incurable metastasis occurring in patients with advanced gastric cancer (GC). However, molecular mechanisms driving peritoneal dissemination still remain poorly understood. Here, we aimed to provide novel insights into the molecular mechanisms that drive the peritoneal dissemination of GC. We performed combined expression analysis with in vivo-selected metastatic cell lines and samples from 200 GC patients to identify driver genes of peritoneal dissemination. The driver-gene functions associated with GC dissemination were examined using a mouse xenograft model. We identified a peritoneal dissemination-associated expression signature, whose profile correlated with those of genes related to development, focal adhesion, and the extracellular matrix. Among the genes comprising the expression signature, we identified that discoidin-domain receptor 2 (DDR2) as a potential regulator of peritoneal dissemination. The DDR2 was upregulated by the loss of DNA methylation and that DDR2 knockdown reduced peritoneal metastasis in a xenograft model. Dasatinib, an inhibitor of the DDR2 signaling pathway, effectively suppressed peritoneal dissemination. DDR2 was identified as a driver gene for GC dissemination from the combined expression signature and can potentially serve as a novel therapeutic target for inhibiting GC peritoneal dissemination.

  11. Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH-Mutant Molecular Profiles

    Directory of Open Access Journals (Sweden)

    Farshad Farshidfar

    2017-03-01

    Full Text Available Cholangiocarcinoma (CCA is an aggressive malignancy of the bile ducts, with poor prognosis and limited treatment options. Here, we describe the integrated analysis of somatic mutations, RNA expression, copy number, and DNA methylation by The Cancer Genome Atlas of a set of predominantly intrahepatic CCA cases and propose a molecular classification scheme. We identified an IDH mutant-enriched subtype with distinct molecular features including low expression of chromatin modifiers, elevated expression of mitochondrial genes, and increased mitochondrial DNA copy number. Leveraging the multi-platform data, we observed that ARID1A exhibited DNA hypermethylation and decreased expression in the IDH mutant subtype. More broadly, we found that IDH mutations are associated with an expanded histological spectrum of liver tumors with molecular features that stratify with CCA. Our studies reveal insights into the molecular pathogenesis and heterogeneity of cholangiocarcinoma and provide classification information of potential therapeutic significance.

  12. Big data visualization identifies the multidimensional molecular landscape of human gliomas

    Science.gov (United States)

    Bolouri, Hamid; Zhao, Lue Ping; Holland, Eric C.

    2016-01-01

    We show that visualizing large molecular and clinical datasets enables discovery of molecularly defined categories of highly similar patients. We generated a series of linked 2D sample similarity plots using genome-wide single nucleotide alterations (SNAs), copy number alterations (CNAs), DNA methylation, and RNA expression data. Applying this approach to the combined glioblastoma (GBM) and lower grade glioma (LGG) The Cancer Genome Atlas datasets, we find that combined CNA/SNA data divide gliomas into three highly distinct molecular groups. The mutations commonly used in clinical evaluation of these tumors are regionally distributed in these plots. One of the three groups is a mixture of GBM and LGG that shows similar methylation and survival characteristics to GBM. Altogether, our approach identifies eight molecularly defined glioma groups with distinct sequence/expression/methylation profiles. Importantly, we show that regionally clustered samples are enriched for specific drug targets. PMID:27118839

  13. Hydrogen in diffuse molecular clouds in the Milky Way. Atomic column densities and molecular fraction along prominent lines of sight

    Science.gov (United States)

    Winkel, B.; Wiesemeyer, H.; Menten, K. M.; Sato, M.; Brunthaler, A.; Wyrowski, F.; Neufeld, D.; Gerin, M.; Indriolo, N.

    2017-03-01

    Context. Recent submillimeter and far-infrared wavelength observations of absorption in the rotational ground-state lines of various simple molecules against distant Galactic continuum sources have opened the possibility of studying the chemistry of diffuse molecular clouds throughout the Milky Way. In order to calculate abundances, the column densities of molecular and atomic hydrogen, H i, must be known. Aims: We aim at determining the atomic hydrogen column densities for diffuse clouds located on the sight lines toward a sample of prominent high-mass star-forming regions that were intensely studied with the HIFI instrument onboard Herschel. Methods: Based on Jansky Very Large Array data, we employ the 21 cm H i absorption-line technique to construct profiles of the H i opacity versus radial velocity toward our target sources. These profiles are combined with lower resolution archival data of extended H i emission to calculate the H i column densities of the individual clouds along the sight lines. We employ Bayesian inference to estimate the uncertainties of the derived quantities. Results: Our study delivers reliable estimates of the atomic hydrogen column density for a large number of diffuse molecular clouds at various Galactocentric distances. Together with column densities of molecular hydrogen derived from its surrogates observed with HIFI, the measurements can be used to characterize the clouds and investigate the dependence of their chemistry on the molecular fraction, for example. The data sets are available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (http://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/600/A2

  14. Dissecting a Molecular Shock: Spatially Resolved H2 Line Ratios Across the HH7 Bow Shock

    Science.gov (United States)

    Pike, Rosemary E.; Geballe, Thomas R.; Burton, Michael G.; Chrysostomou, Antonio; Brand, Peter

    2015-01-01

    We report on a detailed study of the physics of molecular shocks using Gemini NIFS (Near-Infrared Field Spectrometer) K-band spectra of a 3.'2 x 2.'9 region near the tip of the HH7 bow shock. The IFU data have an angular resolution of 0.3", much higher resolution then in any previous study of a molecular shock, and a velocity resolution of 60 km/s. We have detected 20 H2 emission lines with upper state energies as high as 28,000 K, and 6 additional unidentified lines which share the same bow shock morphology as the H2. We use excitation temperatures derived from line pairs measured in 0.15' x 0.15' bins to attempt to constrain the shock type and distinguish between low velocity jump shocks, continuous shocks, and dissociative shocks in which the H2 line emission arises from newly reformed H2.

  15. Theory, Observation, and Modeling of the Zeeman and Paschen-Back Effects in Molecular Lines

    Science.gov (United States)

    Asensio Ramos, A.

    2006-12-01

    We present a historical review of the theory of the Zeeman effect in molecular lines, from its discovery at the end of the 19th century till today. The fast development of the quantum theory owes much to the impulse given by the experimental investigation of the molecular Zeeman effect. Laboratory experiments produced fruitful results after the predictions made by the quantum theory. The introduction by Racah of the powerful angular momentum algebra gave a second impulse to the theory and allowed to fully understand the fine structure and polarization properties of molecular transitions. At present, the theory of the Zeeman and Paschen-Back effects in molecular lines is being applied to spectro-(polarimetric) observations to infer the physical and magnetic properties of cold plasmas in the atmospheres of the Sun and of other stars.

  16. Molecular Hydrogen in the FUSE Translucent Lines of Sight: The Full Sample

    CERN Document Server

    Rachford, Brian L; Destree, Joshua D; Ross, Teresa L; Ferlet, Roger; Friedman, Scott D; Gry, Cecile; Jenkins, Edward B; Morton, Donald C; Savage, Blair D; Shull, J Michael; Sonnentrucker, Paule; Tumlinson, Jason; Vidal-Madjar, Alfred; Welty, Daniel E; York, Donald G

    2008-01-01

    We report total abundances and related parameters for the full sample of the FUSE survey of molecular hydrogen in 38 translucent lines of sight. New results are presented for the "second half" of the survey involving 15 lines of sight to supplement data for the first 23 lines of sight already published. We assess the correlations between molecular hydrogen and various extinction parameters in the full sample, which covers a broader range of conditions than the initial sample. In particular, we are now able to confirm that many, but not all, lines of sight with shallow far-UV extinction curves and large values of the total-to-selective extinction ratio, $R_V$ = $A_V$ / $E(B-V)$ -- characteristic of larger than average dust grains -- are associated with particularly low hydrogen molecular fractions ($f_{\\rm H2}$). In the lines of sight with large $R_V$, there is in fact a wide range in molecular fractions, despite the expectation that the larger grains should lead to less H$_2$ formation. However, we see specif...

  17. Direct determination of three-phase contact line properties on nearly molecular scale

    OpenAIRE

    Winkler, P. M.; McGraw, R. L.; Bauer, P. S.; Rentenberger, C.; Wagner, P. E.

    2016-01-01

    Wetting phenomena in multi-phase systems govern the shape of the contact line which separates the different phases. For liquids in contact with solid surfaces wetting is typically described in terms of contact angle. While in macroscopic systems the contact angle can be determined experimentally, on the molecular scale contact angles are hardly accessible. Here we report the first direct experimental determination of contact angles as well as contact line curvature on a scale of the order of ...

  18. Spectral imaging of the Sagittarius B2 region in multiple 3-mm molecular lines with the Mopra telescope

    CERN Document Server

    Jones, P A; Cunningham, M R; Menten, K M; Schilke, P; Belloche, A; Leurini, S; Ott, J; Walsh, A J

    2007-01-01

    Using the Mopra telescope, we have undertaken a 3-mm spectral-line imaging survey of a 5 x 5 arcmin^2 area around Sgr B2. We covered almost the complete spectral the range from 81.7 to 113.5 GHz, with 2.2 MHz wide spectral channels or ~ 6 km/s, and have observed 24 lines, with 0.033 MHz wide, or ~ 0.1 km/s channels. We discuss the distribution of around 50 lines, and present velocity-integrated emission images for 38 of the lines. In addition, we have detected around 120 more lines, mostly concentrated at the particularly spectral line-rich Sgr B2(N) source. There are significant differences in molecular emission, pointing to both abundance and excitation differences throughout the region. Seven distinct spatial locations are identified for the emitting species, including peaks near the prominent star forming cores of Sgr B2(N), (M) and (S) that are seen in IR-to-radio continuum images. The other features are a 'North Ridge' and a 'North Cloud' to the north of the Sgr B2 N-M-S cores, a 'South-East Peak' and a...

  19. Molecular cytogenetic characterization of a new wheat Secale africanum 2Ra(2D) substitution line for resistance to stripe rust

    Indian Academy of Sciences (India)

    Mengping Lei; Guangrong Li; Sufen Zhang; Cheng Liu; Zujun Yang

    2011-08-01

    A stable, highly fertile wheat Secale africanum substitution line LF24, derived from the F7 generation of a cross between Mianyang11 (MY11) and Triticum durum, S. africanum amphiploid (YF) was identified through molecular cytogenetic analysis. Application of C-banding, in situ hybridization and molecular markers analysis showed that LF24 was a wheat S. africanum 2Ra(2D) substitution line. When inoculated with stripe rust isolates, T. durum and MY11 were highly susceptible, while S. africanum, YF and LF24 were immune. It is confirmed through molecular cytogenetic analysis that the stripe rust resistance of LF24 was derived from S. africanum chromosome 2Ra. We compared the banding patterns and disease resistance of reported chromosomes 2R from different S. cereale introduced into wheat background, and found that there was new stripe rust resistance gene(s) on S. africanum 2Ra. LF24 is a new substitution line which can be used as stripe rust resistant source in wheat improvement.

  20. Molecular Cloud Structure from a CO Spectral Line: Interferometric Observations of MBM-12

    Science.gov (United States)

    Ingalls, J. G.; Reach, W. T.; Bania, T. M.; Carpenter, J. M.

    2007-07-01

    We used the OVRO millimeter interferometer to measure the CO (1-0) surface brightness fluctuations as a function of velocity towards molecular cloud MBM-12. We detect no interferometer visibility at the velocity of the single-dish line core, suggesting a unity surface filling factor of emitting gas. According to our model, the line wing emission is produced by tiny (1-5 milliparsec), dilute clumps, whereas the line core emission comes from large (0.01 pc) surface-filling clumps (the beamsize is about 0.03 pc). If the model is correct, the cloud is made up of mostly transient structures.

  1. Structural analysis of the genome of breast cancer cell line ZR-75-30 identifies twelve expressed fusion genes

    Directory of Open Access Journals (Sweden)

    Schulte Ina

    2012-12-01

    Full Text Available Abstract Background It has recently emerged that common epithelial cancers such as breast cancers have fusion genes like those in leukaemias. In a representative breast cancer cell line, ZR-75-30, we searched for fusion genes, by analysing genome rearrangements. Results We first analysed rearrangements of the ZR-75-30 genome, to around 10kb resolution, by molecular cytogenetic approaches, combining array painting and array CGH. We then compared this map with genomic junctions determined by paired-end sequencing. Most of the breakpoints found by array painting and array CGH were identified in the paired end sequencing—55% of the unamplified breakpoints and 97% of the amplified breakpoints (as these are represented by more sequence reads. From this analysis we identified 9 expressed fusion genes: APPBP2-PHF20L1, BCAS3-HOXB9, COL14A1-SKAP1, TAOK1-PCGF2, TIAM1-NRIP1, TIMM23-ARHGAP32, TRPS1-LASP1, USP32-CCDC49 and ZMYM4-OPRD1. We also determined the genomic junctions of a further three expressed fusion genes that had been described by others, BCAS3-ERBB2, DDX5-DEPDC6/DEPTOR and PLEC1-ENPP2. Of this total of 12 expressed fusion genes, 9 were in the coamplification. Due to the sensitivity of the technologies used, we estimate these 12 fusion genes to be around two-thirds of the true total. Many of the fusions seem likely to be driver mutations. For example, PHF20L1, BCAS3, TAOK1, PCGF2, and TRPS1 are fused in other breast cancers. HOXB9 and PHF20L1 are members of gene families that are fused in other neoplasms. Several of the other genes are relevant to cancer—in addition to ERBB2, SKAP1 is an adaptor for Src, DEPTOR regulates the mTOR pathway and NRIP1 is an estrogen-receptor coregulator. Conclusions This is the first structural analysis of a breast cancer genome that combines classical molecular cytogenetic approaches with sequencing. Paired-end sequencing was able to detect almost all breakpoints, where there was adequate read depth. It supports

  2. Assessing molecular line diagnostics of triggered star formation using synthetic observations

    CERN Document Server

    Haworth, Thomas J; Acreman, David M; Rundle, David A

    2013-01-01

    We investigate observational signatures of triggered star formation in bright rimmed clouds (BRCs) by using molecular line transfer calculations based on radiation-hydrodynamic radiatively-driven-implosion models. We find that for BRCs the separation in velocity between the line profile peak of an optically thick and an optically thin line is determined by both the observer viewing angle and the density of the shell driving into the cloud. In agreement with observations, we find that most BRC line profiles are symmetric and that asymmetries can be either red or blue, in contrast to the blue-dominance expected for a collapsing cloud. Asymmetries in the line profiles arise when an optically thick line is dominated by the shell and an optically thin line is dominated by the cloud interior to the shell. The asymmetries are red or blue depending on whether the shell is moving towards or away from the observer respectively. Using the known motions of the molecular gas in our models we rule out the envelope expansio...

  3. Phenotypic and molecular characterization of selected tomato recombinant inbred lines derived from the cross Solanum lycopersicum × S. pimpinellifolium

    Indian Academy of Sciences (India)

    Guillermo R. Pratta; Gustavo R. Rodriguez; Roxana Zorzoli; Estela M. Valle; Liliana A. Picardi

    2011-08-01

    An important trait defining fresh tomato marketability is fruit shelf life. Exotic germplasm of Solanum pimpinellifolium is able to prolong shelf life. Sixteen recombinant inbred lines with differing values of shelf life and fruit weight were derived by antagonistic-divergent selection from an interspecific cross involving Solanum pimpinellifolium. The objective of this study was to evaluate these recombinant inbred lines for many fruit quality traits such as diameter, height, size, acidity, colour, firmness, shelf life and weight, and to characterize them by amplified fragment length polymorphism markers. For most traits, a wide range of genetic variability was found and a wide range of molecular variation was also detected. Both sets of data allowed the identification of recombinant inbred lines by means of cluster analysis and principal component analysis. Genetic association among some amplified fragment length polymorphism markers and fruit quality traits, suggested by the principal component analysis, could be identified by single point analysis. Potential molecular markers underlying agronomical traits were detected in these recombinant inbred lines.

  4. Molecular line emission in NGC1068 imaged with ALMA. I An AGN-driven outflow in the dense molecular gas

    CERN Document Server

    Garcia-Burillo, S; Usero, A; Aalto, S; Krips, M; Viti, S; Alonso-Herrero, A; Hunt, L K; Schinnerer, E; Baker, A J; Casasola, F Boone V; Colina, L; Costagliola, F; Eckart, A; Fuente, A; Henkel, C; Labiano, A; Martin, S; Marquez, I; Muller, S; Planesas, P; Almeida, C Ramos; Spaans, M; Tacconi, L J; van der Werf, P P

    2014-01-01

    We investigate the fueling and the feedback of star formation and nuclear activity in NGC1068, a nearby (D=14Mpc) Seyfert 2 barred galaxy, by analyzing the distribution and kinematics of the molecular gas in the disk. We have used ALMA to map the emission of a set of dense molecular gas tracers (CO(3-2), CO(6-5), HCN(4-3), HCO+(4-3) and CS(7-6)) and their underlying continuum emission in the central r ~ 2kpc of NGC1068 with spatial resolutions ~ 0.3"-0.5" (~ 20-35pc). Molecular line and dust continuum emissions are detected from a r ~ 200pc off-centered circumnuclear disk (CND), from the 2.6kpc-diameter bar region, and from the r ~ 1.3kpc starburst (SB) ring. Most of the emission in HCO+, HCN and CS stems from the CND. Molecular line ratios show dramatic order-of-magnitude changes inside the CND that are correlated with the UV/X-ray illumination by the AGN, betraying ongoing feedback. The gas kinematics from r ~ 50pc out to r ~ 400pc reveal a massive (M_mol ~ 2.7 (+0.9, -1.2) x 10^7 Msun) outflow in all molec...

  5. Molecular origin of contact line stick-slip motion during droplet evaporation

    Science.gov (United States)

    Wang, Fengchao; Wu, Hengan

    2015-12-01

    Understanding and controlling the motion of the contact line is of critical importance for surface science studies as well as many industrial engineering applications. In this work, we elucidate the molecular origin of contact line stick-slip motion during the evaporation of liquid droplets on flexible nano-pillared surfaces using molecular dynamics simulations. We demonstrate that the evaporation-induced stick-slip motion of the contact line is a consequence of competition between pinning and depinning forces. Furthermore, the tangential force exerted by the pillared substrate on the contact line was observed to have a sawtooth-like oscillation. Our analysis also establishes that variations in the pinning force are accomplished through the self-adaptation of solid-liquid intermolecular distances, especially for liquid molecules sitting directly on top of the solid pillar. Consistent with our theoretical analysis, molecular dynamics simulations also show that the maximum pinning force is quantitatively related to both solid-liquid adhesion strength and liquid-vapor surface tension. These observations provide a fundamental understanding of contact line stick-slip motion on pillared substrates and also give insight into the microscopic interpretations of contact angle hysteresis, wetting transitions and dynamic spreading.

  6. Molecular Gas Kinematics and Line Diagnostics in Early-type Galaxies: NGC4710 and NGC5866

    CERN Document Server

    Topal, Selcuk; Davis, Timothy A; Krips, Melanie; Young, Lisa M; Crocker, Alison F

    2016-01-01

    We present interferometric observations of CO lines (12CO(1-0, 2-1) and 13CO(1-0, 2-1)) and dense gas tracers (HCN(1-0), HCO+(1-0), HNC(1-0) and HNCO(4-3)) in two nearby edge-on barred lenticular galaxies, NGC 4710 and NGC 5866, with most of the gas concentrated in a nuclear disc and an inner ring in each galaxy. We probe the physical conditions of a two-component molecular interstellar medium in each galaxy and each kinematic component by using molecular line ratio diagnostics in three complementary ways. First, we measure the ratios of the position-velocity diagrams of different lines, second we measure the ratios of each kinematic component's integrated line intensities as a function of projected position, and third we model these line ratios using a non-local thermodynamic equilibrium radiative transfer code. Overall, the nuclear discs appear to have a tenuous molecular gas component that is hotter, optically thinner and with a larger dense gas fraction than that in the inner rings, suggesting more dense ...

  7. Systematic analysis of public domain compound potency data identifies selective molecular scaffolds across druggable target families.

    Science.gov (United States)

    Hu, Ye; Wassermann, Anne Mai; Lounkine, Eugen; Bajorath, Jürgen

    2010-01-28

    Molecular scaffolds that yield target family-selective compounds are of high interest in pharmaceutical research. There continues to be considerable debate in the field as to whether chemotypes with a priori selectivity for given target families and/or targets exist and how they might be identified. What do currently available data tell us? We present a systematic and comprehensive selectivity-centric analysis of public domain target-ligand interactions. More than 200 molecular scaffolds are identified in currently available active compounds that are selective for established target families. A subset of these scaffolds is found to produce compounds with high selectivity for individual targets among closely related ones. These scaffolds are currently underrepresented in approved drugs.

  8. Probing molecular mechanisms of the Hsp90 chaperone: biophysical modeling identifies key regulators of functional dynamics.

    Directory of Open Access Journals (Sweden)

    Anshuman Dixit

    Full Text Available Deciphering functional mechanisms of the Hsp90 chaperone machinery is an important objective in cancer biology aiming to facilitate discovery of targeted anti-cancer therapies. Despite significant advances in understanding structure and function of molecular chaperones, organizing molecular principles that control the relationship between conformational diversity and functional mechanisms of the Hsp90 activity lack a sufficient quantitative characterization. We combined molecular dynamics simulations, principal component analysis, the energy landscape model and structure-functional analysis of Hsp90 regulatory interactions to systematically investigate functional dynamics of the molecular chaperone. This approach has identified a network of conserved regions common to the Hsp90 chaperones that could play a universal role in coordinating functional dynamics, principal collective motions and allosteric signaling of Hsp90. We have found that these functional motifs may be utilized by the molecular chaperone machinery to act collectively as central regulators of Hsp90 dynamics and activity, including the inter-domain communications, control of ATP hydrolysis, and protein client binding. These findings have provided support to a long-standing assertion that allosteric regulation and catalysis may have emerged via common evolutionary routes. The interaction networks regulating functional motions of Hsp90 may be determined by the inherent structural architecture of the molecular chaperone. At the same time, the thermodynamics-based "conformational selection" of functional states is likely to be activated based on the nature of the binding partner. This mechanistic model of Hsp90 dynamics and function is consistent with the notion that allosteric networks orchestrating cooperative protein motions can be formed by evolutionary conserved and sparsely connected residue clusters. Hence, allosteric signaling through a small network of distantly connected

  9. Introgression of resistance to pathogens in common bean lines with the aid of molecular markers

    Directory of Open Access Journals (Sweden)

    Alisson Campos Pereira

    2013-06-01

    Full Text Available Aiming to incorporate resistance to the anthracnose and angular leaf spot pathogens in the common bean lines BRSMG Talismã, VC8 and VC9, crosses were made between these lines and the line Rudá-R, donor of the alleles Phg1, Co-4, Co-10, which confer resistance to Pseudocercospora griseola and Colletotrichum lindemuthianum. After the crosses, the backcross populations were obtained, and the RC1F1 plants were inoculated with race 65 of C. lindemuthianum. The resistant plants were genotyped with the markers SCARH13, SCARY20 and SCARF10, linked to the alleles Phg1, Co-4 and Co-10, respectively. Based on the molecular data, 44 plants were selected. The progenies originating from multiplication of these plants were evaluated over three seasons for grain yield, plant architecture and grain aspects. Based on these considerations and molecular data, 13 promising progenies were selected for developing inbreds.

  10. Line Overlap and Self-Shielding of Molecular Hydrogen in Galaxies

    Science.gov (United States)

    Gnedin, Nickolay Y.; Draine, Bruce T.

    2014-11-01

    The effect of line overlap in the Lyman and Werner bands, often ignored in galactic studies of the atomic-to-molecular transition, greatly enhances molecular hydrogen self-shielding in low metallicity environments and dominates over dust shielding for metallicities below about 10% solar. We implement that effect in cosmological hydrodynamics simulations with an empirical model, calibrated against the observational data, and provide fitting formulae for the molecular hydrogen fraction as a function of gas density on various spatial scales and in environments with varied dust abundance and interstellar radiation field. We find that line overlap, while important for detailed radiative transfer in the Lyman and Werner bands, has only a minor effect on star formation on galactic scales, which, to a much larger degree, is regulated by stellar feedback.

  11. Line Overlap and Self-Shielding of Molecular Hydrogen in Galaxies

    CERN Document Server

    Gnedin, Nickolay Y

    2014-01-01

    The effect of line overlap in the Lyman and Werner bands, often ignored in galactic studies of the atomic-to-molecular transition, greatly enhances molecular hydrogen self-shielding in low metallicity environments, and dominates over dust shielding for metallicities below about 10% solar. We implement that effect in cosmological hydrodynamics simulations with an empirical model, calibrated against the observational data, and provide fitting formulae for the molecular hydrogen fraction as a function of gas density on various spatial scales and in environments with varied dust abundance and interstellar radiation field. We find that line overlap, while important for detailed radiative transfer in the Lyman and Werner bands, has only a minor effect on star formation on galactic scales, which, to a much larger degree, is regulated by stellar feedback.

  12. THOR - The HI, OH, Recombination Line Survey of the Milky Way - HI observations of the giant molecular cloud W43

    Science.gov (United States)

    Bihr, Simon; Beuther, Henrik; Johnston, Katharine; Henning, Thomas; Ott, Juergen; Brunthaler, Andreas; THOR Collaboration

    2015-08-01

    To study the atomic, molecular and ionised emission of Giant Molecular Clouds (GMCs) in the Milky Way, we have initiated a Large Program with the VLA: 'THOR - The HI, OH, Recombination Line survey of the Milky Way'. We map the 21cm HI line, 4 OH lines, 19 Hα recombination lines and the continuum from 1-2GHz of a significant fraction of the Milky Way (l=15-67°, |b|thin with properties such as the column density calculated under this assumption. While this approach gives reasonable results for regions of low-mass star-formation, it is not sufficient to describe the atomic gas in close proximity to GMCs. In my talk, I will present a method using strong continuum sources to measure the optical depth, and thus correct the HI 21cm emission for optical depth effects and weak diffuse continuum emission. Our analysis puts a lower limit of M~6.6x106 Msun on the HI mass associated with the W43 GMC, which is a factor of 2.4 larger than the mass obtained using the optically thin assumption. The HI column densities reach NHI~150 Msun pc-2 ~ 1.9x1022 cm-2, which is an order of magnitude higher than seen in low mass star formation regions. This result challenges theoretical models that predict a threshold for the HI column density of ~10 Msun pc-2, at which the formation of molecular hydrogen should set in. Furthermore, we assume an elliptical layered structure for W43 to estimate the particle density profile. The HI particle density shows a linear decrease toward the centre of W43 and the molecular hydrogen, traced via dust observations with Herschel, shows an exponential increase toward the centre. While at the cloud edge atomic and molecular hydrogen are well mixed, the centre of the cloud is dominated by H2. We do not identify a sharp transition between hydrogen in atomic and molecular form. Our results are an important characterization of the atomic to molecular hydrogen transition in an extreme environment that challenges current theoretical models.

  13. Identifying the molecular basis of host-parasite coevolution: merging models and mechanisms.

    Science.gov (United States)

    Dybdahl, Mark F; Jenkins, Christina E; Nuismer, Scott L

    2014-07-01

    Mathematical models of the coevolutionary process have uncovered consequences of host-parasite interactions that go well beyond the traditional realm of the Red Queen, potentially explaining several important evolutionary transitions. However, these models also demonstrate that the specific consequences of coevolution are sensitive to the structure of the infection matrix, which is embedded in models to describe the likelihood of infection in encounters between specific host and parasite genotypes. Traditional cross-infection approaches to estimating infection matrices might be unreliable because evolutionary dynamics and experimental sampling lead to missing genotypes. Consequently, our goal is to identify the likely structure of infection matrices by synthesizing molecular mechanisms of host immune defense and parasite counterdefense with coevolutionary models. This synthesis reveals that the molecular mechanisms of immune reactions, although complex and diverse, conform to two basic models commonly used within coevolutionary theory: matching infection and targeted recognition. Our synthesis also overturns conventional wisdom, revealing that the general models are not taxonomically restricted but are applicable to plants, invertebrates, and vertebrates. Finally, our synthesis identifies several important areas for future research that should improve the explanatory power of coevolutionary models. The most important among these include empirical studies to identify the molecular hotspots of genotypic specificity and theoretical studies examining the consequences of matrices that more accurately represent multistep infection processes and quantitative defenses.

  14. 3D scan line method for identifying void fabric of granular materials

    Science.gov (United States)

    Theocharis, Alexandros I.; Vairaktaris, Emmanouil; Dafalias, Yannis F.

    2017-06-01

    Among other processes measuring the void phase of porous or fractured media, scan line approach is a simplified "graphical" method, mainly used in image processing related procedures. In soil mechanics, the application of scan line method is related to the soil fabric, which is important in characterizing the anisotropic mechanical response of soils. Void fabric is of particular interest, since graphical approaches are well defined experimentally and most of them can also be easily used in numerical experiments, like the scan line method. This is in contrast to the definition of fabric based on contact normal vectors that are extremely difficult to determine, especially considering physical experiments. The scan line method has been proposed by Oda et al [1] and implemented again by Ghedia and O'Sullivan [2]. A modified method based on DEM analysis instead of image measurements of fabric has been previously proposed and implemented by the authors in a 2D scheme [3-4]. In this work, a 3D extension of the modified scan line definition is presented using PFC 3D®. The results show clearly similar trends with the 2D case and the same behaviour of fabric anisotropy is presented.

  15. 3D scan line method for identifying void fabric of granular materials

    Directory of Open Access Journals (Sweden)

    Theocharis Alexandros I.

    2017-01-01

    Full Text Available Among other processes measuring the void phase of porous or fractured media, scan line approach is a simplified “graphical” method, mainly used in image processing related procedures. In soil mechanics, the application of scan line method is related to the soil fabric, which is important in characterizing the anisotropic mechanical response of soils. Void fabric is of particular interest, since graphical approaches are well defined experimentally and most of them can also be easily used in numerical experiments, like the scan line method. This is in contrast to the definition of fabric based on contact normal vectors that are extremely difficult to determine, especially considering physical experiments. The scan line method has been proposed by Oda et al [1] and implemented again by Ghedia and O’Sullivan [2]. A modified method based on DEM analysis instead of image measurements of fabric has been previously proposed and implemented by the authors in a 2D scheme [3-4]. In this work, a 3D extension of the modified scan line definition is presented using PFC 3D®. The results show clearly similar trends with the 2D case and the same behaviour of fabric anisotropy is presented.

  16. Identifying yield-optimizing environments for two cowpea breeding lines by manipulating photoperiod and harvest scenario.

    Science.gov (United States)

    Ohler, T A; Mitchell, C A

    1996-05-01

    Photoperiod and harvest scenario of cowpea (Vigna unguiculata L. Walp) canopies were manipulated to optimize productivity for use in future controlled ecological life-support systems. Productivity was measured by edible yield rate (EYR:g m-2 day-1), shoot harvest index (SHI: g edible biomass [g total shoot dry weight]), and yield-efficiency rate (YER:g edible biomass m-2 day-1 per[g nonedible shoot dry weight]). Breeding lines 'IT84S-2246' (S-2246) and "IT82D-889' (D-889) were grown in a greenhouse under 8-, 12-, or 24-h photoperiods. S-2246 was short-day and D-889 was day-neutral for flowering. Under each photoperiod, cowpeas were harvested either for leaves only, seeds only, or leaves plus seeds (mixed harvest). Photoperiod did not affect EYR of either breeding line for any harvest scenario tested. Averaged over both breeding lines, seed harvest gave the highest EYR at 6.7 g m-2 day-1. The highest SHI (65%) and YER (94 mg m-2 day-1 g-1) were achieved for leaf-only harvest of D-889 under an 8-h photoperiod. For leaf-only harvest of S-2246, both SHI and YER increased with increasing photoperiod, but declined for seed-only and mixed harvests. However, photoperiod had no effect on SHI or YER for D-889 for any harvest scenario. A second experiment utilized the short-day cowpea breeding line 'IT89KD-288' (D-288) and the day-neutral breeding line 'IT87D-941-1' (D-941) to compare yield parameters using photoperiod extension under differing lamp types. This experiment confirmed the photoperiod responses of D-889 and S-2246 to a mixed-harvest scenario and indicated that daylength extension with higher irradiance from high pressure sodium lamps further suppressed EYR, SHI, and YER of the short-day breeding line D-288.

  17. Identifying yield-optimizing environments for two cowpea breeding lines by manipulating photoperiod and harvest scenario

    Science.gov (United States)

    Ohler, T. A.; Mitchell, C. A.

    1996-01-01

    Photoperiod and harvest scenario of cowpea (Vigna unguiculata L. Walp) canopies were manipulated to optimize productivity for use in future controlled ecological life-support systems. Productivity was measured by edible yield rate (EYR:g m-2 day-1), shoot harvest index (SHI: g edible biomass [g total shoot dry weight]), and yield-efficiency rate (YER:g edible biomass m-2 day-1 per[g nonedible shoot dry weight]). Breeding lines 'IT84S-2246' (S-2246) and "IT82D-889' (D-889) were grown in a greenhouse under 8-, 12-, or 24-h photoperiods. S-2246 was short-day and D-889 was day-neutral for flowering. Under each photoperiod, cowpeas were harvested either for leaves only, seeds only, or leaves plus seeds (mixed harvest). Photoperiod did not affect EYR of either breeding line for any harvest scenario tested. Averaged over both breeding lines, seed harvest gave the highest EYR at 6.7 g m-2 day-1. The highest SHI (65%) and YER (94 mg m-2 day-1 g-1) were achieved for leaf-only harvest of D-889 under an 8-h photoperiod. For leaf-only harvest of S-2246, both SHI and YER increased with increasing photoperiod, but declined for seed-only and mixed harvests. However, photoperiod had no effect on SHI or YER for D-889 for any harvest scenario. A second experiment utilized the short-day cowpea breeding line 'IT89KD-288' (D-288) and the day-neutral breeding line 'IT87D-941-1' (D-941) to compare yield parameters using photoperiod extension under differing lamp types. This experiment confirmed the photoperiod responses of D-889 and S-2246 to a mixed-harvest scenario and indicated that daylength extension with higher irradiance from high pressure sodium lamps further suppressed EYR, SHI, and YER of the short-day breeding line D-288.

  18. QTLs for straw quality characteristics identified in recombinant inbred lines of a Hordeum vulgare x H spontaneum cross in a Mediterranean environment

    DEFF Research Database (Denmark)

    Grando, S.; Baum, M.; Ceccarelli, S.;

    2005-01-01

    Barley straw is commonly used as animal feed in many developing countries. Even a small increase in its nutritive value can have a large impact on animal production, and hence, on rural livelihood and human nutrition. Straw quality is strongly affected by environmental factors and is, therefore......, difficult to improve with empirical breeding. The objective of this study was to identify molecular markers to facilitate the improvement of straw quality in barley. For this purpose, we have used the genetic linkage map that was already developed for recombinant inbred lines (RILs) of the cross between...... a Hordeum vulgare cultivar (`Arta') and a H. spontaneum line (H. spontaneum 41-1), covering a total of 890 cM. Straw parameters from RILs grown at Tel Hadya and Breda (ICARDA's research stations) in 2 years (1996/1997 and 1997/1998) were analyzed by NIRS for predicted nutritional characteristics including...

  19. Direct determination of three-phase contact line properties on nearly molecular scale

    Science.gov (United States)

    Winkler, P. M.; McGraw, R. L.; Bauer, P. S.; Rentenberger, C.; Wagner, P. E.

    2016-05-01

    Wetting phenomena in multi-phase systems govern the shape of the contact line which separates the different phases. For liquids in contact with solid surfaces wetting is typically described in terms of contact angle. While in macroscopic systems the contact angle can be determined experimentally, on the molecular scale contact angles are hardly accessible. Here we report the first direct experimental determination of contact angles as well as contact line curvature on a scale of the order of 1nm. For water nucleating heterogeneously on Ag nanoparticles we find contact angles around 15 degrees compared to 90 degrees for the corresponding macroscopically measured equilibrium angle. The obtained microscopic contact angles can be attributed to negative line tension in the order of ‑10‑10 J/m that becomes increasingly dominant with increasing curvature of the contact line. These results enable a consistent theoretical description of heterogeneous nucleation and provide firm insight to the wetting of nanosized objects.

  20. Chemistry in Infrared Dark Cloud Clumps: a Molecular Line Survey at 3 mm

    Science.gov (United States)

    Sanhueza, Patricio; Jackson, J. M.; Foster, J. B.

    2011-05-01

    We have observed 37 Infrared Dark Clouds (IRDCs) containing a total of 159 clumps with the 22-meter ATNF Mopra Telescope in Australia using high-density molecular tracers at 3 mm. We carried out single-pointing observations in the broad-band mode and detected 10 different molecular lines. The detections rates are dominated by HNC (1-0) (98%), N2H+ (1-0) (97%), and HCO+ (1-0) (88%) lines, showing similar values when we divide the sample into active and quiescent clumps (based on Spitzer IRAC and MIPS emission). However, we find differences of 30% in the detection rates for the H13CO+, HN13C, and HC3N lines. We also find that the N2H+ FWHMs of active clumps are broader than those of quiescent clumps, possibly due to ongoing star formation activity driving turbulence. Integrated intensity and abundance ratios of some molecular lines vary between quiescent and active clumps tracing chemical differences which arise from different evolutionary states.

  1. Molecular line radiative transfer in protoplanetary disks: Monte Carlo simulations versus approximate methods

    CERN Document Server

    Pavlyuchenkov, Ya; Henning, T; Guilloteau, St; Pietu, V; Launhardt, R; Dutrey, A

    2007-01-01

    We analyze the line radiative transfer in protoplanetary disks using several approximate methods and a well-tested Accelerated Monte Carlo code. A low-mass flaring disk model with uniform as well as stratified molecular abundances is adopted. Radiative transfer in low and high rotational lines of CO, C18O, HCO+, DCO+, HCN, CS, and H2CO is simulated. The corresponding excitation temperatures, synthetic spectra, and channel maps are derived and compared to the results of the Monte Carlo calculations. A simple scheme that describes the conditions of the line excitation for a chosen molecular transition is elaborated. We find that the simple LTE approach can safely be applied for the low molecular transitions only, while it significantly overestimates the intensities of the upper lines. In contrast, the Full Escape Probability (FEP) approximation can safely be used for the upper transitions ($J_{\\rm up} \\ga 3$) but it is not appropriate for the lowest transitions because of the maser effect. In general, the molec...

  2. Identifying the differences in mechanisms of mycophenolic acid controlling fucose content of glycoproteins expressed in different CHO cell lines.

    Science.gov (United States)

    Zhang, An; Tsang, Valerie Liu; Markely, Lam R; Kurt, Lutfiye; Huang, Yao-Ming; Prajapati, Shashi; Kshirsagar, Rashmi

    2016-11-01

    In the biopharmaceutical industry, glycosylation is a critical quality attribute that can modulate the efficacy of a therapeutic glycoprotein. Obtaining a consistent glycoform profile is desired because molecular function can be defined by its carbohydrate structures. Specifically, the fucose content of oligosaccharides in glycoproteins is one of the most important attributes that can significantly affect antibody-dependent cellular cytotoxicity (ADCC) activity. It is therefore important to understand the fucosylation pathway and be able to control fucosylation at the desired level to match predecessor materials in late stage and biosimilar programs. Several strategies were explored in this study and mycophenolic acid (MPA) was able to finely modulate the fucose content with the least undesired side effects. However, the response was significantly different between CHO cell lines of different lineages. Further experiments were then performed for a deeper understanding of the mechanism of fucosylation in different CHO cell lines. Results indicated that changes in the intracellular nucleotide involved in fucosylation pathway after MPA treatment are the main cause of the differences in fucosylation level response in different CHO cell lines. Differences in MPA metabolism in the various CHO cell lines directly resulted in different levels of afucosylation measured in antibodies produced by the CHO cell lines. Biotechnol. Bioeng. 2016;113: 2367-2376. © 2016 Wiley Periodicals, Inc.

  3. A far-infrared molecular and atomic line survey of the Orion KL region

    CERN Document Server

    Lerate, M R; Swinyard, B M; Goicoechea, J R; Cernicharo, J; Grundy, T W; Lim, T L; Polehampton, E T; Baluteau, J P; Viti, S; Yates, J

    2006-01-01

    We have carried out a high spectral resolution line survey towards the Orion Kleinmann-Low (KL) cluster from 44-188 um. The observations were taken with the Long Wavelength Spectrometer (LWS) in Fabry-Perot mode, on board the Infrared Space Observatory (ISO). A total of 152 lines are clearly detected and a further 34 features are present as possible detections. The spectrum is dominated by the molecular species H2O, OH and CO, along with [OI] and [CII] lines from PDR or shocked gas and [OIII], [NIII] lines from the foreground M42 HII region. Several isotopic species, as well as NH3, are also detected. HDO and H3O+ are tentatively detected for the first time in the far-infrared range towards Orion-KL. A basic analysis of the line observations is carried out, by comparing with previous measurements and published models and deriving rotational temperatures and column densities in the case of the molecular species. The complexity of the region requires more sophisticated models for the interpretation of all the l...

  4. Identifying Stages in a Learning Hierarchy for Use in Formative Assessment--The Example of Line Graphs

    Science.gov (United States)

    Stacey, Kaye; Price, Beth; Steinle, Vicki

    2012-01-01

    This paper discusses issues arising in the design of questions to use in an on-line computer-based formative assessment system, focussing on how best to identify the stages of a learning hierarchy for reporting to teachers. Data from several hundred students is used to illustrate how design decisions have been made for a test on interpreting line…

  5. Understanding star formation in molecular clouds III. Probability distribution functions of molecular lines in Cygnus X

    CERN Document Server

    Schneider, N; Motte, F; Ossenkopf, V; Klessen, R S; Simon, R; Fechtenbaum, S; Herpin, F; Tremblin, P; Csengeri, T; Myers, P C; Hill, T; Cunningham, M; Federrath, C

    2015-01-01

    Column density (N) PDFs serve as a powerful tool to characterize the physical processes that influence the structure of molecular clouds. Star-forming clouds can best be characterized by lognormal PDFs for the lower N range and a power-law tail for higher N, commonly attributed to turbulence and self-gravity and/or pressure, respectively. We report here on PDFs obtained from observations of 12CO, 13CO, C18O, CS, and N2H+ in the Cygnus X North region and compare to a PDF derived from dust observations with the Herschel satellite. The PDF of 12CO is lognormal for Av~1-30, but is cut for higher Av due to optical depth effects. The PDFs of C18O and 13CO are mostly lognormal up for Av~1-15, followed by excess up to Av~40. Above that value, all CO PDFs drop, most likely due to depletion. The high density tracers CS and N2H+ exhibit only a power law distribution between Av~15 and 400, respectively. The PDF from dust is lognormal for Av~2-15 and has a power-law tail up to Av~500. Absolute values for the molecular lin...

  6. Molecular profiling of Mycobacterium tuberculosis identifies tuberculosinyl nucleoside products of the virulence-associated enzyme Rv3378c

    NARCIS (Netherlands)

    Layre, Emilie; Lee, Ho Jun; Young, David C.; Martinot, Amanda Jezek; Buter, Jeffrey; Minnaard, Adriaan J.; Annand, John W.; Fortune, Sarah M.; Snider, Barry B.; Matsunaga, Isamu; Rubin, Eric J.; Alber, Tom; Moody, D. Branch

    2014-01-01

    To identify lipids with roles in tuberculosis disease, we systematically compared the lipid content of virulent Mycobacterium tuberculosis with the attenuated vaccine strain Mycobacterium bovis bacillus Calmette-Guerin. Comparative lipidomics analysis identified more than 1,000 molecular differences

  7. High Resolution Observations of Molecular Lines in Arp 220: Kinematics, Morphology, and Limits on the Applicability of the Ammonia Thermometer

    CERN Document Server

    Zschaechner, Laura K; Walter, Fabian; Meyer, David S; Momjian, Emmanuel; Scoville, Nick

    2016-01-01

    We observe Arp 220, the nearest Ultra-Luminous Infrared Galaxy (ULIRG), over 4 GHz in the K and Ka bands. We provide constraints for the kinematics,morphology, and identify molecular species on scales resolving both nuclei (0.6" or 230 pc). We detect multiple molecular species, including hydroxyl in both cores. We tentatively detect H2O at 21.84 GHz in both nuclei, indicating the likely presence of maser emission. The observed frequency range also contains metastable ammonia transitions from (J,K) = (1,1) to (5,5), as well as the (9,9) inversion line, which, together are a well-known thermometer of dense molecular gas. Furthermore, the non-metastable (4,2) and (10,9) and possibly the (3,1) lines are also detected. We apply a standard temperature analysis to Arp 220. However, the analysis is complicated in that standard LTE assumptions do not hold. There are indications that a substantial fraction of ammonia could be in the non-metastable transitions as opposed to only the metastable ones. Thus, the non-metast...

  8. Cytotoxicity of neolignans identified in Saururus chinensis towards human cancer cell lines.

    Science.gov (United States)

    Hahm, Jong-Cheon; Lee, In-Kyoung; Kang, Won-Ki; Kim, Soo-Un; Ahn, Young-Joon

    2005-05-01

    The cytotoxicity of compounds derived from the aerial parts of Saururus chinensis towards 24 cancer model and six normal cell lines was examined by MTT assay and compared with those of the anticancer agents cisplatin and doxorubicin. The active principles were characterized as the neolignans manassantin A, and its erythro, erythro- and threo, erythro-epimers by spectroscopic analysis. Manassantin A was isolated from S. chinensis as a new cytotoxic principle. Its two epimers were isolated for the first time in nature. The neolignans were more active than cisplatin and doxorubicin, with IC50 values of the neolignans, cisplatin, and doxorubicin against SK-Hep-1, PC-3, DU-145, BT-20, SK-BR-3, T-47D, Hela, T98G, and SK-MEL-28 cancer cell lines, in the ranges 0.018-0.423, 1.175-7.922, and 0.131- >50 microg/mL, respectively. Manassantin A and its threo, erythro-epimer were equicytotoxic towards model cancer cell lines. threo, erythro-Manassantin A was more active than erythro, erythro-manassantin A. Additionally, these three neolignans (IC50 > 10 microg/mL) had very low cytotoxicity towards six normal cell lines, whereas cisplatin (IC50 2.846-0.825 microg/mL) and doxorubicin (IC50 5.222-0.008 microg/mL) exhibited potent cytotoxic effects. Structure-activity relationships indicate that the hydroxy moiety appears to be essential for cytotoxicity. These neolignans merit further study as potential anticancer agents or as leads.

  9. Controlling the transmission line shape of molecular t-stubs and potential thermoelectric applications

    DEFF Research Database (Denmark)

    Stadler, Robert; Markussen, Troels

    2011-01-01

    been only empirically found for just a few rather complex organic molecules where the origins of the line shapes relation to molecular structure were not resolved. In the present, work we introduce a method to analyze the structure dependence of the asymmetry of interference dips from simple two site...... tight-binding models, where one site corresponds to a molecular π orbital of the wire and the other to an atomic pz orbital of a side group, which allows us to characterize analytically the peak shape in terms of just two parameters. We assess our scheme with first-principles electron transport...

  10. Examining Helium Line Intensities and Ratios in a Linear Helium Plasma to Identify Te and ne

    Science.gov (United States)

    Ray, H.; Biewer, T. M.; Unterberg, E. A.; Fehling, D. T.; Isler, R. C.

    2015-11-01

    Oak Ridge National Laboratory's prototype Material Plasma Exposure eXperiment (Proto-MPEX) is a linear plasma device dedicated to the understanding of plasma material interaction physics. A photomultiplier tube (PMT) based diagnostic system called a filterscope examines the visible light emission from Proto-MPEX. The filterscope is a non-invasive, high sensitivity, and high temporal resolution compact system with multiple PMT channels. Three PMTs contain He I narrow bandpass filters of wavelengths 667.9, 723.6, and 706.7 nm for line ratio analysis. Helium line intensities and ratios have been widely applied on astrophysical plasmas and machines such as JET and NSTX to determine profiles of electron temperatures, Te, and densities, ne. Ratios of the He I intensities measured by the filterscope are compared to calculated intensity ratios determined through a collisional radiative model (CRM) as follows: An excited He atom in state P will de-excite to a lower energy level Q by emitting a photon of a specific wavelength. A CRM uses the interactions P has with Q and other energy levels to calculate the population density of P. The calculated population density is used to determine the spectral line intensity of the wavelength analyzed. The aforementioned process is performed for each of the He I bandpass filters, and ratios dependent on Te and ne are calculated and compared to the filterscopes measured ratios. This work was supported by the US. D.O.E. contract DE-AC05-00OR22725.

  11. Gene expression profiles of the NCI-60 human tumor cell lines define molecular interaction networks governing cell migration processes.

    Directory of Open Access Journals (Sweden)

    Kurt W Kohn

    Full Text Available Although there is extensive information on gene expression and molecular interactions in various cell types, integrating those data in a functionally coherent manner remains challenging. This study explores the premise that genes whose expression at the mRNA level is correlated over diverse cell lines are likely to function together in a network of molecular interactions. We previously derived expression-correlated gene clusters from the database of the NCI-60 human tumor cell lines and associated each cluster with function categories of the Gene Ontology (GO database. From a cluster rich in genes associated with GO categories related to cell migration, we extracted 15 genes that were highly cross-correlated; prominent among them were RRAS, AXL, ADAM9, FN14, and integrin-beta1. We then used those 15 genes as bait to identify other correlated genes in the NCI-60 database. A survey of current literature disclosed, not only that many of the expression-correlated genes engaged in molecular interactions related to migration, invasion, and metastasis, but that highly cross-correlated subsets of those genes engaged in specific cell migration processes. We assembled this information in molecular interaction maps (MIMs that depict networks governing 3 cell migration processes: degradation of extracellular matrix, production of transient focal complexes at the leading edge of the cell, and retraction of the rear part of the cell. Also depicted are interactions controlling the release and effects of calcium ions, which may regulate migration in a spaciotemporal manner in the cell. The MIMs and associated text comprise a detailed and integrated summary of what is currently known or surmised about the role of the expression cross-correlated genes in molecular networks governing those processes.

  12. Quantitative proteomics identify molecular targets that are crucial in larval settlement and metamorphosis of bugula neritina

    KAUST Repository

    Zhang, Huoming

    2011-01-07

    The marine invertebrate Bugula neritina has a biphasic life cycle that consists of a swimming larval stage and a sessile juvenile and adult stage. The attachment of larvae to the substratum and their subsequent metamorphosis have crucial ecological consequences. Despite many studies on this species, little is known about the molecular mechanism of these processes. Here, we report a comparative study of swimming larvae and metamorphosing individuals at 4 and 24 h postattachment using label-free quantitative proteomics. We identified more than 1100 proteins at each stage, 61 of which were differentially expressed. Specifically, proteins involved in energy metabolism and structural molecules were generally down-regulated, whereas proteins involved in transcription and translation, the extracellular matrix, and calcification were strongly up-regulated during metamorphosis. Many tightly regulated novel proteins were also identified. Subsequent analysis of the temporal and spatial expressions of some of the proteins and an assay of their functions indicated that they may have key roles in metamorphosis of B. neritina. These findings not only provide molecular evidence with which to elucidate the substantial changes in morphology and physiology that occur during larval attachment and metamorphosis but also identify potential targets for antifouling treatment. © 2011 American Chemical Society.

  13. A molecular line survey of a sample of AGB stars and planetary nebulae

    CERN Document Server

    Smith, Christina L; Fuller, Gary A

    2015-01-01

    A millimeter molecular line survey of three carbon-rich AGB stars and two oxygen-rich planetary nebulae has been carried out over the frequency range 80.5-115.5 GHz. Sixty eight different transitions were detected in the data from 27 different molecular species. The hyperfine structure of C2H and C13CH has been fitted to constrain the optical depth of their transitions. All other transitions have been constrained on the basis of their line profile shapes. Rotation temperatures and column densities have been calculated for all possible species, with adaptations to the methods applied in order to account for the hyperfine structure of various transitions. From the column densities, carbon, silicon and sulphur isotopic ratios have been determined. The results corroborate IRAS 15194-5115 as a J-type star, whilst excluding IRAS 15082-4808 and IRAS 07454-7112 as such.

  14. Third-line chemotherapy in advanced non-small cell lung cancer: identifying the candidates for routine practice.

    Science.gov (United States)

    Girard, Nicolas; Jacoulet, Pascale; Gainet, Marie; Elleuch, Rami; Pernet, Didier; Depierre, Alain; Dalphin, Jean-Charles; Westeel, Virginie

    2009-12-01

    The interest of first- and second-line treatments in non-small cell lung cancer (NSCLC) has been demonstrated by successive randomized trials. Improvements in lung cancer care have routinely allowed a significant proportion of patients to be considered for third-line treatment. A retrospective analysis was performed, including all consecutive patients with advanced NSCLC, who received at least three lines of systemic antineoplastic treatment at our institution. From a population of 613 patients treated with first-line treatment, a total of 173 patients received third-line treatment (cytotoxic chemotherapy in 131 patients; epidermal growth factor (EGFR) tyrosine kinase inhibitors in 42 patients). Only 13 patients (8%) received less than 75% of the theoretical dose intensity; 22 patients (13%) presented with severe toxicities. Symptom relief and performance status (PS) improvement were observed in 121 (92% of the 131 patients with symptoms) and 90 patients (52%), respectively. Using multivariate analysis, survival after third-line treatment was significantly increased in patients younger than 70 years-old (hazard ratio [HR] = 0.73, 95% confidence interval [CI]: 0.53-0.99, p = 0.047), who smoked less than 10 pack-years (HR = 0.82, 95% CI: 0.57-0.93, p = 0.036), with no cancer-related symptoms (HR = 0.75, 95% CI: 0.61-0.92, p = 0.007), a weight loss inferior to 5 kg since the beginning of second-line (HR = 0.63, 95% CI: 0.52-0.75, p = 0.013), a PS 0 to 1 (HR = 0.81, 95% CI: 0.76-0.86, p = 0.008), and no extrathoracic tumor spread at initiation of third-line treatment (HR = 0.67, 95% CI: 0.47-0.94, p = 0.042). Disease control after both first- and second-line treatments was the strongest predictor of prolonged survival after third-line treatment (HR = 0.47, 95% CI: 0.33-0.67, p = 0.001). Patients with advanced NSCLC may benefit from third-line treatment. The best candidates can be identified using standard prognostic factors, such as PS, and disease control after first

  15. Candidate serological biomarkers for cancer identified from the secretomes of 23 cancer cell lines and the human protein atlas.

    Science.gov (United States)

    Wu, Chih-Ching; Hsu, Chia-Wei; Chen, Chi-De; Yu, Chia-Jung; Chang, Kai-Ping; Tai, Dar-In; Liu, Hao-Ping; Su, Wen-Hui; Chang, Yu-Sun; Yu, Jau-Song

    2010-06-01

    Although cancer cell secretome profiling is a promising strategy used to identify potential body fluid-accessible cancer biomarkers, questions remain regarding the depth to which the cancer cell secretome can be mined and the efficiency with which researchers can select useful candidates from the growing list of identified proteins. Therefore, we analyzed the secretomes of 23 human cancer cell lines derived from 11 cancer types using one-dimensional SDS-PAGE and nano-LC-MS/MS performed on an LTQ-Orbitrap mass spectrometer to generate a more comprehensive cancer cell secretome. A total of 31,180 proteins was detected, accounting for 4,584 non-redundant proteins, with an average of 1,300 proteins identified per cell line. Using protein secretion-predictive algorithms, 55.8% of the proteins appeared to be released or shed from cells. The identified proteins were selected as potential marker candidates according to three strategies: (i) proteins apparently secreted by one cancer type but not by others (cancer type-specific marker candidates), (ii) proteins released by most cancer cell lines (pan-cancer marker candidates), and (iii) proteins putatively linked to cancer-relevant pathways. We then examined protein expression profiles in the Human Protein Atlas to identify biomarker candidates that were simultaneously detected in the secretomes and highly expressed in cancer tissues. This analysis yielded 6-137 marker candidates selective for each tumor type and 94 potential pan-cancer markers. Among these, we selectively validated monocyte differentiation antigen CD14 (for liver cancer), stromal cell-derived factor 1 (for lung cancer), and cathepsin L1 and interferon-induced 17-kDa protein (for nasopharyngeal carcinoma) as potential serological cancer markers. In summary, the proteins identified from the secretomes of 23 cancer cell lines and the Human Protein Atlas represent a focused reservoir of potential cancer biomarkers.

  16. Molecular Hydrogen Emission Lines in Far Ultraviolet Spectroscopic Explorer Observations of Mira B

    CERN Document Server

    Wood, B E; Wood, Brian E.; Karovska, Margarita

    2004-01-01

    We present new Far Ultraviolet Spectroscopic Explorer (FUSE) observations of Mira A's wind-accreting companion star, Mira B. We find that the strongest lines in the FUSE spectrum are H2 lines fluoresced by H I Lyman-alpha. A previously analyzed Hubble Space Telescope (HST) spectrum also shows numerous Lyman-alpha fluoresced H2 lines. The HST lines are all Lyman band lines, while the FUSE H2 lines are mostly Werner band lines, many of them never before identified in an astrophysical spectrum. We combine the FUSE and HST data to refine estimates of the physical properties of the emitting H2 gas. We find that the emission can be reproduced by an H2 layer with a temperature and column density of T=3900 K and log N(H2)=17.1, respectively. Another similarity between the HST and FUSE data, besides the prevalence of H2 emission, is the surprising weakness of the continuum and high temperature emission lines, suggesting that accretion onto Mira B has weakened dramatically. The UV fluxes observed by HST on 1999 August ...

  17. Determination of resistance to Fusarium oxysporum f. sp. lycopersici via molecular markers in tomato lines

    Directory of Open Access Journals (Sweden)

    Hasan PINAR

    2013-06-01

    Full Text Available Fusarium oxysporum f. sp. lycopersici (FOL is common in tomato production areas where intensive production causes huge losses. Other plant species as well as biological and chemical control is insufficient to fight with the disease. The most effective solution to this problem is the use of resistant varieties. Fusarium oxysporum f. sp. lycopersici resistance has been transferred to most of the commercial varieties via classical and molecular marker-assisted selection (MAS. The use of molecular markers in the development of new varieties resistant to this disease, but not allelic race-specific resistance genes allows pyramiding to these genes at one cultivar. Markers which linked to resistance genes for FOL races (0, 1, 2 were improved and routinely used in tomato breeding programs. In this study, 450 pure tomato lines from the gene pool of tomato to the fore in terms of yield and some quality characteristics in Alata Horticultural Research Station Directorate were screened for Fusarium oxysporum f. sp. lycopersici (FOL resistance via developed SCAR and CAPS markers linked to I-1 and I-2. The 88 tomato lines had I-1 gene and 74 of tomato lines yielded band of homozygote resistance allele for I-2. Obtained results in this study show that developed molecular markers for Fusarium oxysporum f. sp. resistance can use easily for the developing of new cultivars.

  18. Using molecular tools to identify the geographical origin of a case of human brucellosis.

    Science.gov (United States)

    Muchowski, J K; Koylass, M S; Dainty, A C; Stack, J A; Perrett, L; Whatmore, A M; Perrier, C; Chircop, S; Demicoli, N; Gatt, A B; Caruana, P A; Gopaul, K K

    2015-10-01

    Although Malta is historically linked with the zoonosis brucellosis, there had not been a case of the disease in either the human or livestock population for several years. However, in July 2013 a case of human brucellosis was identified on the island. To determine whether this recent case originated in Malta, four isolates from this case were subjected to molecular analysis. Molecular profiles generated using multilocus sequence analysis and multilocus variable number tandem repeat for the recent human case isolates and 11 Brucella melitensis strains of known Maltese origin were compared with others held on in-house and global databases. While the 11 isolates of Maltese origin formed a distinct cluster, the recent human isolation was not associated with these strains but instead clustered with isolates originating from the Horn of Africa. These data was congruent with epidemiological trace-back showed that the individual had travelled to Malta from Eritrea. This work highlights the potential of using molecular typing data to aid in epidemiological trace-back of Brucella isolations and assist in monitoring of the effectiveness of brucellosis control schemes.

  19. Combined Proteomic-Molecular Epidemiology Approach to Identify Precision Targets in Brain Cancer.

    Science.gov (United States)

    Mostovenko, Ekaterina; Liu, Yanhong; Amirian, E Susan; Tsavachidis, Spiridon; Armstrong, Georgina N; Bondy, Melissa L; Nilsson, Carol L

    2017-07-11

    Primary brain tumors are predominantly malignant gliomas. Grade IV astrocytomas (glioblastomas, GBM) are among the most deadly of all tumors; most patients will succumb to their disease within 2 years of diagnosis despite standard of care. The grim outlook for brain tumor patients indicates that novel precision therapeutic targets must be identified. Our hypothesis is that the cancer proteomes of glioma tumors may contain protein variants that are linked to the aggressive pathology of the disease. To this end, we devised a novel workflow that combined variant proteomics with molecular epidemiological mining of public cancer data sets to identify 10 previously unrecognized variants linked to the risk of death in low grade glioma or GBM. We hypothesize that a subset of the protein variants may be successfully developed in the future as novel targets for malignant gliomas.

  20. Precision Subtypes of T Cell-Mediated Rejection Identified by Molecular Profiles

    Science.gov (United States)

    Kadota, Paul Ostrom; Hajjiri, Zahraa; Finn, Patricia W.; Perkins, David L.

    2015-01-01

    Among kidney transplant recipients, the treatment of choice for acute T cell-mediated rejection (TCMR) with pulse steroids or antibody protocols has variable outcomes. Some rejection episodes are resistant to an initial steroid pulse, but respond to subsequent antibody protocols. The biological mechanisms causing the different therapeutic responses are not currently understood. Histological examination of the renal allograft is considered the gold standard in the diagnosis of acute rejection. The Banff Classification System was established to standardize the histopathological diagnosis and to direct therapy. Although widely used, it shows variability among pathologists and lacks criteria to guide precision individualized therapy. The analysis of the transcriptome in allograft biopsies, which we analyzed in this study, provides a strategy to develop molecular diagnoses that would have increased diagnostic precision and assist the development of individualized treatment. Our hypothesis is that the histological classification of TCMR contains multiple subtypes of rejection. Using R language algorithms to determine statistical significance, multidimensional scaling, and hierarchical, we analyzed differential gene expression based on microarray data from biopsies classified as TCMR. Next, we identified KEGG functions, protein–protein interaction networks, gene regulatory networks, and predicted therapeutic targets using the integrated database ConsesnsusPathDB (CPDB). Based on our analysis, two distinct clusters of biopsies termed TCMR01 and TCMR02 were identified. Despite having the same Banff classification, we identified 1933 differentially expressed genes between the two clusters. These genes were further divided into three major groups: a core group contained within both the TCMR01 and TCMR02 subtypes, as well as genes unique to TCMR01 or TCMR02. The subtypes of TCMR utilized different biological pathways, different regulatory networks and were predicted to

  1. P-Cygni Profiles of Molecular Lines toward Arp 220 Nuclei

    CERN Document Server

    Sakamoto, Kazushi; Wilner, David J; Black, John H; Conway, John E; Costagliola, Francesco; Peck, Alison B; Spaans, Marco; Wang, Junzhi; Wiedner, Martina C

    2009-01-01

    We report ~100 pc (0.3") resolution observations of (sub)millimeter HCO+ and CO lines in the ultraluminous infrared galaxy Arp 220. The lines peak at two merger nuclei, with HCO+ being more spatially concentrated than CO. Asymmetric line profiles with blueshifted absorption and redshifted emission are discovered in HCO+(3-2) and (4-3) toward the two nuclei and in CO(3-2) toward one nucleus. We suggest that these P-Cygni profiles are due to ~100 km/s outward motion of molecular gas from the nuclei. This gas is most likely outflowing from the inner regions of the two nuclear disks rotating around individual nuclei, clearing the shroud around the luminosity sources there.

  2. Using CO line ratios to trace the physical properties of molecular clouds

    Science.gov (United States)

    Peñaloza, Camilo H.; Clark, Paul C.; Glover, Simon C. O.; Shetty, Rahul; Klessen, Ralf S.

    2017-02-01

    The carbon monoxide (CO) rotational transition lines are the most common tracers of molecular gas within giant molecular clouds (MCs). We study the ratio (R2-1/1-0) between CO's first two emission lines and examine what information it provides about the physical properties of the cloud. To study R2-1/1-0, we perform smooth particle hydrodynamic simulations with time-dependent chemistry (using GADGET-2), along with post-process radiative transfer calculations on an adaptive grid (using RADMC-3D) to create synthetic emission maps of a MC. R2-1/1-0 has a bimodal distribution that is a consequence of the excitation properties of each line, given that J = 1 reaches local thermal equilibrium while J = 2 is still sub-thermally excited in the considered clouds. The bimodality of R2-1/1-0 serves as a tracer of the physical properties of different regions of the cloud, and it helps constrain local temperatures, densities and opacities. Additionally, this bimodal structure shows an important portion of the CO emission comes from diffuse regions of the cloud, suggesting that the commonly used conversion factor of R2-1/1-0 ∼ 0.7 between both lines may need to be studied further.

  3. Chemistry in Infrared Dark Cloud Clumps: a Molecular Line Survey at 3 mm

    CERN Document Server

    Sanhueza, Patricio; Foster, Jonathan B; Garay, Guido; Silva, Andrea; Finn, Susanna C

    2012-01-01

    We have observed 37 Infrared Dark Clouds (IRDCs), containing a total of 159 clumps, in high-density molecular tracers at 3 mm using the 22-meter ATNF Mopra Telescope located in Australia. After determining kinematic distances, we eliminated clumps that are not located in IRDCs and clumps with a separation between them of less than one Mopra beam. Our final sample consists of 92 IRDC clumps. The most commonly detected molecular lines are (detection rates higher than 8%): N2H+, HNC, HN13C, HCO+, H13CO+, HCN, C2H, HC3N, HNCO, and SiO. We investigate the behavior of the different molecular tracers and look for chemical variations as a function of an evolutionary sequence based on Spitzer IRAC and MIPS emission. We find that the molecular tracers behave differently through the evolutionary sequence and some of them can be used to yield useful relative age information. The presence of HNC and N2H+ lines do not depend on the star formation activity. On the other hand, HC3N, HNCO, and SiO are predominantly detected i...

  4. Identifying the molecular basis of functions in the transcriptome of the social amoeba Dictyostelium discoideum.

    Science.gov (United States)

    Whitney, T J; Gardner, D G; Mott, M L; Brandon, M

    2010-03-09

    The unusual life cycle of Dictyostelium discoideum, in which an extra-cellular stressor such as starvation induces the development of a multicellular fruiting body consisting of stalk cells and spores from a culture of identical amoebae, provides an excellent model for investigating the molecular control of differentiation and the transition from single- to multi-cellular life, a key transition in development. We utilized serial analysis of gene expression (SAGE), a molecular method that is unbiased by dependence on previously identified genes, to obtain a transcriptome from a high-density culture of amoebae, in order to examine the transition to multi-cellular development. The SAGE method provides relative expression levels, which allows us to rank order the expressed genes. We found that a large number of ribosomal proteins were expressed at high levels, while various components of the proteosome were expressed at low levels. The only identifiable transmembrane signaling system components expressed in amoebae are related to quorum sensing, and their expression levels were relatively low. The most highly expressed gene in the amoeba transcriptome, dutA untranslated RNA, is a molecule with unknown function that may serve as an inhibitor of translation. These results suggest that high-density amoebae have not initiated development, and they also suggest a mechanism by which the transition into the development program is controlled.

  5. Molecular testing of 163 patients with Morquio A (Mucopolysaccharidosis IVA) identifies 39 novel GALNS mutations.

    Science.gov (United States)

    Morrone, A; Tylee, K L; Al-Sayed, M; Brusius-Facchin, A C; Caciotti, A; Church, H J; Coll, M J; Davidson, K; Fietz, M J; Gort, L; Hegde, M; Kubaski, F; Lacerda, L; Laranjeira, F; Leistner-Segal, S; Mooney, S; Pajares, S; Pollard, L; Ribeiro, I; Wang, R Y; Miller, N

    2014-06-01

    Morquio A (Mucopolysaccharidosis IVA; MPS IVA) is an autosomal recessive lysosomal storage disorder caused by partial or total deficiency of the enzyme galactosamine-6-sulfate sulfatase (GALNS; also known as N-acetylgalactosamine-6-sulfate sulfatase) encoded by the GALNS gene. Patients who inherit two mutated GALNS gene alleles have a decreased ability to degrade the glycosaminoglycans (GAGs) keratan sulfate and chondroitin 6-sulfate, thereby causing GAG accumulation within lysosomes and consequently pleiotropic disease. GALNS mutations occur throughout the gene and many mutations are identified only in single patients or families, causing difficulties both in mutation detection and interpretation. In this study, molecular analysis of 163 patients with Morquio A identified 99 unique mutations in the GALNS gene believed to negatively impact GALNS protein function, of which 39 are previously unpublished, together with 26 single-nucleotide polymorphisms. Recommendations for the molecular testing of patients, clear reporting of sequence findings, and interpretation of sequencing data are provided. Copyright © 2014. Published by Elsevier Inc.

  6. Genetic rearrangements of six wheat-agropyron cristatum 6P addition lines revealed by molecular markers.

    Directory of Open Access Journals (Sweden)

    Haiming Han

    Full Text Available Agropyron cristatum (L. Gaertn. (2n = 4x = 28, PPPP not only is cultivated as pasture fodder but also could provide many desirable genes for wheat improvement. It is critical to obtain common wheat-A. cristatum alien disomic addition lines to locate the desired genes on the P genome chromosomes. Comparative analysis of the homoeologous relationships between the P genome chromosome and wheat genome chromosomes is a key step in transferring different desirable genes into common wheat and producing the desired alien translocation line while compensating for the loss of wheat chromatin. In this study, six common wheat-A. cristatum disomic addition lines were produced and analyzed by phenotypic examination, genomic in situ hybridization (GISH, SSR markers from the ABD genomes and STS markers from the P genome. Comparative maps, six in total, were generated and demonstrated that all six addition lines belonged to homoeologous group 6. However, chromosome 6P had undergone obvious rearrangements in different addition lines compared with the wheat chromosome, indicating that to obtain a genetic compensating alien translocation line, one should recombine alien chromosomal regions with homoeologous wheat chromosomes. Indeed, these addition lines were classified into four types based on the comparative mapping: 6PI, 6PII, 6PIII, and 6PIV. The different types of chromosome 6P possessed different desirable genes. For example, the 6PI type, containing three addition lines, carried genes conferring high numbers of kernels per spike and resistance to powdery mildew, important traits for wheat improvement. These results may prove valuable for promoting the development of conventional chromosome engineering techniques toward molecular chromosome engineering.

  7. Integrated Analysis Identifies Molecular Signatures and Specific Prognostic Factors for Different Gastric Cancer Subtypes

    Directory of Open Access Journals (Sweden)

    Li Min

    2017-02-01

    Full Text Available BACKGROUND: Gastric cancer (GC is the fifth leading cause of cancer-related deaths worldwide. As an effective and easily performed method, microscopy-based Lauren classification has been widely accepted by gastrointestinal surgeons and pathologists for GC subtyping, but molecular characteristics of different Lauren subtypes were poorly revealed. METHODS: GSE62254 was used as a derivation cohort, and GSE15459 was used as a validation cohort. The difference between diffuse and intestinal GC on the gene expression level was measured. Gene ontology (GO enrichment analysis was performed for both subgroups. Hierarchical clustering and heatmap exhibition were also performed. Kaplan-Meier plot and Cox proportional hazards model were used to evaluate survival grouped by the given genes or hierarchical clusters. RESULTS: A total of 4598 genes were found differentially expressed between diffuse and intestinal GC. Immunity- and cell adhesion–related GOs were enriched for diffuse GC, whereas DNA repair– and cell cycle–related GOs were enriched for intestinal GC. We proposed a 40-gene signature (χ2 = 30.71, P < .001 that exhibits better discrimination for prognosis than Lauren classification (χ2 = 12.11, P = .002. FRZB [RR (95% CI = 1.824 (1.115-2.986, P = .017] and EFEMP1 [RR (95% CI = 1.537 (0.969-2.437, P = .067] were identified as independent prognostic factors only in diffuse GC but not in intestinal GC patients. KRT23 [RR (95% CI = 1.616 (0.938-2.785, P = .083] was identified as an independent prognostic factor only in intestinal GC patients but not in diffuse GC patients. Similar results were achieved in the validation cohort. CONCLUSION: We found that GCs with different Lauren classifications had different molecular characteristics and identified FRZB, EFEMP1, and KRT23 as subtype-specific prognostic factors for GC patients.

  8. Proteomic analysis of cell lines to identify the irinotecan resistance proteins

    Indian Academy of Sciences (India)

    Xing-Chen Peng; Feng-Ming Gong; Meng Wei; X I Chen; Y E Chen; K E Cheng; Feng Gao; Feng Xu; FENG Bi; Ji-Yan Liu

    2010-12-01

    Chemotherapeutic drug resistance is a frequent cause of treatment failure in colon cancer patients. Several mechanisms have been implicated in drug resistance. However, they are not sufficient to exhaustively account for this resistance emergence. In this study, two-dimensional gel electrophoresis (2-DE) and the PDQuest software analysis were applied to compare the differential expression of irinotecan-resistance-associated protein in human colon adenocarcinoma LoVo cells and irinotecan-resistant LoVo cells (LoVo/irinotecan). The differential protein dots were excised and analysed by ESI-Q-TOF mass spectrometry (MS). Fifteen proteins were identified, including eight proteins with decreased expression and seven proteins with increased expression. The identified known proteins included those that function in diverse biological processes such as cellular transcription, cell apoptosis, electron transport/redox regulation, cell proliferation/differentiation and retinol metabolism pathways. Identification of such proteins could allow improved understanding of the mechanisms leading to the acquisition of chemoresistance.

  9. Observational Approach to Molecular Cloud Evolutation with the Submillimeter-Wave CI Lines

    Science.gov (United States)

    Oka, T.; Yamamoto, S.

    Neutral carbon atoms (CI) play important roles both in chemistry and cooling processes of interstellar molecular clouds. It is thus crucial to explore its large area distribution to obtain information on formation processes and thermal balance of molecular clouds. However, observations of the submillimeter-wave CI lines have been limited to small areas around some representative objects. We have constructed a 1.2 m submillimeter-wave telescope at the summit of Mt.Fuji. The telescope was designed for the exclusive use of surveying molecular clouds in two submillimeter-wave CI lines, 3 P1 -3 P0 (492GHz) and 3 P2 -3 P1 (809 GHz), of atomic carbon. A superconductor-insulator-superconductor (SIS) mixer receiver was equipped on the Nasmyth focus of the telescope. The receiver noise temperatures [Trx(DSB)] are 300 K and 1000 K for the 492 GHz and the 809 GHz mixers, respectively. The intermediate frequency is centered at 2 GHz, having a 700 MHz bandwidth. An acousto-optical spectrometer (AOS) with 1024 channel outputs is used as a receiver backend. The telescope was installed at Nishi-yasugawara (alt. 3725 m), which is 200 m north of the highest peak, Kengamine (3776 m), in July 1998. It has b en operatede successfully during 4 observing seasons in a remote way from the Hongo campus of the University of Tokyo. We have already observed more than 40 square degrees of the sky with the CI 492 GHz line. The distribution of CI emission is found to be different from those of the 13 CO or C1 8 O emission in some clouds. These differences are discussed in relation to formation processes of molecular clouds.

  10. Notch reporter activity in breast cancer cell lines identifies a subset of cells with stem cell activity

    OpenAIRE

    D’Angelo, Rosemarie C.; Ouzounova, Maria; Davis, April; Choi, Daejin; Tchuenkam, Stevie M.; Kim, Gwangil; Luther, Tahra; Quraishi, Ahmed A.; Senbabaoglu, Yasin; Conley, Sarah J; Shawn G Clouthier; Hassan, Khaled A.; Wicha, Max S; Korkaya, Hasan

    2015-01-01

    Developmental pathways such as Notch play a pivotal role in tissue specific stem cell self-renewal as well as in tumor development. However, the role of Notch signaling in breast cancer stem cells (CSC) remains to be determined. We utilized a lentiviral Notch reporter system to identify a subset of cells with a higher Notch activity (Notch+) or reduced activity (Notch-) in multiple breast cancer cell lines. Using in vitro and mouse xenotransplantation assays we investigated the role of Notch ...

  11. Utilization of Lymphoblastoid Cell Lines as a System for the Molecular Modeling of Autism

    Science.gov (United States)

    Baron, Colin A.; Liu, Stephenie Y.; Hicks, Chindo; Gregg, Jeffrey P.

    2006-01-01

    In order to provide an alternative approach for understanding the biology and genetics of autism, we performed statistical analysis of gene expression profiles of lymphoblastoid cell lines derived from children with autism and their families. The goal was to assess the feasibility of using this model in identifying autism-associated genes.…

  12. An HI line search for optically identified dwarf galaxy candidates in the M81 group

    CERN Document Server

    Van Driel, W; Binggeli, B; Huchtmeier, W K

    1997-01-01

    Sensitive 21cm HI line observations were performed for 23 dwarf members and possible members of the nearby M81 group of galaxies, including five objects of a clustering of extremely low-surface brightness objects of unknown nature. With the Nancay decimetric radio telescope the radial velocity range of -529 to 1826 km/s was searched to an rms noise of ~3-5 mJy. Only three objects were detected. However, their high radial velocities (between 600 and 1150 km/s) show them to lie behind the M81 group. These three objects, classified as dS0: (UGC 4998) and Im (Kar 1N and UGC 5658), have HI masses of 0.5, 2.0 and 2.5 10^8 Msun, for the assumed distance of 4 Mpc, and HI mass-to-blue light ratios of 0.05, 0.91 and 0.22 Msun/LBsun, respectively. Considering that half of the observed objects are classified as irregular dwarfs, hence expected to be relatively gas-rich, the resulting detection rate of about 1/3 is quite low. However, the mean redshift and velocity dispersion of the M81 group ( = 101 km/s, sigma=114 km/s)...

  13. Anticancer activity of chemically prepared shrimp low molecular weight chitin evaluation with the human monocyte leukaemia cell line, THP-1.

    Science.gov (United States)

    Salah, R; Michaud, P; Mati, F; Harrat, Z; Lounici, H; Abdi, N; Drouiche, N; Mameri, N

    2013-01-01

    In the present study, anticancer activities of chitin, chitosan and low molecular weight chitin were evaluated using a human tumour cell line, THP-1. A molecular weight-activity relationship and an electrostatic interaction-activity relationship were determined. The cytotoxic effects of chitin and derivatives were also evaluated using a normal human foetal lung fibroblastic cell line, MRC-5 and the specific cytotoxicity of chitin and derivatives to tumour cell lines was demonstrated. The high antitumour effect of low molecular weight of chitin was established.

  14. Identifying self-interstitials of bcc and fcc crystals in molecular dynamics

    Science.gov (United States)

    Bukkuru, S.; Bhardwaj, U.; Warrier, M.; Rao, A. D. P.; Valsakumar, M. C.

    2017-02-01

    Identification of self-interstitials in molecular dynamics (MD) simulations is of critical importance. There exist several criteria for identifying the self-interstitial. Most of the existing methods use an assumed cut-off value for the displacement of an atom from its lattice position to identify the self-interstitial. The results obtained are affected by the chosen cut-off value. Moreover, these chosen cut-off values are independent of temperature. We have developed a novel unsupervised learning algorithm called Max-Space Clustering (MSC) to identify an appropriate cut-off value and its dependence on temperature. This method is compared with some widely used methods such as effective sphere (ES) method and nearest neighbor sphere (NNS) method. The cut-off radius obtained using our method shows a linear variation with temperature. The value of cut-off radius and its temperature dependence is derived for five bcc (Cr, Fe, Mo, Nb, W) and six fcc (Ag, Au, Cu, Ni, Pd, Pt) crystals. It is seen that the ratio of the cut-off values "r" to the lattice constant "a" lies between 0.23 and 0.3 at 300 K and this ratio is on an average smaller for the fcc crystals. Collision cascade simulations are carried out for Primary knock-on Atom (PKA) energies of 5 keV in Fe (at 300 K and 1000 K) and W (at 300 K and 2500 K) and the results are compared using the various methods.

  15. Deciphering causal and statistical relations of molecular aberrations and gene expressions in NCI-60 cell lines

    Directory of Open Access Journals (Sweden)

    Li Shyh-Dar

    2011-11-01

    Full Text Available Abstract Background Cancer cells harbor a large number of molecular alterations such as mutations, amplifications and deletions on DNA sequences and epigenetic changes on DNA methylations. These aberrations may dysregulate gene expressions, which in turn drive the malignancy of tumors. Deciphering the causal and statistical relations of molecular aberrations and gene expressions is critical for understanding the molecular mechanisms of clinical phenotypes. Results In this work, we proposed a computational method to reconstruct association modules containing driver aberrations, passenger mRNA or microRNA expressions, and putative regulators that mediate the effects from drivers to passengers. By applying the module-finding algorithm to the integrated datasets of NCI-60 cancer cell lines, we found that gene expressions were driven by diverse molecular aberrations including chromosomal segments' copy number variations, gene mutations and DNA methylations, microRNA expressions, and the expressions of transcription factors. In-silico validation indicated that passenger genes were enriched with the regulator binding motifs, functional categories or pathways where the drivers were involved, and co-citations with the driver/regulator genes. Moreover, 6 of 11 predicted MYB targets were down-regulated in an MYB-siRNA treated leukemia cell line. In addition, microRNA expressions were driven by distinct mechanisms from mRNA expressions. Conclusions The results provide rich mechanistic information regarding molecular aberrations and gene expressions in cancer genomes. This kind of integrative analysis will become an important tool for the diagnosis and treatment of cancer in the era of personalized medicine.

  16. Methodology of Establishing and Identifying NCI-H2228/Crizotinib-resistant Cell Lines In Vitro

    Directory of Open Access Journals (Sweden)

    Di WU

    2015-06-01

    Full Text Available Background and objective The mechanisms of small molecule targeting drug resistance and ways to overcome resistance are now both urgent need to improve the clinical efficacy. This study aimed to investigate the feasibility of using different methods to establish the crizotinib-resistant non-small cell lung cancer NCI-H2228/Crizotinib cell lines and to clarify the mechanisms of resistance to small molecule targeting drug, thus providing experimental and theoretical bases for further studies to overcome the mechanisms of Crizotinib resistance. Methods The study utilized stepwise increase of drug concentrations and chemical mutagen to induce Crizotinib-resistant NCI-H2228 cells. The drug 50% inhibitory concentration (IC50 values of parental and resistant cells and the population doubling time were determined by MTT assay. The echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK expression was evaluated by RT-PCR and Western blot. Full-length sequencing method was used to compare the EML4-ALK genes in the parent and drug-resistant cells and analyze the mechanisms of drug resistance. Results The method of gradually increasing drug concentration to induce Crizotinib-resistant NCI-H2228 cells was time-consuming because the cell growth recovery was extremely slow. Thus, this method was considered invalid. However, chemical mutagen ENU can effectively induce NCI-H2228 cells resistant to crizotinib in a short time [IC50]= (3.810±1.100 μmol/L, P=0.002,9 vs parental cells]. Furthermore, the gene mutation frequency of EML4-ALK in the resistant cells was significantly higher than that in the parent cells. Conclusion Chemical mutagen-induced cell resistance was easily operated and had effectively shortened the experimental process. Preliminary technical methods and experimental evidence for in-depth study of drug resistance mechanisms and approaches to overcome the targeted drug resistance were also provided.

  17. Tracing planet-induced structures in circumstellar disks using molecular lines

    CERN Document Server

    Ober, F; Uribe, A L; Klahr, H H

    2015-01-01

    Circumstellar disks are considered to be the birthplace of planets. Specific structures like spiral arms, gaps, and cavities are characteristic indicators of planet-disk interaction. Investigating these structures can provide insights into the growth of protoplanets and the physical properties of the disk. We investigate the feasibility of using molecular lines to trace planet-induced structures in circumstellar disks. Based on 3D hydrodynamic simulations of planet-disk interactions, we perform self-consistent temperature calculations and produce N-LTE molecular line velocity-channel maps and spectra of these disks using our new N-LTE line radiative transfer code Mol3D. Subsequently, we simulate ALMA observations using the CASA simulator. We consider two nearly face-on inclinations, 5 disk masses, 7 disk radii, and 2 different typical pre-main-sequence host stars (T Tauri, Herbig Ae). We calculate up to 141 individual velocity-channel maps for five molecules/isotopoloques in a total of 32 rotational transitio...

  18. Star Formation in Bright Rimmed Clouds. I. Millimeter and Submillimeter Molecular Line Surveys

    CERN Document Server

    De Vries, C H; Snell, R L; Vries, Christopher H. De; Narayanan, Gopal; Snell, Ronald L.

    2002-01-01

    We present the results of the first detailed millimeter and submillimeter molecular line survey of bright rimmed clouds, observed at FCRAO in the CO (J=1-0), C18O (J=1-0), HCO+ (J=1-0), H13CO+ (J=1-0), and N2H+ (J=1-0) transitions, and at the HHT in the CO (J=2-1), HCO+ (J=3-2), HCO+ (J=4-3), H13CO+ (J=3-2), and H13CO+ (J=4-3) molecular line transitions. The source list is composed of a selection of bright rimmed clouds from the catalog of such objects compiled by Sugitani et al. (1991). We also present observations of three Bok globules done for comparison with the bright rimmed clouds. We find that the appearance of the millimeter CO and HCO+ emission is dominated by the morphology of the shock front in the bright rimmed clouds. The HCO+ (J=1-0) emission tends to trace the swept up gas ridge and overdense regions which may be triggered to collapse as a result of sequential star formation. Five of the seven bright rimmed clouds we observe seem to have an outflow, however only one shows the spectral line blue...

  19. Using CO line ratios to trace the physical properties of molecular clouds

    CERN Document Server

    Peñaloza, Camilo H; Glover, Simon C O; Shetty, Rahul; Klessen, Ralf S

    2016-01-01

    The carbon monoxide (CO) rotational transition lines are the most common tracers of molecular gas within giant molecular clouds (MCs). We study the ratio ($R_{2-1/1-0}$) between CO's first two emission lines and examine what information it provides about the physical properties of the cloud. To study $R_{2-1/1-0}$ we perform smooth particle hydrodynamic simulations with time dependent chemistry (using GADGET-2), along with post-process radiative transfer calculations on an adaptive grid (using RADMC-3D) to create synthetic emission maps of a MC. $R_{2-1/1-0}$ has a bimodal distribution that is a consequence of the excitation properties of each line, given that $J=1$ reaches local thermal equilibrium (LTE) while $J=2$ is still sub-thermally excited in the considered clouds. The bimodality of $R_{2-1/1-0}$ serves as a tracer of the physical properties of different regions of the cloud and it helps constrain local temperatures, densities and opacities. Additionally this bimodal structure shows an important porti...

  20. Multi-tissue microarray analysis identifies a molecular signature of regeneration.

    Directory of Open Access Journals (Sweden)

    Sarah E Mercer

    Full Text Available The inability to functionally repair tissues that are lost as a consequence of disease or injury remains a significant challenge for regenerative medicine. The molecular and cellular processes involved in complete restoration of tissue architecture and function are expected to be complex and remain largely unknown. Unlike humans, certain salamanders can completely regenerate injured tissues and lost appendages without scar formation. A parsimonious hypothesis would predict that all of these regenerative activities are regulated, at least in part, by a common set of genes. To test this hypothesis and identify genes that might control conserved regenerative processes, we performed a comprehensive microarray analysis of the early regenerative response in five regeneration-competent tissues from the newt Notophthalmus viridescens. Consistent with this hypothesis, we established a molecular signature for regeneration that consists of common genes or gene family members that exhibit dynamic differential regulation during regeneration in multiple tissue types. These genes include members of the matrix metalloproteinase family and its regulators, extracellular matrix components, genes involved in controlling cytoskeleton dynamics, and a variety of immune response factors. Gene Ontology term enrichment analysis validated and supported their functional activities in conserved regenerative processes. Surprisingly, dendrogram clustering and RadViz classification also revealed that each regenerative tissue had its own unique temporal expression profile, pointing to an inherent tissue-specific regenerative gene program. These new findings demand a reconsideration of how we conceptualize regenerative processes and how we devise new strategies for regenerative medicine.

  1. Multi-Tissue Microarray Analysis Identifies a Molecular Signature of Regeneration

    Science.gov (United States)

    Mercer, Sarah E.; Cheng, Chia-Ho; Atkinson, Donald L.; Krcmery, Jennifer; Guzman, Claudia E.; Kent, David T.; Zukor, Katherine; Marx, Kenneth A.; Odelberg, Shannon J.; Simon, Hans-Georg

    2012-01-01

    The inability to functionally repair tissues that are lost as a consequence of disease or injury remains a significant challenge for regenerative medicine. The molecular and cellular processes involved in complete restoration of tissue architecture and function are expected to be complex and remain largely unknown. Unlike humans, certain salamanders can completely regenerate injured tissues and lost appendages without scar formation. A parsimonious hypothesis would predict that all of these regenerative activities are regulated, at least in part, by a common set of genes. To test this hypothesis and identify genes that might control conserved regenerative processes, we performed a comprehensive microarray analysis of the early regenerative response in five regeneration-competent tissues from the newt Notophthalmus viridescens. Consistent with this hypothesis, we established a molecular signature for regeneration that consists of common genes or gene family members that exhibit dynamic differential regulation during regeneration in multiple tissue types. These genes include members of the matrix metalloproteinase family and its regulators, extracellular matrix components, genes involved in controlling cytoskeleton dynamics, and a variety of immune response factors. Gene Ontology term enrichment analysis validated and supported their functional activities in conserved regenerative processes. Surprisingly, dendrogram clustering and RadViz classification also revealed that each regenerative tissue had its own unique temporal expression profile, pointing to an inherent tissue-specific regenerative gene program. These new findings demand a reconsideration of how we conceptualize regenerative processes and how we devise new strategies for regenerative medicine. PMID:23300656

  2. Comparison of molecular signatures from multiple skin diseases identifies mechanisms of immunopathogenesis.

    Science.gov (United States)

    Inkeles, Megan S; Scumpia, Philip O; Swindell, William R; Lopez, David; Teles, Rosane M B; Graeber, Thomas G; Meller, Stephan; Homey, Bernhard; Elder, James T; Gilliet, Michel; Modlin, Robert L; Pellegrini, Matteo

    2015-01-01

    The ability to obtain gene expression profiles from human disease specimens provides an opportunity to identify relevant gene pathways, but is limited by the absence of data sets spanning a broad range of conditions. Here, we analyzed publicly available microarray data from 16 diverse skin conditions in order to gain insight into disease pathogenesis. Unsupervised hierarchical clustering separated samples by disease as well as common cellular and molecular pathways. Disease-specific signatures were leveraged to build a multi-disease classifier, which predicted the diagnosis of publicly and prospectively collected expression profiles with 93% accuracy. In one sample, the molecular classifier differed from the initial clinical diagnosis and correctly predicted the eventual diagnosis as the clinical presentation evolved. Finally, integration of IFN-regulated gene programs with the skin database revealed a significant inverse correlation between IFN-β and IFN-γ programs across all conditions. Our study provides an integrative approach to the study of gene signatures from multiple skin conditions, elucidating mechanisms of disease pathogenesis. In addition, these studies provide a framework for developing tools for personalized medicine toward the precise prediction, prevention, and treatment of disease on an individual level.

  3. Coupled biophysical global ocean model and molecular genetic analyses identify multiple introductions of cryptogenic species.

    Science.gov (United States)

    Dawson, Michael N; Sen Gupta, Alex; England, Matthew H

    2005-08-23

    The anthropogenic introduction of exotic species is one of the greatest modern threats to marine biodiversity. Yet exotic species introductions remain difficult to predict and are easily misunderstood because knowledge of natural dispersal patterns, species diversity, and biogeography is often insufficient to distinguish between a broadly dispersed natural population and an exotic one. Here we compare a global molecular phylogeny of a representative marine meroplanktonic taxon, the moon-jellyfish Aurelia, with natural dispersion patterns predicted by a global biophysical ocean model. Despite assumed high dispersal ability, the phylogeny reveals many cryptic species and predominantly regional structure with one notable exception: the globally distributed Aurelia sp.1, which, molecular data suggest, may occasionally traverse the Pacific unaided. This possibility is refuted by the ocean model, which shows much more limited dispersion and patterns of distribution broadly consistent with modern biogeographic zones, thus identifying multiple introductions worldwide of this cryptogenic species. This approach also supports existing evidence that (i) the occurrence in Hawaii of Aurelia sp. 4 and other native Indo-West Pacific species with similar life histories is most likely due to anthropogenic translocation, and (ii) there may be a route for rare natural colonization of northeast North America by the European marine snail Littorina littorea, whose status as endemic or exotic is unclear.

  4. Global assessment of molecularly identified Anisakis Dujardin, 1845 (Nematoda: Anisakidae) in their teleost intermediate hosts.

    Science.gov (United States)

    Kuhn, Thomas; Hailer, Frank; Palm, Harry W; Klimpel, Sven

    2013-05-01

    Here, we present the ITS ribosomal DNA (rDNA) sequence data on 330 larvae of nematodes of the genus Anisakis Dujardin, 1845 collected from 26 different bony fish species from 21 sampling locations and different climatic zones. New host records are provided for Anisakis simplex (Rudolphi, 1809) sensu stricto (s.s.) and A. pegreffli Campana-Rouget et Biocca, 1955 from Anoplopoma fimbria (Pallas) (Santa Barbara, East Pacific), A. typica (Diesing, 1860) from Caesio cuning (Bloch), Lepturacanthus savala (Cuvier) and Katsuwonus pelamis (Linnaeus) (Indonesia, West Pacific), A. simplex s.s. from Cololabis saira (Brevoort) (Hawaii, Central Pacific), A. simplex C of Nascetti et al. (1986) from Sebastolobus alascanus Bean (Santa Barbara, East Pacific) and A. physeteris Baylis, 1923 from Synaphobranchus kaupii Johnson (Namibia, East Atlantic). Comparison with host records from 60 previous molecular studies of Anisakis species reveals the teleost host range so far recorded for the genus. Perciform (57 species) and gadiform (21) fishes were the most frequently infected orders, followed by pleuronectiforms (15) and scorpaeniforms (15). Most commonly infected fish families were Scombridae (12), Gadidae (10), Carangidae (8) and Clupeidae (7), with Merluccius merluccius (Linnaeus) alone harbouring eight Anisakis species. Different intermediate host compositions implicate differing life cycles for the so far molecularly identified Anisakis sibling species.

  5. Integrative Analysis Identifies Four Molecular and Clinical Subsets in Uveal Melanoma.

    Science.gov (United States)

    Robertson, A Gordon; Shih, Juliann; Yau, Christina; Gibb, Ewan A; Oba, Junna; Mungall, Karen L; Hess, Julian M; Uzunangelov, Vladislav; Walter, Vonn; Danilova, Ludmila; Lichtenberg, Tara M; Kucherlapati, Melanie; Kimes, Patrick K; Tang, Ming; Penson, Alexander; Babur, Ozgun; Akbani, Rehan; Bristow, Christopher A; Hoadley, Katherine A; Iype, Lisa; Chang, Matthew T; Cherniack, Andrew D; Benz, Christopher; Mills, Gordon B; Verhaak, Roel G W; Griewank, Klaus G; Felau, Ina; Zenklusen, Jean C; Gershenwald, Jeffrey E; Schoenfield, Lynn; Lazar, Alexander J; Abdel-Rahman, Mohamed H; Roman-Roman, Sergio; Stern, Marc-Henri; Cebulla, Colleen M; Williams, Michelle D; Jager, Martine J; Coupland, Sarah E; Esmaeli, Bita; Kandoth, Cyriac; Woodman, Scott E

    2017-08-14

    Comprehensive multiplatform analysis of 80 uveal melanomas (UM) identifies four molecularly distinct, clinically relevant subtypes: two associated with poor-prognosis monosomy 3 (M3) and two with better-prognosis disomy 3 (D3). We show that BAP1 loss follows M3 occurrence and correlates with a global DNA methylation state that is distinct from D3-UM. Poor-prognosis M3-UM divide into subsets with divergent genomic aberrations, transcriptional features, and clinical outcomes. We report change-of-function SRSF2 mutations. Within D3-UM, EIF1AX- and SRSF2/SF3B1-mutant tumors have distinct somatic copy number alterations and DNA methylation profiles, providing insight into the biology of these low- versus intermediate-risk clinical mutation subtypes. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Molecular approaches to identify cryptic species and polymorphic species within a complex community of fig wasps.

    Directory of Open Access Journals (Sweden)

    Jin-Hua Xiao

    Full Text Available Cryptic and polymorphic species can complicate traditional taxonomic research and both of these concerns are common in fig wasp communities. Species identification is very difficult, despite great effort and the ecological importance of fig wasps. Herein, we try to identify all chalcidoid wasp species hosted by one species of fig, using both morphological and molecular methods. We compare the efficiency of four different DNA regions and find that ITS2 is highly effective for species identification, while mitochondrial COI and Cytb regions appear less reliable, possibly due to the interference signals from either nuclear copies of mtDNA, i.e. NUMTs, or the effects of Wolbachia infections. The analyses suggest that combining multiple markers is the best choice for inferring species identifications as any one marker may be unsuitable in a given case.

  7. Molecular dynamics study to identify the reactive sites of a liquid squalane surface.

    Science.gov (United States)

    Köhler, Sven P K; Reed, Stewart K; Westacott, Robin E; McKendrick, Kenneth G

    2006-06-22

    Molecular dynamics simulations of liquid squalane, C30H62, were performed, focusing in particular on the liquid-vacuum interface. These theoretical studies were aimed at identifying potentially reactive sites on the surface, knowledge of which is important for a number of inelastic and reactive scattering experiments. A united atom force field (Martin, M. G.; Siepmann, J. I. J. Phys. Chem. B 1999, 103, 4508-4517) was used, and the simulations were analyzed with respect to their interfacial properties. A modest but clearly identifiable preference for methyl groups to protrude into the vacuum has been found at lower temperatures. This effect decreases when going to higher temperatures. Additional simulations tracking the flight paths of projectiles directed at a number of randomly chosen surfaces extracted from the molecular dynamics simulations were performed. The geometrical parameters for these calculations were chosen to imitate a typical abstraction reaction, such as the reaction between ground-state oxygen atoms and hydrocarbons. Despite the preference for methyl groups to protrude further into the vacuum, Monte Carlo tracking simulations suggest, on geometric grounds, that primary and secondary hydrogen atoms are roughly equally likely to react with incoming gas-phase atoms. These geometric simulations also indicate that a substantial fraction of the scattered products is likely to undergo at least one secondary collision with hydrocarbon side chains. These results help to interpret the outcome of previous measurements of the internal and external energy distribution of the gas-phase OH products of the interfacial reaction between oxygen atoms and liquid squalane.

  8. NARROW Na AND K ABSORPTION LINES TOWARD T TAURI STARS: TRACING THE ATOMIC ENVELOPE OF MOLECULAR CLOUDS

    Energy Technology Data Exchange (ETDEWEB)

    Pascucci, I.; Simon, M. N. [Lunar and Planetary Laboratory, The University of Arizona, Tucson, AZ 85721 (United States); Edwards, S. [Five College Astronomy Department, Smith College, Northampton, MA 01063 (United States); Heyer, M. [Department of Astronomy, University of Massachusetts, Amherst, MA 01003-9305 (United States); Rigliaco, E. [Institute for Astronomy, ETH Zurich, Wolfgang-Pauli-Strasse 27, CH-8093 Zurich (Switzerland); Hillenbrand, L. [Department of Astronomy, California Institute of Technology, Pasadena, CA 91125 (United States); Gorti, U.; Hollenbach, D., E-mail: pascucci@lpl.arizona.edu [SETI Institute, Mountain View, CA 94043 (United States)

    2015-11-20

    We present a detailed analysis of narrow Na i and K i absorption resonance lines toward nearly 40 T Tauri stars in Taurus with the goal of clarifying their origin. The Na i λ5889.95 line is detected toward all but one source, while the weaker K i λ7698.96 line is detected in about two-thirds of the sample. The similarity in their peak centroids and the significant positive correlation between their equivalent widths demonstrate that these transitions trace the same atomic gas. The absorption lines are present toward both disk and diskless young stellar objects, which excludes cold gas within the circumstellar disk as the absorbing material. A comparison of Na i and CO detections and peak centroids demonstrates that the atomic gas and molecular gas are not co-located, the atomic gas being more extended than the molecular gas. The width of the atomic lines corroborates this finding and points to atomic gas about an order of magnitude warmer than the molecular gas. The distribution of Na i radial velocities shows a clear spatial gradient along the length of the Taurus molecular cloud filaments. This suggests that absorption is associated with the Taurus molecular cloud. Assuming that the gradient is due to cloud rotation, the rotation of the atomic gas is consistent with differential galactic rotation, whereas the rotation of the molecular gas, although with the same rotation axis, is retrograde. Our analysis shows that narrow Na i and K i absorption resonance lines are useful tracers of the atomic envelope of molecular clouds. In line with recent findings from giant molecular clouds, our results demonstrate that the velocity fields of the atomic and molecular gas are misaligned. The angular momentum of a molecular cloud is not simply inherited from the rotating Galactic disk from which it formed but may be redistributed by cloud–cloud interactions.

  9. Translational informatics approach for identifying the functional molecular communicators linking coronary artery disease, infection and inflammation.

    Science.gov (United States)

    Sharma, Ankit; Ghatge, Madankumar; Mundkur, Lakshmi; Vangala, Rajani Kanth

    2016-05-01

    Translational informatics approaches are required for the integration of diverse and accumulating data to enable the administration of effective translational medicine specifically in complex diseases such as coronary artery disease (CAD). In the current study, a novel approach for elucidating the association between infection, inflammation and CAD was used. Genes for CAD were collected from the CAD‑gene database and those for infection and inflammation were collected from the UniProt database. The cytomegalovirus (CMV)‑induced genes were identified from the literature and the CAD‑associated clinical phenotypes were obtained from the Unified Medical Language System. A total of 55 gene ontologies (GO) termed functional communicator ontologies were identified in the gene sets linking clinical phenotypes in the diseasome network. The network topology analysis suggested that important functions including viral entry, cell adhesion, apoptosis, inflammatory and immune responses networked with clinical phenotypes. Microarray data was extracted from the Gene Expression Omnibus (dataset: GSE48060) for highly networked disease myocardial infarction. Further analysis of differentially expressed genes and their GO terms suggested that CMV infection may trigger a xenobiotic response, oxidative stress, inflammation and immune modulation. Notably, the current study identified γ‑glutamyl transferase (GGT)‑5 as a potential biomarker with an odds ratio of 1.947, which increased to 2.561 following the addition of CMV and CMV‑neutralizing antibody (CMV‑NA) titers. The C‑statistics increased from 0.530 for conventional risk factors (CRFs) to 0.711 for GGT in combination with the above mentioned infections and CRFs. Therefore, the translational informatics approach used in the current study identified a potential molecular mechanism for CMV infection in CAD, and a potential biomarker for risk prediction.

  10. Identifying and characterizing alternative molecular markers for the symbiotic and free-living dinoflagellate genus Symbiodinium.

    Directory of Open Access Journals (Sweden)

    Xavier Pochon

    Full Text Available Dinoflagellates in the genus Symbiodinium are best known as endosymbionts of corals and other invertebrate as well as protist hosts, but also exist free-living in coastal environments. Despite their importance in marine ecosystems, less than 10 loci have been used to explore phylogenetic relationships in this group, and only the multi-copy nuclear ribosomal Internal Transcribed Spacer (ITS regions 1 and 2 have been used to characterize fine-scale genetic diversity within the nine clades (A-I that comprise the genus. Here, we describe a three-step molecular approach focused on 1 identifying new candidate genes for phylogenetic analysis of Symbiodinium spp., 2 characterizing the phylogenetic relationship of these candidate genes from DNA samples spanning eight Symbiodinium clades (A-H, and 3 conducting in-depth phylogenetic analyses of candidate genes displaying genetic divergences equal or higher than those within the ITS-2 of Symbiodinium clade C. To this end, we used bioinformatics tools and reciprocal comparisons to identify homologous genes from 55,551 cDNA sequences representing two Symbiodinium and six additional dinoflagellate EST libraries. Of the 84 candidate genes identified, 7 Symbiodinium genes (elf2, coI, coIII, cob, calmodulin, rad24, and actin were characterized by sequencing 23 DNA samples spanning eight Symbiodinium clades (A-H. Four genes displaying higher rates of genetic divergences than ITS-2 within clade C were selected for in-depth phylogenetic analyses, which revealed that calmodulin has limited taxonomic utility but that coI, rad24, and actin behave predictably with respect to Symbiodinium lineage C and are potential candidates as new markers for this group. The approach for targeting candidate genes described here can serve as a model for future studies aimed at identifying and testing new phylogenetically informative genes for taxa where transcriptomic and genomics data are available.

  11. Identifying and characterizing alternative molecular markers for the symbiotic and free-living dinoflagellate genus Symbiodinium.

    Science.gov (United States)

    Pochon, Xavier; Putnam, Hollie M; Burki, Fabien; Gates, Ruth D

    2012-01-01

    Dinoflagellates in the genus Symbiodinium are best known as endosymbionts of corals and other invertebrate as well as protist hosts, but also exist free-living in coastal environments. Despite their importance in marine ecosystems, less than 10 loci have been used to explore phylogenetic relationships in this group, and only the multi-copy nuclear ribosomal Internal Transcribed Spacer (ITS) regions 1 and 2 have been used to characterize fine-scale genetic diversity within the nine clades (A-I) that comprise the genus. Here, we describe a three-step molecular approach focused on 1) identifying new candidate genes for phylogenetic analysis of Symbiodinium spp., 2) characterizing the phylogenetic relationship of these candidate genes from DNA samples spanning eight Symbiodinium clades (A-H), and 3) conducting in-depth phylogenetic analyses of candidate genes displaying genetic divergences equal or higher than those within the ITS-2 of Symbiodinium clade C. To this end, we used bioinformatics tools and reciprocal comparisons to identify homologous genes from 55,551 cDNA sequences representing two Symbiodinium and six additional dinoflagellate EST libraries. Of the 84 candidate genes identified, 7 Symbiodinium genes (elf2, coI, coIII, cob, calmodulin, rad24, and actin) were characterized by sequencing 23 DNA samples spanning eight Symbiodinium clades (A-H). Four genes displaying higher rates of genetic divergences than ITS-2 within clade C were selected for in-depth phylogenetic analyses, which revealed that calmodulin has limited taxonomic utility but that coI, rad24, and actin behave predictably with respect to Symbiodinium lineage C and are potential candidates as new markers for this group. The approach for targeting candidate genes described here can serve as a model for future studies aimed at identifying and testing new phylogenetically informative genes for taxa where transcriptomic and genomics data are available.

  12. Molecular Spectroscopy in Space: Discovering New Molecules from Line Surveys and Laboratory Spectroscopy

    Science.gov (United States)

    Cernicharo, Jose

    2016-06-01

    The increasing sensitivity offered by the new generation of radio astronomical receivers and radio telescopes (single dishes and radio interferometers) has provided an enormous impact in our capacity to study the molecular content of interstellar and circumstellar clouds. Astronomers face now the challenging problem of interpreting the thousands of lines detected in hot cores which arise from isotopologues and vibrationally excited states of most known molecules. Although all strong features have been already assigned to abundant species, many of the lines still pending to be assigned could arise from very abundant molecular species having low dipole moment and/or very large partition functions. The only way to address this problem in astrophysics is through a close collaboration between astrophysicists and laboratory spectroscopists. In this talk I am going to present the results obtained over the last 10 years in interpreting the line surveys of Orion gathered with the 30m IRAM radio telescope and with ALMA. The most recent molecule found in this cloud is methyl isocyanate, CH3NCO, for which near 400 lines have been found in Oriona in the 80-280 GHz domain. This molecule has an abundance only a factor 5-20 below that of the well-known species HNCO and CH3CN. The molecule has been also found towards the giant cloud SgrB2b in the galactic center. Finally, I will present the case of the submillimeter spectrum of the carbon-rich evolved star IRC+10216 in which we have recently found Si2C with an abundance similar to SiC2. Our recent ALMA observations in a narrow band of 20 GHz around 265 GHz show near 200 features corresponding to the J=3-2 transition of hot HCN (vibrational levels up to 11000 cm-1). In addition to HCN lines, a forest of several hundreds of U lines dominates the spectrum. Most of these lines arise from molecules that condensate very quickly into dust grainsc. aJ. Cernicharo, Z.Kisiel, B.Tercero, et al., A&A 587, L4 (2016). bD.T. Halfen, V

  13. A case study on variability management in software product lines: identifying why real-life projects fail

    Directory of Open Access Journals (Sweden)

    Tom Huysegoms

    2013-01-01

    Full Text Available Economies of scale can be seen as some kind of “holy grail” in state of the art literature on the development of sets of related software systems. Software product line methods are often mentioned in this context, due to the variability management aspects they propose, in order to deal with sets of related software systems. They realize the sought-after reusability. Both variability management and software product lines already have a strong presence in theoretical research, but in real-life software product line projects trying to obtain economies of scale still tend to fall short of target. The objective of this paper is to study this gap between theory and reality through a case study in order to see why such gap exists, and to find a way to bridge this gap. Through analysis of the causes of failure identified by the stakeholders in the case study, the underlying problem, which is found to be located in the requirements engineering phase, is crystallized. The identification of a framework describing the problems will provide practitioners with a better focus for future endeavors in the field of software product lines, so that economies of scale can be achieved.

  14. Stacking Spectra in Protoplanetary Disks: Detecting Intensity Profiles from Hidden Molecular Lines in HD 163296

    Science.gov (United States)

    Yen, Hsi-Wei; Koch, Patrick M.; Liu, Hauyu Baobab; Puspitaningrum, Evaria; Hirano, Naomi; Lee, Chin-Fei; Takakuwa, Shigehisa

    2016-12-01

    We introduce a new stacking method in Keplerian disks that (1) enhances signal-to-noise ratios (S/Ns) of detected molecular lines and (2) makes visible otherwise-undetectable weak lines. Our technique takes advantage of the Keplerian rotational velocity pattern. It aligns spectra according to their different centroid velocities at their different positions in a disk and stacks them. After aligning, the signals are accumulated in a narrower velocity range as compared to the original line width without alignment. Moreover, originally correlated noise becomes decorrelated. Stacked and aligned spectra thus have a higher S/N. We apply our method to Atacama Large Millimeter/Submillimeter Array (ALMA) archival data of DCN (3-2), DCO+ (3-2), N2D+ (3-2), and H2CO (3{}{0,3}-2{}{0,2}), (3{}{2,2}-2{}{2,1}), and (3{}{2,1}-2{}{2,0}) in the protoplanetary disk around HD 163296. As a result, (1) the S/Ns of the originally detected DCN (3-2), DCO+ (3-2), H2CO (3{}{0,3}-2{}{0,2}), and N2D+ (3-2) lines are boosted by a factor of ≳4-5 at their spectral peaks, implying one order of magnitude shorter integration times to reach the original S/N; and (2) the previously undetectable spectra of the H2CO (3{}{2,2}-2{}{2,1}) and (3{}{2,1}-2{}{2,0}) lines are materialized at more than 3σ. These dramatically enhanced S/Ns allow us to measure intensity distributions in all lines with high significance. The principle of our method can be applied not only to Keplerian disks but also to any systems with ordered kinematic patterns.

  15. Interferometric 3mm spectral line and continuum survey of the central molecular zone

    Science.gov (United States)

    Pound, Marc W.; Yusef-Zadeh, Farhad

    2014-05-01

    Because of its large angular extent, the central molecular zone (CMZ) has to date only been mapped in the mm with single dish telescopes, with resolution about 30″ (1.4 pc). We present the first interferometric maps of a 90 × 50 pc region of the CMZ, with spatial resolution of ˜10″ (0.4 pc). We mapped ˜0.25 square degrees of the CMZ with CARMA in 3mm continuum and the spectral lines SiO J = (2 - 1), HCO+ J = (1 - 0), HCN J = (1 - 0), N2H+ J = (1 - 0), and CS J = (2 - 1), covering roughly VLSR = -200 to 200 km s-1 with spectral resolution ΔV ˜ 2.5 km s-1. To recover the large scale structure resolved out by the interferometer, the continuum-subtracted spectral line images were combined with the Mopra 22-m telescope survey.

  16. Synthesis of a high molecular weight thyroglobulin dimer by two ovine thyroid cell lines: the OVNIS.

    Science.gov (United States)

    Hovsépian, S; Aouani, A; Fayet, G

    1986-05-01

    The OVNIS 6H and 5H thyroid cells, 2 permanent cell lines isolated 3 years ago from ovine tissue, synthesize a high molecular weight glycosylated protein, immunologically related to ovine thyroglobulin, which is similar to the prothyroid hormone dimer (17-19) S: thyroglobulin. Using sucrose gradient centrifugation and cell labelling with [14C]Leu or [3H]GlNH2, radioactivity was observed in proteins purified from cell layers and from cell culture media. Addition of thyrotropin to or removal from the media resulted respectively in an increase (+773%) or decrease (-1090%) of the total radioactivity detected in the (17-19)S thyroglobulin fraction. Estimation of thyroglobulin by RIA gave similar though less pronounced effects. These experiments prove (1) that thyroglobulin is still expressed in these OVNIS thyroid cell lines even after 3 years of permanent culture, (2) that TSH modulates the level of this protein through a TSH-receptor functional system.

  17. The JCMT Legacy Survey of the Gould Belt: a molecular line study of the Ophiuchus molecular cloud

    CERN Document Server

    White, Glenn J; Rosolowsky, Erik; Ward-Thompson, Derek; Davis, C J; Gregson, Jon; Hatchell, Jenny; Etxaluze, Mireya; Stickler, Sarah; Buckle, Jane; Johnstone, Doug; Friesen, Rachel; Sadavoy, Sarah; Natt, Kieran V; Currie, Malcolm; Richer, J S; Pattle, Kate; Spaans, Marco; Di Francesco, James; Hogerheijde, M R

    2014-01-01

    CO, $^{13}$CO and C$^{18}$O ${\\it J}$ = 3--2 observations are presented of the Ophiuchus molecular cloud. The $^{13}$CO and C$^{18}$O emission is dominated by the Oph A clump, and the Oph B1, B2, C, E, F and J regions. The optically thin(ner) C$^{18}$O line is used as a column density tracer, from which the gravitational binding energy is estimated to be $4.5 \\times 10^{39}$ J (2282 $M_\\odot$ km$^2$ s$^{-2}$). The turbulent kinetic energy is $6.3 \\times 10^{38}$ J (320 $M_\\odot$ km$^2$ s$^{-2}$), or 7 times less than this, and therefore the Oph cloud as a whole is gravitationally bound. Thirty protostars were searched for high velocity gas, with eight showing outflows, and twenty more having evidence of high velocity gas along their lines-of-sight. The total outflow kinetic energy is $1.3 \\times 10^{38}$ J (67 $M_\\odot$ km$^2$ s$^{-2}$), corresponding to 21$\\%$ of the cloud?s turbulent kinetic energy. Although turbulent injection by outflows is significant, but does ${\\it not}$ appear to be the dominant sourc...

  18. Cell death in mammalian cell culture: molecular mechanisms and cell line engineering strategies.

    Science.gov (United States)

    Krampe, Britta; Al-Rubeai, Mohamed

    2010-07-01

    Cell death is a fundamentally important problem in cell lines used by the biopharmaceutical industry. Environmental stress, which can result from nutrient depletion, by-product accumulation and chemical agents, activates through signalling cascades regulators that promote death. The best known key regulators of death process are the Bcl-2 family proteins which constitute a critical intracellular checkpoint of apoptosis cell death within a common death pathway. Engineering of several members of the anti-apoptosis Bcl-2 family genes in several cell types has extended the knowledge of their molecular function and interaction with other proteins, and their regulation of cell death. In this review, we describe the various modes of cell death and their death pathways at molecular and organelle level and discuss the relevance of the growing knowledge of anti-apoptotic engineering strategies to inhibit cell death and increase productivity in mammalian cell culture.

  19. Stacking Spectra in Protoplanetary Disks: Detecting Intensity Profiles from Hidden Molecular Lines in HD 163296

    CERN Document Server

    Yen, Hsi-Wei; Liu, Hauyu Baobab; Puspitaningrum, Evaria; Hirano, Naomi; Lee, Chin-Fei; Takakuwa, Shigehisa

    2016-01-01

    We introduce a new stacking method in Keplerian disks that (1) enhances signal-to-noise ratios (S/N) of detected molecular lines and (2) that makes visible otherwise undetectable weak lines. Our technique takes advantage of the Keplerian rotational velocity pattern. It aligns spectra according to their different centroid velocities at their different positions in a disk and stacks them. After aligning, the signals are accumulated in a narrower velocity range as compared to the original line width without alignment. Moreover, originally correlated noise becomes de-correlated. Stacked and aligned spectra, thus, have a higher S/N. We apply our method to ALMA archival data of DCN (3-2), DCO+ (3-2), N2D+ (3-2), and H2CO (3_0,3-2_0,2), (3_2,2-2_2,1), and (3_2,1-2_2,0) in the protoplanetary disk around HD 163296. As a result, (1) the S/N of the originally detected DCN (3-2), DCO+ (3-2), and H2CO (3_0,3-2_0,2) and N2D+ (3-2) lines are boosted by a factor of >4-5 at their spectral peaks, implying one order of magnitud...

  20. Identifying ligand binding sites and poses using GPU-accelerated Hamiltonian replica exchange molecular dynamics.

    Science.gov (United States)

    Wang, Kai; Chodera, John D; Yang, Yanzhi; Shirts, Michael R

    2013-12-01

    We present a method to identify small molecule ligand binding sites and poses within a given protein crystal structure using GPU-accelerated Hamiltonian replica exchange molecular dynamics simulations. The Hamiltonians used vary from the physical end state of protein interacting with the ligand to an unphysical end state where the ligand does not interact with the protein. As replicas explore the space of Hamiltonians interpolating between these states, the ligand can rapidly escape local minima and explore potential binding sites. Geometric restraints keep the ligands from leaving the vicinity of the protein and an alchemical pathway designed to increase phase space overlap between intermediates ensures good mixing. Because of the rigorous statistical mechanical nature of the Hamiltonian exchange framework, we can also extract binding free energy estimates for all putative binding sites. We present results of this methodology applied to the T4 lysozyme L99A model system for three known ligands and one non-binder as a control, using an implicit solvent. We find that our methodology identifies known crystallographic binding sites consistently and accurately for the small number of ligands considered here and gives free energies consistent with experiment. We are also able to analyze the contribution of individual binding sites to the overall binding affinity. Our methodology points to near term potential applications in early-stage structure-guided drug discovery.

  1. Molecular markers for identifying a new selected variety of Pacific white shrimp Litopenaeus vannamei

    Science.gov (United States)

    Yu, Yang; Zhang, Xiaojun; Liu, Jingwen; Li, Fuhua; Huang, Hao; Li, Yijun; Liu, Xiaolin; Xiang, Jianhai

    2015-01-01

    Selective breeding of the Pacific white shrimp Litopenaeus vannamei during the last decade has produced new varieties exhibiting high growth rates and disease resistance. However, the identification of new varieties of shrimps from their phenotypic characters is difficult. This study introduces a new approach for identifying varieties of shrimps using molecular markers of microsatellites and mitochondrial control region sequences. The method was employed to identify a new selected variety, Kehai No. 1 (KH-1), from three representative stocks (control group): Zhengda; Tongwei; and a stock collected from Fujian Province, which is now cultured in mainland China. By pooled genotyping of KH-1 and the control group, five microsatellites showing differences between KH-1 and the control group were screened out. Individual genotyping data confirmed the results from pooled genotyping. The genotyping data for the five microsatellites were applied to the assignment analysis of the KH-1 group and the control group using the partial Bayesian assignment method in GENECLASS2. By sequencing the mitochondrial control regions of individuals from the KH-1 and control group, four haplotypes were observed in the KH-1 group, whereas 14 haplotypes were obtained in the control group. By combining the microsatellite assignment analysis with mitochondrial control region analysis, the average accuracy of identification of individuals in the KH-1 group and control group reached 89%. The five selected microsatellite loci and mitochondrial control region sequences were highly polymorphic and could be used to distinguish new selected varieties of L. vannamei from other populations cultured in China.

  2. Barriers Prevent Patient Access to Personalized Therapies Identified by Molecular Tumor Profiling of Gynecologic Malignancies

    Directory of Open Access Journals (Sweden)

    R. Tyler Hillman

    2015-05-01

    Full Text Available Objective. This study was designed to evaluate the ability of commercial molecular tumor profiling to discover actionable mutations and to identify barriers that might prevent patient access to personalized therapies. Methods. We conducted an IRB-approved retrospective review of 26 patients with gynecologic malignancies who underwent commercial tumor profiling at our institution during the first 18 months of test availability. Tumor profiles reported targeted therapies and clinical trials matched to patient-specific mutations. Data analysis consisted of descriptive statistics. Results. Most patients who underwent tumor profiling had serous epithelial ovarian, primary peritoneal, or fallopian tube carcinoma (46%. Patients underwent profiling after undergoing a median of two systemic therapies (range 0 to 13. A median of one targeted therapy was suggested per patient profile. Tumor profiling identified no clinically actionable mutations for seven patients (27%. Six patients sought insurance approval for a targeted therapy and two were declined (33%. One patient (4% received a targeted therapy and this was discontinued due to tumor progression. Conclusions. There are formidable barriers to targeted therapy for patients with gynecologic malignancies. These barriers include a dearth of FDA-approved targeted agents for gynecologic malignancies, lack of third party insurance coverage and limited geographic availability of clinical trials.

  3. Development of SNP-based dCAPS markers for identifying male sterile gene tms5 in two-line hybrid rice.

    Science.gov (United States)

    Song, F S; Ni, J L; Qian, Y L; Li, L; Ni, D H; Yang, J B

    2016-08-29

    Molecular markers can increase both the efficiency and speed of breeding programs. Functional markers that detect the functional mutations causing phenotypic changes offer a precise method for genetic identification. In this study, we used newly derived cleaved amplified polymorphic sequence markers to detect the functional mutations of tms5, which is a male sterile gene that is widely used in rice production in China. In addition, restriction cutting sites were designed to specifically digest amplicons of tms5 but not wild type (TMS5), in order to avoid the risk of false positive results. By optimizing the condition of the polymerase chain reaction amplifications and restriction enzyme digestions, the newly designed markers could accurately distinguish between tms5 and TMS5. These markers can be applied in marker-assisted selection for breeding novel thermo-sensitive genic male sterile (TGMS) lines, as well as to rapidly identify the TGMS hybrid seed purity.

  4. SPECTRAL LINE SURVEY TOWARD MOLECULAR CLOUDS IN THE LARGE MAGELLANIC CLOUD

    Energy Technology Data Exchange (ETDEWEB)

    Nishimura, Yuri; Watanabe, Yoshimasa; Yamamoto, Satoshi [Department of Physics, the University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-0033 (Japan); Shimonishi, Takashi [Frontier Research Institute for Interdisciplinary Sciences, Tohoku University, Aramakiazaaoba 6-3, Aoba-ku, Sendai, Miyagi, 980-8578 (Japan); Sakai, Nami [RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Aikawa, Yuri [Center for Computational Sciences, The University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki 305-8577 (Japan); Kawamura, Akiko [National Astronomical Observatory of Japan, Osawa, Mitaka, Tokyo, 181-8588 (Japan)

    2016-02-20

    Spectral line survey observations of seven molecular clouds in the Large Magellanic Cloud (LMC) have been conducted in the 3 mm band with the Mopra 22 m telescope to reveal chemical compositions in low metallicity conditions. Spectral lines of fundamental species such as CS, SO, CCH, HCN, HCO{sup +}, and HNC are detected in addition to those of CO and {sup 13}CO, while CH{sub 3}OH is not detected in any source and N{sub 2}H{sup +} is marginally detected in two sources. The molecular-cloud scale (10 pc scale) chemical composition is found to be similar among the seven sources regardless of different star formation activities, and hence, it represents the chemical composition characteristic of the LMC without influences by star formation activities. In comparison with chemical compositions of Galactic sources, the characteristic features are (1) deficient N-bearing molecules, (2) abundant CCH, and (3) deficient CH{sub 3}OH. Feature (1) is due to a lower elemental abundance of nitrogen in the LMC, whereas features (2) and (3) seem to originate from extended photodissociation regions and warmer temperature in cloud peripheries due to a lower abundance of dust grains in the low metallicity condition. In spite of general resemblance of chemical abundances among the seven sources, the CS/HCO{sup +} and SO/HCO{sup +} ratios are found to be slightly higher in a quiescent molecular cloud. An origin of this trend is discussed in relation to possible depletion of sulfur along the molecular cloud formation.

  5. Attempt to identify the functional areas of the cerebral cortex on CT slices parallel to the orbito-meatal line

    Energy Technology Data Exchange (ETDEWEB)

    Tanabe, Hirotaka; Okuda, Junichiro; Nishikawa, Takashi; Nishimura, Tsuyoshi (Osaka Univ. (Japan). Faculty of Medicine); Shiraishi, Junzo

    1982-06-01

    In order to identify the functional brain areas, such as Broca's area, on computed tomography slices parallel to the orbito-meatal line, the numbers of Brodmann's cortical mapping were shown on a diagram of representative brain sections parallel to the orbito-meatal line. Also, we described a method, using cerebral sulci as anatomical landmarks, for projecting lesions shown by CT scan onto the lateral brain diagram. The procedures were as follows. The distribution of lesions on CT slices was determined by the identification of major cerebral sulci and fissures, such as the Sylvian fissure, the central sulcus, and the superior frontal sulcus. Those lesions were then projected onto the lateral diagram by comparing each CT slice with the horizontal diagrams of brain sections. The method was demonstrated in three cases developing neuropsychological symptoms.

  6. Comparative analyses identify molecular signature of MRI-classified SVZ-associated glioblastoma.

    Science.gov (United States)

    Lin, Chin-Hsing Annie; Rhodes, Christopher T; Lin, ChenWei; Phillips, Joanna J; Berger, Mitchel S

    2017-04-18

    Glioblastoma (GBM) is a highly aggressive brain cancer with limited therapeutic options. While efforts to identify genes responsible for GBM have revealed mutations and aberrant gene expression associated with distinct types of GBM, patients with GBM are often diagnosed and classified based on MRI features. Therefore, we seek to identify molecular representatives in parallel with MRI classification for group I and group II primary GBM associated with the subventricular zone (SVZ). As group I and II GBM contain stem-like signature, we compared gene expression profiles between these 2 groups of primary GBM and endogenous neural stem progenitor cells to reveal dysregulation of cell cycle, chromatin status, cellular morphogenesis, and signaling pathways in these 2 types of MRI-classified GBM. In the absence of IDH mutation, several genes associated with metabolism are differentially expressed in these subtypes of primary GBM, implicating metabolic reprogramming occurs in tumor microenvironment. Furthermore, histone lysine methyltransferase EZH2 was upregulated while histone lysine demethylases KDM2 and KDM4 were downregulated in both group I and II primary GBM. Lastly, we identified 9 common genes across large data sets of gene expression profiles among MRI-classified group I/II GBM, a large cohort of GBM subtypes from TCGA, and glioma stem cells by unsupervised clustering comparison. These commonly upregulated genes have known functions in cell cycle, centromere assembly, chromosome segregation, and mitotic progression. Our findings highlight altered expression of genes important in chromosome integrity across all GBM, suggesting a common mechanism of disrupted fidelity of chromosome structure in GBM.

  7. Molecular basis for vulnerability to mitochondrial and oxidative stress in a neuroendocrine CRI-G1 cell line.

    Directory of Open Access Journals (Sweden)

    Natasha Chandiramani

    Full Text Available BACKGROUND: Many age-associated disorders (including diabetes, cancer, and neurodegenerative diseases are linked to mitochondrial dysfunction, which leads to impaired cellular bioenergetics and increased oxidative stress. However, it is not known what genetic and molecular pathways underlie differential vulnerability to mitochondrial dysfunction observed among different cell types. METHODOLOGY/PRINCIPAL FINDINGS: Starting with an insulinoma cell line as a model for a neuronal/endocrine cell type, we isolated a novel subclonal line (named CRI-G1-RS that was more susceptible to cell death induced by mitochondrial respiratory chain inhibitors than the parental CRI-G1 line (renamed CRI-G1-RR for clarity. Compared to parental RR cells, RS cells were also more vulnerable to direct oxidative stress, but equally vulnerable to mitochondrial uncoupling and less vulnerable to protein kinase inhibition-induced apoptosis. Thus, differential vulnerability to mitochondrial toxins between these two cell types likely reflects differences in their ability to handle metabolically generated reactive oxygen species rather than differences in ATP production/utilization or in downstream apoptotic machinery. Genome-wide gene expression analysis and follow-up biochemical studies revealed that, in this experimental system, increased vulnerability to mitochondrial and oxidative stress was associated with (1 inhibition of ARE/Nrf2/Keap1 antioxidant pathway; (2 decreased expression of antioxidant and phase I/II conjugation enzymes, most of which are Nrf2 transcriptional targets; (3 increased expression of molecular chaperones, many of which are also considered Nrf2 transcriptional targets; (4 increased expression of β cell-specific genes and transcription factors that specify/maintain β cell fate; and (5 reconstitution of glucose-stimulated insulin secretion. CONCLUSIONS/SIGNIFICANCE: The molecular profile presented here will enable identification of individual genes or

  8. Utilization of molecular methods to identify prognostic markers for recurrent bacterial vaginosis.

    Science.gov (United States)

    Hilbert, David W; Smith, William L; Paulish-Miller, Teresa E; Chadwick, Sean G; Toner, Geoffrey; Mordechai, Eli; Adelson, Martin E; Sobel, Jack D; Gygax, Scott E

    2016-10-01

    Recurrent bacterial vaginosis (BV) after antimicrobial therapy is a major problem, affecting >50% of patients within 1 year. The objective of this study was to determine if prospective identification of patients at risk for recurrence using molecular methods is feasible. Women were evaluated for BV by Amsel criteria and Nugent score. Vaginal specimens were analyzed using a panel of quantitative real-time polymerase chain reactions (qPCRs) at three times: pre-treatment, 7-10days post-treatment and 40-45days post-treatment. The PCRs quantified DNA of the following organisms: Gardnerella vaginalis; Atopobium vaginae; Bacterial Vaginosis-Associated Bacteria-1 (BVAB1), -2 (BVAB2) and -3 (BVAB3); Leptotrichia/Sneathia; Megasphaera Phylotypes 1 and 2; and Lactobacillus spp. (L. crispatus, L. gasseri, L. iners and L. jensenii). Out of 84 women diagnosed with BV (Amsel ≥3 and Nugent ≥4), 77 (91.7%) were successfully treated after 7-10days (asymptomatic and Amsel of either 0 or 1 with elevated vaginal pH and Nugent ≤6). Of these 77 women, 46 (59.7%) remained cured after 40-45days and 31 (40.3%) developed recurrent BV. In univariate analysis, we found that women who would have recurrent BV during the study had greater concentrations of Megasphaera Phylotype 2 (P=0.001) and BVAB2 (P=0.015) at initial diagnosis and greater vaginal pH (P=0.030), higher Nugent score (P=0.043) and a greater concentration of G. vaginalis (P=0.012) post-treatment, when compared to women who were cured during the study. These differences largely remained when cure was defined as Nugent ≤3 or when only women treated with intravaginal metronidazole were evaluated. Molecular analysis of BV is a useful adjunct to clinical and microscopic analysis to prospectively identify patients at high risk for recurrent BV. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Cartography of Pathway Signal Perturbations Identifies Distinct Molecular Pathomechanisms in Malignant and Chronic Lung Diseases.

    Science.gov (United States)

    Arakelyan, Arsen; Nersisyan, Lilit; Petrek, Martin; Löffler-Wirth, Henry; Binder, Hans

    2016-01-01

    Lung diseases are described by a wide variety of developmental mechanisms and clinical manifestations. Accurate classification and diagnosis of lung diseases are the bases for development of effective treatments. While extensive studies are conducted toward characterization of various lung diseases at molecular level, no systematic approach has been developed so far. Here we have applied a methodology for pathway-centered mining of high throughput gene expression data to describe a wide range of lung diseases in the light of shared and specific pathway activity profiles. We have applied an algorithm combining a Pathway Signal Flow (PSF) algorithm for estimation of pathway activity deregulation states in lung diseases and malignancies, and a Self Organizing Maps algorithm for classification and clustering of the pathway activity profiles. The analysis results allowed clearly distinguish between cancer and non-cancer lung diseases. Lung cancers were characterized by pathways implicated in cell proliferation, metabolism, while non-malignant lung diseases were characterized by deregulations in pathways involved in immune/inflammatory response and fibrotic tissue remodeling. In contrast to lung malignancies, chronic lung diseases had relatively heterogeneous pathway deregulation profiles. We identified three groups of interstitial lung diseases and showed that the development of characteristic pathological processes, such as fibrosis, can be initiated by deregulations in different signaling pathways. In conclusion, this paper describes the pathobiology of lung diseases from systems viewpoint using pathway centered high-dimensional data mining approach. Our results contribute largely to current understanding of pathological events in lung cancers and non-malignant lung diseases. Moreover, this paper provides new insight into molecular mechanisms of a number of interstitial lung diseases that have been studied to a lesser extent.

  10. Standardization and Optimization of Intraoperative Molecular Imaging for Identifying Primary Pulmonary Adenocarcinomas.

    Science.gov (United States)

    Predina, Jarrod D; Okusanya, Olugbenga; D Newton, Andrew; Low, Philip; Singhal, Sunil

    2017-05-11

    Intraoperative molecular imaging (IMI) is an emerging technology used to locate pulmonary adenocarcinomas and identify positive margins during surgery. Background noise and tissue autofluorescence have been major obstacles. The goal of this study is to optimize the image quality of folate receptor alpha (FRα) targeted IMI for pulmonary adenocarcinomas by modifying emission data. A total of 15 lung cancer patients were enrolled in a pilot study. In the first cohort, FRα upregulation within pulmonary adenocarcinoma tumors was confirmed by analyzing specimens from five pulmonary adenocarcinoma patients with flow cytometry and immunohistochemistry. Next, in a cohort of five additional patients, autofluorescence of intrathoracic structures and tissues was quantified. Lastly, five patients with tumors at various depths from the pleural surface were enrolled and received the FRα-targeted optical contrast agent, EC17. In this final cohort, resected pulmonary adenocarcinomas were imaged at a wide range of fluorescence exposure times (0 to 200 ms), various laser powers, and with unique filter configurations. Tumor-to-noise ratio (TNR) for images was generated using region of interest software. Pulmonary adenocarcinomas highly express FRα. Significant autofluorescence from native thoracic tissues was found with the highest fluorescent signals at the bronchial stump (547 ± 98, range 423-699), the pulmonary artery (267 ± 64, range 200-374), and cortical bone (266 ± 17, range 243-287). High levels of autofluorescence were appreciated after systemic administration of EC17; however, TNR was improved by altering exposure settings at the time of the imaging. Optimal fluorescent exposure time occurs at 40 ms (25 frames/s). Exposure properties can be manipulated to maximize TNR thus allowing for successful intraoperative detection of pulmonary adenocarcinomas during surgery. Optimization of the conditions for intraoperative molecular imaging sets the stage for future

  11. Warm gas in the rotating disk of the Red Rectangle: accurate models of molecular line emission

    CERN Document Server

    Bujarrabal, V

    2013-01-01

    We aim to study the excitation conditions of the molecular gas in the rotating disk of the Red Rectangle, the only post-Asymptotic-Giant-Branch object in which the existence of an equatorial rotating disk has been demonstrated. For this purpose, we developed a complex numerical code that accurately treats radiative transfer in 2-D, adapted to the study of molecular lines from rotating disks. We present far-infrared Herschel/HIFI observations of the 12CO and 13CO J=6-5, J=10-9, and J=16-15 transitions in the Red Rectangle. We also present our code in detail and discuss the accuracy of its predictions, from comparison with well-tested codes. Theoretical line profiles are compared with the empirical data to deduce the physical conditions in the disk by means of model fitting. We conclude that our code is very efficient and produces reliable results. The comparison of the theoretical predictions with our observations reveals that the temperature of the Red Rectangle disk is typically ~ 100-150 K, about twice as h...

  12. Multi-line spectral imaging of dense cores in the Lupus molecular cloud

    CERN Document Server

    Benedettini, Milena; Burton, Micheal G; Viti, Serena; Molinari, Sergio; Caselli, Paola; Testi, Leonardo

    2011-01-01

    The molecular clouds Lupus 1, 3 and 4 were mapped with the Mopra telescope at 3 and 12 mm. Emission lines from high density molecular tracers were detected, i.e. NH$_3$ (1,1), NH$_3$ (2,2), N$_2$H$^+$ (1-0), HC$_3$N (3-2), HC$_3$N (10-9), CS (2-1), CH$_3$OH (2$_0-1_0$)A$^+$ and CH$_3$OH (2$_{-1}-1_{-1}$)E. Velocity gradients of more than 1 km s$^{-1}$ are present in Lupus 1 and 3 and multiple gas components are present in these clouds along some lines of sight. Lupus 1 is the cloud richest in high density cores, 8 cores were detected in it, 5 cores were detected in Lupus 3 and only 2 in Lupus 4. The intensity of the three species HC$_3$N, NH$_3$ and N$_2$H$^+$ changes significantly in the various cores: cores that are brighter in HC$_3$N are fainter or undetected in NH$_3$ and N$_2$H$^+$ and vice versa. We found that the column density ratios HC$_3$N/N$_2$H$^+$ and HC$_3$N/NH$_3$ change by one order of magnitude between the cores, indicating that also the chemical abundance of these species is different. The ...

  13. Evaluation of genetically modified sugarcane lines carrying Cry 1AC gene using molecular marker techniques.

    Science.gov (United States)

    Ismail, Roba M

    2013-01-01

    Five genetically modified insect resistant sugarcane lines harboring the Bt Cry 1AC gene to produce insecticidal proteins were compared with non-transgenic control by using three types of molecular marker techniques namely, RAPD, ISSR and AFLP. These techniques were applied on transgenic and non-transgenic plants to investigate the genetic variations, which may appear in sugarcane clones. This variation might demonstrate the genomic changes associated with the transformation process, which could change important molecular basis of various biological phenomena. Genetic variations were screened using 22 different RAPD primers, 10 ISSR primers and 13 AFLP primer combinations. Analysis of RAPD and ISSR banding patterns gave no exclusive evidence for genetic variations. Meanwhile, the percentage of polymorphic bands was 0.45% in each of RAPD and ISSR, while the polymorphism generated by AFLP analysis was 1.8%. The maximum percentage of polymorphic bands was 1.4%, 1.1% and 5.5% in RAPD, ISSR and AFLP, respectively. These results demonstrate that most transgenic lines showed genomic homogeneity and verified minor genomic changes. Dendrograms revealing the relationships among the transgenic and control plants were developed from the data of each of the three marker types.

  14. Spectral Line Survey toward Molecular Clouds in the Large Magellanic Cloud

    CERN Document Server

    Nishimura, Yuri; Watanabe, Yoshimasa; Sakai, Nami; Aikawa, Yuri; Kawamura, Akiko; Yamamoto, Satoshi

    2015-01-01

    Spectral line survey observations of 7 molecular clouds in the Large Magellanic Cloud (LMC) have been conducted in the 3 mm band with the Mopra 22 m telescope to reveal chemical compositions in low metallicity conditions. Spectral lines of fundamental species such as CS, SO, CCH, HCN, HCO+, and HNC are detected in addition to those of CO and 13CO, while CH3OH is not detected in any source and N2H+ is marginally detected in two sources. The molecular-cloud scale (10 pc scale) chemical composition is found to be similar among the 7 sources regardless of different star formation activities, and hence, it represents the chemical composition characteristic to the LMC without influences of star formation activities. In comparison with chemical compositions of Galactic sources, the characteristic features are (1) deficient N-bearing molecules, (2) abundant CCH, and (3) deficient CH3OH. The feature (1) is due to a lower elemental abundance of nitrogen in the LMC, whereas the features (2) and (3) seem to originate fro...

  15. A molecular line survey of the extreme carbon star CRL 3068 at millimeter wavelengths

    CERN Document Server

    Zhang, Yong; Nakashima, Jun-ichi

    2009-01-01

    We present the results of a molecular line survey of the extreme carbon star CRL 3068. The observations were carried out with the Arizona Radio Observatory (ARO) 12m telescope and the Heinrich Hertz Submillimeter Telescope (SMT) at the 2mm and 1.3mm atmospheric windows. The observations cover the frequency bands from 130--162 GHz and 219.5--267.5 GHz. The typical sensitivities achieved are T_R<15 mK and T_R<7 mK for the ARO 12m and SMT, respectively. Seventy two individual emission features belonging to 23 molecular species and isotopologues were detected. Only three faint lines remain unidentified. The species c-C3H, CH3CN, SiC2, and the isotopologues, C17O and C18O, HC15N, HN13C, C33S, C34S, 13CS, 29SiS, and 30SiS are detected in this object for the first time. Rotational diagram analysis is carried out to determine the column densities and excitation temperatures. The isotopic ratios of the elements C, N, O, S, and Si have also been estimated. The results are consistent with stellar CNO processing an...

  16. A reduced density-matrix theory of absorption line shape of molecular aggregate.

    Science.gov (United States)

    Yang, Mino

    2005-09-22

    A theory for the absorption line shape of molecular aggregates in condensed phase is formulated based on a reduced density-matrix approach. Intermolecular couplings in the aggregates are assumed to be weak (Förster type of energy transfer mechanism). The spin-Boson model is employed to include the effect of electron-phonon coupling. Using the projection operator technique, we derive kinetic equations for the reduced electronic density matrix associated with the absorption spectrum. General expressions of time-dependent rate constants in the kinetic equations are derived by using the cumulant expansion technique. The resulting time-dependent kinetic equations are solved numerically. We illustrate the applicability of the present theory by calculating the line shape of a dimer (a pair of donor and acceptor of energy transfer). For a J-aggregate type of molecular pair (with excitonic redshift), a tail appears on the blue side of the absorption spectrum due to the existence of inhomogeneity in electronic state mixing which is originated from the electron-phonon coupling.

  17. Observational Approach to Molecular Cloud Evolution with the Submillimeter CI Lines

    Science.gov (United States)

    Oka, T.; Yamamoto, S.; Mt. Fuji Submillimeter-Wave Telescope Group

    Neutral carbon atoms (CI) play important role both in chemistry and cooling processes of interstellar molecular clouds. It is thus crucial to explore its large area distribution to investigate formation processes and thermal balance of molecular clouds. We have constructed a 1.2 m submillimeter-wave telescope at the summit of Mt.Fuji. The telescope was designed for the exclusive use of surveying molecular clouds in two submillimeter CI lines, 3P1--3P0 (492 GHz) and 3P2--3P1 (809 GHz), of atomic carbon. It has been operated successfully during 4 observing seasons since July 1998 in a remote way from the Hongo campus of the University of Tokyo. We have already revealed large-scale CI 492 GHz distributions of many giant molecular clouds, including Orion MC, Taurus MC, DR15, DR21, NGC2264, M17, W3, W44, W51, Rosette MC, covering more than 40 square degrees of the sky. The distribution of CI 492 GHz emission is found to be different from those of the 13CO or C18O emission in some clouds. We found the spatial order of C+/CO/C from UV sources. This is the general property of the cloud illuminated by intense UV radiation, whereas it is apparently inconsistent with the standard photodissociation region (PDR) picture. We also found CI-rich areas (C/CO˜1) in several dark clouds without strong UV sources. These results are discussed in relation to formation processes of molecular clouds and dense cloud cores.

  18. Applying universal scaling laws to identify the best molecular design paradigms for second-order nonlinear optics

    CERN Document Server

    Perez-Moreno, Javier; Kuzyk, Mark G

    2016-01-01

    We apply scaling and the theory of the fundamental limits of the second-order molecular susceptibility to identify material classes with ultralarge nonlinear-optical response. Size effects are removed by normalizing all nonlinearities to get intrinsic values so that the scaling behavior of a series of molecular homologues can be determined. Several new figures of merit are proposed that quantify the desirable properties for molecules that can be designed by adding a sequence of repeat units, and used in the assessment of the data. Three molecular classes are found. They are characterized by sub-scaling, nominal scaling, or super-scaling. Super-scaling homologues most efficiently take advantage of increased size. We apply our approach to data currently available in the literature to identify the best super-scaling molecular paradigms with the aim of identifying desirable traits of new materials.

  19. A systems biology strategy to identify molecular mechanisms of action and protein indicators of traumatic brain injury.

    Science.gov (United States)

    Yu, Chenggang; Boutté, Angela; Yu, Xueping; Dutta, Bhaskar; Feala, Jacob D; Schmid, Kara; Dave, Jitendra; Tawa, Gregory J; Wallqvist, Anders; Reifman, Jaques

    2015-02-01

    The multifactorial nature of traumatic brain injury (TBI), especially the complex secondary tissue injury involving intertwined networks of molecular pathways that mediate cellular behavior, has confounded attempts to elucidate the pathology underlying the progression of TBI. Here, systems biology strategies are exploited to identify novel molecular mechanisms and protein indicators of brain injury. To this end, we performed a meta-analysis of four distinct high-throughput gene expression studies involving different animal models of TBI. By using canonical pathways and a large human protein-interaction network as a scaffold, we separately overlaid the gene expression data from each study to identify molecular signatures that were conserved across the different studies. At 24 hr after injury, the significantly activated molecular signatures were nonspecific to TBI, whereas the significantly suppressed molecular signatures were specific to the nervous system. In particular, we identified a suppressed subnetwork consisting of 58 highly interacting, coregulated proteins associated with synaptic function. We selected three proteins from this subnetwork, postsynaptic density protein 95, nitric oxide synthase 1, and disrupted in schizophrenia 1, and hypothesized that their abundance would be significantly reduced after TBI. In a penetrating ballistic-like brain injury rat model of severe TBI, Western blot analysis confirmed our hypothesis. In addition, our analysis recovered 12 previously identified protein biomarkers of TBI. The results suggest that systems biology may provide an efficient, high-yield approach to generate testable hypotheses that can be experimentally validated to identify novel mechanisms of action and molecular indicators of TBI.

  20. Low-variance RNAs identify Parkinson's disease molecular signature in blood.

    Science.gov (United States)

    Chikina, Maria D; Gerald, Christophe P; Li, Xianting; Ge, Yongchao; Pincas, Hanna; Nair, Venugopalan D; Wong, Aaron K; Krishnan, Arjun; Troyanskaya, Olga G; Raymond, Deborah; Saunders-Pullman, Rachel; Bressman, Susan B; Yue, Zhenyu; Sealfon, Stuart C

    2015-05-01

    The diagnosis of Parkinson's disease (PD) is usually not established until advanced neurodegeneration leads to clinically detectable symptoms. Previous blood PD transcriptome studies show low concordance, possibly resulting from the use of microarray technology, which has high measurement variation. The Leucine-rich repeat kinase 2 (LRRK2) G2019S mutation predisposes to PD. Using preclinical and clinical studies, we sought to develop a novel statistically motivated transcriptomic-based approach to identify a molecular signature in the blood of Ashkenazi Jewish PD patients, including LRRK2 mutation carriers. Using a digital gene expression platform to quantify 175 messenger RNA (mRNA) markers with low coefficients of variation (CV), we first compared whole-blood transcript levels in mouse models (1) overexpressing wild-type (WT) LRRK2, (2) overexpressing G2019S LRRK2, (3) lacking LRRK2 (knockout), and (4) and in WT controls. We then studied an Ashkenazi Jewish cohort of 34 symptomatic PD patients (both WT LRRK2 and G2019S LRRK2) and 32 asymptomatic controls. The expression profiles distinguished the four mouse groups with different genetic background. In patients, we detected significant differences in blood transcript levels both between individuals differing in LRRK2 genotype and between PD patients and controls. Discriminatory PD markers included genes associated with innate and adaptive immunity and inflammatory disease. Notably, gene expression patterns in levodopa-treated PD patients were significantly closer to those of healthy controls in a dose-dependent manner. We identify whole-blood mRNA signatures correlating with LRRK2 genotype and with PD disease state. This approach may provide insight into pathogenesis and a route to early disease detection.

  1. Molecular profiling of low grade serous ovarian tumours identifies novel candidate driver genes.

    Science.gov (United States)

    Hunter, Sally M; Anglesio, Michael S; Ryland, Georgina L; Sharma, Raghwa; Chiew, Yoke-Eng; Rowley, Simone M; Doyle, Maria A; Li, Jason; Gilks, C Blake; Moss, Phillip; Allan, Prue E; Stephens, Andrew N; Huntsman, David G; deFazio, Anna; Bowtell, David D; Gorringe, Kylie L; Campbell, Ian G

    2015-11-10

    Low grade serous ovarian tumours are a rare and under-characterised histological subtype of epithelial ovarian tumours, with little known of the molecular drivers and facilitators of tumorigenesis beyond classic oncogenic RAS/RAF mutations. With a move towards targeted therapies due to the chemoresistant nature of this subtype, it is pertinent to more fully characterise the genetic events driving this tumour type, some of which may influence response to therapy and/or development of drug resistance. We performed genome-wide high-resolution genomic copy number analysis (Affymetrix SNP6.0) and mutation hotspot screening (KRAS, BRAF, NRAS, HRAS, ERBB2 and TP53) to compare a large cohort of ovarian serous borderline tumours (SBTs, n = 57) with low grade serous carcinomas (LGSCs, n = 19). Whole exome sequencing was performed for 13 SBTs, nine LGSCs and one mixed low/high grade carcinoma. Copy number aberrations were detected in 61% (35/57) of SBTs, compared to 100% (19/19) of LGSCs. Oncogenic RAS/RAF/ERBB2 mutations were detected in 82.5% (47/57) of SBTs compared to 63% (12/19) of LGSCs, with NRAS mutations detected only in LGSC. Some copy number aberrations appeared to be enriched in LGSC, most significantly loss of 9p and homozygous deletions of the CDKN2A/2B locus. Exome sequencing identified BRAF, KRAS, NRAS, USP9X and EIF1AX as the most frequently mutated genes. We have identified markers of progression from borderline to LGSC and novel drivers of LGSC. USP9X and EIF1AX have both been linked to regulation of mTOR, suggesting that mTOR inhibitors may be a key companion treatment for targeted therapy trials of MEK and RAF inhibitors.

  2. Exploring star formation in high-z galaxies using atomic and molecular emission lines

    Science.gov (United States)

    Gullberg, Bitten

    2016-03-01

    The conditions under which stars are formed and the reasons for triggering and quenching of starburst events in high-z galaxies, are still not well understood. Studying the interstellar medium (ISM) and the morphology of high-z galaxies are therefore key points in order to understand galaxy evolution. The cosmic star formation rate density peaks between 1thesis presents three studies of the ISM in high-z galaxies and their morphologies by: Exploring the physical conditions of the ISM in a sample of dusty star-forming galaxies (DSFGs) using the relative observed line strength of ionised carbon ([CII]) and carbon monoxide (CO). We find that the line ratios can best be described by a medium of [CII] and CO emitting gas with a higher [CII] than CO excitation temperature, high CO optical depth tau(CO)>>1, and low to moderate [CII] optical depth tau(CII)2, pave the road for future investigations of the star-forming ISM in high-z galaxies, by illustrating the importance of multi-wavelength, fine structure- and molecular line studies.

  3. The molecular mechanism of different sensitivity of breast cancer cell lines to TRAIL

    Institute of Scientific and Technical Information of China (English)

    ZHANG Jindan; LIU Yanxin; LIU Shilian; ZHENG Dexian

    2004-01-01

    Although Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis of various cancer cells, some caner cell lines are resistant to TRAIL-induced cell death. To investigate the molecular mechanisms underlying TRAIL-resistance, two human breast cancer cell lines, MCF-7 (resistant to TRAIL) and MDA-MB-231 (sensitive to TRAIL), were used as a model system to analyze the different sensitivities to TRAIL cytotoxicity. PKCδ inhibitor rottlerin, but not MEK and ERK1/2 inhibitor U0126 nor PI3K inhibitor LY294002, was shown to enhance TRAIL-induced apoptosis in MCF-7 cells significantly, suggesting that PKCδ might play an important role in the resistance of MCF-7 cells to TRAIL. In contrast, rottlerin, U0126, and Ly294002 had no effect on MDA-MB-231 apoptosis induced by TRAIL under the same conditions. Further experiment showed that the combination of rottlerin and TRAIL cleaved PARP in the MCF-7 cells synergistically, but not in the MDA-MB-231 cells. The role of PKCδ in TRAIL-resistant MCF-7 cells was confirmed by knocking down the endogenous PKCδ expression using RNAi technology. Furthermore, caspase-3 reconstitution in MCF-7 cells was unable to alter PKCδ expression, suggesting that innate caspase-3 deficient in the cells does not cause PKCδ high expression. These data provide evidence for the first time that PKCδ plays a critical role in breast cancer cell lines to TRAIL cytotoxicity.

  4. Back to the sea twice: identifying candidate plant genes for molecular evolution to marine life

    Directory of Open Access Journals (Sweden)

    Reusch Thorsten BH

    2011-01-01

    Full Text Available Abstract Background Seagrasses are a polyphyletic group of monocotyledonous angiosperms that have adapted to a completely submerged lifestyle in marine waters. Here, we exploit two collections of expressed sequence tags (ESTs of two wide-spread and ecologically important seagrass species, the Mediterranean seagrass Posidonia oceanica (L. Delile and the eelgrass Zostera marina L., which have independently evolved from aquatic ancestors. This replicated, yet independent evolutionary history facilitates the identification of traits that may have evolved in parallel and are possible instrumental candidates for adaptation to a marine habitat. Results In our study, we provide the first quantitative perspective on molecular adaptations in two seagrass species. By constructing orthologous gene clusters shared between two seagrasses (Z. marina and P. oceanica and eight distantly related terrestrial angiosperm species, 51 genes could be identified with detection of positive selection along the seagrass branches of the phylogenetic tree. Characterization of these positively selected genes using KEGG pathways and the Gene Ontology uncovered that these genes are mostly involved in translation, metabolism, and photosynthesis. Conclusions These results provide first insights into which seagrass genes have diverged from their terrestrial counterparts via an initial aquatic stage characteristic of the order and to the derived fully-marine stage characteristic of seagrasses. We discuss how adaptive changes in these processes may have contributed to the evolution towards an aquatic and marine existence.

  5. Luminosity Functions of Spitzer Identified Protostars in Nine Nearby Molecular Clouds

    CERN Document Server

    Kryukova, E; Gutermuth, R A; Pipher, J; Allen, T S; Allen, L E; Myers, P C; Muzerolle, J

    2012-01-01

    We identify protostars in Spitzer surveys of nine star-forming molecular clouds within 1 kpc: Serpens, Perseus, Ophiuchus, Chamaeleon, Lupus, Taurus, Orion, Cep OB3, and Mon R2, which combined host over 700 protostar candidates. Our diverse cloud sample allows us to compare protostar luminosity functions in these varied environments. We combine photometry from 2MASS J, H, and Ks bands and Spitzer IRAC and MIPS 24 micron bands to create 1 - 24 micron spectral energy distributions (SEDs). Using protostars from the c2d survey with well-determined bolometric luminosities (Lbol), we derive a relationship between Lbol, L_MIR (integrated from 1 - 24 microns), and SED slope. Estimations of Lbol for protostar candidates are combined to create luminosity functions for each cloud. Contamination due to edge-on disks, reddened Class II sources, and galaxies is estimated and removed from the luminosity functions. We find that luminosity functions for high mass star forming clouds peak near 1 Lsun and show a tail extending ...

  6. Multiplatform molecular profiling identifies potentially targetable biomarkers in malignant phyllodes tumors of the breast.

    Science.gov (United States)

    Gatalica, Zoran; Vranic, Semir; Ghazalpour, Anatole; Xiu, Joanne; Ocal, Idris Tolgay; McGill, John; Bender, Ryan P; Discianno, Erin; Schlum, Aaron; Sanati, Souzan; Palazzo, Juan; Reddy, Sandeep; Pockaj, Barbara

    2016-01-12

    Malignant phyllodes tumor is a rare breast malignancy with sarcomatous overgrowth and with limited effective treatment options for recurrent and metastatic cases. Recent clinical trials indicated a potential for anti-angiogenic, anti-EGFR and immunotherapeutic approaches for patients with sarcomas, which led us to investigate these and other targetable pathways in malignant phyllodes tumor of the breast. Thirty-six malignant phyllodes tumors (including 8 metastatic tumors with two cases having matched primary and metastatic tumors) were profiled using gene sequencing, gene copy number analysis, whole genome expression, and protein expression. Whole genome expression analysis demonstrated consistent over-expression of genes involved in angiogenesis including VEGFA, Angiopoietin-2, VCAM1, PDGFRA, and PTTG1. EGFR protein overexpression was observed in 26/27 (96%) of cases with amplification of the EGFR gene in 8/24 (33%) cases. Two EGFR mutations were identified including EGFRvIII and a presumed pathogenic V774M mutation, respectively. The most common pathogenic mutations included TP53 (50%) and PIK3CA (15%). Cases with matched primary and metastatic tumors harbored identical mutations in both sites (PIK3CA/KRAS and RB1 gene mutations, respectively). Tumor expression of PD-L1 immunoregulatory protein was observed in 3/22 (14%) of cases. Overexpression of molecular biomarkers of increased angiogenesis, EGFR and immune checkpoints provides novel targeted therapy options in malignant phyllodes tumors of the breast.

  7. A novel molecular marker of breast cancer stem cells identified by cell-SELEX method.

    Science.gov (United States)

    Lu, Min; Zhou, Lei; Zheng, Xiaohui; Quan, Yi; Wang, Xiaoli; Zhou, Xinna; Ren, Jun

    2015-01-01

    Breast cancer stem cells (CSCs) are thought to initiate mammary tumors and render them resistant to anti-cancer therapies. However, there are currently no ideal biomarkers to identify this minority population in breast cancer. To find out the oligonucleotides with high specificity and affinity for mammosphere cells using a high capacity ssDNA library. We used the cell-SELEX (systematic evolution of ligands by exponential enrichment process) method. MCF-7 cells were cultured in serum-free media to form mammosphere cells as enriched stem cells, and were used as the positive target cells. The normal breast epithelial MCF-10A and MCF-7sal cells, which are MCF-7 cells treated with Salinomycin, were used as the negative target cells. We collected the ssDNA pools that were bound to positive target cells, and could not bind negative target cells. After 13 rounds of selection, we isolated the MS03 aptamer with high specificity and affinity for mammosphere cells. When compared with CD44(+)/CD24(-/low) cells, MS03(+) cells did not show any significant difference in sphere formation ability in vitro. In addition, 63.3% of MS03 aptamer-selected cells exhibited the CD44(+)/CD24(-/low) phenotype. Because the MS03 aptamer is synthesized easily and non-immunogenic, it is much more flexible than CD44/CD24 as a breast CSC biomarker. The MS03 aptamer may become a promising molecular probe during diagnostic and therapeutic applications in breast cancer.

  8. Toward an efficient approach to identify molecular scaffolds possessing selective or promiscuous compounds.

    Science.gov (United States)

    Yongye, Austin B; Medina-Franco, José L

    2013-10-01

    The concept of a recurrent scaffold present in a series of structures is common in medicinal drug discovery. We present a scaffold analysis of compounds screened across 100 sequence-unrelated proteins to identify scaffolds that drive promiscuity or selectivity. Selectivity and promiscuity play a major role in traditional and poly-pharmacological drug design considerations. The collection employed here is the first publicly available data set containing the complete screening profiles of more than 15 000 compounds from different sources. In addition, no scaffold analysis of this data set has been reported. The protocol described here employs the Molecular Equivalence Index tool to facilitate the selection of Bemis-Murcko frameworks in the data set, which contain at least five compounds and Scaffold Hunter to generate a hierarchical tree of scaffolds. The annotation of the scaffold tree with protein-binding profile data enabled the successful identification of mostly highly specific compounds, due to data set constraints. We also applied this approach to a public set of 1497 small molecules screened non-uniformly across a panel of 172 protein kinases. The approach is general and can be applied to any other data sets and activity readout.

  9. Deep RNA profiling identified CLOCK and molecular clock genes as pathophysiological signatures in collagen VI myopathy.

    Science.gov (United States)

    Scotton, Chiara; Bovolenta, Matteo; Schwartz, Elena; Falzarano, Maria Sofia; Martoni, Elena; Passarelli, Chiara; Armaroli, Annarita; Osman, Hana; Rodolico, Carmelo; Messina, Sonia; Pegoraro, Elena; D'Amico, Adele; Bertini, Enrico; Gualandi, Francesca; Neri, Marcella; Selvatici, Rita; Boffi, Patrizia; Maioli, Maria Antonietta; Lochmüller, Hanns; Straub, Volker; Bushby, Katherine; Castrignanò, Tiziana; Pesole, Graziano; Sabatelli, Patrizia; Merlini, Luciano; Braghetta, Paola; Bonaldo, Paolo; Bernardi, Paolo; Foley, Reghan; Cirak, Sebahattin; Zaharieva, Irina; Muntoni, Francesco; Capitanio, Daniele; Gelfi, Cecilia; Kotelnikova, Ekaterina; Yuryev, Anton; Lebowitz, Michael; Zhang, Xiping; Hodge, Brian A; Esser, Karyn A; Ferlini, Alessandra

    2016-04-15

    Collagen VI myopathies are genetic disorders caused by mutations in collagen 6 A1, A2 and A3 genes, ranging from the severe Ullrich congenital muscular dystrophy to the milder Bethlem myopathy, which is recapitulated by collagen-VI-null (Col6a1(-/-)) mice. Abnormalities in mitochondria and autophagic pathway have been proposed as pathogenic causes of collagen VI myopathies, but the link between collagen VI defects and these metabolic circuits remains unknown. To unravel the expression profiling perturbation in muscles with collagen VI myopathies, we performed a deep RNA profiling in both Col6a1(-/-)mice and patients with collagen VI pathology. The interactome map identified common pathways suggesting a previously undetected connection between circadian genes and collagen VI pathology. Intriguingly, Bmal1(-/-)(also known as Arntl) mice, a well-characterized model displaying arrhythmic circadian rhythms, showed profound deregulation of the collagen VI pathway and of autophagy-related genes. The involvement of circadian rhythms in collagen VI myopathies is new and links autophagy and mitochondrial abnormalities. It also opens new avenues for therapies of hereditary myopathies to modulate the molecular clock or potential gene-environment interactions that might modify muscle damage pathogenesis.

  10. In-Line Detection and Measurement of Molecular Contamination in Semiconductor Process Solutions

    Science.gov (United States)

    Wang, Jason; West, Michael; Han, Ye; McDonald, Robert C.; Yang, Wenjing; Ormond, Bob; Saini, Harmesh

    2005-09-01

    This paper discusses a fully automated metrology tool for detection and quantitative measurement of contamination, including cationic, anionic, metallic, organic, and molecular species present in semiconductor process solutions. The instrument is based on an electrospray ionization time-of-flight mass spectrometer (ESI-TOF/MS) platform. The tool can be used in diagnostic or analytical modes to understand process problems in addition to enabling routine metrology functions. Metrology functions include in-line contamination measurement with near real-time trend analysis. This paper discusses representative organic and molecular contamination measurement results in production process problem solving efforts. The examples include the analysis and identification of organic compounds in SC-1 pre-gate clean solution; urea, NMP (N-Methyl-2-pyrrolidone) and phosphoric acid contamination in UPW; and plasticizer and an organic sulfur-containing compound found in isopropyl alcohol (IPA). It is expected that these unique analytical and metrology capabilities will improve the understanding of the effect of organic and molecular contamination on device performance and yield. This will permit the development of quantitative correlations between contamination levels and process degradation. It is also expected that the ability to perform routine process chemistry metrology will lead to corresponding improvements in manufacturing process control and yield, the ability to avoid excursions and will improve the overall cost effectiveness of the semiconductor manufacturing process.

  11. ALMA resolves the torus of NGC 1068: continuum and molecular line emission

    CERN Document Server

    Garcia-Burillo, S; Almeida, C Ramos; Usero, A; Krips, M; Alonso-Herrero, A; Aalto, S; Casasola, V; Hunt, L K; Martin, S; Viti, S; Colina, L; Costagliola, F; Eckart, A; Fuente, A; Henkel, C; Marquez, I; Neri, R; Schinnerer, E; Tacconi, L J; van der Werf, P P

    2016-01-01

    We have used the Atacama Large Millimeter Array (ALMA) to map the emission of the CO(6-5) molecular line and the 432 {\\mu}m continuum emission from the 300 pc-sized circumnuclear disk (CND) of the nearby Seyfert 2 galaxy NGC 1068 with a spatial resolution of ~4 pc. These observations spatially resolve the CND and image, for the first time, the dust emission and the molecular gas distribution and kinematics from a 7-10 pc-diameter disk that represents the submillimeter counterpart of the putative torus of NGC 1068. We fitted the nuclear spectral energy distribution of the torus using ALMA and near and mid-infrared (NIR/MIR) data with CLUMPY models. The mass and radius of the best-fit solution for the torus are both consistent with the values derived from the ALMA data alone: Mgas_torus=(1+-0.3)x10^5 Msun and Rtorus=3.5+-0.5 pc. The dynamics of the molecular gas in the torus show non-circular motions and enhanced turbulence superposed on the rotating pattern of the disk. The kinematic major axis of the CO torus...

  12. Inhibitors of alphavirus entry and replication identified with a stable Chikungunya replicon cell line and virus-based assays.

    Directory of Open Access Journals (Sweden)

    Leena Pohjala

    Full Text Available Chikungunya virus (CHIKV, an alphavirus, has recently caused epidemic outbreaks and is therefore considered a re-emerging pathogen for which no effective treatment is available. In this study, a CHIKV replicon containing the virus replicase proteins together with puromycin acetyltransferase, EGFP and Renilla luciferase marker genes was constructed. The replicon was transfected into BHK cells to yield a stable cell line. A non-cytopathic phenotype was achieved by a Pro718 to Gly substitution and a five amino acid insertion within non-structural protein 2 (nsP2, obtained through selection for stable growth. Characterization of the replicon cell line by Northern blotting analysis revealed reduced levels of viral RNA synthesis. The CHIKV replicon cell line was validated for antiviral screening in 96-well format and used for a focused screen of 356 compounds (natural compounds and clinically approved drugs. The 5,7-dihydroxyflavones apigenin, chrysin, naringenin and silybin were found to suppress activities of EGFP and Rluc marker genes expressed by the CHIKV replicon. In a concomitant screen against Semliki Forest virus (SFV, their anti-alphaviral activity was confirmed and several additional inhibitors of SFV with IC₅₀ values between 0.4 and 24 µM were identified. Chlorpromazine and five other compounds with a 10H-phenothiazinyl structure were shown to inhibit SFV entry using a novel entry assay based on a temperature-sensitive SFV mutant. These compounds also reduced SFV and Sindbis virus-induced cytopathic effect and inhibited SFV virion production in virus yield experiments. Finally, antiviral effects of selected compounds were confirmed using infectious CHIKV. In summary, the presented approach for discovering alphaviral inhibitors enabled us to identify potential lead structures for the development of alphavirus entry and replication phase inhibitors as well as demonstrated the usefulness of CHIKV replicon and SFV as biosafe surrogate

  13. Inhibitors of alphavirus entry and replication identified with a stable Chikungunya replicon cell line and virus-based assays.

    Science.gov (United States)

    Pohjala, Leena; Utt, Age; Varjak, Margus; Lulla, Aleksei; Merits, Andres; Ahola, Tero; Tammela, Päivi

    2011-01-01

    Chikungunya virus (CHIKV), an alphavirus, has recently caused epidemic outbreaks and is therefore considered a re-emerging pathogen for which no effective treatment is available. In this study, a CHIKV replicon containing the virus replicase proteins together with puromycin acetyltransferase, EGFP and Renilla luciferase marker genes was constructed. The replicon was transfected into BHK cells to yield a stable cell line. A non-cytopathic phenotype was achieved by a Pro718 to Gly substitution and a five amino acid insertion within non-structural protein 2 (nsP2), obtained through selection for stable growth. Characterization of the replicon cell line by Northern blotting analysis revealed reduced levels of viral RNA synthesis. The CHIKV replicon cell line was validated for antiviral screening in 96-well format and used for a focused screen of 356 compounds (natural compounds and clinically approved drugs). The 5,7-dihydroxyflavones apigenin, chrysin, naringenin and silybin were found to suppress activities of EGFP and Rluc marker genes expressed by the CHIKV replicon. In a concomitant screen against Semliki Forest virus (SFV), their anti-alphaviral activity was confirmed and several additional inhibitors of SFV with IC₅₀ values between 0.4 and 24 µM were identified. Chlorpromazine and five other compounds with a 10H-phenothiazinyl structure were shown to inhibit SFV entry using a novel entry assay based on a temperature-sensitive SFV mutant. These compounds also reduced SFV and Sindbis virus-induced cytopathic effect and inhibited SFV virion production in virus yield experiments. Finally, antiviral effects of selected compounds were confirmed using infectious CHIKV. In summary, the presented approach for discovering alphaviral inhibitors enabled us to identify potential lead structures for the development of alphavirus entry and replication phase inhibitors as well as demonstrated the usefulness of CHIKV replicon and SFV as biosafe surrogate models for anti

  14. Molecular line contamination in the SCUBA-2 450 {\\mu}m and 850 {\\mu}m continuum data

    CERN Document Server

    Drabek, E; Friberg, P; Richer, J; Graves, S; Buckle, J V; Nutter, D; Johnstone, D; Di Francesco, J

    2012-01-01

    Observations of the dust emission using millimetre/submillimetre bolometer arrays can be contaminated by molecular line flux, such as flux from 12CO. As the brightest molecular line in the submillimetre, it is important to quantify the contribution of CO flux to the dust continuum bands. Conversion factors were used to convert molecular line integrated intensities to flux detected by bolometer arrays in mJy per beam. These factors were calculated for 12CO line integrated intensities to the SCUBA-2 850 {\\mu}m and 450 {\\mu}m bands. The conversion factors were then applied to HARP 12CO 3-2 maps of NGC 1333 in the Perseus complex and NGC 2071 and NGC 2024 in the Orion B molecular cloud complex to quantify the respective 12CO flux contribution to the 850 {\\mu}m dust continuum emission. Sources with high molecular line contamination were analysed in further detail for molecular outflows and heating by nearby stars to determine the cause of the 12CO contribution. The majority of sources had a 12CO 3-2 flux contribut...

  15. Molecular evolution of rbcL in three gymnosperm families: identifying adaptive and coevolutionary patterns

    LENUS (Irish Health Repository)

    Sen, Lin

    2011-06-03

    Abstract Background The chloroplast-localized ribulose-1, 5-biphosphate carboxylase\\/oxygenase (Rubisco), the primary enzyme responsible for autotrophy, is instrumental in the continual adaptation of plants to variations in the concentrations of CO2. The large subunit (LSU) of Rubisco is encoded by the chloroplast rbcL gene. Although adaptive processes have been previously identified at this gene, characterizing the relationships between the mutational dynamics at the protein level may yield clues on the biological meaning of such adaptive processes. The role of such coevolutionary dynamics in the continual fine-tuning of RbcL remains obscure. Results We used the timescale and phylogenetic analyses to investigate and search for processes of adaptive evolution in rbcL gene in three gymnosperm families, namely Podocarpaceae, Taxaceae and Cephalotaxaceae. To understand the relationships between regions identified as having evolved under adaptive evolution, we performed coevolutionary analyses using the software CAPS. Importantly, adaptive processes were identified at amino acid sites located on the contact regions among the Rubisco subunits and on the interface between Rubisco and its activase. Adaptive amino acid replacements at these regions may have optimized the holoenzyme activity. This hypothesis was pinpointed by evidence originated from our analysis of coevolution that supported the correlated evolution between Rubisco and its activase. Interestingly, the correlated adaptive processes between both these proteins have paralleled the geological variation history of the concentration of atmospheric CO2. Conclusions The gene rbcL has experienced bursts of adaptations in response to the changing concentration of CO2 in the atmosphere. These adaptations have emerged as a result of a continuous dynamic of mutations, many of which may have involved innovation of functional Rubisco features. Analysis of the protein structure and the functional implications of such

  16. QTLs for straw quality characteristics identified in recombinant inbred lines of a Hordeum vulgare x H. spontaneum cross in a Mediterranean environment.

    Science.gov (United States)

    Grando, S; Baum, M; Ceccarelli, S; Goodchild, A; El-Haramein, F Jaby; Jahoor, A; Backes, G

    2005-02-01

    Barley straw is commonly used as animal feed in many developing countries. Even a small increase in its nutritive value can have a large impact on animal production, and hence, on rural livelihood and human nutrition. Straw quality is strongly affected by environmental factors and is, therefore, difficult to improve with empirical breeding. The objective of this study was to identify molecular markers to facilitate the improvement of straw quality in barley. For this purpose, we have used the genetic linkage map that was already developed for recombinant inbred lines (RILs) of the cross between a Hordeum vulgare cultivar ('Arta') and a H. spontaneum line (H. spontaneum 41-1), covering a total of 890 cM. Straw parameters from RILs grown at Tel Hadya and Breda (ICARDA's research stations) in 2 years (1996/1997 and 1997/1998) were analyzed by NIRS for predicted nutritional characteristics including neutral detergent fiber, acid detergent fiber, lignin, digestible organic matter in dry matter, voluntary intake, crude protein, and straw morphology (the percentage of blades, sheaths, and stems). Localization of QTLs was performed using Windows QTL Cartographer, version 2.0. Seventy-three QTLs were identified, the majority of which (17) in the driest of the four environments. Only six QTLs were identified in two environments; in five cases, one of the two was the wettest environment. This is discussed in relation to the possibility of improving straw quality in favorable environments where yields are higher, rather than in dry environments where straw quality is already relatively good.

  17. Quantitative trait loci analysis of flowering time related traits identified in recombinant inbred lines of cowpea (Vigna unguiculata).

    Science.gov (United States)

    Andargie, Mebeasealassie; Pasquet, Remy S; Muluvi, Geoffrey M; Timko, Michael P

    2013-05-01

    Flowering time is a major adaptive trait in plants and an important selection criterion in the breeding for genetic improvement of crop species. QTLs for the time of flower opening and days to flower were identified in a cross between a short duration domesticated cowpea (Vigna unguiculata (L.) Walp.) variety, 524B, and a relatively long duration wild accession, 219-01. A set of 159 F7 lines was grown under greenhouse conditions and scored for the flowering time associated phenotypes of time of flower opening and days to flower. Using a LOD threshold of 2.0, putative QTLs were identified and placed on a linkage map consisting of 202 SSR markers and four morphological loci. A total of five QTLs related to the time of flower opening were identified, accounting for 8.8%-29.8% of the phenotypic variation. Three QTLs for days to flower were detected, accounting for 5.7%-18.5% of the phenotypic variation. The major QTL of days to flower and time of flower opening were both mapped on linkage group 1. The QTLs identified in this study provide a strong foundation for further validation and fine mapping for developing an efficient way to restrain the gene flow between the cultivated and wild plants.

  18. LUMINOSITY FUNCTIONS OF SPITZER-IDENTIFIED PROTOSTARS IN NINE NEARBY MOLECULAR CLOUDS

    Energy Technology Data Exchange (ETDEWEB)

    Kryukova, E.; Megeath, S. T.; Allen, T. S. [Department of Physics and Astronomy, University of Toledo, Toledo, OH (United States); Gutermuth, R. A. [Department of Astronomy, University of Massachusetts, Amherst, MA (United States); Pipher, J. [Department of Physics and Astronomy, University of Rochester, Rochester, NY (United States); Allen, L. E. [National Optical Astronomy Observatories, Tucson, AZ (United States); Myers, P. C. [Harvard-Smithsonian Center for Astrophysics, Cambridge, MA (United States); Muzerolle, J. [Space Telescope Science Institute, Baltimore, MD (United States)

    2012-08-15

    We identify protostars in Spitzer surveys of nine star-forming (SF) molecular clouds within 1 kpc: Serpens, Perseus, Ophiuchus, Chamaeleon, Lupus, Taurus, Orion, Cep OB3, and Mon R2, which combined host over 700 protostar candidates. These clouds encompass a variety of SF environments, including both low-mass and high-mass SF regions, as well as dense clusters and regions of sparsely distributed star formation. Our diverse cloud sample allows us to compare protostar luminosity functions in these varied environments. We combine near- and mid-infrared photometry from the Two Micron All Sky Survey and Spitzer to create 1-24 {mu}m spectral energy distributions (SEDs). Using protostars from the c2d survey with well-determined bolometric luminosities, we derive a relationship between bolometric luminosity, mid-IR luminosity (integrated from 1-24 {mu}m), and SED slope. Estimations of the bolometric luminosities for protostar candidates are combined to create luminosity functions for each cloud. Contamination due to edge-on disks, reddened Class II sources, and galaxies is estimated and removed from the luminosity functions. We find that luminosity functions for high-mass SF clouds (Orion, Mon R2, and Cep OB3) peak near 1 L{sub Sun} and show a tail extending toward luminosities above 100 L{sub Sun }. The luminosity functions of the low-mass SF clouds (Serpens, Perseus, Ophiuchus, Taurus, Lupus, and Chamaeleon) do not exhibit a common peak, however the combined luminosity function of these regions peaks below 1 L{sub Sun }. Finally, we examine the luminosity functions as a function of the local surface density of young stellar objects. In the Orion molecular clouds, we find a significant difference between the luminosity functions of protostars in regions of high and low stellar density, the former of which is biased toward more luminous sources. This may be the result of primordial mass segregation, although this interpretation is not unique. We compare our luminosity

  19. Molecular line emission in NGC 1068 imaged with ALMA. II. The chemistry of the dense molecular gas

    Science.gov (United States)

    Viti, S.; García-Burillo, S.; Fuente, A.; Hunt, L. K.; Usero, A.; Henkel, C.; Eckart, A.; Martin, S.; Spaans, M.; Muller, S.; Combes, F.; Krips, M.; Schinnerer, E.; Casasola, V.; Costagliola, F.; Marquez, I.; Planesas, P.; van der Werf, P. P.; Aalto, S.; Baker, A. J.; Boone, F.; Tacconi, L. J.

    2014-10-01

    Aims: We present a detailed analysis of Atacama Large Millimeter/submillimeter Array (ALMA) Bands 7 and 9 data of CO, HCO+, HCN, and CS, augmented with Plateau de Bure Interferometer (PdBI) data of the ~200 pc circumnuclear disc (CND) and the ~1.3 kpc starburst ring (SB ring) of NGC 1068, a nearby (D = 14 Mpc) Seyfert 2 barred galaxy. We aim to determine the physical characteristics of the dense gas present in the CND, and to establish whether the different line intensity ratios we find within the CND, as well as between the CND and the SB ring, are due to excitation effects (gas density and temperature differences) or to a different chemistry. Methods: We estimate the column densities of each species in local thermodynamic equilibrium (LTE). We then compute large one-dimensional, non-LTE radiative transfer grids (using RADEX) by using only the CO transitions first, and then all the available molecules to constrain the densities, temperatures, and column densities within the CND. We finally present a preliminary set of chemical models to determine the origin of the gas. Results: We find that, in general, the gas in the CND is very dense (>105 cm-3) and hot (T> 150 K), with differences especially in the temperature across the CND. The AGN position has the lowest CO/HCO+, CO/HCN, and CO/CS column density ratios. The RADEX analyses seem to indicate that there is chemical differentiation across the CND. We also find differences between the chemistry of the SB ring and some regions of the CND; the SB ring is also much colder and less dense than the CND. Chemical modelling does not succeed in reproducing all the molecular ratios with one model per region, suggesting the presence of multi-gas phase components. Conclusions: The LTE, RADEX, and chemical analyses all indicate that more than one gas-phase component is necessary to uniquely fit all the available molecular ratios within the CND. A higher number of molecular transitions at the ALMA resolution is necessary to

  20. ALMA Resolves the Torus of NGC 1068: Continuum and Molecular Line Emission

    Science.gov (United States)

    García-Burillo, S.; Combes, F.; Ramos Almeida, C.; Usero, A.; Krips, M.; Alonso-Herrero, A.; Aalto, S.; Casasola, V.; Hunt, L. K.; Martín, S.; Viti, S.; Colina, L.; Costagliola, F.; Eckart, A.; Fuente, A.; Henkel, C.; Márquez, I.; Neri, R.; Schinnerer, E.; Tacconi, L. J.; van der Werf, P. P.

    2016-05-01

    We used the Atacama Large Millimeter Array (ALMA) to map the emission of the CO(6-5) molecular line and the 432 μm continuum emission from the 300 pc sized circumnuclear disk (CND) of the nearby Seyfert 2 galaxy NGC 1068 with a spatial resolution of ˜4 pc. These observations spatially resolve the CND and, for the first time, image the dust emission, the molecular gas distribution, and the kinematics from a 7-10 pc diameter disk that represents the submillimeter counterpart of the putative torus of NGC 1068. We fitted the nuclear spectral energy distribution of the torus using ALMA and near- and mid-infrared (NIR/MIR) data with CLUMPY torus models. The mass and radius of the best-fit solution for the torus are both consistent with the values derived from the ALMA data alone: {M}{{gas}}{{torus}}=(1+/- 0.3)× {10}5 {M}⊙ and R torus = 3.5 ± 0.5 pc. The dynamics of the molecular gas in the torus show strong non-circular motions and enhanced turbulence superposed on a surprisingly slow rotation pattern of the disk. By contrast with the nearly edge-on orientation of the H2O megamaser disk, we found evidence suggesting that the molecular torus is less inclined (i = 34°-66°) at larger radii. The lopsided morphology and complex kinematics of the torus could be the signature of the Papaloizou-Pringle instability, long predicted to likely drive the dynamical evolution of active galactic nuclei tori.

  1. Molecular line mapping of the giant molecular cloud associated with RCW 106 - IV. Ammonia towards dust emission

    CERN Document Server

    Lowe, Vicki; Urquhart, James S; Marshall, Jonathan P; Horiuchi, Shinji; Lo, Nadia; Walsh, Andrew J; Jordan, Christopher H; Jones, Paul A

    2014-01-01

    Here we report observations of the two lowest inversion transitions of ammonia with the 70-m Tidbinbilla radio telescope. They were conducted to determine the kinetic temperatures in the dense clumps of the G333 giant molecular cloud associated with RCW 106 and to examine the effect that accurate temperatures have on the calculation of derived quantities such as mass. This project is part of a larger investigation to understand the timescales and evolutionary sequence associated with high-mass star formation, particularly its earliest stages. Assuming that the initial chemical composition of a giant molecular cloud is uniform, any abundance variations within will be due to evolutionary state. We have identified 63 clumps using SIMBA 1.2-mm dust continuum maps and have calculated gas temperatures for most (78 per cent) of these dense clumps. After using Spitzer GLIMPSE 8.0 $\\mu$m emission to separate the sample into IR-bright and IR-faint clumps, we use statistical tests to examine whether our classification s...

  2. MOLECULAR LINE OBSERVATIONS OF MCLD 123.5+24.9 IN THE POLARIS CIRRUS

    Energy Technology Data Exchange (ETDEWEB)

    Shimoikura, Tomomi; Dobashi, Kazuhito; Sakurai, Tohko; Nishiura, Shingo [Department of Astronomy and Earth Sciences, Tokyo Gakugei University, Koganei, Tokyo 184-8501 (Japan); Takano, Shuro [Nobeyama Radio Observatory, National Astronomical Observatory of Japan, 462-2 Nobeyama, Minamimaki, Minamisaku, Nagano 384-1305 (Japan); Hirota, Tomoya, E-mail: ikura@u-gakugei.ac.jp [National Astronomical Observatory of Japan, Mitaka, Tokyo 181-8588 (Japan)

    2012-02-01

    In this paper, we present results of millimeter-wave observations with various molecular lines made toward MCLD 123.5+24.9 in the Polaris cirrus using the 45 m telescope at Nobeyama Radio Observatory. MCLD 123.5+24.9 is one of the rare dense cores forming in diffuse cirrus clouds where star formation may rarely take place. In order to investigate the structure, dynamics, the evolutionary stage of MCLD 123.5+24.9, we observed this core in 17 emission lines from 13 different molecular species. Emission lines of CS, CCS, and HC{sub 3}N are strongly detected all over the core, while those of SO and N{sub 2}H{sup +} are weak or remain undetected, indicating that MCLD 123.5+24.9 is in an early stage of core evolution in terms of chemical composition. Based on comparison of the fractional abundances of CCS and HC{sub 3}N, which are considered indicators of chemical age, with those of other cores with and without star formation as well as with model calculations in the literature, we suggest that MCLD 123.5+24.9 is in a phase prior to star formation. From the C{sup 18}O data obtained, we derived the total molecular mass of MCLD 123.5+24.9 to be {approx}3 M{sub Sun} at an assumed distance of 150 pc. There are three subcores in MCLD 123.5+24.9, called CS-A, CS-B, and CS-C. We derived their masses to be 0.2-0.6 M{sub Sun }. We also investigated the dynamical stability of MCLD 123.5+24.9 and the subcores by applying the virial theorem to find that MCLD 123.5+24.9 is not gravitationally bound as a whole, while the individual subcores are in the virial equilibrium and can collapse with a small increase of external pressure imposed on their surfaces.

  3. MHOs toward HMOs: A Search for Molecular Hydrogen Emission-Line Objects toward High-mass Outflows

    Science.gov (United States)

    Wolf-Chase, Grace; Arvidsson, Kim; Smutko, Michael

    2017-07-01

    We present the results of a narrow-band near-infrared imaging survey for Molecular Hydrogen emission-line Objects (MHOs) toward 26 regions containing high-mass protostellar candidates and massive molecular outflows. We have detected a total of 236 MHOs, 156 of which are new detections, in 22 out of the 26 regions. We use H2 2.12 μm/H2 2.25 μm flux ratios, together with morphology, to separate the signatures of fluorescence associated with photo-dissociation regions (PDRs) from shocks associated with outflows in order to identify the MHOs. PDRs have typical low flux ratios of ˜1.5-3, while the vast majority of MHOs display flux ratios typical of C-type shocks (˜6-20). A few MHOs exhibit flux ratios consistent with expected values for J-type shocks (˜3-4), but these are located in regions that may be contaminated with fluorescent emission. Some previously reported MHOs have low flux ratios, and are likely parts of PDRs rather than shocks indicative of outflows. We identify a total of 36 outflows across the 22 target regions where MHOs were detected. In over half these regions, MHO arrangements and fluorescent structures trace features present in CO outflow maps, suggesting that the CO emission traces a combination of dynamical effects, which may include gas entrained in expanding PDRs as well as bipolar outflows. Where possible, we link MHO complexes to distinct outflows and identify candidate driving sources.

  4. Applying universal scaling laws to identify the best molecular design paradigms for third-order nonlinear optics

    CERN Document Server

    Perez-Moreno, Javier; Kuzyk, Mark G

    2016-01-01

    The scaling of the fundamental limits of the second hyperpolarizability is used to define the intrinsic second hyperpolarizability, which aids in identifying material classes with ultralarge nonlinear-optical response per unit of molecular size. The intrinsic nonlinear response is a size-independent metric that we apply to comparing classes of molecular homologues, which are made by adding repeat units to extend their lengths. Several new figures of merit are proposed that quantify not only the intrinsic nonlinear response, but also how the second hyperpolarizability increases with size within a molecular class. Scaling types can be classified into sub-scaling, nominal scaling that follows the theory of limits, and super-scaling behavior. Super-scaling homologues that have large intrinsic nonlinearity are the most promising because they efficiently take advantage of increased size. We apply our approach to data in the literature to identify the best super-scaling molecular paradigms and articulate the importa...

  5. Statistical techniques to construct assays for identifying likely responders to a treatment under evaluation from cell line genomic data

    Directory of Open Access Journals (Sweden)

    Shi Xiaoyan

    2010-10-01

    Full Text Available Abstract Background Developing the right drugs for the right patients has become a mantra of drug development. In practice, it is very difficult to identify subsets of patients who will respond to a drug under evaluation. Most of the time, no single diagnostic will be available, and more complex decision rules will be required to define a sensitive population, using, for instance, mRNA expression, protein expression or DNA copy number. Moreover, diagnostic development will often begin with in-vitro cell-line data and a high-dimensional exploratory platform, only later to be transferred to a diagnostic assay for use with patient samples. In this manuscript, we present a novel approach to developing robust genomic predictors that are not only capable of generalizing from in-vitro to patient, but are also amenable to clinically validated assays such as qRT-PCR. Methods Using our approach, we constructed a predictor of sensitivity to dacetuzumab, an investigational drug for CD40-expressing malignancies such as lymphoma using genomic measurements of cell lines treated with dacetuzumab. Additionally, we evaluated several state-of-the-art prediction methods by independently pairing the feature selection and classification components of the predictor. In this way, we constructed several predictors that we validated on an independent DLBCL patient dataset. Similar analyses were performed on genomic measurements of breast cancer cell lines and patients to construct a predictor of estrogen receptor (ER status. Results The best dacetuzumab sensitivity predictors involved ten or fewer genes and accurately classified lymphoma patients by their survival and known prognostic subtypes. The best ER status classifiers involved one or two genes and led to accurate ER status predictions more than 85% of the time. The novel method we proposed performed as well or better than other methods evaluated. Conclusions We demonstrated the feasibility of combining feature

  6. Gene expression correlations in human cancer cell lines define molecular interaction networks for epithelial phenotype.

    Directory of Open Access Journals (Sweden)

    Kurt W Kohn

    Full Text Available Using gene expression data to enhance our knowledge of control networks relevant to cancer biology and therapy is a challenging but urgent task. Based on the premise that genes that are expressed together in a variety of cell types are likely to functions together, we derived mutually correlated genes that function together in various processes in epithelial-like tumor cells. Expression-correlated genes were derived from data for the NCI-60 human tumor cell lines, as well as data from the Broad Institute's CCLE cell lines. NCI-60 cell lines that selectively expressed a mutually correlated subset of tight junction genes served as a signature for epithelial-like cancer cells. Those signature cell lines served as a seed to derive other correlated genes, many of which had various other epithelial-related functions. Literature survey yielded molecular interaction and function information about those genes, from which molecular interaction maps were assembled. Many of the genes had epithelial functions unrelated to tight junctions, demonstrating that new function categories were elicited. The most highly correlated genes were implicated in the following epithelial functions: interactions at tight junctions (CLDN7, CLDN4, CLDN3, MARVELD3, MARVELD2, TJP3, CGN, CRB3, LLGL2, EPCAM, LNX1; interactions at adherens junctions (CDH1, ADAP1, CAMSAP3; interactions at desmosomes (PPL, PKP3, JUP; transcription regulation of cell-cell junction complexes (GRHL1 and 2; epithelial RNA splicing regulators (ESRP1 and 2; epithelial vesicle traffic (RAB25, EPN3, GRHL2, EHF, ADAP1, MYO5B; epithelial Ca(+2 signaling (ATP2C2, S100A14, BSPRY; terminal differentiation of epithelial cells (OVOL1 and 2, ST14, PRSS8, SPINT1 and 2; maintenance of apico-basal polarity (RAB25, LLGL2, EPN3. The findings provide a foundation for future studies to elucidate the functions of regulatory networks specific to epithelial-like cancer cells and to probe for anti-cancer drug targets.

  7. Novel high-molecular weight fucosylated milk oligosaccharides identified in dairy streams.

    Directory of Open Access Journals (Sweden)

    Raj Mehra

    Full Text Available Oligosaccharides are the third largest component in human milk. This abundance is remarkable because oligosaccharides are not digestible by the newborn, and yet they have been conserved and amplified during evolution. In addition to encouraging the growth of a protective microbiota dominated by bifidobacteria, oligosaccharides have anti-infective activity, preventing pathogens from binding to intestinal cells. Although it would be advantageous adding these valuable molecules to infant milk formula, the technologies to reproduce the variety and complexity of human milk oligosaccharides by enzymatic/organic synthesis are not yet mature. Consequently, there is an enormous interest in alternative sources of these valuable oligosaccharides. Recent research has demonstrated that bovine milk and whey permeate also contain oligosaccharides. Thus, a thorough characterization of oligosaccharides in bovine dairy streams is an important step towards fully assessing their specific functionalities. In this study, bovine milk oligosaccharides (BMOs were concentrated by membrane filtration from a readily available dairy stream called "mother liquor", and analyzed by high accuracy MALDI FT-ICR mass spectrometry. The combination of HPLC and accurate mass spectrometry allowed the identification of ideal processing conditions leading to the production of Kg amount of BMO enriched powders. Among the BMOs identified, 18 have high-molecular weight and corresponded in size to the most abundant oligosaccharides present in human milk. Notably 6 oligosaccharides contained fucose, a sugar monomer that is highly abundant in human milk, but is rarely observed in bovine milk. This work shows that dairy streams represent a potential source of complex milk oligosaccharides for commercial development of unique dairy ingredients in functional foods that reproduce the benefits of human milk.

  8. Subtracted diversity array identifies novel molecular markers including retrotransposons for fingerprinting Echinacea species.

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    Alexandra Olarte

    Full Text Available Echinacea, native to the Canadian prairies and the prairie states of the United States, has a long tradition as a folk medicine for the Native Americans. Currently, Echinacea are among the top 10 selling herbal medicines in the U.S. and Europe, due to increasing popularity for the treatment of common cold and ability to stimulate the immune system. However, the genetic relationship within the species of this genus is unclear, making the authentication of the species used for the medicinal industry more difficult. We report the construction of a novel Subtracted Diversity Array (SDA for Echinacea species and demonstrate the potential of this array for isolating highly polymorphic sequences. In order to selectively isolate Echinacea-specific sequences, a Suppression Subtractive Hybridization (SSH was performed between a pool of twenty-four Echinacea genotypes and a pool of other angiosperms and non-angiosperms. A total of 283 subtracted genomic DNA (gDNA fragments were amplified and arrayed. Twenty-seven Echinacea genotypes including four that were not used in the array construction could be successfully discriminated. Interestingly, unknown samples of E. paradoxa and E. purpurea could be unambiguously identified from the cluster analysis. Furthermore, this Echinacea-specific SDA was also able to isolate highly polymorphic retrotransposon sequences. Five out of the eleven most discriminatory features matched to known retrotransposons. This is the first time retrotransposon sequences have been used to fingerprint Echinacea, highlighting the potential of retrotransposons as based molecular markers useful for fingerprinting and studying diversity patterns in Echinacea.

  9. Subtracted Diversity Array Identifies Novel Molecular Markers Including Retrotransposons for Fingerprinting Echinacea Species

    Science.gov (United States)

    Olarte, Alexandra; Mantri, Nitin; Nugent, Gregory; Pang, Edwin C. K.

    2013-01-01

    Echinacea, native to the Canadian prairies and the prairie states of the United States, has a long tradition as a folk medicine for the Native Americans. Currently, Echinacea are among the top 10 selling herbal medicines in the U.S. and Europe, due to increasing popularity for the treatment of common cold and ability to stimulate the immune system. However, the genetic relationship within the species of this genus is unclear, making the authentication of the species used for the medicinal industry more difficult. We report the construction of a novel Subtracted Diversity Array (SDA) for Echinacea species and demonstrate the potential of this array for isolating highly polymorphic sequences. In order to selectively isolate Echinacea-specific sequences, a Suppression Subtractive Hybridization (SSH) was performed between a pool of twenty-four Echinacea genotypes and a pool of other angiosperms and non-angiosperms. A total of 283 subtracted genomic DNA (gDNA) fragments were amplified and arrayed. Twenty-seven Echinacea genotypes including four that were not used in the array construction could be successfully discriminated. Interestingly, unknown samples of E. paradoxa and E. purpurea could be unambiguously identified from the cluster analysis. Furthermore, this Echinacea-specific SDA was also able to isolate highly polymorphic retrotransposon sequences. Five out of the eleven most discriminatory features matched to known retrotransposons. This is the first time retrotransposon sequences have been used to fingerprint Echinacea, highlighting the potential of retrotransposons as based molecular markers useful for fingerprinting and studying diversity patterns in Echinacea. PMID:23940565

  10. Gene expression profiling identifies molecular pathways associated with collagen VI deficiency and provides novel therapeutic targets.

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    Sonia Paco

    Full Text Available Ullrich congenital muscular dystrophy (UCMD, caused by collagen VI deficiency, is a common congenital muscular dystrophy. At present, the role of collagen VI in muscle and the mechanism of disease are not fully understood. To address this we have applied microarrays to analyse the transcriptome of UCMD muscle and compare it to healthy muscle and other muscular dystrophies. We identified 389 genes which are differentially regulated in UCMD relative to controls. In addition, there were 718 genes differentially expressed between UCMD and dystrophin deficient muscle. In contrast, only 29 genes were altered relative to other congenital muscular dystrophies. Changes in gene expression were confirmed by real-time PCR. The set of regulated genes was analysed by Gene Ontology, KEGG pathways and Ingenuity Pathway analysis to reveal the molecular functions and gene networks associated with collagen VI defects. The most significantly regulated pathways were those involved in muscle regeneration, extracellular matrix remodelling and inflammation. We characterised the immune response in UCMD biopsies as being mainly mediated via M2 macrophages and the complement pathway indicating that anti-inflammatory treatment may be beneficial to UCMD as for other dystrophies. We studied the immunolocalisation of ECM components and found that biglycan, a collagen VI interacting proteoglycan, was reduced in the basal lamina of UCMD patients. We propose that biglycan reduction is secondary to collagen VI loss and that it may be contributing towards UCMD pathophysiology. Consequently, strategies aimed at over-expressing biglycan and restore the link between the muscle cell surface and the extracellular matrix should be considered.

  11. Gene Expression Profiling Identifies Molecular Pathways Associated with Collagen VI Deficiency and Provides Novel Therapeutic Targets

    Science.gov (United States)

    Paco, Sonia; Kalko, Susana G.; Jou, Cristina; Rodríguez, María A.; Corbera, Joan; Muntoni, Francesco; Feng, Lucy; Rivas, Eloy; Torner, Ferran; Gualandi, Francesca; Gomez-Foix, Anna M.; Ferrer, Anna; Ortez, Carlos; Nascimento, Andrés; Colomer, Jaume; Jimenez-Mallebrera, Cecilia

    2013-01-01

    Ullrich congenital muscular dystrophy (UCMD), caused by collagen VI deficiency, is a common congenital muscular dystrophy. At present, the role of collagen VI in muscle and the mechanism of disease are not fully understood. To address this we have applied microarrays to analyse the transcriptome of UCMD muscle and compare it to healthy muscle and other muscular dystrophies. We identified 389 genes which are differentially regulated in UCMD relative to controls. In addition, there were 718 genes differentially expressed between UCMD and dystrophin deficient muscle. In contrast, only 29 genes were altered relative to other congenital muscular dystrophies. Changes in gene expression were confirmed by real-time PCR. The set of regulated genes was analysed by Gene Ontology, KEGG pathways and Ingenuity Pathway analysis to reveal the molecular functions and gene networks associated with collagen VI defects. The most significantly regulated pathways were those involved in muscle regeneration, extracellular matrix remodelling and inflammation. We characterised the immune response in UCMD biopsies as being mainly mediated via M2 macrophages and the complement pathway indicating that anti-inflammatory treatment may be beneficial to UCMD as for other dystrophies. We studied the immunolocalisation of ECM components and found that biglycan, a collagen VI interacting proteoglycan, was reduced in the basal lamina of UCMD patients. We propose that biglycan reduction is secondary to collagen VI loss and that it may be contributing towards UCMD pathophysiology. Consequently, strategies aimed at over-expressing biglycan and restore the link between the muscle cell surface and the extracellular matrix should be considered. PMID:24223098

  12. A molecular line study towards massive extended green object clumps in the southern sky: chemical properties

    CERN Document Server

    Yu, Naiping

    2016-01-01

    We present a molecular line study towards 31 extended green object (EGO) clumps in the southern sky using data from MALT90 (Millimetre Astronomy Legacy Team 90 GHz). According to previous multiwavelength observations, we divide our sample into two groups: massive young stellar objects (MYSOs) and HII regions. Our results seem to support that N2H+ and C2H emissions mainly come from the gas inside quiescent clumps. In addition, we also find that the [N2H+]/[H13CO+] and [C2H]/[H13CO+] relative abundance ratios decrease from MYSOs to HII regions. These results suggest depletion of N2H+ and C2H in the late stages of massive-star formation, probably caused by the formation of HII regions inside. N2H+ and C2H might be used as chemical clocks for massive-star formation by comparing with other molecules such as H13CO+ and HC3N.

  13. Isotopic ratios at z=0.68 from molecular absorption lines toward B 0218+357

    CERN Document Server

    Wallstrom, S H J; Guelin, M

    2016-01-01

    Isotopic ratios of heavy elements are a key signature of the nucleosynthesis processes in stellar interiors. The contribution of successive generations of stars to the metal enrichment of the Universe is imprinted on the evolution of isotopic ratios over time. We investigate the isotopic ratios of carbon, nitrogen, oxygen, and sulfur through millimeter molecular absorption lines arising in the z=0.68 absorber toward the blazar B 0218+357. We find that these ratios differ from those observed in the Galactic interstellar medium, but are remarkably close to those in the only other source at intermediate redshift for which isotopic ratios have been measured to date, the z=0.89 absorber in front of PKS1830-211. The isotopic ratios in these two absorbers should reflect enrichment mostly from massive stars, and they are indeed close to the values observed toward local starburst galaxies. Our measurements set constraints on nucleosynthesis and chemical evolution models.

  14. The ExoMol database: molecular line lists for exoplanet and other hot atmospheres

    CERN Document Server

    Tennyson, Jonathan; Al-Refaie, Ahmed F; Barton, Emma J; Chubb, Katy L; Coles, Phillip A; Diamantopoulou, S; Gorman, Maire N; Hill, Christian; Lam, Aden Z; Lodi, Lorenzo; McKemmish, Laura K; Na, Yueqi; Owens, Alec; Polyansky, Oleg L; Sousa-Silva, Clara; Underwood, Daniel S; Yachmenev, Andrey; Zak, Emil

    2016-01-01

    The ExoMol database (www.exomol.com) provides extensive line lists of molecular transitions which are valid over extended temperatures ranges. The status of the current release of the database is reviewed and a new data structure is specified. This structure augments the provision of energy levels (and hence transition frequencies) and Einstein $A$ coefficients with other key properties, including lifetimes of individual states, temperature-dependent cooling functions, Land\\'e $g$-factors, partition functions, cross sections, $k$-coefficients and transition dipoles with phase relations. Particular attention is paid to the treatment of pressure broadening parameters. The new data structure includes a definition file which provides the necessary information for utilities accessing ExoMol through its application programming interface (API). Prospects for the inclusion of new species into the database are discussed.

  15. LINES

    Directory of Open Access Journals (Sweden)

    Minas Bakalchev

    2015-10-01

    Full Text Available The perception of elements in a system often creates their interdependence, interconditionality, and suppression. The lines from a basic geometrical element have become the model of a reductive world based on isolation according to certain criteria such as function, structure, and social organization. Their traces are experienced in the contemporary world as fragments or ruins of a system of domination of an assumed hierarchical unity. How can one release oneself from such dependence or determinism? How can the lines become less “systematic” and forms more autonomous, and less reductive? How is a form released from modernistic determinism on the new controversial ground? How can these elements or forms of representation become forms of action in the present complex world? In this paper, the meaning of lines through the ideas of Le Corbusier, Leonidov, Picasso, and Hitchcock is presented. Spatial research was made through a series of examples arising from the projects of the architectural studio “Residential Transformations”, which was a backbone for mapping the possibilities ranging from playfulness to exactness, as tactics of transformation in the different contexts of the contemporary world.

  16. Direct evaluation of phase coexistence by molecular simulation via integration along the saturation line

    Science.gov (United States)

    Kofke, David A.

    1993-03-01

    Thermodynamic integration along a path that coincides with the saturation line is proposed as an efficient means for evaluation of phase equilibria by molecular simulation. The technique allows coexistence to be determined by just one simulation, without ever attempting or performing particle insertions. Prior knowledge of one coexistence point is required to start the procedure. Integration then advances from this state according to the Clapeyron formula—a first-order ordinary differential equation that prescribes how the pressure must change with temperature to maintain coexistence. The method is unusual in the context of thermodynamic integration in that the path is not known at the outset of the process; results from each simulation determine the course that the integration subsequently takes. Predictor-corrector methods among standard numerical techniques are shown to be particularly well suited for this type of integration. A typical integration step along the saturation line proceeds as follows: An increment in the temperature is chosen, and the saturation pressure at the new temperature is ``predicted'' from previous data (the initial coexistence datum and/or previous simulations). Simultaneous but independent NPT simulations of the coexisting phases are initiated at the said conditions. Averages taken throughout the simulations are repeatedly used to ``correct'' the estimate of the pressure to convergence. Thus strictly the pressure is not fixed during the simulation. Vapor-liquid coexistence of the van der Waals model is first used to study the numerical integration method without the complications of molecular simulation. In a second application the phase envelope of the Lennard-Jones model fluid is computed, and many variations of the technique are examined. Overall, the results are remarkably consistent and in agreement with previous simulation studies. Difficulty is encountered upon approach of the critical point, but, by artificially coupling the

  17. Using Homology Modeling, Molecular Dynamics and Molecular Docking Techniques to Identify Inhibitor Binding Regions of Somatostatin Receptor 1

    Institute of Scientific and Technical Information of China (English)

    LAN Hai-nan; WANG Yue-xi; ZHENG Ming-zhu; HAN Wei-wei; ZHENG Xin

    2013-01-01

    The G protein coupled receptor(GPCR),one of the members in the superfamily,which consists of thousands of integral membrane proteins,exerts a wide variety of physiological functions and responses to a large portion of the drug targets.The 3D structure of somatostatin receptor 1(SSTR1) was modeled and refined by means of homology modeling and molecular dynamics simulation.This model was assessed by Verify-3D and Vadar,which confirmed the reliability of the refined model.The interaction between the inhibitor cysteamine,somatostatin(SST) and SSTRI was investigated by a molecular docking program,Affinity.The binding module not only showed the crucial residues involved in the interaction,but also provided important information about the interaction between SSTR1 on the one hand and ligands on the other,which might be the significant evidence for the structure-based design.

  18. NanoCAGE analysis of the mouse olfactory epithelium identifies the expression of vomeronasal receptors and of proximal LINE elements

    Directory of Open Access Journals (Sweden)

    Giovanni ePascarella

    2014-02-01

    Full Text Available By coupling laser capture microdissection to nanoCAGE technology and next-generation sequencing we have identified the genome-wide collection of active promoters in the mouse Main Olfactory Epithelium (MOE. Transcription start sites (TSSs for the large majority of Olfactory Receptors (ORs have been previously mapped increasing our understanding of their promoter architecture.Here we show that in our nanoCAGE libraries of the mouse MOE we detect a large number of tags mapped in loci hosting Type-1 and Type-2 Vomeronasal Receptors genes (V1Rs and V2Rs. These loci also show a massive expression of Long Interspersed Nuclear Elements (LINEs. We have validated the expression of selected receptors detected by nanoCAGE with in situ hybridization, RT-PCR and qRT-PCR. This work extends the repertory of receptors capable of sensing chemical signals in the MOE, suggesting intriguing interplays between MOE and VNO for pheromone processing. It positions transcribed LINEs as candidate regulatory RNAs for VRs expression.

  19. Using crossover breakpoints in recombinant inbred lines to identify quantitative trait loci controlling the global recombination frequency.

    Science.gov (United States)

    Esch, Elisabeth; Szymaniak, Jessica M; Yates, Heather; Pawlowski, Wojciech P; Buckler, Edward S

    2007-11-01

    Recombination is a crucial component of evolution and breeding, producing new genetic combinations on which selection can act. Rates of recombination vary tremendously, not only between species but also within species and for specific chromosomal segments. In this study, by examining recombination events captured in recombinant inbred mapping populations previously created for maize, wheat, Arabidopsis, and mouse, we demonstrate that substantial variation exists for genomewide crossover rates in both outcrossed and inbred plant and animal species. We also identify quantitative trait loci (QTL) that control this variation. The method that we developed and employed here holds promise for elucidating factors that regulate meiotic recombination and for creation of hyperrecombinogenic lines, which can help overcome limited recombination that hampers breeding progress.

  20. A novel high-throughput in vivo molecular screen for shade avoidance mutants identifies a novel phyA mutation.

    Science.gov (United States)

    Wang, Xuewen; Roig-Villanova, Irma; Khan, Safina; Shanahan, Hugh; Quail, Peter H; Martinez-Garcia, Jaime F; Devlin, Paul F

    2011-05-01

    The shade avoidance syndrome (SAS) allows plants to anticipate and avoid shading by neighbouring plants by initiating an elongation growth response. The phytochrome photoreceptors are able to detect a reduction in the red:far red ratio in incident light, the result of selective absorption of red and blue wavelengths by proximal vegetation. A shade-responsive luciferase reporter line (PHYB::LUC) was used to carry out a high-throughput screen to identify novel SAS mutants. The dracula 1 (dra1) mutant, that showed no avoidance of shade for the PHYB::LUC response, was the result of a mutation in the PHYA gene. Like previously characterized phyA mutants, dra1 showed a long hypocotyl in far red light and an enhanced hypocotyl elongation response to shade. However, dra1 additionally showed a long hypocotyl in red light. Since phyB levels are relatively unaffected in dra1, this gain-of-function red light phenotype strongly suggests a disruption of phyB signalling. The dra1 mutation, G773E within the phyA PAS2 domain, occurs at a residue absolutely conserved among phyA sequences. The equivalent residue in phyB is absolutely conserved as a threonine. PAS domains are structurally conserved domains involved in molecular interaction. Structural modelling of the dra1 mutation within the phyA PAS2 domain shows some similarity with the structure of the phyB PAS2 domain, suggesting that the interference with phyB signalling may be the result of non-functional mimicry. Hence, it was hypothesized that this PAS2 residue forms a key distinction between the phyA and phyB phytochrome species.

  1. A miRNA signature of chemoresistant mesenchymal phenotype identifies novel molecular targets associated with advanced pancreatic cancer.

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    Alakesh Bera

    Full Text Available In this study a microRNA (miRNA signature was identified in a gemcitabine resistant pancreatic ductal adenocarcinoma (PDAC cell line model (BxPC3-GZR and this signature was further examined in advanced PDAC tumor specimens from The Cancer Genome Atlas (TCGA database. BxPC3-GZR showed a mesenchymal phenotype, expressed high levels of CD44 and showed a highly significant deregulation of 17 miRNAs. Based on relevance to cancer, a seven-miRNA signature (miR-100, miR-125b, miR-155, miR-21, miR-205, miR-27b and miR-455-3p was selected for further studies. A strong correlation was observed for six of the seven miRNAs in 43 advanced tumor specimens compared to normal pancreas tissue. To assess the functional relevance we initially focused on miRNA-125b, which is over-expressed in both the BxPC3-GZR model and advanced PDAC tumor specimens. Knockdown of miRNA-125b in BxPC3-GZR and Panc-1 cells caused a partial reversal of the mesenchymal phenotype and enhanced response to gemcitabine. Moreover, RNA-seq data from each of 40 advanced PDAC tumor specimens from the TCGA data base indicate a negative correlation between expression of miRNA-125b and five of six potential target genes (BAP1, BBC3, NEU1, BCL2, STARD13. Thus far, two of these target genes, BBC3 and NEU1, that are tumor suppressor genes but not yet studied in PDAC, appear to be functional targets of miR-125b since knockdown of miR125b caused their up regulation. These miRNAs and their molecular targets may serve as targets to enhance sensitivity to chemotherapy and reduce metastatic spread.

  2. A miRNA signature of chemoresistant mesenchymal phenotype identifies novel molecular targets associated with advanced pancreatic cancer.

    Science.gov (United States)

    Bera, Alakesh; VenkataSubbaRao, Kolaparthi; Manoharan, Muthu Saravanan; Hill, Ping; Freeman, James W

    2014-01-01

    In this study a microRNA (miRNA) signature was identified in a gemcitabine resistant pancreatic ductal adenocarcinoma (PDAC) cell line model (BxPC3-GZR) and this signature was further examined in advanced PDAC tumor specimens from The Cancer Genome Atlas (TCGA) database. BxPC3-GZR showed a mesenchymal phenotype, expressed high levels of CD44 and showed a highly significant deregulation of 17 miRNAs. Based on relevance to cancer, a seven-miRNA signature (miR-100, miR-125b, miR-155, miR-21, miR-205, miR-27b and miR-455-3p) was selected for further studies. A strong correlation was observed for six of the seven miRNAs in 43 advanced tumor specimens compared to normal pancreas tissue. To assess the functional relevance we initially focused on miRNA-125b, which is over-expressed in both the BxPC3-GZR model and advanced PDAC tumor specimens. Knockdown of miRNA-125b in BxPC3-GZR and Panc-1 cells caused a partial reversal of the mesenchymal phenotype and enhanced response to gemcitabine. Moreover, RNA-seq data from each of 40 advanced PDAC tumor specimens from the TCGA data base indicate a negative correlation between expression of miRNA-125b and five of six potential target genes (BAP1, BBC3, NEU1, BCL2, STARD13). Thus far, two of these target genes, BBC3 and NEU1, that are tumor suppressor genes but not yet studied in PDAC, appear to be functional targets of miR-125b since knockdown of miR125b caused their up regulation. These miRNAs and their molecular targets may serve as targets to enhance sensitivity to chemotherapy and reduce metastatic spread.

  3. Molecular Line Emission from Massive Protostellar Disks: Predictions for ALMA and the EVLA

    Energy Technology Data Exchange (ETDEWEB)

    Krumholz, M R; Klein, R I; McKee, C F

    2007-05-07

    We compute the molecular line emission of massive protostellar disks by solving the equation of radiative transfer through the cores and disks produced by the recent radiation-hydrodynamic simulations of Krumholz, Klein, & McKee. We find that in several representative lines the disks show brightness temperatures of hundreds of Kelvin over velocity channels {approx} 10 km s{sup -1} wide, extending over regions hundreds of AU in size. We process the computed intensities to model the performance of next-generation radio and submillimeter telescopes. Our calculations show that observations using facilities such as the EVLA and ALMA should be able to detect massive protostellar disks and measure their rotation curves, at least in the nearest massive star-forming regions. They should also detect significant sub-structure and non-axisymmetry in the disks, and in some cases may be able to detect star-disk velocity offsets of a few km s{sup -1}, both of which are the result of strong gravitational instability in massive disks. We use our simulations to explore the strengths and weaknesses of different observational techniques, and we also discuss how observations of massive protostellar disks may be used to distinguish between alternative models of massive star formation.

  4. Molecular mapping of leaf rust resistance genes in the wheat line Yu 356-9

    Institute of Scientific and Technical Information of China (English)

    HAN Liu-sha; LI Zai-feng; WANG Jia-zhen; SHI Ling-zhi; ZHU Lin; LI Xing; LIU Da-qun; Syed J A Shah

    2015-01-01

    The Chinese wheat line Yu 356-9 exhibits a high level of resistance to leaf rust. In order to decipher the genetic base of resistance in Yu 356-9, gene postulation, inheritance analyses, and chromosome linkage mapping were carried out. Gene postulation completed using 15 leaf rust pathotypes and 36 isogenic lines indicated that Yu 356-9 was resistant to al pathotypes tested. F1 and F2 plants from the cross Yu 356-9 (resistant)/Zhengzhou 5389 (susceptible) were tested with leaf rust pathotype“FHNQ”in the greenhouse. Results indicated a 3:1 segregation ratio, indicative of the presence of a single dominant leaf rust resistance gene in Yu 356-9 which was temporarily designated as LrYu. Bulk segregant analysis and molecular marker assays were used to map LrYu. Five simple sequence repeat (SSR) markers on chromosome 2BS were found closely linked to LrYu. Among these markers, Xwmc770 is the most closely linked, with a genetic distance of 5.7 cM.

  5. Molecular line study of the very young protostar IRAM 04191 in Taurus Infall, rotation, and outflow

    CERN Document Server

    Belloche, A; Despois, D; Blinder, S M

    2002-01-01

    We present a detailed millimeter line study of the circumstellar environment of the low-luminosity Class 0 protostar IRAM 04191+1522 in the Taurus molecular cloud. New line observations demonstrate that the ~14000 AU radius protostellar envelope is undergoing both extended infall and fast, differential rotation. Radiative transfer modeling of multitransition CS and C34S maps indicate an infall velocity v_inf ~ 0.15 km/s at r ~ 1500 AU and v_inf ~ 0.1 km/s up to r ~ 11000 AU, as well as a rotational angular velocity Omega ~ 3.9 x 10^{-13} rad/s, strongly decreasing with radius beyond 3500 AU down to a value Omega ~ 1.5-3 x 10^{-14} rad/s at ~ 11000 AU. Two distinct regions, which differ in both their infall and their rotation properties, therefore seem to stand out: the inner part of the envelope (r ~< 2000-4000 AU) is rapidly collapsing and rotating, while the outer part undergoes only moderate infall/contraction and slower rotation. These contrasted features suggest that angular momentum is conserved in t...

  6. Diagnostics of the molecular component of PDRs with mechanical heating. II: line intensities and ratios

    CERN Document Server

    Kazandjian, M V; Pelupessy, I; Israel, F P; Spaans, M

    2014-01-01

    CO observations in active galactic nuclei and star-bursts reveal high kinetic temperatures. Those environments are thought to be very turbulent due to dynamic phenomena such as outflows and high supernova rates. We investigate the effect of mechanical heating (MH) on atomic fine-structure and molecular lines, and their ratios. We use those ratios as a diagnostic to constrain the amount of MH in an object and also study its significance on estimating the H2 mass. Equilibrium PDRs models were used to compute the thermal and chemical balance for the clouds. The equilibria were solved for numerically using the optimized version of the Leiden PDR-XDR code. Large velocity gradient calculations were done as post-processing on the output of the PDR models using RADEX. High-J CO line ratios are very sensitive to MH. Emission becomes at least one order of magnitude brighter in clouds with n~10^5~cm^-3 and a star formation rate of 1 Solar Mass per year (corresponding to a MH rate of 2 * 10^-19 erg cm^-3 s^-1). Emission ...

  7. Cellular and molecular portrait of eleven human glioblastoma cell lines under photon and carbon ion irradiation.

    Science.gov (United States)

    Ferrandon, S; Magné, N; Battiston-Montagne, P; Hau-Desbat, N-H; Diaz, O; Beuve, M; Constanzo, J; Chargari, C; Poncet, D; Chautard, E; Ardail, D; Alphonse, G; Rodriguez-Lafrasse, C

    2015-04-28

    This study aimed to examine the cellular and molecular long-term responses of glioblastomas to radiotherapy and hadrontherapy in order to better understand the biological effects of carbon beams in cancer treatment. Eleven human glioblastoma cell lines, displaying gradual radiosensitivity, were irradiated with photons or carbon ions. Independently of p53 or O(6)-methylguanine-DNA methyltransferase(1) status, all cell lines responded to irradiation by a G2/M phase arrest followed by the appearance of mitotic catastrophe, which was concluded by a ceramide-dependent-apoptotic cell death. Statistical analysis demonstrated that: (i) the SF2(2) and the D10(3) values for photon are correlated with that obtained in response to carbon ions; (ii) regardless of the p53, MGMT status, and radiosensitivity, the release of ceramide is associated with the induction of late apoptosis; and (iii) the appearance of polyploid cells after photon irradiation could predict the Relative Biological Efficiency(4) to carbon ions. This large collection of data should increase our knowledge in glioblastoma radiobiology in order to better understand, and to later individualize, appropriate radiotherapy treatment for patients who are good candidates.

  8. Very High Excitation Lines of H2 in the Orion Molecular Cloud Outflow

    Science.gov (United States)

    Geballe, T. R.; Burton, M. G.; Pike, R. E.

    2017-03-01

    Vibration-rotation lines of H2 from highly excited levels approaching the dissociation limit have been detected at a number of locations in the shocked gas of the Orion Molecular Cloud (OMC-1), including in a Herbig-Haro object near the tip of one of the OMC-1 “fingers.” Population diagrams show that, while the excited H2 is almost entirely at a kinetic temperature of ˜1800 K (typical for vibrationally shock-excited H2), as in the previously reported case of Herbig-Haro object HH 7 up to a few percent of the H2 is at a kinetic temperature of ˜5000 K. The location with the largest fraction of hot H2 is the Herbig-Haro object, where the outflowing material is moving at a higher speed than at the other locations. Although theoretical work is required for a better understanding of the 5000 K H2 (including how it cools), its existence and the apparent dependence of its abundance relative to that of the cooler component on the relative velocities of the outflow and the surrounding ambient gas appear broadly consistent with it having recently reformed. The existence of this high-temperature H2 appears to be a common characteristic of shock-excited molecular gas.

  9. A molecular line study of the filamentary infrared dark cloud G304.74+01.32

    CERN Document Server

    Miettinen, Oskari

    2012-01-01

    The aim of this study is to better understand the physical and chemical properties of the filamentary IRDC G304.74+01.32. In particular, we aim to investigate the kinematics and dynamical state of the cloud and clumps within it, and the amount of CO depletion. All the submillimetre peak positions in the cloud identified from our previous LABOCA 870-micron map were observed in C17O(2-1) with APEX. Selected positions were also observed in the 13CO(2-1), SiO(5-4), and CH3OH(5_k-4_k) transitions at ~1 mm wavelength. The C17O lines were detected towards all target positions at similar radial velocities, indicating that G304.74 is a coherent filamentary structure. CO does not appear to be significantly depleted in the clumps. Two- to three methanol 5_k-4_k lines near ~241.8 GHz were detected towards all selected target positions, whereas SiO(5-4) was seen in only one of these positions. The 13CO(2-1) lines show blue asymmetric profiles, indicating large-scale infall motions. The clumps show trans- to supersonic non...

  10. Modeling and simulations for molecular scale hydrodynamics of the moving contact line in immiscible two-phase flows

    KAUST Repository

    Qian, Tiezheng

    2009-10-29

    This paper starts with an introduction to the Onsager principle of minimum energy dissipation which governs the optimal paths of deviation and restoration to equilibrium. Then there is a review of the variational approach to moving contact line hydrodynamics. To demonstrate the validity of our continuum hydrodynamic model, numerical results from model calculations and molecular dynamics simulations are presented for immiscible Couette and Poiseuille flows past homogeneous solid surfaces, with remarkable overall agreement. Our continuum model is also used to study the contact line motion on surfaces patterned with stripes of different contact angles (i.e. surfaces of varying wettability). Continuum calculations predict the stick-slip motion for contact lines moving along these patterned surfaces, in quantitative agreement with molecular dynamics simulation results. This periodic motion is tunable through pattern period (geometry) and contrast in wetting property (chemistry). The consequence of stick-slip contact line motion on energy dissipation is discussed. © 2009 IOP Publishing Ltd.

  11. Modeling and simulations for molecular scale hydrodynamics of the moving contact line in immiscible two-phase flows

    Energy Technology Data Exchange (ETDEWEB)

    Qian Tiezheng; Wu Congmin; Lei Siu Long; Wang Xiaoping [Department of Mathematics, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon (Hong Kong); Sheng Ping, E-mail: maqian@ust.h [Department of Physics and William Mong Institute of Nano Science and Technology, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon (Hong Kong)

    2009-11-18

    This paper starts with an introduction to the Onsager principle of minimum energy dissipation which governs the optimal paths of deviation and restoration to equilibrium. Then there is a review of the variational approach to moving contact line hydrodynamics. To demonstrate the validity of our continuum hydrodynamic model, numerical results from model calculations and molecular dynamics simulations are presented for immiscible Couette and Poiseuille flows past homogeneous solid surfaces, with remarkable overall agreement. Our continuum model is also used to study the contact line motion on surfaces patterned with stripes of different contact angles (i.e. surfaces of varying wettability). Continuum calculations predict the stick-slip motion for contact lines moving along these patterned surfaces, in quantitative agreement with molecular dynamics simulation results. This periodic motion is tunable through pattern period (geometry) and contrast in wetting property (chemistry). The consequence of stick-slip contact line motion on energy dissipation is discussed.

  12. Modeling and simulations for molecular scale hydrodynamics of the moving contact line in immiscible two-phase flows.

    Science.gov (United States)

    Qian, Tiezheng; Wu, Congmin; Lei, Siu Long; Wang, Xiao-Ping; Sheng, Ping

    2009-11-18

    This paper starts with an introduction to the Onsager principle of minimum energy dissipation which governs the optimal paths of deviation and restoration to equilibrium. Then there is a review of the variational approach to moving contact line hydrodynamics. To demonstrate the validity of our continuum hydrodynamic model, numerical results from model calculations and molecular dynamics simulations are presented for immiscible Couette and Poiseuille flows past homogeneous solid surfaces, with remarkable overall agreement. Our continuum model is also used to study the contact line motion on surfaces patterned with stripes of different contact angles (i.e. surfaces of varying wettability). Continuum calculations predict the stick-slip motion for contact lines moving along these patterned surfaces, in quantitative agreement with molecular dynamics simulation results. This periodic motion is tunable through pattern period (geometry) and contrast in wetting property (chemistry). The consequence of stick-slip contact line motion on energy dissipation is discussed.

  13. Breeding Rice Restorer Lines with High Resistance to Bacterial Blight by Using Molecular Marker-Assisted Selection

    Institute of Scientific and Technical Information of China (English)

    DENG Qi-ming; WANG Shi-quan; ZHENG Ai-ping; ZHANG Hong-yu; LI Ping

    2006-01-01

    Two bacterial blight (BB) resistance genes, Xa21 and Xa4, from IRBB24 were introduced into hybrid rice restorer line Mianhui 725, which is highly susceptible to BB, by using hybridization and molecular marker-assisted selection technology. Four homologous restorer lines were obtained through testing the R target genes with molecular markers and analyzing parental genetic background. Inoculation of the four lines and their hybrids with the specific strains of Xanthomonas oryzae pv. oryzae, P1, P6 and seven representative strains of Chinese pathotype, C Ⅰ -CⅦ, showed that all of the four lines and their hybrids were highly resistant and presented broad resistance-spectrum to BB. The hybrids of G46A / R207-2 displayed good agronomic characters and high yield potential, and R207-2 was named Shuhui 207.

  14. Metastatic non-small-cell lung cancer: consensus on pathology and molecular tests, first-line, second-line, and third-line therapy: 1st ESMO Consensus Conference in Lung Cancer; Lugano 2010

    DEFF Research Database (Denmark)

    Felip, E; Gridelli, C; Baas, P;

    2011-01-01

    the conference, the expert panel prepared clinically relevant questions concerning five areas: early and locally advanced non-small-cell lung cancer (NSCLC), first-line metastatic NSCLC, second-/third-line NSCLC, NSCLC pathology and molecular testing, and small-cell lung cancer to be addressed through discussion......The 1st ESMO Consensus Conference on lung cancer was held in Lugano, Switzerland on 21 and 22 May 2010 with the participation of a multidisciplinary panel of leading professionals in pathology and molecular diagnostics, medical oncology, surgical oncology and radiation oncology. Before...

  15. REAL-TIME DETECTION OF SURVIVIN mRNA EXPRESSION IN CERVICAL CANCER CELL LINES USING MOLECULAR BEACON IMAGING

    Institute of Scientific and Technical Information of China (English)

    An Ruifang; He Dalin; Xue Yan; Wang Shu; Xie Li; Zhao Jun; Wang Xinyang; Yang Lili

    2006-01-01

    Objective To detect the expression of survivin mRNA in cervical cancer cell lines using molecular beacon imaging technology. Methods Human cervical cancer cells (HeLa and SiHa) and human fetal lung fibroblast HFL-I were cultured in vitro. After adding 100 nmol/L survivin mRNA molecular beacon, the fluorescent signals were observed under fluorescent microscope. The expressions of survivin in cervical cancer cells and HFL-I cell were examined by immunocytochemical streptravidin-biothin peroxidase (SP) assay at the same time. Results Two kinds of survivin mRNA molecular beacon, with different color fluorescence, had strong fluorescent signal in cervical cancer cell lines, and the signal in SiHa cell line was stronger, but these signals were not found in HFL-I ; Immunocytochemical staining of positive survivin was located in the cytoplasm of cervical cancer cell lines HeLa and SiHa, whereas, no expression of survivin was detected in HFL-I cell line. Conclusion The technology of molecular beacon imaging can be used to detect the expression of survivin mRNA in viable cells successfully, and may provide a new approach to the diagnosis of early stage cervical cancer and the following-up in the clinic.

  16. Molecular characterization of permanent cell lines from primary, metastatic and recurrent malignant peripheral nerve sheath tumors (MPNST) with underlying neurofibromatosis-1.

    Science.gov (United States)

    Fang, Yuqiang; Elahi, Abul; Denley, Ryan C; Rao, Pulivarthi H; Brennan, Murray F; Jhanwar, Suresh C

    2009-04-01

    lines was observed, as reported by others. The role of biallelic inactivation of p53 gene in MPNST with underlying NF1 mutations, however, needs further study. Overexpression of Rb1-protein observed in metastatic and recurrent cell lines is indicative of its role in the progression of the disease. One of the most important observations of this study is that Nm23-H1 expression is closely associated with advanced or metastatic disease. In summary, MPNST cell lines derived from a patient with metastatic and recurrent disease with NF1 disorder were characterized and a gene associated with metastatic potential which is amenable to therapeutic and chemo-preventative approaches was identified. These cell lines with extensive characterization of genetic abnormalities are likely to provide important reagents for biochemical, molecular and pharmacological studies related to MPNST.

  17. Network modeling identifies molecular functions targeted by miR-204 to suppress head and neck tumor metastasis.

    Directory of Open Access Journals (Sweden)

    Younghee Lee

    2010-04-01

    Full Text Available Due to the large number of putative microRNA gene targets predicted by sequence-alignment databases and the relative low accuracy of such predictions which are conducted independently of biological context by design, systematic experimental identification and validation of every functional microRNA target is currently challenging. Consequently, biological studies have yet to identify, on a genome scale, key regulatory networks perturbed by altered microRNA functions in the context of cancer. In this report, we demonstrate for the first time how phenotypic knowledge of inheritable cancer traits and of risk factor loci can be utilized jointly with gene expression analysis to efficiently prioritize deregulated microRNAs for biological characterization. Using this approach we characterize miR-204 as a tumor suppressor microRNA and uncover previously unknown connections between microRNA regulation, network topology, and expression dynamics. Specifically, we validate 18 gene targets of miR-204 that show elevated mRNA expression and are enriched in biological processes associated with tumor progression in squamous cell carcinoma of the head and neck (HNSCC. We further demonstrate the enrichment of bottleneckness, a key molecular network topology, among miR-204 gene targets. Restoration of miR-204 function in HNSCC cell lines inhibits the expression of its functionally related gene targets, leads to the reduced adhesion, migration and invasion in vitro and attenuates experimental lung metastasis in vivo. As importantly, our investigation also provides experimental evidence linking the function of microRNAs that are located in the cancer-associated genomic regions (CAGRs to the observed predisposition to human cancers. Specifically, we show miR-204 may serve as a tumor suppressor gene at the 9q21.1-22.3 CAGR locus, a well established risk factor locus in head and neck cancers for which tumor suppressor genes have not been identified. This new strategy

  18. The GuideLine Implementability Appraisal (GLIA: development of an instrument to identify obstacles to guideline implementation

    Directory of Open Access Journals (Sweden)

    Hsiao Allen

    2005-07-01

    Full Text Available Abstract Background Clinical practice guidelines are not uniformly successful in influencing clinicians' behaviour toward best practices. Implementability refers to a set of characteristics that predict ease of (and obstacles to guideline implementation. Our objective is to develop and validate a tool for appraisal of implementability of clinical guidelines. Methods Indicators of implementability were identified from the literature and used to create items and dimensions of the GuideLine Implementability Appraisal (GLIA. GLIA consists of 31 items, arranged into 10 dimensions. Questions from 9 of the 10 dimensions are applied individually to each recommendation of the guideline. Decidability and Executability are critical dimensions. Other dimensions are Global, Presentation and Formatting, Measurable Outcomes, Apparent Validity, Flexibility, Effect on Process of Care, Novelty/Innovation, and Computability. We conducted a series of validation activities, including validation of the construct of implementability, expert review of content for clarity, relevance, and comprehensiveness, and assessment of construct validity of the instrument. Finally, GLIA was applied to a draft guideline under development by national professional societies. Results Evidence of content validity and preliminary support for construct validity were obtained. The GLIA proved to be useful in identifying barriers to implementation in the draft guideline and the guideline was revised accordingly. Conclusion GLIA may be useful to guideline developers who can apply the results to remedy defects in their guidelines. Likewise, guideline implementers may use GLIA to select implementable recommendations and to devise implementation strategies that address identified barriers. By aiding the design and operationalization of highly implementable guidelines, our goal is that application of GLIA may help to improve health outcomes, but further evaluation will be required to support

  19. IS element IS16 as a molecular screening tool to identify hospital-associated strains of Enterococcus faecium

    NARCIS (Netherlands)

    Werner, Guido; Fleige, Carola; Geringer, Uta; van Schaik, Willem; Klare, Ingo; Witte, Wolfgang

    2011-01-01

    Background: Hospital strains of Enterococcus faecium could be characterized and typed by various molecular methods (MLST, AFLP, MLVA) and allocated to a distinct clonal complex known as MLST CC17. However, these techniques are laborious, time-consuming and cost-intensive. Our aim was to identify hos

  20. Comparison of phenotypic and molecular tests to identify lactic acid bacteria

    Directory of Open Access Journals (Sweden)

    Paula Mendonça Moraes

    2013-01-01

    Full Text Available Twenty-nine lactic acid bacteria (LAB isolates were submitted for identification using Biolog, API50CHL, 16S rDNA sequencing, and species-specific PCR reactions. The identification results were compared, and it was concluded that a polyphasic approach is necessary for proper LAB identification, being the molecular analyzes the most reliable.

  1. Research Advances: Nanoscale Molecular Tweezers; Cinnamon as Pesticide?; Recently Identified Dietary Sources of Antioxidants

    Science.gov (United States)

    King, Angela G.

    2004-12-01

    This Report from Other Journals surveys articles of interest to chemists that have been recently published in other science journals. Topics surveyed include reports that receptors have been designed to act as molecular tweezers; cinnamon has potential in the fight against mosquitoes; and high levels of antioxidants are found in some surprising foods. See Featured Molecules .

  2. Whole-genome sequencing and comprehensive molecular profiling identify new driver mutations in gastric cancer

    NARCIS (Netherlands)

    Wang, Kai; Yuen, Siu Tsan; Xu, Jiangchun; Lee, Siu Po; Yan, Helen H N; Shi, Stephanie T; Siu, Hoi Cheong; Deng, Shibing; Chu, Kent Man; Law, Simon; Chan, Kok Hoe; Chan, Annie S Y; Tsui, Wai Yin; Ho, Siu Lun; Chan, Anthony K W; Man, Jonathan L K; Foglizzo, Valentina; Ng, Man Kin; Chan, April S; Ching, Yick Pang; Cheng, Grace H W; Xie, Tao; Fernandez, Julio; Li, Vivian S W; Clevers, Hans; Rejto, Paul A; Mao, Mao; Leung, Suet Yi

    2014-01-01

    Gastric cancer is a heterogeneous disease with diverse molecular and histological subtypes. We performed whole-genome sequencing in 100 tumor-normal pairs, along with DNA copy number, gene expression and methylation profiling, for integrative genomic analysis. We found subtype-specific genetic and e

  3. Discovery of Broad Molecular lines and of Shocked Molecular Hydrogen from the Supernova Remnant G357.7+0.3: HHSMT, APEX, Spitzer and SOFIA Observations

    CERN Document Server

    Rho, J; Hewitt, J; Andersen, M; Reach, W T; Guesten, R

    2016-01-01

    We report a discovery of shocked gas from the supernova remnant (SNR) G357.7+0.3. Our millimeter and submillimeter observations reveal broad molecular lines of CO(2-1), CO(3-2), CO(4-3), 13CO (2-1) and 13CO (3-2), HCO^+ and HCN using HHSMT, Arizona 12-Meter Telescope, APEX and MOPRA Telescope. The widths of the broad lines are 15-30 kms, and the detection of such broad lines is unambiguous, dynamic evidence showing that the SNR G357.7+0.3 is interacting with molecular clouds. The broad lines appear in extended regions (>4.5'x5'). We also present detection of shocked H2 emission in mid-infrared but lacking ionic lines using the Spitzer IRS observations to map a few arcmin area. The H2 excitation diagram shows a best-fit with a two-temperature LTE model with the temperatures of ~200 and 660 K. We observed [C II] at 158um and high-J CO(11-10) with the GREAT on SOFIA. The GREAT spectrum of [C II], a 3 sigma detection, shows a broad line profile with a width of 15.7 km/s that is similar to those of broad CO molecu...

  4. Molecular dissection of the migrating posterior lateral line primordium during early development in zebrafish

    Directory of Open Access Journals (Sweden)

    Villablanca Eduardo J

    2010-12-01

    Full Text Available Abstract Background Development of the posterior lateral line (PLL system in zebrafish involves cell migration, proliferation and differentiation of mechanosensory cells. The PLL forms when cranial placodal cells delaminate and become a coherent, migratory primordium that traverses the length of the fish to form this sensory system. As it migrates, the primordium deposits groups of cells called neuromasts, the specialized organs that contain the mechanosensory hair cells. Therefore the primordium provides both a model for studying collective directional cell migration and the differentiation of sensory cells from multipotent progenitor cells. Results Through the combined use of transgenic fish, Fluorescence Activated Cell Sorting and microarray analysis we identified a repertoire of key genes expressed in the migrating primordium and in differentiated neuromasts. We validated the specific expression in the primordium of a subset of the identified sequences by quantitative RT-PCR, and by in situ hybridization. We also show that interfering with the function of two genes, f11r and cd9b, defects in primordium migration are induced. Finally, pathway construction revealed functional relationships among the genes enriched in the migrating cell population. Conclusions Our results demonstrate that this is a robust approach to globally analyze tissue-specific expression and we predict that many of the genes identified in this study will show critical functions in developmental events involving collective cell migration and possibly in pathological situations such as tumor metastasis.

  5. Identifying clinically relevant drug resistance genes in drug-induced resistant cancer cell lines and post-chemotherapy tissues.

    Science.gov (United States)

    Tong, Mengsha; Zheng, Weicheng; Lu, Xingrong; Ao, Lu; Li, Xiangyu; Guan, Qingzhou; Cai, Hao; Li, Mengyao; Yan, Haidan; Guo, You; Chi, Pan; Guo, Zheng

    2015-12-01

    Until recently, few molecular signatures of drug resistance identified in drug-induced resistant cancer cell models can be translated into clinical practice. Here, we defined differentially expressed genes (DEGs) between pre-chemotherapy colorectal cancer (CRC) tissue samples of non-responders and responders for 5-fluorouracil and oxaliplatin-based therapy as clinically relevant drug resistance genes (CRG5-FU/L-OHP). Taking CRG5-FU/L-OHP as reference, we evaluated the clinical relevance of several types of genes derived from HCT116 CRC cells with resistance to 5-fluorouracil and oxaliplatin, respectively. The results revealed that DEGs between parental and resistant cells, when both were treated with the corresponding drug for a certain time, were significantly consistent with the CRG5-FU/L-OHP as well as the DEGs between the post-chemotherapy CRC specimens of responders and non-responders. This study suggests a novel strategy to extract clinically relevant drug resistance genes from both drug-induced resistant cell models and post-chemotherapy cancer tissue specimens.

  6. Molecular Imaging to Identify Tumor Recurrence following Chemoradiation in a Hostile Surgical Environment

    Directory of Open Access Journals (Sweden)

    Olugbenga T. Okusanya

    2015-01-01

    Full Text Available Surgical biopsy of potential tumor recurrence is a common challenge facing oncologists, surgeons, and cancer patients. Imaging modalities have limited ability to accurately detect recurrent cancer in fields affected by previous surgery, chemotherapy, or radiation. However, definitive tissue diagnosis is often needed to initiate treatment and to direct therapy. We sought to determine if a targeted fluorescent intraoperative molecular imaging technique could be applied in a clinical setting to assist a surgical biopsy in a “hostile” field. We describe the use of a folate-fluorescein conjugate to direct the biopsy of a suspected recurrent lung adenocarcinoma invading the mediastinum that had been previously treated with chemoradiation. We found that intraoperative imaging allowed the identification of small viable tumor deposits that were otherwise indistinguishable from scar and necrosis. Our operative observations were confirmed by histology, fluorescence microscopy, and immunohistochemistry. Our results demonstrate one possible application and clinical value of intraoperative molecular imaging.

  7. A systems biology approach identifies molecular networks defining skeletal muscle abnormalities in chronic obstructive pulmonary disease.

    Directory of Open Access Journals (Sweden)

    Nil Turan

    2011-09-01

    Full Text Available Chronic Obstructive Pulmonary Disease (COPD is an inflammatory process of the lung inducing persistent airflow limitation. Extensive systemic effects, such as skeletal muscle dysfunction, often characterize these patients and severely limit life expectancy. Despite considerable research efforts, the molecular basis of muscle degeneration in COPD is still a matter of intense debate. In this study, we have applied a network biology approach to model the relationship between muscle molecular and physiological response to training and systemic inflammatory mediators. Our model shows that failure to co-ordinately activate expression of several tissue remodelling and bioenergetics pathways is a specific landmark of COPD diseased muscles. Our findings also suggest that this phenomenon may be linked to an abnormal expression of a number of histone modifiers, which we discovered correlate with oxygen utilization. These observations raised the interesting possibility that cell hypoxia may be a key factor driving skeletal muscle degeneration in COPD patients.

  8. An efficient algorithm for identifying matches with errors in multiple long molecular sequences.

    Science.gov (United States)

    Leung, M Y; Blaisdell, B E; Burge, C; Karlin, S

    1991-10-20

    An efficient algorithm is described for finding matches, repeats and other word relations, allowing for errors, in large data sets of long molecular sequences. The algorithm entails hashing on fixed-size words in conjunction with the use of a linked list connecting all occurrences of the same word. The average memory and run time requirement both increase almost linearly with the total sequence length. Some results of the program's performance on a database of Escherichia coli DNA sequences are presented.

  9. Coupled biophysical global ocean model and molecular genetic analyses identify multiple introductions of cryptogenic species

    OpenAIRE

    Dawson, Michael N; Gupta, Alex Sen; England, Matthew H.

    2005-01-01

    The anthropogenic introduction of exotic species is one of the greatest modern threats to marine biodiversity. Yet exotic species introductions remain difficult to predict and are easily misunderstood because knowledge of natural dispersal patterns, species diversity, and biogeography is often insufficient to distinguish between a broadly dispersed natural population and an exotic one. Here we compare a global molecular phylogeny of a representative marine meroplanktonic taxon, the moon-jelly...

  10. Properties of interstellar filaments derived from Herschel, Planck, and molecular line observations

    Science.gov (United States)

    Arzoumanian, Doris

    2015-08-01

    The highly filamentary structure of the interstellar medium (ISM) is now impressively revealed by Herschel and Planck images. Previous observations have shown that clouds are filamentary, however, only recently the mapping capabilities of Herscheland Planck have discovered their ubiquity in the ISM. In particular, Herschel images, with their high spatial and intensity dynamic ranges, show that dense filaments are associated with the main sites of star formation, demonstrating their key role in the star formation process.The analysis of the column density profiles of filaments indicates that they all share a common central width of 0.1pc, while they span a wide range in length, column density, mass per unit length. The results derived from observations tracing cold dust and gas emission, in total and polarised intensity, suggest that filaments can be divided into two families: On the one hand, low column density, unbound, and quiescent filaments mostly aligned with the magnetic field orientation, and on the other hand, dense, self-gravitating filaments, which fragment into star forming cores.I will present the properties of the filamentary structures derived from Herschel, Planck, and molecular line observations, and I will discuss the observational constraints on the formation and evolution of interstellar filaments.

  11. Genetic and molecular analysis of chlorambucil-induced germ-line mutations in the mouse

    Energy Technology Data Exchange (ETDEWEB)

    Rinchik, E.M.; Bangham, J.W.; Hunsicker, P.R.; Cacheiro, N.L.A.; Russell, L.B. (Oak Ridge National Lab., TN (USA)); Kwon, B.S. (Indiana Univ. School of Medicine, Indianapolis (USA)); Jackson, I.J. (Western General Hospital, Edinburgh (England))

    1990-02-01

    Eighteen variants recovered from specific locus mutation rate experiments involving the mutagen chlorambucil were subjected to several genetic and molecular analyses. Most mutations were found to be homozygous lethal. Because lethality is often presumptive evidence for multilocus-deletion events, 10 mutations were analyzed by Southern blot analysis with probes at, or closely linked to, several of the specific locus test markers, namely, albino (c), brown (b), and dilute (d). All eight mutations (two c; three b; two d; and one dilute-short ear (Df(d se))) that arose in post-spermatogonial germ cells were deleted for DNA sequences. No evidence for deletion of two d-se region probes was obtained for the remaining two d mutations that arose in stem-cell spermatogonia. Six of the primary mutants also produced low litter sizes (semisterility). Karyotypic analysis has, to date, confirmed the presence of reciprocal translocations in four of the six. The high frequency of deletions and translocations among the mutations induced in post-spermatogonial stages by chlorambucil, combined with its overall high efficiency in inducing mutations in these stages, should make chlorambucil mutagenesis useful for generating experimentally valuable germ-line deletions throughout the mouse genome.

  12. Isotopic ratios at z = 0.68 from molecular absorption lines toward B 0218+357

    Science.gov (United States)

    Wallström, S. H. J.; Muller, S.; Guélin, M.

    2016-11-01

    Isotopic ratios of heavy elements are a key signature of the nucleosynthesis processes in stellar interiors. The contribution of successive generations of stars to the metal enrichment of the Universe is imprinted on the evolution of isotopic ratios over time. We investigate the isotopic ratios of carbon, nitrogen, oxygen, and sulfur through millimeter molecular absorption lines arising in the z = 0.68 absorber toward the blazar B 0218+357. We find that these ratios differ from those observed in the Galactic interstellar medium, but are remarkably close to those in the only other source at intermediate redshift for which isotopic ratios have been measured to date, the z = 0.89 absorber in front of PKS 1830-211. The isotopic ratios in these two absorbers should reflect enrichment mostly from massive stars, and they are indeed close to the values observed toward local starburst galaxies. Our measurements set constraints on nucleosynthesis and chemical evolution models. The reduced spectra are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (http://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/595/A96

  13. Extended Carbon Line Emission in the Galaxy: Searching for Dark Molecular Gas along the G328 Sightline

    CERN Document Server

    Burton, Michael G; Braiding, Catherine; Freeman, Matthew; Kulesa, Craig; Wolfire, Mark G; Hollenbach, David J; Rowell, Gavin; Lau, James

    2015-01-01

    We present spectral data cubes of the [CI] 809GHz, 12CO 115GHz, 13CO 110GHz and HI 1.4GHz line emission from an 1 square degree region along the l = 328{\\deg} (G328) sightline in the Galactic Plane. Emission arises principally from gas in three spiral arm crossings along the sight line. The distribution of the emission in the CO and [CI] lines is found to be similar, with the [CI] slightly more extended, and both are enveloped in extensive HI. Spectral line ratios per voxel in the data cubes are found to be similar across the entire extent of the Galaxy. However, towards the edges of the molecular clouds the [CI]/13CO and 12CO/13CO line ratios rise by ~50%, and the [CI]/HI ratio falls by ~10$%. We attribute this to these sightlines passing predominantly through the surfaces of photodissociation regions (PDRs), where the carbon is found mainly as C or C+, while the H2 is mostly molecular, and the proportion of atomic gas also increases. We undertake modelling of the PDR emission from low density molecular clou...

  14. Determination of molecular line parameters for acrolein (C(3)H(4)O) using infrared tunable diode laser absorption spectroscopy.

    Science.gov (United States)

    Harward, Charles N; Thweatt, W David; Baren, Randall E; Parrish, Milton E

    2006-04-01

    Acrolein (C(3)H(4)O) molecular line parameters, including infrared (IR) absorption positions, strengths, and nitrogen broadened half-widths, must be determined since they are not included in the high resolution transmission (HITRAN) molecular absorption database of spectral lines. These parameters are required for developing a quantitative analytical method for measuring acrolein in a single puff of cigarette smoke using tunable diode laser absorption spectroscopy (TDLAS). The task is complex since acrolein has many highly overlapping infrared absorption lines in the room temperature spectrum and the cigarette smoke matrix contains thousands of compounds. This work describes the procedure for estimating the molecular line parameters for these overlapping absorption lines in the wavenumber range (958.7-958.9 cm(-1)) using quantitative reference spectra taken with the infrared lead-salt TDLAS instrument at different pressures and concentrations. The nitrogen broadened half-width for acrolein is 0.0937 cm(-1)atm(-1) and to our knowledge, is the first time it has been reported in the literature.

  15. Quantitative trait loci identified for blood chemistry components of an advanced intercross line of chickens under heat stress.

    Science.gov (United States)

    Van Goor, Angelica; Ashwell, Christopher M; Persia, Michael E; Rothschild, Max F; Schmidt, Carl J; Lamont, Susan J

    2016-04-14

    Heat stress in poultry results in considerable economic losses and is a concern for both animal health and welfare. Physiological changes occur during periods of heat stress, including changes in blood chemistry components. A highly advanced intercross line, created from a broiler (heat susceptible) by Fayoumi (heat resistant) cross, was exposed to daily heat cycles for seven days starting at 22 days of age. Blood components measured pre-heat treatment and on the seventh day of heat treatment included pH, pCO2, pO2, base excess, HCO3, TCO2, K, Na, ionized Ca, hematocrit, hemoglobin, sO2, and glucose. A genome-wide association study (GWAS) for these traits and their calculated changes was conducted to identify quantitative trait loci (QTL) using a 600 K SNP panel. There were significant increases in pH, base excess, HCO3, TCO2, ionized Ca, hematocrit, hemoglobin, and sO2, and significant decreases in pCO2 and glucose after 7 days of heat treatment. Heritabilities ranged from 0.01-0.21 for pre-heat measurements, 0.01-0.23 for measurements taken during heat, and 0.00-0.10 for the calculated change due to heat treatment. All blood components were highly correlated within measurement days, but not correlated between measurement days. The GWAS revealed 61 QTL for all traits, located on GGA (Gallus gallus chromosome) 1, 3, 6, 9, 10, 12-14, 17, 18, 21-28, and Z. A functional analysis of the genes in these QTL regions identified the Angiopoietin pathway as significant. The QTL that co-localized for three or more traits were on GGA10, 22, 26, 28, and Z and revealed candidate genes for birds' response to heat stress. The results of this study contribute to our knowledge of levels and heritabilities of several blood components of chickens under thermoneutral and heat stress conditions. Most components responded to heat treatment. Mapped QTL may serve as markers for genomic selection to enhance heat tolerance in poultry. The Angiopoietin pathway is likely involved in the

  16. Discovery of Time Variation of the Intensity of Molecular Lines in IRC+10216 in The Submillimeter and Far Infrared Domains

    CERN Document Server

    Cernicharo, J; Quintana-Lacaci, G; Daniel, F; Agúndez, M; Prieto, L Velilla; Decin, L; Guélin, M; Encrenaz, P; García-Lario, P; de Beck, E; Barlow, M J; Groenewegen, M A T; Neufeld, D; Pearson, J

    2014-01-01

    We report on the discovery of strong intensity variations in the high rotational lines of abundant molecular species towards the archetypical circumstellar envelope of IRC+10216. The observations have been carried out with the HIFI instrument on board \\textit{Herschel}\\thanks{\\textit{Herschel} is an ESA space observatory with science instruments provided by European-led Principal Investigator consortia and with important participation from NASA} and with the IRAM\\thanks{This work was based on observations carried out with the IRAM 30-meter telescope. IRAM is supported by INSU/CNRS (France), MPG (Germany) and IGN (Spain)} 30-m telescope. They cover several observing periods spreading over 3 years. The line intensity variations for molecules produced in the external layers of the envelope most probably result from time variations in the infrared pumping rates. We analyze the main implications this discovery has on the interpretation of molecular line emission in the envelopes of Mira-type stars. Radiative trans...

  17. Molecular glass positive i-line photoresist materials containing 2,1,4-DNQ and acid labile group

    Science.gov (United States)

    Wang, Liyuan; Yu, Jinxing; Xu, Na

    2010-04-01

    Recent years increasing attention has been given to molecular glass resist materials. In this paper, maleopimaric acid, cycloaddition reaction product of rosin with maleic anhydride, was reacted with hydroxylamine and then further esterified with 2-diazo-1-naphthoquinone-4-sulfonyl chloride to give N-hydroxy maleopimarimide sulfonate. The carboxylic acid group of the compound was then protected by the reaction of this compound with vinyl ethyl ether or dihydropyran. Thus obtained compounds were amorphous. When irradiated with i-line light, the 2,1,4-DNQ group undergo photolysis not only to give off nitrogen gas but also generate sulfonic acid which can result in the decomposition of the acid labile group. So, a novel chemically amplified positive i-line molecular glass photoresists can be formed by the compound and other acidolytic molecular glass compounds. The lithographic performance of the resist materials is evaluated.

  18. Identification and Molecular Mapping of a Stripe Rust Resistance Gene from a Common Wheat Line Qzl80

    Institute of Scientific and Technical Information of China (English)

    DENGZhi-Yong; ZHANGXiang-Qi; WANGXian-Ping; JINGJian-Kang; WANGDao-Wen

    2004-01-01

    YrQz, a stripe rust disease resistance gene was identified in a common wheat (Triticumaestivum L.) line Qz180. This resistance was controlled by a single dominant gene, which was confirmed bygenetic analysis of two 1:2 populations derived from the crosses using Qz180 and two susceptible parents(Mingxian 169 and WL1). Bulked segregant analysis using simple sequence repeat (SSR) and amplifiedfragment length polymorphism (AFLP) markers was conducted in order to map the chromosomal locationof YrQz. The results indicated that YrQzwas located on the long arm of wheat chromosome 2B and residedin a re,on flanked by two SSR loci Xgwm388and Xgwm526. Two AFLP markers P35M48(452) and P36M61(163) were closely linked to KrQz with the genetic distance of 3.4 cM and 4.1 cM, respectively. To ourknowledge, this is the first molecularly mapped stripe rust resistance gene on wheat chromosome 2B.

  19. Herschel observations of EXtraordinary Sources: Analysis of the full Herschel/HIFI molecular line survey of Sagittarius B2(N)

    CERN Document Server

    Neill, Justin L; Lis, Dariusz C; Schilke, Peter; Crockett, Nathan R; Favre, Cecile; Emprechtinger, Martin; Comito, Claudia; Qin, Sheng-Li; Anderson, Dana E; Burkhardt, Andrew M; Chen, Jo-Hsin; Harris, Brent J; Lord, Steven D; McGuire, Brett A; McNeill, Trevor D; Monje, Raquel R; Phillips, Thomas G; Steber, Amanda L; Vasyunina, Tatiana; Yu, Shanshan

    2014-01-01

    A sensitive broadband molecular line survey of the Sagittarius B2(N) star-forming region has been obtained with the HIFI instrument on the Herschel Space Observatory, offering the first high-spectral resolution look at this well-studied source in a wavelength region largely inaccessible from the ground (625-157 um). From the roughly 8,000 spectral features in the survey, a total of 72 isotopologues arising from 44 different molecules have been identified, ranging from light hydrides to complex organics, and arising from a variety of environments from cold and diffuse to hot and dense gas. We present an LTE model to the spectral signatures of each molecule, constraining the source sizes for hot core species with complementary SMA interferometric observations, and assuming that molecules with related functional group composition are cospatial. For each molecule, a single model is given to fit all of the emission and absorption features of that species across the entire 480-1910 GHz spectral range, accounting fo...

  20. Molecular diagnosis of Theileria and Babesia species infecting cattle in Northern Spain using reverse line blot macroarrays

    Directory of Open Access Journals (Sweden)

    Juste Ramón A

    2006-05-01

    Full Text Available Abstract Background Piroplasmosis in cattle is caused by tick-borne haemoprotozoan parasites of the genera Theileria and Babesia. Molecular detection techniques offer higher sensitivity and specificity than microscopy examination methods and serological tests. A reverse line blot (RLB macroarray that included generic and species-specific probes for Theileria annulata, Theileria buffeli, Babesia bovis, Babesia bigemina, Babesia divergens and Babesia major was used to study the presence and identity of the piroplasm species infecting 263 bovine blood samples from 79 farms, most of them in Northern Spain. Microscopy examination of blood smears and haematology were also performed whenever possible to identify animals with parasitaemia. Results RLB hybridisation identified infection in 54.0% of the samples, whereas only 28.8% were positive by microscopy examination. The most frequently found species was T. buffeli, present in 42.6% of the samples. T. annulata was found in 22 samples (8.4% from 12 farms, including 9 farms (14 samples located in Northern Spain where presence of the vector is not very common. Babesia infections were less frequently detected: B. major was found in 3.0% of the samples, B. bigemina in 2.7%, B. bovis in 2.3% and B. divergens in 1.1%. Mixed infections were detected in 14 samples, accounting for six different combinations of species. Conclusion This is the first report in which B. major and B. divergens have been detected in Spain using molecular identification techniques and the first time that B. bovis has been detected in Northern Spain. The detection of T. annulata in Northern Spain suggests that the distribution of Mediterranean theileriosis might be changing. Samples with positive RLB hybridisation but negative microscopy had haematology values within the normal ranges suggesting that they corresponded to chronic carriers that may serve as reservoirs of the infection. In this sense, sensitive and specific laboratorial

  1. Molecular dissection of colorectal cancer in pre-clinical models identifies biomarkers predicting sensitivity to EGFR inhibitors

    Science.gov (United States)

    Schütte, Moritz; Risch, Thomas; Abdavi-Azar, Nilofar; Boehnke, Karsten; Schumacher, Dirk; Keil, Marlen; Yildiriman, Reha; Jandrasits, Christine; Borodina, Tatiana; Amstislavskiy, Vyacheslav; Worth, Catherine L.; Schweiger, Caroline; Liebs, Sandra; Lange, Martin; Warnatz, Hans- Jörg; Butcher, Lee M.; Barrett, James E.; Sultan, Marc; Wierling, Christoph; Golob-Schwarzl, Nicole; Lax, Sigurd; Uranitsch, Stefan; Becker, Michael; Welte, Yvonne; Regan, Joseph Lewis; Silvestrov, Maxine; Kehler, Inge; Fusi, Alberto; Kessler, Thomas; Herwig, Ralf; Landegren, Ulf; Wienke, Dirk; Nilsson, Mats; Velasco, Juan A.; Garin-Chesa, Pilar; Reinhard, Christoph; Beck, Stephan; Schäfer, Reinhold; Regenbrecht, Christian R. A.; Henderson, David; Lange, Bodo; Haybaeck, Johannes; Keilholz, Ulrich; Hoffmann, Jens; Lehrach, Hans; Yaspo, Marie-Laure

    2017-01-01

    Colorectal carcinoma represents a heterogeneous entity, with only a fraction of the tumours responding to available therapies, requiring a better molecular understanding of the disease in precision oncology. To address this challenge, the OncoTrack consortium recruited 106 CRC patients (stages I–IV) and developed a pre-clinical platform generating a compendium of drug sensitivity data totalling >4,000 assays testing 16 clinical drugs on patient-derived in vivo and in vitro models. This large biobank of 106 tumours, 35 organoids and 59 xenografts, with extensive omics data comparing donor tumours and derived models provides a resource for advancing our understanding of CRC. Models recapitulate many of the genetic and transcriptomic features of the donors, but defined less complex molecular sub-groups because of the loss of human stroma. Linking molecular profiles with drug sensitivity patterns identifies novel biomarkers, including a signature outperforming RAS/RAF mutations in predicting sensitivity to the EGFR inhibitor cetuximab. PMID:28186126

  2. Whole Blood Transcriptomics Is Relevant to Identify Molecular Changes in Response to Genetic Selection for Feed Efficiency and Nutritional Status in the Pig.

    Science.gov (United States)

    Jégou, Maëva; Gondret, Florence; Vincent, Annie; Tréfeu, Christine; Gilbert, Hélène; Louveau, Isabelle

    2016-01-01

    The molecular mechanisms underlying feed efficiency need to be better understood to improve animal efficiency, a research priority to support a competitive and sustainable livestock production. This study was undertaken to determine whether pig blood transcriptome was affected by differences in feed efficiency and by ingested nutrients. Growing pigs from two lines divergently selected for residual feed intake (RFI) and fed isoproteic and isocaloric diets contrasted in energy source and nutrients were considered. Between 74 and 132 days of age, pigs (n = 12 by diet and by line) received a regular diet rich in cereals and low in fat (LF) or a diet where cereals where partially substituted by lipids and fibers (HF). At the end of the feeding trial, the total number of white blood cells was not affected by the line or by the diet, whereas the red blood cell number was higher (Plipid metabolism. Altogether, this study demonstrates the usefulness of the blood transcriptome to identify the main biological processes affected by genetic selection and feeding strategies.

  3. Using Genetic Buffering Relationships Identified in Fission Yeast To Elucidate the Molecular Pathology of Tuberous Sclerosis

    Science.gov (United States)

    2016-07-01

    sclerosis. Our ongoing study has identified two genes, fft3 (a SMARCAD1 family ATP -dependent DNA helicase) and ypa1 (protein phosphatase type 2A...TERMS Tuberous Sclerosis, Genetic Buffering, Fission Yeast, Recombinase-Mediated Cassette Exchange, protein phosphatase type 2A regulator, ATP -dependent...identified two genes, fft3 (encoding a SMARCAD1 family ATP -dependent DNA helicase) and ypa1 (encoding a PTPA family protein phosphatase regulator) as

  4. Combined molecular and biochemical approach identifies Aspergillus japonicus and Aspergillus aculeatus as two species

    DEFF Research Database (Denmark)

    Parenicova, L.; Skouboe, P.; Frisvad, Jens Christian

    2001-01-01

    We examined nine Aspergillus japonicus isolates and 10 Aspergillus aculeatus isolates by using molecular and biochemical markers, including DNA sequences of the ITS1-5.8S rRNA gene-ITS2 region, restriction fragment length polymorphisms (RFLP), and secondary-metabolite profiles. The DNA sequence...... of the internal transcribed spacers (ITS1 and ITS2) and the 5.8S rRNA gene could not be used to distinguish between A. japonicus and A. aculeatus but did show that these two taxa are more closely related to each other than to other species of black aspergilli. Aspergillus niger pyruvate kinase (pkiA) and pectin...

  5. Identifying Molecular Culprits of Cervical Cancer Progression | Center for Cancer Research

    Science.gov (United States)

    Human papillomavirus (HPV) DNA is found in 99.7% of invasive cervical carcinomas, providing strong evidence that the virus is a causative agent in the development of this disease. However, most women who become infected with HPV do not develop invasive cervical lesions, indicating that additional exogenous or genetic factors may determine whether HPV preclinical lesions will progress to cancer. Identification of these factors would be facilitated by a deeper understanding of the cellular and molecular changes that accompany progression to malignancy. In addition, knowledge of which women are at greatest risk for disease progression would be a significant clinical advancement in the management of patients with premalignant cervical lesions.

  6. More on contamination: the use of asymmetric molecular behavior to identify authentic ancient human DNA

    DEFF Research Database (Denmark)

    Malmström, Helena; Svensson, Emma M; Gilbert, M Thomas P;

    2007-01-01

    the reliability of one of the proposed criteria, that of appropriate molecular behavior. Using real-time polymerase chain reaction (PCR) and pyrosequencing, we have quantified the relative levels of authentic aDNA and contaminant human DNA sequences recovered from archaeological dog and cattle remains. In doing....... Furthermore, we find that there is a substantial increase in the relative proportions of authentic DNA to contaminant DNA as the PCR target fragment size is decreased. We therefore conclude that the degradation pattern in aDNA provides a quantifiable difference between authentic aDNA and modern contamination...

  7. Herschel SPIRE and PACS observations of the red supergiant VY CMa: analysis of the molecular line spectra

    CERN Document Server

    Matsuura, Mikako; Barlow, M J; Swinyard, B M; Royer, P; Cernicharo, J; Decin, L; Wesson, R; Polehampton, E T; Blommaert, J A D L; Groenewegen, M A T; Van de Steene, G C; van Hoof, P A M

    2013-01-01

    We present an analysis of the far-infrared and submillimetre molecular emission line spectrum of the luminous M-supergiant VY CMa, observed with the SPIRE and PACS spectrometers aboard the Herschel Space Observatory. Over 260 emission lines were detected in the 190-650-micron SPIRE FTS spectra, with one-third of the observed lines being attributable to H2O. Other detected species include CO, 13CO, H2^18O, SiO, HCN, SO, SO2, CS, H2S, and NH3. Our model fits to the observed 12CO and 13CO line intensities yield a 12C/13C ratio of 5.6+-1.8, consistent with measurements of this ratio for other M supergiants, but significantly lower than previously estimated for VY CMa from observations of lower-J lines. The spectral line energy distribution for twenty SiO rotational lines shows two temperature components: a hot component at 1000 K, which we attribute to the stellar atmosphere and inner wind, plus a cooler ~200 K component, which we attribute to an origin in the outer circumstellar envelope. We fit the line fluxes ...

  8. The diverse heterogeneity of molecular alterations in prostate cancer identified through next-generation sequencing

    Institute of Scientific and Technical Information of China (English)

    Alexander W Wyatt; Fan Mo; Yuzhuo Wang; Colin C Collins

    2013-01-01

    Prostate cancer is a leading cause of global cancer-related death but attempts to improve diagnoses and develop novel therapies have been confounded by significant patient heterogeneity.In recent years,the application of next-generation sequencing to hundreds of prostate tumours has defined novel molecular subtypes and characterized extensive genomic aberration underlying disease initiation and progression.It is now clear that the heterogeneity observed in the clinic is underpinned by a molecular landscape rife with complexity,where genomic rearrangements and rare mutations combine to amplify transcriptomic diversity.This review dissects our current understanding of prostate cancer ‘omics',including the sentinel role of copy number variation,the growing spectrum of oncogenic fusion genes,the potential influence of chromothripsis,and breakthroughs in defining mutation-associated subtypes.Increasing evidence suggests that genomic lesions frequently converge on specific cellular functions and signalling pathways,yet recurrent gene aberration appears rare.Therefore,it is critical that we continue to define individual tumour genomes,especially in the context of their expressed transcriptome.Only through improved characterisation of tumour to tumour variability can we advance to an age of precision therapy and personalized oncology.

  9. Molecular characterization of effluent organic matter identified by ultrahigh resolution mass spectrometry.

    Science.gov (United States)

    Gonsior, Michael; Zwartjes, Matthew; Cooper, William J; Song, Weihua; Ishida, Kenneth P; Tseng, Linda Y; Jeung, Matthew K; Rosso, Diego; Hertkorn, Norbert; Schmitt-Kopplin, Philippe

    2011-04-01

    Effluent dissolved organic matter (EfOM) collected from the secondary-treated wastewater of the Orange County Sanitation District (OCSD) located in Fountain Valley, California, USA was compared to natural organic matter collected from the Suwannee River (SRNOM), Florida using ultrahigh resolution electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS). Furthermore, the two different treatment processes at OCSD, activated sludge and trickling filter, were separately investigated. The blend of these two effluents was further evaluated after it had passed through the microfiltration process of the Advanced Water Purification Facility (AWPF) at Orange County Water District (OCWD). EfOM contained 872 different m/z peaks that were unambiguously assigned to exact molecular formulae containing a single sulfur atom and carbon, hydrogen and oxygen atoms (CHOS formulae). In contrast, the SRNOM sample only contained 152 CHOS formulae. The trend in CHO molecular compositions was opposite with 2500 CHO formulae assigned for SRNOM but only about 1000 for EfOM. The CHOS-derived mass peaks with highest abundances in EfOM could be attributed to surfactants such as linear alkyl benzene sulfonates (LAS), their co-products dialkyl tetralin sulfonates (DATS) and their biodegraded metabolites such as sulfophenyl carboxylic acids (SPC). The differences between the treatments were found minor with greater differences between sampling dates than treatment methods used.

  10. RNA sequencing of Populus x canadensis roots identifies key molecular mechanisms underlying physiological adaption to excess zinc.

    Science.gov (United States)

    Ariani, Andrea; Di Baccio, Daniela; Romeo, Stefania; Lombardi, Lara; Andreucci, Andrea; Lux, Alexander; Horner, David Stephen; Sebastiani, Luca

    2015-01-01

    Populus x canadensis clone I-214 exhibits a general indicator phenotype in response to excess Zn, and a higher metal uptake in roots than in shoots with a reduced translocation to aerial parts under hydroponic conditions. This physiological adaptation seems mainly regulated by roots, although the molecular mechanisms that underlie these processes are still poorly understood. Here, differential expression analysis using RNA-sequencing technology was used to identify the molecular mechanisms involved in the response to excess Zn in root. In order to maximize specificity of detection of differentially expressed (DE) genes, we consider the intersection of genes identified by three distinct statistical approaches (61 up- and 19 down-regulated) and validate them by RT-qPCR, yielding an agreement of 93% between the two experimental techniques. Gene Ontology (GO) terms related to oxidation-reduction processes, transport and cellular iron ion homeostasis were enriched among DE genes, highlighting the importance of metal homeostasis in adaptation to excess Zn by P. x canadensis clone I-214. We identified the up-regulation of two Populus metal transporters (ZIP2 and NRAMP1) probably involved in metal uptake, and the down-regulation of a NAS4 gene involved in metal translocation. We identified also four Fe-homeostasis transcription factors (two bHLH38 genes, FIT and BTS) that were differentially expressed, probably for reducing Zn-induced Fe-deficiency. In particular, we suggest that the down-regulation of FIT transcription factor could be a mechanism to cope with Zn-induced Fe-deficiency in Populus. These results provide insight into the molecular mechanisms involved in adaption to excess Zn in Populus spp., but could also constitute a starting point for the identification and characterization of molecular markers or biotechnological targets for possible improvement of phytoremediation performances of poplar trees.

  11. RNA sequencing of Populus x canadensis roots identifies key molecular mechanisms underlying physiological adaption to excess zinc.

    Directory of Open Access Journals (Sweden)

    Andrea Ariani

    Full Text Available Populus x canadensis clone I-214 exhibits a general indicator phenotype in response to excess Zn, and a higher metal uptake in roots than in shoots with a reduced translocation to aerial parts under hydroponic conditions. This physiological adaptation seems mainly regulated by roots, although the molecular mechanisms that underlie these processes are still poorly understood. Here, differential expression analysis using RNA-sequencing technology was used to identify the molecular mechanisms involved in the response to excess Zn in root. In order to maximize specificity of detection of differentially expressed (DE genes, we consider the intersection of genes identified by three distinct statistical approaches (61 up- and 19 down-regulated and validate them by RT-qPCR, yielding an agreement of 93% between the two experimental techniques. Gene Ontology (GO terms related to oxidation-reduction processes, transport and cellular iron ion homeostasis were enriched among DE genes, highlighting the importance of metal homeostasis in adaptation to excess Zn by P. x canadensis clone I-214. We identified the up-regulation of two Populus metal transporters (ZIP2 and NRAMP1 probably involved in metal uptake, and the down-regulation of a NAS4 gene involved in metal translocation. We identified also four Fe-homeostasis transcription factors (two bHLH38 genes, FIT and BTS that were differentially expressed, probably for reducing Zn-induced Fe-deficiency. In particular, we suggest that the down-regulation of FIT transcription factor could be a mechanism to cope with Zn-induced Fe-deficiency in Populus. These results provide insight into the molecular mechanisms involved in adaption to excess Zn in Populus spp., but could also constitute a starting point for the identification and characterization of molecular markers or biotechnological targets for possible improvement of phytoremediation performances of poplar trees.

  12. Molecular-targeted first-line therapy for advanced gastric cancer.

    Science.gov (United States)

    Song, Huan; Zhu, Jianwei; Lu, DongHao

    2016-07-19

    95% confidence intervals (CI). We included 11 studies randomizing 4014 participants to molecular-targeted therapy plus conventional chemotherapy or chemotherapy alone. Five were at low risk of bias, and we considered the risk of bias in the other six studies to be high, mainly due to their open-label design. All identified studies reported data regarding survival. We found low-quality evidence that molecular-targeted may have a small effect on mortality (HR 0.92, 95% CI 0.80 to 1.05, 10 studies) compared with conventional chemotherapy alone. Similarly, it may have little effect on progression-free survival when compared with conventional chemotherapy alone (HR 0.90, 95% CI 0.78 to 1.04, 11 studies; low-quality evidence). We did not find evidence from subgroup analysis that survival outcomes differed by type of molecular-targeted agent (EGFR- or VEGF-targeting agents) or tumor type, meaning that we were unable to explain the variation in effect across the studies by the presence or absence of prognostic biomarkers or type of molecular-targeted agent. From 11 eligible trials, we were able to use data from 3723 participants with measurable tumors. We found low-quality evidence that molecular-targeted therapy may increase tumor response (OR 1.24, 95% CI 1.00 to 1.55, low-quality evidence). Data from one small trial were too limited to determine the effect of treatment on quality of life (very low-quality evidence). The addition of targeted therapy to chemotherapy probably increases the risk of adverse events (OR 2.23, 95% CI 1.27 to 3.92, 5 trials, 2290 participants, moderate-quality evidence) and severe adverse event (OR 1.19, 95% CI 1.03 to 1.37, 8 trials, 3800 participants), compared with receiving chemotherapy alone. There is uncertainty about the effect of adding targeted therapy to chemotherapy on survival outcomes in people with advanced gastric cancer, with very little information on its impact on quality of life. There is more certain evidence of increased risk

  13. Agronomic and molecular evaluation of maize inbred lines for drought tolerance

    Directory of Open Access Journals (Sweden)

    Sanja Mikić

    2016-12-01

    Full Text Available Drought is a severe threat to maize yield stability in Serbia and other temperate Southeast European countries occurring occasionally but with significant yield losses. The development of resilient genotypes that perform well under drought is one of the main focuses of maize breeding programmes. To test the tolerance of newly developed elite maize inbred lines to drought stress, field trials for grain yield performance and anthesis silk interval (ASI were set in drought stressed environments in 2011 and 2012. Inbred lines performing well under drought, clustered into a group with short ASI and a smaller group with long ASI, were considered as a potential source for tolerance. The former contained inbreds from different heterotic groups and with a proportion of local germplasm. The latter consisted of genotypes with mixed exotic and Lancaster germplasm, which performed better in more drought-affected environments. Three inbreds were selected for their potential drought tolerance, showing an above-average yield and small ASI in all environments. Association analysis indicated significant correlations between ASI and grain yield and three microsatellites (bnlg1525, bnlg238 and umc1025. Eight alleles were selected for their favourable concurrent effect on yield increase and ASI decrease. The proportion of phenotypic variation explained by the markers varied across environments from 5.7% to 22.4% and from 4.6% to 8.1% for ASI and yield, respectively. The alleles with strongest effect on performance of particular genotypes and their interactions in specific environments were identified by the mean of partial least square interactions analysis indicating potential suitability of the makers for tolerant genotype selection.

  14. ExoMol: Molecular Line List for Exoplanets and Other Atmospheres

    Science.gov (United States)

    Tennyson, Jonathan; Yurchenko, Sergei N.; Polyansky, Oleg

    2016-06-01

    The discovery of extrasolar planets is one of the major scientific advances of the last two decades. Thousands of planets have now been detected and astronomers are beginning to characterize their composition and physical characteristics. To do this requires a huge quantity of spectroscopic data most of which are not available from laboratory studies. The ExoMol project [1] is generating a comprehensive solution to this problem by providing spectroscopic data on all the molecular transitions of importance in the atmospheres of exoplanets. These data are widely applicable to other problems such studies on cool stars, brown dwarfs and circumstellar environments as well as industrial and technological problems on earth. ExoMol employs a mixture of first principles and empirically tuned quantum mechanical methods to compute comprehensive and very large rotation-vibration and rovibronic line lists. Results span a variety of closed (NaH, SiO, PN, NaCl, KCl, CS) and open (BeH, MgH, CaH, AlO, VO) shell diatomics to triatomics (HCN/HNC, SO_2, H_2S, H_3^+), tetratomics (H_2CO, PH_3, SO_3, H_2O_2), plus methane [2] and nitric acid [3]. This has led directly to the detection of new species in the atmospheres of exoplanets [4]. A new comprehensive data release has just been completed [5]. Progress on and future prospects of the project will be summarised. J. Tennyson, S. N. Yurchenko, Mon. Not. R. astr. Soc., 425, 21, 2012. S. N. Yurchenko, J. Tennyson, J. Bailey, M. D. J. Hollis, G Tinetti, Proc. Nat. Acad. Sci., 111, 9379, 2014. A. I. Pavlyuchko, S. N. Yurchenko, J. Tennyson, Mon. Not. R. astr. Soc., 452, 1702, 2015. A. Tsiaras et al, Astrophys. J., in press. J. Tennyson et al, J. Mol. Spectrosc., in press.

  15. Molecular docking and NMR binding studies to identify novel inhibitors of human phosphomevalonate kinase

    Energy Technology Data Exchange (ETDEWEB)

    Boonsri, Pornthip [Chemical Proteomics Facility at Marquette, Department of Chemistry, Marquette University, Milwaukee, WI 53201 (United States); Department of Chemistry, NANOTEC Center of Nanotechnology, National Nanotechnology Center, Faculty of Science, Kasetsart University, Bangkok 10900 (Thailand); Neumann, Terrence S.; Olson, Andrew L.; Cai, Sheng [Chemical Proteomics Facility at Marquette, Department of Chemistry, Marquette University, Milwaukee, WI 53201 (United States); Herdendorf, Timothy J.; Miziorko, Henry M. [Division of Molecular Biology and Biochemistry, School of Biological Sciences, University of Missouri-Kansas City, Kansas City, MO 64110 (United States); Hannongbua, Supa [Department of Chemistry, NANOTEC Center of Nanotechnology, National Nanotechnology Center, Faculty of Science, Kasetsart University, Bangkok 10900 (Thailand); Sem, Daniel S., E-mail: daniel.sem@cuw.edu [Chemical Proteomics Facility at Marquette, Department of Chemistry, Marquette University, Milwaukee, WI 53201 (United States)

    2013-01-04

    Highlights: Black-Right-Pointing-Pointer Natural and synthetic inhibitors of human phosphomevalonate kinase identified. Black-Right-Pointing-Pointer Virtual screening yielded a hit rate of 15%, with inhibitor K{sub d}'s of 10-60 {mu}M. Black-Right-Pointing-Pointer NMR studies indicate significant protein conformational changes upon binding. -- Abstract: Phosphomevalonate kinase (PMK) phosphorylates mevalonate-5-phosphate (M5P) in the mevalonate pathway, which is the sole source of isoprenoids and steroids in humans. We have identified new PMK inhibitors with virtual screening, using autodock. Promising hits were verified and their affinity measured using NMR-based {sup 1}H-{sup 15}N heteronuclear single quantum coherence (HSQC) chemical shift perturbation and fluorescence titrations. Chemical shift changes were monitored, plotted, and fitted to obtain dissociation constants (K{sub d}). Tight binding compounds with K{sub d}'s ranging from 6-60 {mu}M were identified. These compounds tended to have significant polarity and negative charge, similar to the natural substrates (M5P and ATP). HSQC cross peak changes suggest that binding induces a global conformational change, such as domain closure. Compounds identified in this study serve as chemical genetic probes of human PMK, to explore pharmacology of the mevalonate pathway, as well as starting points for further drug development.

  16. Salmonellosis in the Republic of Georgia: using molecular typing to identify the outbreak-causing strain.

    OpenAIRE

    Sulakvelidze, A; Kekelidze, M.; Turabelidze, D.; Tsanava, S.; Tevsadze, L.; Devdariani, L.; Gautom, R.; Myers, R.; Morris, J G; Imnadze, P.

    2000-01-01

    In May 1998, three large outbreaks of salmonellosis, affecting 91 persons, were identified in the Republic of Georgia. Eighteen Salmonella Typhimurium strains were characterized by arbitrary primed polymerase chain reaction and pulsed-field gel electrophoresis; the results suggested that all cases were part of a single outbreak caused by a distinct clonal strain.

  17. Using molecular genetics to identify immature specimens of the weevil Ceratapion basicorne (Coleoptera, Apionidae)

    Science.gov (United States)

    A field experiment was conducted to evaluate host plant specificity of the yellow starthistle rosette weevil, Ceratapion basicorne. Larvae infesting plants were preserved in 99% ethanol. Adult specimens of C. basicorne and four closely related species were identified using conventional morphologic...

  18. Arterial tortuosity syndrome : Clinical and molecular findings in 12 newly identified families

    NARCIS (Netherlands)

    Callewaert, B. L.; Willaert, A.; Kerstjens-Frederikse, W. S.; De Backer, J.; Devriendt, K.; Albrecht, B.; Ramos-Arroyo, M. A.; Doco-Fenzy, M.; Hennekam, R. C. M.; Pyeritz, R. E.; Krogmann, O. N.; Gillessen-kaesbach, G.; Wakeling, E. L.; Nik-zainal, S.; Francannet, C.; Mauran, P.; Booth, C.; Barrow, M.; Dekens, R.; Loeys, B. L.; Coucke, P. J.; De Paepe, A. M.

    2008-01-01

    Arterial tortuosity syndrome (ATS) is a rare autosomal recessive connective tissue disease, characterized by widespread arterial involvement with elongation, tortuosity, and aneurysms of the large and middle-sized arteries. Recently, SLC2A10 mutations were identified in this condition. This gene enc

  19. Molecular Characterization of Trichomonas vaginalis Strains Based on Identifying Their Probable Variations in Asymptomatic Patients

    Science.gov (United States)

    SPOTIN, Adel; EGHTEDAR, Sanaz TAGHIZADEH; SHAHBAZI, Abbas; SALEHPOUR, Asghar; SARAFRAZ, Seddigheh; SHARIATZADEH, Seyyed Ali; MAHAMI-OSKOUEI, Mahmoud

    2016-01-01

    Background: The aim of this study was to identify the Trichomonas vaginalis strains/haplotypes based on identifying their probable variations in asymptomatic patients referred to Tabriz health centers, northwestern Iran. Methods: Sampling was taken from 50-suspected women to T. vaginalis in northwestern Iran. The obtained samples were smeared and cultured. Fifty DNA samples were extracted, amplified and identified by nested polymerase chain reaction and PCR-RFLP of actin gene using two endonuclease enzymes: MseI and RsaI. To reconfirm, the amplicons of actin gene were directly sequenced in order to identify the strains/haplotypes. Results: PCR-RFLP patterns, sequencing and phylogenetic analyses revealed definitely the presence of the G (n=22; 73.4%) and E (n=8; 26.6%) strains. Multiple alignments findings of genotype G showed five haplotypes and two amino acid substitutions in codons 192 and 211 although, no remarkable unique haplotype was found in genotype E. Conclusion: The accurate identification of T. vaginalis strains based on discrimination of their unknown haplotypes particularly those which are impacted on protein translation should be considered in parasite status, drug resistance, mixed infection with HIV and monitoring of asymptomatic trichomoniasis in the region. PMID:28127362

  20. ApoE4-specific Misfolded Intermediate Identified by Molecular Dynamics Simulations.

    Science.gov (United States)

    Williams, Benfeard; Convertino, Marino; Das, Jhuma; Dokholyan, Nikolay V

    2015-10-01

    The increased risk of developing Alzheimer's disease (AD) is associated with the APOE gene, which encodes for three variants of Apolipoprotein E, namely E2, E3, E4, differing only by two amino acids at positions 112 and 158. ApoE4 is known to be the strongest risk factor for AD onset, while ApoE3 and ApoE2 are considered to be the AD-neutral and AD-protective isoforms, respectively. It has been hypothesized that the ApoE isoforms may contribute to the development of AD by modifying the homeostasis of ApoE physiological partners and AD-related proteins in an isoform-specific fashion. Here we find that, despite the high sequence similarity among the three ApoE variants, only ApoE4 exhibits a misfolded intermediate state characterized by isoform-specific domain-domain interactions in molecular dynamics simulations. The existence of an ApoE4-specific intermediate state can contribute to the onset of AD by altering multiple cellular pathways involved in ApoE-dependent lipid transport efficiency or in AD-related protein aggregation and clearance. We present what we believe to be the first structural model of an ApoE4 misfolded intermediate state, which may serve to elucidate the molecular mechanism underlying the role of ApoE4 in AD pathogenesis. The knowledge of the structure for the ApoE4 folding intermediate provides a new platform for the rational design of alternative therapeutic strategies to fight AD.

  1. ApoE4-specific Misfolded Intermediate Identified by Molecular Dynamics Simulations.

    Directory of Open Access Journals (Sweden)

    Benfeard Williams

    2015-10-01

    Full Text Available The increased risk of developing Alzheimer's disease (AD is associated with the APOE gene, which encodes for three variants of Apolipoprotein E, namely E2, E3, E4, differing only by two amino acids at positions 112 and 158. ApoE4 is known to be the strongest risk factor for AD onset, while ApoE3 and ApoE2 are considered to be the AD-neutral and AD-protective isoforms, respectively. It has been hypothesized that the ApoE isoforms may contribute to the development of AD by modifying the homeostasis of ApoE physiological partners and AD-related proteins in an isoform-specific fashion. Here we find that, despite the high sequence similarity among the three ApoE variants, only ApoE4 exhibits a misfolded intermediate state characterized by isoform-specific domain-domain interactions in molecular dynamics simulations. The existence of an ApoE4-specific intermediate state can contribute to the onset of AD by altering multiple cellular pathways involved in ApoE-dependent lipid transport efficiency or in AD-related protein aggregation and clearance. We present what we believe to be the first structural model of an ApoE4 misfolded intermediate state, which may serve to elucidate the molecular mechanism underlying the role of ApoE4 in AD pathogenesis. The knowledge of the structure for the ApoE4 folding intermediate provides a new platform for the rational design of alternative therapeutic strategies to fight AD.

  2. Using combined morphological, allometric and molecular approaches to identify species of the genus Raillietiella (Pentastomida.

    Directory of Open Access Journals (Sweden)

    Crystal Kelehear

    Full Text Available Taxonomic studies of parasites can be severely compromised if the host species affects parasite morphology; an uncritical analysis might recognize multiple taxa simply because of phenotypically plastic responses of parasite morphology to host physiology. Pentastomids of the genus Raillietiella are endoparasitic crustaceans primarily infecting the respiratory system of carnivorous reptiles, but also recorded from bufonid anurans. The delineation of pentastomids at the generic level is clear, but the taxonomic status of many species is not. We collected raillietiellids from lungs of the invasive cane toad (Rhinella marina, the invasive Asian house gecko (Hemidactylus frenatus, and a native tree frog (Litoria caerulea in tropical Australia, and employed a combination of genetic analyses, and traditional and novel morphological methods to clarify their identity. Conventional analyses of parasite morphology (which focus on raw values of morphological traits revealed two discrete clusters in terms of pentastome hook size, implying two different species of pentastomes: one from toads and a tree frog (Raillietiella indica and another from lizards (Raillietiella frenatus. However, these clusters disappeared in allometric analyses that took pentastome body size into account, suggesting that only a single pentastome taxon may be involved. Our molecular data revealed no genetic differences between parasites in toads versus lizards, confirming that there was only one species: R. frenatus. This pentastome (previously known only from lizards clearly is also capable of maturing in anurans. Our analyses show that the morphological features used in pentastomid taxonomy change as the parasite transitions through developmental stages in the definitive host. To facilitate valid descriptions of new species of pentastomes, future taxonomic work should include both morphological measurements (incorporating quantitative measures of body size and hook bluntness and

  3. Detailed modelling of the circumstellar molecular line emission of the S-type AGB star W Aquilae

    CERN Document Server

    Danilovich, T; Justtanont, K; Lombaert, R; Maercker, M; Olofsson, H; Ramstedt, S; Royer, P

    2014-01-01

    S-type AGB stars have a C/O ratio which suggests that they are transition objects between oxygen-rich M-type stars and carbon-rich C-type stars. As such, their circumstellar compositions of gas and dust are thought to be sensitive to their precise C/O ratio, and it is therefore of particular interest to examine their circumstellar properties. We present new Herschel HIFI and PACS sub-millimetre and far-infrared line observations of several molecular species towards the S-type AGB star W Aql. We use these observations, which probe a wide range of gas temperatures, to constrain the circumstellar properties of W Aql, including mass-loss rate and molecular abundances. We used radiative transfer codes to model the circumstellar dust and molecular line emission to determine circumstellar properties and molecular abundances. We assumed a spherically symmetric envelope formed by a constant mass-loss rate driven by an accelerating wind. Our model includes fully integrated H2O line cooling as part of the solution of th...

  4. Comparison of four molecular approaches to identify Candida parapsilosis complex species

    Science.gov (United States)

    Barbedo, Leonardo Silva; Figueiredo-Carvalho, Maria Helena Galdino; Muniz, Mauro de Medeiros; Zancopé-Oliveira, Rosely Maria

    2017-01-01

    Since the description of Candida orthopsilosis and C. metapsilosis in 2005, several methods have been proposed to identify and differentiate these species from C. parapsilosis sensu stricto. Species-specific uniplex polymerase chain reaction (PCR) was performed and compared with sequencing of the D1/D2 region of the LSU 28S rDNA gene, microsatellite typing of C. parapsilosis sensu stricto, and PCR-restriction fragment length polymorphism patterns in the ITS1-5.8S-ITS2 region of the rDNA gene. There was agreement between results of testing of 98 clinical isolates with the four PCR-based methods, with 59 isolates identified as C. parapsilosis sensu stricto, 37 as C. orthopsilosis, and two as C. metapsilosis. PMID:28225905

  5. Molecular cytogenetic identification of a wheat-rye 1R addition line with multiple spikelets and resistance to powdery mildew.

    Science.gov (United States)

    Yang, Wujuan; Wang, Changyou; Chen, Chunhuan; Wang, Yajuan; Zhang, Hong; Liu, Xinlun; Ji, Wanquan

    2016-04-01

    Alien addition lines are important for transferring useful genes from alien species into common wheat. Rye is an important and valuable gene resource for improving wheat disease resistance, yield, and environment adaptation. A new wheat-rye addition line, N9436B, was developed from the progeny of the cross of common wheat (Triticum aestivum L., 2n = 6x = 42, AABBDD) cultivar Shaanmai 611 and rye (Secale cereal L., 2n = 2x = 14, RR) accession Austrian rye. We characterized this new line by cytology, genomic in situ hybridization (GISH), fluorescence in situ hybridization (FISH), molecular markers, and disease resistance screening. N9436B was stable in morphology and cytology, with a chromosome composition of 2n = 42 + 2t = 22II. GISH investigations showed that this line contained two rye chromosomes. GISH, FISH, and molecular maker identification suggested that the introduced R chromosome and the missing wheat chromosome arms were 1R chromosome and 2DL chromosome arm, respectively. N9436B exhibited 30-37 spikelets per spike and a high level of resistance to powdery mildew (Blumeria graminis f. sp. tritici, Bgt) isolate E09 at the seedling stage. N9436B was cytologically stable, had the trait of multiple spikelets, and was resistant to powdery mildew; this line should thus be useful in wheat improvement.

  6. Galactosemia: A strategy to identify new biochemical phenotypes and molecular genotypes

    Energy Technology Data Exchange (ETDEWEB)

    Elsas, L.J.; Langley, S.; Steele, E.; Evinger, J.; Brown, A.; Singh, R.; Fernhoff, P.; Hjelm, L.N.; Dembure, P.P.; Fridovich-Keil, J.L. [Emory Univ. School of Medicine, Atlanta, GA (United States)

    1995-03-01

    We describe a stratagem for identifying new mutations in the galactose-1-phosphate uridyl transferase (GALT) gene. GALT enzyme activity and isoforms were defined in erythrocytes from probands and their first-degree relatives. If the biochemical phenotypes segregated in an autosomal recesssive pattern, we screened for common mutations by using multiplex PCR and restriction endonuclease digestions. If common mutant alleles were not present, the 11 exons of the GALT gene were amplified by PCR, and variations from the normal nucleotide sequences were identified by SSCP. The suspected region(s) was then analyzed by direct DNA sequencing. We identified 86 mutant GALT alleles that reduced erythrocyte GALT activity. Seventy-five of these GALT genomes had abnormal SSCP patterns, of which 41 were sequenced, yielding 12 new and 21 previously reported, rare mutations. Among the novel group of 12 new mutations, an unusual biochemical phenotype was found in a family whose newborn proband has classical galactosemia. He had inherited two mutations in cis (N314D-E204K) from his father, whose GALT activity was near normal, and an additional GALT mutation in the splice-acceptor site of intron C (IVSC) from his mother. The substitution of a positively charged E204K mutation created a unique isoform-banding pattern. An asymptomatic sister`s GALT genes carries three mutations (E203K-N314D/N314D) with eight distinct isoform bands. Surprisingly, her erythrocytes have normal GALT activity. We conclude that the synergism of pedigree, biochemical, SSCP, and direct GALT gene analyses is an efficient protocol for identifying new mutations and speculate that E203K and N314D codon changes produce intra-allelic complementation when in cis. 40 refs., 4 figs., 3 tabs.

  7. Identifying possible sister groups of Cryptocercidae+Isoptera: a combined molecular and morphological phylogeny of Dictyoptera.

    Science.gov (United States)

    Djernæs, Marie; Klass, Klaus-Dieter; Eggleton, Paul

    2015-03-01

    Termites (Isoptera) offer an alternative model for the development of eusociality which is not dependent on a high degree of relatedness as found between sisters in hymenopterans (bees, wasps, ants). Recent phylogenetic studies have established that termites belong within the cockroaches as sister to the subsocial Cryptocercidae. Cryptocercidae shares several important traits with termites, thus we need to understand the phylogenetic position of Cryptocercidae+Isoptera to determine how these traits evolved. However, placement of Cryptocercidae+Isoptera is still uncertain. We used both molecular (12S, 16S, COII, 18S, 28S, H3) and morphological characters to reconstruct the phylogeny of Dictyoptera. We included all previously suggested sister groups of Cryptocercidae+Isoptera as well as taxa which might represent additional major cockroach lineages. We used Bayes factors to test different sister groups for Cryptocercidae+Isoptera and assessed character support for the consensus tree based on morphological characters and COII amino acid data. We used the molecular data and fossil calibration to estimate divergence times. We found the most likely sister groups of Cryptocercidae+Isoptera to be Tryonicidae, Anaplecta or Tryonicidae+Anaplecta. Anaplecta has never previously been suggested as sister group or even close to Cryptocercidae+Isoptera, but was formerly placed in Blaberoidea as sister to the remaining taxa. Topological tests firmly supported our new placement of Anaplecta. We discuss the morphological characters (e.g. retractable genitalic hook) that have contributed to the previous placement of Anaplecta in Blaberoidea as well as the factors that might have contributed to a parallel development of genitalic features in Anaplecta and Blaberoidea. Cryptocercidae+Isoptera is placed in a clade with Tryonicidae, Anaplecta and possibly Lamproblattidae. Based on this, we suggest that wood-feeding, and the resultant need to conserve nitrogen, may have been an important

  8. REAL-TIME DETECTION OF SURVIVIN mRNA EXPRESSION IN CERVICAL CANCER CELL LINES USING MOLECULAR BEACON IMAGING

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    The initiated growth of human cancer cells of-ten mostly come fromthe abnor mal expression ofgenes.Survivinis anapotosis inhibitor of IAPfami-ly,cloned by Ambrosini in1997usingthe cDNAofeffector cell protease receptor-1(EPR-1),and is thekey gene for the development and advancement oftumor.Inthe present study,the feasibility of detec-ting the expression of survivin mRNA was exam-inedincervical cancer cell lines using molecular bea-coni maging technology.MATERIALS AND METHODS1Cervical cancer cell lines and ce...

  9. Whole Blood Transcriptomics Is Relevant to Identify Molecular Changes in Response to Genetic Selection for Feed Efficiency and Nutritional Status in the Pig.

    Directory of Open Access Journals (Sweden)

    Maëva Jégou

    Full Text Available The molecular mechanisms underlying feed efficiency need to be better understood to improve animal efficiency, a research priority to support a competitive and sustainable livestock production. This study was undertaken to determine whether pig blood transcriptome was affected by differences in feed efficiency and by ingested nutrients. Growing pigs from two lines divergently selected for residual feed intake (RFI and fed isoproteic and isocaloric diets contrasted in energy source and nutrients were considered. Between 74 and 132 days of age, pigs (n = 12 by diet and by line received a regular diet rich in cereals and low in fat (LF or a diet where cereals where partially substituted by lipids and fibers (HF. At the end of the feeding trial, the total number of white blood cells was not affected by the line or by the diet, whereas the red blood cell number was higher (P<0.001 in low RFI than in high RFI pigs. Analysis of the whole blood transcriptome using a porcine microarray reveals a higher number of probes differentially expressed (DE between RFI lines than between diets (2,154 versus 92 probes DE, P<0.01. This corresponds to 528 overexpressed genes and 477 underexpressed genes in low RFI pigs compared with high RFI pigs, respectively. Overexpressed genes were predominantly associated with translational elongation. Underexpressed genes were mainly involved in the immune response, regulation of inflammatory response, anti-apoptosis process, and cell organization. These findings suggest that selection for RFI has affected the immune status and defense mechanisms of pigs. Genes DE between diets were mainly related to the immune system and lipid metabolism. Altogether, this study demonstrates the usefulness of the blood transcriptome to identify the main biological processes affected by genetic selection and feeding strategies.

  10. A systems biology pipeline identifies new immune and disease related molecular signatures and networks in human cells during microgravity exposure

    Science.gov (United States)

    Mukhopadhyay, Sayak; Saha, Rohini; Palanisamy, Anbarasi; Ghosh, Madhurima; Biswas, Anupriya; Roy, Saheli; Pal, Arijit; Sarkar, Kathakali; Bagh, Sangram

    2016-05-01

    Microgravity is a prominent health hazard for astronauts, yet we understand little about its effect at the molecular systems level. In this study, we have integrated a set of systems-biology tools and databases and have analysed more than 8000 molecular pathways on published global gene expression datasets of human cells in microgravity. Hundreds of new pathways have been identified with statistical confidence for each dataset and despite the difference in cell types and experiments, around 100 of the new pathways are appeared common across the datasets. They are related to reduced inflammation, autoimmunity, diabetes and asthma. We have identified downregulation of NfκB pathway via Notch1 signalling as new pathway for reduced immunity in microgravity. Induction of few cancer types including liver cancer and leukaemia and increased drug response to cancer in microgravity are also found. Increase in olfactory signal transduction is also identified. Genes, based on their expression pattern, are clustered and mathematically stable clusters are identified. The network mapping of genes within a cluster indicates the plausible functional connections in microgravity. This pipeline gives a new systems level picture of human cells under microgravity, generates testable hypothesis and may help estimating risk and developing medicine for space missions.

  11. Molecular markers and imaging tools to identify malignant potential in Barrett’s esophagus

    Institute of Scientific and Technical Information of China (English)

    Michael; Bennett; Hiroshi; Mashimo

    2014-01-01

    Due to its rapidly rising incidence and high mortality, esophageal adenocarcinoma is a major public health concern, particularly in Western countries. The steps involved in the progression from its predisposing condition, gastroesophageal reflux disease, to its premalignant disorder, Barrett’s esophagus, and to cancer, are incompletely understood. Current screening and surveillance methods are limited by the lack of population-wide utility, incomplete sampling of standard biopsies, and subjectivity of evaluation. Advances in endoscopic ablation have raised the hope of effective therapy for eradication of high-risk Barrett’s lesions, but improvements are needed in determining when to apply this treatment and how to follow patients clinically. Researchers have evaluated numerous potential molecular biomarkers with the goal of detecting dysplasia, with varying degrees of success. The combination of biomarker panels with epidemiologic risk factors to yield clinical risk scoring systems is promising. New approaches to sample tissue may also be combined with these biomarkers for less invasive screening and sur-veillance. The development of novel endoscopic imaging tools in recent years has the potential to markedly improve detection of small foci of dysplasia in vivo. Current and future efforts will aim to determine the combination of markers and imaging modalities that will most effectively improve the rate of early detection of highrisk lesions in Barrett’s esophagus.

  12. How do we identify RHD variants using a practical molecular approach?

    Science.gov (United States)

    Arnoni, Carine Prisco; Latini, Flavia Roche Moreira; Muniz, Janaína Guilhem; Gazito, Diana; Person, Rosangela de Medeiros; de Paula Vendrame, Tatiane Aparecida; Barreto, José Augusto; Castilho, Lilian

    2014-04-01

    Serologic resolution of Rh discrepancies due to partial D or weak D phenotypes is a frequent problem encountered during routine typing that can be solved by RHD genotyping because it provides better characterization of these variants. The objective of the current study was to develop algorithms for identification of D variants in multiethnic populations based on a logic sequence of molecular tests using a large number of atypical RhD specimens. Thus, a total of 360 blood samples with atypical D antigen expression were analyzed. A previously published multiplex polymerase chain reaction (PCR) procedure was performed and depending on multiplex PCR analysis, the associated RHCE allele, and D variant frequency in our population, an algorithm was developed composed of six flow charts using specific PCR-restriction fragment length polymorphism and/or specific exon sequencing. This strategy allowed the identification of 22 different variants with few assays and a much reduced cost. This study describes a simple and practical algorithm that we use to determine RHD genotypes in samples with unknown RHD. This strategy is relatively easy to implement and the algorithm can be adapted to populations with various ethnic backgrounds after an initial assessment of the type and frequency of D variants. Essentially, we demonstrate that sequencing of all RHD exons is not necessary for the identification of the majority of known D variants.

  13. Fuzzy logic selection as a new reliable tool to identify molecular grade signatures in breast cancer--the INNODIAG study.

    Science.gov (United States)

    Kempowsky-Hamon, Tatiana; Valle, Carine; Lacroix-Triki, Magali; Hedjazi, Lyamine; Trouilh, Lidwine; Lamarre, Sophie; Labourdette, Delphine; Roger, Laurence; Mhamdi, Loubna; Dalenc, Florence; Filleron, Thomas; Favre, Gilles; François, Jean-Marie; Le Lann, Marie-Véronique; Anton-Leberre, Véronique

    2015-02-07

    Personalized medicine has become a priority in breast cancer patient management. In addition to the routinely used clinicopathological characteristics, clinicians will have to face an increasing amount of data derived from tumor molecular profiling. The aims of this study were to develop a new gene selection method based on a fuzzy logic selection and classification algorithm, and to validate the gene signatures obtained on breast cancer patient cohorts. We analyzed data from four published gene expression datasets for breast carcinomas. We identified the best discriminating genes by comparing molecular expression profiles between histologic grade 1 and 3 tumors for each of the training datasets. The most pertinent probes were selected and used to define fuzzy molecular grade 1-like (good prognosis) and fuzzy molecular grade 3-like (poor prognosis) profiles. To evaluate the prognostic performance of the fuzzy grade signatures in breast cancer tumors, a Kaplan-Meier analysis was conducted to compare the relapse-free survival deduced from histologic grade and fuzzy molecular grade classification. We applied the fuzzy logic selection on breast cancer databases and obtained four new gene signatures. Analysis in the training public sets showed good performance of these gene signatures for grade (sensitivity from 90% to 95%, specificity 67% to 93%). To validate these gene signatures, we designed probes on custom microarrays and tested them on 150 invasive breast carcinomas. Good performance was obtained with an error rate of less than 10%. For one gene signature, among 74 histologic grade 3 and 18 grade 1 tumors, 88 cases (96%) were correctly assigned. Interestingly histologic grade 2 tumors (n = 58) were split in these two molecular grade categories. We confirmed the use of fuzzy logic selection as a new tool to identify gene signatures with good reliability and increased classification power. This method based on artificial intelligence algorithms was successfully

  14. Molecular cytogenetic identification of a wheat– Thinopyrum ponticum translocation line resistant to powdery mildew

    Indian Academy of Sciences (India)

    FANG HE; YINGUANG BAO; XIAOLEI QI; YINGXUE MA; XINGFENG LI; HONGGANG WANG

    2017-03-01

    Thinopyrum ponticum (2n = 70) serves as a valuable gene pool for wheat improvement. Line SN0224, derived from crosses between Th. ponticum and the common wheat cultivar Yannong15, was identified in the present study. Cytogenetic observations showed that SN0224 contains 42 chromosomes in the root-tip cells and 21 bivalents in the pollen mother cells, therebydemonstrating its cytogenetic stability. Genomic in situ hybridization, probed with the total genomic DNA of Th. ponticum, produced hybridization signals in the distal region of two wheat chromosome arms. After inoculation with the Blumeriagraminis f. sp. tritici (Bgt) isolates, SN0224 exhibited immunity. Segregation in F1s and F2s from the cross SN0224/cv. Huixianhong indicated that SN0224 carries a single dominant gene for powdery mildew (Pm) resistance, which was temporarily designated PmSn0224. Three markers Barc212, Xwmc522 and Xbarc1138 were detected to be linked with PmSn0224. Based on the locations of the markers, PmSn0224 was located on the chromosome 2A. None of the three markers above is linked with the previously reported PM resistance genes on chromosome 2A, and none of the previously reported PM resistance genes on chromosome 2A is related to Th. ponticum. Therefore, PmSn0224 is likely a novel gene putatively from Th. ponticum.

  15. Identification and molecular characterization of LTR and LINE retrotransposable elements in Fagus sylvatica L.

    Directory of Open Access Journals (Sweden)

    Emiliani G

    2009-06-01

    Full Text Available Retrotransposable elements are important and peculiar genetic components derived from ancient retrovirus insertion inside plants genome. Their ability to move and/or replicate inside the genome is an important evolutionary force, responsible for the increase of genome size and the regulation of gene expression. Retrotransposable elements are well characterized in model or crop species like Arabidopsis thaliana and Oryza sativa, but are poorly known in forest tree species. In this paper the molecular identification of retrotransposable elements in Fagus sylvatica L. is reported. Two retrotransposons, belonging to the two major classes of LTR and non-LTR elements, were characterized trough a SCAR (Sequence Characterized Amplified Region strategy. The analysis demonstrated the presence of multiple copies of retrotransposable elements inside the genome of beech, in accordance with the viral quasi-species theory of retrotransposon evolution. The cloning and sequencing of amplification products and a Cleaved Amplified Polymorphisms (CAPs approach on the identified retrotransposons, showed a high level of diversity among the multiple copies of both elements. The identification of retrotransposable elements in forest trees represents an important step toward the understanding of mechanisms of genome evolution. Furthermore, the high polymorphism of retrotransposable elements can represent a starting point for the development of new genetic variability markers.

  16. Molecular characterization of a novel luteovirus from peach identified by high-throughput sequencing.

    Science.gov (United States)

    Wu, L-P; Liu, H-W; Bateman, M; Liu, Z; Li, R

    2017-05-26

    Contigs with sequence homologies to cherry-associated luteovirus were identified by high-throughput sequencing analysis in two peach accessions. Complete genomic sequences of the two isolates of this virus were determined to be 5,819 and 5,814 nucleotides long, respectively. The genome of the new virus is typical of luteoviruses, containing eight open reading frames in a very similar arrangement. Its genomic sequence is 58-74% identical to those of other members of the genus Luteovirus. These sequences thus belong to a new virus, which we have named "peach-associated luteovirus".

  17. Molecular line emission in NGC 1068 imaged with ALMA : I. An AGN-driven outflow in the dense molecular gas

    NARCIS (Netherlands)

    García-Burillo, S.; Combes, F.; Usero, A.; Aalto, S.; Krips, M.; Viti, S.; Alonso-Herrero, A.; Hunt, L. K.; Schinnerer, E.; Baker, A. J.; Boone, F.; Casasola, V.; Colina, L.; Costagliola, F.; Eckart, A.; Fuente, A.; Henkel, C.; Labiano, A.; Martín, S.; Márquez, I.; Muller, S.; Planesas, P.; Ramos Almeida, C.; Spaans, M.; Tacconi, L. J.; van der Werf, P. P.

    2014-01-01

    Aims: We investigate the fueling and the feedback of star formation and nuclear activity in NGC 1068, a nearby (D = 14 Mpc) Seyfert 2 barred galaxy, by analyzing the distribution and kinematics of the molecular gas in the disk. We aim to understand if and how gas accretion can self-regulate. Methods

  18. Molecular line emission in NGC 1068 imaged with ALMA. I. An AGN-driven outflow in the dense molecular gas

    NARCIS (Netherlands)

    García-Burillo, S.; Combes, F.; Usero, A.; Aalto, S.; Krips, M.; Viti, S.; Alonso-Herrero, A.; Hunt, L. K.; Schinnerer, E.; Baker, A. J.; Boone, F.; Casasola, V.; Colina, L.; Costagliola, F.; Eckart, A.; Fuente, A.; Henkel, C.; Labiano, A.; Martín, S.; Márquez, I.; Muller, S.; Planesas, P.; Ramos Almeida, C.; Spaans, M.; Tacconi, L. J.; van der Werf, P. P.

    2014-01-01

    Aims: We investigate the fueling and the feedback of star formation and nuclear activity in NGC 1068, a nearby (D = 14 Mpc) Seyfert 2 barred galaxy, by analyzing the distribution and kinematics of the molecular gas in the disk. We aim to understand if and how gas accretion can self-regulate. Methods

  19. The use of Multidimensional Data to Identify the Molecular Biomarker for Pancreatic Ductal Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Liwei Zhuang

    2013-01-01

    Full Text Available Pancreatic ductal adenocarcinoma (PDAC is a lethal disease, and the patient has an extremely poor overall survival with a less than 5% 5-year survival rate. Development of potential biomarkers provides a critical foundation for the diagnosis of PDAC. In this project, we have adopted an integrative approach to simultaneously identify biomarker and generate testable hypothesis from multidimensional omics data. We first examine genes for which expression levels are correlated with survival data. The gene list was screened with TF regulation, predicted miRNA targets information, and KEGG pathways. We identified that 273 candidate genes are correlated with patient survival data. 12 TF regulation gene sets, 11 miRNAs targets gene sets, and 15 KEGG pathways are enriched with these survival genes. Notably, CEBPA/miRNA32/PER2 signaling to the clock rhythm qualifies this pathway as a suitable target for therapeutic intervention in PDAC. PER2 expression was highly associated with survival data, thus representing a novel biomarker for earlier detection of PDAC.

  20. Clinical and molecular characterization of a novel INS mutation identified in patients with MODY phenotype.

    Science.gov (United States)

    Piccini, Barbara; Artuso, Rosangela; Lenzi, Lorenzo; Guasti, Monica; Braccesi, Giulia; Barni, Federica; Casalini, Emilio; Giglio, Sabrina; Toni, Sonia

    2016-11-01

    Correct diagnosis of Maturity-Onset Diabetes of the Young (MODY) is based on genetic tests requiring an appropriate subject selection by clinicians. Mutations in the insulin (INS) gene rarely occur in patients with MODY. This study is aimed at determining the genetic background and clinical phenotype in patients with suspected MODY. 34 patients with suspected MODY, negative for mutations in the GCK, HNF1α, HNF4α, HNF1β and PDX1 genes, were screened by next generation sequencing (NGS). A heterozygous INS mutation was identified in 4 members of the same family. First genetic tests performed identified two heterozygous silent nucleotide substitutions in MODY3/HNF1α gene. An ineffective attempt to suspend insulin therapy, administering repaglinide and sulphonylureas, was made. DNA was re-sequenced by NGS investigating a set of 102 genes. Genes implicated in the pathway of pancreatic β-cells, candidate genes for type 2 diabetes mellitus and genes causative of diabetes in mice were selected. A novel heterozygous variant in human preproinsulin INS gene (c.125T > C) was found in the affected family members. The new INS mutation broadens the spectrum of possible INS phenotypes. Screening for INS mutations is warranted not only in neonatal diabetes but also in MODYx patients and in selected patients with type 1 diabetes mellitus negative for autoantibodies. Subjects with complex diseases without a specific phenotype should be studied by NGS because Sanger sequencing is ineffective and time consuming in detecting rare variants.

  1. Identifying Genetic Hotspots by Mapping Molecular Diversity of Widespread Trees: When Commonness Matters.

    Science.gov (United States)

    Souto, Cintia P; Mathiasen, Paula; Acosta, María Cristina; Quiroga, María Paula; Vidal-Russell, Romina; Echeverría, Cristian; Premoli, Andrea C

    2015-01-01

    Conservation planning requires setting priorities at the same spatial scale at which decision-making processes are undertaken considering all levels of biodiversity, but current methods for identifying biodiversity hotspots ignore its genetic component. We developed a fine-scale approach based on the definition of genetic hotspots, which have high genetic diversity and unique variants that represent their evolutionary potential and evolutionary novelties. Our hypothesis is that wide-ranging taxa with similar ecological tolerances, yet of phylogenetically independent lineages, have been and currently are shaped by ecological and evolutionary forces that result in geographically concordant genetic patterns. We mapped previously published genetic diversity and unique variants of biparentally inherited markers and chloroplast sequences for 9 species from 188 and 275 populations, respectively, of the 4 woody dominant families of the austral temperate forest, an area considered a biodiversity hotspot. Spatial distribution patterns of genetic polymorphisms differed among taxa according to their ecological tolerances. Eight genetic hotspots were detected and we recommend conservation actions for some in the southern Coastal Range in Chile. Existing spatially explicit genetic data from multiple populations and species can help to identify biodiversity hotspots and guide conservation actions to establish science-based protected areas that will preserve the evolutionary potential of key habitats and species.

  2. Structure of human phytanoyl-CoA 2-hydroxylase identifies molecular mechanisms of Refsum disease.

    Science.gov (United States)

    McDonough, Michael A; Kavanagh, Kathryn L; Butler, Danica; Searls, Timothy; Oppermann, Udo; Schofield, Christopher J

    2005-12-01

    Refsum disease (RD), a neurological syndrome characterized by adult onset retinitis pigmentosa, anosmia, sensory neuropathy, and phytanic acidaemia, is caused by elevated levels of phytanic acid. Many cases of RD are associated with mutations in phytanoyl-CoA 2-hydroxylase (PAHX), an Fe(II) and 2-oxoglutarate (2OG)-dependent oxygenase that catalyzes the initial alpha-oxidation step in the degradation of phytenic acid in peroxisomes. We describe the x-ray crystallographic structure of PAHX to 2.5 A resolution complexed with Fe(II) and 2OG and predict the molecular consequences of mutations causing RD. Like other 2OG oxygenases, PAHX possesses a double-stranded beta-helix core, which supports three iron binding ligands (His(175), Asp(177), and His(264)); the 2-oxoacid group of 2OG binds to the Fe(II) in a bidentate manner. The manner in which PAHX binds to Fe(II) and 2OG together with the presence of a cysteine residue (Cys(191)) 6.7 A from the Fe(II) and two further histidine residues (His(155) and His(281)) at its active site distinguishes it from that of the other human 2OG oxygenase for which structures are available, factor inhibiting hypoxia-inducible factor. Of the 15 PAHX residues observed to be mutated in RD patients, 11 cluster in two distinct groups around the Fe(II) (Pro(173), His(175), Gln(176), Asp(177), and His(220)) and 2OG binding sites (Trp(193), Glu(197), Ile(199), Gly(204), Asn(269), and Arg(275)). PAHX may be the first of a new subfamily of coenzyme A-binding 2OG oxygenases.

  3. Toward Accurate Reaction Energetics for Molecular Line Growth at Surface: Quantum Monte Carlo and Density Functional Theory Calculations

    Energy Technology Data Exchange (ETDEWEB)

    Kanai, Y; Takeuchi, N

    2009-10-14

    We revisit the molecular line growth mechanism of styrene on the hydrogenated Si(001) 2x1 surface. In particular, we investigate the energetics of the radical chain reaction mechanism by means of diffusion quantum Monte Carlo (QMC) and density functional theory (DFT) calculations. For the exchange correlation (XC) functional we use the non-empirical generalized-gradient approximation (GGA) and meta-GGA. We find that the QMC result also predicts the intra dimer-row growth of the molecular line over the inter dimer-row growth, supporting the conclusion based on DFT results. However, the absolute magnitudes of the adsorption and reaction energies, and the heights of the energy barriers differ considerably between the QMC and DFT with the GGA/meta-GGA XC functionals.

  4. Correlation analyses of clinical and molecular findings identify candidate biological pathways in systemic juvenile idiopathic arthritis

    Directory of Open Access Journals (Sweden)

    Ling Xuefeng B

    2012-10-01

    Full Text Available Abstract Background Clinicians have long appreciated the distinct phenotype of systemic juvenile idiopathic arthritis (SJIA compared to polyarticular juvenile idiopathic arthritis (POLY. We hypothesized that gene expression profiles of peripheral blood mononuclear cells (PBMC from children with each disease would reveal distinct biological pathways when analyzed for significant associations with elevations in two markers of JIA activity, erythrocyte sedimentation rate (ESR and number of affected joints (joint count, JC. Methods PBMC RNA from SJIA and POLY patients was profiled by kinetic PCR to analyze expression of 181 genes, selected for relevance to immune response pathways. Pearson correlation and Student's t-test analyses were performed to identify transcripts significantly associated with clinical parameters (ESR and JC in SJIA or POLY samples. These transcripts were used to find related biological pathways. Results Combining Pearson and t-test analyses, we found 91 ESR-related and 92 JC-related genes in SJIA. For POLY, 20 ESR-related and 0 JC-related genes were found. Using Ingenuity Systems Pathways Analysis, we identified SJIA ESR-related and JC-related pathways. The two sets of pathways are strongly correlated. In contrast, there is a weaker correlation between SJIA and POLY ESR-related pathways. Notably, distinct biological processes were found to correlate with JC in samples from the earlier systemic plus arthritic phase (SAF of SJIA compared to samples from the later arthritis-predominant phase (AF. Within the SJIA SAF group, IL-10 expression was related to JC, whereas lack of IL-4 appeared to characterize the chronic arthritis (AF subgroup. Conclusions The strong correlation between pathways implicated in elevations of both ESR and JC in SJIA argues that the systemic and arthritic components of the disease are related mechanistically. Inflammatory pathways in SJIA are distinct from those in POLY course JIA, consistent with

  5. A molecular signature in blood identifies early Parkinson’s disease

    Directory of Open Access Journals (Sweden)

    Molochnikov Leonid

    2012-05-01

    Full Text Available Abstract Background The search for biomarkers in Parkinson’s disease (PD is crucial to identify the disease early and monitor the effectiveness of neuroprotective therapies. We aim to assess whether a gene signature could be detected in blood from early/mild PD patients that could support the diagnosis of early PD, focusing on genes found particularly altered in the substantia nigra of sporadic PD. Results The transcriptional expression of seven selected genes was examined in blood samples from 62 early stage PD patients and 64 healthy age-matched controls. Stepwise multivariate logistic regression analysis identified five genes as optimal predictors of PD: p19 S-phase kinase-associated protein 1A (odds ratio [OR] 0.73; 95% confidence interval [CI] 0.60–0.90, huntingtin interacting protein-2 (OR 1.32; CI 1.08–1.61, aldehyde dehydrogenase family 1 subfamily A1 (OR 0.86; 95% CI 0.75–0.99, 19 S proteasomal protein PSMC4 (OR 0.73; 95% CI 0.60–0.89 and heat shock 70-kDa protein 8 (OR 1.39; 95% CI 1.14–1.70. At a 0.5 cut-off the gene panel yielded a sensitivity and specificity in detecting PD of 90.3 and 89.1 respectively and the area under the receiving operating curve (ROC AUC was 0.96. The performance of the five-gene classifier on the de novo PD individuals alone composing the early PD cohort (n = 38, resulted in a similar ROC with an AUC of 0.95, indicating the stability of the model and also, that patient medication had no significant effect on the predictive probability (PP of the classifier for PD risk. The predictive ability of the model was validated in an independent cohort of 30 patients at advanced stage of PD, classifying correctly all cases as PD (100% sensitivity. Notably, the nominal average value of the PP for PD (0.95 (SD = 0.09 in this cohort was higher than that of the early PD group (0.83 (SD = 0.22, suggesting a potential for the model to assess disease severity. Lastly, the gene panel fully

  6. Sustained productivity in recombinant Chinese Hamster Ovary (CHO) cell lines: proteome analysis of the molecular basis for a process-related phenotype

    LENUS (Irish Health Repository)

    Meleady, Paula

    2011-07-24

    Abstract Background The ability of mammalian cell lines to sustain cell specific productivity (Qp) over the full duration of bioprocess culture is a highly desirable phenotype, but the molecular basis for sustainable productivity has not been previously investigated in detail. In order to identify proteins that may be associated with a sustained productivity phenotype, we have conducted a proteomic profiling analysis of two matched pairs of monoclonal antibody-producing Chinese hamster ovary (CHO) cell lines that differ in their ability to sustain productivity over a 10 day fed-batch culture. Results Proteomic profiling of inherent differences between the two sets of comparators using 2D-DIGE (Difference Gel Electrophoresis) and LC-MS\\/MS resulted in the identification of 89 distinct differentially expressed proteins. Overlap comparisons between the two sets of cell line pairs identified 12 proteins (AKRIB8, ANXA1, ANXA4, EIF3I, G6PD, HSPA8, HSP90B1, HSPD1, NUDC, PGAM1, RUVBL1 and CNN3) that were differentially expressed in the same direction. Conclusion These proteins may have an important role in sustaining high productivity of recombinant protein over the duration of a fed-batch bioprocess culture. It is possible that many of these proteins could be useful for future approaches to successfully manipulate or engineer CHO cells in order to sustain productivity of recombinant protein.

  7. A molecular method to detect and identify the native species of southwestern Atlantic Crassostrea (Mollusca: Ostreidae

    Directory of Open Access Journals (Sweden)

    Sandra Ludwig

    2011-08-01

    Full Text Available Among oysters, species of Crassostrea (Sacco, 1897 are the most attractive to aquaculture. In Brazil, the genus is represented by C. rhizophorae (Guilding, 1828 and C. brasiliana (Lamarck, 1819. Because the maturation and breeding technology is not well developed for these species, aquaculturists need a reliable method to decide the correct time to place spat collectors in the field, and to identify both species, which are morphologically similar. In this study a specific Multiplex PCR protocol was developed, using one pair of universal primers from 18S rDNA as a positive control and a pair of specific primers for each target species. The sensitivity and specificity of the protocol was evaluated. It detected C. rhizophorae DNA in low concentrations, and C. brasiliana DNA in even lower concentrations. Further, the Multiplex PCR proved efficient in detecting DNA in concentrations equivalent to that of a single larva of each species, either separated or combined, when mixed with total DNA extract of a plankton sample representing 1000 L of filtered water. Field tests confirmed the applicability of the protocol, which holds the promise to become an important tool for aquaculture or conservation programs, allowing for the continuous monitoring of the life cycle of C. brasiliana and C. rhizophorae, by detecting the right periods of larval release and settlement.

  8. Identifying human disease genes: advances in molecular genetics and computational approaches.

    Science.gov (United States)

    Bakhtiar, S M; Ali, A; Baig, S M; Barh, D; Miyoshi, A; Azevedo, V

    2014-07-04

    The human genome project is one of the significant achievements that have provided detailed insight into our genetic legacy. During the last two decades, biomedical investigations have gathered a considerable body of evidence by detecting more than 2000 disease genes. Despite the imperative advances in the genetic understanding of various diseases, the pathogenesis of many others remains obscure. With recent advances, the laborious methodologies used to identify DNA variations are replaced by direct sequencing of genomic DNA to detect genetic changes. The ability to perform such studies depends equally on the development of high-throughput and economical genotyping methods. Currently, basically for every disease whose origen is still unknown, genetic approaches are available which could be pedigree-dependent or -independent with the capacity to elucidate fundamental disease mechanisms. Computer algorithms and programs for linkage analysis have formed the foundation for many disease gene detection projects, similarly databases of clinical findings have been widely used to support diagnostic decisions in dysmorphology and general human disease. For every disease type, genome sequence variations, particularly single nucleotide polymorphisms are mapped by comparing the genetic makeup of case and control groups. Methods that predict the effects of polymorphisms on protein stability are useful for the identification of possible disease associations, whereas structural effects can be assessed using methods to predict stability changes in proteins using sequence and/or structural information.

  9. Molecular genetic analysis of consanguineous families with primary microcephaly identified pathogenic variants in the ASPM gene

    Indian Academy of Sciences (India)

    MUZAMMIL AHMAD KHAN; CHRISTIAN WINDPASSINGER; MUHAMMAD ZEESHAN ALI; MUHAMMAD ZUBAIR; HADIA GUL; SAFDAR ABBAS; SAADULLAH KHAN; MUHAMMAD BADAR; RAMZI M. MOHAMMAD; ZAFAR NAWAZ

    2017-06-01

    Autosomal recessive primary microcephaly is a rare genetic disorder that is characterized by reduced head circumference and a varying degree of intellectual disability. Genetic studies on consanguineous families with primary microcephaly have identified 15 (MCPH) causative genes that include MCPH1, WDR62, CDK5RAP2, CASC5, ASPM, CENPJ, STIL, CEP135,CEP152, ZNF335, PHC1, CDK6, CENPE, SASS6 MFSD2A ANKLE2 and CIT (Khan et al. 2014; Yamamoto et al. 2014; Alakbarzade et al. 2015;Morris-Rosendahl and Kaindl 2015; Basit et al. 2016). Physiologically, most of these MCPH proteins are involved in cell cycle and its regulation. In the present clinical genetic study, we have present two consanguineous Pakistanifamilies segregating primary microcephaly and intellectual disability. These families were ascertained from the Saraiki ethnic part of Khyber-Pakhtunkhwa province in Pakistan. Whole exome sequencing in one family revealed a novel 1-bp deletion NM_018136.4: c.10013delA (p.Asp3338Valfs*2), while the other family showed a previously reported nonsense mutation NM_018136.4: c.9730C>T (rs199422195 (p.Arg3244*)) in ASPM gene. The novel frame-shift mutation (p.Asp3338Valfs*2) in ASPM presumably truncates the protein synthesis that results in loss of armadillo-type fold domain.

  10. Molecular and pathological characterization of Fusarium solani species complex infection in the head and lateral line system of Sphyrna lewini.

    Science.gov (United States)

    Pirarat, Nopadon; Sahatrakul, Komsil; Lacharoje, Sitthichok; Lombardini, Eric; Chansue, Nantarika; Techangamsuwan, Somporn

    2016-08-09

    A severe fungal infection affecting the head and lateral line system was diagnosed in 7 captive scalloped hammerhead sharks Sphyrna lewini in an aquarium in Thailand. Extensive and severe necrotizing cellulitis was consistently observed microscopically along the cephalic and lateral line canals in conjunction with positive fungal cultures for Fusarium sp. Molecular phylogenetic analysis was performed from 3 isolates based on the nucleotide sequences containing internally transcribed spacer (ITS) and a portion of 5.8S and 28S rDNA. The fungus was highly homologous (100%) and closely related to F. solani species complex 2 (FSSC 2), which belongs to Clade 3 of the FSSC. Our results illustrate the histopathological findings and expand upon our knowledge of the prevalence of invasive fusariosis in the head and lateral line system of hammerhead sharks.

  11. Establishment of clonal MIN-O transplant lines for molecular imaging via lentiviral transduction & in vitro culture.

    Science.gov (United States)

    Boucher, David L; Chen, Jane Qian; Cherry, Simon R; Borowsky, Alexander D

    2012-01-01

    As the field of molecular imaging evolves and increasingly is asked to fill the discovery and validation space between basic science and clinical applications, careful consideration should be given to the models in which studies are conducted. The MIN-O mouse model series is an established in vivo model of human mammary precancer ductal carcinoma in situ with progression to invasive carcinoma. This series of transplant lines is propagated in vivo and experiments utilizing this model can be completed in non-engineered immune intact FVB/n wild type mice thereby modeling the tumor microenvironment with biological relevance superior to traditional tumor cell xenografts. Unfortunately, the same qualities that make this and many other transplant lines more biologically relevant than standard cell lines for molecular imaging studies present a significant obstacle as somatic genetic re-engineering modifications common to many imaging applications can be technically challenging. Here, we describe a protocol for the efficient lentiviral transduction of cell slurries derived from precancerous MIN-O lesions, in vitro culture of "MIN-O-spheres" derived from single cell clones, and the subsequent transplantation of these spheres to produce transduced sublines suitable for optical imaging applications. These lines retain the physiologic and pathologic properties, including multilineage differentiation, and complex microanatomic interaction with the host stroma characteristic of the MIN-O model. We also present the in vivo imaging and immunohistochemical analysis of serial transplantation of one such subline and detail the progressive multifocal loss of the transgene in successive generations.

  12. Establishment of clonal MIN-O transplant lines for molecular imaging via lentiviral transduction & in vitro culture.

    Directory of Open Access Journals (Sweden)

    David L Boucher

    Full Text Available As the field of molecular imaging evolves and increasingly is asked to fill the discovery and validation space between basic science and clinical applications, careful consideration should be given to the models in which studies are conducted. The MIN-O mouse model series is an established in vivo model of human mammary precancer ductal carcinoma in situ with progression to invasive carcinoma. This series of transplant lines is propagated in vivo and experiments utilizing this model can be completed in non-engineered immune intact FVB/n wild type mice thereby modeling the tumor microenvironment with biological relevance superior to traditional tumor cell xenografts. Unfortunately, the same qualities that make this and many other transplant lines more biologically relevant than standard cell lines for molecular imaging studies present a significant obstacle as somatic genetic re-engineering modifications common to many imaging applications can be technically challenging. Here, we describe a protocol for the efficient lentiviral transduction of cell slurries derived from precancerous MIN-O lesions, in vitro culture of "MIN-O-spheres" derived from single cell clones, and the subsequent transplantation of these spheres to produce transduced sublines suitable for optical imaging applications. These lines retain the physiologic and pathologic properties, including multilineage differentiation, and complex microanatomic interaction with the host stroma characteristic of the MIN-O model. We also present the in vivo imaging and immunohistochemical analysis of serial transplantation of one such subline and detail the progressive multifocal loss of the transgene in successive generations.

  13. Molecular characterization of neoplastic and normal "sister" lymphoblastoid B-cell lines from chronic lymphocytic leukemia

    DEFF Research Database (Denmark)

    Lanemo Myhrinder, Anna; Hellqvist, Eva; Bergh, Ann-Charlotte;

    2013-01-01

    /short tandem repeat (STR) fingerprinting. Innate B-cell features, i.e. natural Ab production and CD5 receptors, were present in most CLL cell lines, but in none of the normal LCLs. This panel of immortalized CLL-derived cell lines is a valuable reference representing a renewable source of authentic Abs and DNA....

  14. A case study on variability management in software product lines: identifying why real-life projects fail

    NARCIS (Netherlands)

    T. Huysegoms; M. Snoeck; G. Dedene; A. Goderis; F. Stumpe

    2013-01-01

    Economies of scale can be seen as some kind of "holy grail" in state of the art literature on the development of sets of related software systems. Software product line methods are often mentioned in this context, due to the variability management aspects they propose, in order to deal with sets of

  15. An innovative strategy for the molecular diagnosis of Usher syndrome identifies causal biallelic mutations in 93% of European patients

    DEFF Research Database (Denmark)

    Bonnet, Crystel; Riahi, Zied; Chantot-Bastaraud, Sandra

    2016-01-01

    of vestibular dysfunction, and the age of onset of the retinitis pigmentosa. A total of 10 causal genes, 6 for USH1, 3 for USH2, and 1 for USH3, and an USH2 modifier gene, have been identified. A robust molecular diagnosis is required not only to improve genetic counseling, but also to advance gene therapy.......5% mutation characterization rate, the diagnosis efficiency was substantially improved compared with previously reported methods.European Journal of Human Genetics advance online publication, 27 July 2016; doi:10.1038/ejhg.2016.99....

  16. Molecular characterization of irinotecan (SN-38) resistant human breast cancer cell lines

    DEFF Research Database (Denmark)

    Jandu, Haatisha; Aluzaite, Kristina; Fogh, Louise

    2016-01-01

    resistance protein (ABCG2/BCRP) drug efflux pump.Results: We found that the resistant cell lines showed 7-100 fold increased resistance to SN-38 but remained sensitive to docetaxel and the non-camptothecin Top1 inhibitor LMP400. The resistant cell lines were characterized by Top1 down-regulation, changed...... of this study was to lay the groundwork for development of predictive biomarkers for irinotecan treatment in BC.Methods: We established BC cell lines with acquired or de novo resistance to SN-38, by exposing the human BC cell lines MCF 7 and MDA MB 231 to either stepwise increasing concentrations over 6 months...... or an initial high dose of SN-38 (the active metabolite of irinotecan), respectively. The resistant cell lines were analyzed for cross-resistance to other anti-cancer drugs, global gene expression, growth rates, TOP1 and TOP2A gene copy numbers and protein expression, and inhibition of the breast cancer...

  17. Breaking a virus: Identifying molecular level failure modes of a viral capsid by multiscale modeling

    Science.gov (United States)

    Krishnamani, V.; Globisch, C.; Peter, C.; Deserno, M.

    2016-07-01

    We use coarse-grained (CG) simulations to study the deformation of empty Cowpea Chlorotic Mottle Virus (CCMV) capsids under uniaxial compression, from the initial elastic response up to capsid breakage. Our CG model is based on the MARTINI force field and has been amended by a stabilizing elastic network, acting only within individual proteins, that was tuned to capture the fluctuation spectrum of capsid protein dimers, obtained from all atom simulations. We have previously shown that this model predicts force-compression curves that match AFM indentation experiments on empty CCMV capsids. Here we investigate details of the actual breaking events when the CCMV capsid finally fails. We present a symmetry classification of all relevant protein contacts and show that they differ significantly in terms of stability. Specifically, we show that interfaces which break readily are precisely those which are believed to form last during assembly, even though some of them might share the same contacts as other non-breaking interfaces. In particular, the interfaces that form pentamers of dimers never break, while the virtually identical interfaces within hexamers of dimers readily do. Since these units differ in the large-scale geometry and, most noticeably, the cone-angle at the center of the 5- or 6-fold vertex, we propose that the hexameric unit fails because it is pre-stressed. This not only suggests that hexamers of dimers form less frequently during the early stages of assembly; it also offers a natural explanation for the well-known β-barrel motif at the hexameric center as a post-aggregation stabilization mechanism. Finally, we identify those amino acid contacts within all key protein interfaces that are most persistent during compressive deformation of the capsid, thereby providing potential targets for mutation studies aiming to elucidate the key contacts upon which overall stability rests.

  18. Breaking a virus: Identifying molecular level failure modes of a viral capsid by multiscale modeling

    Science.gov (United States)

    Krishnamani, V.; Globisch, C.; Peter, C.; Deserno, M.

    2016-10-01

    We use coarse-grained (CG) simulations to study the deformation of empty Cowpea Chlorotic Mottle Virus (CCMV) capsids under uniaxial compression, from the initial elastic response up to capsid breakage. Our CG model is based on the MARTINI force field and has been amended by a stabilizing elastic network, acting only within individual proteins, that was tuned to capture the fluctuation spectrum of capsid protein dimers, obtained from all atom simulations. We have previously shown that this model predicts force-compression curves that match AFM indentation experiments on empty CCMV capsids. Here we investigate details of the actual breaking events when the CCMV capsid finally fails. We present a symmetry classification of all relevant protein contacts and show that they differ significantly in terms of stability. Specifically, we show that interfaces which break readily are precisely those which are believed to form last during assembly, even though some of them might share the same contacts as other non-breaking interfaces. In particular, the interfaces that form pentamers of dimers never break, while the virtually identical interfaces within hexamers of dimers readily do. Since these units differ in the large-scale geometry and, most noticeably, the cone-angle at the center of the 5- or 6-fold vertex, we propose that the hexameric unit fails because it is pre-stressed. This not only suggests that hexamers of dimers form less frequently during the early stages of assembly; it also offers a natural explanation for the well-known β-barrel motif at the hexameric center as a post-aggregation stabilization mechanism. Finally, we identify those amino acid contacts within all key protein interfaces that are most persistent during compressive deformation of the capsid, thereby providing potential targets for mutation studies aiming to elucidate the key contacts upon which overall stability rests.

  19. Identifying the pattern of molecular evolution for Zaire ebolavirus in the 2014 outbreak in West Africa.

    Science.gov (United States)

    Liu, Si-Qing; Deng, Cheng-Lin; Yuan, Zhi-Ming; Rayner, Simon; Zhang, Bo

    2015-06-01

    The current Ebola virus disease (EVD) epidemic has killed more than all previous Ebola outbreaks combined and, even as efforts appear to be bringing the outbreak under control, the threat of reemergence remains. The availability of new whole-genome sequences from West Africa in 2014 outbreak, together with those from the earlier outbreaks, provide an opportunity to investigate the genetic characteristics, the epidemiological dynamics and the evolutionary history for Zaire ebolavirus (ZEBOV). To investigate the evolutionary properties of ZEBOV in this outbreak, we examined amino acid mutations, positive selection, and evolutionary rates on the basis of 123 ZEBOV genome sequences. The estimated phylogenetic relationships within ZEBOV revealed that viral sequences from the same period or location formed a distinct cluster. The West Africa viruses probably derived from Middle Africa, consistent with results from previous studies. Analysis of the seven protein regions of ZEBOV revealed evidence of positive selection acting on the GP and L genes. Interestingly, all putatively positive-selected sites identified in the GP are located within the mucin-like domain of the solved structure of the protein, suggesting a possible role in the immune evasion properties of ZEBOV. Compared with earlier outbreaks, the evolutionary rate of GP gene was estimated to significantly accelerate in the 2014 outbreak, suggesting that more ZEBOV variants are generated for human to human transmission during this sweeping epidemic. However, a more balanced sample set and next generation sequencing datasets would help achieve a clearer understanding at the genetic level of how the virus is evolving and adapting to new conditions. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Multiple outflows in the bipolar planetary nebula M1-16: A molecular line study

    NARCIS (Netherlands)

    Sahai, Raghvendra; Wootten, Alwyn; Schwarz, Hugo E.; Wild, W.

    1994-01-01

    Extensive observations of the molecular gas in the young, compact planetary nebula M1-16 have been made, using the Swedish-ESO-Submillimeter Telescope. A map of the CO J = 2-1 emission shows that the molecular envelope contains both a slow and a fast outflow with expansion velocities of 19 km/s and

  1. Multiple outflows in the bipolar planetary nebula M1-16: A molecular line study

    NARCIS (Netherlands)

    Sahai, Raghvendra; Wootten, Alwyn; Schwarz, Hugo E.; Wild, W.

    1994-01-01

    Extensive observations of the molecular gas in the young, compact planetary nebula M1-16 have been made, using the Swedish-ESO-Submillimeter Telescope. A map of the CO J = 2-1 emission shows that the molecular envelope contains both a slow and a fast outflow with expansion velocities of 19 km/s and

  2. Identifying Differences and Similarities in Static and Dynamic Contact Angles between Nanoscale and Microscale Textured Surfaces Using Molecular Dynamics Simulations.

    Science.gov (United States)

    Slovin, Mitchell R; Shirts, Michael R

    2015-07-28

    We quantify some of the effects of patterned nanoscale surface texture on static contact angles, dynamic contact angles, and dynamic contact angle hysteresis using molecular dynamics simulations of a moving Lennard-Jones droplet in contact with a solid surface. We observe static contact angles that change with the introduction of surface texture in a manner consistent with theoretical and experimental expectations. However, we find that the introduction of nanoscale surface texture at the length scale of 5-10 times the fluid particle size does not affect dynamic contact angle hysteresis even though it changes both the advancing and receding contact angles significantly. This result differs significantly from microscale experimental results where dynamic contact angle hysteresis decreases with the addition of surface texture due to an increase in the receding contact angle. Instead, we find that molecular-kinetic theory, previously applied only to nonpatterned surfaces, accurately describes dynamic contact angle and dynamic contact angle hysteresis behavior as a function of terminal fluid velocity. Therefore, at length scales of tens of nanometers, the kinetic phenomena such as contact line pinning observed at larger scales become insignificant in comparison to the effects of molecular fluctuations for moving droplets, even though the static properties are essentially scale-invariant. These findings may have implications for the design of highly hierarchical structures with particular wetting properties. We also find that quantitatively determining the trends observed in this article requires the careful selection of system and analysis parameters in order to achieve sufficient accuracy and precision in calculated contact angles. Therefore, we provide a detailed description of our two-surface, circular-fit approach to calculating static and dynamic contact angles on surfaces with nanoscale texturing.

  3. THOR: The H i, OH, Recombination line survey of the Milky Way. The pilot study: H i observations of the giant molecular cloud W43

    Science.gov (United States)

    Bihr, S.; Beuther, H.; Ott, J.; Johnston, K. G.; Brunthaler, A.; Anderson, L. D.; Bigiel, F.; Carlhoff, P.; Churchwell, E.; Glover, S. C. O.; Goldsmith, P. F.; Heitsch, F.; Henning, T.; Heyer, M. H.; Hill, T.; Hughes, A.; Klessen, R. S.; Linz, H.; Longmore, S. N.; McClure-Griffiths, N. M.; Menten, K. M.; Motte, F.; Nguyen-Luong, Q.; Plume, R.; Ragan, S. E.; Roy, N.; Schilke, P.; Schneider, N.; Smith, R. J.; Stil, J. M.; Urquhart, J. S.; Walsh, A. J.; Walter, F.

    2015-08-01

    To study the atomic, molecular, and ionized emission of giant molecular clouds (GMCs) in the Milky Way, we initiated a large program with the Karl G. Jansky Very Large Array (VLA): "THOR: The H i, OH, Recombination line survey of the Milky Way". We map the 21 cm H i line, 4 OH lines, up to 19 Hα recombination lines and thecontinuum from 1 to 2 GHz of a significant fraction of the Milky Way (l = 15°-67°, | b | ≤ 1°) at an angular resolution of ~ 20″. Starting in 2012, as a pilot study we mapped 4 square degrees of the GMC associated with the W43 star formation complex. The rest of the THOR survey area was observed during 2013 and 2014. In this paper, we focus on the H i emission from the W43 GMC complex. Classically, the H i 21 cm line is treated as optically thin with properties such as the column density calculated under this assumption. This approach might yield reasonable results for regions of low-mass star formation, however, it is not sufficient to describe GMCs. We analyzed strong continuum sources to measure the optical depth along the line of sight, and thus correct the H i 21 cm emission for optical depth effects and weak diffuse continuum emission. Hence, we are able to measure the H i mass of this region more accurately and our analysis reveals a lower limit for the H i mass of M = 6.6-1.8 × 106 M⊙ (vLSR = 60-120 km s-1), which is a factor of 2.4 larger than the mass estimated with the assumption of optically thin emission. The H i column densities are as high as NH i ~ 150 M⊙ pc-2 ≈ 1.9 × 1022 cm-2, which is an order of magnitude higher than for low-mass star formation regions. This result challenges theoretical models that predict a threshold for the H i column density of ~10 M⊙ pc-2, at which the formation of molecular hydrogen should set in. By assuming an elliptical layered structure for W43, we estimate the particle density profile. For the atomic gas particle density, we find a linear decrease toward the center of W43 with

  4. Identifying initial molecular targets of PDT: protein and lipid oxidation products

    Science.gov (United States)

    Oleinick, Nancy L.; Kim, Junhwan; Rodriguez, Myriam E.; Xue, Liang-yan; Kenney, Malcolm E.; Anderson, Vernon E.

    2009-06-01

    Photodynamic Therapy (PDT) generates singlet oxygen (1O2) which oxidizes biomolecules in the immediate vicinity of its formation. The phthalocyanine photosensitizer Pc 4 localizes to mitochondria and endoplasmic reticulum, and the primary targets of Pc 4-PDT are expected to be lipids and proteins of those membranes. The initial damage then causes apoptosis in cancer cells via the release of cytochrome c (Cyt-c) from mitochondria into the cytosol, followed by the activation of caspases. That damage also triggers the induction of autophagy, an attempt by the cells to eliminate damaged organelles, or when damage is too extensive, to promote cell death. Cyt-c is bound to the cytosolic side of the mitochondrial inner membrane through association with cardiolipin (CL), a phospholipid containing four unsaturated fatty acids and thus easily oxidized by 1O2 or by other oxidizing agents. Increasing evidence suggests that oxidation of CL loosens its association with Cyt-c, and that the peroxidase activity of Cyt-c can oxidize CL. In earlier studies of Cyt-c in homogeneous medium by MALDI-TOF-MS and LC-ESI-MS, we showed that 1O2 generated by Pc 4-PDT oxidized histidine, methionine, tryptophan, and unexpectedly phenylalanine but not tyrosine. Most of the oxidation products were known to be formed by other oxidizing agents, such as hydroxyl radical, superoxide radical anion, and peroxynitrite. However, two products of histidine were unique to 1O2 and may be useful for reporting the action of 1O2 in cells and tissues. These products, as well as CL oxidation products, have now been identified in liposomes and mitochondria after Pc 4-PDT. In mitochondria, the PDT dose-dependent oxidations can be related to specific changes in mitochondrial function, Bcl-2 photodamage, and Cyt-c release. Thus, the role of PDT-generated 1O2 in oxidizing Cyt-c and CL and the interplay between protein and lipid targets may be highly relevant to understanding one mechanism for cell killing by PDT.

  5. Morphological and molecular characterization of an undifferentiated soft tissue sarcoma cell line and derivative clones.

    Science.gov (United States)

    Taubert, H; Schmidt, H; Wurl, P; Hinze, R; Meye, A; Bache, M; Berger, D; Holzhausen, H; Dralle, H; Rath, F

    1997-09-01

    From an undifferentiated soft tissue sarcoma (STS) a cell line designated US8-93 has been established. At subcloning the cell line US8-93 three different lines (US8-93A, B and C) could be set up. In a subsequent study characteristics for ultrastructure, growth, cell cycle distribution, karyotype, protein overexpression detected by immunohistochemistry (IHC) and p53 mutational status were determined. The cell line US8-93 as well as subclones contain mainly bipolar spindle-shaped cells and additionally some polygonal and multinucleated cells. Cells possess the characteristics of primitive mesenchymal cells based on their positive reactions with anti-vimentin and negative reactions for desmin, cytokeratin, myoglobin, S100, and NSE, implying a classification as an undifferentiated STS. Cytogenetic analysis revealed nearly diploid cells with several structural and numerical aberrations for chromosomes 1, 3, 4, 6, 9, 10, 12, 13, 15 and 18. IHC positivity was found for the tumor suppressor proteins p53 and Rb, the oncogene products Bcl-2, K-ras, N-ras, P-glycoprotein Mdr-1 and MDM-2. In the p53 gene a nonsense mutation in exon 4 was detected, that was confirmed in the original primary tumor and in three derivative clonal lines. The described STS cell line represents a valuable supplementation to the relatively small number of human STS cell lines currently available and may also provide a good in vitro model for studies of STS tumorigenesis in respect to a mutated p53 gene.

  6. Quantitative proteomics identifies central players in erlotinib resistance of the non-small cell lung cancer cell line HCC827

    DEFF Research Database (Denmark)

    Jacobsen, Kirstine; Lund, Rikke Raaen; Beck, Hans Christian

    compared to the parental cell line. By network analysis, we found cell survival, proliferation and migration to be induced, and apoptosis and adhesion to be repressed across the 3 resistant clones vs the parental cell line. The resistant cells generally lost phosphorylation of EGFR, MET, FGFR and Src......Background: Erlotinib (Tarceva®, Roche) has significantly changed the treatment of non-small cell lung cancer (NSCLC) as 70% of patients show significant tumor regression when treated. However, all patients relapse due to development of acquired resistance, which in 43-50% of cases are caused......, but surprisingly not of AKT and FOXO1/3a, indicating that AKT is the main signaling hub for survival. Also Erk1/2 phsphorylation is pertained although at decreased levels. Conclusions: In conclusion, cancer-related networks such as proliferation and apoptosis were found to be regulated, supporting the validity...

  7. Metabolomic approach for identifying and visualizing molecular tissue markers in tadpoles of Xenopus tropicalis by mass spectrometry imaging

    Directory of Open Access Journals (Sweden)

    Naoko Goto-Inoue

    2016-09-01

    Full Text Available In developmental and cell biology it is crucial to evaluate the dynamic profiles of metabolites. An emerging frog model system using Xenopus tropicalis, whose genome sequence and inbred strains are available, is now ready for metabolomics investigation in amphibians. In this study we applied matrix-assisted laser desorption/ionization (MALDI-mass spectrometry imaging (MSI analysis to identify and visualize metabolomic molecular markers in tadpoles of Xenopus tropicalis. We detected tissue-specific peaks and visualized their distribution in tissues, and distinguished 19 tissues and their specific peaks. We identified, for the first time, some of their molecular localizations via tandem mass spectrometric analysis: hydrocortisone in artery, L-DOPA in rhombencephalon, taurine in eye, corticosterone in gill, heme in heart, inosine monophosphate and carnosine in muscle, dopamine in nerves, and phosphatidylethanolamine (16:0/20:4 in pharynx. This is the first MALDI-MSI study of X. tropicalis tadpoles, as in small tadpoles it is hard to distinguish and dissect the various organs. Furthermore, until now there has been no data about the metabolomic profile of each organ. Our results suggest that MALDI-MSI is potentially a powerful tool for examining the dynamics of metabolomics in metamorphosis as well as conformational changes due to metabolic changes.

  8. Whole-exome sequencing identifies ATRX mutation as a key molecular determinant in lower-grade glioma.

    Science.gov (United States)

    Kannan, Kasthuri; Inagaki, Akiko; Silber, Joachim; Gorovets, Daniel; Zhang, Jianan; Kastenhuber, Edward R; Heguy, Adriana; Petrini, John H; Chan, Timothy A; Huse, Jason T

    2012-10-01

    The molecular foundations of lower-grade gliomas (LGGs)-astrocytoma, oligodendroglioma, and oligoastrocytoma-remain less well characterized than those of their fully malignant counterpart, glioblastoma. Mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) likely represent initiating pathogenic events. However, while IDH mutations appear to dramatically alter cellular epigenomic landscapes, definitive downstream transformative mechanisms have not been characterized. It remains likely, therefore, that additional genomic abnormalities collaborate with IDH mutation to drive oncogenesis in LGG. We performed whole exome sequencing in 4 LGGs, followed by focused resequencing in an additional 28, and found a high incidence of mutations in the ATRX gene (α thalassemia/mental retardation syndrome X-linked). ATRX forms a core component of a chromatin remodeling complex active in telomere biology. Mutations in ATRX have been identified in multiple tumor types and appear to cause alternative lengthening of telomeres (ALT), a presumed precursor to genomic instability. In our samples, ATRX mutation was entirely restricted to IDH-mutant tumors, closely correlated with TP53 mutation and astrocytic differentiation, and mutually exclusive with 1p/19q codeletion, the molecular hallmark of oligodendroglioma. Moreover, ATRX mutation was highly enriched in tumors of so-called early progenitor-like transcriptional subclass (~85%), which our prior work has linked to specific cells of origin in the forebrain subventricular zone. Finally, ATRX mutation correlated with ALT, providing a mechanistic link to genomic instability. In summary, our findings both identify ATRX mutation as a defining molecular determinant for a large subset of IDH-mutant gliomas and have direct implications on pathogenic mechanisms across the wide spectrum of LGGs.

  9. ExoMol molecular line lists: IX The spectrum of AlO

    CERN Document Server

    Patrascu, Andrei T; Tennyson, Jonathan

    2015-01-01

    Accurate line lists are calculated for aluminium monoxide covering the pure rotation, rotation-vibration and electronic (B -- X blue-green and A -- X infrared bands) spectrum. Line lists are presented for the main isotopologue, $^{27}$Al$^{16}$O, as well as for $^{27}$Al$^{17}$O, $^{27}$Al$^{18}$O and $^{26}$Al$^{16}$O. These line lists are suitable for high temperatures (up to 8000 K) including those relevant to exoplanetary atmospheres and cool stars. A combination of empirical and \\textit{ab initio} methods is used: the potential energy curves were previously determined to high accuracy by fitting to extensive data from analysis of laboratory spectra; a high quality {\\it ab initio} dipole moment curve is calculated using quadruple zeta basis set and the multi-reference configuration interaction (MRCI) method. Partition functions plus full line lists of transitions are made available in an electronic form as supplementary data to this article and at \\url{www.exomol.com}.

  10. On the widths of Stokes lines in Raman scattering from molecules adsorbed at metal surfaces and in molecular conduction junctions

    Science.gov (United States)

    Gao, Yi; Galperin, Michael; Nitzan, Abraham

    2016-06-01

    Within a generic model we analyze the Stokes linewidth in surface enhanced Raman scattering (SERS) from molecules embedded as bridges in molecular junctions. We identify four main contributions to the off-resonant Stokes signal and show that under zero voltage bias (a situation pertaining also to standard SERS experiments) and at low bias junctions only one of these contributions is pronounced. The linewidth of this component is determined by the molecular vibrational relaxation rate, which is dominated by interactions with the essentially bosonic thermal environment when the relevant molecular electronic energy is far from the metal(s) Fermi energy(ies). It increases when the molecular electronic level is close to the metal Fermi level so that an additional vibrational relaxation channel due to electron-hole (eh) exciton in the molecule opens. Other contributions to the Raman signal, of considerably broader linewidths, can become important at larger junction bias.

  11. Herschel observations of extraordinary sources: Analysis of the full Herschel/HIFI molecular line survey of sagittarius B2(N)

    Energy Technology Data Exchange (ETDEWEB)

    Neill, Justin L.; Bergin, Edwin A.; Crockett, Nathan R.; Favre, Cécile; Anderson, Dana E.; Burkhardt, Andrew M.; McNeill, Trevor D. [Department of Astronomy, University of Michigan, 500 Church Street, Ann Arbor, MI 48109 (United States); Lis, Dariusz C.; Emprechtinger, Martin; Monje, Raquel R.; Phillips, Thomas G. [California Institute of Technology, Cahill Center for Astronomy and Astrophysics 301-17, Pasadena, CA 91125 (United States); Schilke, Peter; Comito, Claudia; Qin, Sheng-Li [Physikalisches Institut, Universität zu Köln, Zülpicher Str. 77, D-50937 Köln (Germany); Chen, Jo-Hsin [Jet Propulsion Laboratory, California Institute of Technology, 4800 Oak Grove Drive, Pasadena, CA 91109 (United States); Harris, Brent J.; Steber, Amanda L.; Vasyunina, Tatiana [Department of Chemistry, University of Virginia, McCormick Road, Charlottesville, VA 22904 (United States); Lord, Steven D. [National Herschel Science Center, California Institute of Technology, Pasadena, CA 91125 (United States); McGuire, Brett A., E-mail: jneill@umich.edu, E-mail: ebergin@umich.edu [Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125 (United States); and others

    2014-07-01

    A sensitive broadband molecular line survey of the Sagittarius B2(N) star-forming region has been obtained with the Heterodyne Instrument for the Far-Infrared (HIFI) instrument on the Herschel Space Observatory, offering the first high spectral resolution look at this well-studied source in a wavelength region largely inaccessible from the ground (625-157 μm). From the roughly 8000 spectral features in the survey, a total of 72 isotopologues arising from 44 different molecules have been identified, ranging from light hydrides to complex organics, and arising from a variety of environments from cold and diffuse to hot and dense gas. We present a local thermodynamic equilibrium (LTE) model to the spectral signatures of each molecule, constraining the source sizes for hot core species with complementary Submillimeter Array interferometric observations and assuming that molecules with related functional group composition are cospatial. For each molecule, a single model is given to fit all of the emission and absorption features of that species across the entire 480-1910 GHz spectral range, accounting for multiple temperature and velocity components when needed to describe the spectrum. As with other HIFI surveys toward massive star-forming regions, methanol is found to contribute more integrated line intensity to the spectrum than any other species. We discuss the molecular abundances derived for the hot core where the LTE approximation is generally found to describe the spectrum well, in comparison to abundances derived for the same molecules in the Orion KL region from a similar HIFI survey. Notably, we find significantly higher abundances of amine- and amide-bearing molecules (CH{sub 3}NH{sub 2}, CH{sub 2}NH, and NH{sub 2}CHO) toward Sgr B2(N) than Orion KL and lower abundances of some complex oxygen-bearing molecules (CH{sub 3}OCHO in particular). In addition to information on the chemical composition of the hot core, the strong far-infrared dust continuum allows

  12. Assessment of genetic variation in tomato (Solanum lycopersicum L.) inbred lines using SSR molecular markers

    Institute of Scientific and Technical Information of China (English)

    Solomon Benor; Mengyu Zhang; Zhoufei Wang; Hongsheng Zhang

    2008-01-01

    A study was conducted to determine the genetic diversity of 39 determinate and indeterminate tomato inbred lines collected from China, Japan, S. Korea, and USA. Using 35 SSR polymorphic markers, a total of 150 alleles were found with moderate levels of diversity, and a high number of unique alleles existing in these tomato lines. The mean number of alleles per locus was 4.3 and the average polymorphism information content (PIC) was 0.31. Unweighted Pair Group Method with Arithmetic Mean (UPGMA) clustering at genetic similarity value of 0.85 grouped the inbred lines into four groups, where one USA cultivar formed a separate and more distant cluster. The most similar inbred lines are from USA, both with determinate type, whereas the most different lines are from USA (Us-16) and Japan (Ja-2) with determinate and indeterminate growth habit, respectively. Clustering was consistent with the known information regarding geographical location and growth habit. The genetic distance information reported in this study might be used by breeders when planning future crosses among these inbred lines.

  13. Integration of molecular biology tools for identifying promoters and genes abundantly expressed in flowers of Oncidium Gower Ramsey

    Directory of Open Access Journals (Sweden)

    Tung Shu-Yun

    2011-04-01

    Full Text Available Abstract Background Orchids comprise one of the largest families of flowering plants and generate commercially important flowers. However, model plants, such as Arabidopsis thaliana do not contain all plant genes, and agronomic and horticulturally important genera and species must be individually studied. Results Several molecular biology tools were used to isolate flower-specific gene promoters from Oncidium 'Gower Ramsey' (Onc. GR. A cDNA library of reproductive tissues was used to construct a microarray in order to compare gene expression in flowers and leaves. Five genes were highly expressed in flower tissues, and the subcellular locations of the corresponding proteins were identified using lip transient transformation with fluorescent protein-fusion constructs. BAC clones of the 5 genes, together with 7 previously published flower- and reproductive growth-specific genes in Onc. GR, were identified for cloning of their promoter regions. Interestingly, 3 of the 5 novel flower-abundant genes were putative trypsin inhibitor (TI genes (OnTI1, OnTI2 and OnTI3, which were tandemly duplicated in the same BAC clone. Their promoters were identified using transient GUS reporter gene transformation and stable A. thaliana transformation analyses. Conclusions By combining cDNA microarray, BAC library, and bombardment assay techniques, we successfully identified flower-directed orchid genes and promoters.

  14. The 9.7 and 18 um silicate absorption profiles towards diffuse and molecular cloud lines-of-sight

    CERN Document Server

    van Breemen, J M; Chiar, J E; Waters, L B F M; Kemper, F; Boogert, A C A; Cami, J; Decin, L; Knez, C; Sloan, G C; Tielens, A G G M

    2010-01-01

    Studying the composition of dust in the interstellar medium (ISM) is crucial in understanding the cycle of dust in our galaxy. The mid-infrared spectral signature of amorphous silicates, the most abundant dust species in the ISM, is studied in different lines-of-sight through the Galactic plane, thus probing different conditions in the ISM. We have analysed 10 spectra from the Spitzer archive, of which 6 lines-of-sight probe diffuse interstellar medium material and 4 probe molecular cloud material. The 9.7 um silicate absorption features in 7 of these spectra were studied in terms of their shape and strength. In addition, the shape of the 18 um silicate absorption features in 4 of the diffuse sightline spectra were analysed. The 9.7 um silicate absorption bands in the diffuse sightlines show a strikingly similar band shape. This is also the case for all but one of the 18 um silicate absorption bands observed in diffuse lines-of-sight. The 9.7 um bands in the 4 molecular sightlines show small variations in sha...

  15. A molecular and phenotypic integrative approach to identify a no-effect dose level for antiandrogen-induced testicular toxicity.

    Science.gov (United States)

    Ludwig, Sophie; Tinwell, Helen; Schorsch, Frédéric; Cavaillé, Christel; Pallardy, Marc; Rouquié, David; Bars, Rémi

    2011-07-01

    The safety assessment of chemicals for humans relies on identifying no-observed adverse effect levels (NOAELs) in animal toxicity studies using standard methods. With the advent of high information content technologies, especially microarrays, it is pertinent to determine the impact of molecular data on the NOAELs. Consequently, we conducted an integrative study to identify a no-transcriptomic effect dose using microarray analyses coupled with quantitative reverse transcriptase PCR (RT-qPCR) and determined how this correlated with the NOAEL. We assessed the testicular effects of the antiandrogen, flutamide (FM), in a rat 28-day toxicity study using doses of 0.2-30 mg/kg/day. Plasma testosterone levels and testicular histopathology indicated a NOAEL of 1 mg/kg/day. A no-effect dose of 0.2 mg/kg/day was established based on molecular data relevant to the phenotypic changes. We observed differential gene expression starting from 1 mg/kg/day and a deregulation of more than 1500 genes at 30 mg/kg/day. Dose-related changes were identified for the major pathways (e.g., fatty acid metabolism) associated with the testicular lesion (Leydig cell hyperplasia) that were confirmed by RT-qPCR. These data, along with protein accumulation profiles and FM metabolite concentrations in testis, supported the no-effect dose of 0.2 mg/kg/day. Furthermore, the microarray data indicated a dose-dependent change in the fatty acid catabolism pathway, a biological process described for the first time to be affected by FM in testicular tissue. In conclusion, the present data indicate the existence of a transcriptomic threshold, which must be exceeded to progress from a normal state to an adaptative state and subsequently to adverse toxicity.

  16. A multi-transition molecular line study of infrared dark cloud G331.71+00.59

    CERN Document Server

    Yu, Nai-Ping

    2016-01-01

    Using archive data from the Millimeter Astronomy Legacy Team Survey at 90 GHz (MALT90), carried out using the Mopra 22-m telescope, we made the first multi-transition molecular line study of infrared dark cloud (IRDC) MSXDC G331.71+00.59. Two molecular cores were found embedded in this IRDC. Each of these cores is associated with a known extended green object (EGO), indicating places of massive star formation. The HCO+ (1-0) and HNC (1-0) transitions show prominent blue or red asymmetric structures, suggesting outflow and inflow activities of young stellar objects (YSOs). Other detected molecular lines include H13CO+ (1-0), C2H (1-0), HC3N (10-9), HNCO(404-303) and SiO (2-1), which are typical of hot cores and outflows. We regard the two EGOs as evolving from the IRDC to hot cores. Using public GLIMPS data, we investigate the spectral energy distribution of EGO G331.71+0.60. Our results support this EGO being a massive YSO driving the outflow. G331.71+0.58 may be at an earlier evolutionary stage.

  17. A 3D model for carbon monoxide molecular line emission as a potential cosmic microwave background polarization contaminant

    Science.gov (United States)

    Puglisi, G.; Fabbian, G.; Baccigalupi, C.

    2017-08-01

    We present a model for simulating carbon monoxide (CO) rotational line emission in molecular clouds, taking account of their 3D spatial distribution in galaxies with different geometrical properties. The model implemented is based on recent results in the literature and has been designed for performing Monte Carlo (MC) simulations of this emission. We compare the simulations produced with this model and calibrate them, both on the map and the power spectrum levels, using the second release of data from the Planck satellite for the Galactic plane, where the signal-to-noise ratio is highest. We use the calibrated model to extrapolate the CO power spectrum at low Galactic latitudes where no high sensitivity observations are available yet. We then forecast the level of unresolved polarized emission from CO molecular clouds which could contaminate the power spectrum of cosmic microwave background polarization B modes away from the Galactic plane. Assuming realistic levels of the polarization fraction, we show that the level of contamination is equivalent to a cosmological signal with r ≲ 0.02. The MC MOlecular Line Emission (mcmole3d) python package, which implements this model, is being made publicly available.

  18. Molecular and atomic line surveys of galaxies I: the dense, star-forming phase as a beacon

    CERN Document Server

    Geach, James E

    2012-01-01

    We predict the space density of molecular gas reservoirs in the Universe, and place a lower limit on the number counts of carbon monoxide (CO), hydrogen cyanide (HCN) molecular and [CII] atomic emission lines in blind redshift surveys in the submillimeter-centimeter spectral regime. Our model uses: (a) recently available HCN Spectral Line Energy Distributions (SLEDs) of local Luminous Infrared Galaxies (LIRGs, L_IR>10^11 L_sun), (b) a value for epsilon=SFR/M_dense(H_2) provided by new developments in the study of star formation feedback on the interstellar medium and (c) a model for the evolution of the infrared luminosity density. Minimal 'emergent' CO SLEDs from the dense gas reservoirs expected in all star-forming systems in the Universe are then computed from the HCN SLEDs since warm, HCN-bright gas will necessarily be CO-bright, with the dense star-forming gas phase setting an obvious minimum to the total molecular gas mass of any star-forming galaxy. We include [CII] as the most important of the far-inf...

  19. A multi-transition molecular line study of infrared dark cloud G331.71+00.59

    Institute of Scientific and Technical Information of China (English)

    Nai-Ping Yu; Jun-Jie Wang

    2013-01-01

    Using archive data from the Millimeter Astronomy Legacy Team Survey at 90 GHz (MALT90),carried out using the Mopra 22-m telescope,we made the first multi-transition molecular line study of infrared dark cloud (IRDC) MSXDC G331.71+00.59.Two molecular cores were found embedded in this IRDC.Each of these cores is associated with a known extended green object (EGO),indicating places of massive star formation.The HCO+ (1-0) and HNC (1-0) transitions show prominent blue or red asymmetric structures,suggesting outflow and inflow activities of young stellar objects (YSOs).Other detected molecular lines include H13CO+ (1-0),C2H (1-0),HC3N (10-9),HNCO(40,4-30,3) and SiO (2-1),which are typical of hot cores and outflows.We regard the two EGOs as evolving from the IRDC to hot cores.Using public GLIMPS data,we investigate the spectral energy distribution of EGO G331.71+0.60.Our results support this EGO being a massive YSO driving the outflow.G331.71+0.58 may be at an earlier evolutionary stage.

  20. Molecular line emission in NGC1068 imaged with ALMA: II. The chemistry of the dense molecular gas

    CERN Document Server

    Viti, S; Fuente, A; Hunt, L K; Usero, A; Henkel, C; Eckart, A; Martin, S; Spaans, M; Muller, S; Combes, F; Krips, M; Schinnerer, E; Casasola, V; Costagliola, F; Marquez, I; Planesas, P; van der Werf, P P; Aalto, S; Baker, A J; Boone, F; Tacconi, L J

    2014-01-01

    We present a detailed analysis of ALMA Bands 7 and 9 data of CO, HCO+, HCN and CS, augmented with Plateau de Bure Interferometer (PdBI) data of the ~ 200 pc circumnuclear disk (CND) and the ~ 1.3 kpc starburst ring (SB ring) of NGC~1068, a nearby (D = 14 Mpc) Seyfert 2 barred galaxy. We aim at determining the physical characteristics of the dense gas present in the CND and whether the different line intensity ratios we find within the CND as well as between the CND and the SB ring are due to excitation effects (gas density and temperature differences) or to a different chemistry. We estimate the column densities of each species in Local Thermodynamic Equilibrium (LTE). We then compute large one-dimensional non-LTE radiative transfer grids (using RADEX) by using first only the CO transitions, and then all the available molecules in order to constrain the densities, temperatures and column densities within the CND. We finally present a preliminary set of chemical models to determine the origin of the gas. We fi...

  1. Morphological and molecular characterization of new Drosophila cell lines established from a strain permissive for gypsy transposition.

    Science.gov (United States)

    Chalvet, F; Debec, A; Marcaillou, C; Rougeau, C; Bucheton, A

    1998-01-01

    The gypsy element of Drosophila melanogaster is the first retrovirus identified in invertebrates. Its transposition is controlled by a host gene called flamenco (flam): restrictive alleles of this gene maintain the retrovirus in a repressed state while permissive alleles allow high levels of transposition. To develop a cell system to study the gypsy element, we established four independent cell lines derived from the Drosophila strain SS, which contains a permissive allele of flamenco, and which is devoid of transposing copies of gypsy. The ultrastructural analysis of three SS cell lines revealed some remarkable characteristics, such as many nuclear virus-like particles, cytoplasmic dense particles, and massive cisternae filled with a fibrous material of unknown origin. Gypsy intragenomic distribution has been compared between the three cell lines and the original SS fly strain, and revealed in two of the cell lines an increase in copy number of a restriction fragment usually present in active gypsy elements. This multiplication seems to have occurred during the passage to the cell culture. Availability of SS cell lines should assist studies of gypsy transposition and infectivity and might be useful to produce high amounts of gypsy viral particles. These new lines already allowed us to show that the Envelope-like products of gypsy can be expressed as membrane proteins.

  2. Discovery of molecular gas around HD 131835 in an APEX molecular line survey of bright debris disks

    CERN Document Server

    Moór, A; Juhász, A; Ábrahám, P; Balog, Z; Kóspál, Á; Pascucci, I; Szabó, Gy M; Vavrek, R; Curé, M; Csengeri, T; Grady, C; Güsten, R; Kiss, Cs

    2015-01-01

    Debris disks are considered to be gas-poor, but recent observations revealed molecular or atomic gas in several 10-40 Myr old systems. We used the APEX and IRAM 30m radiotelescopes to search for CO gas in 20 bright debris disks. In one case, around the 16 Myr old A-type star HD 131835, we discovered a new gas-bearing debris disk, where the CO 3-2 transition was successfully detected. No other individual system exhibited a measurable CO signal. Our Herschel Space Observatory far-infrared images of HD 131835 marginally resolved the disk both at 70 and 100$\\mu$m, with a characteristic radius of ~170 au. While in stellar properties HD 131835 resembles $\\beta$ Pic, its dust disk properties are similar to those of the most massive young debris disks. With the detection of gas in HD 131835 the number of known debris disks with CO content has increased to four, all of them encircling young ($\\leq$40 Myr) A-type stars. Based on statistics within 125 pc, we suggest that the presence of detectable amount of gas in the m...

  3. ExoMol molecular line lists - XIV: The rotation-vibration spectrum of hot SO$_2$

    CERN Document Server

    Underwood, Daniel S; Yurchenko, Sergei N; Huang, Xinchuan; Schwenke, David W; Lee, Timothy J; Clausen, Sønnik; Fateev, Alexander

    2016-01-01

    Sulphur dioxide is well-known in the atmospheres of planets and satellites, where its presence is often associated with volcanism, and in circumstellar envelopes of young and evolved stars as well as the interstellar medium. This work presents a line list of 1.3 billion $^{32}$S$^{16}$O$_2$ vibration-rotation transitions computed using an empirically-adjusted potential energy surface and an ab initio dipole moment surface. The list gives complete coverage up to 8000 cm$^{-1}$ (wavelengths longer than 1.25 $\\mu$m) for temperatures below 2000 K. Infrared absorption cross sections are recorded at 300 and 500 C are used to validated the resulting ExoAmes line list. The line list is made available in electronic form as supplementary data to this article and at www.exomol.com.

  4. ExoMol molecular line lists - XIV. The rotation-vibration spectrum of hot SO2

    Science.gov (United States)

    Underwood, Daniel S.; Tennyson, Jonathan; Yurchenko, Sergei N.; Huang, Xinchuan; Schwenke, David W.; Lee, Timothy J.; Clausen, Sønnik; Fateev, Alexander

    2016-07-01

    Sulphur dioxide is well-known in the atmospheres of planets and satellites, where its presence is often associated with volcanism, and in circumstellar envelopes of young and evolved stars as well as the interstellar medium. This work presents a line list of 1.3 billion 32S16O2 vibration-rotation transitions computed using an empirically adjusted potential energy surface and an ab initio dipole moment surface. The list gives complete coverage up to 8000 cm-1 (wavelengths longer than 1.25 μm) for temperatures below 2000 K. Infrared absorption cross-sections are recorded at 300 and 500 C are used to validated the resulting ExoAmes line list. The line list is made available in electronic form as supplementary data to this article and at www.exomol.com.

  5. ExoMol molecular line lists - XVII. The rotation-vibration spectrum of hot SO3

    Science.gov (United States)

    Underwood, Daniel S.; Yurchenko, Sergei N.; Tennyson, Jonathan; Al-Refaie, Ahmed F.; Clausen, Sønnik; Fateev, Alexander

    2016-11-01

    Sulphur trioxide (SO3) is a trace species in the atmospheres of the Earth and Venus, as well as being an industrial product and an environmental pollutant. A variational line list for 32S16O3, named UYT2, is presented containing 21 billion vibration-rotation transitions. UYT2 can be used to model infrared spectra of SO3 at wavelengths longwards of 2 μm (ν Infrared absorption cross-sections recorded at 300 and 500 C are used to validate the UYT2 line list. The intensities in UYT2 are scaled to match the measured cross-sections. The line list is made available in electronic form as supplementary data to this article and at www.exomol.com.

  6. Molecular and Functional Characterization of GR2-R1 Event Based Backcross Derived Lines of Golden Rice in the Genetic Background of a Mega Rice Variety Swarna

    Science.gov (United States)

    Bollinedi, Haritha; S., Gopala Krishnan; Prabhu, Kumble Vinod; Singh, Nagendra Kumar; Mishra, Sushma; Khurana, Jitendra P.; Singh, Ashok Kumar

    2017-01-01

    Homozygous Golden Rice lines developed in the background of Swarna through marker assisted backcross breeding (MABB) using transgenic GR2-R1 event as a donor for the provitamin A trait have high levels of provitamin A (up to 20 ppm) but are dwarf with pale green leaves and drastically reduced panicle size, grain number and yield as compared to the recurrent parent, Swarna. In this study, we carried out detailed morphological, biochemical and molecular characterization of these lines in a quest to identify the probable reasons for their abnormal phenotype. Nucleotide blast analysis with the primer sequences used to amplify the transgene revealed that the integration of transgene disrupted the native OsAux1 gene, which codes for an auxin transmembrane transporter protein. Real time expression analysis of the transgenes (ZmPsy and CrtI) driven by endosperm-specific promoter revealed the leaky expression of the transgene in the vegetative tissues. We propose that the disruption of OsAux1 disturbed the fine balance of plant growth regulators viz., auxins, gibberellic acid and abscisic acid, leading to the abnormalities in the growth and development of the lines homozygous for the transgene. The study demonstrates the conserved roles of OsAux1 gene in rice and Arabidopsis. PMID:28068433

  7. Molecular and Functional Characterization of GR2-R1 Event Based Backcross Derived Lines of Golden Rice in the Genetic Background of a Mega Rice Variety Swarna.

    Science.gov (United States)

    Bollinedi, Haritha; S, Gopala Krishnan; Prabhu, Kumble Vinod; Singh, Nagendra Kumar; Mishra, Sushma; Khurana, Jitendra P; Singh, Ashok Kumar

    2017-01-01

    Homozygous Golden Rice lines developed in the background of Swarna through marker assisted backcross breeding (MABB) using transgenic GR2-R1 event as a donor for the provitamin A trait have high levels of provitamin A (up to 20 ppm) but are dwarf with pale green leaves and drastically reduced panicle size, grain number and yield as compared to the recurrent parent, Swarna. In this study, we carried out detailed morphological, biochemical and molecular characterization of these lines in a quest to identify the probable reasons for their abnormal phenotype. Nucleotide blast analysis with the primer sequences used to amplify the transgene revealed that the integration of transgene disrupted the native OsAux1 gene, which codes for an auxin transmembrane transporter protein. Real time expression analysis of the transgenes (ZmPsy and CrtI) driven by endosperm-specific promoter revealed the leaky expression of the transgene in the vegetative tissues. We propose that the disruption of OsAux1 disturbed the fine balance of plant growth regulators viz., auxins, gibberellic acid and abscisic acid, leading to the abnormalities in the growth and development of the lines homozygous for the transgene. The study demonstrates the conserved roles of OsAux1 gene in rice and Arabidopsis.

  8. Composition and functional analysis of low-molecular-weight glutenin alleles with Aroona near-isogenic lines of bread wheat

    Directory of Open Access Journals (Sweden)

    Zhang Xiaofei

    2012-12-01

    Full Text Available Abstract Background Low-molecular-weight glutenin subunits (LMW-GS strongly influence the bread-making quality of bread wheat. These proteins are encoded by a multi-gene family located at the Glu-A3, Glu-B3 and Glu-D3 loci on the short arms of homoeologous group 1 chromosomes, and show high allelic variation. To characterize the genetic and protein compositions of LMW-GS alleles, we investigated 16 Aroona near-isogenic lines (NILs using SDS-PAGE, 2D-PAGE and the LMW-GS gene marker system. Moreover, the composition of glutenin macro-polymers, dough properties and pan bread quality parameters were determined for functional analysis of LMW-GS alleles in the NILs. Results Using the LMW-GS gene marker system, 14–20 LMW-GS genes were identified in individual NILs. At the Glu-A3 locus, two m-type and 2–4 i-type genes were identified and their allelic variants showed high polymorphisms in length and nucleotide sequences. The Glu-A3d allele possessed three active genes, the highest number among Glu-A3 alleles. At the Glu-B3 locus, 2–3 m-type and 1–3 s-type genes were identified from individual NILs. Based on the different compositions of s-type genes, Glu-B3 alleles were divided into two groups, one containing Glu-B3a, B3b, B3f and B3g, and the other comprising Glu-B3c, B3d, B3h and B3i. Eight conserved genes were identified among Glu-D3 alleles, except for Glu-D3f. The protein products of the unique active genes in each NIL were detected using protein electrophoresis. Among Glu-3 alleles, the Glu-A3e genotype without i-type LMW-GS performed worst in almost all quality properties. Glu-B3b, B3g and B3i showed better quality parameters than the other Glu-B3 alleles, whereas the Glu-B3c allele containing s-type genes with low expression levels had an inferior effect on bread-making quality. Due to the conserved genes at Glu-D3 locus, Glu-D3 alleles showed no significant differences in effects on all quality parameters. Conclusions This work

  9. Proteomic investigation of embryonic rat heart-derived H9c2 cell line sheds new light on the molecular phenotype of the popular cell model.

    Science.gov (United States)

    Lenčo, Juraj; Lenčová-Popelová, Olga; Link, Marek; Jirkovská, Anna; Tambor, Vojtěch; Potůčková, Eliška; Stulík, Jiří; Šimůnek, Tomáš; Štěrba, Martin

    2015-12-10

    Due to their cardiac origin, H9c2 cells rank among the most popular cell lines in current cardiovascular research, yet molecular phenotype remains elusive. Hence, in this study we used proteomic approach to describe molecular phenotype of H9c2 cells in their undifferentiated (i.e., most frequently used) state, and its functional response to cardiotoxic drug doxorubicin. Of 1671 proteins identified by iTRAQ IEF/LC-MSMS analysis, only 12 proteins were characteristic for striated muscle cells and none was cardiac phenotype-specific. Targeted LC-SRM and western blot analyses confirmed that undifferentiated H9c2 cells are phenotypically considerably different to both primary neonatal cardiomyocytes and adult myocardium. These cells lack proteins essential for formation of striated muscle myofibrils or they express only minor amounts thereof. They also fail to express many proteins important for metabolism of muscle cells. The challenge with clinically relevant concentrations of doxorubicin did not induce a proteomic signature that has been previously noted in primary cardiomyocytes or adult hearts. Instead, several alterations previously described in other cells of mesodermal origin, such as fibroblasts, were observed (e.g., severe down-regulation of collagen synthesis pathway). In conclusion, the molecular phenotype of H9c2 cells resembles very immature myogenic cells with skeletal muscle commitment upon differentiation and thus, translatability of findings obtained in these cells deserves caution.

  10. DISCOVERY OF MOLECULAR GAS AROUND HD 131835 IN AN APEX MOLECULAR LINE SURVEY OF BRIGHT DEBRIS DISKS

    Energy Technology Data Exchange (ETDEWEB)

    Moór, A.; Ábrahám, P.; Kóspál, Á.; Szabó, Gy. M.; Kiss, Cs. [Konkoly Observatory, Research Centre for Astronomy and Earth Sciences, Hungarian Academy of Sciences, P.O. Box 67, H-1525 Budapest (Hungary); Henning, Th.; Balog, Z. [Max-Planck-Institut für Astronomie, Königstuhl 17, D-69117 Heidelberg (Germany); Juhász, A. [Institute of Astronomy, Madingley Road, Cambridge CB3, OHA (United Kingdom); Pascucci, I. [Lunar and Planetary Laboratory, University of Arizona, Tucson, AZ 85721 (United States); Vavrek, R. [Herschel Science Centre, ESA/ESAC, P.O. Box 78, Villanueva de la Cañada, E-28691, Madrid (Spain); Curé, M. [Instituto de Física y Astronomía, Universidad de Valparaíso (Chile); Csengeri, T.; Güsten, R. [Max-Planck-Institut für Radioastronomie, Auf dem Hügel 69, D-53121 Bonn (Germany); Grady, C., E-mail: moor@konkoly.hu [NASA Goddard Space Flight Center, Code 667, Greenbelt, MD 20771 (United States)

    2015-11-20

    Debris disks are considered to be gas-poor, but recent observations revealed molecular or atomic gas in several 10–40 Myr old systems. We used the APEX and IRAM 30 m radio telescopes to search for CO gas in 20 bright debris disks. In one case, around the 16 Myr old A-type star HD 131835, we discovered a new gas-bearing debris disk, where the CO 3–2 transition was successfully detected. No other individual system exhibited a measurable CO signal. Our Herschel Space Observatory far-infrared images of HD 131835 marginally resolved the disk at both 70 and 100 μm, with a characteristic radius of ∼170 AU. While in stellar properties HD 131835 resembles β Pic, its dust disk properties are similar to those of the most massive young debris disks. With the detection of gas in HD 131835 the number of known debris disks with CO content has increased to four, all of them encircling young (≤40 Myr) A-type stars. Based on statistics within 125 pc, we suggest that the presence of a detectable amount of gas in the most massive debris disks around young A-type stars is a common phenomenon. Our current data cannot conclude on the origin of gas in HD 131835. If the gas is secondary, arising from the disruption of planetesimals, then HD 131835 is a comparably young, and in terms of its disk, more massive analog of the β Pic system. However, it is also possible that this system, similar to HD 21997, possesses a hybrid disk, where the gas material is predominantly primordial, while the dust grains are mostly derived from planetesimals.

  11. Discovery of Molecular Gas around HD 131835 in an APEX Molecular Line Survey of Bright Debris Disks

    Science.gov (United States)

    Moór, A.; Henning, Th.; Juhász, A.; Ábrahám, P.; Balog, Z.; Kóspál, Á.; Pascucci, I.; Szabó, Gy. M.; Vavrek, R.; Curé, M.; Csengeri, T.; Grady, C.; Güsten, R.; Kiss, Cs.

    2015-11-01

    Debris disks are considered to be gas-poor, but recent observations revealed molecular or atomic gas in several 10-40 Myr old systems. We used the APEX and IRAM 30 m radio telescopes to search for CO gas in 20 bright debris disks. In one case, around the 16 Myr old A-type star HD 131835, we discovered a new gas-bearing debris disk, where the CO 3-2 transition was successfully detected. No other individual system exhibited a measurable CO signal. Our Herschel Space Observatory far-infrared images of HD 131835 marginally resolved the disk at both 70 and 100 μm, with a characteristic radius of ˜170 AU. While in stellar properties HD 131835 resembles β Pic, its dust disk properties are similar to those of the most massive young debris disks. With the detection of gas in HD 131835 the number of known debris disks with CO content has increased to four, all of them encircling young (≤40 Myr) A-type stars. Based on statistics within 125 pc, we suggest that the presence of a detectable amount of gas in the most massive debris disks around young A-type stars is a common phenomenon. Our current data cannot conclude on the origin of gas in HD 131835. If the gas is secondary, arising from the disruption of planetesimals, then HD 131835 is a comparably young, and in terms of its disk, more massive analog of the β Pic system. However, it is also possible that this system, similar to HD 21997, possesses a hybrid disk, where the gas material is predominantly primordial, while the dust grains are mostly derived from planetesimals.

  12. Factors that affect the molecular nature of germ-line mutations recovered in the mouse specific-locus test

    Energy Technology Data Exchange (ETDEWEB)

    Russell, L.B. (Oak Ridge National Lab., TN (United States))

    1991-01-01

    The morphological specific locus test (SLT), which allows the scoring of 2,000 loci/hr/person, has been in use for four decades for measuring mammalian germ-line mutation rates under various conditions of exposure. More recently, the SLT's capabilities for the qualitative characterization of mutations have been exploited. The large sets of mutations centered on specific loci that have been accumulated over the years, including sets of nested deletions, have provided prime material for fine-structure genetic analyses. Subsequent molecular entry to these regions has led to intensive physical/functional mapping of megabase segments of the genome. In turn, these investigations have generated genetic and molecular tools for analyzing individual mutations as to extent and nature of the genomic lesion. These and related quantitative findings now make it possible to optimize conditions for the use of mutagens in providing desired types of mutations as tools.

  13. Screening and Identifying Two Specific Molecular Markers in Maintainer Line of Cytoplasmic Male Sterility Cauliflower (Brassica oleracea var.botrytis)

    Institute of Scientific and Technical Information of China (English)

    C.G. Wang; J.M. Gao; H. Li; Y. Gu; X.Q. Chen; W.Q. Song

    2007-01-01

    @@ Cytoplasmic male sterility (CMS) is a maternally inherited trait that prevents the production of function pollen, but maintains female fertility. It has been widely used in breeding programs to product F1 hybrid seed in some crops (Hanson, 1991).

  14. New Paramecium quadecaurelia strains (P. aurelia spp. complex, Ciliophora) identified by molecular markers (rDNA and mtDNA).

    Science.gov (United States)

    Przyboś, Ewa; Tarcz, Sebastian; Dusi, Eike

    2013-08-01

    Paramecium quadecaurelia is a rare species (previously known only from two locations) belonging to the P. aurelia species complex. In the present paper, fragments of an rDNA gene (ITS1-5.8S-ITS2-5' rDNA) and mtDNA genes (cytochrome oxidase subunit I and cytochrome b regions) were employed to assist in the identification and characterization of three new strains collected from Ecuador and Thailand. Molecular data were confirmed by mating reactions. In rDNA and mtDNA trees constructed for species of the P. aurelia complex, all P. quadecaurelia strains, including the three new strains discussed in this study and two known previously from Australia and Africa, form a monophyletic but differentiated clade. The present study shows that genetic differentiation among the strains of P. quadecaurelia is equal to or even greater than the distances between some other P. aurelia species, e.g., P. primaurelia and P. pentaurelia. Such great intra-specific differentiation may indicate a future splitting of the P. quadecaurelia species into reproductively isolated lines. Copyright © 2012 Elsevier GmbH. All rights reserved.

  15. Using molecular repertoires to identify high-affinity peptide ligands of the WW domain of human and mouse YAP.

    Science.gov (United States)

    Linn, H; Ermekova, K S; Rentschler, S; Sparks, A B; Kay, B K; Sudol, M

    1997-06-01

    The WW domain is a globular protein domain that is involved in mediating protein-protein interaction and that ultimately participates in various intracellular signaling events. The domain binds to polyproline ligands containing the xPPxY consensus (where x signifies any amino acid, P is proline and Y is tyrosine). One of the first WW domain-ligand links that was characterized in vitro was the WW domain of Yes-Associated Protein (YAP) and its WBP-1 ligand. To further characterize this molecular interaction, we used two independent approaches, both of which focused on the mutational analysis of the WBP-1 ligand. We screened repertoires of synthetic decamer peptides containing the xPPxY core of WBP-1 in which all ten positions were sequentially replaced with the remaining amino acids. In addition, we screened decamer repertoires with all permutations of the amino acids which individually increased the binding to the WW domain of YAP, as compared to the wild type. In a parallel approach, we used a phage-displayed combinatorial peptide library biased for the presence of two consecutive prolines to study ligand preferences for the WW domain of YAP. Interestingly, these two lines of investigation converged and yielded the core sequence PPPPYP, which is preferred by the YAP-WW domain. This sequence was found within the p53 (tumor suppressor) binding protein-2, a probable cognate or alternative ligand interacting with YAP.

  16. ExoMol molecular line lists - XVII. The rotation-vibration spectrum of hot SO3

    DEFF Research Database (Denmark)

    Underwood, Daniel S.; Yurchenko, Sergei N.; Tennyson, Jonathan

    2016-01-01

    Sulphur trioxide (SO3) is a trace species in the atmospheres of the Earth and Venus, as well as being an industrial product and an environmental pollutant. A variational line list for 32S16O3, named UYT2, is presented containing 21 billion vibration-rotation transitions. UYT2 can be used to model...

  17. Breeding and molecular cytogenetic identification of wheat-Thinopyrum intermedium addition lines resistant to powdery mildew

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Wheat-related species Th. intermedium was used to cross with common wheat Yannong 15. In the self progenies of the hybrid, two addition lines, Ⅱ-1-7-1 and Ⅱ-3-3-2, stable in cytology, were developed by cytology and powdery mildew resistance identification. Their chromosome number were 2n = 44 and formed 22 bivalents at PMC MI. In F1 of the two addition lines crossing with Yannong 15, there appeared about one univalent at PMC MI, respectively. Resistance identification in greenhouse and field using the No. 15 and mixed strains of E. gramnis f. sp. tritici showed that they were immune to powdery mildew. Chromosome number and resistance identification using the F2 single plants of the addition line crossing with Yannong 15 indicated that the resistant gene was located on the alien chromosomes. In situ hybridization using St and E genomic DNA as probe showed that the added chromosome in the two addition lines probably came from the E genome of Th. intermedium, which indicated that a pair of E genome chromosomes carried a new resistant gene to powdery mildew.

  18. ExoMol molecular line lists - XIV. The rotation-vibration spectrum of hot SO2

    DEFF Research Database (Denmark)

    Underwood, Daniel S.; Tennyson, Jonathan; Yurchenko, Sergei N.;

    2016-01-01

    Sulphur dioxide is well-known in the atmospheres of planets and satellites, where its presence is often associated with volcanism, and in circumstellar envelopes of young and evolved stars as well as the interstellar medium. This work presents a line list of 1.3 billion 32S16O2 vibration-rotation...

  19. ExoMol molecular line lists: XI The spectrum of nitric acid

    CERN Document Server

    Pavlyuchko, Anatoly I; Tennyson, Jonathan

    2015-01-01

    Nitric acid is a possible biomarker in the atmospheres of exoplanets. An accurate line list of rotational and rotational-vibrational transitions is computed for nitric acid (HNO$_3$). This line list covers wavelengths longer than 1.42 $\\mu$m (0 - 7000 cm$^{-1}$) and temperatures up to 500 K. The line list is computed using a hybrid variational -- perturbation theory and empirically tuned potential energy and dipole surfaces. It comprises almost 7 billion transitions involving rotations up to $J=100$. Comparisons with spectra from the HITRAN and PNNL databases demonstrate the accuracy of our calculations. Synthetic spectra of water - nitric acid mixturessuggest that nitric acid has features at 7.5 and 11.25 $\\mu$m that are capable of providing a clear signature for HNO$_3$; the feature at 11.25 $\\mu$m is particularly promising. Partition functions plus full line lists of transitions are made available in an electronic form as supplementary data to the article and at www.exomol.com.

  20. Inheritance and molecular mapping of anthracnose resistance gene present in the differential line PI533918

    Science.gov (United States)

    Anthracnose (Collectrotichum sublineolum) is considered one of the most destructive diseases of sorghum (Sorghum bicolor L. Moench) because it infects all aerial tissues of the plant. The best strategy to control the disease is the incorporation of resistance genes. At present, eighteen sorghum line...

  1. Dynamically Influenced Molecular Clouds in the Nucleus of NGC 6946: Variations in the CO Isotopic Line Ratios

    CERN Document Server

    Meier, D S; Meier, David S.; Turner, Jean L.

    2004-01-01

    We present high resolution (~5'') maps of the J = 1 - 0 transitions of ^{13}CO and C^{18}O towards the nucleus of NGC 6946, made with the Owens Valley Millimeter Array. The images are compared with existing ^{12}CO(1-0) maps to investigate localized changes in gas properties across the nucleus. As compared to ^{12}CO, both ^{13}CO and C^{18}O are more confined to the central ring of molecular gas associated with the nuclear star formation; that is, ^{12}CO is stronger relative to ^{13}CO and C^{18}O away from the nucleus and along the spiral arms. The ^{12}CO(1-0)/^{13}CO(1-0) line ratio reaches very high values of >40. We attribute the relative ^{13}CO weakness to a rapid change in the interstellar medium from dense star forming cores in a central ring to diffuse, low density molecular gas in and behind the molecular arms. This change is abrupt, occurring in less than a beamsize (90 pc), about the size of a giant molecular cloud. Column densities determined from ^{13}CO(1-0), C^{18}O(1-0), and 1.4 mm dust co...

  2. Colon cancer molecular subtypes identified by expression profiling and associated to stroma, mucinous type and different clinical behavior

    Directory of Open Access Journals (Sweden)

    Perez Villamil Beatriz

    2012-06-01

    Full Text Available Abstract Background Colon cancer patients with the same stage show diverse clinical behavior due to tumor heterogeneity. We aimed to discover distinct classes of tumors based on microarray expression patterns, to analyze whether the molecular classification correlated with the histopathological stages or other clinical parameters and to study differences in the survival. Methods Hierarchical clustering was performed for class discovery in 88 colon tumors (stages I to IV. Pathways analysis and correlations between clinical parameters and our classification were analyzed. Tumor subtypes were validated using an external set of 78 patients. A 167 gene signature associated to the main subtype was generated using the 3-Nearest-Neighbor method. Coincidences with other prognostic predictors were assesed. Results Hierarchical clustering identified four robust tumor subtypes with biologically and clinically distinct behavior. Stromal components (p BRAF mutations. Tumor subtypes were validated using an external set of 78 patients. A 167 gene signature associated to the Low-stroma-subtype distinguished low risk patients from high risk patients in the external cohort (Dukes B and C:HR = 8.56(2.53-29.01; Dukes B,C and D:HR = 1.87(1.07-3.25. Eight different reported survival gene signatures segregated our tumors into two groups the Low-stroma-subtype and the other tumor subtypes. Conclusions We have identified novel molecular subtypes in colon cancer with distinct biological and clinical behavior that are established from the initiation of the tumor. Tumor microenvironment is important for the classification and for the malignant power of the tumor. Differential gene sets and biological pathways characterize each tumor subtype reflecting underlying mechanisms of carcinogenesis that may be used for the selection of targeted therapeutic procedures. This classification may contribute to an improvement in the management of the patients with CRC and to a

  3. Herschel-PACS Observations of Far-IR CO Line Emission in NGC 1068: Highly Excited Molecular Gas in the Circumnuclear Disk

    Science.gov (United States)

    2012-08-10

    reserved. Printed in the U.S.A. HERSCHEL-PACS OBSERVATIONS OF FAR-IR CO LINE EMISSION IN NGC 1068: HIGHLY EXCITED MOLECULAR GAS IN THE CIRCUMNUCLEAR DISK∗ S...20375, USA 3 Sackler School of Physics & Astronomy, Tel Aviv University, Ramat Aviv 69978, Israel 4 Departamento de Fisica , Universidad de Alcalá de...the mass budget in the nuclear region. We compare the CO line profiles with those of other molecular tracers observed at higher spatial and spectral

  4. Whole-Genome Resequencing of a Cucumber Chromosome Segment Substitution Line and Its Recurrent Parent to Identify Candidate Genes Governing Powdery Mildew Resistance

    Science.gov (United States)

    Yu, Ting; Xu, Xuewen; Yan, Yali; Qi, Xiaohua; Chen, Xuehao

    2016-01-01

    Cucumber is an economically important vegetable crop worldwide. Powdery mildew (PM) is one of the most severe diseases that can affect cucumber crops. There have been several research efforts to isolate PM resistance genes for breeding PM-resistant cucumber. In the present study, we used a chromosome segment substitution line, SSL508-28, which carried PM resistance genes from the donor parent, JIN5-508, through twelve generations of backcrossing with a PM-susceptible inbred line, D8. We performed whole-genome resequencing of SSL508-28 and D8 to identify single nucleotide polymorphisms (SNPs), and insertions and deletions (indels). When compared against the reference genome of the inbred cucumber line 9930, a total of 468,616 SNPs and 67,259 indels were identified in SSL508-28, and 537,352 SNPs and 91,698 indels were identified in D8. Of these, 3,014 non-synonymous SNPs and 226 frameshift indels in SSL508-28, and 3,104 non-synonymous SNPs and 251 frameshift indels in D8, were identified. Bioinformatics analysis of these variations revealed a total of 15,682 SNPs and 6,262 indels between SSL508-28 and D8, among which 120 non-synonymous SNPs and 30 frameshift indels in 94 genes were detected between SSL508-28 and D8. Finally, out of these 94 genes, five resistance genes with nucleotide-binding sites and leucine-rich repeat domains were selected for qRT-PCR analysis. This revealed an upregulation of two transcripts, Csa2M435460.1 and Csa5M579560.1, in SSL508-28. Furthermore, the results of qRT-PCR analysis of these two genes in ten PM resistant and ten PM susceptible cucumber lines showed that when exposed to PM, Csa2M435460.1 and Csa5M579560.1 exhibited a higher expression level of resistant lines than susceptible lines. This indicates that Csa2M435460.1 and Csa5M579560.1 are candidate genes for PM resistance in cucumber. In addition, the non-synonymous SNPs in Csa2M435460.1 and Csa5M579560.1, identified in SSL508-28 and D8, might be the key to high PM-resistance in

  5. Molecular Breeding of Rice Restorer Lines and Hybrids for Brown Planthopper (BPH) Resistance Using the Bph14 and Bph15 Genes.

    Science.gov (United States)

    Wang, Hongbo; Ye, Shengtuo; Mou, Tongmin

    2016-12-01

    The development of hybrid rice is a practical approach for increasing rice production. However, the brown planthopper (BPH), Nilaparvata lugens Stål, causes severe yield loss of rice (Oryza sativa L.) and can threaten food security. Therefore, breeding hybrid rice resistant to BPH is the most effective and economical strategy to maintain high and stable production. Fortunately, numerous BPH resistance genes have been identified, and abundant linkage markers are available for molecular marker-assisted selection (MAS) in breeding programs. Hence, we pyramided two BPH resistance genes, Bph14 and Bph15, into a susceptive CMS restorer line Huahui938 and its derived hybrids using MAS to improve the BPH resistance of hybrid rice. Three near-isogenic lines (NILs) with pyramided Bph14 and Bph15 were obtained by molecular marker-assisted backcross (MAB) and phenotypic selection. The genomic components of these NILs were detected using the whole-genome SNP (Single nucleotide polymorphism) array, RICE6K, suggesting that the recurrent parent genome (RPG) recovery of the NILs was 87.88, 87.70 and 86.62 %, respectively. BPH bioassays showed that the improved NILs and their derived hybrids carrying homozygous Bph14 and Bph15 were resistant to BPH. However, the hybrids with heterozygous Bph14 and Bph15 remained susceptible to BPH. The developed NILs showed no significant differences in major agronomic traits and rice qualities compared with the recurrent parent. Moreover, the improved hybrids derived from the NILs exhibited better agronomic performance and rice quality compared with the controls under natural field conditions. This study demonstrates that it is essential to stack Bph14 and Bph15 into both the maternal and paternal parents for developing BPH-resistant hybrid rice varieties. The SNP array with abundant DNA markers is an efficient tool for analyzing the RPG recovery of progenies and can be used to monitor the donor segments in NILs, thus being extremely important

  6. Analysis of gene expression data from non-small cell lung carcinoma cell lines reveals distinct sub-classes from those identified at the phenotype level.

    Directory of Open Access Journals (Sweden)

    Andrew R Dalby

    Full Text Available Microarray data from cell lines of Non-Small Cell Lung Carcinoma (NSCLC can be used to look for differences in gene expression between the cell lines derived from different tumour samples, and to investigate if these differences can be used to cluster the cell lines into distinct groups. Dividing the cell lines into classes can help to improve diagnosis and the development of screens for new drug candidates. The micro-array data is first subjected to quality control analysis and then subsequently normalised using three alternate methods to reduce the chances of differences being artefacts resulting from the normalisation process. The final clustering into sub-classes was carried out in a conservative manner such that sub-classes were consistent across all three normalisation methods. If there is structure in the cell line population it was expected that this would agree with histological classifications, but this was not found to be the case. To check the biological consistency of the sub-classes the set of most strongly differentially expressed genes was be identified for each pair of clusters to check if the genes that most strongly define sub-classes have biological functions consistent with NSCLC.

  7. Study for on-line system to identify inadvertent control rod drops in PWR reactors using ex-core detector and thermocouple measures

    Energy Technology Data Exchange (ETDEWEB)

    Souza, Thiago J.; Medeiros, Jose A.C.C.; Goncalves, Alessandro C., E-mail: tsouza@nuclear.ufrj.br, E-mail: canedo@lmp.ufrj.br, E-mail: alessandro@nuclear.ufrj.br [Coordenacao dos Programas de Pos-Graduacao em Engenharia (COPPE/UFRJ), Rio de Janeiro, RJ (Brazil). Programa de Engenharia Nuclear

    2015-07-01

    Accidental control rod drops event in PWR reactors leads to an unsafe operating condition. It is important to quickly identify the rod to minimize undesirable effects in such a scenario. In this event, there is a distortion in the power distribution and temperature in the reactor core. The goal of this study is to develop an on-line model to identify the inadvertent control rod dropped in PWR reactor. The proposed model is based on physical correlations and pattern recognition of ex-core detector responses and thermocouples measures. The results of the study demonstrated the feasibility of an on-line system, contributing to safer operation conditions and preventing undesirable effects, as its shutdown. (author)

  8. ExoMol molecular line lists - XVII The rotation-vibration spectrum of hot SO$_3$

    CERN Document Server

    Underwood, Daniel S; Tennyson, Jonathan; Al-Refaie, Ahmed F; Clausen, Sønnik; Fateev, Alexander

    2016-01-01

    Sulphur trioxide (SO$_3$) is a trace species in the atmospheres of the Earth and Venus, as well as well as being an industrial product and an environmental pollutant. A variational line list for $^{32}$S$^{16}$O$_{3}$, named UYT2, is presented containing 21 billion vibration-rotation transitions. UYT2 can be used to model infrared spectra of SO$_3$ at wavelengths longwards of 2 $\\mu$m ($\

  9. Cell death in mammalian cell culture: molecular mechanisms and cell line engineering strategies

    OpenAIRE

    Krampe, Britta; Al-Rubeai, Mohamed

    2010-01-01

    Cell death is a fundamentally important problem in cell lines used by the biopharmaceutical industry. Environmental stress, which can result from nutrient depletion, by-product accumulation and chemical agents, activates through signalling cascades regulators that promote death. The best known key regulators of death process are the Bcl-2 family proteins which constitute a critical intracellular checkpoint of apoptosis cell death within a common death pathway. Engineering of several members o...

  10. The ExoMol project: Software for computing large molecular line lists

    CERN Document Server

    Tennyson, Jonathan

    2016-01-01

    The use of variational nuclear motion programs to compute line lists of transition frequencies and intensities is now a standard procedure. The ExoMol project has used this technique to generate line lists for studies of hot bodies such as the atmospheres of exoplanets and cool stars. The resulting line list can be huge: many contain 10 billion or more transitions. This software update considers changes made to our programs during the course of the project to allow for such calculations. This update considers three programs: {\\sc Duo} which computed vibronic spectra for diatomics, {\\sc DVR3D} which computes rotation-vibration spectra for triatomics, and {\\sc TROVE} which computes rotation-vibration spectra for general polyatomic systems. Important updates in functionality include the calculation of quasibound (resonance) states and Land\\'e $g$-factors by {\\sc Duo} and the calculation of resonance states by {\\sc DVR3D}. Significant algorithmic improvements are reported for both {\\sc DVR3D} and {\\sc TROVE}. All...

  11. Determination of very rapid molecular rotation by using the central electron paramagnetic resonance line.

    Science.gov (United States)

    Kurban, Mark R

    2013-02-21

    Picosecond rotational correlation times of perdeuterated tempone (PDT) are found in alkane and aromatic liquids by directly using the spectral width of the central electron paramagnetic resonance line. This is done by mathematically eliminating the nonsecular spectral density from the spectral parameter equations, thereby removing the need to assume a particular form for it. This is preferable to fitting a constant correction factor to the spectral density, because such a factor does not fit well in the low picosecond range. The electron-nuclear spin dipolar interaction between the probe and solvent is shown to be negligible for the very rapid rotation of PDT in these liquids at the temperatures of the study. The rotational correlation times obtained with the proposed method generally agree to within experimental uncertainty with those determined by using the traditional parameters. Using the middle line width offers greater precision and smoother trends. Previous work with the central line width is discussed, and past discrepancies are explained as possibly resulting from residual inhomogeneous broadening. The rotational correlation time almost forms a common curve across all of the solvents when plotted with respect to isothermal compressibility, which shows the high dependence of rotation on liquid free volume.

  12. A Molecular Line Observation toward Massive Clumps Associated with Infrared Dark Clouds

    CERN Document Server

    Sakai, Takeshi; Kamegai, Kazuhisa; Hirota, Tomoya; Yamaguchi, Nobuyuki; Shiba, Shoichi; Yamamoto, Satoshi

    2008-01-01

    We have surveyed the N2H+ J=1-0, HC3N J=5-4, CCS J_N=4_3-3_2, NH3 (J, K) = (1, 1), (2, 2), (3, 3), and CH3OH J=7-6 lines toward the 55 massive clumps associated with infrared dark clouds by using the Nobeyama Radio Observatory 45 m telescope and the Atacama Submillimeter Telescope Experiment 10 m telescope. The N2H+, HC3N, and NH3 lines are detected toward most of the objects. On the other hand, the CCS emission is detected toward none of the objects. The [CCS]/[N2H+] ratios are found to be mostly lower than unity even in the Spitzer 24 micron dark objects. This suggests that most of the massive clumps are chemically more evolved than the low-mass starless cores. The CH3OH emission is detected toward 18 out of 55 objects. All the CH3OH-detected objects are associated with the Spitzer 24 micron sources, suggesting that star formation has already started in all the CH3OH-detected objects. The velocity widths of the CH3OH J_K=7_0-6_0 A+ and 7_{-1}-6_{-1} E lines are broader than those of N2H+ J=1-0. The CH3OH J_...

  13. Automated Protein Biomarker Analysis: on-line extraction of clinical samples by Molecularly Imprinted Polymers

    Science.gov (United States)

    Rossetti, Cecilia; Świtnicka-Plak, Magdalena A.; Grønhaug Halvorsen, Trine; Cormack, Peter A. G.; Sellergren, Börje; Reubsaet, Léon

    2017-03-01

    Robust biomarker quantification is essential for the accurate diagnosis of diseases and is of great value in cancer management. In this paper, an innovative diagnostic platform is presented which provides automated molecularly imprinted solid-phase extraction (MISPE) followed by liquid chromatography-mass spectrometry (LC-MS) for biomarker determination using ProGastrin Releasing Peptide (ProGRP), a highly sensitive biomarker for Small Cell Lung Cancer, as a model. Molecularly imprinted polymer microspheres were synthesized by precipitation polymerization and analytical optimization of the most promising material led to the development of an automated quantification method for ProGRP. The method enabled analysis of patient serum samples with elevated ProGRP levels. Particularly low sample volumes were permitted using the automated extraction within a method which was time-efficient, thereby demonstrating the potential of such a strategy in a clinical setting.

  14. Automated Protein Biomarker Analysis: on-line extraction of clinical samples by Molecularly Imprinted Polymers

    Science.gov (United States)

    Rossetti, Cecilia; Świtnicka-Plak, Magdalena A.; Grønhaug Halvorsen, Trine; Cormack, Peter A.G.; Sellergren, Börje; Reubsaet, Léon

    2017-01-01

    Robust biomarker quantification is essential for the accurate diagnosis of diseases and is of great value in cancer management. In this paper, an innovative diagnostic platform is presented which provides automated molecularly imprinted solid-phase extraction (MISPE) followed by liquid chromatography-mass spectrometry (LC-MS) for biomarker determination using ProGastrin Releasing Peptide (ProGRP), a highly sensitive biomarker for Small Cell Lung Cancer, as a model. Molecularly imprinted polymer microspheres were synthesized by precipitation polymerization and analytical optimization of the most promising material led to the development of an automated quantification method for ProGRP. The method enabled analysis of patient serum samples with elevated ProGRP levels. Particularly low sample volumes were permitted using the automated extraction within a method which was time-efficient, thereby demonstrating the potential of such a strategy in a clinical setting. PMID:28303910

  15. Statistical analysis of molecular line emission from T tauri disk models

    Directory of Open Access Journals (Sweden)

    Itziar de Gregorio-Monsalvo

    2007-01-01

    Full Text Available En este trabajo modelamos la emisión esperada de la línea molecular C17O(J=3!2 en discos protoplanetarios, modificando diferentes parámetros físicos para obtener distintas características observacionales. Nuestra meta es determinar la clase de observaciones que nos permitirán extraer información sobre los parámetros físicos de los discos. Con este propósito realizamos un análisis estadístico de componentes principales y una correlación lineal múltiple en el conjunto de resultados obtenidos a partir de los modelos. Además, presentamos un estudio sobre futuras observaciones de línea molecular en discos protoplanetarios usando SMA y ALMA.

  16. Theory and Modeling of the Zeeman and Paschen-Back Effects in Molecular Lines

    Science.gov (United States)

    Asensio Ramos, A.; Trujillo Bueno, J.

    2006-01-01

    This paper describes a very general approach to the calculation of the Zeeman splitting effect produced by an external magnetic field on the rotational levels of diatomic molecules. The method is valid for arbitrary values of the total electronic spin and of the magnetic field strength-that is, it holds for molecular electronic states of any multiplicity and for both the Zeeman and incomplete Paschen-Back regimes. It is based on an efficient numerical diagonalization of the effective Zeeman Hamiltonian, which can incorporate easily all the contributions one may eventually be interested in, such as the hyperfine interaction of the external magnetic field with the spin motions of the nuclei. The reliability of the method is demonstrated by comparing our results with previous ones obtained via formulae valid only for doublet states. We also present results for molecular transitions arising between nondoublet electronic states, illustrating that their Zeeman patterns show signatures produced by the Paschen-Back effect.

  17. Theory and Modeling of the Zeeman and Paschen-Back effects in Molecular Lines

    CERN Document Server

    Bueno, A A R J T

    2005-01-01

    This paper describes a very general approach to the calculation of the Zeeman splitting effect produced by an external magnetic field on the rotational levels of diatomic molecules. The method is valid for arbitrary values of the total electronic spin and of the magnetic field strength -that is, it holds for molecular electronic states of any multiplicity and for both the Zeeman and incomplete Paschen-Back regimes. It is based on an efficient numerical diagonalization of the effective Zeeman Hamiltonian, which can incorporate easily all the contributions one may eventually be interested in, such as the hyperfine interaction of the external magnetic field with the spin motions of the nuclei. The reliability of the method is demonstrated by comparing our results with previous ones obtained via formulae valid only for doublet states. We also present results for molecular transitions arising between non-doublet electronic states, illustrating that their Zeeman patterns show signatures produced by the Paschen-Back...

  18. Molecular analysis of primary gastric cancer, corresponding xenografts, and 2 novel gastric carcinoma cell lines reveals novel alterations in gastric carcinogenesis.

    NARCIS (Netherlands)

    Milne, A.N.; Sitarz, R.; Carvalho, R.; Polak, M.M.; Ligtenberg, M.J.L.; Pauwels, P.; Offerhaus, G.J.; Weterman, M.A.J.

    2007-01-01

    We report the molecular characterization of 8 primary gastric carcinomas, corresponding xenografts, and 2 novel gastric carcinoma cell lines. We compared the tumors and cell lines, with respect to histology, immunohistochemistry, copy number, and hypermethylation of up to 38 genes using

  19. Molecular approaches identify known species, reveal cryptic species and verify host specificity of Chinese Philotrypesis (Hymenoptera: Pteromalidae).

    Science.gov (United States)

    Zhou, Mei-Jiao; Xiao, Jin-Hua; Bian, Sheng-Nan; Li, Yan-Wei; Niu, Li-Ming; Hu, Hao-Yuan; Wu, Wen-Shan; Murphy, Robert W; Huang, Da-Wei

    2012-07-01

    Philotrypesis, a major component of the fig wasp community (Hymenoptera: Pteromalidae), is a model taxon for studying male fighting and mating behaviour. Its extreme sexual dimorphism and male polymorphism render species identification uncertain and in-depth research on its ecology, behaviour and other evolutionary topics challenging. The fig wasps' enclosed habitat within the syconia makes their mating behaviour inaccessible, to the extent of matching conspecific females and males. In this study, we combine morphological and molecular analyses to identify species of Philotrypesis sampled from south China and to associate their extraordinarily dimorphic genders and labile male morphologies. Morphological evaluations of females identify 22 species and 28 male morphs. The mitochondrial cytochrome c oxidase I and nuclear internal transcribed spacer 2 data detect 21 species using females, and 15 species among the males. Most of the males match the species as delimited by females. Both markers reveal cryptic species in P. quadrisetosa on Ficus vasculosa. Most species of wasps live on one species of fig but three species co-occur in two hosts (F. microcarpa and F. benjamina), which indicates host switching.

  20. Integrated Bioinformatics, Environmental Epidemiologic and Genomic Approaches to Identify Environmental and Molecular Links between Endometriosis and Breast Cancer

    Directory of Open Access Journals (Sweden)

    Deodutta Roy

    2015-10-01

    Full Text Available We present a combined environmental epidemiologic, genomic, and bioinformatics approach to identify: exposure of environmental chemicals with estrogenic activity; epidemiologic association between endocrine disrupting chemical (EDC and health effects, such as, breast cancer or endometriosis; and gene-EDC interactions and disease associations. Human exposure measurement and modeling confirmed estrogenic activity of three selected class of environmental chemicals, polychlorinated biphenyls (PCBs, bisphenols (BPs, and phthalates. Meta-analysis showed that PCBs exposure, not Bisphenol A (BPA and phthalates, increased the summary odds ratio for breast cancer and endometriosis. Bioinformatics analysis of gene-EDC interactions and disease associations identified several hundred genes that were altered by exposure to PCBs, phthalate or BPA. EDCs-modified genes in breast neoplasms and endometriosis are part of steroid hormone signaling and inflammation pathways. All three EDCs–PCB 153, phthalates, and BPA influenced five common genes—CYP19A1, EGFR, ESR2, FOS, and IGF1—in breast cancer as well as in endometriosis. These genes are environmentally and estrogen responsive, altered in human breast and uterine tumors and endometriosis lesions, and part of Mitogen Activated Protein Kinase (MAPK signaling pathways in cancer. Our findings suggest that breast cancer and endometriosis share some common environmental and molecular risk factors.

  1. Integrated Bioinformatics, Environmental Epidemiologic and Genomic Approaches to Identify Environmental and Molecular Links between Endometriosis and Breast Cancer

    Science.gov (United States)

    Roy, Deodutta; Morgan, Marisa; Yoo, Changwon; Deoraj, Alok; Roy, Sandhya; Yadav, Vijay Kumar; Garoub, Mohannad; Assaggaf, Hamza; Doke, Mayur

    2015-01-01

    We present a combined environmental epidemiologic, genomic, and bioinformatics approach to identify: exposure of environmental chemicals with estrogenic activity; epidemiologic association between endocrine disrupting chemical (EDC) and health effects, such as, breast cancer or endometriosis; and gene-EDC interactions and disease associations. Human exposure measurement and modeling confirmed estrogenic activity of three selected class of environmental chemicals, polychlorinated biphenyls (PCBs), bisphenols (BPs), and phthalates. Meta-analysis showed that PCBs exposure, not Bisphenol A (BPA) and phthalates, increased the summary odds ratio for breast cancer and endometriosis. Bioinformatics analysis of gene-EDC interactions and disease associations identified several hundred genes that were altered by exposure to PCBs, phthalate or BPA. EDCs-modified genes in breast neoplasms and endometriosis are part of steroid hormone signaling and inflammation pathways. All three EDCs–PCB 153, phthalates, and BPA influenced five common genes—CYP19A1, EGFR, ESR2, FOS, and IGF1—in breast cancer as well as in endometriosis. These genes are environmentally and estrogen responsive, altered in human breast and uterine tumors and endometriosis lesions, and part of Mitogen Activated Protein Kinase (MAPK) signaling pathways in cancer. Our findings suggest that breast cancer and endometriosis share some common environmental and molecular risk factors. PMID:26512648

  2. Comparative genomic analyses identify common molecular pathways modulated upon exposure to low doses of arsenic and cadmium

    Directory of Open Access Journals (Sweden)

    Fry Rebecca C

    2011-04-01

    Full Text Available Abstract Background Exposure to the toxic metals arsenic and cadmium is associated with detrimental health effects including cancers of various organs. While arsenic and cadmium are well known to cause adverse health effects at high doses, the molecular impact resulting from exposure to environmentally relevant doses of these metals remains largely unexplored. Results In this study, we examined the effects of in vitro exposure to either arsenic or cadmium in human TK6 lymphoblastoid cells using genomics and systems level pathway mapping approaches. A total of 167 genes with differential expression were identified following exposure to either metal with surprisingly no overlap between the two. Real-time PCR was used to confirm target gene expression changes. The gene sets were overlaid onto protein-protein interaction maps to identify metal-induced transcriptional networks. Interestingly, both metal-induced networks were significantly enriched for proteins involved in common biological processes such as tumorigenesis, inflammation, and cell signaling. These findings were further supported by gene set enrichment analysis. Conclusions This study is the first to compare the transcriptional responses induced by low dose exposure to cadmium and arsenic in human lymphoblastoid cells. These results highlight that even at low levels of exposure both metals can dramatically influence the expression of important cellular pathways.

  3. Advanced computational biology methods identify molecular switches for malignancy in an EGF mouse model of liver cancer.

    Directory of Open Access Journals (Sweden)

    Philip Stegmaier

    Full Text Available The molecular causes by which the epidermal growth factor receptor tyrosine kinase induces malignant transformation are largely unknown. To better understand EGFs' transforming capacity whole genome scans were applied to a transgenic mouse model of liver cancer and subjected to advanced methods of computational analysis to construct de novo gene regulatory networks based on a combination of sequence analysis and entrained graph-topological algorithms. Here we identified transcription factors, processes, key nodes and molecules to connect as yet unknown interacting partners at the level of protein-DNA interaction. Many of those could be confirmed by electromobility band shift assay at recognition sites of gene specific promoters and by western blotting of nuclear proteins. A novel cellular regulatory circuitry could therefore be proposed that connects cell cycle regulated genes with components of the EGF signaling pathway. Promoter analysis of differentially expressed genes suggested the majority of regulated transcription factors to display specificity to either the pre-tumor or the tumor state. Subsequent search for signal transduction key nodes upstream of the identified transcription factors and their targets suggested the insulin-like growth factor pathway to render the tumor cells independent of EGF receptor activity. Notably, expression of IGF2 in addition to many components of this pathway was highly upregulated in tumors. Together, we propose a switch in autocrine signaling to foster tumor growth that was initially triggered by EGF and demonstrate the knowledge gain form promoter analysis combined with upstream key node identification.

  4. Determination of resistance to Fusarium oxysporum f. sp. lycopersici via molecular markers in tomato lines

    OpenAIRE

    PINAR, Hasan; ATA, Atilla; Keleş, Davut; Mutlu,Nedim; DENLİ, Nihal; ÜNLÜ, Mustafa

    2013-01-01

    Fusarium oxysporum f. sp. lycopersici (FOL) is common in tomato production areas where intensive production causes huge losses. Other plant species as well as biological and chemical control is insufficient to fight with the disease. The most effective solution to this problem is the use of resistant varieties. Fusarium oxysporum f. sp. lycopersici resistance has been transferred to most of the commercial varieties via classical and molecular marker-assisted selection (MAS). The use of molecu...

  5. Theory and Modeling of the Zeeman and Paschen-Back effects in Molecular Lines

    OpenAIRE

    Ramos, A. Asensio; Bueno, J. Trujillo

    2005-01-01

    This paper describes a very general approach to the calculation of the Zeeman splitting effect produced by an external magnetic field on the rotational levels of diatomic molecules. The method is valid for arbitrary values of the total electronic spin and of the magnetic field strength -that is, it holds for molecular electronic states of any multiplicity and for both the Zeeman and incomplete Paschen-Back regimes. It is based on an efficient numerical diagonalization of the effective Zeeman ...

  6. Altered Expression of High Molecular Weight Heat Shock Proteins after OCT4B1 Suppression in Human Tumor Cell Lines

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Mirzaei

    2016-02-01

    Full Text Available Objective: OCT4B1, a novel variant of OCT4, is expressed in cancer cell lines and tissues. Based on our previous reports, OCT4B1 appears to have a crucial role in regulating apoptosis as well as stress response [heat shock proteins (HSPs] pathways. The aim of the present study was to determine the effects of OCT4B1 silencing on the expression of high molecular weight HSPs in three different human tumor cell lines. Materials and Methods: In this experimental study, OCT4B1 expression was suppressed in AGS (gastric adenocarcinoma, 5637 (bladder tumor and U-87MG (brain tumor cell lines using RNAi strategy. Real-time polymerase chain reaction (PCR array was employed for expression level analysis and the fold changes were calculated using RT2 Profiler PCR array data analysis software version 3.5. Results: Our data revealed up-regulation of HSPD1 (from HSP60 family as well as HSPA14, HSPA1L, HSPA4, HSPA5 and HSPA8 (from HSP70 family following OCT4B1 knock-down in all three cell lines. In contrast, the expression of HSP90AA1 and HSP- 90AB1 (from HSP90 family as well as HSPA1B and HSPA6 (from HSP70 family was down-regulated under similar conditions. Other stress-related genes showed varying expression pattern in the examined tumor cell lines. Conclusion: Our data suggest a direct or indirect correlation between the expression of OCT4B1 and HSP90 gene family. However, OCT4B1 expression was not strongly correlated with the expression of HSP70 and HSP60 gene families.

  7. Phylogenetic analysis and molecular signatures defining a monophyletic clade of heterocystous cyanobacteria and identifying its closest relatives.

    Science.gov (United States)

    Howard-Azzeh, Mohammad; Shamseer, Larissa; Schellhorn, Herb E; Gupta, Radhey S

    2014-11-01

    Detailed phylogenetic and comparative genomic analyses are reported on 140 genome sequenced cyanobacteria with the main focus on the heterocyst-differentiating cyanobacteria. In a phylogenetic tree for cyanobacteria based upon concatenated sequences for 32 conserved proteins, the available cyanobacteria formed 8-9 strongly supported clades at the highest level, which may correspond to the higher taxonomic clades of this phylum. One of these clades contained all heterocystous cyanobacteria; within this clade, the members exhibiting either true (Nostocales) or false (Stigonematales) branching of filaments were intermixed indicating that the division of the heterocysts-forming cyanobacteria into these two groups is not supported by phylogenetic considerations. However, in both the protein tree as well as in the 16S rRNA gene tree, the akinete-forming heterocystous cyanobacteria formed a distinct clade. Within this clade, the members which differentiate into hormogonia or those which lack this ability were also separated into distinct groups. A novel molecular signature identified in this work that is uniquely shared by the akinete-forming heterocystous cyanobacteria provides further evidence that the members of this group are specifically related and they shared a common ancestor exclusive of the other cyanobacteria. Detailed comparative analyses on protein sequences from the genomes of heterocystous cyanobacteria reported here have also identified eight conserved signature indels (CSIs) in proteins involved in a broad range of functions, and three conserved signature proteins, that are either uniquely or mainly found in all heterocysts-forming cyanobacteria, but generally not found in other cyanobacteria. These molecular markers provide novel means for the identification of heterocystous cyanobacteria, and they provide evidence of their monophyletic origin. Additionally, this work has also identified seven CSIs in other proteins which in addition to the heterocystous

  8. An ALMA Early Science survey of molecular absorption lines toward PKS1830-211 -- Analysis of the absorption profiles

    CERN Document Server

    Muller, S; Guelin, M; Gerin, M; Aalto, S; Beelen, A; Black, J H; Curran, S J; Darling, J; Dinh-V-Trung,; Garcia-Burillo, S; Henkel, C; Horellou, C; Martin, S; Marti-Vidal, I; Menten, K M; Murphy, M T; Ott, J; Wiklind, T; Zwaan, M A

    2014-01-01

    We present the first results of an ALMA spectral survey of strong absorption lines for common interstellar species in the z=0.89 molecular absorber toward the lensed blazar PKS1830-211. The dataset brings essential information on the structure and composition of the absorbing gas in the foreground galaxy. In particular, we find absorption over large velocity intervals (gtrsim 100 km/s) toward both lensed images of the blazar. This suggests either that the galaxy inclination is intermediate and that we sample velocity gradients or streaming motions in the disk plane, that the molecular gas has a large vertical distribution or extraplanar components, or that the absorber is not a simple spiral galaxy but might be a merger system. The number of detected species is now reaching a total of 42 different species plus 14 different rare isotopologues toward the SW image, and 14 species toward the NE line-of-sight. The abundances of CH, H2O, HCO+, HCN, and NH3 relative to H2 are found to be comparable to those in the G...

  9. Genetic Analysis and Molecular Mapping of a Stripe Rust Resistance Gene YrH9014 in Wheat Line H9014-14-4-6-1

    Institute of Scientific and Technical Information of China (English)

    MA Dong-fang; HOU Lu; TANG Ming-shuang; WANG Hai-ge; LI Qiang; JING Jin-xue

    2013-01-01

    Stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is one of the most widespread and destructive wheat diseases in many wheat-growing regions of the world. The winter wheat translocation line H9014-14-4-6-1 has all stage resistance. To identify stripe rust resistance genes, the segregating populations were developed from the cross between H9014-14-4-6-1 and Mingxian 169 (a wheat cultivar susceptible to all Pst races identified in China). The seedlings of the parents and F1 plants, F2, F3 and BC1 generations were tested with Pst races under controlled greenhouse conditions. Two genes for resistance to stripe rust were identified, one dominant gene conferred resistance to SUN11-4, temporarily designated YrH9014 and the other recessive gene conferred resistance to CYR33. The bulked segregant analysis and simple sequence repeat (SSR) markers were used to identify polymorphic markers associated with YrH9014. Seven polymorphic SSR markers were used to genotype the F2 population inoculated with SUN11-4. A linkage map was constructed according to the genotypes of seven SSR markers and resistance gene. The molecular map spanned 24.3 cM, and the genetic distance of the two closest markers Xbarc13 and Xbarc55 to gene locus was 1.4 and 3.6 cM, respectively. Based on the position of SSR marker, the resistance gene YrH9014 was located on chromosome arm 2BS. Amplification of a set of nulli-tetrasomic Chinese Spring lines with SSR marker Xbarc13 indicated that YrH9014 was located on chromosome 2B. Based on chromosomal location, the reaction patterns and pedigree analysis, YrH9014 should be a novel resistance gene to stripe rust. This new gene and flanking markers got from this study should be useful for marker-assisted selection (MAS) in breeding programs for stripe rust.

  10. Systems Genetics Reveals the Functional Context of PCOS Loci and Identifies Genetic and Molecular Mechanisms of Disease Heterogeneity.

    Directory of Open Access Journals (Sweden)

    Michelle R Jones

    2015-08-01

    Full Text Available Genome wide association studies (GWAS have revealed 11 independent risk loci for polycystic ovary syndrome (PCOS, a common disorder in young women characterized by androgen excess and oligomenorrhea. To put these risk loci and the single nucleotide polymorphisms (SNPs therein into functional context, we measured DNA methylation and gene expression in subcutaneous adipose tissue biopsies to identify PCOS-specific alterations. Two genes from the LHCGR region, STON1-GTF2A1L and LHCGR, were overexpressed in PCOS. In analysis stratified by obesity, LHCGR was overexpressed only in non-obese PCOS women. Although not differentially expressed in the entire PCOS group, INSR was underexpressed in obese PCOS subjects only. Alterations in gene expression in the LHCGR, RAB5B and INSR regions suggest that SNPs in these loci may be functional and could affect gene expression directly or indirectly via epigenetic alterations. We identified reduced methylation in the LHCGR locus and increased methylation in the INSR locus, changes that are concordant with the altered gene expression profiles. Complex patterns of meQTL and eQTL were identified in these loci, suggesting that local genetic variation plays an important role in gene regulation. We propose that non-obese PCOS women possess significant alterations in LH receptor expression, which drives excess androgen secretion from the ovary. Alternatively, obese women with PCOS possess alterations in insulin receptor expression, with underexpression in metabolic tissues and overexpression in the ovary, resulting in peripheral insulin resistance and excess ovarian androgen production. These studies provide a genetic and molecular basis for the reported clinical heterogeneity of PCOS.

  11. Systems Genetics Reveals the Functional Context of PCOS Loci and Identifies Genetic and Molecular Mechanisms of Disease Heterogeneity.

    Science.gov (United States)

    Jones, Michelle R; Brower, Meredith A; Xu, Ning; Cui, Jinrui; Mengesha, Emebet; Chen, Yii-Der I; Taylor, Kent D; Azziz, Ricardo; Goodarzi, Mark O

    2015-08-01

    Genome wide association studies (GWAS) have revealed 11 independent risk loci for polycystic ovary syndrome (PCOS), a common disorder in young women characterized by androgen excess and oligomenorrhea. To put these risk loci and the single nucleotide polymorphisms (SNPs) therein into functional context, we measured DNA methylation and gene expression in subcutaneous adipose tissue biopsies to identify PCOS-specific alterations. Two genes from the LHCGR region, STON1-GTF2A1L and LHCGR, were overexpressed in PCOS. In analysis stratified by obesity, LHCGR was overexpressed only in non-obese PCOS women. Although not differentially expressed in the entire PCOS group, INSR was underexpressed in obese PCOS subjects only. Alterations in gene expression in the LHCGR, RAB5B and INSR regions suggest that SNPs in these loci may be functional and could affect gene expression directly or indirectly via epigenetic alterations. We identified reduced methylation in the LHCGR locus and increased methylation in the INSR locus, changes that are concordant with the altered gene expression profiles. Complex patterns of meQTL and eQTL were identified in these loci, suggesting that local genetic variation plays an important role in gene regulation. We propose that non-obese PCOS women possess significant alterations in LH receptor expression, which drives excess androgen secretion from the ovary. Alternatively, obese women with PCOS possess alterations in insulin receptor expression, with underexpression in metabolic tissues and overexpression in the ovary, resulting in peripheral insulin resistance and excess ovarian androgen production. These studies provide a genetic and molecular basis for the reported clinical heterogeneity of PCOS.

  12. Can inbound and domestic medical tourism improve your bottom line? Identifying the potential of a U.S. tourism market.

    Science.gov (United States)

    Fottler, Myron D; Malvey, Donna; Asi, Yara; Kirchner, Sarah; Warren, Natalia A

    2014-01-01

    In large part due to current economic conditions and the political uncertainties of healthcare reform legislation, hospitals need to identify new sources of revenue. Two potentially untapped sources are inbound (international) and domestic (within the United States) medical tourists. This case study uses data from a large, urban healthcare system in the southeastern United States to quantify its potential market opportunities for medical tourism. The data were mined from electronic health records, and descriptive frequency analysis was used to provide a preliminary market assessment. This approach permits healthcare systems to move beyond anecdotal information and assess the relative market potential of their particular geographic area and the diagnostic services they offer for attracting inbound and domestic medical tourists. Implications for healthcare executives and guidance on how they can focus marketing efforts are discussed.

  13. Study of molecular mechanisms of pro-apoptotic activity of NCX 4040, a novel nitric oxide-releasing aspirin, in colon cancer cell lines

    Directory of Open Access Journals (Sweden)

    Vannini Ivan

    2007-10-01

    Full Text Available Abstract Background Despite numerous studies aimed at verifying the antitumor activity of nitric oxide-releasing nonsteroidal antiflammatory drugs (NO-NSAIDs, little is known about the molecular targets responsible for their antineoplastic properties. In the present study, we investigated the mechanisms underlying the cytotoxicity of NCX 4040, a novel NO-aspirin with promising antineoplastic action, in in vitro human colon cancer models. Methods The effect on tumor growth was evaluated in four human colon cancer cell lines (LoVo, LRWZ, WiDr and LoVo Dx by sulforhodamine B assay, oxidative stress by immunohistochemistry, apoptosis by laddering assay, mitochondrial membrane potential (ΔΨm by flow cytometry, and apoptosis- and chemoresistance-related markers by western-blot and real-time method, respectively. Prostaglandin E2 levels were determined by ELISA. Results NCX 4040 produced a higher cytotoxic effect in all the cell lines than that produced by other NO donors tested. In particular, in LoVo and LRWZ cells, NCX 4040 induced a cytocidal effect and apoptosis through p53 and NAG-1 expression, an early ΔΨm collapse, and a sequential release of cytoplasmatic cytochrome c and caspase -9 and -3 active forms. 8-hydroxyguanine lesions, indicative of oxidative stress, were also observed. Conversely, in WiDr line, the drug caused a cytocidal effect, albeit not through apoptosis, and a concomitant increase in COX-2 activity. In LoVo Dx line, characterized by high levels drug resistance and DNA repair-related markers, only a cytostatic effect was observed, again in concomitance with the increase in COX-2 enzyme activity. Conclusion This study highlights the multiplicity of mechanisms involved in sensitivity or resistance to NCX 4040 and could provide useful indications for tailored therapy by identifying potentially drug-responsive tumors.

  14. Infrared Line Emission from Molecular Gas Heated by X-Rays and Energetic Electrons

    Science.gov (United States)

    Maloney, Philip R.

    1997-01-01

    "I propose to carry out a detailed study using infrared observations (and in some cases, optical and ultraviolet observations) of dense interstellar gas exposed to intense fluxes of X-rays and/or energetic electrons. This is undoubtedly the dominant source of line emission for clouds exposed to X-rays from active galactic nuclei, supernova shocks, or embedded X-ray sources (e.g., X-ray binaries), or to high-temperature or relativistic electrons in galaxy clusters, near powerful radio sources, or supernova remnants. Detailed physical and chemical models of such clouds will be used to analyze infrared observations of the Great Annihilator X-ray source in the Galactic Center, cD galaxies in massive cooling flows, and the nuclei of Seyfert galaxies which will be obtained with the Infrared Space Observatory (ISO), UV and optical observations of the Crab Nebula obtained with the Hubble Space Telescope, and ground-based near-infrared observations of Seyfert nuclei. Results from this work will also be of great relevance to observations obtained with the Submillimeter Wave Astronomical Satellite (SWAS). In the first year of funding of this proposal, my chief collaborators (D.J. Hollenbach and A.G.G.M. Tielens, both of NASA Ames Research Center) and I concentrated on completing our models of the physical conditions in, and the resulting line emission from, dense gas irradiated by X-rays. As noted in the original proposal, some important physical processes were not yet thoroughly incorporated into our models at the time of submission. We completed our modeling of the physical conditions and line emission for essentially the entire range of parameter space (five orders of magnitude in X-ray flux to gas density ratio) occupied by typical dense interstellar clouds in which the gas is mostly neutral and X-rays are important for the ionization, chemistry, and thermal balance.

  15. Molecular Line Lists for Scandium and Titanium Hydride Using the DUO Program

    Science.gov (United States)

    Lodi, Lorenzo; Yurchenko, Sergei N.; Tennyson, Jonathan

    2015-06-01

    Transition-metal-containing (TMC) molecules often have very complex electronic spectra because of their large number of low-lying, interacting electronic states, of the large multi-reference character of the electronic states and of the large magnitude of spin-orbit and relativistic effects. As a result, fully ab initio calculations of line positions and intensities of TMC molecules have an accuracy which is considerably worse than the one usually achievable for molecules made up by main-group atoms only. In this presentation we report on new theoretical line lists for scandium hydride ScH and titanium hydride TiH. Scandium and titanium are the lightest transition metal atoms and by virtue of their small number of valence electrons are amenable to high-level electronic-structure treatments and serve as ideal benchmark systems. We report for both systems energy curves, dipole curves and various coupling curves (including spin-orbit) characterising their electronic spectra up to about 20 000 cm-1. Curves were obtained using Internally-Contracted Multi Reference Configuration Interaction (IC-MRCI) as implemented in the quantum chemistry package MOLPRO. The curves where used for the solution of the coupled-surface ro-vibronic problem using the in-house program DUO. DUO is a newly-developed, general program for the spectroscopy of diatomic molecules and its main functionality will be described. The resulting line lists for ScH and TiH are made available as part of the Exomol project. L. Lodi, S. N. Yurchenko and J. Tennyson, Mol. Phys. (Handy special issue) in press. S. N. Yurchenko, L. Lodi, J. Tennyson and A. V. Stolyarov, Computer Phys. Comms., to be submitted.

  16. Cytogenetic and Molecular Characterization of B-Genome Introgression Lines of Brassica napus L.

    Science.gov (United States)

    Dhaliwal, Inderpreet; Mason, Annaliese S.; Banga, Shashi; Bharti, Sakshi; Kaur, Beerpal; Gurung, Allison Mary; Salisbury, Phillip Anthony; Batley, Jacqueline; Banga, Surinder Singh

    2016-01-01

    Brassica napus introgression lines (ILs), having B-genome segments from B. carinata, were assessed genetically for extent of introgression and phenotypically for siliqua shatter resistance. Introgression lines had 7–9% higher DNA content, were meiotically stable, and had almost normal pollen fertility/seed set. Segment introgressions were confirmed by fluorescent genomic in situ hybridization (fl-GISH), SSR analyses, and SNP studies. Genotyping with 48 B-genome specific SSRs detected substitutions from B3, B4, B6, and B7 chromosomes on 39 of the 69 ILs whereas SNP genotyping detected a total of 23 B-segments (≥3 Mb) from B4, B6, and B7 introgressed into 10 of the 19 (C1, C2, C3, C5, C6, C8, C9, A3, A9, A10) chromosomes in 17 ILs. The size of substitutions varied from 3.0 Mb on chromosome A9 (IL59) to 42.44 Mb on chromosome C2 (IL54), ranging from 7 to 83% of the recipient chromosome. Average siliqua strength in ILs was observed to be higher than that of B. napus parents (2.2–6.0 vs. 1.9–4.0 mJ) while siliqua strength in some of the lines was almost equal to that of the donor parent B. carinata (6.0 vs.7.2 mJ). These ILs, with large chunks of substituted B-genome, can prove to be a useful prebreeding resource for germplasm enhancement in B. napus, especially for siliqua shatter resistance. PMID:27821632

  17. Molecular reconstruction of extinct LINE-1 elements and their interaction with nonautonomous elements.

    Science.gov (United States)

    Wagstaff, Bradley J; Kroutter, Emily N; Derbes, Rebecca S; Belancio, Victoria P; Roy-Engel, Astrid M

    2013-01-01

    Non-long terminal repeat retroelements continue to impact the human genome through cis-activity of long interspersed element-1 (LINE-1 or L1) and trans-mobilization of Alu. Current activity is dominated by modern subfamilies of these elements, leaving behind an evolutionary graveyard of extinct Alu and L1 subfamilies. Because Alu is a nonautonomous element that relies on L1 to retrotranspose, there is the possibility that competition between these elements has driven selection and antagonistic coevolution between Alu and L1. Through analysis of synonymous versus nonsynonymous codon evolution across L1 subfamilies, we find that the C-terminal ORF2 cys domain experienced a dramatic increase in amino acid substitution rate in the transition from L1PA5 to L1PA4 subfamilies. This observation coincides with the previously reported rapid evolution of ORF1 during the same transition period. Ancestral Alu sequences have been previously reconstructed, as their short size and ubiquity have made it relatively easy to retrieve consensus sequences from the human genome. In contrast, creating constructs of extinct L1 copies is a more laborious task. Here, we report our efforts to recreate and evaluate the retrotransposition capabilities of two ancestral L1 elements, L1PA4 and L1PA8 that were active ~18 and ~40 Ma, respectively. Relative to the modern L1PA1 subfamily, we find that both elements are similarly active in a cell culture retrotransposition assay in HeLa, and both are able to efficiently trans-mobilize Alu elements from several subfamilies. Although we observe some variation in Alu subfamily retrotransposition efficiency, any coevolution that may have occurred between LINEs and SINEs is not evident from these data. Population dynamics and stochastic variation in the number of active source elements likely play an important role in individual LINE or SINE subfamily amplification. If coevolution also contributes to changing retrotransposition rates and the progression of

  18. On-chip multi spectral frequency standard replication by stabilizing a microring resonator to a molecular line

    Science.gov (United States)

    Zektzer, Roy; Stern, Liron; Mazurski, Noa; Levy, Uriel

    2016-07-01

    Stabilized laser lines are highly desired for myriad of applications ranging from precise measurements to optical communications. While stabilization can be obtained by using molecular or atomic absorption references, these are limited to specific frequencies. On the other hand, resonators can be used as wide band frequency references. Unfortunately, such resonators are unstable and inaccurate. Here, we propose and experimentally demonstrate a chip-scale multispectral frequency standard replication operating in the spectral range of the near IR. This is obtained by frequency locking a microring resonator (MRR) to an acetylene absorption line. The MRR consists of a Si3N4 waveguides with microheater on top of it. The thermo-optic effect is utilized to lock one of the MRR resonances to an acetylene line. This locked MRR is then used to stabilize other laser sources at 980 nm and 1550 nm wavelength. By beating the stabilized laser to another stabilized laser, we obtained frequency instability floor of 4 ×10-9 at around 100 s in terms of Allan deviation. Such stable and accurate chip scale sources are expected to serve as important building block in diverse fields such as communication and metrology.

  19. 3D simulations of M star atmosphere velocities and their influence on molecular FeH lines

    CERN Document Server

    Wende, S; Ludwig, H -G

    2009-01-01

    We present an investigation of the velocity fields in early to late M-type star hydrodynamic models, and we simulate their influence on FeH molecular line shapes. The M star model parameters range between log g of 3.0 - 5.0 and Teff of 2500 K and 4000 K. Our aim is to characterize the Teff- and log g -dependence of the velocity fields and express them in terms of micro- and macro-turbulent velocities in the one dimensional sense. We present also a direct comparison between 3D hydrodynamical velocity fields and 1D turbulent velocities. The velocity fields strongly affect the line shapes of FeH, and it is our goal to give a rough estimate for the log g and Teff parameter range in which 3D spectral synthesis is necessary and where 1D synthesis suffices. In order to calculate M-star structure models we employ the 3D radiative-hydrodynamics (RHD) code CO5BOLD. The spectral synthesis on these models is performed with the line synthesis code LINFOR3D. We describe the 3D velocity fields in terms of a Gaussian standar...

  20. Molecular line intensities as measures of cloud masses - I. Sensitivity of CO emissions to physical parameter variations

    CERN Document Server

    Bell, T A; Viti, S; Williams, D A

    2006-01-01

    A reliable estimate of the molecular gas content in galaxies plays a crucial role in determining their dynamical and star-forming properties. However, H2, the dominant molecular species, is difficult to observe directly, particularly in the regions where most molecular gas is thought to reside. Its mass is therefore commonly inferred by assuming a direct proportionality with the integrated intensity of the CO(J=1-0) emission line, using a CO-to-H2 conversion factor, X. Although a canonical value for X is used extensively in such estimates, there is increasing evidence, both theoretical and observational, that the conversion factor may vary by over an order of magnitude under conditions different to those of the local neighbourhood. In an effort to understand the influence of changing environmental conditions on the conversion factor, we derive theoretical estimates of X for a wide range of physical parameters using a photon-dominated region (PDR) time-dependent chemical model, benchmarking key results against...

  1. Molecular cytogenetic identification of a novel dwarf wheat line with introgressed Thinopyrum ponticum chromatin

    Indian Academy of Sciences (India)

    Guiling Chen; Q I Zheng; Yinguang Bao; Shubing Liu; Honggang Wang; Xingfeng Li

    2012-03-01

    Novel dwarfing germplasms and dwarfing genes are valuable for the wheat breeding. A novel semi-dwarf line, 31505-1, with reduced height compared with its common wheat parent, was derived from a cross between common wheat and Thinopyrum ponticum. Cytological studies demonstrated that 31505-1 contained 42 chromosomes and formed 21 bivalents at meiotic metaphase I. Genomic in situ hybridization (GISH) analysis showed that 31505-1 had no large Th. ponticum chromosome fragments. Fluorescence in situ hybridization (FISH) results revealed the absence of a pAs1 hybridization band on 2DL chromosome of 31505-1. Two SSR markers (Xwmc41 and Xcfd168) and two STS markers (Xmag4059 and Xmag3596), which were located on 2D chromosome, amplified unique bands of Th. Ponticum in 31505-1. These revealed presence of an introgressed Th. ponticum segment in 2DL chromosome of dwarf line 31505-1, although the alien segment could not be detected by GISH.

  2. Structure and stability in TMC-1: analysis of NH$_3$ molecular line and Herschel continuum data

    CERN Document Server

    Fehér, O; Ward-Thompson, D; Kirk, J; Kraus, A; Pelkonen, V -M; Pintér, S; Zahorecz, S

    2016-01-01

    We observed high S/N, high velocity resolution NH$_3$(1,1) and (2,2) emission on an extended map in TMC-1, a filamentary cloud in a nearby quiescent star forming area. By fitting multiple hyperfine-split line profiles to the NH$_3$(1,1) spectra we derived the velocity distribution of the line components and calculated gas parameters on several positions. Herschel SPIRE continuum observations were reduced and used to calculate the physical parameters of the Planck Galactic Cold Clumps in the region. The Herschel-based column density map of TMC-1 shows a main ridge with two local maxima and a separated peak to the south-west. H$_2$-column densities and dust temperatures are in the range of 0.5-3.3 $\\times$ 10$^{22}$ cm$^{-2}$ and 10.5-12 K, respectively. NH$_3$-column densities are 2.8-14.2 $\\times$ 10$^{14}$ cm$^{-2}$ and and H$_2$-volume densities are 0.4-2.8 $\\times$ 10$^4$ cm$^{-3}$. Kinetic temperatures are typically very low with a minimum of 9 K, and a maximum of 13.7 K was found at the Class I protostar...

  3. Identifying cell and molecular stress after radiation in a three-dimensional (3-D) model of oral mucositis

    Energy Technology Data Exchange (ETDEWEB)

    Lambros, Maria Polikandritou, E-mail: mlambros@westernu.edu [Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766 (United States); Parsa, Cyrus [Department of Clinical Sciences, College of Osteopathic Medicine, Western University of Health Sciences, Pomona, CA 91766 (United States); Mulamalla, HariChandana [Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766 (United States); Orlando, Robert [Department of Clinical Sciences, College of Osteopathic Medicine, Western University of Health Sciences, Pomona, CA 91766 (United States); Lau, Bernard [Center for Advancement of Drug Research and Evaluation (CADRE), Western University of Health Sciences, Pomona, CA 91766 (United States); Huang, Ying [Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766 (United States); Center for Advancement of Drug Research and Evaluation (CADRE), Western University of Health Sciences, Pomona, CA 91766 (United States); Pon, Doreen [Department of Pharmacy Practice and Administration, College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766 (United States); Chow, Moses [Department of Pharmacy Practice and Administration, College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766 (United States); Center for Advancement of Drug Research and Evaluation (CADRE), Western University of Health Sciences, Pomona, CA 91766 (United States)

    2011-02-04

    Research highlights: {yields} We irradiated a 3-D human oral cell culture of keratinocytes and fibroblasts with 12 and 2 Gy. {yields} 6 h after irradiation the histopathology and apoptosis of the 3-D culture were evaluated. Microarrays were used to assess the gene expression in the irradiated 3-D tissue. {yields} 12 Gy induced significant histopathologic changes and cellular apoptosis. {yields} 12 Gy significantly affected genes of the NF-kB pathway, inflammatory cytokines and DAMPs. -- Abstract: Mucositis is a debilitating adverse effect of chemotherapy and radiation treatment. It is important to develop a simple and reliable in vitro model, which can routinely be used to screen new drugs for prevention and treatment of mucositis. Furthermore, identifying cell and molecular stresses especially in the initiation phase of mucositis in this model will help towards this end. We evaluated a three-dimensional (3-D) human oral cell culture that consisted of oral keratinocytes and fibroblasts as a model of oral mucositis. The 3-D cell culture model was irradiated with 12 or 2 Gy. Six hours after the irradiation we evaluated microscopic sections of the cell culture for evidence of morphologic changes including apoptosis. We used microarrays to compare the expression of several genes from the irradiated tissue with identical genes from tissue that was not irradiated. We found that irradiation with 12 Gy induced significant histopathologic effects including cellular apoptosis. Irradiation significantly affected the expression of several genes of the NF-kB pathway and several inflammatory cytokines, such as IL-1B, 1L-8, NF-kB1, and FOS compared to tissue that was not irradiated. We identified significant upregulation of several genes that belong to damage-associated molecular patterns (DAMPs) such as HMB1, S100A13, SA10014, and SA10016 in the 3-D tissues that received 12 Gy but not in tissues that received 2 Gy. In conclusion, this model quantifies radiation damage and this

  4. Probing the feeding and feedback of AGN through molecular line maps

    CERN Document Server

    García-Burillo, S; Usero, A; Gracia-Carpio, J

    2006-01-01

    Current mm-interferometers can provide a complete view of the distribution and kinematics of molecular gas in the circumnuclear disks of nearby galaxies. High-resolution CO maps are paramount in order to track down the feeding of active nuclei and quantitatively address the issue of how and for how long nuclear activity can be sustained in galaxies. Going beyond CO mapping, the use of more specific molecular tracers of dense gas can probe the feedback influence of activity on the chemistry and energy balance/redistribution in the interstellar medium of nearby galaxies, a prerequisite to interpret how feedback may operate at higher redshift galaxies. In this context we present the latest results issued from the NUclei of GAlaxies (NUGA) project, a high-resolution (0.5''-1'') CO survey of low luminosity AGNs conducted with the IRAM interferometer. The efficiency of gravity torques as a mechanism to account for the feeding of low luminosity AGNs (LLAGNs) can be analyzed. We discuss an evolutionary scenario in wh...

  5. Molecular Line Observations of a Carbon-Chain-Rich Core L492

    CERN Document Server

    Hirota, T; Hirota, Tomoya; Yamamoto, Satoshi

    2006-01-01

    We report on molecular abundances and distributions in a starless dense core L492. We have found that the abundances of carbon-chain molecules such as CCS, C$_{3}$S, HC$_{3}$N, HC$_{5}$N, and HC$_{7}$N are comparable to those in chemically young dark cloud cores called "carbon-chain--producing regions", such as L1495B, L1521B, L1521E, and TMC-1. This is the first dark cloud core with extremely rich in carbon-chain-molecules that is found outside the Taurus region. In addition, the deuterium fractionation ratios of DNC/HNC and DCO$^{+}$/HCO$^{+}$ are also comparable to those in carbon-chain--producing regions, being significantly lower than those in the evolved prestellar cores such as L1498 and L1544. On the other hand, the abundances of NH$_{3}$ and N$_{2}$H$^{+}$ are systematically higher than those in carbon-chain--producing regions. Our mapping observations reveal that the central hole of molecular distributions, which were reported for CCS and C$^{34}$S in evolved prestellar cores is not significant in L...

  6. Molecular mapping of a stripe rust resistance gene in wheat line C51

    Indian Academy of Sciences (India)

    Jianmin Zheng; Zehong Yan; Li Zhao; Shizhao Li; Zengyan Zhang; Resewarne Garry; Wuyun Yang; Zongjun Pu

    2014-08-01

    Stripe rust, a major disease in areas where cool temperatures prevail, can strongly influence grain yield. To control this disease, breeders have incorporated seedling resistance genes from a variety of sources outside the primary wheat gene pool. The wheat line C51, introduced from the International Center for Agricultural Research in the Dry Areas (ICARDA), Syria, confers resistance to all races of Puccinia striiformis f. sp. tritici (PST) in China. To map the resistant gene(s) against stripe rust in wheat line C51, 212 F8 recombinant inbred lines (RILs) derived from the cross X440 × C51 were inoculated with Chinese PST race CYR33 (Chinese yellow rust, CYR) in the greenhouse. The result showed that C51 carried a single dominant gene for resistance (designated YrC51) to CYR33. Simple sequence repeat (SSR) and resistance gene-analogue polymorphism (RGAP) markers that were polymorphic between the parents were used for genotyping the 212 F8 RILs. YrC51 was closely linked to two SSR loci on chromosome 2BS with genetic distances of 5.1 cM (Xgwm429) and 7.2 cM (Xwmc770), and to three RGAP markers C51R1 (XLRR For / NLRR For), C51R2 (CLRR Rev / Cre3LR-F) and C51R3 (Pto kin4/ NLRRINV2) with genetic distances of 5.6, 1.6 and 9.2 cM, respectively. These RGAP-linked markers were then converted into STS markers.Among them, one STS marker, C51STS-4, was located at a genetic distance of 1.4 cM to YrC51 and was closely associated with resistance when validated in several populations derived from crosses between C51 and Sichuan cultivars. The results indicated that C51STS-4 can be used for marker assisted selection (MAS) and would facilitate the pyramiding of YrC51 with other genes for stripe rust resistance.

  7. An innovative strategy for the molecular diagnosis of Usher syndrome identifies causal biallelic mutations in 93% of European patients.

    Science.gov (United States)

    Bonnet, Crystel; Riahi, Zied; Chantot-Bastaraud, Sandra; Smagghe, Luce; Letexier, Mélanie; Marcaillou, Charles; Lefèvre, Gaëlle M; Hardelin, Jean-Pierre; El-Amraoui, Aziz; Singh-Estivalet, Amrit; Mohand-Saïd, Saddek; Kohl, Susanne; Kurtenbach, Anne; Sliesoraityte, Ieva; Zobor, Ditta; Gherbi, Souad; Testa, Francesco; Simonelli, Francesca; Banfi, Sandro; Fakin, Ana; Glavač, Damjan; Jarc-Vidmar, Martina; Zupan, Andrej; Battelino, Saba; Martorell Sampol, Loreto; Claveria, Maria Antonia; Catala Mora, Jaume; Dad, Shzeena; Møller, Lisbeth B; Rodriguez Jorge, Jesus; Hawlina, Marko; Auricchio, Alberto; Sahel, José-Alain; Marlin, Sandrine; Zrenner, Eberhart; Audo, Isabelle; Petit, Christine

    2016-12-01

    Usher syndrome (USH), the most prevalent cause of hereditary deafness-blindness, is an autosomal recessive and genetically heterogeneous disorder. Three clinical subtypes (USH1-3) are distinguishable based on the severity of the sensorineural hearing impairment, the presence or absence of vestibular dysfunction, and the age of onset of the retinitis pigmentosa. A total of 10 causal genes, 6 for USH1, 3 for USH2, and 1 for USH3, and an USH2 modifier gene, have been identified. A robust molecular diagnosis is required not only to improve genetic counseling, but also to advance gene therapy in USH patients. Here, we present an improved diagnostic strategy that is both cost- and time-effective. It relies on the sequential use of three different techniques to analyze selected genomic regions: targeted exome sequencing, comparative genome hybridization, and quantitative exon amplification. We screened a large cohort of 427 patients (139 USH1, 282 USH2, and six of undefined clinical subtype) from various European medical centers for mutations in all USH genes and the modifier gene. We identified a total of 421 different sequence variants predicted to be pathogenic, about half of which had not been previously reported. Remarkably, we detected large genomic rearrangements, most of which were novel and unique, in 9% of the patients. Thus, our strategy led to the identification of biallelic and monoallelic mutations in 92.7% and 5.8% of the USH patients, respectively. With an overall 98.5% mutation characterization rate, the diagnosis efficiency was substantially improved compared with previously reported methods.

  8. Ultracold molecular spectroscopy: toward the narrow-line cooling of molecules

    Science.gov (United States)

    Kobayashi, Jun; Ogino, Atsushi; Inouye, Shin

    2015-03-01

    A new spectroscopic method that utilizes microwave transition of ultracold molecules is demonstrated. The narrow spectral linewidth (approximately 100 Hz) was guaranteed by preparing molecules at low temperature, and a high signal-to-noise ratio was achieved by preparing a significant fraction of molecules in the target internal state. The repetition rate of the experiment was approximately 10 Hz, which was only limited by the time needed to load ultracold atoms into the magneto-optical trap. To demonstrate the performance, we investigated the hyperfine structures of the vibrational ground states of the {{X}1}{{Σ }+} and {{b}3}{{\\Pi }{{0+}}} states of KRb molecules. This technique not only allows us to pursue the narrow-line laser cooling of KRb molecules, but also provided us with essential information for realizing precision spectroscopies e.g., the search for the temporal variation of the electron-to-proton mass ratio.

  9. Cell and molecular biology of SAE, a cell line from the spiny dogfish shark, Squalus acanthias.

    Science.gov (United States)

    Parton, Angela; Forest, David; Kobayashi, Hiroshi; Dowell, Lori; Bayne, Christopher; Barnes, David

    2007-02-01

    Cartilaginous fish, primarily sharks, rays and skates (elasmobranchs), appeared 450 million years ago. They are the most primitive vertebrates, exhibiting jaws and teeth, adaptive immunity, a pressurized circulatory system, thymus, spleen, and a liver comparable to that of humans. The most used elasmobranch in biomedical research is the spiny dogfish shark, Squalus acanthias. Comparative genomic analysis of the dogfish shark, the little skate (Leucoraja erincea), and other elasmobranchs have yielded insights into conserved functional domains of genes associated with human liver function, multidrug resistance, cystic fibrosis, and other biomedically relevant processes. While genomic information from these animals is informative in an evolutionary framework, experimental verification of functions of genomic sequences depends heavily on cell culture approaches. We have derived the first multipassage, continuously proliferating cell line of a cartilaginous fish. The line was initiated from embryos of the spiny dogfish shark. The cells were maintained in a medium modified for fish species and supplemented with cell type-specific hormones, other proteins and sera, and plated on a collagen substrate. SAE cells have been cultured continuously for three years. These cells can be transfected by plasmids and have been cryopreserved. Expressed Sequence Tags generated from a normalized SAE cDNA library included a number of markers for cartilage and muscle, as well as proteins influencing tissue differentiation and development, suggesting that SAE cells may be of mesenchymal stem cell origin. Examination of SAE EST sequences also revealed a cartilaginous fish-specific repetitive sequence that may be evidence of an ancient mobile genetic element that most likely was introduced into the cartilaginous fish lineage after divergence from the lineage leading to teleosts.

  10. The molecular basis for carcinogenesis in metaplastic columnar-lined esophagus.

    Science.gov (United States)

    Souza, R F; Meltzer, S J

    1997-09-01

    A wide variety of biologic events and mechanisms appear to have roles in the development and progression of Barrett's esophagus-associated neoplastic lesions. Figure 5 is a schematic depiction of these events. This is known as an infernogram (named after Dante's Inferno) (S. Kern, unpublished presentations, 1996). Events at the bottom rings of the inferno are high-frequency mutations; nearer to the top of the inferno are the less common events. The next several years promise many further discoveries of not only high-frequency and low-frequency events, but also their application. Some of the molecular alterations already studied show promise as markers for early cancer detection or prognostication. Eventually, applications of these discoveries should yield new and more effective means of preventing and treating the deadly complications of this troublesome premalignant condition.

  11. Molecular Line Emission from Multifluid Shock Waves. I. Numerical Methods and Benchmark Tests

    CERN Document Server

    Ciolek, Glenn E

    2013-01-01

    We describe a numerical scheme for studying time-dependent, multifluid, magnetohydrodynamic shock waves in weakly ionized interstellar clouds and cores. Shocks are modeled as propagating perpendicular to the magnetic field and consist of a neutral molecular fluid plus a fluid of ions and electrons. The scheme is based on operator splitting, wherein time integration of the governing equations is split into separate parts. In one part independent homogeneous Riemann problems for the two fluids are solved using Godunov's method. In the other equations containing the source terms for transfer of mass, momentum, and energy between the fluids are integrated using standard numerical techniques. We show that, for the frequent case where the thermal pressures of the ions and electrons are << magnetic pressure, the Riemann problems for the neutral and ion-electron fluids have a similar mathematical structure which facilitates numerical coding. Implementation of the scheme is discussed and several benchmark tests ...

  12. Molecular evolution of hepatitis A virus in a human diploid cell line

    Institute of Scientific and Technical Information of China (English)

    Cai-Hua Tang; Jiang-Sen Mao; Shao-Ai Chai; Yong Chen; Fang-Cheng Zhuang

    2007-01-01

    AIM: To investigate the hotspots, direction, and the time course of evolution of hepatitis A virus in the process of consecutive cell culture passage in human KMB17 diploid cells.METHODS: Wild type hepatitis A virus H2w was serially propagated in KMB17 cells until passage 30, and the full-length genomes of H2w and its six chosen progenies were determined by directly sequencing RT-PCR products amplified from viral genomic RNA. Alignment comparison of sequences from H2w with its six progenies and phylogenetic analysis of the whole VP1 region from H2w, progenies of H2w, and other cell culture adapted hepatitis A virus were then carried out to obtain data on the molecular evolution of hepatitis A virus in the process of consecutive passage in KMB17 cells.RESULTS: Most of the mutations occurred by passage 5 and several hotspots related to adaptation of the virus during cell growth were observed. After that stage, few additional mutations occurred through the remaining duration of passage in KMB17 cells except for mutation in the virulence determinants, which occurred in the vicinity of passage 15. The phylogenetic analysis of the whole VP1 region suggested that the progenies of H2w evolved closely to other cell culture adapted hepatitis A virus, i.e. MBB, L-A-1, other than its progenitor H2w.CONCLUSION: Hepatitis A virus served as a useful model for studying molecular evolution of viruses in a given environment. The information obtained in this study may provide assistance in cultivating the next generation of a seed virus for live hepatitis A vaccine production.

  13. Molecular evaluation of soil organic matter characteristics in three agricultural soils by improved off-line thermochemolysis: the effect of hydrofluoric acid demineralisation treatment.

    Science.gov (United States)

    Spaccini, Riccardo; Song, XiangYun; Cozzolino, Vincenza; Piccolo, Alessandro

    2013-11-13

    The molecular composition of soil organic matter (SOM) in three agricultural fields under different managements, was evaluated by off-line thermochemolysis followed by gas chromatography mass spectrometry analysis (THM-GC-MS). While this technique enabled the characterization of SOM components in coarse textured soil, its efficiency in heavy textured soils was seriously affected by the interference of clay minerals, which catalyzed the formation of secondary artifacts in pyrolysates. Soil demineralization with hydrofluoric acid (HF) solutions effectively improved the reliable characterization of organic compounds in clayey soils by thermochemolysis, while did not alter significantly the results of coarse textured soil. A wide range of lignin monomers and lipids molecules, of plant and microbial origin, were identified in the pyrograms of HF treated soils, thereby revealing interesting molecular differences between SOM management practices. Our results indicated that clay removal provided by HF pretreatment enhanced the capacity of thermochemolysis to be a valuable and accurate technique to study the SOM dynamics also in heavy-textured and OC-depleted cultivated soils.

  14. Molecular conservation of estrogen-response associated with cell cycle regulation, hormonal carcinogenesis and cancer in zebrafish and human cancer cell lines

    Directory of Open Access Journals (Sweden)

    Govindarajan Kunde R

    2011-05-01

    Full Text Available Abstract Background The zebrafish is recognized as a versatile cancer and drug screening model. However, it is not known whether the estrogen-responsive genes and signaling pathways that are involved in estrogen-dependent carcinogenesis and human cancer are operating in zebrafish. In order to determine the potential of zebrafish model for estrogen-related cancer research, we investigated the molecular conservation of estrogen responses operating in both zebrafish and human cancer cell lines. Methods Microarray experiment was performed on zebrafish exposed to estrogen (17β-estradiol; a classified carcinogen and an anti-estrogen (ICI 182,780. Zebrafish estrogen-responsive genes sensitive to both estrogen and anti-estrogen were identified and validated using real-time PCR. Human homolog mapping and knowledge-based data mining were performed on zebrafish estrogen responsive genes followed by estrogen receptor binding site analysis and comparative transcriptome analysis with estrogen-responsive human cancer cell lines (MCF7, T47D and Ishikawa. Results Our transcriptome analysis captured multiple estrogen-responsive genes and signaling pathways that increased cell proliferation, promoted DNA damage and genome instability, and decreased tumor suppressing effects, suggesting a common mechanism for estrogen-induced carcinogenesis. Comparative analysis revealed a core set of conserved estrogen-responsive genes that demonstrate enrichment of estrogen receptor binding sites and cell cycle signaling pathways. Knowledge-based and network analysis led us to propose that the mechanism involving estrogen-activated estrogen receptor mediated down-regulation of human homolog HES1 followed by up-regulation cell cycle-related genes (human homologs E2F4, CDK2, CCNA, CCNB, CCNE, is highly conserved, and this mechanism may involve novel crosstalk with basal AHR. We also identified mitotic roles of polo-like kinase as a conserved signaling pathway with multiple entry

  15. Stability of arsenic peptides in plant extracts: off-line versus on-line parallel elemental and molecular mass spectrometric detection for liquid chromatographic separation.

    Science.gov (United States)

    Bluemlein, Katharina; Raab, Andrea; Feldmann, Jörg

    2009-01-01

    The instability of metal and metalloid complexes during analytical processes has always been an issue of an uncertainty regarding their speciation in plant extracts. Two different speciation protocols were compared regarding the analysis of arsenic phytochelatin (As(III)PC) complexes in fresh plant material. As the final step for separation/detection both methods used RP-HPLC simultaneously coupled to ICP-MS and ES-MS. However, one method was the often used off-line approach using two-dimensional separation, i.e. a pre-cleaning step using size-exclusion chromatography with subsequent fraction collection and freeze-drying prior to the analysis using RP-HPLC-ICP-MS and/or ES-MS. This approach revealed that less than 2% of the total arsenic was bound to peptides such as phytochelatins in the root extract of an arsenate exposed Thunbergia alata, whereas the direct on-line method showed that 83% of arsenic was bound to peptides, mainly as As(III)PC(3) and (GS)As(III)PC(2). Key analytical factors were identified which destabilise the As(III)PCs. The low pH of the mobile phase (0.1% formic acid) using RP-HPLC-ICP-MS/ES-MS stabilises the arsenic peptide complexes in the plant extract as well as the free peptide concentration, as shown by the kinetic disintegration study of the model compound As(III)(GS)(3) at pH 2.2 and 3.8. But only short half-lives of only a few hours were determined for the arsenic glutathione complex. Although As(III)PC(3) showed a ten times higher half-life (23 h) in a plant extract, the pre-cleaning step with subsequent fractionation in a mobile phase of pH 5.6 contributes to the destabilisation of the arsenic peptides in the off-line method. Furthermore, it was found that during a freeze-drying process more than 90% of an As(III)PC(3) complex and smaller free peptides such as PC(2) and PC(3) can be lost. Although the two-dimensional off-line method has been used successfully for other metal complexes, it is concluded here that the fractionation and

  16. Molecular line survey of Sagittarius B2(M) from 330 to 355 GHz and comparison with Sagittarius B2(N)

    Science.gov (United States)

    Sutton, E. C.; Jaminet, P. A.; Danchi, W. C.; Blake, Geoffrey A.

    1991-01-01

    A submillimeter survey of Sgr B2 is described in which sufficient spatial resolution permitted the observation of some of the source structure. The position Sgr B2(M) is examined in relation to the submillimeter emission of Sgr B2(N) and previous millimeter observational data of source (M) at a lower spatial resolution. Because the submillimeter observations are more sensitive to core emission, the molecules SO2 and CH3OH tend to dominate the spectrum. The core emission is found to be similar to that of the Orion molecular cloud, and the submillimeter and millimeter lines have high optical depths. The (N) source has a much higher column density than that of (M) except for SO and SO2, and (N) also appears to have a higher excitation which can indicate a core with a higher density.

  17. Molecular events induced in the HL 60 cell line following treatment with gamma-interferon.

    Science.gov (United States)

    Dubreuil, P; Courcoul, M; Mannoni, P

    1988-01-01

    Gamma-interferon (gamma IFN), like the phorbol ester TPA, is able to induce the differentiation of the HL 60 human promyelocytic cell line in the monocytic pathway. Morphological and serological data show a differential expression of cell surface markers upon treatment with these two inducers. It was reported that TPA treatment alters the expression of some protooncogenes, like c-myc and c-fos, involved in the induction of cell proliferation, and c-fos and c-fms (CSF.1 receptor), linked to monocytic differentiation. We have analyzed the variations in the levels of expression of these oncogenes upon gamma IFN treatment of HL 60 cells. c-myc expression was unchanged during the whole induction period. The early increase reported in c-fos expression was not observed; however, c-fos levels increased upon 24 hr of gamma IFN treatment. These results suggest either that TPA and gamma IFN act at different steps, or, alternatively, that different pathways exist in the monocytic differentiation.

  18. ExoMol molecular line lists - XIII: The spectrum of CaO

    CERN Document Server

    Yurchenko, Sergei N; Asari, Usama; Vasilios, Marcus; Hill, Christian; Tennyson, Jonathan

    2015-01-01

    An accurate line list for calcium oxide is presented covering transitions between all bound ro-vibronic levels from the five lowest electronic states \\X, \\Ap, \\A, \\astate, and \\bstate. The ro-vibronic energies and corresponding wavefunctionts were obtained by solving the fully coupled Schr\\"{o}dinger equation. \\textit{Ab initio} potential energy, spin-orbit, and electronic angular momentum curves were refined by fitting to the experimental frequencies and experimentally derived energies available in the literature. Using our refined model we could (i) reassign the vibronic states for a large portion of the experimentally derived energies [van Groenendael A., Tudorie M., Focsa C., Pinchemel B., Bernath P. F., 2005, J. Mol. Spectrosc., 234, 255], (ii) extended this list of energies to $J=79-118$ and (iii) suggest a new description of the resonances from the \\A--\\X\\ system. We used high level \\textit{ab initio} electric dipole moments reported previously [Khalil H., Brites V., Le Quere F., Leonard C., 2011, Chem...

  19. Line-Based Object Recognition using Hausdorff Distance: From Range Images to Molecular Secondary Structure

    Energy Technology Data Exchange (ETDEWEB)

    Guerra, C; Pascucci, V

    2004-12-13

    Object recognition algorithms are fundamental tools in automatic matching of geometric shapes within a background scene. Many approaches have been proposed in the past to solve the object recognition problem. Two of the key aspects that distinguish them in terms of their practical usability are: (i) the type of input model description and (ii) the comparison criteria used. In this paper we introduce a novel scheme for 3D object recognition based on line segment representation of the input shapes and comparison using the Hausdor distance. This choice of model representation provides the flexibility to apply the scheme in different application areas. We define several variants of the Hausdor distance to compare the models within the framework of well defined metric spaces. We present a matching algorithm that efficiently finds a pattern in a 3D scene. The algorithm approximates a minimization procedure of the Hausdor distance. The output error due to the approximation is guaranteed to be within a known constant bound. Practical results are presented for two classes of objects: (i) polyhedral shapes extracted from segmented range images and (ii) secondary structures of large molecules. In both cases the use of our approximate algorithm allows to match correctly the pattern in the background while achieving the efficiency necessary for practical use of the scheme. In particular the performance is improved substantially with minor degradation of the quality of the matching.

  20. Molecular line emission from a protoplanetary disk irradiated externally by a nearby massive star

    CERN Document Server

    Walsh, Catherine; Nomura, Hideko; 10.1088/2041-8205/766/2/L23

    2013-01-01

    Star formation often occurs within or nearby stellar clusters. Irradiation by nearby massive stars can photoevaporate protoplanetary disks around young stars (so-called proplyds) which raises questions regarding the ability of planet formation to take place in these environments. We investigate the two-dimensional physical and chemical structure of a protoplanetary disk surrounding a low-mass (T Tauri) star which is irradiated by a nearby massive O-type star to determine the survivability and observability of molecules in proplyds. Compared with an isolated star-disk system, the gas temperature ranges from a factor of a few (in the disk midplane) to around two orders of magnitude (in the disk surface) higher in the irradiated disk. Although the UV flux in the outer disk, in particular, is several orders of magnitude higher, the surface density of the disk is sufficient for effective shielding of the disk midplane so that the disk remains predominantly molecular in nature. We also find that non-volatile molecu...

  1. Galactic Edge Clouds I: Molecular Line Observations and Chemical Modelling of Edge Cloud 2

    CERN Document Server

    Ruffle, P M E; Roberts, H; Lubowich, D A; Henkel, C; Pasachoff, J M; Brammer, G

    2007-01-01

    Edge Cloud 2 (EC2) is a molecular cloud, about 35 pc in size, with one of the largest galactocentric distances known to exist in the Milky Way. We present observations of a peak CO emission region in the cloud and use these to determine its physical characteristics. We calculate a gas temperature of 20 K and a density of n(H2) ~ 10^4 cm^-3. Based on our CO maps, we estimate the mass of EC2 at around 10^4 M_sun and continuum observations suggest a dust-to-gas mass ratio as low as 0.001. Chemical models have been developed to reproduce the abundances in EC2 and they indicate that: heavy element abundances may be reduced by a factor of five relative to the solar neighbourhood (similar to dwarf irregular galaxies and damped Lyman alpha systems); very low extinction (Av < 4 mag) due to a very low dust-to-gas ratio; an enhanced cosmic ray ionisation rate; and a higher UV field compared to local interstellar values. The reduced abundances may be attributed to the low level of star formation in this region and are...

  2. Improving Blast Resistance of a Thermo-Sensitive Genic Male Sterile Rice Line GD-8S by Molecular Marker-Assisted Selection

    Directory of Open Access Journals (Sweden)

    Wu-ge LIU

    2008-09-01

    Full Text Available The broad-spectrum blast resistance gene Pi-1, from donor line BL122, was introduced into a thermo-sensitive genic male sterile rice line GD-8S, which possessed good grain quality but high susceptibility to rice blast, by using backcross breeding and molecular marker-assisted selection. Five elite improved male sterile lines, RGD8S-1, RGD8S-2, RGD8S-3, RGD8S-4 and RGD8S-5, were selected based on the results of molecular marker analysis, spikelet sterility, recovery rate of genetic background and agronomic traits. Thirty-three representative blast isolates collected from Guangdong Province, China were used to inoculate the improved lines and the original line GD-8S artificially. The resistance frequencies of the improved lines ranged from 76.47% to 100%, much higher than that of the original line GD-8S (9.09%. On the agronomic characters, there were no significant differences between the improved lines and GD-8S except for flag leaf length and panicle number per plant. The improved lines could be used for breeding hybrid rice with high blast resistance.

  3. Improving Blast Resistance of a Thermo-Sensitive Genic Male Sterile Rice Line GD-8S by Molecular Marker-Assisted Selection

    Institute of Scientific and Technical Information of China (English)

    LIU Wu-ge; LIU Yi-bai; JIN Su-juan; ZHU Xiao-yuan; WANG Feng; LI Jin-hua; LIU Zhen-rong; LIAO Yi-long; ZHU Man-shan; HUANG Hui-jun

    2008-01-01

    The broad-spectrum blast resistance gene Pi-1, from donor line BL122, was introduced into a thermo-sensitive genic male sterile rice line GD-8S, which possessed good grain quality but high susceptibility to rice blast, by using backcross breeding and molecular marker-assisted selection. Five elite improved male sterile lines, RGD8S-1, RGD8S-2, RGD8S-3, RGD8S-4 and RGD8S-5, were selected based on the results of molecular marker analysis, spikelet sterility, recovery rate of genetic background and agronomic traits. Thirty-three representative blast isolates collected from Guangdong Province,China were used to inoculate the improved lines and the original line GD-8S artificially. The resistance frequencies of the improved lines ranged from 76.47% to 100%, much higher than that of the original line GD-8S (9.09%). On the agronomic characters, there were no significant differences between the improved lines and GD-8S except for flag leaf length and panicle number per plant. The improved lines could be used for breeding hybrid rice with high blast resistance.

  4. Molecular Characterization of Atlas 66-Derived Wheat Near-Isogenic Lines Contrasting in Aluminum (Al) Tolerance

    Institute of Scientific and Technical Information of China (English)

    GUO Pei-guo; BAI Gui-hua; LI Rong-hua; Brett Carver; Michael Baum

    2007-01-01

    Aluminum (Al) toxicity is the major limiting factor for wheat growth in acidic soils. Genetic improvement of Al tolerance is one of the most cost-effective solutions to improve wheat productivity. The objective of this study was to characterize near isogenic lines (NILs) contrasting in Al tolerance derived from Atlas 66 in the backgrounds of Al-sensitive cultivars Chisholm and Century using amplified fragment length polymorphism (AFLP) and simple sequence repeat (SSR). A total of 200 AFLP and 88 SSR primer pairs were screened and 12 markers (11 AFLPs and one SSR) were associated with Altolerance in NILs of at least one recurrent parental background. Among them, nine were linked to Al tolerance in the Chisholm-derived NILs, seven were associated with Al-tolerance in the Century-derived NILs, and three AFLPs derived from the primer combinations of pAG/mGCAG, pCAG/mAGC and pGTG/mGCG, and one SSR, Xwmc331 on chromosome4D, associated with Al tolerance in NILs of both recurrent parental backgrounds. Those common markers across two backgrounds may be the major marker loci associated with Al-tolerance in Atlas 66 and could be useful for marker-assisted breeding to improve Al tolerance in wheat. In addition, evaluation of Al tolerance among different genotypes using hematoxylin stain and relative root growth revealed that Atlas 66 was more tolerant to Al stress than the NILs, therefore suggested that the Al-tolerant NILs might not carry all Al-tolerance loci from Atlas 66 and inheritance of Al tolerance in Atlas 66 is more likely multigenic.

  5. Biomolecule-loaded chitosan nanoparticles induce apoptosis and molecular changes in cancer cell line (SiHa).

    Science.gov (United States)

    Sujima Anbu, Anbu; Velmurugan, Palanivel; Lee, Jeong-Ho; Oh, Byung-Taek; Venkatachalam, Perumal

    2016-07-01

    The present study reports on the synthesis of chitosan nanoparticles (CNPs) using methanol extracts of Gymnema sylvestre (GS) leaves and Cinnamomum zeylanicum (CZ) bark. Biomolecule-loaded nanoparticles induced apoptosis in a human cervical cancer (SiHa) cell line, and experiments were carried out to elucidate the underlying molecular mechanisms. FT-IR and XRD showed possible functional groups of the biomolecules and the crystalline nature of CNPs, respectively. Transmission electron microscopy images revealed that synthesized GSCNPs and CZCNPs had a smooth spherical shape with average sizes of about 58-80 and 60-120nm, respectively. Dynamic light scattering studies indicated that both GSCNPs and CZCNs were structurally stable with homogenous and heterogeneous natures, respectively. Furthermore, synthesized GSCNPs and CZCNPs exhibited dose-dependent cytotoxicity against the SiHa cancer cell line, with inhibitory concentration (IC50) values of 102.17μg/ml, 87.75μg/ml, 132.74μg/ml and 90.35μg/ml for GS leaf extract, GSCNPs, CZBE and CZCNPs, respectively.

  6. Molecular Line Emission from Multifluid Shock Waves. I. Numerical Methods and Benchmark Tests

    Science.gov (United States)

    Ciolek, Glenn E.; Roberge, Wayne G.

    2013-05-01

    We describe a numerical scheme for studying time-dependent, multifluid, magnetohydrodynamic shock waves in weakly ionized interstellar clouds and cores. Shocks are modeled as propagating perpendicular to the magnetic field and consist of a neutral molecular fluid plus a fluid of ions and electrons. The scheme is based on operator splitting, wherein time integration of the governing equations is split into separate parts. In one part, independent homogeneous Riemann problems for the two fluids are solved using Godunov's method. In the other, equations containing the source terms for transfer of mass, momentum, and energy between the fluids are integrated using standard numerical techniques. We show that, for the frequent case where the thermal pressures of the ions and electrons are Lt magnetic pressure, the Riemann problems for the neutral and ion-electron fluids have a similar mathematical structure which facilitates numerical coding. Implementation of the scheme is discussed and several benchmark tests confirming its accuracy are presented, including (1) MHD wave packets ranging over orders of magnitude in length- and timescales, (2) early evolution of multifluid shocks caused by two colliding clouds, and (3) a multifluid shock with mass transfer between the fluids by cosmic-ray ionization and ion-electron recombination, demonstrating the effect of ion mass loading on magnetic precursors of MHD shocks. An exact solution to an MHD Riemann problem forming the basis for an approximate numerical solver used in the homogeneous part of our scheme is presented, along with derivations of the analytic benchmark solutions and tests showing the convergence of the numerical algorithm.

  7. MOLECULAR LINE EMISSION FROM MULTIFLUID SHOCK WAVES. I. NUMERICAL METHODS AND BENCHMARK TESTS

    Energy Technology Data Exchange (ETDEWEB)

    Ciolek, Glenn E.; Roberge, Wayne G., E-mail: cioleg@rpi.edu, E-mail: roberw@rpi.edu [New York Center for Astrobiology (United States); Department of Physics, Applied Physics, and Astronomy, Rensselaer Polytechnic Institute, 110 8th Street, Troy, NY 12180 (United States)

    2013-05-01

    We describe a numerical scheme for studying time-dependent, multifluid, magnetohydrodynamic shock waves in weakly ionized interstellar clouds and cores. Shocks are modeled as propagating perpendicular to the magnetic field and consist of a neutral molecular fluid plus a fluid of ions and electrons. The scheme is based on operator splitting, wherein time integration of the governing equations is split into separate parts. In one part, independent homogeneous Riemann problems for the two fluids are solved using Godunov's method. In the other, equations containing the source terms for transfer of mass, momentum, and energy between the fluids are integrated using standard numerical techniques. We show that, for the frequent case where the thermal pressures of the ions and electrons are << magnetic pressure, the Riemann problems for the neutral and ion-electron fluids have a similar mathematical structure which facilitates numerical coding. Implementation of the scheme is discussed and several benchmark tests confirming its accuracy are presented, including (1) MHD wave packets ranging over orders of magnitude in length- and timescales, (2) early evolution of multifluid shocks caused by two colliding clouds, and (3) a multifluid shock with mass transfer between the fluids by cosmic-ray ionization and ion-electron recombination, demonstrating the effect of ion mass loading on magnetic precursors of MHD shocks. An exact solution to an MHD Riemann problem forming the basis for an approximate numerical solver used in the homogeneous part of our scheme is presented, along with derivations of the analytic benchmark solutions and tests showing the convergence of the numerical algorithm.

  8. Establishment and Molecular Characterization of Mesenchymal Stem Cell Lines Derived From Human Visceral & Subcutaneous Adipose Tissues

    Directory of Open Access Journals (Sweden)

    Jyoti Prakash Sutar

    2010-01-01

    Full Text Available Mesenchymal stem cells (MSCs, are multipotent stem cells that can differentiate into osteoblasts, chondrocytes, myocytes and adipocytes. We utilized adipose tissue as our primary source, since it is a rich source of MSCs as well as it can be harvested using a minimally invasive surgical procedure. Both visceral and subcutaneous adipose tissue (VSAT, SCAT respectively samples were cultured using growth medium without using any substratum for their attachment. We observed growth of mesenchymal like cells within 15 days of culturing. In spite of the absence of any substratum, the cells adhered to the bottom of the petri dish, and spread out within 2 hours. Presently VSAT cells have reached at passage 10 whereas; SCAT cells have reached at passage 14. Morphologically MSCs obtained from visceral adipose tissue were larger in shape than subcutaneous adipose tissue. We checked these cells for presence or absence of specific stem cell molecular markers. We found that VSAT and SCAT cells confirmed their MSC phenotype by expression of specific MSC markers CD 105 and CD13 and absence of CD34 and CD 45 markers which are specific for haematopoietic stem cells. These cells also expressed SOX2 gene confirming their ability of self-renewal as well as expressed OCT4, LIF and NANOG for their properties for pluripotency & plasticity. Overall, it was shown that adipose tissue is a good source of mesenchymal stem cells. It was also shown that MSCs, isolated from adipose tissue are multipotent stem cells that can differentiate into osteoblasts, chondrocytes, cardiomyocytes, adipocytes and liver cells which may open a new era for cell based regenerative therapies for bone, cardiac and liver disorders.

  9. Diagnosis of lubricating oil by evaluating cyanide and carbon molecular emission lines in laser induced breakdown spectra

    Science.gov (United States)

    Elnasharty, I. Y.; Kassem, A. K.; Sabsabi, M.; Harith, M. A.

    2011-08-01

    To prevent engine failure it is essential to change lubricating oil regularly before it loses its protective properties. It is also necessary to monitor the physical and chemical conditions of the oil to reliably determine the optimum oil-change intervals. The present work focuses on studying evolution of the cyanide (CN) and carbon (C 2) molecular spectral emission lines in the laser induced breakdown spectra of lubricating oil as a function of its consumption. The intensities of these molecular bands have been taken as indicator of engine oil degradation at certain mileage. Furthermore, the percentage of decay of CN and C 2 integral intensity values at the corresponding mileage was calculated in order to relate it to the degree of consumption of the motor oil. Such percentage decay of the CN and C 2 integral intensities have been found to increase gradually with increasing mileage which is accompanied with increasing depletion of engine oil. The results of using LIBS technique in the present measurements proved that it is possible to have a direct, straightforward and easy method for prediction of lubricating oil degree of consumption. This may facilitate scheduling the proper time and/or mileage intervals for changing the oil to avoid any possibility of engine failure.

  10. A Network Biology Approach Identifies Molecular Cross-Talk between Normal Prostate Epithelial and Prostate Carcinoma Cells.

    Directory of Open Access Journals (Sweden)

    Victor Trevino

    2016-04-01

    Full Text Available The advent of functional genomics has enabled the genome-wide characterization of the molecular state of cells and tissues, virtually at every level of biological organization. The difficulty in organizing and mining this unprecedented amount of information has stimulated the development of computational methods designed to infer the underlying structure of regulatory networks from observational data. These important developments had a profound impact in biological sciences since they triggered the development of a novel data-driven investigative approach. In cancer research, this strategy has been particularly successful. It has contributed to the identification of novel biomarkers, to a better characterization of disease heterogeneity and to a more in depth understanding of cancer pathophysiology. However, so far these approaches have not explicitly addressed the challenge of identifying networks representing the interaction of different cell types in a complex tissue. Since these interactions represent an essential part of the biology of both diseased and healthy tissues, it is of paramount importance that this challenge is addressed. Here we report the definition of a network reverse engineering strategy designed to infer directional signals linking adjacent cell types within a complex tissue. The application of this inference strategy to prostate cancer genome-wide expression profiling data validated the approach and revealed that normal epithelial cells exert an anti-tumour activity on prostate carcinoma cells. Moreover, by using a Bayesian hierarchical model integrating genetics and gene expression data and combining this with survival analysis, we show that the expression of putative cell communication genes related to focal adhesion and secretion is affected by epistatic gene copy number variation and it is predictive of patient survival. Ultimately, this study represents a generalizable approach to the challenge of deciphering cell

  11. A Network Biology Approach Identifies Molecular Cross-Talk between Normal Prostate Epithelial and Prostate Carcinoma Cells

    Science.gov (United States)

    Trevino, Victor; Cassese, Alberto; Nagy, Zsuzsanna; Zhuang, Xiaodong; Herbert, John; Antzack, Philipp; Clarke, Kim; Davies, Nicholas; Rahman, Ayesha; Campbell, Moray J.; Bicknell, Roy; Vannucci, Marina; Falciani, Francesco

    2016-01-01

    Abstract The advent of functional genomics has enabled the genome-wide characterization of the molecular state of cells and tissues, virtually at every level of biological organization. The difficulty in organizing and mining this unprecedented amount of information has stimulated the development of computational methods designed to infer the underlying structure of regulatory networks from observational data. These important developments had a profound impact in biological sciences since they triggered the development of a novel data-driven investigative approach. In cancer research, this strategy has been particularly successful. It has contributed to the identification of novel biomarkers, to a better characterization of disease heterogeneity and to a more in depth understanding of cancer pathophysiology. However, so far these approaches have not explicitly addressed the challenge of identifying networks representing the interaction of different cell types in a complex tissue. Since these interactions represent an essential part of the biology of both diseased and healthy tissues, it is of paramount importance that this challenge is addressed. Here we report the definition of a network reverse engineering strategy designed to infer directional signals linking adjacent cell types within a complex tissue. The application of this inference strategy to prostate cancer genome-wide expression profiling data validated the approach and revealed that normal epithelial cells exert an anti-tumour activity on prostate carcinoma cells. Moreover, by using a Bayesian hierarchical model integrating genetics and gene expression data and combining this with survival analysis, we show that the expression of putative cell communication genes related to focal adhesion and secretion is affected by epistatic gene copy number variation and it is predictive of patient survival. Ultimately, this study represents a generalizable approach to the challenge of deciphering cell communication

  12. A Network Biology Approach Identifies Molecular Cross-Talk between Normal Prostate Epithelial and Prostate Carcinoma Cells.

    Science.gov (United States)

    Trevino, Victor; Cassese, Alberto; Nagy, Zsuzsanna; Zhuang, Xiaodong; Herbert, John; Antczak, Philipp; Clarke, Kim; Davies, Nicholas; Rahman, Ayesha; Campbell, Moray J; Guindani, Michele; Bicknell, Roy; Vannucci, Marina; Falciani, Francesco

    2016-04-01

    The advent of functional genomics has enabled the genome-wide characterization of the molecular state of cells and tissues, virtually at every level of biological organization. The difficulty in organizing and mining this unprecedented amount of information has stimulated the development of computational methods designed to infer the underlying structure of regulatory networks from observational data. These important developments had a profound impact in biological sciences since they triggered the development of a novel data-driven investigative approach. In cancer research, this strategy has been particularly successful. It has contributed to the identification of novel biomarkers, to a better characterization of disease heterogeneity and to a more in depth understanding of cancer pathophysiology. However, so far these approaches have not explicitly addressed the challenge of identifying networks representing the interaction of different cell types in a complex tissue. Since these interactions represent an essential part of the biology of both diseased and healthy tissues, it is of paramount importance that this challenge is addressed. Here we report the definition of a network reverse engineering strategy designed to infer directional signals linking adjacent cell types within a complex tissue. The application of this inference strategy to prostate cancer genome-wide expression profiling data validated the approach and revealed that normal epithelial cells exert an anti-tumour activity on prostate carcinoma cells. Moreover, by using a Bayesian hierarchical model integrating genetics and gene expression data and combining this with survival analysis, we show that the expression of putative cell communication genes related to focal adhesion and secretion is affected by epistatic gene copy number variation and it is predictive of patient survival. Ultimately, this study represents a generalizable approach to the challenge of deciphering cell communication networks

  13. Molecular genetic analysis of para-Bombay phenotypes in Chinese: a novel non-functional FUT1 allele is identified.

    Science.gov (United States)

    Yip, S P; Chee, K Y; Chan, P Y; Chow, E Y D; Wong, H F

    2002-10-01

    The para-Bombay phenotype (also known as H-deficient secretor) is characterized by a lack of ABH antigens on red cells, but ABH substances are found in saliva. Molecular genetic analysis was performed for five Chinese individuals serologically typed as para-Bombay. ABO genotyping and mutational analysis of both FUT1 (or H) and FUT2 (or Se) loci were performed for these individuals using the polymerase chain reaction, single-strand conformation polymorphism analysis and direct DNA sequencing. The ABO genotypes of these para-Bombay individuals correlated with the types of ABH substances found in the saliva. Their FUT1 genotypes were h1h2 (three individuals), h2h2 (one individual) and h2h6 (one individual). Alleles h1 (547-552delAG) and h2 (880-882delTT) were known frameshift mutations, while h6 (522C > A) was a missense mutation (Phe174Leu) not previously reported. These three mutations were rare sequence variations, each with an allele frequency of less than 0.005. Phe174 might be functionally important because this residue is conserved from mouse to human. Their FUT2 genotypes were Se357se357,385 for the h2h6 individual and Se357Se357) for the others. Both FUT2 alleles were known: one functional (Se357) and one weakly functional (se357,385). That they carried at least one copy of a functional FUT2 allele was consistent with their secretor status. As FUT1 and FUT2 are adjacent on 19q13.3, there are three possible haplotypes in these para-Bombay individuals: h1-Se357; h2-Se357; and h6-se357,385. A novel non-functional FUT1 allele (522C > A, or Phe174Leu) was identified in a para-Bombay individual and on a se357,385 haplotype background.

  14. A scalable method for molecular network reconstruction identifies properties of targets and mutations in acute myeloid leukemia.

    Science.gov (United States)

    Ong, Edison; Szedlak, Anthony; Kang, Yunyi; Smith, Peyton; Smith, Nicholas; McBride, Madison; Finlay, Darren; Vuori, Kristiina; Mason, James; Ball, Edward D; Piermarocchi, Carlo; Paternostro, Giovanni

    2015-04-01

    A key aim of systems biology is the reconstruction of molecular networks. We do not yet, however, have networks that integrate information from all datasets available for a particular clinical condition. This is in part due to the limited scalability, in terms of required computational time and power, of existing algorithms. Network reconstruction methods should also be scalable in the sense of allowing scientists from different backgrounds to efficiently integrate additional data. We present a network model of acute myeloid leukemia (AML). In the current version (AML 2.1), we have used gene expression data (both microarray and RNA-seq) from 5 different studies comprising a total of 771 AML samples and a protein-protein interactions dataset. Our scalable network reconstruction method is in part based on the well-known property of gene expression correlation among interacting molecules. The difficulty of distinguishing between direct and indirect interactions is addressed by optimizing the coefficient of variation of gene expression, using a validated gold-standard dataset of direct interactions. Computational time is much reduced compared to other network reconstruction methods. A key feature is the study of the reproducibility of interactions found in independent clinical datasets. An analysis of the most significant clusters, and of the network properties (intraset efficiency, degree, betweenness centrality, and PageRank) of common AML mutations demonstrated the biological significance of the network. A statistical analysis of the response of blast cells from 11 AML patients to a library of kinase inhibitors provided an experimental validation of the network. A combination of network and experimental data identified CDK1, CDK2, CDK4, and CDK6 and other kinases as potential therapeutic targets in AML.

  15. Evolution of the indigenous microbiota in modified atmosphere packaged Atlantic horse mackerel (Trachurus trachurus) identified by conventional and molecular methods.

    Science.gov (United States)

    Alfaro, Begoña; Hernandez, Igor

    2013-10-15

    A combination of conventional methods and genetic identification (PCR sequencing) was used to study the dynamics of the bacterial population during the spoilage of modified atmosphere packaged (MAP) Atlantic horse mackerel (Trachurus trachurus) fillets. The cultivable microflora in Atlantic horse mackerel samples packaged in a modified atmosphere (48% CO2, 50% N2 and 2% O2) at refrigeration temperature (6 °C) was measured on days 1, 5 and 7 using non-selective (Long and Hammer agar) and selective media (Kligler's iron agar, STAA and MRS). The microflora was genetically characterised using partial amplification of 16S rRNA gene sequences from 309 bacterial isolates obtained from Long and Hammer agar. At the end of the shelf life (5 days), the total viable counts (TVC) on Long and Hammer agar were not significantly different to the LAB counts on MRS agar (p>0.05). The molecular approach showed that Photobacterium, Arthrobacter, Chryseobacterium and Pseudoclavibacter (44.5% of total) dominated the microbial composition of the fish at the beginning of storage. However, Serratia, Shewanella and Yersinia dominated at the late spoilage stages (over 57.2% of the total). Carnobacterium was the most important species of the lactic acid bacteria (LAB) and was identified at the beginning and end of the storage period. Vibrio spp. was only found at the end of the shelf life. This research demonstrates that the microbial biodiversity in MAP Atlantic horse mackerel is enormous and the dominant species change over the storage time. The results presented here on the dominant communities in fish products will make it possible to accurately select the best preservation practices. © 2013.

  16. 自动识别发射线恒星光谱的新方法%A New Automated Method to Identify Emission Line Star from Massive Spectra

    Institute of Scientific and Technical Information of China (English)

    潘景昌; 张彩明; 韦鹏; 罗阿理; 赵永恒

    2012-01-01

    Stellar spectra are characterized by obvious absorption lines or absorption bands, while those with emission lines are usually special stars such as cataclysmic variable stars (CVs), HerbigAe/Be etc. The further study of this kind of spectra is meaningful. The present paper proposed a new method to identify emission line stars (ELS) spectra automatically. After the continuum normalization is done for the original spectral flux, line detection is made by comparing the normalized flux with the mean and standard deviation of the flux in its neighbor region. The results of the experiment on massive spectra from SDSS DR8 indicate that the method can identify ELS spectra completely and accurately. Since no complex transformation and computation are involved in this method, the identifying process is fast and it is ideal for the ELS detection in large sky survey projects like LAMOST and SDSS.%恒星光谱一般具有明显的吸收线或者吸收带特征,而具有发射线的恒星光谱对应着特殊类型的恒星、如激变变星、Herbig Ae/Be等.对这些光谱的后续研究有着重要的意义.本文提出了一种能够自动识别发射线恒星光谱的方法.该方法首先对光谱进行连续谱归一化,然后通过比较谱线对应的流量及其邻域流量的均值和标准差,来判断是否存在发射线.对SDSS DR8大样本数据的实验表明,该方法能够完整、准确地识别发射线恒星.而且,由于该方法不涉及复杂的变换和运算,因而识别速度非常快,可用于诸如LAMOST和SDSS这样大型光谱巡天项目中发现发射线恒星光谱.

  17. Detection of inter-species contaminations in a cell line collection using isoenzymes and molecular markers

    Directory of Open Access Journals (Sweden)

    M. Ferarri

    2011-03-01

    Full Text Available As in human research, also in livestock species the use of continuous cell cultures is an important tool for the study of physiological and tissue developmental processes, as well as for immunological, virological and toxicological assays. This widespread use of animal cell cultures needs that quality control tests are systematically performed in order to evaluate the authenticity of the cells used. Cell cross-contamination (CCC can occur with cells from other species (interspecies contamination or with unrelated cells from the same species (intraspecies contamination. Several methods have been used to identify inter- and intraspecies CCC: isoenzyme profile (Nims, 1998, cytogenetic analysis (Macville et al., 1996, DNA fingerprinting (Stacey et al., 1992, and, more recently, PCR-based methods (Matsuo et al., 1999. Amplified Fragment Length Polymorphism (AFLP technology is a PCR-based technique (Vos et al., 1995 able to reveal polymorphism, with no need of prior sequence information or probe isolation..........

  18. New molecular scaffolds for the design of Mycobacterium tuberculosis type II dehydroquinase inhibitors identified using ligand and receptor based virtual screening.

    Science.gov (United States)

    Kumar, Ashutosh; Siddiqi, Mohammad Imran; Miertus, Stanislav

    2010-04-01

    Using ligand and receptor based virtual screening approaches we have identified potential virtual screening hits targeting type II dehydroquinase from Mycobacterium tuberculosis, an effective and validated anti-mycobacterial target. Initially, we applied a virtual screening workflow based on a combination of 2D structural fingerprints, 3D pharmacophore and molecular docking to identify compounds that rigidly match specific aspects of ligand bioactive conformation. Subsequently, the resulting compounds were ranked and prioritized using receptor interaction fingerprint based scoring and quantitative structure activity relationship model developed using already known actives. The virtual screening hits prioritized belong to several classes of molecular scaffolds with several available substitution positions that could allow chemical modification to enhance binding affinity. Finally, identified hits may be useful to a medicinal chemist or combinatorial chemist to pick up the new molecular starting points for medicinal chemistry optimization for the design of novel type II dehydroquinase inhibitors.

  19. Useful condition of chromoendoscopy with indigo carmine and acetic acid for identifying a demarcation line prior to endoscopic submucosal dissection for early gastric cancer.

    Science.gov (United States)

    Numata, Norifumi; Oka, Shiro; Tanaka, Shinji; Yoshifuku, Yoshikazu; Miwata, Tomohiro; Sanomura, Yoji; Arihiro, Koji; Shimamoto, Fumio; Chayama, Kazuaki

    2016-07-19

    Identifying a precise demarcation line (DL) is indispensable for pathological complete en bloc endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). We evaluated the useful condition of chromoendoscopy with indigo carmine and acetic acid for marking dots around lesions before ESD for EGC. We examined 98 consecutive patients with 109 intramucosal EGCs (mean diameter, 17.8 ± 12.4 mm; main histologic type, 96 intestinal and 13 diffuse) resected by en bloc ESD after chromoendoscopy with indigo carmine and acetic acid between December 2012 and February 2014. The DL was identified by this technique just before ESD (mean chromoendoscopy observation time, 71.6 s); subsequently, marking dots were placed around the EGC. EGCs were classified into two groups: useful for identifying the DL or useless. Clinicopathological characteristics and clinical outcomes were evaluated in each group. Forty-two of the 109 cases (38.5 %) were determined useful for chromoendoscopy with indigo carmine and acetic acid. Multivariate analysis with logistic regression showed that macroscopic type (protruded or flat elevated-type) and atrophic border (the oral side of tumor) were independently associated with the usefulness of chromoendoscopy using indigo carmine and acetic acid for identifying the DL of EGCs (P acetic acid can be used for creating precise markings in protruded or flat elevated-type EGC or at the atrophic border on the oral side of EGCs.

  20. A Patient-Derived, Pan-Cancer EMT Signature Identifies Global Molecular Alterations and Immune Target Enrichment Following Epithelial-to-Mesenchymal Transition.

    Science.gov (United States)

    Mak, Milena P; Tong, Pan; Diao, Lixia; Cardnell, Robert J; Gibbons, Don L; William, William N; Skoulidis, Ferdinandos; Parra, Edwin R; Rodriguez-Canales, Jaime; Wistuba, Ignacio I; Heymach, John V; Weinstein, John N; Coombes, Kevin R; Wang, Jing; Byers, Lauren Averett

    2016-02-01

    We previously demonstrated the association between epithelial-to-mesenchymal transition (EMT) and drug response in lung cancer using an EMT signature derived in cancer cell lines. Given the contribution of tumor microenvironments to EMT, we extended our investigation of EMT to patient tumors from 11 cancer types to develop a pan-cancer EMT signature. Using the pan-cancer EMT signature, we conducted an integrated, global analysis of genomic and proteomic profiles associated with EMT across 1,934 tumors including breast, lung, colon, ovarian, and bladder cancers. Differences in outcome and in vitro drug response corresponding to expression of the pan-cancer EMT signature were also investigated. Compared with the lung cancer EMT signature, the patient-derived, pan-cancer EMT signature encompasses a set of core EMT genes that correlate even more strongly with known EMT markers across diverse tumor types and identifies differences in drug sensitivity and global molecular alterations at the DNA, RNA, and protein levels. Among those changes associated with EMT, pathway analysis revealed a strong correlation between EMT and immune activation. Further supervised analysis demonstrated high expression of immune checkpoints and other druggable immune targets, such as PD1, PD-L1, CTLA4, OX40L, and PD-L2, in tumors with the most mesenchymal EMT scores. Elevated PD-L1 protein expression in mesenchymal tumors was confirmed by IHC in an independent lung cancer cohort. This new signature provides a novel, patient-based, histology-independent tool for the investigation of EMT and offers insights into potential novel therapeutic targets for mesenchymal tumors, independent of cancer type, including immune checkpoints. ©2015 American Association for Cancer Research.

  1. A patient-derived, pan-cancer EMT signature identifies global molecular alterations and immune target enrichment following epithelial to mesenchymal transition

    Science.gov (United States)

    Mak, Milena P.; Tong, Pan; Diao, Lixia; Cardnell, Robert J.; Gibbons, Don L.; William, William N.; Skoulidis, Ferdinandos; Parra, Edwin R.; Rodriguez-Canales, Jaime; Wistuba, Ignacio I.; Heymach, John V.; Weinstein, John N.; Coombes, Kevin R.; Wang, Jing; Byers, Lauren Averett

    2015-01-01

    Purpose We previously demonstrated the association between epithelial-to-mesenchymal transition (EMT) and drug response in lung cancer using an EMT signature derived in cancer cell lines. Given the contribution of tumor microenvironments to EMT, we extended our investigation of EMT to patient tumors from 11 cancer types to develop a pan-cancer EMT signature. Experimental Design Using the pan-cancer EMT signature, we conducted an integrated, global analysis of genomic and proteomic profiles associated with EMT across 1,934 tumors including breast, lung, colon, ovarian, and bladder cancers. Differences in outcome and in vitro drug response corresponding to expression of the pan-cancer EMT signature were also investigated. Results Compared to the lung cancer EMT signature, the patient-derived, pan-cancer EMT signature encompasses a set of core EMT genes that correlate even more strongly with known EMT markers across diverse tumor types and identifies differences in drug sensitivity and global molecular alterations at the DNA, RNA, and protein levels. Among those changes associated with EMT, pathway analysis revealed a strong correlation between EMT and immune activation. Further supervised analysis demonstrated high expression of immune checkpoints and other druggable immune targets such as PD1, PD-L1, CTLA4, OX40L, and PDL2, in tumors with the most mesenchymal EMT scores. Elevated PD-L1 protein expression in mesenchymal tumors was confirmed by immunohistochemistry in an independent lung cancer cohort. Conclusions This new signature provides a novel, patient-based, histology-independent tool for the investigation of EMT and offers insights into potential novel therapeutic targets for mesenchymal tumors, independent of cancer type, including immune checkpoints. PMID:26420858

  2. Molecular Line Observations of Infrared Dark Clouds: Seeking the Precursors to Intermediate and Massive Star Formation

    CERN Document Server

    Ragan, S E; Plume, R; Gibson, D L; Wilner, D J; O'Brien, S; Hails, E; Ragan, Sarah E.; Bergin, Edwin A.; Plume, Rene; Gibson, David L.; Wilner, David J.; Brien, Shawn O'; Hails, Erin

    2006-01-01

    We have identified 41 infrared dark clouds from the 8 micron maps of the Midcourse Space Experiment (MSX), selected to be found within one square degree areas centered on known ultracompact HII regions. We have mapped these infrared dark clouds in N2H+(1-0), CS(2-1) and C18O(1-0) emission using the Five College Radio Astronomy Observatory. The maps of the different species often show striking differences in morphologies, indicating differences in evolutionary state and/or the presence of undetected, deeply embedded protostars. We derive an average mass for these clouds using N2H+ column densities of ~2500 solar masses, a value comparable to that found in previous studies of high mass star forming cores using other mass tracers. The linewidths of these clouds are typically ~2.0 - 2.9 km/s. Based on the fact that they are dark at 8 micron, compact, massive, and have large velocity dispersions, we suggest that these clouds may be the precursor sites of intermediate and high mass star formation.

  3. Multiple-Line Study of NGC 1068: Hot Molecular Gas Caused by Jet-Gas Interaction in the Central 100pc?

    Science.gov (United States)

    Krips, Melanie

    2012-07-01

    A multiple molecular line and line transition study is presented for the circumnuclear disk (CND) of the proto-typical Seyfert galaxy NGC 1068. A detailed analysis of the kinematics and excitation conditions of the molecular gas, as traced by 12CO, 13CO, HCN and HCO+, suggests that part of the molecular gas in the CND is shocked, expanding and heated to high kinetic temperatures most likely as a consequence of an interaction between the radio jet and the CND. We further find support for an X-ray altered chemistry of the molecular gas in the CND based on the significantly elevated abundance of HCN when compared to star-forming, starbursting or quiescent gas regions.

  4. DISCOVERY OF TIME VARIATION OF THE INTENSITY OF MOLECULAR LINES IN IRC+10216 IN THE SUBMILLIMETER AND FAR-INFRARED DOMAINS

    Energy Technology Data Exchange (ETDEWEB)

    Cernicharo, J.; Quintana-Lacaci, G.; Agúndez, M.; Velilla-Prieto, L. [Group of Molecular Astrophysics, ICMM, CSIC, C/Sor Juana Inés de La Cruz N3, E-28049 Madrid (Spain); Teyssier, D.; García-Lario, P. [ESA, ESAC, P.O. Box 78, Villanueva de la Cañada, E-28691 Madrid (Spain); Daniel, F. [Univ. Grenoble Alpes, IPAG, F-38000 Grenoble (France); Decin, L. [Instituut voor Sterrenkunde, Katholieke Universiteit Leuven, Celestijnenlaan 200D, B-3001 Leuven (Belgium); Guélin, M. [Institut de Radioastronomie Millimétrique, 300 rue de la Piscine, F-38406 St-Martin d' Hères (France); Encrenaz, P. [LERMA, Observatoire de Paris, 61 Av. de l' Observatoire, F-75014 Paris (France); De Beck, E. [Department of Earth and Space Sciences, Chalmers University of Technology, Onsala Space Observatory, SE 439 92 Onsala (Sweden); Barlow, M. J. [Department of Physics and Astronomy, University College London, Gower Street, London WC1E 6BT (United Kingdom); Groenewegen, M. A. T. [Koninklijke Sterrenwacht van België, Ringlaan 3, B-1180 Brussels (Belgium); Neufeld, D. [Department of Physics and Astronomy, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218 (United States); Pearson, J. [Jet Propulsion Laboratory, California Institute of Technology, Pasadena, CA 91109 (United States)

    2014-11-20

    We report on the discovery of strong intensity variations in the high rotational lines of abundant molecular species toward the archetypical circumstellar envelope of IRC+10216. The observations have been carried out with the Heterodyne Instrument for the Far-Infrared (HIFI) instrument on board Herschel and with the IRAM30 m telescope. They cover several observing periods spreading over three years. The line intensity variations for molecules produced in the external layers of the envelope most likely result from time variations in the infrared pumping rates. We analyze the main implications this discovery has on the interpretation of molecular line emission in the envelopes of Mira-type stars. Radiative transfer calculations must take into account both the time variability of infrared pumping and the possible variation of the dust and gas temperatures with stellar phase in order to reproduce the observation of molecular lines at different epochs. The effect of gas temperature variations with stellar phase could be particularly important for lines produced in the innermost regions of the envelope. Each layer of the circumstellar envelope sees the stellar light radiation with a different lag time (phase). Our results show that this effect must be included in the models. The submillimeter and far infrared lines of asymptotic giant branch stars can no longer be considered as safe intensity calibrators.

  5. Monocyte-macrophage differentiation of acute myeloid leukemia cell lines by small molecules identified through interrogation of the Connectivity Map database.

    Science.gov (United States)

    Manzotti, Gloria; Parenti, Sandra; Ferrari-Amorotti, Giovanna; Soliera, Angela Rachele; Cattelani, Sara; Montanari, Monica; Cavalli, Daniel; Ertel, Adam; Grande, Alexis; Calabretta, Bruno

    2015-01-01

    The transcription factor C/EBPα is required for granulocytic differentiation of normal myeloid progenitors and is frequently inactivated in acute myeloid leukemia (AML) cells. Ectopic expression of C/EBPα in AML cells suppresses proliferation and induces differentiation suggesting that restoring C/EBPα expression/activity in AML cells could be therapeutically useful. Unfortunately, current approaches of gene or protein delivery in leukemic cells are unsatisfactory. However, "drug repurposing" is becoming a very attractive strategy to identify potential new uses for existing drugs. In this study, we assessed the biological effects of candidate C/EBPα-mimetics identified by interrogation of the Connectivity Map database. We found that amantadine, an antiviral and anti-Parkinson agent, induced a monocyte-macrophage-like differentiation of HL60, U937, Kasumi-1 myeloid leukemia cell lines, as indicated by morphology and differentiation antigen e