SUPER-AGB-AGB EVOLUTION AND THE CHEMICAL INVENTORY IN NGC 2419

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Ventura, Paolo; D' Antona, Francesca; Carini, Roberta [INAF-Osservatorio Astronomico di Roma, via Frascati 33, I-00040 Monteporzio (Italy); Di Criscienzo, Marcella [INAF-Osservatorio Astronomico di Capodimonte, Salita Moiariello 16, I-80131 Napoli (Italy); D' Ercole, Annibale [INAF-Osservatorio Astronomico di Bologna, via Ranzani 1, I-40127 Bologna (Italy); Vesperini, Enrico, E-mail: paolo.ventura@oa-roma.inaf.it [Department of Astronomy, Indiana University, Bloomington (United States)

2012-12-20

We follow the scenario of formation of second-generation stars in globular clusters by matter processed by hot bottom burning (HBB) in massive asymptotic giant branch (AGB) stars and super-AGB stars (SAGB). In the cluster NGC 2419 we assume the presence of an extreme population directly formed from the AGB and SAGB ejecta, so we can directly compare the yields for a metallicity Z = 0.0003 with the chemical inventory of the cluster NGC 2419. At such a low metallicity, the HBB temperatures (well above 10{sup 8} K) allow a very advanced nucleosynthesis. Masses {approx}6 M{sub Sun} deplete Mg and synthesize Si, going beyond Al, so this latter element is only moderately enhanced; sodium cannot be enhanced. The models are consistent with the observations, although the predicted Mg depletion is not as strong as in the observed stars. We predict that the oxygen abundance must be depleted by a huge factor (>50) in the Mg-poor stars. The HBB temperatures are close to the region where other p-capture reactions on heavier nuclei become possible. We show that high potassium abundance found in Mg-poor stars can be achieved during HBB by p-captures on the argon nuclei, if the relevant cross section(s) are larger than listed in the literature or if the HBB temperature is higher. Finally, we speculate that some calcium production is occurring owing to proton capture on potassium. We emphasize the importance of a strong effort to measure a larger sample of abundances in this cluster.

The AGB bump: a calibrator for core mixing

Directory of Open Access Journals (Sweden)

Bossini Diego

2015-01-01

Full Text Available The efficiency of convection in stars affects many aspects of their evolution and remains one of the key-open questions in stellar modelling. In particular, the size of the mixed core in core-He-burning low-mass stars is still uncertain and impacts the lifetime of this evolutionary phase and, e.g., the C/O profile in white dwarfs. One of the known observables related to the Horizontal Branch (HB and Asymptotic Giant Branch (AGB evolution is the AGB bump. Its luminosity depends on the position in mass of the helium-burning shell at its first ignition, that is affected by the extension of the central mixed region. In this preliminary work we show how various assumptions on near-core mixing and on the thermal stratification in the overshooting region affect the luminosity of the AGB bump, as well as the period spacing of gravity modes in core-He-burning models.

Fluorine Abundances in AGB Carbon Stars: New Results?

Science.gov (United States)

Abia, C.; de Laverny, P.; Recio-Blanco, A.; Domínguez, I.; Cristallo, S.; Straniero, O.

2009-09-01

A recent reanalysis of the fluorine abundance in three Galactic Asymptotic Giant Branch (AGB) carbon stars (TX Psc, AQ Sgr and R Scl) by Abia et al. (2009) results in estimates of fluorine abundances systematically lower by ~0.8 dex on average, with respect to the sole previous estimates by Jorissen, Smith & Lambert (1992). The new F abundances are in better agreement with the predictions of full-network stellar models of low-mass (<3 Msolar) AGB stars.

Luminosity Variations in Post-AGB Stars

Science.gov (United States)

Mesler, Robert; Henson, G.

2007-12-01

Although much is known about AGB stars and planetary nebulae, relatively little is known about the phase of a star's life in which it transitions between those two states. We have measured the variations in luminosity of a sample of known Post-AGB stars (as well as several candidates) relative to nearby, non-variable stars in order to compare them with theoretical models. The typical behavior of the observed variations is described and an attempt is made to discern whether any periodicity might be present. Luminosity variations were found to be on the order of a few hundredths to a few tenths of a magnitude for the stars that were surveyed, with occasional fluctuations of up to a magnitude. This agrees with current models of Post-AGB stars. Each star fell into one of three categories, which were termed groups 1, 2, and 3. Group 1 stars showed long term, non-periodic luminosity variations on the scale of weeks or longer and were most likely to display some sort of short term, coherent luminosity oscillation (each of which lasted for only a few cycles). Group 2 stars showed erratic, short-term magnitude variations occurring on scales of several days. Group 3 stars showed little or no variation in magnitude. Of the 27 Post-AGB stars that were sampled, five fell into group 1, fifteen fell into group 2, and seven fell into group 3. The luminosity variations tended to be color-independent, and occurred on timescales ranging nearly continuously from a few days to more than a year. No clear periodic behavior was found in any star in our sample. This project was funded by a partnership between the National Science Foundation (NSF AST-0552798), Research Experiences for Undergraduates (REU), and the Department of Defense (DoD) ASSURE (Awards to Stimulate and Support Undergraduate Research Experiences) programs.

TP508 accelerates fracture repair by promoting cell growth over cell death

International Nuclear Information System (INIS)

Li Xinmin; Wang Hali; Touma, Edward; Qi Yuchen; Rousseau, Emma; Quigg, Richard J.; Ryaby, James T.

2007-01-01

TP508 is a synthetic 23-amino acid peptide representing a receptor-binding domain of human thrombin. We have previously shown that a single injection of TP508 accelerates fracture healing in a rat femoral fracture model. To understand how TP508 acts at the protein level during fracture healing, we compared the translational profiles between saline-control and fractured femur at six time points after TP508 treatment using the second generation of BD Clontech TM Antibody Microarray. Here, we demonstrate that TP508 accelerates fracture healing by modulating expression levels of proteins primarily involved in the functional categories of cell cycle, cellular growth and proliferation, and cell death. The majority of those proteins are physically interrelated and functionally overlapped. The action of those proteins is highlighted by a central theme of promoting cell growth via balance of cell survival over cell death signals. This appears to occur through the stimulation of several bone healing pathways including cell cycle-G1/S checkpoint regulation, apoptosis, JAK/STAT, NF-κB, PDGF, PI3K/AKT, PTEN, and ERK/MAPK

TP-model transformation-based-control design frameworks

CERN Document Server

Baranyi, Péter

2016-01-01

This book covers new aspects and frameworks of control, design, and optimization based on the TP model transformation and its various extensions. The author outlines the three main steps of polytopic and LMI based control design: 1) development of the qLPV state-space model, 2) generation of the polytopic model; and 3) application of LMI to derive controller and observer. He goes on to describe why literature has extensively studied LMI design, but has not focused much on the second step, in part because the generation and manipulation of the polytopic form was not tractable in many cases. The author then shows how the TP model transformation facilitates this second step and hence reveals new directions, leading to powerful design procedures and the formulation of new questions. The chapters of this book, and the complex dynamical control tasks which they cover, are organized so as to present and analyze the beneficial aspect of the family of approaches (control, design, and optimization). Additionally, the b...

Third dredge-up in cluster AGB stars : observational constraints and improved opacity data for models

International Nuclear Information System (INIS)

Lederer, M. T.

2009-01-01

The extant stellar evolution models largely agree on the theoretical picture of a low- or intermediate-mass star that has evolved towards the end of the asymptotic giant branch (AGB). During this evolutionary phase, chemical elements (mainly carbon, helium and products of the s-process) are synthesised in a series of recurring shell burning episodes. The burning products are then transported to the outer layers of the star by convective mixing events. This mechanism is usually condensed in the term third dredge-up (TDU). Subsequently, the chemically enriched matter is ejected into the interstellar medium by means of strong stellar winds that develop in the late stages of stellar evolution. As low- and intermediate-mass stars appear in a large number, it is crucial to assess their role within the cosmic matter cycle which requires detailed knowledge of the TDU onset and efficiency as a function of the stellar mass and metallicity. The material presented in this thesis intends to contribute to the improvement of AGB star models in two ways. The first approach is to constrain the models with results from observations. I present high-resolution near-infrared spectra of AGB stars that belong to intermediate-age globular clusters (GC) in the Large Magellanic Cloud (LMC). A sample of GC stars has the advantage that fundamental stellar parameters like mass, metallicity, and age are usually well-defined and that the sample is 'more or less' homogeneous in this respect, contrary to the situation that we find for a sample of field stars. The analysis of the observed spectra is done by a comparison with synthetic spectra based on hydrostatic atmosphere models computed with the MARCS code. We use features of the molecules CO and OH comprised in our observed wavelength range to derive the number ratio of carbon to oxygen atoms (C/O) and the carbon isotopic ratio 12 C/ 13 C together with the stellar parameters of each target. Eventually, we confront the outcomes of stellar

THE MASS-LOSS RETURN FROM EVOLVED STARS TO THE LARGE MAGELLANIC CLOUD. IV. CONSTRUCTION AND VALIDATION OF A GRID OF MODELS FOR OXYGEN-RICH AGB STARS, RED SUPERGIANTS, AND EXTREME AGB STARS

International Nuclear Information System (INIS)

Sargent, Benjamin A.; Meixner, M.; Srinivasan, S.

2011-01-01

To measure the mass loss from dusty oxygen-rich (O-rich) evolved stars in the Large Magellanic Cloud (LMC), we have constructed a grid of models of spherically symmetric dust shells around stars with constant mass-loss rates using 2Dust. These models will constitute the O-rich model part of the 'Grid of Red supergiant and Asymptotic giant branch star ModelS' (GRAMS). This model grid explores four parameters-stellar effective temperature from 2100 K to 4700 K; luminosity from 10 3 to 10 6 L sun ; dust shell inner radii of 3, 7, 11, and 15 R star ; and 10.0 μm optical depth from 10 -4 to 26. From an initial grid of ∼1200 2Dust models, we create a larger grid of ∼69,000 models by scaling to cover the luminosity range required by the data. These models are available online to the public. The matching in color-magnitude diagrams and color-color diagrams to observed O-rich asymptotic giant branch (AGB) and red supergiant (RSG) candidate stars from the SAGE and SAGE-Spec LMC samples and a small sample of OH/IR stars is generally very good. The extreme AGB star candidates from SAGE are more consistent with carbon-rich (C-rich) than O-rich dust composition. Our model grid suggests lower limits to the mid-infrared colors of the dustiest AGB stars for which the chemistry could be O-rich. Finally, the fitting of GRAMS models to spectral energy distributions of sources fit by other studies provides additional verification of our grid and anticipates future, more expansive efforts.

The FRUITY database on AGB stars: past, present and future

Science.gov (United States)

Cristallo, S.; Piersanti, L.; Straniero, O.

2016-01-01

We present and show the features of the FRUITY database, an interactive web- based interface devoted to the nucleosynthesis in AGB stars. We describe the current available set of AGB models (largely expanded with respect to the original one) with masses in the range 1.3≤M/M⊙≤3.0 and metallicities -2.15 ≤[Fe/H]≤+0.15. We illustrate the details of our s-process surface distributions and we compare our results to observations. Moreover, we introduce a new set of models where the effects of rotation are taken into account. Finally, we shortly describe next planned upgrades.

The 13C-pocket structure in AGB models: constraints from zirconium isotope abundances in single mainstream SiC grains

International Nuclear Information System (INIS)

Liu, Nan; Davis, Andrew M.; Pellin, Michael J.; Gallino, Roberto; Bisterzo, Sara; Savina, Michael R.

2014-01-01

We present postprocess asymptotic giant branch (AGB) nucleosynthesis models with different 13 C-pocket internal structures to better explain zirconium isotope measurements in mainstream presolar SiC grains by Nicolussi et al. and Barzyk et al. We show that higher-than-solar 92 Zr/ 94 Zr ratios can be predicted by adopting a 13 C-pocket with a flat 13 C profile, instead of the previous decreasing-with-depth 13 C profile. The improved agreement between grain data for zirconium isotopes and AGB models provides additional support for a recent proposal of a flat 13 C profile based on barium isotopes in mainstream SiC grains by Liu et al.

Global 3D radiation-hydrodynamics models of AGB stars. Effects of convection and radial pulsations on atmospheric structures

Science.gov (United States)

Freytag, B.; Liljegren, S.; Höfner, S.

2017-04-01

Context. Observations of asymptotic giant branch (AGB) stars with increasing spatial resolution reveal new layers of complexity of atmospheric processes on a variety of scales. Aims: To analyze the physical mechanisms that cause asymmetries and surface structures in observed images, we use detailed 3D dynamical simulations of AGB stars; these simulations self-consistently describe convection and pulsations. Methods: We used the CO5BOLD radiation-hydrodynamics code to produce an exploratory grid of global "star-in-a-box" models of the outer convective envelope and the inner atmosphere of AGB stars to study convection, pulsations, and shock waves and their dependence on stellar and numerical parameters. Results: The model dynamics are governed by the interaction of long-lasting giant convection cells, short-lived surface granules, and strong, radial, fundamental-mode pulsations. Radial pulsations and shorter wavelength, traveling, acoustic waves induce shocks on various scales in the atmosphere. Convection, waves, and shocks all contribute to the dynamical pressure and, thus, to an increase of the stellar radius and to a levitation of material into layers where dust can form. Consequently, the resulting relation of pulsation period and stellar radius is shifted toward larger radii compared to that of non-linear 1D models. The dependence of pulsation period on luminosity agrees well with observed relations. The interaction of the pulsation mode with the non-stationary convective flow causes occasional amplitude changes and phase shifts. The regularity of the pulsations decreases with decreasing gravity as the relative size of convection cells increases. The model stars do not have a well-defined surface. Instead, the light is emitted from a very extended inhomogeneous atmosphere with a complex dynamic pattern of high-contrast features. Conclusions: Our models self-consistently describe convection, convectively generated acoustic noise, fundamental-mode radial

Yunnan-III models for evolutionary population synthesis

Science.gov (United States)

Zhang, F.; Li, L.; Han, Z.; Zhuang, Y.; Kang, X.

2013-02-01

We build the Yunnan-III evolutionary population synthesis (EPS) models by using the mesa stellar evolution code, BaSeL stellar spectra library and the initial mass functions (IMFs) of Kroupa and Salpeter, and present colours and integrated spectral energy distributions (ISEDs) of solar-metallicity stellar populations (SPs) in the range of 1 Myr to 15 Gyr. The main characteristic of the Yunnan-III EPS models is the usage of a set of self-consistent solar-metallicity stellar evolutionary tracks (the masses of stars are from 0.1 to 100 M⊙). This set of tracks is obtained by using the state-of-the-art mesa code. mesa code can evolve stellar models through thermally pulsing asymptotic giant branch (TP-AGB) phase for low- and intermediate-mass stars. By comparisons, we confirm that the inclusion of TP-AGB stars makes the V - K, V - J and V - R colours of SPs redder and the infrared flux larger at ages log(t/yr) ≳ 7.6 [the differences reach the maximum at log(t/yr) ˜ 8.6, ˜0.5-0.2 mag for colours, approximately two times for K-band flux]. We also find that the colour-evolution trends of Model with-TPAGB at intermediate and large ages are similar to those from the starburst99 code, which employs the Padova-AGB stellar library, BaSeL spectral library and the Kroupa IMF. At last, we compare the colours with the other EPS models comprising TP-AGB stars (such as CB07, M05, V10 and POPSTAR), and find that the B - V colour agrees with each other but the V-K colour shows a larger discrepancy among these EPS models [˜1 mag when 8 ≲ log(t/yr) ≲ 9]. The stellar evolutionary tracks, isochrones, colours and ISEDs can be obtained on request from the first author or from our website (http://www1.ynao.ac.cn/~zhangfh/). Using the isochrones, you can build your EPS models. Now the format of stellar evolutionary tracks is the same as that in the starburst99 code; you can put them into the starburst99 code and get the SP's results. Moreover, the colours involving other passbands

EARLY-TYPE GALAXIES AT z ∼ 1.3. II. MASSES AND AGES OF EARLY-TYPE GALAXIES IN DIFFERENT ENVIRONMENTS AND THEIR DEPENDENCE ON STELLAR POPULATION MODEL ASSUMPTIONS

International Nuclear Information System (INIS)

Raichoor, A.; Mei, S.; Huertas-Company, M.; Nakata, F.; Kodama, T.; Stanford, S. A.; Rettura, A.; Jee, M. J.; Holden, B. P.; Illingworth, G.; Postman, M.; White, R. L.; Rosati, P.; Blakeslee, J. P.; Demarco, R.; Eisenhardt, P.; Tanaka, M.

2011-01-01

We have derived masses and ages for 79 early-type galaxies (ETGs) in different environments at z ∼ 1.3 in the Lynx supercluster and in the GOODS/CDF-S field using multi-wavelength (0.6-4.5 μm; KPNO, Palomar, Keck, Hubble Space Telescope, Spitzer) data sets. At this redshift the contribution of the thermally pulsing asymptotic giant branch (TP-AGB) phase is important for ETGs, and the mass and age estimates depend on the choice of the stellar population model used in the spectral energy distribution fits. We describe in detail the differences among model predictions for a large range of galaxy ages, showing the dependence of these differences on age. Current models still yield large uncertainties. While recent models from Maraston and Charlot and Bruzual offer better modeling of the TP-AGB phase with respect to less recent Bruzual and Charlot models, their predictions do not often match. The modeling of this TP-AGB phase has a significant impact on the derived parameters for galaxies observed at high redshift. Some of our results do not depend on the choice of the model: for all models, the most massive galaxies are the oldest ones, independent of the environment. When using the Maraston and Charlot and Bruzual models, the mass distribution is similar in the clusters and in the groups, whereas in our field sample there is a deficit of massive (M ∼> 10 11 M sun ) ETGs. According to those last models, ETGs belonging to the cluster environment host on average older stars with respect to group and field populations. This difference is less significant than the age difference in galaxies of different masses.

Synthetic H-R diagrams as an observational test of stellar evolution theory

International Nuclear Information System (INIS)

Mathews, G.J.; Becker, S.A.; Brunish, W.M.

1983-07-01

Synthetic H-R diagrams are constructed from a grid of stellar models. These are compared directly with observations of young clusters in the LMC and SMC as a test of the models and as a means to determine the age, age dispersion, and composition of the clusters. Significant discrepancies between the observed and model H-R diagrams indicate the possible influences of convective overshoot, large AGB mass-loss rates, and the best value for the mixing length parameter

Tp53 gene mediates distinct dopaminergic neuronal damage in different dopaminergic neurotoxicant models

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Tao Lu

2017-01-01

Full Text Available Tp53, a stress response gene, is involved in diverse cell death pathways and its activation is implicated in the pathogenesis of Parkinson's disease. However, whether the neuronal Tp53 protein plays a direct role in regulating dopaminergic (DA neuronal cell death or neuronal terminal damage in different neurotoxicant models is unknown. In our recent studies, in contrast to the global inhibition of Tp53 function by pharmacological inhibitors and in traditional Tp53 knock-out mice, we examined the effects of DA-specific Tp53 gene deletion after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and methamphetamine exposure. Our data suggests that the Tp53 gene might be involved in both neuronal apoptosis and neuronal terminal damage caused by different neurotoxicants. Additional results from other studies also suggest that as a master regulator of many pathways that regulate apoptosis and synaptic terminal damage, it is possible that Tp53 may function as a signaling hub to integrate different signaling pathways to mediate distinctive target pathways. Tp53 protein as a signaling hub might be able to evaluate the microenvironment of neurons, assess the forms and severities of injury incurred, and determine whether apoptotic cell death or neuronal terminal degeneration occurs. Identification of the precise mechanisms activated in distinct neuronal damage caused by different forms and severities of injuries might allow for development of specific Tp53 inhibitors or ways to modulate distinct downstream target pathways involved.

Abundances in Planetary Nebulae: an Autopsy of Low and Intermediate Mass Stars

Science.gov (United States)

Buell, James Francis

In this work we report on the results of synthetic thermally pulsing asymptotic giant branch models (TP-AGB) and compare the results to the abundance ratios in a sample of planetary nebulae. We use updated the input parameters for mass-loss, the stellar luminosity, and dredge-up. We calculated models with masses between 0.8 solar masses and 8 solar masses. We also calculated models with (Fe/H) between -2.5 and 0.3. The effect of the first, second, and third dredge-up as well as hot-bottom burning are reported on. The analysis of a sample of Galactic bulge and disk planetary nebulae is also reported on.

The 2014 AGB Survey of Higher Education Governance

Science.gov (United States)

Hodge-Clark, Kristen

2014-01-01

"The 2014 AGB Survey of Higher Education Governance" is the fourth in AGB's studies of college and university governance. This report, based on survey responses from 592 public and independent boards, addresses a range of important governance topics that are receiving attention from boards and the news media, including presidential…

AGB sodium abundances in the globular cluster 47 Tucanae (NGC 104)

Energy Technology Data Exchange (ETDEWEB)

Johnson, Christian I. [Harvard–Smithsonian Center for Astrophysics, 60 Garden Street, MS-15, Cambridge, MA 02138 (United States); McDonald, Iain; Zijlstra, Albert A., E-mail: cjohnson@cfa.harvard.edu, E-mail: iain.mcdonald-2@manchester.ac.uk, E-mail: albert.zijlstra@manchester.ac.uk [Jodrell Bank Centre for Astrophysics, Alan Turing Building, Manchester M13 9PL (United Kingdom); and others

2015-02-01

A recent analysis comparing the [Na/Fe] distributions of red giant branch (RGB) and asymptotic giant branch (AGB) stars in the Galactic globular cluster NGC 6752 found that the ratio of Na-poor to Na-rich stars changes from 30:70 on the RGB to 100:0 on the AGB. The surprising paucity of Na-rich stars on the AGB in NGC 6752 warrants additional investigations to determine if the failure of a significant fraction of stars to ascend the AGB is an attribute common to all globular clusters. Therefore, we present radial velocities, [Fe/H], and [Na/Fe] abundances for 35 AGB stars in the Galactic globular cluster 47 Tucanae (47 Tuc; NGC 104), and compare the AGB [Na/Fe] distribution with a similar RGB sample published previously. The abundances and velocities were derived from high-resolution spectra obtained with the Michigan/Magellan Fiber System and MSpec spectrograph on the Magellan–Clay 6.5 m telescope. We find the average heliocentric radial velocity and [Fe/H] values to be 〈RV{sub helio.}〉 = −18.56 km s{sup −1} (σ = 10.21 km s{sup −1}) and 〈[Fe/H]〉 = −0.68 (σ = 0.08), respectively, in agreement with previous literature estimates. The average [Na/Fe] abundance is 0.12 dex lower in the 47 Tuc AGB sample compared to the RGB sample, and the ratio of Na-poor to Na-rich stars is 63:37 on the AGB and 45:55 on the RGB. However, in contrast to NGC 6752, the two 47 Tuc populations have nearly identical [Na/Fe] dispersion and interquartile range values. The data presented here suggest that only a small fraction (≲20%) of Na-rich stars in 47 Tuc may fail to ascend the AGB, which is a similar result to that observed in M13. Regardless of the cause for the lower average [Na/Fe] abundance in AGB stars, we find that Na-poor stars and at least some Na-rich stars in 47 Tuc evolve through the early AGB phase. The contrasting behavior of Na-rich stars in 47 Tuc and NGC 6752 suggests that the RGB [Na/Fe] abundance alone is insufficient for predicting if a star will

THE ACS NEARBY GALAXY SURVEY TREASURY. IX. CONSTRAINING ASYMPTOTIC GIANT BRANCH EVOLUTION WITH OLD METAL-POOR GALAXIES

International Nuclear Information System (INIS)

Girardi, Leo; Williams, Benjamin F.; Gilbert, Karoline M.; Rosenfield, Philip; Dalcanton, Julianne J.; Marigo, Paola; Boyer, Martha L.; Dolphin, Andrew; Weisz, Daniel R.; Skillman, Evan; Melbourne, Jason; Olsen, Knut A. G.; Seth, Anil C.

2010-01-01

In an attempt to constrain evolutionary models of the asymptotic giant branch (AGB) phase at the limit of low masses and low metallicities, we have examined the luminosity functions and number ratios between AGB and red giant branch (RGB) stars from a sample of resolved galaxies from the ACS Nearby Galaxy Survey Treasury. This database provides Hubble Space Telescope optical photometry together with maps of completeness, photometric errors, and star formation histories for dozens of galaxies within 4 Mpc. We select 12 galaxies characterized by predominantly metal-poor populations as indicated by a very steep and blue RGB, and which do not present any indication of recent star formation in their color-magnitude diagrams. Thousands of AGB stars brighter than the tip of the RGB (TRGB) are present in the sample (between 60 and 400 per galaxy), hence, the Poisson noise has little impact in our measurements of the AGB/RGB ratio. We model the photometric data with a few sets of thermally pulsing AGB (TP-AGB) evolutionary models with different prescriptions for the mass loss. This technique allows us to set stringent constraints on the TP-AGB models of low-mass, metal-poor stars (with M sun , [Fe/H]∼ sun . This is also in good agreement with recent observations of white dwarf masses in the M4 old globular cluster. These constraints can be added to those already derived from Magellanic Cloud star clusters as important mileposts in the arduous process of calibrating AGB evolutionary models.

ALMA reveals sunburn: CO dissociation around AGB stars in the globular cluster 47 Tucanae

OpenAIRE

McDonald, Iain; Zijlstra, Albert A.; Lagadec, Eric; Sloan, Gregory C.; Boyer, Martha L.; Matsuura, Mikako; Smith, Rowan J.; Smith, Christina L.; Yates, Jeremy A.; van Loon, Jacco Th.; Jones, Olivia C.; Ramstedt, Sofia; Avison, Adam; Justtanont, Kay; Olofsson, Hans

2015-01-01

Atacama Large Millimetre Array observations show a non-detection of carbon monoxide around the four most luminous asymptotic giant branch (AGB) stars in the globular cluster 47 Tucanae. Stellar evolution models and star counts show that the mass-loss rates from these stars should be similar to 1.2-3.5x10(-7) M-circle dot yr(-1). We would naively expect such stars to be detectable at this distance (4.5 kpc). By modelling the ultraviolet radiation field from post-AGB stars and white dwarfs in 4...

The Core Mass Growth and Stellar Lifetime of Thermally Pulsing Asymptotic Giant Branch Stars

Science.gov (United States)

Kalirai, Jason S.; Marigo, Paola; Tremblay, Pier-Emmanuel

2014-02-01

We establish new constraints on the intermediate-mass range of the initial-final mass relation, and apply the results to study the evolution of stars on the thermally pulsing asymptotic giant branch (TP-AGB). These constraints derive from newly discovered (bright) white dwarfs in the nearby Hyades and Praesepe star clusters, including a total of 18 high signal-to-noise ratio measurements with progenitor masses of M initial = 2.8-3.8 M ⊙. We also include a new analysis of existing white dwarfs in the older NGC 6819 and NGC 7789 star clusters, M initial = 1.6 and 2.0 M ⊙. Over this range of initial masses, stellar evolutionary models for metallicity Z initial = 0.02 predict the maximum growth of the core of TP-AGB stars. By comparing the newly measured remnant masses to the robust prediction of the core mass at the first thermal pulse on the AGB (i.e., from stellar interior models), we establish several findings. First, we show that the stellar core mass on the AGB grows rapidly from 10% to 30% for stars with M initial = 1.6 to 2.0 M ⊙. At larger masses, the core-mass growth decreases steadily to ~10% at M initial = 3.4 M ⊙, after which there is a small hint of a upturn out to M initial = 3.8 M ⊙. These observations are in excellent agreement with predictions from the latest TP-AGB evolutionary models in Marigo et al. We also compare to models with varying efficiencies of the third dredge-up and mass loss, and demonstrate that the process governing the growth of the core is largely the stellar wind, while the third dredge-up plays a secondary, but non-negligible role. Based on the new white dwarf measurements, we perform an exploratory calibration of the most popular mass-loss prescriptions in the literature, as well as of the third dredge-up efficiency as a function of the stellar mass. Finally, we estimate the lifetime and the integrated luminosity of stars on the TP-AGB to peak at t ~ 3 Myr and E = 1.2 × 1010 L ⊙ yr for M initial ~ 2 M ⊙ (t ~ 2 Myr

Improving the distances of post-AGB objects in the Milky Way

International Nuclear Information System (INIS)

Vickers, Shane B; Owers, Matt S; Frew, David J; Parker, Quentin A; Bojičič, Ivan S

2016-01-01

Post-AGB (PAGB) stars are short-lived, low-intermediate mass objects transitioning from the asymptotic giant branch (AGB) to the white dwarf (WD) phase. These objects are characterised by a constant, core-mass dependent luminosity and a large infrared excess from the dusty envelope ejected at the top of the AGB. PAGB stars provide insights into the evolution of their direct descendants, planetary nebulae (PNe). Calculation of physical characteristics of PAGB are dependent on accurately determined distances scarcely available in the literature. Using the Torun catalogue for PAGB objects, supplemented with archival data, we have determined distances to the known population of Galactic PAGB stars. This is by modelling their spectral energy distributions (SED) with black bodies and numerically integrating over the entire wavelength range to determine the total integrated object flux. For most PAGB stars we assumed their luminosities are based on their positional characteristics and stellar evolution models. RV Tauri stars however are known to follow a period-luminosity relation (PLR) reminiscent of type-2 Cepheids. For these variable PAGB stars we determined their luminosities via the PLR and hence their distances. This allows us to overcome the biggest obstacle to characterising these poorly understood objects that play a vital part in Galactic chemical enrichment. (paper)

Estimating the Above-Ground Biomass in Miombo Savanna Woodlands (Mozambique, East Africa Using L-Band Synthetic Aperture Radar Data

Directory of Open Access Journals (Sweden)

Maria J. Vasconcelos

2013-03-01

Full Text Available The quantification of forest above-ground biomass (AGB is important for such broader applications as decision making, forest management, carbon (C stock change assessment and scientific applications, such as C cycle modeling. However, there is a great uncertainty related to the estimation of forest AGB, especially in the tropics. The main goal of this study was to test a combination of field data and Advanced Land Observing Satellite (ALOS Phased Array L-band Synthetic Aperture Radar (PALSAR backscatter intensity data to reduce the uncertainty in the estimation of forest AGB in the Miombo savanna woodlands of Mozambique (East Africa. A machine learning algorithm, based on bagging stochastic gradient boosting (BagSGB, was used to model forest AGB as a function of ALOS PALSAR Fine Beam Dual (FBD backscatter intensity metrics. The application of this method resulted in a coefficient of correlation (R between observed and predicted (10-fold cross-validation forest AGB values of 0.95 and a root mean square error of 5.03 Mg·ha−1. However, as a consequence of using bootstrap samples in combination with a cross validation procedure, some bias may have been introduced, and the reported cross validation statistics could be overoptimistic. Therefore and as a consequence of the BagSGB model, a measure of prediction variability (coefficient of variation on a pixel-by-pixel basis was also produced, with values ranging from 10 to 119% (mean = 25% across the study area. It provides additional and complementary information regarding the spatial distribution of the error resulting from the application of the fitted model to new observations.

INFRARED COLOR-COLOR DIAGRAMS FOR AGB STARS

Directory of Open Access Journals (Sweden)

Kyung-Won Suh

2007-09-01

Full Text Available We present infrared color-color diagrams of AGB stars from the observations at near and mid infrared bands. We compile the observations for hundreds of OH/IR stars and carbon stars using the data from the Midcourse Space Experiment (MSX, the two micron sky survey (2MASS, and the IRAS point source catalog (PSC. We compare the observations with the theoretical evolutionary tracks of AGB stars. From the new observational data base and the theoretical evolution tracks, we discuss the meaning of the infrared color-color diagrams at different wavelengths.

Luminosities and mass-loss rates of Local Group AGB stars and red supergiants

Science.gov (United States)

Groenewegen, M. A. T.; Sloan, G. C.

2018-01-01

Context. Mass loss is one of the fundamental properties of asymptotic giant branch (AGB) stars, and through the enrichment of the interstellar medium, AGB stars are key players in the life cycle of dust and gas in the universe. However, a quantitative understanding of the mass-loss process is still largely lacking. Aims: We aim to investigate mass loss and luminosity in a large sample of evolved stars in several Local Group galaxies with a variety of metalliticies and star-formation histories: the Small and Large Magellanic Cloud, and the Fornax, Carina, and Sculptor dwarf spheroidal galaxies (dSphs). Methods: Dust radiative transfer models are presented for 225 carbon stars and 171 oxygen-rich evolved stars in several Local Group galaxies for which spectra from the Infrared Spectrograph on Spitzer are available. The spectra are complemented with available optical and infrared photometry to construct spectral energy distributions. A minimization procedure was used to determine luminosity and mass-loss rate (MLR). Pulsation periods were derived for a large fraction of the sample based on a re-analysis of existing data. Results: New deep K-band photometry from the VMC survey and multi-epoch data from IRAC (at 4.5 μm) and AllWISE and NEOWISE have allowed us to derive pulsation periods longer than 1000 days for some of the most heavily obscured and reddened objects. We derive (dust) MLRs and luminosities for the entire sample. The estimated MLRs can differ significantly from estimates for the same objects in the literature due to differences in adopted optical constants (up to factors of several) and details in the radiative transfer modelling. Updated parameters for the super-AGB candidate MSX SMC 055 (IRAS 00483-7347) are presented. Its current mass is estimated to be 8.5 ± 1.6 M⊙, suggesting an initial mass well above 8 M⊙ in agreement with estimates based on its large Rubidium abundance. Using synthetic photometry, we present and discuss colour-colour and

Discovery of a Metal-poor, Luminous Post-AGB Star that Failed the Third Dredge-up

Energy Technology Data Exchange (ETDEWEB)

Kamath, D.; Winckel, H. Van [Instituut voor Sterrenkunde, K.U.Leuven, Celestijnenlaan 200D bus 2401, B-3001 Leuven (Belgium); Wood, P. R.; Asplund, M.; Karakas, A. I. [Research School of Astronomy and Astrophysics, Australian National University, Canberra ACT 2611 (Australia); Lattanzio, J. C. [Monash Centre for Astrophysics, School of Physics and Astronomy, Monash University, VIC 3800 (Australia)

2017-02-10

Post-asymptotic giant branch (post-AGB) stars are known to be chemically diverse. In this paper we present the first observational evidence of a star that has failed the third dredge-up (TDU). J005252.87-722842.9 is an A-type ( T {sub eff} = 8250 ± 250 K) luminous (8200 ± 700 L {sub ⊙}) metal-poor ([Fe/H] = −1.18 ± 0.10) low-mass ( M {sub initial} ≈ 1.5–2.0 M {sub ⊙}) post-AGB star in the Small Magellanic Cloud. Through a systematic abundance study, using high-resolution optical spectra from UVES, we found that this likely post-AGB object shows an intriguing photospheric composition with no confirmed carbon-enhancement (upper limit of [C/Fe] < 0.50) nor enrichment of s -process elements. We derived an oxygen abundance of [O/Fe] = 0.29 ± 0.1. For Fe and O, we took the effects of nonlocal thermodynamic equilibrium into account. We could not derive an upper limit for the nitrogen abundance as there are no useful nitrogen lines within our spectral coverage. The chemical pattern displayed by this object has not been observed in single or binary post-AGBs. Based on its derived stellar parameters and inferred evolutionary state, single-star nucleosynthesis models predict that this star should have undergone TDU episodes while on the AGB, and it should be carbon enriched. However, our observations are in contrast with these predictions. We identify two possible Galactic analogs that are likely to be post-AGB stars, but the lack of accurate distances (hence luminosities) to these objects does not allow us to confirm their post-AGB status. If they have low luminosities, then they are likely to be dusty post-RGB stars. The discovery of J005252.87-722842.9 reveals a new stellar evolutionary channel whereby a star evolves without any TDU episodes.

A view of the H-band light-element chemical patterns in globular clusters under the AGB self-enrichment scenario

Science.gov (United States)

Dell'Agli, F.; García-Hernández, D. A.; Ventura, P.; Mészáros, Sz; Masseron, T.; Fernández-Trincado, J. G.; Tang, B.; Shetrone, M.; Zamora, O.; Lucatello, S.

2018-04-01

We discuss the self-enrichment scenario by asymptotic giant branch (AGB) stars for the formation of multiple populations in globular clusters (GCs) by analysing data set of giant stars observed in nine Galactic GCs, covering a wide range of metallicities and for which the simultaneous measurements of C, N, O, Mg, Al, and Si are available. To this aim, we calculated six sets of AGB models, with the same chemical composition as the stars belonging to the first generation of each GC. We find that the AGB yields can reproduce the set of observations available, not only in terms of the degree of contamination shown by stars in each GC but, more important, also the observed trend with metallicity, which agrees well with the predictions from AGB evolution modelling. While further observational evidences are required to definitively fix the main actors in the pollution of the interstellar medium from which new generation of stars formed in GCs, the present results confirm that the gas ejected by stars of mass in the range 4 M_{⊙} ≤ M ≤ 8 M_{⊙} during the AGB phase share the same chemical patterns traced by stars in GCs.

Catalytic oxidation of methanol on Pt/X (X = CaTP, NaTP electrodes in sulfuric acid solution

Directory of Open Access Journals (Sweden)

Said Benmokhtar

2013-10-01

Full Text Available In this paper, we report the synthesis and characterization of electrodes based on NASICON type phosphates. The study of the electrochemical oxidation of methanol at ambient temperature on electrodes based on NASICON type Ca0,5Ti2(PO43 (CaTP and Na5Ti(PO43 (NaTP compared to that of the platinum electrode model has been conducted by cyclic voltammetry in acidic medium. The results showed a significant increase of current density on the electro oxidation of methanol on the material developed based NASICON structure CaTP, cons deactivation of the electro oxidation is observed the closed structure type NaTP.

The Uncertainty of Biomass Estimates from Modeled ICESat-2 Returns Across a Boreal Forest Gradient

Science.gov (United States)

Montesano, P. M.; Rosette, J.; Sun, G.; North, P.; Nelson, R. F.; Dubayah, R. O.; Ranson, K. J.; Kharuk, V.

2014-01-01

The Forest Light (FLIGHT) radiative transfer model was used to examine the uncertainty of vegetation structure measurements from NASA's planned ICESat-2 photon counting light detection and ranging (LiDAR) instrument across a synthetic Larix forest gradient in the taiga-tundra ecotone. The simulations demonstrate how measurements from the planned spaceborne mission, which differ from those of previous LiDAR systems, may perform across a boreal forest to non-forest structure gradient in globally important ecological region of northern Siberia. We used a modified version of FLIGHT to simulate the acquisition parameters of ICESat-2. Modeled returns were analyzed from collections of sequential footprints along LiDAR tracks (link-scales) of lengths ranging from 20 m-90 m. These link-scales traversed synthetic forest stands that were initialized with parameters drawn from field surveys in Siberian Larix forests. LiDAR returns from vegetation were compiled for 100 simulated LiDAR collections for each 10 Mg · ha(exp -1) interval in the 0-100 Mg · ha(exp -1) above-ground biomass density (AGB) forest gradient. Canopy height metrics were computed and AGB was inferred from empirical models. The root mean square error (RMSE) and RMSE uncertainty associated with the distribution of inferred AGB within each AGB interval across the gradient was examined. Simulation results of the bright daylight and low vegetation reflectivity conditions for collecting photon counting LiDAR with no topographic relief show that 1-2 photons are returned for 79%-88% of LiDAR shots. Signal photons account for approximately 67% of all LiDAR returns, while approximately 50% of shots result in 1 signal photon returned. The proportion of these signal photon returns do not differ significantly (p greater than 0.05) for AGB intervals greater than 20 Mg · ha(exp -1). The 50m link-scale approximates the finest horizontal resolution (length) at which photon counting LiDAR collection provides strong model

A PILOT DEEP SURVEY FOR X-RAY EMISSION FROM fuvAGB STARS

Energy Technology Data Exchange (ETDEWEB)

Sahai, R. [Jet Propulsion Laboratory, MS 183-900, California Institute of Technology, Pasadena, CA 91109 (United States); Sanz-Forcada, J.; Sánchez Contreras, C. [Astrobiology Center (CSIC-INTA), ESAC campus, E-28691 Villanueva de la Canada, Madrid (Spain); Stute, M. [Institute for Astronomy and Astrophysics, Eberhard Karls Universität Tübingen, Auf der Morgenstelle 10, D-72076, Tübingen (Germany)

2015-09-01

We report the results of a pilot survey for X-ray emission from a newly discovered class of AGB stars with far-ultraviolet excesses (fuvAGB stars) using XMM-Newton and Chandra. We detected X-ray emission in three of six fuvAGB stars observed—the X-ray fluxes are found to vary in a stochastic or quasi-periodic manner on roughly hour-long timescales, and simultaneous UV observations using the Optical Monitor on XMM for these sources show similar variations in the UV flux. These data, together with previous studies, show that X-ray emission is found only in fuvAGB stars. From modeling the spectra, we find that the observed X-ray luminosities are ∼(0.002–0.2) L{sub ⊙} and the X-ray-emitting plasma temperatures are ∼(35–160) × 10{sup 6} K. The high X-ray temperatures argue against the emission arising in stellar coronae, or directly in an accretion shock, unless it occurs on a WD companion. However, none of the detected objects is a known WD-symbiotic star, suggesting that if WD companions are present, they are relatively cool (<20,000 K). In addition, the high X-ray luminosities specifically argue against emission originating in the coronae of main-sequence companions. We discuss several models for the X-ray emission and its variability and find that the most likely scenario for the origin of the X-ray (and FUV) emission involves accretion activity around a companion star, with confinement by strong magnetic fields associated with the companion and/or an accretion disk around it.

ALMA reveals sunburn: CO dissociation around AGB stars in the globular cluster 47 Tucanae

Science.gov (United States)

McDonald, I.; Zijlstra, A. A.; Lagadec, E.; Sloan, G. C.; Boyer, M. L.; Matsuura, M.; Smith, R. J.; Smith, C. L.; Yates, J. A.; van Loon, J. Th.; Jones, O. C.; Ramstedt, S.; Avison, A.; Justtanont, K.; Olofsson, H.; Blommaert, J. A. D. L.; Goldman, S. R.; Groenewegen, M. A. T.

2015-11-01

Atacama Large Millimetre Array observations show a non-detection of carbon monoxide around the four most luminous asymptotic giant branch (AGB) stars in the globular cluster 47 Tucanae. Stellar evolution models and star counts show that the mass-loss rates from these stars should be ˜1.2-3.5 × 10-7 M⊙ yr-1. We would naïvely expect such stars to be detectable at this distance (4.5 kpc). By modelling the ultraviolet radiation field from post-AGB stars and white dwarfs in 47 Tuc, we conclude that CO should be dissociated abnormally close to the stars. We estimate that the CO envelopes will be truncated at a few hundred stellar radii from their host stars and that the line intensities are about two orders of magnitude below our current detection limits. The truncation of CO envelopes should be important for AGB stars in dense clusters. Observing the CO (3-2) and higher transitions and targeting stars far from the centres of clusters should result in the detections needed to measure the outflow velocities from these stars.

Prolonged Tp-e Interval, Tp-e/QT Ratio and Tp-e/QTc Ratio in Patients with Type 2 Diabetes Mellitus

Directory of Open Access Journals (Sweden)

Alptug Tokatli

2016-03-01

Full Text Available BackgroundType 2 diabetes mellitus (T2DM is associated with increased risk of malignant ventricular arrhythmias. Cardiac electrical inhomogeneity may be the leading cause of the increased arrhythmic risk in patients with T2DM. The peak and the end of the T wave (Tp-e interval and associated Tp-e/QT ratio are promising measures of ventricular repolarization indicating transmural dispersion of repolarization. The aim of this study was to assess ventricular repolarization in patients with T2DM by using Tp-e interval, Tp-e/QT ratio and Tp-e/corrected QT interval (QTc ratio.MethodsForty-three patients with T2DM and 43 healthy control subjects, matched by gender and age, were studied. All participants underwent electrocardiography (ECG recording. PR, RR and QT intervals represents the ECG intervals. These are not abbreviations. In all literature these ECG intervals are written like in this text. Tp-e intervals were measured from 12-lead ECG. Rate QTc was calculated by using the Bazett's formula. Tp-e/QT ratio and Tp-e/QTc ratio were also calculated.ResultsMean Tp-e interval was significantly prolonged in patients with T2DM compared to controls (79.4±10.3, 66.4±8.1 ms, respectively; P<0.001. We also found significantly higher values of Tp-e/QT ratio and Tp-e/QTc ratio in patients with diabetes than controls (0.21±0.03, 0.17±0.02 and 0.19±0.02, 0.16±0.02, respectively; P<0.001. There was no difference in terms of the other ECG parameters between the groups.ConclusionTp-e interval, Tp-e/QT ratio and Tp-e/QTc ratio were prolonged in patients with T2DM. We concluded that T2DM leads to augmentation of transmural dispersion of repolarization suggesting increased risk for ventricular arrhythmogenesis.

Si and C isotopic ratios in AGB stars: SiC grain data, models, and the galactic evolution of the Si Isotopes

NARCIS (Netherlands)

Zinner, E.; Nittler, L.R.; Gallino, R.; Karakas, A.I.; Lugaro, M.A.; Straniero, O.; Lattanzio, J.C.

2006-01-01

Presolar grains of the mainstream, Y and Z type are believed to have an origin in carbon stars. We compared the C and Si isotopic ratios of these grains [1] with the results of theoretical models for the envelope compositions of AGB stars. Two sets of models (FRANEC, Monash) use a range of stellar

The core mass growth and stellar lifetime of thermally pulsing asymptotic giant branch stars

International Nuclear Information System (INIS)

Kalirai, Jason S.; Tremblay, Pier-Emmanuel; Marigo, Paola

2014-01-01

We establish new constraints on the intermediate-mass range of the initial-final mass relation, and apply the results to study the evolution of stars on the thermally pulsing asymptotic giant branch (TP-AGB). These constraints derive from newly discovered (bright) white dwarfs in the nearby Hyades and Praesepe star clusters, including a total of 18 high signal-to-noise ratio measurements with progenitor masses of M initial = 2.8-3.8 M ☉ . We also include a new analysis of existing white dwarfs in the older NGC 6819 and NGC 7789 star clusters, M initial = 1.6 and 2.0 M ☉ . Over this range of initial masses, stellar evolutionary models for metallicity Z initial = 0.02 predict the maximum growth of the core of TP-AGB stars. By comparing the newly measured remnant masses to the robust prediction of the core mass at the first thermal pulse on the AGB (i.e., from stellar interior models), we establish several findings. First, we show that the stellar core mass on the AGB grows rapidly from 10% to 30% for stars with M initial = 1.6 to 2.0 M ☉ . At larger masses, the core-mass growth decreases steadily to ∼10% at M initial = 3.4 M ☉ , after which there is a small hint of a upturn out to M initial = 3.8 M ☉ . These observations are in excellent agreement with predictions from the latest TP-AGB evolutionary models in Marigo et al. We also compare to models with varying efficiencies of the third dredge-up and mass loss, and demonstrate that the process governing the growth of the core is largely the stellar wind, while the third dredge-up plays a secondary, but non-negligible role. Based on the new white dwarf measurements, we perform an exploratory calibration of the most popular mass-loss prescriptions in the literature, as well as of the third dredge-up efficiency as a function of the stellar mass. Finally, we estimate the lifetime and the integrated luminosity of stars on the TP-AGB to peak at t ∼ 3 Myr and E = 1.2 × 10 10 L ☉ yr for M initial ∼ 2 M �

The core mass growth and stellar lifetime of thermally pulsing asymptotic giant branch stars

Energy Technology Data Exchange (ETDEWEB)

Kalirai, Jason S.; Tremblay, Pier-Emmanuel [Space Telescope Science Institute, 3700 San Martin Drive, Baltimore, MD 21218 (United States); Marigo, Paola, E-mail: jkalirai@stsci.edu, E-mail: paola.marigo@unipd.it, E-mail: ptremblay@lsw.uni-heidelberg.de [Department of Physics and Astronomy, University of Padova, Vicolo dell' Osservatorio 3, I-35122 Padova (Italy)

2014-02-10

We establish new constraints on the intermediate-mass range of the initial-final mass relation, and apply the results to study the evolution of stars on the thermally pulsing asymptotic giant branch (TP-AGB). These constraints derive from newly discovered (bright) white dwarfs in the nearby Hyades and Praesepe star clusters, including a total of 18 high signal-to-noise ratio measurements with progenitor masses of M {sub initial} = 2.8-3.8 M {sub ☉}. We also include a new analysis of existing white dwarfs in the older NGC 6819 and NGC 7789 star clusters, M {sub initial} = 1.6 and 2.0 M {sub ☉}. Over this range of initial masses, stellar evolutionary models for metallicity Z {sub initial} = 0.02 predict the maximum growth of the core of TP-AGB stars. By comparing the newly measured remnant masses to the robust prediction of the core mass at the first thermal pulse on the AGB (i.e., from stellar interior models), we establish several findings. First, we show that the stellar core mass on the AGB grows rapidly from 10% to 30% for stars with M {sub initial} = 1.6 to 2.0 M {sub ☉}. At larger masses, the core-mass growth decreases steadily to ∼10% at M {sub initial} = 3.4 M {sub ☉}, after which there is a small hint of a upturn out to M {sub initial} = 3.8 M {sub ☉}. These observations are in excellent agreement with predictions from the latest TP-AGB evolutionary models in Marigo et al. We also compare to models with varying efficiencies of the third dredge-up and mass loss, and demonstrate that the process governing the growth of the core is largely the stellar wind, while the third dredge-up plays a secondary, but non-negligible role. Based on the new white dwarf measurements, we perform an exploratory calibration of the most popular mass-loss prescriptions in the literature, as well as of the third dredge-up efficiency as a function of the stellar mass. Finally, we estimate the lifetime and the integrated luminosity of stars on the TP-AGB to peak at t �

AGB stars as tracers to IC 1613 evolution.

Science.gov (United States)

Hashemi, S. A.; Javadi, A.; van Loon, J. Th.

We are going to apply AGB stars to find star formation history for IC 1613 galaxy; this a new and simple method that works well for nearby galaxies. IC 1613 is a Local Group dwarf irregular galaxy that is located at distance of 750 kpc, a gas rich and isolated dwarf galaxy that has a low foreground extinction. We use the long period variable stars (LPVs) that represent the very final stage of evolution of stars with low and intermediate mass at the AGB phase and are very luminous and cool so that they emit maximum brightness in near-infrared bands. Thus near-infrared photometry with using stellar evolutionary models help us to convert brightness to birth mass and age and from this drive star formation history of the galaxy. We will use the luminosity distribution of the LPVs to reconstruct the star formation history-a method we have successfully applied in other Local Group galaxies. Our analysis shows that the IC 1613 has had a nearly constant star formation rate, without any dominant star formation episode.

CONSTRAINTS OF THE PHYSICS OF LOW-MASS AGB STARS FROM CH AND CEMP STARS

Energy Technology Data Exchange (ETDEWEB)

Cristallo, S.; Piersanti, L.; Gobrecht, D. [INAF—Osservatorio Astronomico di Teramo, I-64100 (Italy); Karinkuzhi, D.; Goswami, A. [Indian Institute of Astrophysics, Koramangala, Bangalore 560034 (India)

2016-12-20

We analyze a set of published elemental abundances from a sample of CH stars which are based on high resolution spectral analysis of ELODIE and SUBARU/HDS spectra. All the elemental abundances were derived from local thermodynamic equilibrium analysis using model atmospheres, and thus they represent the largest homogeneous abundance data available for CH stars to date. For this reason, we can use the set to constrain the physics and the nucleosynthesis occurring in low mass asymptotic giant branch (AGB) s.tars. CH stars have been polluted in the past from an already extinct AGB companion and thus show s-process enriched surfaces. We discuss the effects induced on the surface AGB s-process distributions by different prescriptions for convection and rotation. Our reference theoretical FRUITY set fits only part of the observations. Moreover, the s-process observational spread for a fixed metallicity cannot be reproduced. At [Fe/H] > −1, a good fit is found when rotation and a different treatment of the inner border of the convective envelope are simultaneously taken into account. In order to increase the statistics at low metallicities, we include in our analysis a selected number of CEMP stars and, therefore, we compute additional AGB models down to [Fe/H] = −2.85. Our theoretical models are unable to attain the large [hs/ls] ratios characterizing the surfaces of those objects. We speculate on the reasons for such a discrepancy, discussing the possibility that the observed distribution is a result of a proton mixing episode leading to a very high neutron density (the so-called i-process).

Stellar Evolution with Rotation: Mixing Processes in AGB Stars

Science.gov (United States)

Driebe, T.; Blöcker, T.

We included diffusive angular momentum transport and rotationally induced mixing processes in our stellar evolution code and studied the influence of rotation on the evolution of intermediate mass stars (M*=2dots6 Msolar) towards and along the asymptotic giant branch (AGB). The calculations start in the fully convective pre-main sequence phase and the initial angular momentu m was adjusted such that on the zero-age main sequence vrot=200 km/ s is achieved. The diffusion coefficients for the five rotational instabilities considered (dynamical shear, secular shear, Eddington-Sweet (ES) circulation, Solberg-Høiland-instability and Goldreich-Schubert-Fricke (GSF) instability) were adopted from Heger et al. (2000, ApJ 528, 368). Mixing efficiency and sensitivity of these processes against molecular weight gradients have been determined by calibration of the main sequence width. In this study we focus on the abundance evolution of carbon. On the one hand, the surface abundance ratios of 12C/13C a nd 12C/16O at the base of the AGB were found to be ≈ 7dots 10 and ≈ 0.1, resp., being a factor of two lower than in non-rotating models. This results from the slow but continuously operating rotationally induced mixing due to the ES-circulation and the GSF-instability during the long main sequence phase. On the other hand, 13C serves as neutron source for interior s-process nucleosynthesis in AGB stars vi a 13C(α,n)16O. Herwig et al. (1997, A&A 324, L81) found that a 13C pocket is forme d in the intershell region of 3 Msolar AGB star if diffusive overshoot is considered. Our calculations show, that mixing processes due to rotation open an alternative channel for the formation of a 13C pocket as found by Langer et al. (1999, A&A 346, L37). Again, ES-circulation and GSF-instability are the predominant rotational mixing processes.

Evaluation of Tp-E Interval and Tp-E/QT Ratio in Patients with Aortic Stenosis.

Science.gov (United States)

Yayla, Çağrı; Bilgin, Murat; Akboğa, Mehmet Kadri; Gayretli Yayla, Kadriye; Canpolat, Uğur; Dinç Asarcikli, Lale; Doğan, Mehmet; Turak, Osman; Çay, Serkan; Özeke, Özcan; Akyel, Ahmet; Yeter, Ekrem; Aydoğdu, Sinan

2016-05-01

The risk of syncope and sudden cardiac death due to ventricular arrhythmias increased in patients with aortic stenosis (AS). Recently, it was shown that Tp-e interval, Tp-e/QT, and Tp-e/QTc ratio can be novel indicators for prediction of ventricular arrhythmias and mortality. We aimed to investigate the association between AS and ventricular repolarization using Tp-e interval and Tp-e/QT ratio. Totally, 105 patients with AS and 60 control subjects were enrolled to this study. The severity of AS was defined by transthoracic echocardiographic examination. Tp-e interval, Tp-e/QT, and Tp-e/QTc ratios were measured from the 12-lead electrocardiogram. Tp-e interval, Tp-e/QT, and Tp-e/QTc ratios were significantly increased in parallel to the severity of AS (P ratio had significant positive correlation with mean aortic gradient (r = 0.192, P = 0.049). In multivariate logistic regression analysis, Tp-e/QTc ratio and left ventricular mass were found to be independent predictors of severe AS (P = 0.03 and P = 0.04, respectively). Our study showed that Tp-e interval, Tp-e/QT, and Tp-e/QTc ratios were increased in patients with severe AS. Tp-e/QTc ratio and left ventricular mass were found as independent predictors of severe AS. © 2015 Wiley Periodicals, Inc.

Modelling the carbon AGB star R Sculptoris. Constraining the dust properties in the detached shell based on far-infrared and sub-millimeter observations

Science.gov (United States)

Brunner, M.; Maercker, M.; Mecina, M.; Khouri, T.; Kerschbaum, F.

2018-06-01

Context. On the asymptotic giant branch (AGB), Sun-like stars lose a large portion of their mass in an intensive wind and enrich the surrounding interstellar medium with nuclear processed stellar material in the form of molecular gas and dust. For a number of carbon-rich AGB stars, thin detached shells of gas and dust have been observed. These shells are formed during brief periods of increased mass loss and expansion velocity during a thermal pulse, and open up the possibility to study the mass-loss history of thermally pulsing AGB stars. Aims: We study the properties of dust grains in the detached shell around the carbon AGB star R Scl and aim to quantify the influence of the dust grain properties on the shape of the spectral energy distribution (SED) and the derived dust shell mass. Methods: We modelled the SED of the circumstellar dust emission and compared the models to observations, including new observations of Herschel/PACS and SPIRE (infrared) and APEX/LABOCA (sub-millimeter). We derived present-day mass-loss rates and detached shell masses for a variation of dust grain properties (opacities, chemical composition, grain size, and grain geometry) to quantify the influence of changing dust properties to the derived shell mass. Results: The best-fitting mass-loss parameters are a present-day dust mass-loss rate of 2 × 10-10 M⊙ yr-1 and a detached shell dust mass of (2.9 ± 0.3) × 10-5 M⊙. Compared to similar studies, the uncertainty on the dust mass is reduced by a factor of 4. We find that the size of the grains dominates the shape of the SED, while the estimated dust shell mass is most strongly affected by the geometry of the dust grains. Additionally, we find a significant sub-millimeter excess that cannot be reproduced by any of the models, but is most likely not of thermal origin. Herschel is an ESA space observatory with science instruments provided by European-led Principal Investigator consortia and with important participation from NASA.

细粒棘球绦虫AgB8/1-AgB8/2重组嵌合抗原表达系统的构建%Establishment of Echinococcus granulosus AgB8/1-AgB8/2 chimeric recombinant protein expression system

Institute of Scientific and Technical Information of China (English)

古力帕丽·麦曼提依明; 马海梅; 吾拉木·马木提; 陈洁; 陈璐; 丁剑冰; 马秀敏; 温浩

2011-01-01

目的 构建pET32a-AgB8/1-AgB8/2原核表达载体,并对其重组蛋白进行原核细胞表达.方法 从细粒棘球绦虫原头蚴中提取总RNA,反转录生成cDNA,以此cDNA为模板,用基因特异性引物分别扩增EgAgB8/1和EgAgB8/2基因编码其分泌型多肽的片段,经测序后,以此两条基因片段为依据,人工合成EgAgB8/1-EgAgB8/2嵌合抗原编码核酸序列,将其克隆至pUCm-T载体,测序鉴定其正确性.通过对pUCm-T/AgB8/1-AgB8/2重组质粒进行双酶切,将获得的AgB8/1-AgB8/2嵌合抗原编码核酸序列用定向克隆技术克隆至原核表达质粒pET32a上,测序鉴定插入片段正确后,转化至E.coli BL21(DE3)Lys S,IPTG初步诱导表达pET32a-AgB8/1-AgB8/2重组嵌合蛋白.用SDS-PAGE电泳分析鉴定重组蛋白的表达水平.结果 测序表明,AgB8/1-AgB8/2嵌合抗原编码核酸序列正方向插入至pET32a质粒.SDS-PAGE电泳分析显示,IPTG诱导后重组嵌合蛋白得到成功表达,在相对分子量约38 kD处有表达条带.结论 成功构建了pET32a-AgB8/1-AgB8/2原核表达质粒,并初步诱导表达出AgB8/1-AgB8/2嵌合重组蛋白,为进一步研究其免疫学特性奠定了基础.%In order to construct the pET32a-AgB8/1-AgB8/2 chimeric antigen prokaryotic expression recombinant plasmid and the expression of its recombinant protein, the total RNA was extracted from protoscoleces of Echinococcus granulosus,and reverse transcribed into cDNA, the cDNA encoding mature form of EgAgB8/land EgAgB8/2 antigen were amplified by PCR using gene specific primers.Based on the both gene fragments, a nucleotide sequence encoding EgAgB8/1-EgAgB8/2 chimeric antigen were artificially synthesized after sequence confirmation.The synthesized nucleotide sequence encoding EgAgB8/1-EgAgB8/2 chimeric antigen were conformed by sequencing after cloning into pUCm-T vector, then the target sequence was directionally ligated into pET32a plasmid after double digestion with restriction enzymes for prokaryotic

New observations and models of circumstellar CO line emission of AGB stars in the Herschel SUCCESS programme

Science.gov (United States)

Danilovich, T.; Teyssier, D.; Justtanont, K.; Olofsson, H.; Cerrigone, L.; Bujarrabal, V.; Alcolea, J.; Cernicharo, J.; Castro-Carrizo, A.; García-Lario, P.; Marston, A.

2015-09-01

Context. Asymptotic giant branch (AGB) stars are in one of the latest evolutionary stages of low to intermediate-mass stars. Their vigorous mass loss has a significant effect on the stellar evolution, and is a significant source of heavy elements and dust grains for the interstellar medium. The mass-loss rate can be well traced by carbon monoxide (CO) line emission. Aims: We present new Herschel/HIFI and IRAM 30 m telescope CO line data for a sample of 53 galactic AGB stars. The lines cover a fairly large range of excitation energy from the J = 1 → 0 line to the J = 9 → 8 line, and even the J = 14 → 13 line in a few cases. We perform radiative transfer modelling for 38 of these sources to estimate their mass-loss rates. Methods: We used a radiative transfer code based on the Monte Carlo method to model the CO line emission. We assume spherically symmetric circumstellar envelopes that are formed by a constant mass-loss rate through a smoothly accelerating wind. Results: We find models that are consistent across a broad range of CO lines for most of the stars in our sample, i.e., a large number of the circumstellar envelopes can be described with a constant mass-loss rate. We also find that an accelerating wind is required to fit, in particular, the higher-J lines and that a velocity law will have a significant effect on the model line intensities. The results cover a wide range of mass-loss rates (~10-8 to 2 × 10-5 M⊙ yr-1) and gas expansion velocities (2 to 21.5 km s-1) , and include M-, S-, and C-type AGB stars. Our results generally agree with those of earlier studies, although we tend to find slightly lower mass-loss rates by about 40%, on average. We also present "bonus" lines detected during our CO observations. Herschel is an ESA space observatory with science instruments provided by European-led Principal Investigator consortia and with important participation from NASA.Based on observations carried out with the IRAM 30 m Telescope. IRAM is

Estimation of aboveground biomass in Mediterranean forests by statistical modelling of ASTER fraction images

Science.gov (United States)

Fernández-Manso, O.; Fernández-Manso, A.; Quintano, C.

2014-09-01

Aboveground biomass (AGB) estimation from optical satellite data is usually based on regression models of original or synthetic bands. To overcome the poor relation between AGB and spectral bands due to mixed-pixels when a medium spatial resolution sensor is considered, we propose to base the AGB estimation on fraction images from Linear Spectral Mixture Analysis (LSMA). Our study area is a managed Mediterranean pine woodland (Pinus pinaster Ait.) in central Spain. A total of 1033 circular field plots were used to estimate AGB from Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) optical data. We applied Pearson correlation statistics and stepwise multiple regression to identify suitable predictors from the set of variables of original bands, fraction imagery, Normalized Difference Vegetation Index and Tasselled Cap components. Four linear models and one nonlinear model were tested. A linear combination of ASTER band 2 (red, 0.630-0.690 μm), band 8 (short wave infrared 5, 2.295-2.365 μm) and green vegetation fraction (from LSMA) was the best AGB predictor (Radj2=0.632, the root-mean-squared error of estimated AGB was 13.3 Mg ha-1 (or 37.7%), resulting from cross-validation), rather than other combinations of the above cited independent variables. Results indicated that using ASTER fraction images in regression models improves the AGB estimation in Mediterranean pine forests. The spatial distribution of the estimated AGB, based on a multiple linear regression model, may be used as baseline information for forest managers in future studies, such as quantifying the regional carbon budget, fuel accumulation or monitoring of management practices.

Expression signature based on TP53 target genes doesn't predict response to TP53-MDM2 inhibitor in wild type TP53 tumors

OpenAIRE

Sonkin, Dmitriy

2015-01-01

eLife digest Damaged cells in the human body can develop into tumors if left unchecked. TP53 (also called p53) is a protein that normally helps to repair or eliminate these damaged cells and prevent tumors from forming. About half of all cancerous tumors have mutations that prevent TP53 from working. In tumors with normal TP53 (called TP53 wild type tumors), another protein that acts to keep TP53 in check is often overly active. This overactive protein (called MDM2) prevents TP53 from suppres...

AGB mass-loss variations: What can we learn from (sub)millimetre observations?

NARCIS (Netherlands)

Dehaes, S.; Groenewegen, M.A.T.; Decin, L.; Hony, S.; Raskin, G.; Blommaert, J.A.D.L.

2008-01-01

It is generally acknowledged that the mass loss of Asymptotic Giant Branch (AGB) stars undergoes variations on different time scales. We address here the question of the influence of these variations on the spectral energy distribution (SED) of these sources. We therefore constructed models for the

S-process nucleosynthesis in low mass AGB Stars: do we really need an improved determination of the 13C(α, n)16O reaction rate?

International Nuclear Information System (INIS)

Cristallo, S.; Straniero, O.; Gallino, R.

2005-01-01

Thermally pulsing Asymptotic Giant Branch stars are responsible for the nucleosynthesis of the main component of the cosmic s-elements. The most important neutron source is the 13 C(α, n) 16 O reaction. Owing to the presence of a subthreshold resonance, the low energy extrapolation is a rather complex task. The rate quoted in the literature differ up to a factor of 4 at typical stellar energies. The latest improvements in computer power allows us to calculate the evolution of TP-AGB stars coupled with a full nuclear network, extending from hydrogen to lead. Here we discuss the effects of the variation of the 13 C(α, n) 16 O rate on the predicted neutron capture nucleosynthesis

Tp-e interval and Tp-e/QT ratio in patients with celiac disease.

Science.gov (United States)

Demirtaş, K; Yayla, Ç; Yüksel, M; Açar, B; Ünal, S; Ertem, A G; Kaplan, M; Akpinar, M Y; Kiliç, Z M Y; Kayaçetin, E

2017-11-01

Celiac disease is a chronic immune-mediated disease of the small intestine. It has been known that dilated cardiomyopathy and ischemic coronary artery disease have become more frequent in patients with celiac disease. The aim of the study was to assess Tp-e interval and Tp-e/QT ratio in patients with celiac disease. This study was conducted at a single center in collaboration with gastroenterology and cardiology clinics. Between January 2014 and June 2015, a total of 76 consecutive patients were enrolled (38 patients with celiac disease and 38 control subjects). Tp-e interval, Tp-e/QT and Tp-e/QTc ratio were measured from the 12-lead electrocardiogram. Tp-e interval (64.2±11.0 vs. 44.5±6.0; pceliac disease than control subjects. There was a significant positive correlation between Tp-e/QTc ratio and disease duration in patients with celiac disease (r=0.480, p=0.003) and also there was a significant positive correlation between Tp-e/QTc ratio and erythrocyte sedimentation rate (r=0.434, pceliac disease. Whether these changes increase the risk of ventricular arrhythmia deserve further studies. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Evaluation of Tp-Te Interval and Tp-Te/QT Ratio in Patients with Coronary Slow Flow Tp-Te/QT Ratio and Coronary Slow Flow.

Science.gov (United States)

Tenekecioglu, Erhan; Karaagac, Kemal; Yontar, Osman Can; Agca, Fahriye Vatansever; Ozluk, Ozlem Arican; Tutuncu, Ahmet; Arslan, Burhan; Yilmaz, Mustafa

2015-06-01

Coronary slow flow (CSF) phenomenon is described by angiographically normal coronary arteries with delayed opacification of the distal vasculature. Several studies have suggested that the interval from the peak to the end of the electrocardiographic T wave (Tp-Te) may correspond to the transmural dispersion of the repolarization and that increased Tp-Te interval and Tp-Te/QT ratio are associated with malignant ventricular arrhythmias. The aim of this study was to evaluate the ventricular repolarization by using Tp-Te interval and Tp-Te/QT ratio in patients with CSF. This study included 50 CSF patients (40 male, mean age 48.6±12.5 years) and 40 control individuals (23 male, mean age 47.8±12.5 years). Tp-Te interval and Tp-Te/QT ratio were measured from the 12-lead electrocardiogram. These parameters were compared in groups. Baseline characteristics of the study groups were comparable. In electrocardiographic parameters analysis, QT and corrected QT were similar in CSF patients compared to the controls (357±35.2 vs 362±38.0 milliseconds and 419±25.8 vs 430±44.2 milliseconds, all p value >0.05). Tp-Te interval, Tp-Te/QT and Tp-Te/QTc ratio were significantly higher in CSF patients (85±13.7 vs 74±9.9 milliseconds and 0.24±0.03 vs 0.20±0.02 and 0.20±0.03 vs 0.17±0.02 all p value ratio are prolonged in patients with CSF.

The Case of the Missing Cyanogen-rich AGB Stars in Galactic Globular Clusters

DEFF Research Database (Denmark)

Campbell, S. W.; Yong, D.; Wylie-de Boer, E. C.

2012-01-01

The handful of available observations of AGB stars in Galactic Globular Clusters suggest that the GC AGB populations are dominated by cyanogen-weak stars (eg. Norris et al. 1981; Sneden et al. 2000). This contrasts strongly with the distributions on the RGB (and other) populations, which generall...

On the introduction of {sup 17}O+p reaction rates evaluated through the THM in AGB nucleosynthesis calculations

Energy Technology Data Exchange (ETDEWEB)

Palmerini, S.; Sergi, M. L.; La Cognata, M.; Pizzone, R. G. [I.N.F.N. Laboratori Nazionali del Sud, via Santa Sofia 62, Catania (Italy); Lamia, L.; Spitaleri, C. [Dipartimento di Fisica e Astronomia, Universitá degli Studi di Catania (Italy)

2014-05-09

The rates for the {sup 17}O(p,αα{sup 14}N, {sup 17}O(p,α){sup 18}F and {sup 18}O(p,α){sup 15}N reactions deduced trough the Trojan Horse Method (THM) have been introduced into a state-of-the-art asymptotic giant branch (AGB) models for proton-capture nucleosynthesis and cool bottom process. The predicted abundances have been compared with isotopic compositions provided by geochemical analysis of presolar grains. As a result, an improved agreement is found between the models and the isotopic mix of oxide grains of AGB origins, whose composition is the signature of low-temperature proton-capture nucleosynthesis.

First evidence of multiple populations along the AGB from Strömgren photometry

Science.gov (United States)

Gruyters, Pieter; Casagrande, Luca; Milone, Antonino P.; Hodgkin, Simon T.; Serenelli, Aldo; Feltzing, Sofia

2017-07-01

Spectroscopic studies have demonstrated that nearly all Galactic globular clusters (GCs) harbour multiple stellar populations with different chemical compositions. Moreover, colour-magnitude diagrams based exclusively on Strömgrem photometry have allowed us to identify and characterise multiple populations along the RGB of a large number of clusters. In this paper we show for the first time that Strömgren photometry is also very efficient at identifying multiple populations along the AGB, and demonstrate that the AGB of M 3, M 92, NGC 362, NGC 1851, and NGC 6752 are not consistent with a single stellar population. We also provide a catalogue of RGB and AGB stars photometrically identified in these clusters for further spectroscopic follow-up studies. We combined photometry and elemental abundances from the literature for RGB and AGB stars in NGC 6752 where the presence of multiple populations along the AGB has been widely debated. We find that, while the MS, SGB, and RGB host three stellar populations with different helium and light element abundances, only two populations of AGB stars are present in the cluster. These results are consistent with standard evolutionary theory. Based on observations made with the Isaac Newton Telescope operated on the island of La Palma by the Isaac Newton Group in the Spanish Observatorio del Roque de los Muchachos of the Instituto de Astrofísica de Canarias.Full Tables B.1 and B.2 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/603/A37

RITA displays anti-tumor activity in medulloblastomas independent of TP53 status.

Science.gov (United States)

Gottlieb, Aline; Althoff, Kristina; Grunewald, Laura; Thor, Theresa; Odersky, Andrea; Schulte, Marc; Deubzer, Hedwig E; Heukamp, Lukas; Eggert, Angelika; Schramm, Alexander; Schulte, Johannes H; Künkele, Annette

2017-04-25

Current therapy of medulloblastoma, the most common malignant brain tumor of childhood, achieves 40-70% survival. Secondary chemotherapy resistance contributes to treatment failure, where TP53 pathway dysfunction plays a key role. MDM2 interaction with TP53 leads to its degradation. Reactivating TP53 functionality using small-molecule inhibitors, such as RITA, to disrupt TP53-MDM2 binding may have therapeutic potential. We show here that RITA decreased viability of all 4 analyzed medulloblastoma cell lines, regardless of TP53 functional status. The decrease in cell viability was accompanied in 3 of the 4 medulloblastoma cell lines by accumulation of TP53 protein in the cells and increased CDKN1A expression. RITA treatment in mouse models inhibited medulloblastoma xenograft tumor growth. These data demonstrate that RITA treatment reduces medulloblastoma cell viability in both in vitro and in vivo models, and acts independently of cellular TP53 status, identifying RITA as a potential therapeutic agent to treat medulloblastoma.

Modelling above Ground Biomass in Tanzanian Miombo Woodlands Using TanDEM-X WorldDEM and Field Data

Directory of Open Access Journals (Sweden)

Stefano Puliti

2017-09-01

Full Text Available The use of Interferometric Synthetic Aperture Radar (InSAR data has great potential for monitoring large scale forest above ground biomass (AGB in the tropics due to the increased ability to retrieve 3D information even under cloud cover. To date; results in tropical forests have been inconsistent and further knowledge on the accuracy of models linking AGB and InSAR height data is crucial for the development of large scale forest monitoring programs. This study provides an example of the use of TanDEM-X WorldDEM data to model AGB in Tanzanian woodlands. The primary objective was to assess the accuracy of a model linking AGB with InSAR height from WorldDEM after the subtraction of ground heights. The secondary objective was to assess the possibility of obtaining InSAR height for field plots when the terrain heights were derived from global navigation satellite systems (GNSS; i.e., as an alternative to using airborne laser scanning (ALS. The results revealed that the AGB model using InSAR height had a predictive accuracy of R M S E = 24.1 t·ha−1; or 38.8% of the mean AGB when terrain heights were derived from ALS. The results were similar when using terrain heights from GNSS. The accuracy of the predicted AGB was improved when compared to a previous study using TanDEM-X for a sub-area of the area of interest and was of similar magnitude to what was achieved in the same sub-area using ALS data. Overall; this study sheds new light on the opportunities that arise from the use of InSAR data for large scale AGB modelling in tropical woodlands.

Evaluation of Tp-e interval and Tp-e/QT ratio in patients with ankylosing spondylitis.

Science.gov (United States)

Acar, Gurkan; Yorgun, Hikmet; Inci, Mehmet Fatih; Akkoyun, Murat; Bakan, Betul; Nacar, Alper Bugra; Dirnak, Imran; Cetin, Gozde Yildirim; Bozoglan, Orhan

2014-03-01

Ankylosing spondylitis (AS) is a chronic multi-systemic inflammatory rheumatic disorder. Several studies have suggested that the interval from the peak to the end of the electrocardiographic T wave (Tp-e) may correspond to the transmural dispersion of repolarization and that increased Tp-e interval and Tp-e/QT ratio are associated with malignant ventricular arrhythmias. The aim of this study was to evaluate ventricular repolarization by using Tp-e interval and Tp-e/QT ratio in patients with AS, and to assess the relation with inflammation. Sixty-two patients with AS and 50 controls were included. Tp-e interval and Tp-e/QT ratio were measured from a 12-lead electrocardiogram, and the Tp-e interval corrected for heart rate. The plasma level of high sensitive C-reactive protein (hsCRP) was measured. These parameters were compared between groups. In electrocardiographic parameters analysis, QT dispersion (QTd) and corrected QTd were significantly increased in AS patients compared to the controls (31.7 ± 9.6 vs 28.2 ± 7.4 and 35.8 ± 11.5 vs 30.6 ± 7.9 ms, P = 0.03 and P = 0.007, respectively). cTp-e interval and Tp-e/QT ratio were also significantly higher in AS patients (92.1 ± 10.2 vs 75.8 ± 8.4 and 0.22 ± 0.02 vs 0.19 ± 0.02 ms, all P values ratio were significantly correlated with hsCRP (r = 0.63, P ratio were increased in AS patients. These electrocardiographic ventricular repolarization indexes were significantly correlated with the plasma level of hsCRP.

Modelling above Ground Biomass of Mangrove Forest Using SENTINEL-1 Imagery

Science.gov (United States)

Labadisos Argamosa, Reginald Jay; Conferido Blanco, Ariel; Balidoy Baloloy, Alvin; Gumbao Candido, Christian; Lovern Caboboy Dumalag, John Bart; Carandang Dimapilis, Lee, , Lady; Camero Paringit, Enrico

2018-04-01

Many studies have been conducted in the estimation of forest above ground biomass (AGB) using features from synthetic aperture radar (SAR). Specifically, L-band ALOS/PALSAR (wavelength 23 cm) data is often used. However, few studies have been made on the use of shorter wavelengths (e.g., C-band, 3.75 cm to 7.5 cm) for forest mapping especially in tropical forests since higher attenuation is observed for volumetric objects where energy propagated is absorbed. This study aims to model AGB estimates of mangrove forest using information derived from Sentinel-1 C-band SAR data. Combinations of polarisations (VV, VH), its derivatives, grey level co-occurrence matrix (GLCM), and its principal components were used as features for modelling AGB. Five models were tested with varying combinations of features; a) sigma nought polarisations and its derivatives; b) GLCM textures; c) the first five principal components; d) combination of models a-c; and e) the identified important features by Random Forest variable importance algorithm. Random Forest was used as regressor to compute for the AGB estimates to avoid over fitting caused by the introduction of too many features in the model. Model e obtained the highest r2 of 0.79 and an RMSE of 0.44 Mg using only four features, namely, σ°VH GLCM variance, σ°VH GLCM contrast, PC1, and PC2. This study shows that Sentinel-1 C-band SAR data could be used to produce acceptable AGB estimates in mangrove forest to compensate for the unavailability of longer wavelength SAR.

The Audit Committee. AGB Effective Committee Series

Science.gov (United States)

Staisloff, Richard L.

2011-01-01

This publication is part of an Association of Governing Boards of Universities and Colleges (AGB) series devoted to strengthening the role of key standing committees of governing boards. While there is no optimum committee system for institutions of higher education, certain principles, practices, and procedures prevail. The best practices…

NEAR-INFRARED SPECTROSCOPY OF POST-AGB STARS

NARCIS (Netherlands)

OUDMAIJER, RD; WATERS, LBFM; VANDERVEEN, WECJ; GEBALLE, TR

The results of a medium resolution near-infrared spectral survey of 18 post-AGB candidate stars are presented. Most of the stars have near-infrared hydrogen lines in absorption, which is normal for their spectral types. Three stars, HD 101584, HD 179821 and HD 170756 have the CO first overtone bands

Cloning and sequencing of V genes from anti-osteosarcoma monoclonal antibodies TP-1 and TP-3: Location of lysine residues and implications for radiolabeling

International Nuclear Information System (INIS)

Olafsen, Tove; Bruland, Oeyvind S.; Zalutsky, Michael R.; Sandlie, Inger

1995-01-01

Monoclonal antibodies TP-1 and TP-3 are of potential utility for the radioimmunodiagnosis of osteosarcoma in both human and canine patients. The V genes of these antibodies were cloned and sequenced and to facilitate radiolabeling of these proteins, the location of the lysine residues within these sequences have been determined. The V-domains of TP-1 contain a total of 12 lysines, 10 in the framework region and 2 in the CDR region, while the V-domains of TP-3 contain a total of 14 lysines, 11 in the framework region and 3 in the CDR regions. Using space-filling models, the availability of each lysine residue for radiolabeling, and potential interference with antigen binding was predicted

Cloning and sequencing of V genes from anti-osteosarcoma monoclonal antibodies TP-1 and TP-3: Location of lysine residues and implications for radiolabeling

Energy Technology Data Exchange (ETDEWEB)

Olafsen, Tove; Bruland, Oeyvind S.; Zalutsky, Michael R.; Sandlie, Inger

1995-08-01

Monoclonal antibodies TP-1 and TP-3 are of potential utility for the radioimmunodiagnosis of osteosarcoma in both human and canine patients. The V genes of these antibodies were cloned and sequenced and to facilitate radiolabeling of these proteins, the location of the lysine residues within these sequences have been determined. The V-domains of TP-1 contain a total of 12 lysines, 10 in the framework region and 2 in the CDR region, while the V-domains of TP-3 contain a total of 14 lysines, 11 in the framework region and 3 in the CDR regions. Using space-filling models, the availability of each lysine residue for radiolabeling, and potential interference with antigen binding was predicted.

Short-lived Isotopes from a Close-by AGB Star Triggering the Protosolar Nebula

Science.gov (United States)

Gallino, R.; Busso, M.; Wasserburg, G. J.; Straniero, O.

The presence of short-lived isotopes in the early solar system, in particular 26Al, 41Ca, 60Fe, and 107Pd, point to a close-by and fresh nucleosynthesis source, possibly triggering the collapse of the protosolar nebula. We present the results of nucleosynthesis calculations based on an AGB polluting hypothesis. A general concordance of the predicted yields of the above radioactivities relative to 26Al can be obtained in the case of an intermediate mass AGB star with hot bottom burning in the envelope (thus producing 26Al), and mixing through a series of third dredge-up episodes a fraction of the C-rich and s-processed material from the He intershell with the extended envelope. Polution of the protosolar nebula with freshly synthesized material may derive from the efficient winds of the AGB star. In AGB stars, the s-process nucleosynthesis occurs both during the maximum phase of every thermal runaway, driven by the partial activation of the 22Ne(alpha,n)25Mg reaction, and in the interpulse phase, where the 13C nuclei are fully consumed in radiative conditions by the activation of the 13C(alpha,n)16O reaction. We have used different prescriptions for the amount of the 13C nuclei present in the intershell. A minimum amount of 13C is naturally expected in the ashes of H-shell burning. Possible formation of an extra "13C-pocket" derives from the injection of a small amount of protons from the envelope into the 12C-rich intershell during any third dredge-up episode, when the H-shell is inactivated. Prediction for other short-lived, 36Cl, 135Cs, and 205Pb, are given. General consequences for the pollution of the protosolar nebula with newly synthesized stable isotopes from the AGB winds are outlined. The origin of other detected short-lived nuclei, in particular 53Mn, 129I, and 182Hf, which cannot come from an AGB source, is analysed. The alternative trigger hypothesis by a close-by Supernova is discussed.

AGB nucleosynthesis in the Large Magellanic Cloud. Detailed abundance analysis of the RV Tauri star MACHO 47.2496.8

NARCIS (Netherlands)

Reyniers, M.; Abia, C.; van Winckel, H.; Lloyd Evans, T.; Decin, L.K.E.; Eriksson, K.; Pollard, K.R.

2007-01-01

Context: .Abundance analysis of post-AGB objects as probes of AGB nucleosynthesis. Aims: .A detailed photospheric abundance study is performed on the carbon-rich post-AGB candidate MACHO 47.2496.8 in the LMC. Methods: .High-resolution, high signal-to-noise ESO VLT-UVES spectra of MACHO 47.2496.8 are

Super-AGB Stars and their Role as Electron Capture Supernova Progenitors

Science.gov (United States)

Doherty, Carolyn L.; Gil-Pons, Pilar; Siess, Lionel; Lattanzio, John C.

2017-11-01

We review the lives, deaths and nucleosynthetic signatures of intermediate-mass stars in the range ≈6-12 M⊙, which form super-AGB stars near the end of their lives. The critical mass boundaries both between different types of massive white dwarfs (CO, CO-Ne, ONe), and between white dwarfs and supernovae, are examined along with the relative fraction of super-AGB stars that end life either as an ONe white dwarf or as a neutron star (or an ONeFe white dwarf), after undergoing an electron capture supernova event. The contribution of the other potential single-star channel to electron-capture supernovae, that of the failed massive stars, is also discussed. The factors that influence these different final fates and mass limits, such as composition, rotation, the efficiency of convection, the nuclear reaction rates, mass-loss rates, and third dredge-up efficiency, are described. We stress the importance of the binary evolution channels for producing electron-capture supernovae. Recent nucleosynthesis calculations and elemental yield results are discussed and a new set of s-process heavy element yields is presented. The contribution of super-AGB star nucleosynthesis is assessed within a Galactic perspective, and the (super-)AGB scenario is considered in the context of the multiple stellar populations seen in globular clusters. A brief summary of recent works on dust production is included. Last, we conclude with a discussion of the observational constraints and potential future advances for study into these stars on the low mass/high mass star boundary.

Evaluation of Tp-e interval and Tp-e/QT ratio in patients with non-dipper hypertension.

Science.gov (United States)

Demir, Mehmet; Uyan, Umut

2014-01-01

Non-dipper hypertension is associated with increased cardiovascular morbidity and mortality. Several studies have suggested that the interval from the peak to the end of the electrocardiographic T wave (Tp-e) may correspond to the transmural dispersion of repolarization and that increased Tp-e interval and Tp-e/QT ratio are associated with malignant ventricular arrhythmias. The aim of this study was to evaluate ventricular repolarization by using Tp-e interval and Tp-e/QT ratio in patients with non-dipper hypertension. This study included 80 hypertensive patients. Hypertensive patients were divided into two groups: 50 dipper patients (29 male, mean age 51.5 ± 8 years) and 30 non-dipper patients (17 male, mean age 50.6 ± 5.4 years). Tp-e interval and Tp-e/QT ratio were measured from the 12-lead electrocardiogram. These parameters were compared between groups. No statistically significant difference was found between two groups in terms of basic characteristics. In electrocardiographic parameters analysis, QT dispersion (QTd) and corrected QTd were significantly increased in non-dipper patients compared to the dippers (39.4 ± 11.5 versus 27.3 ± 7.5 ms and 37.5 ± 9.5 versus 29.2 ± 6.5 ms, p = 0.001 and p = 0.01, respectively). Tp-e interval and Tp-e/QT ratio were also significantly higher in non-dipper patients (97.5 ± 11.2 versus 84.2 ± 8.3 ms and 0.23 ± 0.02 versus 0.17 ± 0.02, all p value ratio are prolonged in patients with non-dipper hypertension.

On the formation of molecules and solid-state compounds from the AGB to the PN phases

Science.gov (United States)

García-Hernández, D. A.; Manchado, A.

2016-07-01

During the asymptoyic giant branch (AGB) phase, different elements are dredge- up to the stellar surface depending on progenitor mass and metallicity. When the mass loss increases at the end of the AGB, a circumstellar dust shell is formed, where different (C-rich or O-rich) molecules and solid-state compounds are formed. These are further processed in the transition phase between AGB stars and planetary nebulae (PNe) to create more complex organic molecules and inorganic solid-state compounds (e.g., polycyclic aromatic hydrocarbons, fullerenes, and graphene precursors in C-rich environments and oxides and crystalline silicates in O-rich ones). We present an observational review of the different molecules and solid-state materials that are formed from the AGB to the PN phases. We focus on the formation routes of complex fullerene (and fullerene-based) molecules as well as on the level of dust processing depending on metallicity.

TFP5/TP5 peptide provides neuroprotection in the MPTP model of Parkinson′s disease

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B K Binukumar

2016-01-01

Full Text Available Cyclin-dependent kinase 5 (Cdk5 is a member of the serine-threonine kinase family of cyclin-dependent kinases. Cdk5 is critical to normal mammalian nervous system development and plays important regulatory roles in multiple cellular functions. Recent evidence indicates that Cdk5 is inappropriately activated in several neurodegenerative conditions, including Parkinson′s disease (PD. PD is a chronic neurodegenerative disorder characterized by the loss of dopamine neurons in the substantia nigra, decreased striatal dopamine levels, and consequent extrapyramidal motor dysfunction. During neurotoxicity, p35 is cleaved to form p25. Binding of p25 with Cdk5 leads deregulation of Cdk5 resulting in number of neurodegenerative pathologies. To date, strategies to specifically inhibit Cdk5 hyperactivity have not been successful without affecting normal Cdk5 activity. Here we show that inhibition of p25/Cdk5 hyperactivation through TFP5/TP5, truncated 24-aa peptide derived from the Cdk5 activator p35 rescues nigrostriatal dopaminergic neurodegeneration induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP/MPP + in a mouse model of PD. TP5 peptide treatment also blocked dopamine depletion in the striatum and improved gait dysfunction after MPTP administration. The neuroprotective effect of TFP5/TP5 peptide is also associated with marked reduction in neuroinflammation and apoptosis. Here we show inhibition of Cdk5/p25-hyperactivation by TFP5/TP5 peptide, which identifies Cdk5/p25 as a potential therapeutic target to reduce neurodegeneration in PD.

Fischer-344 Tp53-knockout rats exhibit a high rate of bone and brain neoplasia with frequent metastasis

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Sarah A. Hansen

2016-10-01

Full Text Available Somatic mutations in the Tp53 tumor suppressor gene are the most commonly seen genetic alterations in cancer, and germline mutations in Tp53 predispose individuals to a variety of early-onset cancers. Development of appropriate translational animal models that carry mutations in Tp53 and recapitulate human disease are important for drug discovery, biomarker development and disease modeling. Current Tp53 mouse and rat models have significant phenotypic and genetic limitations, and often do not recapitulate certain aspects of human disease. We used a marker-assisted speed congenic approach to transfer a well-characterized Tp53-mutant allele from an outbred rat to the genetically inbred Fischer-344 (F344 rat to create the F344-Tp53tm1(EGFP-PacQly/Rrrc (F344-Tp53 strain. On the F344 genetic background, the tumor spectrum shifted, with the primary tumor types being osteosarcomas and meningeal sarcomas, compared to the hepatic hemangiosarcoma and lymphoma identified in the original outbred stock model. The Fischer model is more consistent with the early onset of bone and central nervous system sarcomas found in humans with germline Tp53 mutations. The frequency of osteosarcomas in F344-Tp53 homozygous and heterozygous animals was 57% and 36%, respectively. Tumors were highly representative of human disease radiographically and histologically, with tumors found primarily on long bones with frequent pulmonary metastases. Importantly, the rapid onset of osteosarcomas in this promising new model fills a current void in animal models that recapitulate human pediatric osteosarcomas and could facilitate studies to identify therapeutic targets.

H2O Formation in C-rich AGB Winds

NARCIS (Netherlands)

Lombaert, R.; Decin, L.; Royer, P.; de Koter, A.; Cox, N.L.J.; De Ridder, J.; Khouri, T.; Agúndez, M.; Blommaert, J.A.D.L.; Gernicharo, J.; González-Alfonso, E.; Groenewegen, M.A.T.; Kerschbaum, F.; Neufeld, D.; Vandenbussche, B.; Waelkens, C.

2015-01-01

The Herschel detection of warm H2O vapor emission from C-rich winds of AGB stars challenges the current understanding of circumstellar chemistry. Two mechanisms have been invoked to explain warm H2O formation. In the first, penetration of UV interstellar radiation through a clumpy circumstellar

Carbon stars in lmc clusters revisited

OpenAIRE

Marigo, Paola; Girardi, Leo Alberto; Chiosi, Cesare

1996-01-01

Examining the available data for AGB stars in the Large Magellanic Cloud (LMC) clusters, we address the question about the mass interval of low- and intermediate-mass stars which eventually evolve into carbon stars (C stars) during the TP-AGB phase. We combine the data compiled by Frogel, Mould & Blanco (1990) - near infrared photometry and spectral classification for luminous AGB stars in clusters - with the ages for individual clusters derived from independent methods. The resulting distrib...

Human TP53 polymorphism (rs1042522) modelled in mouse does not affect glucose metabolism and body composition.

Science.gov (United States)

Reiling, Erwin; Speksnijder, Ewoud N; Pronk, Amanda C M; van den Berg, Sjoerd A A; Neggers, Silvia J W; Rietbroek, Ilma; van Steeg, Harry; Dollé, Martijn E T

2014-02-13

Variation in TP53 has been associated with cancer. The pro-allele of a TP53 polymorphism in codon 72 (rs1042522) has been associated with longevity. Recently, we showed that the same allele might be involved in preservation of glucose metabolism, body composition and blood pressure during ageing. Here, we assessed glucose tolerance and body composition in mice carrying the human polymorphism. Our data do not support the previous findings in humans, suggesting that this polymorphism does not play a major role in development of glucose metabolism and body composition during ageing. Alternatively, the mouse model may not be suitable to validate these rs1042522-associated traits up to the age tested.

EVIDENCE OF AGB POLLUTION IN GALACTIC GLOBULAR CLUSTERS FROM THE Mg–Al ANTICORRELATIONS OBSERVED BY THE APOGEE SURVEY

Energy Technology Data Exchange (ETDEWEB)

Ventura, P.; Dell’Agli, F.; D’Antona, F.; Di Criscienzo, M.; Tailo, M. [INAF–Osservatorio Astronomico di Roma, via Frascati 33, I-00077 Monteporzio (Italy); García-Hernández, D. A.; Zamora, O. [Instituto de Astrofísica de Canarias (IAC), E-38205 La Laguna, Tenerife (Spain); Mészáros, Sz. [ELTE Gothard Astrophysical Observatory, H-9704 Szombat-hely, Szent Imre Herceg st. 112 (Hungary); Lucatello, S. [INAF–Osservatorio Astronomico di Padova, vicolo dell’Osservatorio 5, I-35122 Padova (Italy); Shetrone, M. [University of Texas at Austin, McDonald Observatory, Austin, TX (United States); Tang, Baitian [Departamento de Astronomía, Casilla, 160-C, Universidad de Concepción, Concepción (Chile)

2016-11-10

We study the formation of multiple populations in globular clusters (GCs), under the hypothesis that stars in the second generation formed from the winds of intermediate-mass stars, ejected during the asymptotic giant branch (AGB) phase, possibly diluted with pristine gas, sharing the same chemical composition of first-generation stars. To this aim, we use the recent Apache Point Observatory Galactic Evolution Experiment (APOGEE) data, which provide the surface chemistry of a large sample of giant stars, belonging to clusters that span a wide metallicity range. The APOGEE data set is particularly suitable to discriminate among the various pollution scenarios proposed so far, as it provides the surface abundances of Mg and Al, the two elements involved in a nuclear channel extremely sensitive to the temperature, hence to the metallicity of the polluters. The present analysis shows a remarkable agreement between the observations and the theoretical yields from massive AGB stars. In particular, the observed extension of the depletion of Mg and O and the increase in Al is well reproduced by the models and the trend with the metallicity is also fully accounted for. This study further supports the idea that AGB stars were the key players in the pollution of the intra-cluster medium, from which additional generations of stars formed in GCs.

Models for synthetic biology.

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Kaznessis, Yiannis N

2007-11-06

Synthetic biological engineering is emerging from biology as a distinct discipline based on quantification. The technologies propelling synthetic biology are not new, nor is the concept of designing novel biological molecules. What is new is the emphasis on system behavior. The objective is the design and construction of new biological devices and systems to deliver useful applications. Numerous synthetic gene circuits have been created in the past decade, including bistable switches, oscillators, and logic gates, and possible applications abound, including biofuels, detectors for biochemical and chemical weapons, disease diagnosis, and gene therapies. More than fifty years after the discovery of the molecular structure of DNA, molecular biology is mature enough for real quantification that is useful for biological engineering applications, similar to the revolution in modeling in chemistry in the 1950s. With the excitement that synthetic biology is generating, the engineering and biological science communities appear remarkably willing to cross disciplinary boundaries toward a common goal.

OPACOS: OVRO POST-AGB CO (1-0) EMISSION SURVEY. I. DATA AND DERIVED NEBULAR PARAMETERS

Energy Technology Data Exchange (ETDEWEB)

Sanchez Contreras, C. [Centro de Astrobiologia, INTA-CSIC, E-28691 Villanueva de la Canada, Madrid (Spain); Sahai, R. [Jet Propulsion Laboratory, MS 183-900, California Institute of Technology, Pasadena, CA 91109 (United States)

2012-11-15

We have performed interferometric observations of the {sup 12}CO (J = 1-0) emission in a sample of 27 objects spanning different evolutionary stages from the late asymptotic giant branch (late-AGB), through the post-AGB (pAGB) phase, and to the planetary nebula (PN) stage, but dominated by pAGB objects and young PNs ({>=}81%). In this paper (the first in a series) we present our maps and main nebular properties derived for the whole sample. Observations were performed with the Caltech Millimeter Array at the Owens Valley Radio Observatory. The angular resolution obtained in our survey ranges between 2.''3 and 10.''7. The {sup 13}CO and C{sup 18}O (J = 1-0) transitions as well as the 2.6 mm continuum emission have also been observed in several objects. The detection statistics in the {sup 12}CO, {sup 13}CO, C{sup 18}O transitions and 2.6 mm continuum are 89%, 83%, 0%, and 37%, respectively. We report first detections of {sup 12}CO (J = 1-0) emission in 13 targets and confirm emission from several previous marginal detections. The molecular envelope probed by {sup 12}CO (J = 1-0) emission is extended for 18 (out of 24) sources; envelope asymmetries and/or velocity gradients are found in most extended objects. Our data have been used to derive accurate target coordinates and systemic velocities and to characterize the envelope size, morphology, and kinematics. We also provide an estimate of the total molecular mass and the fraction of it contained in fast flows, lower limits to the linear momentum and to the isotopic {sup 12}C/{sup 13}C ratio, as well as the AGB mass-loss rate and timescale for sources with extended CO emission.

TP53 Mutations in Nonsmall Cell Lung Cancer

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Akira Mogi

2011-01-01

Full Text Available The tumor suppressor gene TP53 is frequently mutated in human cancers. Abnormality of the TP53 gene is one of the most significant events in lung cancers and plays an important role in the tumorigenesis of lung epithelial cells. Human lung cancers are classified into two major types, small cell lung cancer (SCLC and nonsmall cell lung cancer (NSCLC. The latter accounts for approximately 80% of all primary lung cancers, and the incidence of NSCLC is increasing yearly. Most clinical studies suggest that NSCLC with TP53 alterations carries a worse prognosis and may be relatively more resistant to chemotherapy and radiation. A deep understanding of the role of TP53 in lung carcinogenesis may lead to a more reasonably targeted clinical approach, which should be exploited to enhance the survival rates of patients with lung cancer. This paper will focus on the role of TP53 in the molecular pathogenesis, epidemiology, and therapeutic strategies of TP53 mutation in NSCLC.

Current Mysteries of AGB Stars

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Tout, Christopher A.

We pay tribute to the memory of Manuel Forestini by recalling his contributions to astronomy and in particular to our understanding of AGB stars. We critically examine the current status of this understanding amongst the community and deduce that major uncertainties arise in the physics of convection, any form of extra mixing beyond convection and the mass loss from the stellar surface. Coupled with these are numerical difficulties associated with the short and similar timescales for structural changes, nuclear burning and convective mixing. We hope that workshops such as this will promote familiarity amongst our diverse international community young and old and so promote effective dialogue that will ultimately lead to solutions to our problems along with the creation of new ones for the future!

Study of the Antimicrobial Activity of Tilapia Piscidin 3 (TP3) and TP4 and Their Effects on Immune Functions in Hybrid Tilapia (Oreochromis spp.)

Science.gov (United States)

Pan, Chieh-Yu; Tsai, Tsung-Yu; Su, Bor-Chyuan; Hui, Cho-Fat; Chen, Jyh-Yih

2017-01-01

To address the growing concern over antibiotic-resistant microbial infections in aquatic animals, we tested several promising alternative agents that have emerged as new drug candidates. Specifically, the tilapia piscidins are a group of peptides that possess antimicrobial, wound-healing, and antitumor functions. In this study, we focused on tilapia piscidin 3 (TP3) and TP4, which are peptides derived from Oreochromis niloticus, and investigated their inhibition of acute bacterial infections by infecting hybrid tilapia (Oreochromis spp.) with Vibrio vulnificus and evaluating the protective effects of pre-treating, co-treating, and post-treating fish with TP3 and TP4. In vivo experiments showed that co-treatment with V. vulnificus and TP3 (20 μg/fish) or TP4 (20 μg/fish) achieved 95.3% and 88.9% survival rates, respectively, after seven days. When we co-injected TP3 or TP4 and V. vulnificus into tilapia and then re-challenged the fish with V. vulnificus after 28 days, the tilapia exhibited survival rates of 35.6% and 42.2%, respectively. Pre-treatment with TP3 (30 μg/fish) or TP4 (20 μg/fish) for 30 minutes prior to V. vulnificus infection resulted in high survival rates of 28.9% and 37.8%, respectively, while post-treatment with TP3 (20 μg/fish or 30 μg/fish) or TP4 (20 μg/fish) 30 minutes after V. vulnificus infection yielded high survival rates of 33.3% and 48.9%. In summary, pre-treating, co-treating, and post-treating fish with TP3 or TP4 all effectively decreased the number of V. vulnificus bacteria and promoted significantly lower mortality rates in tilapia. The minimum inhibitory concentrations (MICs) of TP3 and TP4 that were effective for treating fish infected with V. vulnificus were 7.8 and 62.5 μg/ml, respectively, whereas the MICs of kanamycin and ampicillin were 31.2 and 3.91 μg/ml. The antimicrobial activity of these peptides was confirmed by transmission electron microscopy (TEM) and scanning electron microscopy (SEM), both of which showed

An independent distance estimate to the AGB star R Sculptoris

Science.gov (United States)

Maercker, M.; Brunner, M.; Mecina, M.; De Beck, E.

2018-04-01

Context. Distance measurements to astronomical objects are essential for understanding their intrinsic properties. For asymptotic giant branch (AGB) stars it is particularly difficult to derive accurate distance estimates. Period-luminosity relationships rely on the correlation of different physical properties of the stars, while the angular sizes and variability of AGB stars make parallax measurements inherently inaccurate. For the carbon AGB star R Sculptoris, the uncertain distance significantly affects the interpretation of observations regarding the evolution of the stellar mass loss during and after the most recent thermal pulse. Aim. We aim to provide a new, independent measurement of the distance to R Sculptoris, reducing the absolute uncertainty of the distance estimate to this source. Methods: R Scl is a semi-regular pulsating star, surrounded by a thin shell of dust and gas created during a thermal pulse ≈2000 years ago. The stellar light is scattered by the dust particles in the shell at a radius of ≈19″. The variation in the stellar light affects the amount of dust-scattered light with the same period and amplitude ratio, but with a phase lag that depends on the absolute size of the shell. We measured this phase lag by observing the star R Scl and the dust-scattered stellar light from the shell at five epochs between June-December 2016. By observing in polarised light, we imaged the shell in the plane of the sky, removing any uncertainty due to geometrical effects. The phase lag gives the absolute size of the shell, and together with the angular size of the shell directly gives the absolute distance to R Sculptoris. Results: We measured a phase lag between the stellar variations and the variation in the shell of 40.0 ± 4.0 days. The angular size of the shell is measured to be 19.″1 ± 0.″7. Combined, this gives an absolute distance to R Sculptoris of 361 ± 44 pc. Conclusions: We independently determined the absolute distance to R Scl with

A synthetic NO reduction cycle on a bis(pyrazolato)-bridged dinuclear ruthenium complex including photo-induced transformation.

Science.gov (United States)

Arikawa, Yasuhiro; Hiura, Junko; Tsuchii, Chika; Kodama, Mika; Matsumoto, Naoki; Umakoshi, Keisuke

2018-05-17

A synthetic NO reduction cycle (2NO + 2H+ + 2e- → N2O + H2O) on a dinuclear platform {(TpRu)2(μ-pz)2} (Tp = HB(pyrazol-1-yl)3) was achieved, where an unusual N-N coupling complex was included. Moreover, an interesting photo-induced conversion of the N-N coupling complex to an oxido-bridged complex was revealed.

TP53 dysfunction in CLL: Implications for prognosis and treatment.

Science.gov (United States)

Te Raa, Gera D; Kater, Arnon P

2016-03-01

Despite the availability of novel targeted agents, TP53 defects remain the most important adverse prognostic factor in chronic lymphocytic leukemia (CLL). Detection of deletion of TP53 locus (17p deletion) by fluorescent in situ hybridization (FISH) has become standard and performed prior to every line of treatment as the incidence dramatically increases as relapses occur. As monoallelic mutations of TP53 equally affect outcome, novel methods are being developed to improve detection of TP53 defects and include next-generation sequencing (NGS) and functional assays. TP53 defects highly affect outcome of immunochemotherapy but also alter response durations of tyrosine kinase inhibitors. Although BCR-targeting agents and Bcl-2-inhibitos have achieved durable responses in some patients with TP53 defects, long-term follow-up is currently lacking. In this review biological and clinical consequences of TP53 dysfunction as well as applicability of currently available methods to detect TP53 defects are described. In addition, proposed novel therapeutic strategies specifically for patients with TP53 dysfunction are discussed. In summary, the only curative treatment option for TP53-defective CLL is still allogeneic hematopoietic stem cell transplantation. Other treatment strategies such as rationale combinations of agents with different (TP53 independent) targets, including kinase inhibitors and inhibitors of anti-apoptotic molecules but also immunomodulatory agents need to be further explored. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cfd modeling of a synthetic jet actuator

International Nuclear Information System (INIS)

Dghim, Marouane; Ben Chiekh, Maher; Ben Nasrallah, Sassi

2009-01-01

Synthetic jet actuators show good promise as an enabling technology for innovative boundary layer flow control applied to external surfaces, like airplane wings, and to internal flows, like those occurring in a curved engine inlet. The appealing characteristics of a synthetic jet are zero-net-mass flux operation and an efficient control effect that takes advantages of unsteady fluid phenomena. The formation of a synthetic jet in a quiescent external air flow is only beginning to be understood and a rational understanding of these devices is necessary before they can be applied to the control of flows outside of the laboratory. The synthetic jet flow generated by a planar orifice is investigated here using computational approach. Computations of the 2D synthetic jet are performed with unsteady RANS modeled with the Realizable κ - ε turbulence model available in FLUENT environment. In this present work, the ability of the first order turbulence model, employed in our computations, to model the formation of the counter-rotating-vortex pair (CVP) that appears in the flow-field was investigated. Computational results were in good agreement with experimental measurements. The effectiveness of such control actuator was tested on separated boundary layer. Preliminary investigation were presented and discussed

Circumstellar grain extinction properties of recently discovered post AGB stars

International Nuclear Information System (INIS)

Buss, R.H. Jr.; Lamers, H.J.G.L.M.; Snow, T.P. Jr.

1989-01-01

The circumstellar grains of two hot evolved post asymptotic giant branch (post AGB) stars, HD 89353 and HD 213985 were examined. From ultraviolet spectra, energy balance of the flux, and Kurucz models, the extinction around 2175 A was derived. With visual spectra, an attempt was made to detect 6614 A diffuse band absorption arising from the circumstellar grains so that we could examine the relationship of these features to the infrared features. For both stars, we did not detect any diffuse band absorption at 6614 A, implying the carrier of this diffuse band is not the carrier of the unidentified infrared features not of the 2175 A bump. The linear ultraviolet extinction of the carbon-rich star HD 89353 was determined to continue across the 2175 A region with no sign of the bump; for HD 213985 it was found to be the reverse: a strong, wide bump in the mid-ultraviolet. The 213985 bump was found to be positioned at 2340 A, longward of its usual position in the interstellar medium. Since HD 213985 was determined to have excess carbon, the bump probably arises from a carbonaceous grain. Thus, in view of the ultraviolet and infrared properties of the two post AGB stars, ubiquitous interstellar infrared emission features do not seem to be associated with the 2175 A bump. Instead, the infrared features seem related to the linear ultraviolet extinction component: hydrocarbon grains of radius less than 300 A are present with the linear HD 89353 extinction; amorphous anhydrous carbonaceous grains of radius less than 50 A might cause the shifted ultraviolet extinction bump of HD 213985

A G-protein β subunit, AGB1, negatively regulates the ABA response and drought tolerance by down-regulating AtMPK6-related pathway in Arabidopsis.

Directory of Open Access Journals (Sweden)

Dong-bei Xu

Full Text Available Heterotrimeric G-proteins are versatile regulators involved in diverse cellular processes in eukaryotes. In plants, the function of G-proteins is primarily associated with ABA signaling. However, the downstream effectors and the molecular mechanisms in the ABA pathway remain largely unknown. In this study, an AGB1 mutant (agb1-2 was found to show enhanced drought tolerance, indicating that AGB1 might negatively regulate drought tolerance in Arabidopsis. Data showed that AGB1 interacted with protein kinase AtMPK6 that was previously shown to phosphorylate AtVIP1, a transcription factor responding to ABA signaling. Our study found that transcript levels of three ABA responsive genes, AtMPK6, AtVIP1 and AtMYB44 (downstream gene of AtVIP1, were significantly up-regulated in agb1-2 lines after ABA or drought treatments. Other ABA-responsive and drought-inducible genes, such as RD29A (downstream gene of AtMYB44, were also up-regulated in agb1-2 lines. Furthermore, overexpression of AtVIP1 resulted in hypersensitivity to ABA at seed germination and seedling stages, and significantly enhanced drought tolerance in transgenic plants. These results suggest that AGB1 was involved in the ABA signaling pathway and drought tolerance in Arabidopsis through down-regulating the AtMPK6, AtVIP1 and AtMYB44 cascade.

Overexpressed TP73 induces apoptosis in medulloblastoma

International Nuclear Information System (INIS)

Castellino, Robert C; De Bortoli, Massimiliano; Lin, Linda L; Skapura, Darlene G; Rajan, Jessen A; Adesina, Adekunle M; Perlaky, Laszlo; Irwin, Meredith S; Kim, John YH

2007-01-01

Medulloblastoma is the most common malignant brain tumor of childhood. Children who relapse usually die of their disease, which reflects resistance to radiation and/or chemotherapy. Improvements in outcome require a better understanding of the molecular basis of medulloblastoma growth and treatment response. TP73 is a member of the TP53 tumor suppressor gene family that has been found to be overexpressed in a variety of tumors and mediates apoptotic responses to genotoxic stress. In this study, we assessed expression of TP73 RNA species in patient tumor specimens and in medulloblastoma cell lines, and manipulated expression of full-length TAp73 and amino-terminal truncated ΔNp73 to assess their effects on growth. We analyzed medulloblastoma samples from thirty-four pediatric patients and the established medulloblastoma cell lines, Daoy and D283MED, for expression of TP73 RNA including the full-length transcript and the 5'-terminal variants that encode the ΔNp73 isoform, as well as TP53 RNA using quantitative real time-RTPCR. Protein expression of TAp73 and ΔNp73 was quantitated with immunoblotting methods. Clinical outcome was analyzed based on TP73 RNA and p53 protein expression. To determine effects of overexpression or knock-down of TAp73 and ΔNp73 on cell cycle and apoptosis, we analyzed transiently transfected medulloblastoma cell lines with flow cytometric and TUNEL methods. Patient medulloblastoma samples and cell lines expressed full-length and 5'-terminal variant TP73 RNA species in 100-fold excess compared to non-neoplastic brain controls. Western immunoblot analysis confirmed their elevated levels of TAp73 and amino-terminal truncated ΔNp73 proteins. Kaplan-Meier analysis revealed trends toward favorable overall and progression-free survival of patients whose tumors display TAp73 RNA overexpression. Overexpression of TAp73 or ΔNp73 induced apoptosis under basal growth conditions in vitro and sensitized them to cell death in response to

Overexpressed TP73 induces apoptosis in medulloblastoma

Directory of Open Access Journals (Sweden)

Perlaky Laszlo

2007-07-01

Full Text Available Abstract Background Medulloblastoma is the most common malignant brain tumor of childhood. Children who relapse usually die of their disease, which reflects resistance to radiation and/or chemotherapy. Improvements in outcome require a better understanding of the molecular basis of medulloblastoma growth and treatment response. TP73 is a member of the TP53 tumor suppressor gene family that has been found to be overexpressed in a variety of tumors and mediates apoptotic responses to genotoxic stress. In this study, we assessed expression of TP73 RNA species in patient tumor specimens and in medulloblastoma cell lines, and manipulated expression of full-length TAp73 and amino-terminal truncated ΔNp73 to assess their effects on growth. Methods We analyzed medulloblastoma samples from thirty-four pediatric patients and the established medulloblastoma cell lines, Daoy and D283MED, for expression of TP73 RNA including the full-length transcript and the 5'-terminal variants that encode the ΔNp73 isoform, as well as TP53 RNA using quantitative real time-RTPCR. Protein expression of TAp73 and ΔNp73 was quantitated with immunoblotting methods. Clinical outcome was analyzed based on TP73 RNA and p53 protein expression. To determine effects of overexpression or knock-down of TAp73 and ΔNp73 on cell cycle and apoptosis, we analyzed transiently transfected medulloblastoma cell lines with flow cytometric and TUNEL methods. Results Patient medulloblastoma samples and cell lines expressed full-length and 5'-terminal variant TP73 RNA species in 100-fold excess compared to non-neoplastic brain controls. Western immunoblot analysis confirmed their elevated levels of TAp73 and amino-terminal truncated ΔNp73 proteins. Kaplan-Meier analysis revealed trends toward favorable overall and progression-free survival of patients whose tumors display TAp73 RNA overexpression. Overexpression of TAp73 or ΔNp73 induced apoptosis under basal growth conditions in vitro and

Potential use of Pseudomonas koreensis AGB-1 in association with Miscanthus sinensis to remediate heavy metal(loid)-contaminated mining site soil.

Science.gov (United States)

Babu, A Giridhar; Shea, Patrick J; Sudhakar, D; Jung, Ik-Boo; Oh, Byung-Taek

2015-03-15

Endophytic bacteria have the potential to promote plant growth and heavy metal(loid) (HM) removal from contaminated soil. Pseudomonas koreensis AGB-1, isolated from roots of Miscanthus sinensis growing in mine-tailing soil, exhibited high tolerance to HMs and plant growth promoting traits. Transmission electron microscope (TEM) analysis revealed that AGB-1 sequestered HMs extracellularly and their accumulation was visible as dark metal complexes on bacterial surfaces and outside of the cells. DNA sequencing of HM resistance marker genes indicated high homology to the appropriate regions of the arsB, ACR3(1), aoxB, and bmtA determinants. Inoculating mining site soil with AGB-1 increased M. sinensis biomass by 54%, chlorophyll by 27%, and protein content by 28%. High superoxide dismutase and catalase activities, and the lower malondialdehyde content of plants growing in AGB-1-inoculated soil indicate reduced oxidative stress. Metal(loid) concentrations in roots and shoots of plants grown in inoculated soil were higher than those of the controls in pot trials with mine tailing soil. Results suggest that AGB-1 can be used in association with M. sinensis to promote phytostabilization and remediation of HM-contaminated sites. Copyright © 2015 Elsevier Ltd. All rights reserved.

AGB Statement on Board Responsibility for the Oversight of Educational Quality

Science.gov (United States)

Association of Governing Boards of Universities and Colleges, 2011

2011-01-01

This "Statement on Board Responsibility for the Oversight of Educational Quality," approved by the Board of Directors of the Association of Governing Boards (AGB) in March 2011, urges institutional administrators and governing boards to engage fully in this area of board responsibility. The seven principles in this statement offer suggestions to…

TP53 gene status affects survival in advanced mycosis fungoides

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Gitte Wooler

2016-11-01

Full Text Available TP53 is frequently mutated in different types of neoplasms including leukemia and lymphomas. Mutations of TP53 have also been reported in mycosis fungoides (MF, the most common type of cutaneous lymphoma. However, little is known about the frequency, spectrum of mutations and their prognostic significance in MF. In this study we have optimized the protocol for Sanger sequencing of TP53 using DNA extracted from archival paraffin-embedded biopsies. Of 19 samples from patients with stage IIB MF or higher, 31% harboured mutations in TP53. Overall survival of the patients with mutated TP53 was significantly shorter than median survival in the age- and stage-matched patients treated in our Institution. Distribution of mutations was heterogenous in TP53 exons, however C>T transitions were common suggesting the causal role of ultraviolet radiation. We propose that TP53 mutation status would be useful for risk stratification of patients with advanced MF.

Prolonged Tp-e Interval in Down Syndrome Patients with Congenitally Normal Hearts.

Science.gov (United States)

Kucuk, Mehmet; Karadeniz, Cem; Ozdemir, Rahmi; Meşe, Timur

2018-03-25

Heterogeneity of ventricular repolarization has been assessed by using the QT dispersion in Down syndrome (DS) patients with congenitally normal hearts. However, novel repolarization indexes, the Tp-e interval and Tp-e/QT ratio, have not previously been evaluated in these patients. The aim of this study was to evaluate the Tp-e interval and Tp-e/QT ratio in DS patients without congenital heart defects. Twelve-lead surface electrocardiograms of 160 DS patients and 110 age- and sex-matched healthy controls were used to evaluate and compare the Tp-e interval, Tp-e dispersion, and Tp-e/QT ratio. Heart rate, Tp-e interval, Tp-e dispersion, Tp-e/QT and Tp-e/QTc ratios were significantly higher in DS group than in the controls. Myocardial repolarization indexes in DS patients with congenitally normal hearts were found to be prolonged compared to those in normal controls. Further evaluation is warranted to reveal a relationship between prolonged repolarization indexes and arrhythmic events in these patients. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Combining Multi-Source Remotely Sensed Data and a Process-Based Model for Forest Aboveground Biomass Updating.

Science.gov (United States)

Lu, Xiaoman; Zheng, Guang; Miller, Colton; Alvarado, Ernesto

2017-09-08

Monitoring and understanding the spatio-temporal variations of forest aboveground biomass (AGB) is a key basis to quantitatively assess the carbon sequestration capacity of a forest ecosystem. To map and update forest AGB in the Greater Khingan Mountains (GKM) of China, this work proposes a physical-based approach. Based on the baseline forest AGB from Landsat Enhanced Thematic Mapper Plus (ETM+) images in 2008, we dynamically updated the annual forest AGB from 2009 to 2012 by adding the annual AGB increment (ABI) obtained from the simulated daily and annual net primary productivity (NPP) using the Boreal Ecosystem Productivity Simulator (BEPS) model. The 2012 result was validated by both field- and aerial laser scanning (ALS)-based AGBs. The predicted forest AGB for 2012 estimated from the process-based model can explain 31% ( n = 35, p forest AGBs, respectively. However, due to the saturation of optical remote sensing-based spectral signals and contribution of understory vegetation, the BEPS-based AGB tended to underestimate/overestimate the AGB for dense/sparse forests. Generally, our results showed that the remotely sensed forest AGB estimates could serve as the initial carbon pool to parameterize the process-based model for NPP simulation, and the combination of the baseline forest AGB and BEPS model could effectively update the spatiotemporal distribution of forest AGB.

An Infrared Census of DUST in Nearby Galaxies with Spitzer (DUSTiNGS). IV. Discovery of High-redshift AGB Analogs

Science.gov (United States)

Boyer, M. L.; McQuinn, K. B. W.; Groenewegen, M. A. T.; Zijlstra, A. A.; Whitelock, P. A.; van Loon, J. Th.; Sonneborn, G.; Sloan, G. C.; Skillman, E. D.; Meixner, M.; McDonald, I.; Jones, O. C.; Javadi, A.; Gehrz, R. D.; Britavskiy, N.; Bonanos, A. Z.

2017-12-01

The survey for DUST in Nearby Galaxies with Spitzer (DUSTiNGS) identified several candidate Asymptotic Giant Branch (AGB) stars in nearby dwarf galaxies and showed that dust can form even in very metal-poor systems ({\\boldsymbol{Z}}∼ 0.008 {Z}ȯ ). Here, we present a follow-up survey with WFC3/IR on the Hubble Space Telescope (HST), using filters that are capable of distinguishing carbon-rich (C-type) stars from oxygen-rich (M-type) stars: F127M, F139M, and F153M. We include six star-forming DUSTiNGS galaxies (NGC 147, IC 10, Pegasus dIrr, Sextans B, Sextans A, and Sag DIG), all more metal-poor than the Magellanic Clouds and spanning 1 dex in metallicity. We double the number of dusty AGB stars known in these galaxies and find that most are carbon rich. We also find 26 dusty M-type stars, mostly in IC 10. Given the large dust excess and tight spatial distribution of these M-type stars, they are most likely on the upper end of the AGB mass range (stars undergoing Hot Bottom Burning). Theoretical models do not predict significant dust production in metal-poor M-type stars, but we see evidence for dust excess around M-type stars even in the most metal-poor galaxies in our sample (12+{log}({{O}}/{{H}})=7.26{--}7.50). The low metallicities and inferred high stellar masses (up to ∼10 {M}ȯ ) suggest that AGB stars can produce dust very early in the evolution of galaxies (∼30 Myr after they form), and may contribute significantly to the dust reservoirs seen in high-redshift galaxies. Based on observations made with the NASA/ESA Hubble Space Telescope at the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., under NASA contract NAS 5-26555. These observations are associated with program GO-14073.

Agent-based modelling in synthetic biology.

Science.gov (United States)

Gorochowski, Thomas E

2016-11-30

Biological systems exhibit complex behaviours that emerge at many different levels of organization. These span the regulation of gene expression within single cells to the use of quorum sensing to co-ordinate the action of entire bacterial colonies. Synthetic biology aims to make the engineering of biology easier, offering an opportunity to control natural systems and develop new synthetic systems with useful prescribed behaviours. However, in many cases, it is not understood how individual cells should be programmed to ensure the emergence of a required collective behaviour. Agent-based modelling aims to tackle this problem, offering a framework in which to simulate such systems and explore cellular design rules. In this article, I review the use of agent-based models in synthetic biology, outline the available computational tools, and provide details on recently engineered biological systems that are amenable to this approach. I further highlight the challenges facing this methodology and some of the potential future directions. © 2016 The Author(s).

METAL-POOR STARS OBSERVED WITH THE MAGELLAN TELESCOPE. I. CONSTRAINTS ON PROGENITOR MASS AND METALLICITY OF AGB STARS UNDERGOING s-PROCESS NUCLEOSYNTHESIS

Energy Technology Data Exchange (ETDEWEB)

Placco, Vinicius M.; Rossi, Silvia [Departamento de Astronomia-Instituto de Astronomia, Geofisica e Ciencias Atmosfericas, Universidade de Sao Paulo, Sao Paulo, SP 05508-900 (Brazil); Frebel, Anna [Massachusetts Institute of Technology and Kavli Institute for Astrophysics and Space Research, 77 Massachusetts Avenue, Cambridge, MA 02139 (United States); Beers, Timothy C. [National Optical Astronomy Observatory, Tucson, AZ 85719 (United States); Karakas, Amanda I.; Kennedy, Catherine R. [Research School of Astronomy and Astrophysics, The Australian National University, Cotter Road, Weston, ACT 2611 (Australia); Christlieb, Norbert [Zentrum fuer Astronomie der Universitaet Heidelberg, Landessternwarte, Koenigstuhl 12, D-69117 Heidelberg (Germany); Stancliffe, Richard J. [Argelander-Institut fuer Astronomie der Universitaet Bonn, Auf dem Huegel 71, D-53121 Bonn (Germany)

2013-06-20

We present a comprehensive abundance analysis of two newly discovered carbon-enhanced metal-poor (CEMP) stars. HE 2138-3336 is a s-process-rich star with [Fe/H] = -2.79, and has the highest [Pb/Fe] abundance ratio measured thus far, if non-local thermodynamic equilibrium corrections are included ([Pb/Fe] = +3.84). HE 2258-6358, with [Fe/H] = -2.67, exhibits enrichments in both s- and r-process elements. These stars were selected from a sample of candidate metal-poor stars from the Hamburg/ESO objective-prism survey, and followed up with medium-resolution (R {approx} 2000) spectroscopy with GEMINI/GMOS. We report here on derived abundances (or limits) for a total of 34 elements in each star, based on high-resolution (R {approx} 30, 000) spectroscopy obtained with Magellan-Clay/MIKE. Our results are compared to predictions from new theoretical asymptotic giant branch (AGB) nucleosynthesis models of 1.3 M{sub Sun} with [Fe/H] = -2.5 and -2.8, as well as to a set of AGB models of 1.0 to 6.0 M{sub Sun} at [Fe/H] = -2.3. The agreement with the model predictions suggests that the neutron-capture material in HE 2138-3336 originated from mass transfer from a binary companion star that previously went through the AGB phase, whereas for HE 2258-6358, an additional process has to be taken into account to explain its abundance pattern. We find that a narrow range of progenitor masses (1.0 {<=} M(M{sub Sun }) {<=} 1.3) and metallicities (-2.8 {<=} [Fe/H] {<=}-2.5) yield the best agreement with our observed elemental abundance patterns.

Shell and explosive hydrogen burning. Nuclear reaction rates for hydrogen burning in RGB, AGB and Novae

Energy Technology Data Exchange (ETDEWEB)

Boeltzig, A. [Gran Sasso Science Institute, L' Aquila (Italy); Bruno, C.G.; Davinson, T. [University of Edinburgh, SUPA, School of Physics and Astronomy, Edinburgh (United Kingdom); Cavanna, F.; Ferraro, F. [Dipartimento di Fisica, Universita di Genova (Italy); INFN, Genova (Italy); Cristallo, S. [Osservatorio Astronomico di Collurania, INAF, Teramo (Italy); INFN, Napoli (Italy); Depalo, R. [Dipartimento di Fisica e Astronomia, Universita di Padova, Padova (Italy); INFN, Padova (Italy); DeBoer, R.J.; Wiescher, M. [University of Notre Dame, Institute for Structure and Nuclear Astrophysics, Joint Institute for Nuclear Astrophysics, Notre Dame, Indiana (United States); Di Leva, A.; Imbriani, G. [Dipartimento di Fisica, Universita di Napoli Federico II, Napoli (Italy); INFN, Napoli (Italy); Marigo, P. [Dipartimento di Fisica e Astronomia, Universita di Padova, Padova (Italy); Terrasi, F. [Dipartimento di Matematica e Fisica Seconda Universita di Napoli, Caserta (Italy); INFN, Napoli (Italy)

2016-04-15

The nucleosynthesis of light elements, from helium up to silicon, mainly occurs in Red Giant and Asymptotic Giant Branch stars and Novae. The relative abundances of the synthesized nuclides critically depend on the rates of the nuclear processes involved, often through non-trivial reaction chains, combined with complex mixing mechanisms. In this paper, we summarize the contributions made by LUNA experiments in furthering our understanding of nuclear reaction rates necessary for modeling nucleosynthesis in AGB stars and Novae explosions. (orig.)

The pathways of C: from AGB stars, to the Interstellar Medium, and finally into the protoplanetary disk

Science.gov (United States)

Trigo-Rodriguez, J. M.; Garcia-Hernandez, D. A.

2011-05-01

The origin, and role of C in the formation of first solar system aggregates is described. Stellar grains evidence demonstrates that Asymptotic Giant Branch (AGB) stars were nearby to the solar nebula at the time of solar system formation. Such stars continue to burn H and He in shells that surround the C-O core. During their evolution, flashes occur in the He shell and the C, and O produced are eventually dredged up into the star's envelop and then to the stellar surface, and finally masively ejected to the interstellar medium (IM). Once in a molecular cloud, the electrophilicity of C makes this element reactable with the surrounding gas to produce different molecular species. Primitive meteorites, particularly these known as chondrites, preserved primeval materials of the disk. The abundances of short-lived radionuclides (SLN), inferred to have been present in the early solar system (ESS), are a constraint on the birth and early evolution of the solar system as their relatively short half lives do not allow the observed abundances to be explained by galactic chemical evolution processes. We present a model of a 6.5 solar masses star of solar metallicity that simultaneously match the abundances of SLNs inferred to have been present in the ESS by using a dilution factor of 1 part of AGB material per 300 parts of original solar nebula material, and taking into account a time interval between injection of SLNs and consolidation of chondrites equal to 0.53 Myr [2]. Such a polluting source does not overproduce 53Mn, as supernova models do, and only marginally affects isotopic ratios of stable elements. The AGB stars released O- and C-rich gas with important oxidizing implications to first solar system materials as recently detected in circumstellar environments [3]. REF: [1] Lada C.J. and Lada E.A. 2003. Ann. Rev. A&A. 41: 57; [2] Trigo-Rodriguez J.M. et al. 2009. MAPS 44: 627; [3] Decin L. et al. 2010. Nature 467: 64.

Main - TP Atlas | LSDB Archive [Life Science Database Archive metadata

Lifescience Database Archive (English)

Full Text Available switchLanguage; BLAST Search Image Search Home About Archive Update History Data ...me: tp_atlas_en.zip File URL: ftp://ftp.biosciencedbc.jp/archive/tp_atlas/LATEST/...d License Update History of This Database Site Policy | Contact Us Main - TP Atlas | LSDB Archive ...

Molecular processes from the AGB to the PN stage

Science.gov (United States)

García-Hernández, D. Anibal

2012-08-01

Many complex organic molecules and inorganic solid-state compounds have been observed in the circumstellar shell of stars (both C-rich and O-rich) in the transition phase between Asymptotic Giant Branch (AGB) stars and Planetary Nebulae (PNe). This short (~102-104 years) phase of stellar evolution represents a wonderful laboratory for astrochemistry and provides severe constraints on any model of gas-phase and solid-state chemistry. One of the major challenges of present day astrophysics and astrochemistry is to understand the formation pathways of these complex organic molecules and inorganic solid-state compounds (e.g., polycyclic aromatic hydrocarbons, fullerenes, and graphene in the case of a C-rich chemistry and oxides and crystalline silicates in O-rich environments) in space. In this review, I present an observational review of the molecular processes in the late stages of stellar evolution with a special emphasis on the first detections of fullerenes and graphene in PNe.

Detection of CI line emission towards the oxygen-rich AGB star omi Ceti

Science.gov (United States)

Saberi, M.; Vlemmings, W. H. T.; De Beck, E.; Montez, R.; Ramstedt, S.

2018-05-01

We present the detection of neutral atomic carbon CI(3P1-3P0) line emission towards omi Cet. This is the first time that CI is detected in the envelope around an oxygen-rich M-type asymptotic giant branch (AGB) star. We also confirm the previously tentative CI detection around V Hya, a carbon-rich AGB star. As one of the main photodissociation products of parent species in the circumstellar envelope (CSE) around evolved stars, CI can be used to trace sources of ultraviolet (UV) radiation in CSEs. The observed flux density towards omi Cet can be reproduced by a shell with a peak atomic fractional abundance of 2.4 × 10-5 predicted based on a simple chemical model where CO is dissociated by the interstellar radiation field. However, the CI emission is shifted by 4 km s-1 from the stellar velocity. Based on this velocity shift, we suggest that the detected CI emission towards omi Cet potentially arises from a compact region near its hot binary companion. The velocity shift could, therefore, be the result of the orbital velocity of the binary companion around omi Cet. In this case, the CI column density is estimated to be 1.1 × 1019 cm-2. This would imply that strong UV radiation from the companion and/or accretion of matter between two stars is most likely the origin of the CI enhancement. However, this hypothesis can be confirmed by high-angular resolution observations.

Cooperative effects in differentiation and proliferation between PDGF-BB and matrix derived synthetic peptides in human osteoblasts

Directory of Open Access Journals (Sweden)

Vordemvenne Thomas

2011-11-01

Full Text Available Abstract Background Enhancing osteogenic capabilities of bone matrix for the treatment of fractures and segmental defects using growth factors is an active area of research. Recently, synthetic peptides like AC- 100, TP508 or p-15 corresponding to biologically active sequences of matrix proteins have been proven to stimulate bone formation. The platelet-derived growth factor (PDGF BB has been identified as an important paracrine factor in early bone healing. We hypothesized that the combined use of PDGF-BB with synthetic peptides could result in an increase in proliferation and calcification of osteoblast-like cells. Methods Osteoblast-like cell cultures were treated with PDGF and synthetic peptides, singly and as combinations, and compared to non-treated control cell cultures. The cultures were evaluated at days 2, 5, and 10 in terms of cell proliferation, calcification and gene expression of alkaline phosphate, collagen I and osteocalcin. Results Experimental findings revealed that the addition of PDGF, p-15 and TP508 and combinations of PDGF/AC-100, PDGF/p-15 and PDGF/TP508 resulted in an increase in proliferating osteoblasts, especially in the first 5 days of cultivation. Proliferation did not significantly differ between single factors and factor combinations (p > 0.05. The onset of calcification in osteoblasts occurred earlier and was more distinct compared to the corresponding control or PDGF stimulation alone. Significant difference was found for the combined use of PDGF/p-15 and PDGF/AC-100 (p Conclusions Our findings indicate that PDGF exhibits cooperative effects with synthetic peptides in differentiation and proliferation. These cooperative effects cause a significant early calcification of osteoblast-like cells (p

The IARC TP53 mutation database: a resource for studying the significance of TP53 mutations in human cancers

Directory of Open Access Journals (Sweden)

Magali Olivier

2007-02-01

yeast and human cells to measure the impact of these mutations on various protein properties: (1 transactivation activities (TA of mutant proteins on reporter genes placed under the control of various p53 responseelements, (2 capacity of mutant proteins to induce cellcycle arrest or apoptosis, (3 ability to exert dominantnegative effect (DNE over the wild-type protein, (4 activities of mutant proteins that are independent and unrelated to the wild-type protein (gain of function, GOF. Prediction models based on interspecies protein sequence conservation have also been developed to predict the functional impact of all possible single amino-acid substitutions.

These data have been used to produce systematic functional classifications of mutant proteins and these classifications have been integrated in the IARC TP53 database. New tools have been implemented to visualize these data and analyze mutation frequencies in relation to their functional impact and intrinsic nucleotide substitution rates.

Thus, the database allows systematic analyses of the factors that shape the patterns and influence the phenotype of missense mutations in human cancers. In a recent analysis of the database, we showed that that loss of TA capacity is a key factor for the selection of missense mutations, and that difference in mutation frequencies is closely related to nucleotide substitution rates along TP53 coding sequence. TA capacity of inherited missense mutations was also found to be related the age at onset of specific tumor types, mutations with total loss of TA being associated with earlier cancer onset cancers compared to mutations that retain partial trans-activation capacity. Furthermore, 80% of the most common mutants show a capacity to exert dominant-negative effect (DNE over wildtype p53, compared to only 45% of

Models of the Hydrodynamic Histories of Post-AGB Stars. I. Multiflow Shaping of OH 231.8+04.2

Energy Technology Data Exchange (ETDEWEB)

Balick, Bruce [Department of Astronomy, University of Washington, Seattle, WA 98195-1580 (United States); Frank, Adam; Liu, Baowei [Department of Physics and Astronomy, University of Rochester, Rochester, NY 14627 (United States); Huarte-Espinosa, Martín, E-mail: balick@uw.edu, E-mail: afrank@pas.rochester.edu, E-mail: baowei.liu@rochester.edu, E-mail: mhuartee@central.uh.edu [Center for Advanced Comp and Data Systems, University of Houston, 4718 Calhoun Rd., Houston, TX 77204-3058 (United States)

2017-07-10

We present a detailed hydrodynamic model that matches the present structure of the well-observed preplanetary nebula (“pPN”) OH 231.8+04.2 (“OH231”). The purpose of the model is to present a physically justified and coherent picture of its evolutionary history from about 100 years from the start of the formation of its complex outer structures to the present. We have adopted a set of initial conditions that are heavily constrained by high-quality observations of its present structure and kinematics. The shaping of the nebula occurs while the densities of the flows are “light,” i.e., less than the surrounding AGB-wind environment. The simulations show that pairs of essentially coeval clumps and sprays of the same extent and density, but different outflow speeds, sculpted both the pair of thin axial flow “or spine” and the bulbs. The total ejected mass and momentum in the best-fit model are surprisingly large—3 M {sub ⊙} and 2.2 × 10{sup 41} gm cm s{sup −1}, respectively—however, these values are reduced by up to a factor of 10 in other models that fit the data almost as well. Our ultimate goal is to combine the present model results of masses, momenta, flow speeds, and flow geometries for OH231 with those of other models to be published in the future in order to find common attributes of their ejection histories.

TP Organics - maheuuringute tehnoloogiaplatvorm

Index Scriptorium Estoniae

2015-01-01

TP Organics on 2008. a loodud Euroopa mahepõllumajanduse ja mahetoidu ning vähese sisendiga põllumajanduse tehnoloogiaplatvorm. Platvormi eesmärk on selgitada välja teadustöö ja uuenduste vajadused ning edastada see info poliitikutele

Association of mRNA expression of TP53 and the TP53 codon 72 Arg/Pro gene polymorphism with colorectal cancer risk in Asian population: a bioinformatics analysis and meta-analysis.

Science.gov (United States)

Dong, Zhiyong; Zheng, Longzhi; Liu, Weimin; Wang, Cunchuan

2018-01-01

The relationship between TP53 codon 72 Pro/Arg gene polymorphism and colorectal cancer risk in Asians is still controversial, and this bioinformatics analysis and meta-analysis was performed to assess the associations. The association studies were identified from PubMed, and eligible reports were included. RevMan 5.3.1 software, Oncolnc, cBioPortal, and Oncomine online tools were used for statistical analysis. A random/fixed effects model was used in meta-analysis. The data were reported as risk ratios or mean differences with corresponding 95% CI. We confirmed that TP53 was associated with colorectal cancer, the alteration frequency of TP53 was 53% mutation and 7% deep deletion, and TP53 mRNA expression was different in different types of colorectal cancer based on The Cancer Genome Atlas database. Then, 18 studies were included that examine the association of TP53 codon 72 gene polymorphism with colorectal cancer risk in Asians. The meta-analysis indicated that TP53 Pro allele and Pro/Pro genotype were associated with colorectal cancer risk in Asian population, but Arg/Arg genotype was not (Pro allele: odds ratios [OR]=1.20, 95% CI: 1.06 to 1.35, P =0.003; Pro/Pro genotype: OR=1.39, 95% CI: 1.15 to 1.69, P =0.0007; Arg/Arg genotype: OR=0.86, 95% CI: 0.74 to 1.00, P =0.05). Interestingly, in the meta-analysis of the controls from the population-based studies, we found that TP53 codon 72 Pro/Arg gene polymorphism was associated with colorectal cancer risk (Pro allele: OR=1.33, 95% CI: 1.15 to 1.55, P =0.0002; Pro/Pro genotype: OR=1.61, 95% CI: 1.28 to 2.02, P colorectal cancer, but the different value levels of mRNA expression were not associated with survival rate of colon and rectal cancer. TP53 Pro allele and Pro/Pro genotype were associated with colorectal cancer risk in Asians.

Observações espectroscópicas da candidata a pós-AGB IRAS 19386+0155

Science.gov (United States)

Lorenz-Martins, S.; Pereira, C. B.

2003-08-01

Nesse trabalho apresentamos a análise fotosférica da estrela candidata a pós-AGB IRAS 19386+0155. Com os dados obtidos no espectrógrafo FEROS foram determinados os parâmetros atmosféricos e abundâncias fotosféricas utilizando o código MOOG. A análise do espectro mostrou que IRAS 19386+0155 possui os seguintes parâmetros atmosféricos : Teff = 6800K, log g = 1.4, [M/H] = -1.5 e Vt = 8.4 km/s. O padrão de abundância obtido para os elementos mais leves (Carbono, Nitrogênio e Oxigênio) e elementos a (Magnésio, Silício e Cálcio) foi inferior ao solar (log C = 7.74, log N = 7.28, Log O = 8.43, log Mg = 7.14, log Si = 7.54 e log Ca = 5.91). Uma inspeção visual do espectro ISO deste objeto revela a presença de poeira fria na forma de silicatos cristalinos. Embora as bandas mais marcantes de silicatos amorfos (em 10 mm e 18mm) não sejam observadas, a emissão em 21 mm, presente em algumas pós-AGBs também não está presente. O espectro ISO parece revelar um meio rico em oxigênio, mas a forma da distribuição de energia no infravermelho não obedece ao padrão apresentado por outras pós-AGBs. Nossos resultados nos levam a sugerir que IRAS 19386+0155 talvez faça parte de um sistema binário, uma vez que outras pós-AGBs que são membros de sistemas binários apresentam padrão de abundância semelhante.

Analytical and clinical comparison of Elecsys syphilis (Roche®) - Architect syphilis TP and reformulated Architect syphilis TP (Abbott®) assay.

Science.gov (United States)

De Keukeleire, Steven; Desmet, Stefanie; Lagrou, Katrien; Oosterlynck, Julie; Verhulst, Manon; Van Besien, Jessica; Saegeman, Veroniek; Reynders, Marijke

2017-03-01

The performance of Elecsys Syphilis was compared to Architect Syphilis TP and Reformulated Architect Syphilis TP. The overall sensitivity and specificity were 98.4% and 99.5%, 97.7% and 97.1%, and 99.2% and 99.7% respectively. The assays are comparable and considered adequate for syphilis screening. Copyright © 2016 Elsevier Inc. All rights reserved.

Modelling of bubbly and annular two-phase flow in subchannel geometries with BACCHUS-3D/TP

International Nuclear Information System (INIS)

Bottoni, M.; Lyczkowski, R.W.

1992-01-01

The theoretical and computational bases of the BACCHUS-3D/TP computer program are reviewed. The computer program is used for thermal-hydraulic analyses of nuclear fuel bundles under normal and accident conditions. The present program combines two models and solution procedures previously used separately, namely, the Improved Slip Model (ISM) and the Separated-Phases Model (SPM). The former model uses mixture equations with accounting for slip between the phases, whereas the latter uses separate continuity and momentum equations. At the present stage of development, both assume thermodynamic equilibrium. Techniques used to affect smooth transition between the two models are described. including treatment of frictional pressure drop and solution of the Poisson and momentum equations. A detailed derivation of the computation of mass transfer between the phases is given because it is a central and novel feature of the model

Accuracy of Genomic Selection in a Rice Synthetic Population Developed for Recurrent Selection Breeding.

Science.gov (United States)

Grenier, Cécile; Cao, Tuong-Vi; Ospina, Yolima; Quintero, Constanza; Châtel, Marc Henri; Tohme, Joe; Courtois, Brigitte; Ahmadi, Nourollah

2015-01-01

Genomic selection (GS) is a promising strategy for enhancing genetic gain. We investigated the accuracy of genomic estimated breeding values (GEBV) in four inter-related synthetic populations that underwent several cycles of recurrent selection in an upland rice-breeding program. A total of 343 S2:4 lines extracted from those populations were phenotyped for flowering time, plant height, grain yield and panicle weight, and genotyped with an average density of one marker per 44.8 kb. The relative effect of the linkage disequilibrium (LD) and minor allele frequency (MAF) thresholds for selecting markers, the relative size of the training population (TP) and of the validation population (VP), the selected trait and the genomic prediction models (frequentist and Bayesian) on the accuracy of GEBVs was investigated in 540 cross validation experiments with 100 replicates. The effect of kinship between the training and validation populations was tested in an additional set of 840 cross validation experiments with a single genomic prediction model. LD was high (average r2 = 0.59 at 25 kb) and decreased slowly, distribution of allele frequencies at individual loci was markedly skewed toward unbalanced frequencies (MAF average value 15.2% and median 9.6%), and differentiation between the four synthetic populations was low (FST ≤0.06). The accuracy of GEBV across all cross validation experiments ranged from 0.12 to 0.54 with an average of 0.30. Significant differences in accuracy were observed among the different levels of each factor investigated. Phenotypic traits had the biggest effect, and the size of the incidence matrix had the smallest. Significant first degree interaction was observed for GEBV accuracy between traits and all the other factors studied, and between prediction models and LD, MAF and composition of the TP. The potential of GS to accelerate genetic gain and breeding options to increase the accuracy of predictions are discussed.

Detection of HCN and C2H2 in ISO Spectra of Oxygen-Rich AGB Stars

Science.gov (United States)

Carbon, Duane F.; Chiar, Jean; Goorvitch, David; Kwak, Dochan (Technical Monitor)

2002-01-01

Cool oxygen-rich AGB stars were not expected to have organic molecules like HCN in either their photospheres or circumstellar envelopes (CSEs). The discovery of HCN and CS microwave emission from the shallowest CSE layers of these stars was a considerable surprise and much theoretical effort has been expended in explaining the presence of such organics. To further explore this problem, we have undertaken a systematic search of oxygen-rich AGB stellar spectra in the Infrared Space Observatory (ISO) data archive. Our purposes are to find evidence regarding critical molecular species that could be of value in choosing among the proposed theoretical models, to locate spectral features which might give clues to conditions deeper in the CSEs, and to lay the groundwork for future SIRTF (Space Infrared Telescope Facility) and SOFIA (Stratospheric Observatory for Infrared Astronomy) observations. Using carefully reduced observations, we have detected weak absorption features arising from HCN and possibly C2H2 in a small number of oxygen-rich AGB stars. The most compelling case is NML Cyg which shows both HCN (14 microns) and CO2 (15 microns). VY CMa, a similar star, shows evidence for HCN, but not CO2. Two S-type stars show evidence for the C-H bending transitions: W Aql at 14 microns (HCN) and both W Aql and S Cas at 13.7 microns (C2H2). Both W Aql and S Cas as well as S Lyr, a SC-type star, show 3 micron absorption which may arise from the C-H stretch of HCN and C2H2. In the case of NML Cyg, we show that the HCN and CO2 spectral features are formed in the CSE at temperatures well above those of the outermost CSE layers and derive approximate column densities. In the case of the S-stars, we discuss the evidence for the organic features and their photospheric origin.

WNT activation by lithium abrogates TP53 mutation associated radiation resistance in medulloblastoma.

Science.gov (United States)

Zhukova, Nataliya; Ramaswamy, Vijay; Remke, Marc; Martin, Dianna C; Castelo-Branco, Pedro; Zhang, Cindy H; Fraser, Michael; Tse, Ken; Poon, Raymond; Shih, David J H; Baskin, Berivan; Ray, Peter N; Bouffet, Eric; Dirks, Peter; von Bueren, Andre O; Pfaff, Elke; Korshunov, Andrey; Jones, David T W; Northcott, Paul A; Kool, Marcel; Pugh, Trevor J; Pomeroy, Scott L; Cho, Yoon-Jae; Pietsch, Torsten; Gessi, Marco; Rutkowski, Stefan; Bognár, Laszlo; Cho, Byung-Kyu; Eberhart, Charles G; Conter, Cecile Faure; Fouladi, Maryam; French, Pim J; Grajkowska, Wieslawa A; Gupta, Nalin; Hauser, Peter; Jabado, Nada; Vasiljevic, Alexandre; Jung, Shin; Kim, Seung-Ki; Klekner, Almos; Kumabe, Toshihiro; Lach, Boleslaw; Leonard, Jeffrey R; Liau, Linda M; Massimi, Luca; Pollack, Ian F; Ra, Young Shin; Rubin, Joshua B; Van Meir, Erwin G; Wang, Kyu-Chang; Weiss, William A; Zitterbart, Karel; Bristow, Robert G; Alman, Benjamin; Hawkins, Cynthia E; Malkin, David; Clifford, Steven C; Pfister, Stefan M; Taylor, Michael D; Tabori, Uri

2014-12-24

TP53 mutations confer subgroup specific poor survival for children with medulloblastoma. We hypothesized that WNT activation which is associated with improved survival for such children abrogates TP53 related radioresistance and can be used to sensitize TP53 mutant tumors for radiation. We examined the subgroup-specific role of TP53 mutations in a cohort of 314 patients treated with radiation. TP53 wild-type or mutant human medulloblastoma cell-lines and normal neural stem cells were used to test radioresistance of TP53 mutations and the radiosensitizing effect of WNT activation on tumors and the developing brain. Children with WNT/TP53 mutant medulloblastoma had higher 5-year survival than those with SHH/TP53 mutant tumours (100% and 36.6%±8.7%, respectively (p<0.001)). Introduction of TP53 mutation into medulloblastoma cells induced radioresistance (survival fractions at 2Gy (SF2) of 89%±2% vs. 57.4%±1.8% (p<0.01)). In contrast, β-catenin mutation sensitized TP53 mutant cells to radiation (p<0.05). Lithium, an activator of the WNT pathway, sensitized TP53 mutant medulloblastoma to radiation (SF2 of 43.5%±1.5% in lithium treated cells vs. 56.6±3% (p<0.01)) accompanied by increased number of γH2AX foci. Normal neural stem cells were protected from lithium induced radiation damage (SF2 of 33%±8% for lithium treated cells vs. 27%±3% for untreated controls (p=0.05). Poor survival of patients with TP53 mutant medulloblastoma may be related to radiation resistance. Since constitutive activation of the WNT pathway by lithium sensitizes TP53 mutant medulloblastoma cells and protect normal neural stem cells from radiation, this oral drug may represent an attractive novel therapy for high-risk medulloblastomas.

TP53 mutation spectrum in smokers and never smoking lung cancer patients

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Ann Rita Halvorsen

2016-05-01

Full Text Available AbstractBackground: TP53 mutations are among the most common mutations found in lung cancers, identified as an independent prognostic factor in many types of cancers. The purpose of this study was to investigate the frequency and prognostic impact of TP53 mutations in never-smokers and in different histological subtypes of lung cancer.Methods: We analysed tumour tissue from 394 non-small cell carcinomas including adenocarcinomas (n=229, squamous cell carcinomas (n=112, large cell carcinomas (n=30 and others (n=23 for mutations in TP53 by the use of Sanger sequencing (n=394 and next generation sequencing (n=100. Results: TP53 mutations were identified in 47.2% of the samples, with the highest frequency (65% of mutations among squamous cell carcinomas. Among never-smokers, 36% carried a TP53 mutation, identified as a significant independent negative prognostic factor in this subgroup. For large cell carcinomas, a significantly prolonged progression free survival was found for those carrying a TP53 mutation. In addition, the frequency of frameshift mutations was doubled in squamous cell carcinomas (20.3% compared to adenocarcinomas (9.1%.Conclusion: TP53 mutation patterns differ between the histological subgroups of lung cancers, as also influenced by smoking history. This indicates that the histological subtypes in lung cancer are genetically different, and that smoking-induced TP53 mutations may have a different biological impact than TP53 mutations occurring in never-smokers.

TP53 status and taxane-platinum versus platinum-based therapy in ovarian cancer patients: A non-randomized retrospective study

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Markowska Janina

2008-01-01

Full Text Available Abstract Background Taxane-platinum therapy (TP has replaced platinum-based therapy (PC or PAC, DNA damaging chemotherapy in the postoperative treatment of ovarian cancer patients; however, it is not always effective. TP53 protein plays a differential role in response to DNA-damaging agents and taxanes. We sought to define profiles of patients who benefit the most from TP and also of those who can be treated with PC. Methods We compared the effectiveness of PC/PAC (n = 253 and TP (n = 199 with respect to tumor TP53 accumulation in ovarian cancer patients with FIGO stage IIB-IV disease; this was a non-randomized retrospective study. Immunohistochemical analysis was performed on 452 archival tumors; univariate and multivariate analysis by the Cox's and logistic regression models was performed in all patients and in subgroups with [TP53(+] and without TP53 accumulation [TP53(-]. Results The advantage of taxane-platinum therapy over platinum-based therapy was seen in the TP53(+, and not in the TP53(- group. In the TP53(+ group taxane-platinum therapy enhanced the probability of complete remission (p = .018, platinum sensitivity (p = .014, platinum highly sensitive response (p = .038 and longer survival (OS, p = .008. Poor tumor differentiation diminished the advantage from taxane-platinum therapy in the TP53(+ group. In the TP53(- group PC/PAC was at least equally efficient as taxane-platinum therapy and it enhanced the chance of platinum highly sensitive response (p = .010. However, in the TP53(- group taxane-platinum therapy possibly diminished the risk of death in patients over 53 yrs (p = .077. Among factors that positively interacted with taxane-platinum therapy in some analyses were endometrioid and clear cell type, FIGO III stage, bulky residual tumor, more advanced age of patient and moderate tumor differentiation. Conclusion Our results suggest that taxane-platinum therapy is particularly justified in patients with TP53(+ tumors or older

SPITZER survey of dust grain processing in stable discs around binary post-AGB stars

NARCIS (Netherlands)

Gielen, C.; van Winckel, H.; Min, M.; Waters, L.B.F.M.; Lloyd Evans, T.

2008-01-01

Aims. We investigate the mineralogy and dust processing in the circumbinary discs of binary post-AGB stars using high-resolution TIMMI2 and SPITZER infrared spectra. Methods: We perform a full spectral fitting to the infrared spectra using the most recent opacities of amorphous and crystalline dust

Long-period variables in the Large Magellanic Cloud. II. Infrared photometry, spectral classification, AGB evolution, and spatial distribution

International Nuclear Information System (INIS)

Hughes, S.M.G.; Wood, P.R.

1990-01-01

Infrared JHK photometry and visual spectra have been obtained for a large sample of long-period variables (LPVs) in the Large Magellanic Cloud (LMC). Various aspects of the asymptotic giant branch (AGB) evolution of LPVs are discussed using these data. The birth/death rate of LPVs of different ages in the LMC is compared with the birth rates of appropriate samples of planetary nebulas, clump stars, Cepheids, and OH/IR stars. It appears that there are much fewer large-amplitude LPVs per unit galactic stellar mass in the LMC than in the Galaxy. It is suggested that this may be due to the fact that the evolved intermediate-age AGB stars in the LMC often turn into carbon stars, which tend to have smaller pulsation amplitudes than M stars. There is also a major discrepancy between the number of LPVs in the LMC (and in the Galaxy) and the number predicted by the theories of AGB evolution, pulsation, and mass loss. A distance modulus to the LMC of 18.66 + or - 0.05 is derived by comparing the LMC LPVs with P about 200 days with the 47 Tucanae Mira variables in the (K, log P) plane. 64 refs

METABOLIC MODELLING IN THE DEVELOPMENT OF CELL FACTORIES BY SYNTHETIC BIOLOGY

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Paula Jouhten

2012-10-01

Full Text Available Cell factories are commonly microbial organisms utilized for bioconversion of renewable resources to bulk or high value chemicals. Introduction of novel production pathways in chassis strains is the core of the development of cell factories by synthetic biology. Synthetic biology aims to create novel biological functions and systems not found in nature by combining biology with engineering. The workflow of the development of novel cell factories with synthetic biology is ideally linear which will be attainable with the quantitative engineering approach, high-quality predictive models, and libraries of well-characterized parts. Different types of metabolic models, mathematical representations of metabolism and its components, enzymes and metabolites, are useful in particular phases of the synthetic biology workflow. In this minireview, the role of metabolic modelling in synthetic biology will be discussed with a review of current status of compatible methods and models for the in silico design and quantitative evaluation of a cell factory.

Synthetic vision and memory model for virtual human - biomed 2010.

Science.gov (United States)

Zhao, Yue; Kang, Jinsheng; Wright, David

2010-01-01

This paper describes the methods and case studies of a novel synthetic vision and memory model for virtual human. The synthetic vision module simulates the biological / optical abilities and limitations of the human vision. The module is based on a series of collision detection between the boundary of virtual humans field of vision (FOV) volume and the surface of objects in a recreated 3D environment. The memory module simulates a short-term memory capability by employing a simplified memory structure (first-in-first-out stack). The synthetic vision and memory model has been integrated into a virtual human modelling project, Intelligent Virtual Modelling. The project aimed to improve the realism and autonomy of virtual humans.

Modeling Forest Biomass and Growth: Coupling Long-Term Inventory and Lidar Data

Science.gov (United States)

Babcock, Chad; Finley, Andrew O.; Cook, Bruce D.; Weiskittel, Andrew; Woodall, Christopher W.

2016-01-01

Combining spatially-explicit long-term forest inventory and remotely sensed information from Light Detection and Ranging (LiDAR) datasets through statistical models can be a powerful tool for predicting and mapping above-ground biomass (AGB) at a range of geographic scales. We present and examine a novel modeling approach to improve prediction of AGB and estimate AGB growth using LiDAR data. The proposed model accommodates temporal misalignment between field measurements and remotely sensed data-a problem pervasive in such settings-by including multiple time-indexed measurements at plot locations to estimate AGB growth. We pursue a Bayesian modeling framework that allows for appropriately complex parameter associations and uncertainty propagation through to prediction. Specifically, we identify a space-varying coefficients model to predict and map AGB and its associated growth simultaneously. The proposed model is assessed using LiDAR data acquired from NASA Goddard's LiDAR, Hyper-spectral & Thermal imager and field inventory data from the Penobscot Experimental Forest in Bradley, Maine. The proposed model outperformed the time-invariant counterpart models in predictive performance as indicated by a substantial reduction in root mean squared error. The proposed model adequately accounts for temporal misalignment through the estimation of forest AGB growth and accommodates residual spatial dependence. Results from this analysis suggest that future AGB models informed using remotely sensed data, such as LiDAR, may be improved by adapting traditional modeling frameworks to account for temporal misalignment and spatial dependence using random effects.

Purification, crystallization and preliminary X-ray analysis of TP0435 (Tp17) from the syphilis spirochete Treponema pallidum

International Nuclear Information System (INIS)

Brautigam, Chad A.; Deka, Ranjit K.; Norgard, Michael V.

2013-01-01

The soluble portion of TP0435, a putative periplasmic lipoprotein from the syphilis spirochete T. pallidum, has been purified and crystallized in a rhombohedral space group. A complete native data set has been collected to 2.4 Å resolution. Syphilis, caused by the bacterial spirochete Treponema pallidum, remains a prominent sexually transmitted infection worldwide. Despite sequencing of the genome of this obligate human pathogen 15 years ago, the functions of a large number of the gene products of T. pallidum are still unknown, particularly with respect to those of the organism’s periplasmic lipoproteins. To better understand their functions, a structural biology approach has been pursued. To this end, the soluble portion of the T. pallidum TP0435 lipoprotein (also known as Tp17) was cloned, hyper-expressed in Escherichia coli and purified to apparent homogeneity. The protein crystals obtained from this preparation diffracted to 2.4 Å resolution and had the symmetry of space group R3. In the hexagonal setting, the unit-cell parameters were a = b = 85.7, c = 85.4 Å

Tilapia Piscidin 4 (TP4 Stimulates Cell Proliferation and Wound Closure in MRSA-Infected Wounds in Mice

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Hang-Ning Huang

2015-05-01

Full Text Available Antimicrobial peptides (AMPs are endogenous antibiotics that directly affect microorganisms, and also have a variety of receptor-mediated functions. One such AMP, Tilapia piscidin 4 (TP4, was isolated from Nile tilapia (Oreochromis niloticus; TP4 has antibacterial effects and regulates the innate immune system. The aim of the present study was to characterize the role of TP4 in the regulation of wound closure in mice and proliferation of a keratinocyte cell line (HaCaT and fibroblast cell line (Hs-68. In vitro, TP4 stimulated cell proliferation and activated collagen I, collagen III, and keratinocyte growth factor (KGF gene expression in Hs-68 cells, which induces keratin production by HaCaT cells. This effect was detectable at TP4 concentrations of 6.25 µg/mL in both cell lines. In vivo, TP4 was found to be highly effective at combating peritonitis and wound infection caused by MRSA in mouse models, without inducing adverse behavioral effects or liver or kidney toxicity. Taken together, our results indicate that TP4 enhances the survival rate of mice infected with the bacterial pathogen MRSA through both antimicrobial and wound closure activities mediated by epidermal growth factor (EGF, transforming growth factor (TGF, and vascular endothelial growth factor (VEGF. The peptide is likely involved in antibacterial processes and regulation of tissue homeostasis in infected wounds in mice. Overall, these results suggest that TP4 may be suitable for development as a novel topical agent for wound dressing.

Performance of suspended and attached growth MBR systems in treating high strength synthetic wastewater.

Science.gov (United States)

Jamal Khan, S; Ilyas, Shazia; Javid, Sadaf; Visvanathan, C; Jegatheesan, V

2011-05-01

The performance of laboratory-scale attached growth (AG) and suspended growth (SG) membrane bioreactors (MBRs) was evaluated in treating synthetic wastewater simulating high strength domestic wastewater. This study investigated the influence of sponge suspended carriers in AG-MBR system, occupying 15% reactor volume, on the removal of chemical oxygen demand (COD), total nitrogen (TN) and total phosphorus (TP), and compared it to that of SG-MBR. Results showed that the removal efficiencies of COD, TN and TP in AG-MBR were 98%, 89% and 58%, respectively as compared to 98%, 74% and 38%, respectively in SG-MBR. Improved TN removal in AG-MBR systems was primarily based on simultaneous nitrification and denitrification (SND) process. These results infer that the presence of small bio-particles having higher microbial activity and the growth of complex biomass captured within the suspended sponge carriers resulted in improved TN and TP removal in AG-MBR. Copyright © 2010 Elsevier Ltd. All rights reserved.

Basic science through engineering? Synthetic modeling and the idea of biology-inspired engineering.

Science.gov (United States)

Knuuttila, Tarja; Loettgers, Andrea

2013-06-01

Synthetic biology is often understood in terms of the pursuit for well-characterized biological parts to create synthetic wholes. Accordingly, it has typically been conceived of as an engineering dominated and application oriented field. We argue that the relationship of synthetic biology to engineering is far more nuanced than that and involves a sophisticated epistemic dimension, as shown by the recent practice of synthetic modeling. Synthetic models are engineered genetic networks that are implanted in a natural cell environment. Their construction is typically combined with experiments on model organisms as well as mathematical modeling and simulation. What is especially interesting about this combinational modeling practice is that, apart from greater integration between these different epistemic activities, it has also led to the questioning of some central assumptions and notions on which synthetic biology is based. As a result synthetic biology is in the process of becoming more "biology inspired." Copyright © 2013 Elsevier Ltd. All rights reserved.

Prediction of Microcystis Blooms Based on TN:TP Ratio and Lake Origin

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Yoshimasa Amano

2008-01-01

Full Text Available We evaluated the relationship between TN:TP ratio and Microcystis growth via a database that includes worldwide lakes based on four types of lake origin (dammed, tectonic, coastal, and volcanic lakes. We used microcosm and mesocosm for the nutrient elution tests with lake water and four kinds of sediment (nontreated, MgO sprinkling treated, dissolved air flotation [DAF] treated, and combined treated sediment in order to control TN:TP ratio and to suppress Microcystis growth. Microcystis growth was related to TN:TP ratio, with the maximum value at an optimum TN:TP ratio and the minimum values when the TN:TP ratios reached to 0 or ∞. The kurtosis of the distribution curve varied with the type of lake origin; the lowest kurtosis was found in dammed lakes, while the highest was found in volcanic lakes. The lake trophic state could affect the change in the kurtosis, providing much lower kurtosis at eutrophic lakes (dammed lakes than that at oligotrophic lakes (volcanic lakes. The relationship between TN:TP ratio and Microcystis growth could be explained by the nutrient elution tests under controlled TN:TP ratios through the various sediment treatments. A significant suppression of Microcystis growth of 70% could be achieved when the TN:TP ratios exceeded 21. Lake origin could be regarded as an index including morphological and geographical factors, and controlling the trophic state in lakes. The origin rather than trophic state for lakes could be considered as an important factor of TN:TP influences on Microcystis growth.

Jet creation in post-AGB binaries: the circum-companion accretion disk around BD+46°442

Science.gov (United States)

Bollen, Dylan; Van Winckel, Hans; Kamath, Devika

2017-11-01

Aims: We aim at describing and understanding binary interaction processes in systems with very evolved companions. Here, we focus on understanding the origin and determining the properties of the high-velocity outflow observed in one such system. Methods: We present a quantitative analysis of BD+46°442, a post-AGB binary that shows active mass transfer that leads to the creation of a disk-driven outflow or jet. We obtained high-resolution optical spectra from the HERMES spectrograph, mounted on the 1.2 m Flemish Mercator Telescope. By performing a time-series analysis of the Hα profile, we identified the different components of the system. We deduced the jet geometry by comparing the orbital phased data with our jet model. In order to image the accretion disk around the companion of BD+46°442, we applied the technique of Doppler tomography. Results: The orbital phase-dependent variations in the Hα profile can be related to an accretion disk around the companion, from which a high-velocity outflow or jet is launched. Our model shows that there is a clear correlation between the inclination angle and the jet opening angle. The latitudinally dependent velocity structure of our jet model shows a good correspondence to the data, with outflow velocities higher than at least 400 km s-1. The intensity peak in the Doppler map might be partly caused by a hot spot in the disk, or by a larger asymmetrical structure in the disk. Conclusions: We show that BD+46°442 is a result of a binary interaction channel. The origin of the fast outflow in this system might be to a gaseous disk around the secondary component, which is most likely a main-sequence star. Our analysis suggests that the outflow has a rather wide opening angle and is not strongly collimated. Our time-resolved spectral monitoring reveals the launching site of the jet in the binary BD+46°442. Similar orbital phase-dependent Hα profiles are commonly observed in post-AGB binaries. Post-AGB binaries provide ideal

TP53 and lacZ mutagenesis induced by 3-nitrobenzanthrone in Xpa-deficient human TP53 knock-in mouse embryo fibroblasts.

Science.gov (United States)

Kucab, Jill E; Zwart, Edwin P; van Steeg, Harry; Luijten, Mirjam; Schmeiser, Heinz H; Phillips, David H; Arlt, Volker M

2016-03-01

3-Nitrobenzanthrone (3-NBA) is a highly mutagenic compound and possible human carcinogen found in diesel exhaust. 3-NBA forms bulky DNA adducts following metabolic activation and induces predominantly G:CT:A transversions in a variety of experimental systems. Here we investigated the influence of nucleotide excision repair (NER) on 3-NBA-induced mutagenesis of the human tumour suppressor gene TP53 and the reporter gene lacZ. To this end we utilised Xpa -knockout (Xpa-Null) human TP53 knock-in (Hupki) embryo fibroblasts (HUFs). As Xpa is essential for NER of bulky DNA adducts, we hypothesized that DNA adducts induced by 3-NBA would persist in the genomes of Xpa-Null cells and lead to an increased frequency of mutation. The HUF immortalisation assay was used to select for cells harbouring TP53 mutations following mutagen exposure. We found that Xpa-Null Hupki mice and HUFs were more sensitive to 3-NBA treatment than their wild-type (Xpa-WT) counterparts. However, following 3-NBA treatment and immortalisation, a similar frequency of TP53-mutant clones arose from Xpa-WT and Xpa-Null HUF cultures. In cells from both Xpa genotypes G:CT:A transversion was the predominant TP53 mutation type and mutations exhibited bias towards the non-transcribed strand. Thirty-two percent of 3-NBA-induced TP53 mutations occurred at CpG sites, all of which are hotspots for mutation in smokers' lung cancer (codons 157, 158, 175, 245, 248, 273, 282). We also examined 3-NBA-induced mutagenesis of an integrated lacZ reporter gene in HUFs, where we again observed a similar mutant frequency in Xpa-WT and Xpa-Null cells. Our findings suggest that 3-NBA-DNA adducts may evade removal by global genomic NER; the persistence of 3-NBA adducts in DNA may be an important factor in its mutagenicity. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Clear Plaque Mutants of Lactococcal Phage TP901-1

DEFF Research Database (Denmark)

Kot, Witold; Kilstrup, Mogens; Vogensen, Finn K.

2016-01-01

We report a method for obtaining turbid plaques of the lactococcal bacteriophage TP901-1 and its derivative TP901-BC1034. We have further used the method to isolate clear plaque mutants of this phage. Analysis of 8 such mutants that were unable to lysogenize the host included whole genome...

Defects in mitophagy promote redox-driven metabolic syndrome in the absence of TP53INP1.

Science.gov (United States)

Seillier, Marion; Pouyet, Laurent; N'Guessan, Prudence; Nollet, Marie; Capo, Florence; Guillaumond, Fabienne; Peyta, Laure; Dumas, Jean-François; Varrault, Annie; Bertrand, Gyslaine; Bonnafous, Stéphanie; Tran, Albert; Meur, Gargi; Marchetti, Piero; Ravier, Magalie A; Dalle, Stéphane; Gual, Philippe; Muller, Dany; Rutter, Guy A; Servais, Stéphane; Iovanna, Juan L; Carrier, Alice

2015-06-01

The metabolic syndrome covers metabolic abnormalities including obesity and type 2 diabetes (T2D). T2D is characterized by insulin resistance resulting from both environmental and genetic factors. A genome-wide association study (GWAS) published in 2010 identified TP53INP1 as a new T2D susceptibility locus, but a pathological mechanism was not identified. In this work, we show that mice lacking TP53INP1 are prone to redox-driven obesity and insulin resistance. Furthermore, we demonstrate that the reactive oxygen species increase in TP53INP1-deficient cells results from accumulation of defective mitochondria associated with impaired PINK/PARKIN mitophagy. This chronic oxidative stress also favors accumulation of lipid droplets. Taken together, our data provide evidence that the GWAS-identified TP53INP1 gene prevents metabolic syndrome, through a mechanism involving prevention of oxidative stress by mitochondrial homeostasis regulation. In conclusion, this study highlights TP53INP1 as a molecular regulator of redox-driven metabolic syndrome and provides a new preclinical mouse model for metabolic syndrome clinical research. © 2015 The Authors. Published under the terms of the CC BY 4.0 license.

[Evaluation of the Performance of Two Kinds of Anti-TP Enzyme-Linked Immunosorbent Assay].

Science.gov (United States)

Gao, Nan; Huang, Li-Qin; Wang, Rui; Jia, Jun-Jie; Wu, Shuo; Zhang, Jing; Ge, Hong-Wei

2018-06-01

To evaluate the accuracy and precision of 2 kinds of anti-treponema pallidum (anti-TP) ELISA reagents in our laboratory for detecting the anti-TP in voluntary blood donors, so as to provide the data support for use of ELISA reagents after introduction of chemiluminescene immunoassay (CLIA). The route detection of anti-TP was performed by using 2 kinds of ELISA reagents, then 546 responsive positive samples detected by anti-TP ELISA were collected, and the infections status of samples confirmed by treponema pallidum particle agglutination (TPPA) test was identified. The confirmed results of responsive samples detected by 2 kinds of anti-TP ELISA reagents were compared, the accuracy of 2 kinds of anti-TP ELISA reagents was analyzed by drawing ROC and comparing area under curve (AUC), and precision of 2 kinds of anti-TP ELISA reagents was compared by statistical analysis of quality control data from 7.1 2016 to 6.30 2017. There were no statistical difference in confirmed positive rate of responsive samples and weak positive samples between 2 kinds of anti-TP ELISA reagents. The responsive samples detected by 2 kinds of anti-TP ELISA reagents accounted for 85.53%(467/546) of all responsive samples, the positive rate confirmed by TPPA test was 82.87%. 44 responsive samples detected by anti-TP ELISA reagent A and 35 responsive samples detected by anti-TP ELISA reagent B were confirmed to be negative by TPPA test. Comparison of AUC showed that the accuracy of 2 kinds of anti-TP ELISA reagents was more high, the difference between 2 reagents was not statistically significant. The coefficient of variation (CV) of anti-TP ELISA reagent A and B was 14.98% and 18.04% respectively, which met the precision requirement of ELISA test. The accuracy and precision of 2 kinds of anti-TP ELISA reagents used in our laboratory are similar, and using any one of anti-TP ELISA reagents all can satisfy the requirements of blood screening.

Diagnostic value of recombinant Tp0821 protein in serodiagnosis for syphilis.

Science.gov (United States)

Xie, Y; Xu, M; Wang, C; Xiao, J; Xiao, Y; Jiang, C; You, X; Zhao, F; Zeng, T; Liu, S; Kuang, X; Wu, Y

2016-04-01

Syphilis is a multistage sexually transmitted disease that remains a serious public health concern worldwide. The coexistence of Treponema pallidum with other closely related members of spirochaeta, such as Leptospira spp. and Borrelia burgdorferi, has complicated the serodiagnosis due to cross-reactive antigens. In this study, recombinant Tp0821 protein was expressed in Escherichia coli and purified by metal affinity chromatography. Then enzyme-linked immunosorbent assays (ELISAs) based on Tp0821 for the detection of specific antibodies were established. The relative positive rates of the IgM ELISA and the IgG ELISA were found to be 91·0 and 98·3%, respectively, when screening 578 syphilis specimens. The specificities were 94·3 and 100%, respectively, when cross-checking with serum samples obtained from 30 patients with Lyme disease, five patients with leptospirosis, and 52 uninfected controls. In addition, relative positive rates and specificities of Tp0821 for human sera were all 100% in Western blotting. When compared to the syphilis diagnostic tests commonly used in clinical settings, we found that the results of Tp0821-based ELISAs correlated well with the results of the treponemal tests, specifically the T. pallidum particle agglutination (TP-PA) test and the chemiluminescent immunoassay (CIA). Thus, these findings identify Tp0821 as a novel serodiagnostic candidate for syphilis. In this study, we expressed and purified the Treponema pallidum protein Tp0821 and developed Tp0821-based enzyme-linked immunosorbent assays (ELISAs) for the detection of specific antibodies. The serodiagnostic performance of the recombinant protein was then evaluated. When compared to the results of syphilis diagnostic tests commonly used in clinical settings, we found that the reactivities of syphilitic sera with the recombinant antigen correlated well with the results of the treponemal tests, specifically the T. pallidum particle agglutination (TP-PA) test and the

A Statistical Approach For Modeling Tropical Cyclones. Synthetic Hurricanes Generator Model

Energy Technology Data Exchange (ETDEWEB)

Pasqualini, Donatella [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

2016-05-11

This manuscript brie y describes a statistical ap- proach to generate synthetic tropical cyclone tracks to be used in risk evaluations. The Synthetic Hur- ricane Generator (SynHurG) model allows model- ing hurricane risk in the United States supporting decision makers and implementations of adaptation strategies to extreme weather. In the literature there are mainly two approaches to model hurricane hazard for risk prediction: deterministic-statistical approaches, where the storm key physical parameters are calculated using physi- cal complex climate models and the tracks are usually determined statistically from historical data; and sta- tistical approaches, where both variables and tracks are estimated stochastically using historical records. SynHurG falls in the second category adopting a pure stochastic approach.

Probing the mass-loss history of AGB and red supergiant stars from CO rotational line profiles - I. Theoretical model - Mass-loss history unravelled in VYCMa

NARCIS (Netherlands)

Decin, L.; Hony, S.; de Koter, A.; Justtanont, K.; Tielens, A. G. G. M.; Waters, L. B. F. M.

Context. Mass loss plays a dominant role in the evolution of low mass stars while they are on the Asymptotic Giant Branch (AGB). The gas and dust ejected during this phase are a major source in the mass budget of the interstellar medium. Recent studies have pointed towards the importance of

Alterations of the TP53 Gene in Gastric and Esophageal Carcinogenesis

Directory of Open Access Journals (Sweden)

Marilanda Ferreira Bellini

2012-01-01

Full Text Available TP53 genes is one of more important tumor suppressor gene, which acts as a potent transcription factor with fundamental role in the maintenance of genetic stability. The development of esophageal and gastric cancers is a multistep process resulting in successive accumulation of genetic alterations that culminates in the malignant transformation. Thus, this study highlights the participation of the main genetic alterations of the TP53 gene in esophageal and gastric carcinogenesis. Among these changes, high frequency of TP53 mutations, loss of heterozygosity (LOH, overexpression of the p53 protein, and consequently loss of p53 function, which would be early events in esophageal and gastric cancers, as well as an important biomarker of the prognosis and treatment response. Furthermore, Single Nucleotide Polymorphisms (SNPs of TP53 have been implicated in the development and prognosis of several cancers, mainly TP53 codon 72 polymorphism whose role has been extensively studied in relation to susceptibility for esophageal and gastric cancer development.

Bioinformatics and phylogenetic analysis of human Tp73 gene ...

African Journals Online (AJOL)

The Tp73 gene encoding p73 protein belongs to the Tp53 gene family and it functions in the initiation of cell-cycle arrest or apoptosis and also involves in regulating a series of pathways including breast cancer, neuroblastoma and cholorectal cancer. New discoveries about the control and function of p73 are still in progress ...

Key Players in the Genetic Switch of Bacteriophage TP901-1

DEFF Research Database (Denmark)

Alsing, Anne; Pedersen, Margit; Sneppen, Kim

2011-01-01

the bistable genetic switch of bacteriophage TP901-1 through experiments and statistical mechanical modeling. We examine the activity of the lysogenic promoter Pr at different concentrations of the phage repressor, CI, and compare the effect of CI on Pr in the presence or absence of the phage-encoded MOR...

Protein - TP Atlas | LSDB Archive [Life Science Database Archive metadata

Lifescience Database Archive (English)

Full Text Available switchLanguage; BLAST Search Image Search Home About Archive Update History Data ...p_atlas_protein.zip File URL: ftp://ftp.biosciencedbc.jp/archive/tp_atlas/LATEST/...story of This Database Site Policy | Contact Us Protein - TP Atlas | LSDB Archive ...

Low Prevalence of TP53 Mutations and MDM2 Amplifications in Pediatric Rhabdomyosarcoma

Directory of Open Access Journals (Sweden)

Simona Ognjanovic

2012-01-01

Full Text Available The tumor suppressor gene TP53 is the most commonly mutated gene in human cancer. The reported prevalence of mutations in rhabdomyosarcoma (RMS varies widely, with recent larger studies suggesting that TP53 mutations in pediatric RMS may be extremely rare. Overexpression of MDM2 also attenuates p53 function. We have performed TP53 mutation/MDM2 amplification analyses in the largest series analyzed thus far, including DNA isolated from 37 alveolar and 38 embryonal RMS tumor samples obtained from the Cooperative Human Tissue Network (CHTN. Available samples were frozen tumor tissues (N=48 and histopathology slides. TP53 mutations in exons 4–9 were analyzed by direct sequencing in all samples, and MDM2 amplification analysis was performed by differential PCR on a subset of 22 samples. We found only one sample (1/75, 1.3% carrying a TP53 mutation at codon 259 (p.D259Y and no MDM2 amplification. Two SNPs in the TP53 pathway, associated with accelerated tumor onset in germline TP53 mutation carriers, (TP53 SNP72 (rs no. 1042522 and MDM2 SNP309 (rs no. 2279744, were not found to confer earlier tumor onset. In conclusion, we confirm the extremely low prevalence of TP53 mutations/MDM2 amplifications in pediatric RMS (1.33% and 0%, respectively. The possible inactivation of p53 function by other mechanisms thus remains to be elucidated.

Long Memory Models to Generate Synthetic Hydrological Series

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Guilherme Armando de Almeida Pereira

2014-01-01

Full Text Available In Brazil, much of the energy production comes from hydroelectric plants whose planning is not trivial due to the strong dependence on rainfall regimes. This planning is accomplished through optimization models that use inputs such as synthetic hydrologic series generated from the statistical model PAR(p (periodic autoregressive. Recently, Brazil began the search for alternative models able to capture the effects that the traditional model PAR(p does not incorporate, such as long memory effects. Long memory in a time series can be defined as a significant dependence between lags separated by a long period of time. Thus, this research develops a study of the effects of long dependence in the series of streamflow natural energy in the South subsystem, in order to estimate a long memory model capable of generating synthetic hydrologic series.

TP53 dysfunction in CLL: Implications for prognosis and treatment

NARCIS (Netherlands)

te Raa, Gera D.; Kater, Arnon P.

2016-01-01

Despite the availability of novel targeted agents, TP53 defects remain the most important adverse prognostic factor in chronic lymphocytic leukemia (CLL). Detection of deletion of TP53 locus (17p deletion) by fluorescent in situ hybridization (FISH) has become standard and performed prior to every

Limited importance of the dominant-negative effect of TP53 missense mutations

International Nuclear Information System (INIS)

Stoczynska-Fidelus, Ewelina; Liberski, Pawel P; Rieske, Piotr; Szybka, Malgorzata; Piaskowski, Sylwester; Bienkowski, Michal; Hulas-Bigoszewska, Krystyna; Banaszczyk, Mateusz; Zawlik, Izabela; Jesionek-Kupnicka, Dorota; Kordek, Radzislaw

2011-01-01

Heterozygosity of TP53 missense mutations is related to the phenomenon of the dominant-negative effect (DNE). To estimate the importance of the DNE of TP53 mutations, we analysed the percentage of cancer cases showing a single heterozygous mutation of TP53 and searched for a cell line with a single heterozygous mutation of this gene. This approach was based on the knowledge that genes with evident DNE, such as EGFR and IDH1, represent nearly 100% of single heterozygous mutations in tumour specimens and cell lines. Genetic analyses (LOH and sequencing) performed for early and late passages of several cell lines originally described as showing single heterozygous TP53 mutations (H-318, G-16, PF-382, MOLT-13, ST-486 and LS-123). Statistical analysis of IARC TP53 and SANGER databases. Genetic analyses of N-RAS, FBXW7, PTEN and STR markers to test cross-contamination and cell line identity. Cell cloning, fluorescence-activated cell sorting and SSCP performed for the PF-382 cell line. A database study revealed TP53 single heterozygous mutations in 35% of in vivo (surgical and biopsy) samples and only 10% of cultured cells (in vitro), although those numbers appeared to be overestimated. We deem that published in vivo TP53 mutation analyses are not as rigorous as studies in vitro, and we did not find any cell line showing a stable, single heterozygous mutation. G16, PF-382 and MOLT-13 cells harboured single heterozygous mutations temporarily. ST-486, H-318 and LS-123 cell lines were misclassified. Specific mutations, such as R175H, R273H, R273L or R273P, which are reported in the literature to exert a DNE, showed the lowest percentage of single heterozygous mutations in vitro (about 5%). We suggest that the currently reported percentage of TP53 single heterozygous mutations in tumour samples and cancer cell lines is overestimated. Thus, the magnitude of the DNE of TP53 mutations is questionable. This scepticism is supported by database investigations showing that retention

Pediatric oncologist willingness to offer germline TP53 testing in osteosarcoma.

Science.gov (United States)

Shaul, Eliana; Roth, Michael; Lo, Yungtai; Geller, David S; Hoang, Bang; Yang, Rui; Malkin, David; Gorlick, Richard; Gill, Jonathan

2018-03-15

Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome caused by mutations in the tumor-suppressor gene TP53. Osteosarcoma is a sentinel cancer in LFS. Prior studies using Sanger sequencing platforms have demonstrated that 3% of individuals with osteosarcoma harbor a mutation in TP53. New data from next-generation sequencing have demonstrated that 3.8% of patients with osteosarcoma have a known pathogenic variant, and an additional 5.7% carry exonic variants of unknown significance in TP53. Pediatric oncologists were e-mailed an anonymous 18-question survey assessing their willingness to offer TP53 germline testing to a child with osteosarcoma with or without a family history, and they were evaluated for changes in their choices with the prior data and the new data. One hundred seventy-seven pediatric oncologists (22%) responded to the survey. Respondents were more likely to offer TP53 testing to a patient with a positive family history (77.4% vs 12.4%; P offer TP53 testing once they were provided with the new data (25.4% vs 12.4%; P = .0038). The proportion of providers who responded that they were unsure increased significantly when they were presented with the new data (25.4% vs 10.2%; P = .0002). Potential implications for other family members and the possibility that surveillance imaging would detect new malignancies at an earlier stage were important factors influencing a provider's decision to offer TP53 testing. Recent data increase the proportion of providers willing to offer testing, and this suggests concern on the part of pediatric oncologists that variants of unknown significance may be disease-defining in rare cancers. Cancer 2018;124:1242-50. © 2018 American Cancer Society. © 2018 American Cancer Society.

TP53inp1 Gene Is Implicated in Early Radiation Response in Human Fibroblast Cells

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Nikolett Sándor

2015-10-01

Full Text Available Tumor protein 53-induced nuclear protein-1 (TP53inp1 is expressed by activation via p53 and p73. The purpose of our study was to investigate the role of TP53inp1 in response of fibroblasts to ionizing radiation. γ-Ray radiation dose-dependently induces the expression of TP53inp1 in human immortalized fibroblast (F11hT cells. Stable silencing of TP53inp1 was done via lentiviral transfection of shRNA in F11hT cells. After irradiation the clonogenic survival of TP53inp1 knockdown (F11hT-shTP cells was compared to cells transfected with non-targeting (NT shRNA. Radiation-induced senescence was measured by SA-β-Gal staining and autophagy was detected by Acridine Orange dye and microtubule-associated protein-1 light chain 3 (LC3B immunostaining. The expression of TP53inp1, GDF-15, and CDKN1A and alterations in radiation induced mitochondrial DNA deletions were evaluated by qPCR. TP53inp1 was required for radiation (IR induced maximal elevation of CDKN1A and GDF-15 expressions. Mitochondrial DNA deletions were increased and autophagy was deregulated following irradiation in the absence of TP53inp1. Finally, we showed that silencing of TP53inp1 enhances the radiation sensitivity of fibroblast cells. These data suggest functional roles for TP53inp1 in radiation-induced autophagy and survival. Taken together, we suppose that silencing of TP53inp1 leads radiation induced autophagy impairment and induces accumulation of damaged mitochondria in primary human fibroblasts.

Accuracy of Genomic Selection in a Rice Synthetic Population Developed for Recurrent Selection Breeding.

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Cécile Grenier

Full Text Available Genomic selection (GS is a promising strategy for enhancing genetic gain. We investigated the accuracy of genomic estimated breeding values (GEBV in four inter-related synthetic populations that underwent several cycles of recurrent selection in an upland rice-breeding program. A total of 343 S2:4 lines extracted from those populations were phenotyped for flowering time, plant height, grain yield and panicle weight, and genotyped with an average density of one marker per 44.8 kb. The relative effect of the linkage disequilibrium (LD and minor allele frequency (MAF thresholds for selecting markers, the relative size of the training population (TP and of the validation population (VP, the selected trait and the genomic prediction models (frequentist and Bayesian on the accuracy of GEBVs was investigated in 540 cross validation experiments with 100 replicates. The effect of kinship between the training and validation populations was tested in an additional set of 840 cross validation experiments with a single genomic prediction model. LD was high (average r2 = 0.59 at 25 kb and decreased slowly, distribution of allele frequencies at individual loci was markedly skewed toward unbalanced frequencies (MAF average value 15.2% and median 9.6%, and differentiation between the four synthetic populations was low (FST ≤0.06. The accuracy of GEBV across all cross validation experiments ranged from 0.12 to 0.54 with an average of 0.30. Significant differences in accuracy were observed among the different levels of each factor investigated. Phenotypic traits had the biggest effect, and the size of the incidence matrix had the smallest. Significant first degree interaction was observed for GEBV accuracy between traits and all the other factors studied, and between prediction models and LD, MAF and composition of the TP. The potential of GS to accelerate genetic gain and breeding options to increase the accuracy of predictions are discussed.

Variation in stem mortality rates determines patterns of above-ground biomass in Amazonian forests: implications for dynamic global vegetation models.

Science.gov (United States)

Johnson, Michelle O; Galbraith, David; Gloor, Manuel; De Deurwaerder, Hannes; Guimberteau, Matthieu; Rammig, Anja; Thonicke, Kirsten; Verbeeck, Hans; von Randow, Celso; Monteagudo, Abel; Phillips, Oliver L; Brienen, Roel J W; Feldpausch, Ted R; Lopez Gonzalez, Gabriela; Fauset, Sophie; Quesada, Carlos A; Christoffersen, Bradley; Ciais, Philippe; Sampaio, Gilvan; Kruijt, Bart; Meir, Patrick; Moorcroft, Paul; Zhang, Ke; Alvarez-Davila, Esteban; Alves de Oliveira, Atila; Amaral, Ieda; Andrade, Ana; Aragao, Luiz E O C; Araujo-Murakami, Alejandro; Arets, Eric J M M; Arroyo, Luzmila; Aymard, Gerardo A; Baraloto, Christopher; Barroso, Jocely; Bonal, Damien; Boot, Rene; Camargo, Jose; Chave, Jerome; Cogollo, Alvaro; Cornejo Valverde, Fernando; Lola da Costa, Antonio C; Di Fiore, Anthony; Ferreira, Leandro; Higuchi, Niro; Honorio, Euridice N; Killeen, Tim J; Laurance, Susan G; Laurance, William F; Licona, Juan; Lovejoy, Thomas; Malhi, Yadvinder; Marimon, Bia; Marimon, Ben Hur; Matos, Darley C L; Mendoza, Casimiro; Neill, David A; Pardo, Guido; Peña-Claros, Marielos; Pitman, Nigel C A; Poorter, Lourens; Prieto, Adriana; Ramirez-Angulo, Hirma; Roopsind, Anand; Rudas, Agustin; Salomao, Rafael P; Silveira, Marcos; Stropp, Juliana; Ter Steege, Hans; Terborgh, John; Thomas, Raquel; Toledo, Marisol; Torres-Lezama, Armando; van der Heijden, Geertje M F; Vasquez, Rodolfo; Guimarães Vieira, Ima Cèlia; Vilanova, Emilio; Vos, Vincent A; Baker, Timothy R

2016-12-01

Understanding the processes that determine above-ground biomass (AGB) in Amazonian forests is important for predicting the sensitivity of these ecosystems to environmental change and for designing and evaluating dynamic global vegetation models (DGVMs). AGB is determined by inputs from woody productivity [woody net primary productivity (NPP)] and the rate at which carbon is lost through tree mortality. Here, we test whether two direct metrics of tree mortality (the absolute rate of woody biomass loss and the rate of stem mortality) and/or woody NPP, control variation in AGB among 167 plots in intact forest across Amazonia. We then compare these relationships and the observed variation in AGB and woody NPP with the predictions of four DGVMs. The observations show that stem mortality rates, rather than absolute rates of woody biomass loss, are the most important predictor of AGB, which is consistent with the importance of stand size structure for determining spatial variation in AGB. The relationship between stem mortality rates and AGB varies among different regions of Amazonia, indicating that variation in wood density and height/diameter relationships also influences AGB. In contrast to previous findings, we find that woody NPP is not correlated with stem mortality rates and is weakly positively correlated with AGB. Across the four models, basin-wide average AGB is similar to the mean of the observations. However, the models consistently overestimate woody NPP and poorly represent the spatial patterns of both AGB and woody NPP estimated using plot data. In marked contrast to the observations, DGVMs typically show strong positive relationships between woody NPP and AGB. Resolving these differences will require incorporating forest size structure, mechanistic models of stem mortality and variation in functional composition in DGVMs. © 2016 The Authors. Global Change Biology Published by John Wiley & Sons Ltd.

Analisis Jaringan VPN Menggunakan PPTP dan L2TP

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Syariful Ikhwan

2017-08-01

Full Text Available VPN adalah teknologi yang membuat jaringan private (pribadi dengan menggunakan jaringan publik agar proses pertukaran data menjadi aman. Teknologi VPN biasanya diterapkan untuk koneksi antara kantor pusat dan kantor cabang. Dinhubkominfo Kabupaten Banyumas sebagai tempat penelitian memiliki beberapa kantor cabang (SKPD. Data yang dipertukarkan antar kantor cabang pada Dinhubkominfo terdiri dari beberapa jenis, namun pada penelitian ini hanya difokuskan pada pertukaran layanan FTP. Teknologi vpn yang saat ini digunakan pada jaringan Dinhubkominfo adalah PPTP. Akan tetapi, penggunaan teknologi tersebut belum tersebut masih belum diketahui tingkat performansi jaringan dibandingkan dengan penggunaan teknologi vpn yang lain. Pada penelitian ini akan dibandingkan penggunaan dua teknologi vpn yang berbeda yaitu antara PPTP dan L2TP, dimana parameter yang digunakan adalah throughput, delay, jitter, dan packet loss. Proses pengambilan data dilakukan dengan menambahkan beban trafik sebesar 512 kbps, 1024 kbps, dan 2048 kbps. Dari hasil penelitian diperoleh data bahwa, rata-rata nilai Delay pada L2TP lebih besar hingga 41% dibanding saat menggunakan PPTP, rata-rata Throughput PPTP naik hingga 34% dibandingkan L2TP, Rata-rata Jitter pada PPTP lebih besar hingga 44% dibandingkan L2TP, sedangkan packet loss yang terjadi pada masing-masing layanan vpn adalah 0

Evolution and nucleosynthesis of asymptotic giant branch stellar models of low metallicity

Energy Technology Data Exchange (ETDEWEB)

Fishlock, Cherie K.; Karakas, Amanda I.; Yong, David [Research School of Astronomy and Astrophysics, Australian National University, Canberra ACT 2611 (Australia); Lugaro, Maria, E-mail: cherie.fishlock@anu.edu.au, E-mail: amanda.karakas@anu.edu.au, E-mail: david.yong@anu.edu.au, E-mail: maria.lugaro@monash.edu [Monash Centre for Astrophysics, Monash University, Clayton VIC 3800 (Australia)

2014-12-10

We present stellar evolutionary tracks and nucleosynthetic predictions for a grid of stellar models of low- and intermediate-mass asymptotic giant branch (AGB) stars at Z = 0.001 ([Fe/H] =–1.2). The models cover an initial mass range from 1 M {sub ☉} to 7 M {sub ☉}. Final surface abundances and stellar yields are calculated for all elements from hydrogen to bismuth as well as isotopes up to the iron group. We present the first study of neutron-capture nucleosynthesis in intermediate-mass AGB models, including a super-AGB model, of [Fe/H] = –1.2. We examine in detail a low-mass AGB model of 2 M {sub ☉} where the {sup 13}C(α,n){sup 16}O reaction is the main source of neutrons. We also examine an intermediate-mass AGB model of 5 M {sub ☉} where intershell temperatures are high enough to activate the {sup 22}Ne neutron source, which produces high neutron densities up to ∼10{sup 14} n cm{sup –3}. Hot bottom burning is activated in models with M ≥ 3 M {sub ☉}. With the 3 M {sub ☉} model, we investigate the effect of varying the extent in mass of the region where protons are mixed from the envelope into the intershell at the deepest extent of each third dredge-up. We compare the results of the low-mass models to three post-AGB stars with a metallicity of [Fe/H] ≅ – 1.2. The composition is a good match to the predicted neutron-capture abundances except for Pb and we confirm that the observed Pb abundances are lower than what is calculated by AGB models.

Development of a Regional Lidar-Derived Above-Ground Biomass Model with Bayesian Model Averaging for Use in Ponderosa Pine and Mixed Conifer Forests in Arizona and New Mexico, USA

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Karis Tenneson

2018-03-01

Full Text Available Historical forest management practices in the southwestern US have left forests prone to high-severity, stand-replacement fires. Reducing the cost of forest-fire management and reintroducing fire to the landscape without negative impact depends on detailed knowledge of stand composition, in particular, above-ground biomass (AGB. Lidar-based modeling techniques provide opportunities to increase ability of managers to monitor AGB and other forest metrics at reduced cost. We developed a regional lidar-based statistical model to estimate AGB for Ponderosa pine and mixed conifer forest systems of the southwestern USA, using previously collected field data. Model selection was performed using Bayesian model averaging (BMA to reduce researcher bias, fully explore the model space, and avoid overfitting. The selected model includes measures of canopy height, canopy density, and height distribution. The model selected with BMA explains 71% of the variability in field-estimates of AGB, and the RMSE of the two independent validation data sets are 23.25 and 32.82 Mg/ha. The regional model is structured in accordance with previously described local models, and performs equivalently to these smaller scale models. We have demonstrated the effectiveness of lidar for developing cost-effective, robust regional AGB models for monitoring and planning adaptively at the landscape scale.

KFUPM-KAUST Red Sea model: Digital viscoelastic depth model and synthetic seismic data set

KAUST Repository

Al-Shuhail, Abdullatif A.; Mousa, Wail A.; Alkhalifah, Tariq Ali

2017-01-01

The Red Sea is geologically interesting due to its unique structures and abundant mineral and petroleum resources, yet no digital geologic models or synthetic seismic data of the Red Sea are publicly available for testing algorithms to image and analyze the area's interesting features. This study compiles a 2D viscoelastic model of the Red Sea and calculates a corresponding multicomponent synthetic seismic data set. The models and data sets are made publicly available for download. We hope this effort will encourage interested researchers to test their processing algorithms on this data set and model and share their results publicly as well.

KFUPM-KAUST Red Sea model: Digital viscoelastic depth model and synthetic seismic data set

KAUST Repository

Al-Shuhail, Abdullatif A.

2017-06-01

The Red Sea is geologically interesting due to its unique structures and abundant mineral and petroleum resources, yet no digital geologic models or synthetic seismic data of the Red Sea are publicly available for testing algorithms to image and analyze the area\\'s interesting features. This study compiles a 2D viscoelastic model of the Red Sea and calculates a corresponding multicomponent synthetic seismic data set. The models and data sets are made publicly available for download. We hope this effort will encourage interested researchers to test their processing algorithms on this data set and model and share their results publicly as well.

Modeling aboveground tree woody biomass using national-scale allometric methods and airborne lidar

Science.gov (United States)

Chen, Qi

2015-08-01

Estimating tree aboveground biomass (AGB) and carbon (C) stocks using remote sensing is a critical component for understanding the global C cycle and mitigating climate change. However, the importance of allometry for remote sensing of AGB has not been recognized until recently. The overarching goals of this study are to understand the differences and relationships among three national-scale allometric methods (CRM, Jenkins, and the regional models) of the Forest Inventory and Analysis (FIA) program in the U.S. and to examine the impacts of using alternative allometry on the fitting statistics of remote sensing-based woody AGB models. Airborne lidar data from three study sites in the Pacific Northwest, USA were used to predict woody AGB estimated from the different allometric methods. It was found that the CRM and Jenkins estimates of woody AGB are related via the CRM adjustment factor. In terms of lidar-biomass modeling, CRM had the smallest model errors, while the Jenkins method had the largest ones and the regional method was between. The best model fitting from CRM is attributed to its inclusion of tree height in calculating merchantable stem volume and the strong dependence of non-merchantable stem biomass on merchantable stem biomass. This study also argues that it is important to characterize the allometric model errors for gaining a complete understanding of the remotely-sensed AGB prediction errors.

Common Envelope Evolution: Implications for Post-AGB Stars and Planetary Nebulae

Science.gov (United States)

Nordhaus, J.

2017-10-01

Common envelopes (CE) are of broad interest as they represent one method by which binaries with initially long-period orbits of a few years can be converted into short-period orbits of a few hours. Despite their importance, the brief lifetimes of CE phases make them difficult to directly observe. Nevertheless, CE interactions are potentially common, can produce a diverse array of nebular shapes, and can accommodate current post-AGB and planetary nebula outflow constraints. Here, I discuss ongoing theoretical and computational work on CEs and speculate on what lies ahead for determining accurate outcomes of this elusive phase of evolution.

Reactivating TP53 signaling by the novel MDM2 inhibitor DS-3032b as a therapeutic option for high-risk neuroblastoma

Science.gov (United States)

Arnhold, Viktor; Schmelz, Karin; Proba, Jutta; Winkler, Annika; Wünschel, Jasmin; Toedling, Joern; Deubzer, Hedwig E.; Künkele, Annette; Eggert, Angelika; Schulte, Johannes H.; Hundsdoerfer, Patrick

2018-01-01

Fewer than 50% of patients with high-risk neuroblastoma survive five years after diagnosis with current treatment protocols. Molecular targeted therapies are expected to improve survival. Although MDM2 has been validated as a promising target in preclinical models, no MDM2 inhibitors have yet entered clinical trials for neuroblastoma patients. Toxic side effects, poor bioavailability and low efficacy of the available MDM2 inhibitors that have entered phase I/II trials drive the development of novel MDM2 inhibitors with an improved risk-benefit profile. We investigated the effect of the novel MDM2 small molecular inhibitor, DS-3032b, on viability, proliferation, senescence, migration, cell cycle arrest and apoptosis in a panel of six neuroblastoma cell lines with different TP53 and MYCN genetic backgrounds, and assessed efficacy in a murine subcutaneous model for high-risk neuroblastoma. Re-analysis of existing expression data from 476 primary neuroblastomas showed that high-level MDM2 expression correlated with poor patient survival. DS-3032b treatment enhanced TP53 target gene expression and induced G1 cell cycle arrest, senescence and apoptosis. CRISPR-mediated MDM2 knockout in neuroblastoma cells mimicked DS-3032b treatment. TP53 signaling was selectively activated by DS-3032b in neuroblastoma cells with wildtype TP53, regardless of the presence of MYCN amplification, but was significantly reduced by TP53 mutations or expression of a dominant-negative TP53 mutant. Oral DS-3032b administration inhibited xenograft tumor growth and prolonged mouse survival. Our in vitro and in vivo data demonstrate that DS-3032b reactivates TP53 signaling even in the presence of MYCN amplification in neuroblastoma cells, to reduce proliferative capacity and cause cytotoxicity. PMID:29416773

Update History of This Database - TP Atlas | LSDB Archive [Life Science Database Archive metadata

Lifescience Database Archive (English)

Full Text Available switchLanguage; BLAST Search Image Search Home About Archive Update History Data ...List Contact us TP Atlas Update History of This Database Date Update contents 2013/12/16 The email address i...s ( http://www.tanpaku.org/tpatlas/ ) is opened. About This Database Database Description Download License Update History of Thi...s Database Site Policy | Contact Us Update History of This Database - TP Atlas | LSDB Archive ... ...n the contact information is corrected. 2013/11/19 TP Atlas English archive site is opened. 2008/4/1 TP Atla

TLR4 has a TP53-dependent dual role in regulating breast cancer cell growth.

Science.gov (United States)

Haricharan, Svasti; Brown, Powel

2015-06-23

Breast cancer is a leading cause of cancer-related death, and it is important to understand pathways that drive the disease to devise effective therapeutic strategies. Our results show that Toll-like receptor 4 (TLR4) drives breast cancer cell growth differentially based on the presence of TP53, a tumor suppressor. TP53 is mutationally inactivated in most types of cancer and is mutated in 30-50% of diagnosed breast tumors. We demonstrate that TLR4 activation inhibits growth of TP53 wild-type cells, but promotes growth of TP53 mutant breast cancer cells by regulating proliferation. This differential effect is mediated by changes in tumor cell cytokine secretion. Whereas TLR4 activation in TP53 mutant breast cancer cells increases secretion of progrowth cytokines, TLR4 activation in TP53 wild-type breast cancer cells increases type I IFN (IFN-γ) secretion, which is both necessary and sufficient for mediating TLR4-induced growth inhibition. This study identifies a novel dichotomous role for TLR4 as a growth regulator and a modulator of tumor microenvironment in breast tumors. These results have translational relevance, demonstrating that TP53 mutant breast tumor growth can be suppressed by pharmacologic TLR4 inhibition, whereas TLR4 inhibitors may in fact promote growth of TP53 wild-type tumors. Furthermore, using data generated by The Cancer Genome Atlas consortium, we demonstrate that the effect of TP53 mutational status on TLR4 activity may extend to ovarian, colon, and lung cancers, among others, suggesting that the viability of TLR4 as a therapeutic target depends on TP53 status in many different tumor types.

Heavy-element yields and abundances of asymptotic giant branch models with a Small Magellanic Cloud metallicity

Science.gov (United States)

Karakas, Amanda I.; Lugaro, Maria; Carlos, Marília; Cseh, Borbála; Kamath, Devika; García-Hernández, D. A.

2018-06-01

We present new theoretical stellar yields and surface abundances for asymptotic giant branch (AGB) models with a metallicity appropriate for stars in the Small Magellanic Cloud (SMC, Z = 0.0028, [Fe/H] ≈ -0.7). New evolutionary sequences and post-processing nucleosynthesis results are presented for initial masses between 1 and 7 M⊙, where the 7 M⊙ is a super-AGB star with an O-Ne core. Models above 1.15 M⊙ become carbon rich during the AGB, and hot bottom burning begins in models M ≥ 3.75 M⊙. We present stellar surface abundances as a function of thermal pulse number for elements between C to Bi and for a selection of isotopic ratios for elements up to Fe and Ni (e.g. 12C/13C), which can be compared to observations. The integrated stellar yields are presented for each model in the grid for hydrogen, helium, and all stable elements from C to Bi. We present evolutionary sequences of intermediate-mass models between 4 and 7 M⊙ and nucleosynthesis results for three masses (M = 3.75, 5, and 7 M⊙) including s-process elements for two widely used AGB mass-loss prescriptions. We discuss our new models in the context of evolved AGB and post-AGB stars in the SMCs, barium stars in our Galaxy, the composition of Galactic globular clusters including Mg isotopes with a similar metallicity to our models, and to pre-solar grains which may have an origin in metal-poor AGB stars.

Examining effective use of data sources and modeling algorithms for improving biomass estimation in a moist tropical forest of the Brazilian Amazon

Science.gov (United States)

Yunyun Feng; Dengsheng Lu; Qi Chen; Michael Keller; Emilio Moran; Maiza Nara dos-Santos; Edson Luis Bolfe; Mateus Batistella

2017-01-01

Previous research has explored the potential to integrate lidar and optical data in aboveground biomass (AGB) estimation, but how different data sources, vegetation types, and modeling algorithms influence AGB estimation is poorly understood. This research conducts a comparative analysis of different data sources and modeling approaches in improving AGB estimation....

VizieR Online Data Catalog: Water maser emission toward post-AGB and PN (Gomez+, 2015)

Science.gov (United States)

Gomez, J. F.; Rizzo, J. R.; Suarez, O.; Palau, A.; Miranda, L. F.; Guerrero, M. A.; Ramos-Larios, G.; Torrelles, J. M.

2015-09-01

The observed sources are listed in Table 1. They comprise most of the sources in Ramos-Larios et al. (2009A&A...501.1207R). They are post-AGB stars and PN candidates with the IRAS color criteria of Suarez et al. (2006A&A...458..173S) and with signs of strong optical obscuration. We have also included some optically visible post-AGB stars from Suarez et al. (2006A&A...458..173S) that were not included in our previous water maser observations of Suarez et al. (2007A&A...467.1085S, 2009A&A...505..217S) or for which those observations had poor sensitivity. We observed the 616-523 transition of H2O (rest frequency = 22235.08MHz) using three different telescopes: the DSS-63 antenna (70m diameter) at the Madrid Deep Space Communications Complex (MDSCC) near Robledo de Chavela (Spain), the 64m antenna at the Parkes Observatory of the Australia Telescope National Facility (ATNF), and the 100m Robert C. Byrd Green Bank Telescope (GBT) of the National Radio Astronomy Observatory. The observed positions, rms noise per spectral channel, and observing dates are listed in Table 1. (3 data files).

Phase I study of TP300 in patients with advanced solid tumors with pharmacokinetic, pharmacogenetic and pharmacodynamic analyses

International Nuclear Information System (INIS)

Anthoney, D Alan; Miwa, Masanori; Twelves, Christopher; Evans, TRJ; Naik, Jay; MacPherson, Iain RJ; Crawford, Donna; Hartley, John M; Hartley, Janet A; Saito, Tomohisa; Abe, Masaichi; Jones, Keith

2012-01-01

A Phase I dose escalation first in man study assessed maximum tolerated dose (MTD), dose-limiting toxicity (DLT) and recommended Phase II dose of TP300, a water soluble prodrug of the Topo-1 inhibitor TP3076, and active metabolite, TP3011. Eligible patients with refractory advanced solid tumors, adequate performance status, haematologic, renal, and hepatic function. TP300 was given as a 1-hour i.v. infusion 3-weekly and pharmacokinetic (PK) profiles of TP300, TP3076 and TP3011 were analysed. Polymorphisms in CYP2D6, AOX1 and UGT1A1 were studied and DNA strand-breaks measured in peripheral blood mononuclear cells (PBMCs). 32 patients received TP300 at 1, 2, 4, 6, 8, 10, 12 mg/m 2 . MTD was 10 mg/m 2 ; DLTs at 12 (2/4 patients) and 10 mg/m 2 (3/12) included thrombocytopenia and febrile neutropenia; diarrhoea was uncommon. Six patients (five had received irinotecan), had stable disease for 1.5-5 months. TP3076 showed dose proportionality in AUC and C max from 1–10 mg/m 2 . Genetic polymorphisms had no apparent influence on exposure. DNA strand-breaks were detected after TP300 infusion. TP300 had predictable hematologic toxicity, and diarrhoea was uncommon. AUC at MTD is substantially greater than for SN38. TP3076 and TP3011 are equi-potent with SN38, suggesting a PK advantage. EU-CTR2006-001345-33

CNPY2 promoted the proliferation of renal cell carcinoma cells and increased the expression of TP53

International Nuclear Information System (INIS)

Taniguchi, Hidefumi; Ito, Saya; Ueda, Takashi; Morioka, Yukako; Kayukawa, Naruhiro; Ueno, Akihisa; Nakagawa, Hideo; Fujihara, Atsuko; Ushijima, So; Kanazawa, Motohiro; Hongo, Fumiya; Ukimura, Osamu

2017-01-01

Renal cell carcinoma (RCC) is the most common type of kidney cancer. However, the mechanisms underlying the progression of the disease are not well understood. The data in this report suggest that canopy FGF signaling regulator 2 (CNPY2) is a promoter of RCC progression. We found that CNPY2 significantly promoted growth of RCC cells and upregulated TP53 gene expression. Although TP53 is widely known as a tumor suppressor, in RCC TP53 promoted tumor cell growth. A typical p53 target gene, CDKN1A, was upregulated by both p53 and CNPY2 in RCC cells, suggesting that CNPY2 increased the expression level of TP53. Consistent with these results, CNPY2 and TP53 expression levels were positively correlated in RCC patients. These findings suggested that CNPY2 promoted cancer cell growth in RCC through regulating TP53 gene expression. - Highlights: • CNPY2 promoted growth of renal cell carcinoma (RCC) cells. • TP53 expression levels were increased by CNPY2 in RCC cells. • Growth of RCC cells was promoted by TP53. • CNPY2 expression positively correlated with TP53 expression in RCC patients.

TLR4 has a TP53-dependent dual role in regulating breast cancer cell growth

OpenAIRE

Haricharan, Svasti; Brown, Powel

2015-01-01

This study fundamentally alters our understanding of how TLR4 drives breast cancer. Although TLR4 was previously considered a tumor promoter, we demonstrate a complex, TP53-dependent role for TLR4 in regulating tumor growth. TP53 is a tumor suppressor commonly inactivated across cancer types. In TP53 wild-type cancer cells, TLR4 activation causes secretion of IFN-γ into the microenvironment, resulting in induction of p21 and inhibition of cell growth. Conversely, TLR4 activation in TP53 mutan...

High resolution melting for mutation scanning of TP53 exons 5–8

International Nuclear Information System (INIS)

Krypuy, Michael; Dobrovic, Alexander; Ahmed, Ahmed Ashour; Etemadmoghadam, Dariush; Hyland, Sarah J; Australian Ovarian Cancer Study Group; Fazio, Anna de; Fox, Stephen B; Brenton, James D; Bowtell, David D

2007-01-01

p53 is commonly inactivated by mutations in the DNA-binding domain in a wide range of cancers. As mutant p53 often influences response to therapy, effective and rapid methods to scan for mutations in TP53 are likely to be of clinical value. We therefore evaluated the use of high resolution melting (HRM) as a rapid mutation scanning tool for TP53 in tumour samples. We designed PCR amplicons for HRM mutation scanning of TP53 exons 5 to 8 and tested them with DNA from cell lines hemizygous or homozygous for known mutations. We assessed the sensitivity of each PCR amplicon using dilutions of cell line DNA in normal wild-type DNA. We then performed a blinded assessment on ovarian tumour DNA samples that had been previously sequenced for mutations in TP53 to assess the sensitivity and positive predictive value of the HRM technique. We also performed HRM analysis on breast tumour DNA samples with unknown TP53 mutation status. One cell line mutation was not readily observed when exon 5 was amplified. As exon 5 contained multiple melting domains, we divided the exon into two amplicons for further screening. Sequence changes were also introduced into some of the primers to improve the melting characteristics of the amplicon. Aberrant HRM curves indicative of TP53 mutations were observed for each of the samples in the ovarian tumour DNA panel. Comparison of the HRM results with the sequencing results revealed that each mutation was detected by HRM in the correct exon. For the breast tumour panel, we detected seven aberrant melt profiles by HRM and subsequent sequencing confirmed the presence of these and no other mutations in the predicted exons. HRM is an effective technique for simple and rapid scanning of TP53 mutations that can markedly reduce the amount of sequencing required in mutational studies of TP53

TMACS Test Procedure TP011: Panalarm Interface

International Nuclear Information System (INIS)

Seghers, R.; Washburn, S.J.

1994-01-01

The TMACS Software Test Procedures translate the project's acceptance criteria into test steps. The TMACS Test Plan (WHC-SD-WM-TP-148) is fulfilled when all Test Cases are approved. This Test Procedure tests the TMACS Panalarm Interface functions

Genetic variation in the TP53 pathway and bladder cancer risk. a comprehensive analysis.

Directory of Open Access Journals (Sweden)

Silvia Pineda

Full Text Available Germline variants in TP63 have been consistently associated with several tumors, including bladder cancer, indicating the importance of TP53 pathway in cancer genetic susceptibility. However, variants in other related genes, including TP53 rs1042522 (Arg72Pro, still present controversial results. We carried out an in depth assessment of associations between common germline variants in the TP53 pathway and bladder cancer risk.We investigated 184 tagSNPs from 18 genes in 1,058 cases and 1,138 controls from the Spanish Bladder Cancer/EPICURO Study. Cases were newly-diagnosed bladder cancer patients during 1998-2001. Hospital controls were age-gender, and area matched to cases. SNPs were genotyped in blood DNA using Illumina Golden Gate and TaqMan assays. Cases were subphenotyped according to stage/grade and tumor p53 expression. We applied classical tests to assess individual SNP associations and the Least Absolute Shrinkage and Selection Operator (LASSO-penalized logistic regression analysis to assess multiple SNPs simultaneously.Based on classical analyses, SNPs in BAK1 (1, IGF1R (5, P53AIP1 (1, PMAIP1 (2, SERINPB5 (3, TP63 (3, and TP73 (1 showed significant associations at p-value≤0.05. However, no evidence of association, either with overall risk or with specific disease subtypes, was observed after correction for multiple testing (p-value≥0.8. LASSO selected the SNP rs6567355 in SERPINB5 with 83% of reproducibility. This SNP provided an OR = 1.21, 95%CI 1.05-1.38, p-value = 0.006, and a corrected p-value = 0.5 when controlling for over-estimation.We found no strong evidence that common variants in the TP53 pathway are associated with bladder cancer susceptibility. Our study suggests that it is unlikely that TP53 Arg72Pro is implicated in the UCB in white Europeans. SERPINB5 and TP63 variation deserve further exploration in extended studies.

Mutations in TP53 tumor suppressor gene in wood dust-related sinonasal cancer

DEFF Research Database (Denmark)

Holmila, Reetta; Bornholdt, Jette; Heikkilä, Pirjo

2010-01-01

The causal role of work-related exposure to wood dust in the development of sinonasal cancer has long been established by numerous epidemiologic studies. To study molecular changes in these tumors, we analyzed TP53 gene mutations in 358 sinonasal cancer cases with or without occupational exposure...... affected the ORs only slightly. Smoking did not influence the occurrence of TP53 mutation; however, it was associated with multiple mutations (p = 0.03). As far as we are aware, this is the first study to demonstrate a high prevalence of TP53 mutation-positive cases in a large collection of sinonasal...... cancers with data on occupational exposure. Our results indicate that mutational mechanisms, in particular TP53 mutations, are associated with work-related exposure to wood dust in sinonasal cancer....

Tumor protein 53-induced nuclear protein 1 (TP53INP1 enhances p53 function and represses tumorigenesis

Directory of Open Access Journals (Sweden)

Jeyran eShahbazi

2013-05-01

Full Text Available Tumor protein 53-induced nuclear protein 1 (TP53INP1 is a stress-induced p53 target gene whose expression is modulated by transcription factors such as p53, p73 and E2F1. TP53INP1 gene encodes two isoforms of TP53INP1 proteins, TP53INP1α and TP53INP1β, both of which appear to be key elements in p53 function. When associated with homeodomain-interacting protein kinase-2 (HIPK2, TP53INP1 phosphorylates p53 protein at Serine 46, enhances p53 protein stability and its transcriptional activity, leading to transcriptional activation of p53 target genes such as p21, PIG-3 and MDM2, cell growth arrest and apoptosis upon DNA damage stress. The anti-proliferative and pro-apoptotic activities of TP53INP1 indicate that TP53INP1 has an important role in cellular homeostasis and DNA damage response. Deficiency in TP53INP1 expression results in increased tumorigenesis; while TP53INP1 expression is repressed during early stages of cancer by factors such as miR-155. This review aims to summarize the roles of TP53INP1 in blocking tumor progression through p53-dependant and p53-independent pathways, as well as the elements which repress TP53INP1 expression, hence highlighting its potential as a therapeutic target in cancer treatment.

Indirect Measurement of 15N(p,α)12C and 18O(p,α)15N. Applications to the AGB Star Nucleosynthesis

International Nuclear Information System (INIS)

La Cognata, M.; Spitaleri, C.; Cherubini, S.; Crucilla, V.; Gulino, M.; Lamia, L.; Pizzone, R. G.; Puglia, S. M. R.; Rapisarda, G. G.; Romano, S.; Sergi, M. L.; Tumino, A.; Tribble, R.; Al-Abdullah, T.; Banu, A.; Fu, C.; Goldberg, V.; Mukhamedzhanov, A.; Tabacaru, G.; Trache, L.

2008-01-01

The Trojan Horse Method has been recently applied to the study of reactions involved in fluorine nucleosynthesis inside AGB stars. Fluorine abundance is important since it allows to constrain mixing models from the comparison of the observed fluorine abundances with the ones predicted by models. Anyway direct measurements of the cross section do not extend down to the Gamow peak, which is the astrophysically relevant energy region. In particular the study focuses on the 15 N(p,α) 12 C and the 18 O(p,α) 15 N reactions which can influence fluorine yield as they are part of 19 F production/destruction network

Generating Systems Biology Markup Language Models from the Synthetic Biology Open Language.

Science.gov (United States)

Roehner, Nicholas; Zhang, Zhen; Nguyen, Tramy; Myers, Chris J

2015-08-21

In the context of synthetic biology, model generation is the automated process of constructing biochemical models based on genetic designs. This paper discusses the use cases for model generation in genetic design automation (GDA) software tools and introduces the foundational concepts of standards and model annotation that make this process useful. Finally, this paper presents an implementation of model generation in the GDA software tool iBioSim and provides an example of generating a Systems Biology Markup Language (SBML) model from a design of a 4-input AND sensor written in the Synthetic Biology Open Language (SBOL).

Sequential mutations in Notch1, Fbxw7, and Tp53 in radiation-induced mouse thymic lymphomas.

Science.gov (United States)

Jen, Kuang-Yu; Song, Ihn Young; Banta, Karl Luke; Wu, Di; Mao, Jian-Hua; Balmain, Allan

2012-01-19

T-cell acute lymphoblastic lymphomas commonly demonstrate activating Notch1 mutations as well as mutations or deletions in Fbxw7. However, because Fbxw7 targets Notch1 for degradation, genetic alterations in these genes are expected to be mutually exclusive events in lymphomagenesis. Previously, by using a radiation-induced Tp53-deficient mouse model for T-cell acute lymphoblastic lymphoma, we reported that loss of heterozygosity at the Fbxw7 locus occurs frequently in a Tp53-dependent manner. In the current study, we show that these thymic lymphomas also commonly exhibit activating Notch1 mutations in the proline-glutamic acid-serine-threonine (PEST) domain. Moreover, concurrent activating Notch1 PEST domain mutations and single-copy deletions at the Fbxw7 locus occur with high frequency in the same individual tumors, indicating that these changes are not mutually exclusive events. We further demonstrate that although Notch1 PEST domain mutations are independent of Tp53 status, they are completely abolished in mice with germline Fbxw7 haploinsufficiency. Therefore, Notch1 PEST domain mutations only occur when Fbxw7 expression levels are intact. These data suggest a temporal sequence of mutational events involving these important cancer-related genes, with Notch1 PEST domain mutations occurring first, followed by Fbxw7 deletion, and eventually by complete loss of Tp53.

Synthetic biology, inspired by synthetic chemistry.

Science.gov (United States)

Malinova, V; Nallani, M; Meier, W P; Sinner, E K

2012-07-16

The topic synthetic biology appears still as an 'empty basket to be filled'. However, there is already plenty of claims and visions, as well as convincing research strategies about the theme of synthetic biology. First of all, synthetic biology seems to be about the engineering of biology - about bottom-up and top-down approaches, compromising complexity versus stability of artificial architectures, relevant in biology. Synthetic biology accounts for heterogeneous approaches towards minimal and even artificial life, the engineering of biochemical pathways on the organismic level, the modelling of molecular processes and finally, the combination of synthetic with nature-derived materials and architectural concepts, such as a cellular membrane. Still, synthetic biology is a discipline, which embraces interdisciplinary attempts in order to have a profound, scientific base to enable the re-design of nature and to compose architectures and processes with man-made matter. We like to give an overview about the developments in the field of synthetic biology, regarding polymer-based analogs of cellular membranes and what questions can be answered by applying synthetic polymer science towards the smallest unit in life, namely a cell. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Estimates of long-term water total phosphorus (TP) concentrations in three large shallow lakes in the Yangtze River basin, China.

Science.gov (United States)

Wu, Pan; Qin, Boqiang; Yu, Ge

2016-03-01

The shallow lakes in the eastern China developed on alluvial plains with high-nutrient sediments, and most overflow into the Yangtze River with short hydraulic residence times, whereas they become eutrophic over long time periods. Assuming strong responses to hydrogeological changes in the basin, we attempted to determine the dynamic eutrophication history of these lakes. Although evaluation models for internal total phosphorus (TP) loading are widely used for deep lakes in Europe and North America, the accuracy of these models for shallow lakes that have smaller water volumes controlled by the geometrical morphology and greater basin area of alluvial plains is unknown. To describe the magnitude of changes in velocity of trophic state for the studied shallow lakes, we first evaluated the P retention model in relation to the major forces driving lake morphology, basin climate, and external discharge and then used the model to estimate changes in TP in three large shallow lakes (Taihu, Chao, and Poyang) over 60 years (1950-2009 AD). The observed levels of TP were verified against the relative error of the three lakes (Yangtze River basin. This work will contribute to the development of an internal P loading model for further evaluating trophic states.

Tropical-forest biomass estimation at X-Band from the spaceborne TanDEM-X interferometer

Science.gov (United States)

R. Treuhaft; F. Goncalves; J.R. dos Santos; M. Keller; M. Palace; S.N. Madsen; F. Sullivan; P.M.L.A. Graca

2014-01-01

This letter reports the sensitivity of X-band interferometric synthetic aperture radar (InSAR) data from the first dual-spacecraft radar interferometer, TanDEM-X, to variations in tropical-forest aboveground biomass (AGB). It also reports the first tropical-forest AGB estimates fromTanDEM-X data. Tropical forests account for...

Bilateral wilms tumor with TP53-related anaplasia.

Science.gov (United States)

Popov, Sergey D; Vujanic, Gordan M; Sebire, Neil J; Chagtai, Tasnim; Williams, Richard; Vaidya, Sucheta; Pritchard-Jones, Kathy

2013-01-01

Wilms tumor (WT) with diffuse anaplasia has an unfavorable prognosis and is often (>70%) associated with mutations in the TP53 gene. Although most WTs are unilateral, 5-10% are bilateral, and they are almost always present with nephrogenic rests. The latter are considered a precursor of WT. Two cases of bilateral WTs with nephroblastomatosis, in which anaplastic changes were detected over a period of time, were analyzed using clinical, radiological, histopathological, and molecular-genetic data. TP53 was analyzed by direct sequencing of its full coding sequence and intron-exon boundaries in 11 fragments. DNA was extracted from paraffin-embedded or frozen specimens. High-resolution genomic copy number profiling was carried out by UCL Genomics on the Affymetrix Human Mapping 250K Nsp or Genome-Wide Human SNP Array 6.0 platform. Both cases demonstrated a strong association between the appearance of anaplastic clones and TP53 mutations. Synchronous ganglioneuroma was diagnosed in one case. Our cases are unique as they represent a long disease history and demonstrate the difficulties in managing rare cases of bilateral WT with anaplasia. These cases also emphasize the practical importance of modern molecular-genetic techniques and their clinical application. Moreover, they highlight the issue of the adequate sampling needed in order to gather comprehensive, efficient, and sufficient information about genetic events in a single tumor.

Preclinical efficacy of the MDM2 inhibitor RG7112 in MDM2 amplified and TP53 wild-type glioblastomas

Science.gov (United States)

Verreault, Maite; Schmitt, Charlotte; Goldwirt, Lauriane; Pelton, Kristine; Haidar, Samer; Levasseur, Camille; Guehennec, Jeremy; Knoff, David; Labussiere, Marianne; Marie, Yannick; Ligon, Azra H.; Mokhtari, Karima; Hoang-Xuan, Khe; Sanson, Marc; Alexander, Brian M; Wen, Patrick Y.; Delattre, Jean-Yves; Ligon, Keith L.; Idbaih, Ahmed

2016-01-01

Rationale p53 pathway alterations are key molecular events in glioblastoma (GBM). MDM2 inhibitors increase expression and stability of p53 and are presumed to be most efficacious in patients with TP53 wild-type and MDM2-amplified cancers. However, this biomarker hypothesis has not been tested in patients or patient-derived models for GBM. Methods We performed a preclinical evaluation of RG7112 MDM2 inhibitor, across a panel of 36 patient-derived GBM cell lines (PDCLs), each genetically characterized according to their P53 pathway status. We then performed a pharmacokinetic (PK) profiling of RG7112 distribution in mice and evaluated the therapeutic activity of RG7112 in orthotopic and subcutaneous GBM models. Results MDM2-amplified PDCLs were 44 times more sensitive than TP53 mutated lines that showed complete resistance at therapeutically attainable concentrations (avg. IC50 of 0.52 μM vs 21.9 μM). MDM4 amplified PDCLs were highly sensitive but showed intermediate response (avg. IC50 of 1.2 μM), whereas response was heterogeneous in TP53 wild-type PDCLs with normal MDM2/4 levels (avg. IC50 of 7.7 μM). In MDM2-amplified lines, RG7112 restored p53 activity inducing robust p21 expression and apoptosis. PK profiling of RG7112-treated PDCL intracranial xenografts demonstrated that the compound significantly crosses the blood-brain and the blood-tumor barriers. Most importantly, treatment of MDM2-amplified/TP53 wild-type PDCL-derived model (subcutaneous and orthotopic) reduced tumor growth, was cytotoxic, and significantly increased survival. Conclusion These data strongly support development of MDM2 inhibitors for clinical testing in MDM2-amplified GBM patients. Moreover, significant efficacy in a subset of non-MDM2 amplified models suggests that additional markers of response to MDM2 inhibitors must be identified. PMID:26482041

Significance of TP53 Mutation in Wilms Tumors with Diffuse Anaplasia: A Report from the Children's Oncology Group.

Science.gov (United States)

Ooms, Ariadne H A G; Gadd, Samantha; Gerhard, Daniela S; Smith, Malcolm A; Guidry Auvil, Jaime M; Meerzaman, Daoud; Chen, Qing-Rong; Hsu, Chih Hao; Yan, Chunhua; Nguyen, Cu; Hu, Ying; Ma, Yussanne; Zong, Zusheng; Mungall, Andrew J; Moore, Richard A; Marra, Marco A; Huff, Vicki; Dome, Jeffrey S; Chi, Yueh-Yun; Tian, Jing; Geller, James I; Mullighan, Charles G; Ma, Jing; Wheeler, David A; Hampton, Oliver A; Walz, Amy L; van den Heuvel-Eibrink, Marry M; de Krijger, Ronald R; Ross, Nicole; Gastier-Foster, Julie M; Perlman, Elizabeth J

2016-11-15

To investigate the role and significance of TP53 mutation in diffusely anaplastic Wilms tumors (DAWTs). All DAWTs registered on National Wilms Tumor Study-5 (n = 118) with available samples were analyzed for TP53 mutations and copy loss. Integrative genomic analysis was performed on 39 selected DAWTs. Following analysis of a single random sample, 57 DAWTs (48%) demonstrated TP53 mutations, 13 (11%) copy loss without mutation, and 48 (41%) lacked both [defined as TP53-wild-type (wt)]. Patients with stage III/IV TP53-wt DAWTs (but not those with stage I/II disease) had significantly lower relapse and death rates than those with TP53 abnormalities. In-depth analysis of a subset of 39 DAWTs showed seven (18%) to be TP53-wt: These demonstrated gene expression evidence of an active p53 pathway. Retrospective pathology review of TP53-wt DAWT revealed no or very low volume of anaplasia in six of seven tumors. When samples from TP53-wt tumors known to contain anaplasia histologically were available, abnormal p53 protein accumulation was observed by immunohistochemistry. These data support the key role of TP53 loss in the development of anaplasia in WT, and support its significant clinical impact in patients with residual anaplastic tumor following surgery. These data also suggest that most DAWTs will show evidence of TP53 mutation when samples selected for the presence of anaplasia are analyzed. This suggests that modifications of the current criteria to also consider volume of anaplasia and documentation of TP53 aberrations may better reflect the risk of relapse and death and enable optimization of therapeutic stratification. Clin Cancer Res; 22(22); 5582-91. ©2016 AACR. ©2016 American Association for Cancer Research.

Systemic administration of thrombin peptide TP508 enhances VEGF-stimulated angiogenesis and attenuates effects of chronic hypoxia

Science.gov (United States)

Olszewska-Pazdrak, Barbara; Carney, Darrell H.

2015-01-01

Revascularization of chronic wounds and ischemic tissue is attenuated by endothelial dysfunction and the inability of angiogenic factors to stimulate angiogenesis. We recently showed that TP508, a nonproteolytic thrombin peptide, increases perfusion and NO-dependent vasodilation in hearts with chronic ischemia and stimulates NO production by endothelial cells. In this study, we investigated systemic in vivo effects of TP508 on VEGF-stimulated angiogenesis in vitro using aortic explants in normoxic and hypoxic conditions. Mice were injected with saline or TP508 and 24h later aortas were removed and cultured to quantify endothelial sprouting. TP508 injection increased endothelial sprouting and potentiated the in vitro response to VEGF. Exposure of control explants to hypoxia inhibited basal and VEGF-stimulated endothelial cell sprouting. This effect of hypoxia was significantly prevented by TP508 injection. Thus, TP508 systemic administration increases responsiveness of aortic endothelial cells to VEGF and diminishes the effect of chronic hypoxia on endothelial cell sprouting. Studies using human endothelial cells in culture suggest that protective effects of TP508 during hypoxia may involve stimulation of endothelial cell NO production. These data suggest potential clinical benefit of using a combination of systemic TP508 and local VEGF as a therapy for revascularization of ischemic tissue. PMID:23594718

Techniques for Modeling Human Performance in Synthetic Environments: A Supplementary Review

National Research Council Canada - National Science Library

Ritter, Frank E; Shadbolt, Nigel R; Elliman, David; Young, Richard M; Gobet, Fernand; Baxter, Gordon D

2003-01-01

Selected recent developments and promising directions for improving the quality of models of human performance in synthetic environments are summarized, beginning with the potential uses and goals for behavioral models...

Synthetic LISA: Simulating time delay interferometry in a model LISA

International Nuclear Information System (INIS)

Vallisneri, Michele

2005-01-01

We report on three numerical experiments on the implementation of Time-Delay Interferometry (TDI) for LISA, performed with Synthetic LISA, a C++/Python package that we developed to simulate the LISA science process at the level of scientific and technical requirements. Specifically, we study the laser-noise residuals left by first-generation TDI when the LISA armlengths have a realistic time dependence; we characterize the armlength-measurement accuracies that are needed to have effective laser-noise cancellation in both first- and second-generation TDI; and we estimate the quantization and telemetry bitdepth needed for the phase measurements. Synthetic LISA generates synthetic time series of the LISA fundamental noises, as filtered through all the TDI observables; it also provides a streamlined module to compute the TDI responses to gravitational waves according to a full model of TDI, including the motion of the LISA array and the temporal and directional dependence of the armlengths. We discuss the theoretical model that underlies the simulation, its implementation, and its use in future investigations on system-characterization and data-analysis prototyping for LISA

Synthetic Biology Parts for the Storage of Increased Genetic Information in Cells.

Science.gov (United States)

Morris, Sydney E; Feldman, Aaron W; Romesberg, Floyd E

2017-10-20

To bestow cells with novel forms and functions, the goal of synthetic biology, we have developed the unnatural nucleoside triphosphates dNaMTP and dTPT3TP, which form an unnatural base pair (UBP) and expand the genetic alphabet. While the UBP may be retained in the DNA of a living cell, its retention is sequence-dependent. We now report a steady-state kinetic characterization of the rate with which the Klenow fragment of E. coli DNA polymerase I synthesizes the UBP and its mispairs in a variety of sequence contexts. Correct UBP synthesis is as efficient as for a natural base pair, except in one sequence context, and in vitro performance is correlated with in vivo performance. The data elucidate the determinants of efficient UBP synthesis, show that the dNaM-dTPT3 UBP is the first generally recognized natural-like base pair, and importantly, demonstrate that dNaMTP and dTPT3TP are well optimized and standardized parts for the expansion of the genetic alphabet.

Significance of TP53 Mutation in Wilms Tumors with Diffuse Anaplasia: A Report from the Children’s Oncology Group

Science.gov (United States)

Ooms, Ariadne H.A.G.; Gadd, Samantha; Gerhard, Daniela S.; Smith, Malcolm A.; Guidry Auvil, Jaime M.; Meerzaman, Daoud; Chen, Qing-Rong; Hsu, Chih Hao; Yan, Chunhua; Nguyen, Cu; Hu, Ying; Ma, Yussanne; Zong, Zusheng; Mungall, Andrew J.; Moore, Richard A.; Marra, Marco A.; Huff, Vicki; Dome, Jeffrey S.; Chi, Yueh-Yun; Tian, Jing; Geller, James I.; Mullighan, Charles G.; Ma, Jing; Wheeler, David A.; Hampton, Oliver A.; Walz, Amy L.; van den Heuvel-Eibrink, Marry M.; de Krijger, Ronald R.; Ross, Nicole; Gastier-Foster, Julie M.; Perlman, Elizabeth J.

2016-01-01

Purpose To investigate the role and significance of TP53 mutation in diffusely anaplastic Wilms tumor (DAWT). Experimental Design All DAWTs registered on National Wilms Tumor Study-5 (n=118) with available samples were analyzed for TP53 mutations and copy loss. Integrative genomic analysis was performed on 39 selected DAWTs. Results Following analysis of a single random sample, 57 DAWT (48%) demonstrated TP53 mutations, 13(11%) copy loss without mutation, and 48(41%) lacked both (defined as TP53-wildtype (wt)). Patients with Stage III/IV TP53-wt DAWTs (but not those with Stage I/II disease) had significantly lower relapse and death rates than those with TP53 abnormalities. In-depth analysis of a subset of 39 DAWT showed 7(18%) to be TP53-wt: these demonstrated gene expression evidence of an active p53 pathway. Retrospective pathology review of TP53-wt DAWT revealed no or very low volume of anaplasia in 6/7 tumors. When samples from TP53-wt tumors known to contain anaplasia histologically were available, abnormal p53 protein accumulation was observed by immunohistochemistry. Conclusion These data support the key role of TP53 loss in the development of anaplasia in WT, and support its significant clinical impact in patients with residual anaplastic tumor following surgery. These data also suggest that most DAWTs will show evidence of TP53 mutation when samples selected for the presence of anaplasia are analyzed. This suggests that modifications of the current criteria to also consider volume of anaplasia and documentation of TP53 aberrations may better reflect the risk of relapse and death and enable optimization of therapeutic stratification. PMID:27702824

Synthetic digital radiographs using exposure computer models of Voxels / EGS4 Phantoms

International Nuclear Information System (INIS)

Kenned, Roberto; Vieira, Jose W.; Lima, Fernando R.A.; Loureiro, Eduardo

2008-01-01

The objective of this work is to produce synthetic digital radiographs from synthetic phantoms with the use of a Computational Model of Exposition (MCE). The literature explains a model consisted on a phantom, a Monte Carlo code and an algorithm of a radioactive source. In this work it was used the FAX phantom (Female Adult voXel), besides the EGS4 system code Eletron Shower-range version 4) and an external source, similar to that used in diagnostic radiology. The implementation of MCE creates files with information on external energy deposited in the voxels of fantoma used, here called EnergiaPorVoxel.dat. These files along with the targeted phantom (fax.sgi) worked as data entry for the DIP software (Digital Imaging Processing) to build the synthetic phantoms based on energy and the effective dose. This way you can save each slice that is the stack of pictures of these phantoms synthetics, which have been called synthetic digital radiography. Using this, it is possible to use techniques of emphasis in space to increase the contrast or elineate contours between organs and tissues. The practical use of these images is not only to allow a planning of examinations performed in clinics and hospitals and reducing unnecessary exposure to patients by error of radiographic techniques. (author)

TP53 codon 72 polymorphism in pigmentary phenotypes

Indian Academy of Sciences (India)

2012-01-20

Jan 20, 2012 ... pigmentation by acting as a transcription factor for other genes that are ... skin phototype I-II, burns after exposure to UVR and the development of .... morphisms of TP53 codon 72 with breast carcinoma risk: evidence from ...

TP53 mutational status is a potential marker for risk stratification in Wilms tumour with diffuse anaplasia.

Directory of Open Access Journals (Sweden)

Mariana Maschietto

Full Text Available The presence of diffuse anaplasia in Wilms tumours (DAWT is associated with TP53 mutations and poor outcome. As patients receive intensified treatment, we sought to identify whether TP53 mutational status confers additional prognostic information.We studied 40 patients with DAWT with anaplasia in the tissue from which DNA was extracted and analysed for TP53 mutations and 17p loss. The majority of cases were profiled by copy number (n = 32 and gene expression (n = 36 arrays. TP53 mutational status was correlated with patient event-free and overall survival, genomic copy number instability and gene expression profiling.From the 40 cases, 22 (55% had TP53 mutations (2 detected only after deep-sequencing, 20 of which also had 17p loss (91%; 18 (45% cases had no detectable mutation but three had 17p loss. Tumours with TP53 mutations and/or 17p loss (n = 25 had an increased risk of recurrence as a first event (p = 0.03, hazard ratio (HR, 3.89; 95% confidence interval (CI, 1.26-16.0 and death (p = 0.04, HR, 4.95; 95% CI, 1.36-31.7 compared to tumours lacking TP53 abnormalities. DAWT carrying TP53 mutations showed increased copy number alterations compared to those with wild-type, suggesting a more unstable genome (p = 0.03. These tumours showed deregulation of genes associated with cell cycle and DNA repair biological processes.This study provides evidence that TP53 mutational analysis improves risk stratification in DAWT. This requires validation in an independent cohort before clinical use as a biomarker.

TP53 mutational status is a potential marker for risk stratification in Wilms tumour with diffuse anaplasia.

Science.gov (United States)

Maschietto, Mariana; Williams, Richard D; Chagtai, Tasnim; Popov, Sergey D; Sebire, Neil J; Vujanic, Gordan; Perlman, Elizabeth; Anderson, James R; Grundy, Paul; Dome, Jeffrey S; Pritchard-Jones, Kathy

2014-01-01

The presence of diffuse anaplasia in Wilms tumours (DAWT) is associated with TP53 mutations and poor outcome. As patients receive intensified treatment, we sought to identify whether TP53 mutational status confers additional prognostic information. We studied 40 patients with DAWT with anaplasia in the tissue from which DNA was extracted and analysed for TP53 mutations and 17p loss. The majority of cases were profiled by copy number (n = 32) and gene expression (n = 36) arrays. TP53 mutational status was correlated with patient event-free and overall survival, genomic copy number instability and gene expression profiling. From the 40 cases, 22 (55%) had TP53 mutations (2 detected only after deep-sequencing), 20 of which also had 17p loss (91%); 18 (45%) cases had no detectable mutation but three had 17p loss. Tumours with TP53 mutations and/or 17p loss (n = 25) had an increased risk of recurrence as a first event (p = 0.03, hazard ratio (HR), 3.89; 95% confidence interval (CI), 1.26-16.0) and death (p = 0.04, HR, 4.95; 95% CI, 1.36-31.7) compared to tumours lacking TP53 abnormalities. DAWT carrying TP53 mutations showed increased copy number alterations compared to those with wild-type, suggesting a more unstable genome (p = 0.03). These tumours showed deregulation of genes associated with cell cycle and DNA repair biological processes. This study provides evidence that TP53 mutational analysis improves risk stratification in DAWT. This requires validation in an independent cohort before clinical use as a biomarker.

Synthetic quorum sensing in model microcapsule colonies

Science.gov (United States)

Shum, Henry; Balazs, Anna C.

2017-08-01

Biological quorum sensing refers to the ability of cells to gauge their population density and collectively initiate a new behavior once a critical density is reached. Designing synthetic materials systems that exhibit quorum sensing-like behavior could enable the fabrication of devices with both self-recognition and self-regulating functionality. Herein, we develop models for a colony of synthetic microcapsules that communicate by producing and releasing signaling molecules. Production of the chemicals is regulated by a biomimetic negative feedback loop, the “repressilator” network. Through theory and simulation, we show that the chemical behavior of such capsules is sensitive to both the density and number of capsules in the colony. For example, decreasing the spacing between a fixed number of capsules can trigger a transition in chemical activity from the steady, repressed state to large-amplitude oscillations in chemical production. Alternatively, for a fixed density, an increase in the number of capsules in the colony can also promote a transition into the oscillatory state. This configuration-dependent behavior of the capsule colony exemplifies quorum-sensing behavior. Using our theoretical model, we predict the transitions from the steady state to oscillatory behavior as a function of the colony size and capsule density.

Autophagy is induced through the ROS-TP53-DRAM1 pathway in response to mitochondrial protein synthesis inhibition.

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Xie, Xiaolei; Le, Li; Fan, Yanxin; Lv, Lin; Zhang, Junjie

2012-07-01

Mitoribosome in mammalian cells is responsible for synthesis of 13 mtDNA-encoded proteins, which are integral parts of four mitochondrial respiratory chain complexes (I, III, IV and V). ERAL1 is a nuclear-encoded GTPase important for the formation of the 28S small mitoribosomal subunit. Here, we demonstrate that knockdown of ERAL1 by RNA interference inhibits mitochondrial protein synthesis and promotes reactive oxygen species (ROS) generation, leading to autophagic vacuolization in HeLa cells. Cells that lack ERAL1 expression showed a significant conversion of LC3-I to LC3-II and an enhanced accumulation of autophagic vacuoles carrying the LC3 marker, all of which were blocked by the autophagy inhibitor 3-MA as well as by the ROS scavenger NAC. Inhibition of mitochondrial protein synthesis either by ERAL1 siRNA or chloramphenicol (CAP), a specific inhibitor of mitoribosomes, induced autophagy in HTC-116 TP53 (+/+) cells, but not in HTC-116 TP53 (-/-) cells, indicating that tumor protein 53 (TP53) is essential for the autophagy induction. The ROS elevation resulting from mitochondrial protein synthesis inhibition induced TP53 expression at transcriptional levels by enhancing TP53 promoter activity, and increased TP53 protein stability by suppressing TP53 ubiquitination through MAPK14/p38 MAPK-mediated TP53 phosphorylation. Upregulation of TP53 and its downstream target gene DRAM1, but not CDKN1A/p21, was required for the autophagy induction in ERAL1 siRNA or CAP-treated cells. Altogether, these data indicate that autophagy is induced through the ROS-TP53-DRAM1 pathway in response to mitochondrial protein synthesis inhibition.

IDH1/IDH2 but Not TP53 Mutations Predict Prognosis in Bulgarian Glioblastoma Patients

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Gergana Stancheva

2014-01-01

Full Text Available Mutations in genes encoding isocitrate dehydrogenase isoforms 1 (IDH1 and 2 (IDH2 have been associated with good prognosis for patients with brain neoplasias and have been commonly found together with mutated TP53 gene. To determine the prevalence of IDH1, IDH2, and TP53 mutations and their impact on overall survival 106 glioblastoma patients were analysed. IDH1 mutations were detected in 13 and IDH2 mutation in one patient. Two homozygous samples with R132H mutation in IDH1 gene and a novel aberration K129R in IDH2 gene were found. Sixty-four percent of IDH1/IDH2 mutated tumours harboured also a mutation in TP53 gene. Genetic aberrations in TP53 were present in 37 patients. Statistical analysis of the impact of the studied factors on the overall survival showed that the mutations in IDH1/IDH2, but not the ones in TP53, were associated with longer survival. Also, the impact of age on prognosis was confirmed. This is the first comprehensive study on glioblastomas in Bulgaria. Our results suggest that IDH1/IDH2 but not TP53 mutations together with other prognostic factors such as age might be applied in clinical practice for prediction of outcome in patients with glioblastomas.

Analysis of full coding sequence of the TP53 gene in invasive vulvar cancers: Implications for therapy.

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Kashofer, Karl; Regauer, Sigrid

2017-08-01

This study evaluates the frequency and type of TP53 gene mutations and HPV status in 72 consecutively diagnosed primary invasive vulvar squamous cell carcinomas (SCC) during the past 5years. DNA of formalin-fixed and paraffin embedded tumour tissue was analysed for 32 HPV subtypes and the full coding sequence of the TP53 gene, and correlated with results of p53 immunohistochemistry. 13/72 (18%) cancers were HPV-induced squamous cell carcinomas, of which 1/13 (8%) carcinoma harboured a somatic TP53 mutation. Among the 59/72 (82%) HPV-negative cancers, 59/72 (82%) SCC were HPV-negative with wild-type gene in 14/59 (24%) SCC and somatic TP53 mutations in 45/59 (76%) SCC. 28/45 (62%) SCC carried one (n=20) or two (n=8) missense mutations. 11/45 (24%) carcinomas showed a single disruptive mutation (3× frame shift, 7× stop codon, 1× deletion), 3/45 SCC a splice site mutation. 3/45 (7%) carcinomas had 2 or 3 different mutations. 18 different "hot spot" mutations were observed in 22/45 cancers (49%; 5× R273, 3× R282; 2× each Y220, R278, R248). Immunohistochemical p53 over expression was identified in most SCC with missense mutations, but not in SCC with disruptive TP53 mutations or TP53 wild-type. 14/45 (31%) patients with TP53 mutated SCC died of disease within 12months (range 2-24months) versus 0/13 patients with HPV-induced carcinomas and 0/14 patients with HPV-negative, TP53 wild-type carcinomas. 80% of primary invasive vulvar SCC were HPV-negative carcinomas with a high frequency of disruptive mutations and "hot spot" TP53 gene mutations, which have been linked to chemo- and radioresistance. The death rate of patients with p53 mutated vulvar cancers was 31%. Immunohistochemical p53 over expression could not reliably identify SCC with TP53 gene mutation. Pharmacological therapies targeting mutant p53 will be promising strategies for personalized therapy in patients with TP53 mutated vulvar cancers. Copyright © 2017. Published by Elsevier Inc.

Use of the integration elements encoded by the temperate lactococcal bacteriophage TP901-1

DEFF Research Database (Denmark)

Brøndsted, Lone; Hammer, Karin

1999-01-01

Previously we showed that only one phage-expressed protein (Orf1), a 425-bp region upstream of the orf1 gene (presumably encoding a promoter), and the attP region are necessary and also sufficient for integration of the bacteriophage TP901-1 genome into the chromosome of Lactococcus lactis subsp......P region seem to be necessary for site-specific integration of the temperate bacteriophage TP901-1. By use of the integrative elements (attP and orf1) expressed by the temperate lactococcal bacteriophage TP901-1, a system for obtaining stable chromosomal single-copy transcriptional fusions in L. lactis...

Germline TP53 mutations and single nucleotide polymorphisms in children Mutaciones y polimorfismos de un único nucleótido del gen TP53 en línea germinal en niños

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Pamela Valva

2009-02-01

Full Text Available Mutations in the gene TP53, which codifies the tumor suppressor protein p53, are found in about 50% of tumors. These mutations can occur not only at somatic level, but also in germline. Pediatric cancer patients, mostly with additional family history of malignancy, should be considered as potential TP53 germline mutation carriers. Germline TP53 mutations and polymorphisms have been widely studied to determine their relation with different tumors' pathogenesis. Our aim was to analyze the occurrence frequency of germline TP53 mutations and polymorphisms and to relate these to tumor development in a pediatric series. Peripheral blood mononuclear cell samples from 26 children with solid tumors [PST] and 21 pediatric healthy donors [HD] were analyzed for germline mutations and polymorphisms in TP53 gene spanning from exon 5 to 8 including introns 5 and 7. These PCR amplified fragments were sequenced to determine variations. A heterozygous mutation at codon 245 was found in 1/26 PST and 0/21 HD. Comparative polymorphisms distribution, at position 14181 and 14201(intron 7, between HD and PST revealed a trend of association (p= 0.07 with cancer risk. HD group disclosed a similar polymorphism distribution as published data for Caucasian and Central/South American populations. This is the first study about TP53 variant frequency and distribution in healthy individuals and cancer patients in Argentina.El gen que codifica para la proteína supresora de tumor p53 (TP53 se encuentra mutado en aproximadamente el 50% de los tumores. Estas mutaciones pueden presentarse como somáticas o en línea germinal. Los niños con tumores, sobre todo aquellos con historia familiar de enfermedad oncológica, deben considerarse potenciales portadores de mutaciones en línea germinal. Las mutaciones de TP53 y los polimorfismos son estudiados para determinar su relación con la patogénesis de diferentes tumores. El objetivo del trabajo fue analizar la frecuencia de

TP53 mutations in clinically normal mucosa adjacent to oral carcinomas

DEFF Research Database (Denmark)

Thode, Christenze; Bilde, Anders; von Buchwald, Christian

2010-01-01

BACKGROUND: The tumour-suppressor protein p53 often accumulates in histologically normal epithelium adjacent to oral squamous cell carcinomas (OSCC). We investigated whether this was associated with mutations in TP53, the gene for p53, and might implicate impending malignancy. METHODS: Specimens...... products were separated by denatured gradient gel electrophoresis. Fragments with a deviant DGEE pattern were sequenced. RESULTS: TP53 mutations were found in six of 18 tumours. Fourteen specimens contained histologically normal mucosa adjacent to the tumour; 13 of these showed small clusters of p53...

Optimization of a prognostic biosphere model for terrestrial biomass and atmospheric CO2 variability

International Nuclear Information System (INIS)

Saito, M.; Ito, A.; Maksyutov, S.

2014-01-01

This study investigates the capacity of a prognostic biosphere model to simulate global variability in atmospheric CO 2 concentrations and vegetation carbon dynamics under current environmental conditions. Global data sets of atmospheric CO 2 concentrations, above-ground biomass (AGB), and net primary productivity (NPP) in terrestrial vegetation were assimilated into the biosphere model using an inverse modeling method combined with an atmospheric transport model. In this process, the optimal physiological parameters of the biosphere model were estimated by minimizing the misfit between observed and modeled values, and parameters were generated to characterize various biome types. Results obtained using the model with the optimized parameters correspond to the observed seasonal variations in CO 2 concentration and their annual amplitudes in both the Northern and Southern Hemispheres. In simulating the mean annual AGB and NPP, the model shows improvements in estimating the mean magnitudes and probability distributions for each biome, as compared with results obtained using prior simulation parameters. However, the model is less efficient in its simulation of AGB for forest type biomes. This misfit suggests that more accurate values of input parameters, specifically, grid mean AGB values and seasonal variabilities in physiological parameters, are required to improve the performance of the simulation model. (authors)

Molecular Alterations of TP53 are a Defining Feature of Ovarian High-Grade Serous Carcinoma: A Rereview of Cases Lacking TP53 Mutations in The Cancer Genome Atlas Ovarian Study.

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Vang, Russell; Levine, Douglas A; Soslow, Robert A; Zaloudek, Charles; Shih, Ie-Ming; Kurman, Robert J

2016-01-01

The Cancer Genome Atlas has reported that 96% of ovarian high-grade serous carcinomas (HGSCs) have TP53 somatic mutations suggesting that mutation of this gene is a defining feature of this neoplasm. In the current study, 5 gynecologic pathologists independently evaluated hematoxylin and eosin slides of 14 available cases from The Cancer Genome Atlas classified as HGSC that lacked a TP53 mutation. The histologic diagnoses rendered by these pathologists and the accompanying molecular genetic data are the subject of this report. Only 1 case (Case 5), which contained a homozygous deletion of TP53, had unanimous interobserver agreement for a diagnosis of pure HGSC. In 1 case (Case 3), all 5 observers (100%) rendered a diagnosis of HGSC; however, 3 observers (60%) noted that the histologic features were not classic for HGSC and suggested this case may have arisen from a low-grade serous carcinoma (arisen from an alternate pathway compared with the usual HGSC). In 2 cases (Cases 4 and 12), only 3 observers (60%) in each case, respectively, interpreted it as having a component of HGSC. In the remaining 10 (71%) of tumors (Cases 1, 2, 6-11, 13, and 14), the consensus diagnosis was not HGSC, with individual diagnoses including low-grade serous carcinoma, high-grade endometrioid carcinoma, HGSC, metastatic carcinoma, clear cell carcinoma, atypical proliferative (borderline) serous tumor, and adenocarcinoma, not otherwise specified. Therefore, 13 (93%) of the tumors (Cases 1-4 and 6-14) were either not a pure HGSC or represented a diagnosis other than HGSC, all with molecular results not characteristic of HGSC. Accordingly, our review of the TP53 wild-type HGSCs reported in The Cancer Genome Atlas suggests that 100% of de novo HGSCs contain TP53 somatic mutations or deletions, with the exception of the rare HGSCs that develop from a low-grade serous tumor precursor. We, therefore, propose that lack of molecular alterations of TP53 are essentially inconsistent with the

A polymorphism (rs1042522) in TP53 gene is a risk factor for Down Syndrome in Sicilian mothers.

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Salemi, Michele; Barone, Concetta; Salluzzo, Maria Grazia; Giambirtone, Mariaconcetta; Scillato, Francesco; Galati Rando, Rosanna; Romano, Carmelo; Morale, Maria Concetta; Ridolfo, Federico; Romano, Corrado

2017-11-01

Trisomy 21 is the most frequent genetic cause of intellectual disability. Tumor Protein 53 (TP53) gene down-regulation triggers chromosomal instability. A TP53 gene polymorphism c.215G > C (rs1042522) is associated with accumulation of aneuploid cells. We analyzed the TP53 c.215G > C (rs1042522) polymorphism in Sicilian mothers of subjects with Down Syndrome (DS) within a case-control study. Nucleotide polymorphism was detected by pyrosequencing technology. The distribution of TP53 c.215G > C polymorphism showed significant difference between mothers of subjects with DS and controls. Our data show that TP53 c.215G > C polymorphism is a risk factor for DS in Sicilian mothers.

Total Pancreatectomy (TP) and Islet Autotransplantation (IAT) for Chronic Pancreatitis (CP)

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Sutherland, David E.R.; Radosevich, David M.; Bellin, Melena D.; Hering, Bernard J.; Beilman, Gregory J.; Dunn, Ty B.; Chinnakotla, Srinath; Vickers, Selwyn M.; Bland, Barbara; Balamurugan, A.N.; Freeman, Martin L.; Pruett, Timothy L.

2013-01-01

Background Total-pancreatectomy (TP) with intraportal-islet-auto-transplantation (IAT) can relieve pain and preserve beta-cell-mass in patients with chronic-pancreatitis (CP) when other-therapies fail. Reported is a >30-year-single-center-series. Study Design 409 patients (53 children, 5–18 yrs) with CP underwent TP-IAT from Feb/1977–Sept/2011; (etiology idiopathic-41%; SOD/biliary-9%; genetic-14%; divisum-17%; alcohol-7%; other-12%); mean age-35.3 yrs,); 74% female; prior-surgeries 21%--Puestow procedure 9%, Whipple 6%, distal pancreatectomy 7%; other 2%). Islet-function was classified as insulin-independent for those on no insulin; partial if known C-peptide positive or euglycemic on once-daily-insulin; and insulin-dependent if on standard basal–bolus diabetic regimen. An SF-36-survey for Quality-of-Life (QOL)) was completed before and in serial follow-up by patients done since 2007 with an integrated-survey that added in 2008. Results Actuarial-patient-survival post-TP-IAT was 96% in adults and 98% in children (1-year) and; 89% and 98% (5-years). Complications requiring relaparotomy occurred in 15.9%, bleeding (9.5%) being most common. IAT-function is achieved in 90% (C-peptide >0.6 ng/ml). At 3 years, 30% were insulin-independent (25% in adults, 55% in children) and 33% had partial-function. Mean HbA1C was 5000/kg (24%)] correlated with degree of function with insulin-independent rates at 3 yrs of 12, 22 and 72%, partial function 33, 62 and 24%. All patients had pain before TP-IAT and nearly all were on daily-narcotics. After TP-IAT, 85% had pain-improvement. By two years 59% had ceased-narcotics. All children were on narcotics before, 39% at follow-up; pain improved in 94%; 67% became pain-free. In the SF-36 survey, there was significant improvement from baseline in all dimensions including the Physical and Mental Component Summaries (P2/3 of patients with insulin-independence occurring in one-quarter of adults and half the children. PMID:22397977

Structural Biology of CI from Phage TP901-1

DEFF Research Database (Denmark)

Rasmussen, Kim Krighaar

(CTD), separated by a linker of various lengths. The NTD is responsible for DNA binding and the CTD is responsible for oligomerization of the CI protein. A Helix-turn-Helix motif is usually responsible for DNA binding. This thesis presents a structural characterization of the CI repressor from TP901...... condition of the CTD, responsible for the arrangement of the hexameric CI repressor. The arrangement of the CI repressor for TP901-1 has previously been described to have 32 point group symmetry based on SAXS studies. The CTD crystallizes with P3121 or P3221 symmetry with one molecule in the asymmetric unit......-length CI can only be answered unambiguously by solving the CTD crystal structure or by use of alternative techniques on the full-length CI....

Gaining insights into the codon usage patterns of TP53 gene across eight mammalian species.

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Tarikul Huda Mazumder

Full Text Available TP53 gene is known as the "guardian of the genome" as it plays a vital role in regulating cell cycle, cell proliferation, DNA damage repair, initiation of programmed cell death and suppressing tumor growth. Non uniform usage of synonymous codons for a specific amino acid during translation of protein known as codon usage bias (CUB is a unique property of the genome and shows species specific deviation. Analysis of codon usage bias with compositional dynamics of coding sequences has contributed to the better understanding of the molecular mechanism and the evolution of a particular gene. In this study, the complete nucleotide coding sequences of TP53 gene from eight different mammalian species were used for CUB analysis. Our results showed that the codon usage patterns in TP53 gene across different mammalian species has been influenced by GC bias particularly GC3 and a moderate bias exists in the codon usage of TP53 gene. Moreover, we observed that nature has highly favored the most over represented codon CTG for leucine amino acid but selected against the ATA codon for isoleucine in TP53 gene across all mammalian species during the course of evolution.

Human Treponema pallidum 11q/j isolate belongs to subsp. endemicum but contains two loci with a sequence in TP0548 and TP0488 similar to subsp. pertenue and subsp. pallidum, respectively.

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Lenka Mikalová

2017-03-01

Full Text Available Treponema pallidum subsp. endemicum (TEN is the causative agent of endemic syphilis (bejel. An unusual human TEN 11q/j isolate was obtained from a syphilis-like primary genital lesion from a patient that returned to France from Pakistan.The TEN 11q/j isolate was characterized using nested PCR followed by Sanger sequencing and/or direct Illumina sequencing. Altogether, 44 chromosomal regions were analyzed. Overall, the 11q/j isolate clustered with TEN strains Bosnia A and Iraq B as expected from previous TEN classification of the 11q/j isolate. However, the 11q/j sequence in a 505 bp-long region at the TP0488 locus was similar to Treponema pallidum subsp. pallidum (TPA strains, but not to TEN Bosnia A and Iraq B sequences, suggesting a recombination event at this locus. Similarly, the 11q/j sequence in a 613 bp-long region at the TP0548 locus was similar to Treponema pallidum subsp. pertenue (TPE strains, but not to TEN sequences.A detailed analysis of two recombinant loci found in the 11q/j clinical isolate revealed that the recombination event occurred just once, in the TP0488, with the donor sequence originating from a TPA strain. Since TEN Bosnia A and Iraq B were found to contain TPA-like sequences at the TP0548 locus, the recombination at TP0548 took place in a treponeme that was an ancestor to both TEN Bosnia A and Iraq B. The sequence of 11q/j isolate in TP0548 represents an ancestral TEN sequence that is similar to yaws-causing treponemes. In addition to the importance of the 11q/j isolate for reconstruction of the TEN phylogeny, this case emphasizes the possible role of TEN strains in development of syphilis-like lesions.

Ibrutinib for previously untreated and relapsed or refractory chronic lymphocytic leukaemia with TP53 aberrations

DEFF Research Database (Denmark)

Farooqui, Mohammed Z H; Valdez, Janet; Martyr, Sabrina

2015-01-01

BACKGROUND: Patients with chronic lymphocytic leukaemia (CLL) with TP53 aberrations respond poorly to first-line chemoimmunotherapy, resulting in early relapse and short survival. We investigated the safety and activity of ibrutinib in previously untreated and relapsed or refractory CLL with TP53...... aberrations. METHODS: In this investigator-initiated, single-arm phase 2 study, we enrolled eligible adult patients with active CLL with TP53 aberrations at the National Institutes of Health Clinical Center (Bethesda, MD, USA). Patients received 28-day cycles of ibrutinib 420 mg orally once daily until...... in one (2%) patient. INTERPRETATION: The activity and safety profile of single-agent ibrutinib in CLL with TP53 aberrations is encouraging and supports its consideration as a novel treatment option for patients with this high-risk disease in both first-line and second-line settings. FUNDING: Intramural...

ELISA with double antigen sandwich for screening specific serum anti-TP antibody in blood donors

International Nuclear Information System (INIS)

Wang Yiqing; Shi Zhixu

2002-01-01

Objective: To select a sensitive and specific laboratory examination suitable for screening serum anti-TP antibody in blood donors. Methods: The serum anti-TP antibody in 11271 blood donors were detected using ELISA with double antigen sandwich and the outcomes were compared with those using RPR assay. The conflicting specimen were confirmed by repeating the test with TPHA assay. Results: The positive rates of serum anti-TP antibody by ELISA with double antigen sandwich and RPR was 0.36% (41/11271) and 0.26% (29/11271), respectively. The coincidence of the detecting outcomes by ELISA with double antigen sandwich and RPR with TPHA was 97.5% (40/41) and 63.41%(26/41) respectively. Conclusion: Compared with RPR assay, ELISA with double antigen sandwich has higher sensibility and specificity for screening serum anti-TP antibody in blood donors

Synthetic model for Doppler broadening of neutron absorption resonances in molecular fluids

Energy Technology Data Exchange (ETDEWEB)

Villanueva, Alejandro J., E-mail: villanueva@cab.cnea.gov.a [Comision Nacional de Energia Atomica, Centro Atomico Bariloche and Instituto Balseiro, 8400 S.C. de Bariloche (RN) (Argentina); Consejo Nacional de Investigaciones Cientificas y Tecnicas (Argentina); Granada, J.R. [Comision Nacional de Energia Atomica, Centro Atomico Bariloche and Instituto Balseiro, 8400 S.C. de Bariloche (RN) (Argentina); Consejo Nacional de Investigaciones Cientificas y Tecnicas (Argentina)

2010-08-15

A general and systematic approach expressed in modern language, accounting for molecular motion effects on Doppler Broadening of Neutron Absorption Resonances (DBNAR) is given the form of a new model. It relies on well validated hypothesis: The separability of atomic from nuclear degrees of freedom, the use of the Van Hove scattering formalism and the fact that a conceptually identical approach produced experimentally proved predictions when applied to DBNAR in solid systems. We treat the molecular internal degrees of freedom approximately as harmonic oscillators. As a second contribution of this work, a synthetic model is presented in order to make the more complete model mentioned above suitable for neutron calculation codes. This second synthetic model reduces to the exact expressions of the complete model in the low and high neutron energy regimes and provides a plausible transition in between. Numerical results are presented for a general hypothetical case to show its strengths and limitations. Also, both models are applied to a real case of the {sup 238}U 6.674 eV resonant effective broadened absorption cross-section in UF6 (uranium hexafluoride). A direct experimental validation of our models is still necessary for which a special high resolution neutron transmission experiment ought to be devised at low temperatures and pressures on a gaseous system. It is showed how the synthetic model can be used to make thermometric predictions in an improved fashion in comparison to the effective temperature gas model at low temperatures.

Utilisation of transparent synthetic soil surrogates in geotechnical physical models: A review

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Abideen Adekunle Ganiyu

2016-08-01

Full Text Available Efforts to obtain non-intrusive measurement of deformations and spatial flow within soil mass prior to the advent of transparent soils have perceptible limitations. The transparent soil is a two-phase medium composed of both the synthetic aggregate and fluid components of identical refractive indices aiming at attaining transparency of the resulting soil. The transparency facilitates real life visualisation of soil continuum in physical models. When applied in conjunction with advanced photogrammetry and image processing techniques, transparent soils enable the quantification of the spatial deformation, displacement and multi-phase flow in physical model tests. Transparent synthetic soils have been successfully employed in geotechnical model tests as soil surrogates based on the testing results of their geotechnical properties which replicate those of natural soils. This paper presents a review on transparent synthetic soils and their numerous applications in geotechnical physical models. The properties of the aggregate materials are outlined and the features of the various transparent clays and sands available in the literature are described. The merits of transparent soil are highlighted and the need to amplify its application in geotechnical physical model researches is emphasised. This paper will serve as a concise compendium on the subject of transparent soils for future researchers in this field.

Structure and molecular assignment of lactococcal phage TP901-1 baseplate

DEFF Research Database (Denmark)

Bebeacua, Cecilia; Bron, Patrick; Lai, Livia

2010-01-01

on the host cell surface. We report here the electron microscopic structure of the phage TP901-1 wild-type BP as well as those of two mutants bppL (-) and bppU(-), lacking BppL (the RBPs) or both peripheral BP components (BppL and BppU), respectively. We also achieved an electron microscopic reconstruction...... of a partial BP complex, formed by BppU and BppL. This complex exhibits a tripod shape and is composed of nine BppLs and three BppUs. These structures, combined with light-scattering measurements, led us to propose that the TP901-1 BP harbors six tripods at its periphery, located around the central tube formed...... by ORF46 (Dit) hexamers, at its proximal end, and a ORF47 (Tal) trimer at its distal extremity. A total of 54 BppLs (18 RBPs) are thus available to mediate host anchoring with a large apparent avidity. TP901-1 BP exhibits an infection-ready conformation and differs strikingly from the lactococcal phage p...

Combining Lidar and Synthetic Aperture Radar Data to Estimate Forest Biomass: Status and Prospects

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Sanna Kaasalainen

2015-01-01

Full Text Available Research activities combining lidar and radar remote sensing have increased in recent years. The main focus in combining lidar-radar forest remote sensing has been on the retrieval of the aboveground biomass (AGB, which is a primary variable related to carbon cycle in land ecosystems, and has therefore been identified as an essential climate variable. In this review, we summarize the studies combining lidar and radar in estimating forest AGB. We discuss the complementary use of lidar and radar according to the relevance of the added value. The most promising prospects for combining lidar and radar data are in the use of lidar-derived ground elevations for improving large-area biomass estimates from radar, and in upscaling of lidar-based AGB data across large areas covered by spaceborne radar missions.

Knockdown of HSPA9 induces TP53-dependent apoptosis in human hematopoietic progenitor cells.

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Tuoen Liu

Full Text Available Myelodysplastic syndromes (MDS are the most common adult myeloid blood cancers in the US. Patients have increased apoptosis in their bone marrow cells leading to low peripheral blood counts. The full complement of gene mutations that contribute to increased apoptosis in MDS remains unknown. Up to 25% of MDS patients harbor and acquired interstitial deletion on the long arm of chromosome 5 [del(5q], creating haploinsufficiency for a large set of genes including HSPA9. Knockdown of HSPA9 in primary human CD34+ hematopoietic progenitor cells significantly inhibits growth and increases apoptosis. We show here that HSPA9 knockdown is associated with increased TP53 expression and activity, resulting in increased expression of target genes BAX and p21. HSPA9 protein interacts with TP53 in CD34+ cells and knockdown of HSPA9 increases nuclear TP53 levels, providing a possible mechanism for regulation of TP53 by HSPA9 haploinsufficiency in hematopoietic cells. Concurrent knockdown of TP53 and HSPA9 rescued the increased apoptosis observed in CD34+ cells following knockdown of HSPA9. Reduction of HSPA9 below 50% results in severe inhibition of cell growth, suggesting that del(5q cells may be preferentially sensitive to further reductions of HSPA9 below 50%, thus providing a genetic vulnerability to del(5q cells. Treatment of bone marrow cells with MKT-077, an HSPA9 inhibitor, induced apoptosis in a higher percentage of cells from MDS patients with del(5q compared to non-del(5q MDS patients and normal donor cells. Collectively, these findings indicate that reduced levels of HSPA9 may contribute to TP53 activation and increased apoptosis observed in del(5q-associated MDS.

Evaluation of the Lumipulse G TP-N Chemiluminescent Immunoassay as a Syphilis Screening Test.

Science.gov (United States)

Ortiz, Daniel A; Loeffelholz, Michael J

2017-11-01

A syphilis diagnosis is often aided by the detection of treponemal and nontreponemal antibodies. Automated treponemal antibody detection systems enable high-volume clinical laboratories to perform syphilis screening at a faster pace with lower labor costs. The Lumipulse G TP-N chemiluminescent immunoassay is an automated system that qualitatively detects IgG and IgM antibodies against Treponema pallidum antigens in human serum and plasma. To assess performance characteristics and workflow efficiency, the Lumipulse G TP-N assay was compared to the Bioplex 2200 Syphilis IgG multiplex flow immunoassay. Among the 4,134 routine and HIV samples tested by the two automated assays, the percentage of agreement was excellent at 99.0% (95% confidence interval [CI], 98.6% to 99.2%; κ, 0.89), with the Lumipulse G TP-N having a shorter time to first and subsequent results. All specimens with reactive syphilis screening results were further tested by rapid plasma reagin (RPR) and Treponema pallidum particle agglutination (TP·PA) testing ( n = 231). The results from the RPR-reactive samples ( n = 82) showed complete concordance with the two automated assays, while the TP·PA assay displayed some discrepancies. The positive percent agreement (PPA) and negative percent agreement (NPA) between the TP·PA test and the Lumipulse G TP-N test were 98.9% and 77.3%, respectively. The Bioplex 2200 Syphilis IgG immunoassay displayed a similar PPA (100%) but a substantially lower NPA (15.9%). Patient chart reviews of discrepant results suggested that the Lumipulse G TP-N assay produced 27 fewer falsely reactive results and can reduce the amount of additional confirmatory RPR and TP·PA testing needed. The analogous performance characteristics of the two automated systems indicate that the Lumipulse G TP-N assay is suitable for high-throughput syphilis screening. Copyright © 2017 American Society for Microbiology.

Mathematical modeling of synthetic unit hydrograph case study: Citarum watershed

Science.gov (United States)

Islahuddin, Muhammad; Sukrainingtyas, Adiska L. A.; Kusuma, M. Syahril B.; Soewono, Edy

2015-09-01

Deriving unit hydrograph is very important in analyzing watershed's hydrologic response of a rainfall event. In most cases, hourly measures of stream flow data needed in deriving unit hydrograph are not always available. Hence, one needs to develop methods for deriving unit hydrograph for ungagged watershed. Methods that have evolved are based on theoretical or empirical formulas relating hydrograph peak discharge and timing to watershed characteristics. These are usually referred to Synthetic Unit Hydrograph. In this paper, a gamma probability density function and its variant are used as mathematical approximations of a unit hydrograph for Citarum Watershed. The model is adjusted with real field condition by translation and scaling. Optimal parameters are determined by using Particle Swarm Optimization method with weighted objective function. With these models, a synthetic unit hydrograph can be developed and hydrologic parameters can be well predicted.

The use of synthetic input sequences in time series modeling

International Nuclear Information System (INIS)

Oliveira, Dair Jose de; Letellier, Christophe; Gomes, Murilo E.D.; Aguirre, Luis A.

2008-01-01

In many situations time series models obtained from noise-like data settle to trivial solutions under iteration. This Letter proposes a way of producing a synthetic (dummy) input, that is included to prevent the model from settling down to a trivial solution, while maintaining features of the original signal. Simulated benchmark models and a real time series of RR intervals from an ECG are used to illustrate the procedure

Validación del Cuestionario de Creencias Centrales de los Trastornos de la Personalidad (CCE-TP en población colombiana

Directory of Open Access Journals (Sweden)

Nora Helena Londoño A.

2010-07-01

Full Text Available Se construyó un cuestionario para evaluar creencias centrales asociadas con los trastornos de la personalidad, fundamentadas en el Modelo de la Terapia Cognitiva. Se realizó el análisis estructural y la validez de contenido de la prueba en población universitaria de la ciudad de Medellín, Colombia. La muestra fue representativa y elegida al azar a través de un procedimiento polietápico. Un número de 809 estudiantes universitarios contestaron el cuestionario de creencias centrales de los trastornos de la personalidad (CCE-TP. Se realizó un análisis factorial exploratorio de la prueba, reagrupándose los ítems en 14 factores (F que representan el 61,3% de la varianza. F1: CCE-TP antisocial (8 ítems, a 0,839; F2: CCE-TP esquizotípico/límite (8 ítems, a 0,846; F3: CCE-TP histriónico/patrón seductor (6 ítems, a 0,833; F4: CCE-TP paranoide (6 ítems, a 0,836; F5: CCE-TP por evitación / autopercepción negativa (5 ítems, a 0,755; F6: CCE-TP por dependencia (5 ítems, a 0,797; F7: CCE-TP histriónico/ dependencia emocional (4 ítems, a 0,755; F8: CCETP obsesivo-compulsivo/perfeccionista (4 ítems, a 0,808; F9: CCE-TP por evitación/hipersensible (4 ítems, a 0,766; F10: CCE-TP obsesivo-compulsivo/ crítico frente a los demás (3 ítems, a 0,851; F11: CCE-TP narcisista (4 ítems, a 0,717; F12: CCE-TP pasivo-agresivo / temor a ser dominado (3 ítems, a 0,719; F13: CCE-TP pasivo-agresivo/crítico frente a la autoridad (3 ítems, a 0,685, y F14: CCE-TP esquizoide (2 ítems, a 0,774. El alfa de Cronbach de la prueba fue de 0,931.

Validación del Cuestionario de Creencias Centrales de los Trastornos de la Personalidad (CCE-TP en población colombiana

Directory of Open Access Journals (Sweden)

Diego Castrillón M.

2007-06-01

Full Text Available Se construyó un cuestionario para evaluar creencias centrales asociadas con los trastornos de la personalidad, fundamentadas en el Modelo de la Terapia Cognitiva. Se realizó el análisis estructural y la validez de contenido de la prueba en población universitaria de la ciudad de Medellín, Colombia. La muestra fue representativa y elegida al azar a través de un procedimiento polietápico. Un número de 809 estudiantes universitarios contestaron el cuestionario de creencias centrales de los trastornos de la personalidad (CCE-TP. Se realizó un análisis factorial exploratorio de la prueba, reagrupándose los ítems en 14 factores (F que representan el 61,3% de la varianza. F1: CCE-TP antisocial (8 ítems, a 0,839; F2: CCE-TP esquizotípico/límite (8 ítems, a 0,846; F3: CCE-TP histriónico/patrón seductor (6 ítems, a 0,833; F4: CCE-TP paranoide (6 ítems, a 0,836; F5: CCE-TP por evitación / autopercepción negativa (5 ítems, a 0,755; F6: CCE-TP por dependencia (5 ítems, a 0,797; F7: CCE-TP histriónico/dependencia emocional (4 ítems, a 0,755; F8: CCETP obsesivo-compulsivo/perfeccionista (4 ítems, a 0,808; F9: CCE-TP por evitación/hipersensible (4 ítems, a 0,766; F10: CCE-TP obsesivo-compulsivo/ crítico frente a los demás (3 ítems, a 0,851; F11: CCE-TP narcisista (4 ítems, a 0,717; F12: CCE-TP pasivo-agresivo / temor a ser dominado (3 ítems, a 0,719; F13: CCE-TP pasivo-agresivo/crítico frente a la autoridad (3 ítems, a 0,685, y F14: CCE-TP esquizoide (2 ítems, a 0,774. El alfa de Cronbach de la prueba fue de 0,931.

Diffuse large B-cell lymphoma with combined TP53 mutation and MIR34A> methylation

DEFF Research Database (Denmark)

Asmar, Fazila; Hother, Christoffer; Kulosman, Gorjan

2014-01-01

and MIR34A methylation ("double hit") and these patients have an exceedingly poor prognosis with a median survival of 9.4 months (Phit") influence on survival. The TP53/MIR34A "double-hit" is an independent...... negative prognostic factor for survival (P=0.0002). In 2 DLBCL-cell lines with both TP53 mutation and promoter methylation of MIR34A, miR34A-5p is upregulated by 5-aza-2'deoxycytidine. Thus, the TP53/MIR34A "double hit" characterizes a very aggressive subgroup of DLBCL, which may be treatable...

Crystal growth, structural, optical, thermal, mechanical, laser damage threshold and electrical properties of triphenylphosphine oxide 4-nitrophenol (TP4N) single crystals for nonlinear optical applications

Science.gov (United States)

Karuppasamy, P.; Senthil Pandian, Muthu; Ramasamy, P.; Verma, Sunil

2018-05-01

The optically good quality single crystals of triphenylphosphine oxide 4-nitrophenol (TP4N) with maximum dimension of 15 × 10 × 5 mm3 were grown by slow evaporation solution technique (SEST) at room temperature. The cell dimensions of the grown TP4N crystal were confirmed by single crystal X-ray diffraction (SXRD) and the crystalline purity was confirmed and planes were indexed by powder X-ray diffraction (PXRD) analysis. Functional groups of TP4N crystal were confirmed by Fourier transform infrared (FTIR) spectral analysis. The optical transmittance of the grown crystal was determined by the UV-Vis NIR spectral analysis and it has good optical transparency in the entire visible region. The band tail (Urbach) energy of the grown crystal was analyzed and it appears to be minimum, which indicates that the TP4N has good crystallinity. The position of valence band (Ev) and conduction band (Ec) of the TP4N have been determined from the electron affinity energy (EA) and the ionization energy (EI) of its elements and using the optical band gap. The thermal behaviour of the grown crystal was investigated by thermogravimetric and differential thermal analysis (TG-DTA). Vickers microhardness analysis was carried out to identify the mechanical stability of the grown crystal and their indentation size effect (ISE) was explained by the Meyer's law (ML), Hays-Kendall's (HK) approach, proportional specimen resistance (PSR) model, modified PSR model (MPSR), elastic/plastic deformation (EPD) model and indentation induced cracking (IIC) model. Chemical etching study was carried out to find the etch pit density (EPD) of the grown crystal. Laser damage threshold (LDT) value was measured by using Nd:YAG laser (1064 nm). The dielectric permittivity (ε՛) and dielectric loss (tan δ) as a function of frequency was measured. The electronic polarizability (α) of the TP4N crystal was calculated. It is well matched to the value which was calculated from Clausius-Mossotti relation

Smart-DS: Synthetic Models for Advanced, Realistic Testing: Distribution Systems and Scenarios

Energy Technology Data Exchange (ETDEWEB)

Krishnan, Venkat K [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Palmintier, Bryan S [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Hodge, Brian S [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Hale, Elaine T [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Elgindy, Tarek [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Bugbee, Bruce [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Rossol, Michael N [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Lopez, Anthony J [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Krishnamurthy, Dheepak [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Vergara, Claudio [MIT; Domingo, Carlos Mateo [IIT Comillas; Postigo, Fernando [IIT Comillas; de Cuadra, Fernando [IIT Comillas; Gomez, Tomas [IIT Comillas; Duenas, Pablo [MIT; Luke, Max [MIT; Li, Vivian [MIT; Vinoth, Mohan [GE Grid Solutions; Kadankodu, Sree [GE Grid Solutions

2017-08-09

The National Renewable Energy Laboratory (NREL) in collaboration with Massachusetts Institute of Technology (MIT), Universidad Pontificia Comillas (Comillas-IIT, Spain) and GE Grid Solutions, is working on an ARPA-E GRID DATA project, titled Smart-DS, to create: 1) High-quality, realistic, synthetic distribution network models, and 2) Advanced tools for automated scenario generation based on high-resolution weather data and generation growth projections. Through these advancements, the Smart-DS project is envisioned to accelerate the development, testing, and adoption of advanced algorithms, approaches, and technologies for sustainable and resilient electric power systems, especially in the realm of U.S. distribution systems. This talk will present the goals and overall approach of the Smart-DS project, including the process of creating the synthetic distribution datasets using reference network model (RNM) and the comprehensive validation process to ensure network realism, feasibility, and applicability to advanced use cases. The talk will provide demonstrations of early versions of synthetic models, along with the lessons learnt from expert engagements to enhance future iterations. Finally, the scenario generation framework, its development plans, and co-ordination with GRID DATA repository teams to house these datasets for public access will also be discussed.

Synthetic environments

Science.gov (United States)

Lukes, George E.; Cain, Joel M.

1996-02-01

The Advanced Distributed Simulation (ADS) Synthetic Environments Program seeks to create robust virtual worlds from operational terrain and environmental data sources of sufficient fidelity and currency to interact with the real world. While some applications can be met by direct exploitation of standard digital terrain data, more demanding applications -- particularly those support operations 'close to the ground' -- are well-served by emerging capabilities for 'value-adding' by the user working with controlled imagery. For users to rigorously refine and exploit controlled imagery within functionally different workstations they must have a shared framework to allow interoperability within and between these environments in terms of passing image and object coordinates and other information using a variety of validated sensor models. The Synthetic Environments Program is now being expanded to address rapid construction of virtual worlds with research initiatives in digital mapping, softcopy workstations, and cartographic image understanding. The Synthetic Environments Program is also participating in a joint initiative for a sensor model applications programer's interface (API) to ensure that a common controlled imagery exploitation framework is available to all researchers, developers and users. This presentation provides an introduction to ADS and the associated requirements for synthetic environments to support synthetic theaters of war. It provides a technical rationale for exploring applications of image understanding technology to automated cartography in support of ADS and related programs benefitting from automated analysis of mapping, earth resources and reconnaissance imagery. And it provides an overview and status of the joint initiative for a sensor model API.

Evaluation of FlaB1, FlaB2, FlaB3, and Tp0463 of Treponema pallidum for serodiagnosis of syphilis.

Science.gov (United States)

Jiang, Chuanhao; Xiao, Jinhong; Xie, Yafeng; Xiao, Yongjian; Wang, Chuan; Kuang, Xingxing; Xu, Man; Li, Ranhui; Zeng, Tiebing; Liu, Shuanquan; Yu, Jian; Zhao, Feijun; Wu, Yimou

2016-02-01

Syphilis is a multistage disease caused by the invasive spirochete Treponema pallidum subsp. pallidum, and accurate diagnosis is important for the prevention and treatment of syphilis. Here, to identify appropriate diagnostic antigens for serodiagnosis of syphilis, 6 recombinant proteins were expressed in Escherichia coli and purified, including flagellins (FlaB1 [Tp0868], FlaB2 [Tp0792], and FlaB3 [Tp0870]), Tp0463, Tp0751, and Tp1038. The sensitivities were determined by screening sera from individuals with primary (n=82), secondary (n=115), latent (n=105), and congenital (n=65) syphilis. The specificities were determined by screening sera from uninfected controls (n=30) and potentially cross-reactive infections including Lyme disease (n=30), leptospirosis (n=5), and hepatitis B (n=30). Our data showed that FlaB1, FlaB2, FlaB3, Tp0463, and Tp1038 exhibited higher overall sensitivities and specificities for detecting IgG antibody, with 95.4% and 98.9%, 92.6% and 95.8%, 95.1% and 95.8%, 92.6% and 97.9%, and 95.9% and 98.9%, respectively. In contrast, Tp0751 demonstrated only an overall sensitivity of 39.2%. For comparison, the sensitivity and specificity of Architect Syphilis TP were determined to be 98.1% and 93.7%, respectively. In addition, FlaB1, FlaB2, FlaB3, and Tp0463 demonstrated excellent performance for detecting IgM antibody in primary and congenital syphilis, with sensitivities of 76.8% and 83.1%, 72.0% and 87.7%, 74.4% and 89.2%, and 64.6% and 75.3%, respectively. These results indicate that FlaB1, FlaB2, FlaB3, and Tp0463 could be as novel diagnostic candidates for serodiagnosis of syphilis. Copyright © 2016 Elsevier Inc. All rights reserved.

A meta-analysis of the relationship between FGFR3 and TP53 mutations in bladder cancer.

Science.gov (United States)

Neuzillet, Yann; Paoletti, Xavier; Ouerhani, Slah; Mongiat-Artus, Pierre; Soliman, Hany; de The, Hugues; Sibony, Mathilde; Denoux, Yves; Molinie, Vincent; Herault, Aurélie; Lepage, May-Linda; Maille, Pascale; Renou, Audrey; Vordos, Dimitri; Abbou, Claude-Clément; Bakkar, Ashraf; Asselain, Bernard; Kourda, Nadia; El Gaaied, Amel; Leroy, Karen; Laplanche, Agnès; Benhamou, Simone; Lebret, Thierry; Allory, Yves; Radvanyi, François

2012-01-01

TP53 and FGFR3 mutations are the most common mutations in bladder cancers. FGFR3 mutations are most frequent in low-grade low-stage tumours, whereas TP53 mutations are most frequent in high-grade high-stage tumours. Several studies have reported FGFR3 and TP53 mutations to be mutually exclusive events, whereas others have reported them to be independent. We carried out a meta-analysis of published findings for FGFR3 and TP53 mutations in bladder cancer (535 tumours, 6 publications) and additional unpublished data for 382 tumours. TP53 and FGFR3 mutations were not independent events for all tumours considered together (OR = 0.25 [0.18-0.37], p = 0.0001) or for pT1 tumours alone (OR = 0.47 [0.28-0.79], p = 0.0009). However, if the analysis was restricted to pTa tumours or to muscle-invasive tumours alone, FGFR3 and TP53 mutations were independent events (OR = 0.56 [0.23-1.36] (p = 0.12) and OR = 0.99 [0.37-2.7] (p = 0.35), respectively). After stratification of the tumours by stage and grade, no dependence was detected in the five tumour groups considered (pTaG1 and pTaG2 together, pTaG3, pT1G2, pT1G3, pT2-4). These differences in findings can be attributed to the putative existence of two different pathways of tumour progression in bladder cancer: the CIS pathway, in which FGFR3 mutations are rare, and the Ta pathway, in which FGFR3 mutations are frequent. TP53 mutations occur at the earliest stage of the CIS pathway, whereas they occur would much later in the Ta pathway, at the T1G3 or muscle-invasive stage.

Techniques for Modeling Human Performance in Synthetic Environments: A Supplementary Review

National Research Council Canada - National Science Library

Ritter, Frank E; Shadbolt, Nigel R; Elliman, David; Young, Richard M; Gobet, Fernand; Baxter, Gordon D

2003-01-01

... architectures including hybrid architectures, and agent and Belief, Desires and Intentions (BDI) architectures. A list of projects with high payoff for modeling human performance in synthetic environments is provided as a conclusion.

Long term steam oxidation of TP 347H FG in power plants

DEFF Research Database (Denmark)

Hansson, Anette Nørgaard; Korcakova, Leona; Hald, John

2005-01-01

The long term oxidation behaviour of TP 347H FG at ultra supercritical steam conditions was assessed by exposing the steel in test superheater loops in a Danish coal-fired power plant. The steamside oxide layer was investigated with scanning electron microscopy and energy dispersive Xray diffract......The long term oxidation behaviour of TP 347H FG at ultra supercritical steam conditions was assessed by exposing the steel in test superheater loops in a Danish coal-fired power plant. The steamside oxide layer was investigated with scanning electron microscopy and energy dispersive Xray...

TP53 genetic polymorphisms, interactions with lifestyle factors and lung cancer risk: a case control study in a Chinese population

International Nuclear Information System (INIS)

Li, Yanli; Su, Jia; Cai, Lin; Yu, Shunzhang; Zhang, Zuo-Feng; Mu, Lina; Chang, Shen-Chih; Niu, Rungui; Liu, Li; Crabtree-Ide, Christina R; Zhao, Baoxing; Shi, Jianping; Han, Xiaoyou; Li, Jiawei

2013-01-01

A pathway-based genotyping analysis suggested rs2078486 was a novel TP53 SNP, but very few studies replicate this association. TP53 rs1042522 is the most commonly studied SNP, but very few studies examined its potential interaction with environmental factors in relation to lung cancer risk. This study aims to examine associations between two TP53 single-nucleotide polymorphisms (SNPs) (rs2078486, rs1042522), their potential interaction with environmental factors and risk of lung cancer. A case–control study was conducted in Taiyuan, China. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). Multiplicative and additive interactions between TP53 SNPs and lifestyle factors were evaluated. Variant TP53 rs2078486 SNP was significantly associated with elevated lung cancer risk among smokers (OR: 1.70, 95% CI: 1.08 - 2.67) and individuals with high indoor air pollution exposure (OR: 1.51, 95% CI: 1.00-2.30). Significant or borderline significant multiplicative and additive interactions were found between TP53 rs2078486 polymorphism with smoking and indoor air pollution exposure. The variant genotype of TP53 SNP rs1042522 significantly increased lung cancer risk in the total population (OR: 1.57, 95% CI: 1.11-2.21), but there was no evidence of heterogeneity among individuals with different lifestyle factors. This study confirmed that TP53 rs2078486 SNP is potentially a novel TP53 SNP that may affect lung cancer risk. Our study also suggested potential synergetic effects of TP53 rs2078486 SNP with smoking and indoor air pollution exposure on lung cancer risk

Improving Accuracy Estimation of Forest Aboveground Biomass Based on Incorporation of ALOS-2 PALSAR-2 and Sentinel-2A Imagery and Machine Learning: A Case Study of the Hyrcanian Forest Area (Iran

Directory of Open Access Journals (Sweden)

Sasan Vafaei

2018-01-01

Full Text Available The main objective of this research is to investigate the potential combination of Sentinel-2A and ALOS-2 PALSAR-2 (Advanced Land Observing Satellite -2 Phased Array type L-band Synthetic Aperture Radar-2 imagery for improving the accuracy of the Aboveground Biomass (AGB measurement. According to the current literature, this kind of investigation has rarely been conducted. The Hyrcanian forest area (Iran is selected as the case study. For this purpose, a total of 149 sample plots for the study area were documented through fieldwork. Using the imagery, three datasets were generated including the Sentinel-2A dataset, the ALOS-2 PALSAR-2 dataset, and the combination of the Sentinel-2A dataset and the ALOS-2 PALSAR-2 dataset (Sentinel-ALOS. Because the accuracy of the AGB estimation is dependent on the method used, in this research, four machine learning techniques were selected and compared, namely Random Forests (RF, Support Vector Regression (SVR, Multi-Layer Perceptron Neural Networks (MPL Neural Nets, and Gaussian Processes (GP. The performance of these AGB models was assessed using the coefficient of determination (R2, the root-mean-square error (RMSE, and the mean absolute error (MAE. The results showed that the AGB models derived from the combination of the Sentinel-2A and the ALOS-2 PALSAR-2 data had the highest accuracy, followed by models using the Sentinel-2A dataset and the ALOS-2 PALSAR-2 dataset. Among the four machine learning models, the SVR model (R2 = 0.73, RMSE = 38.68, and MAE = 32.28 had the highest prediction accuracy, followed by the GP model (R2 = 0.69, RMSE = 40.11, and MAE = 33.69, the RF model (R2 = 0.62, RMSE = 43.13, and MAE = 35.83, and the MPL Neural Nets model (R2 = 0.44, RMSE = 64.33, and MAE = 53.74. Overall, the Sentinel-2A imagery provides a reasonable result while the ALOS-2 PALSAR-2 imagery provides a poor result of the forest AGB estimation. The combination of the Sentinel-2A imagery and the ALOS-2 PALSAR-2

Non-Watson-Crick structures in oligodeoxynucleotides: Self-association of d(TpCpGpA) stabilized at acidic pH

International Nuclear Information System (INIS)

Topping, R.J.; Stone, M.P.; Brush, C.K.; Harris, T.M.

1988-01-01

The 1 H NMR spectrum of the tetradeoxynucleotide d(TpCpGpA) was examined as a function of temperature, pH, and concentration. At pH 7 and above the solution conformation for this oligodeoxynucleotide appears to be a mixture of random coil and Watson-Crick duplex. At 25 degree C, a pH titration of d(TpCpGaA) shown that distinct conformational changes occur as the pH is lowered below 7.0. These conformational changes are reversible upon readjusting the pH to neutrality, indicating the presence of a pH-dependent set of conformational equilibria. At 25 degree C, the various conformational state in the mixture are in rapid exchange on the NMR time scale. Examination of the titration curve shown the presence of distinct conformational states at pH greater than 7, and between pH 4 and pH 5. When the pH titration is repeated at 5 degree C, the conformational equilibria are in slow exchange on the NMR time scale; distinct signals from each conformational state are observable. The stable conformational state present between pH 4 and pH 5 represents an ordered conformation of d(TpCpGpA) which dissociates to a less ordered structure upon raising the temperature. The ordered conformation differs from the Watson-Crick helix, as is shown from nuclear Overhauser enhancement experiments, as well as chemical shift data. These results indicate that their ordered conformation is similar to the conformation of d(TpCpGpA) observed between pH 4 and pH 5. In the present case it is likely that stabilization of an ordered duplex conformation for d(TpCpGpA) is achieved by protonation of cytosine. A possible model which could explain the data involves formation of Hoogsteen C + :G base pairs

UARS Particle Environment Monitor (PEM) Level 3TP V001

Data.gov (United States)

National Aeronautics and Space Administration — The Particle Environment Monitor (PEM) Level 3TP data product consists of daily, 65.536 second and 2.048 interval time-ordered, vertical profiles of electron and...

Synthetic miR-34a mimics as a novel therapeutic agent for multiple myeloma: in vitro and in vivo evidence.

Science.gov (United States)

Di Martino, Maria T; Leone, Emanuela; Amodio, Nicola; Foresta, Umberto; Lionetti, Marta; Pitari, Maria R; Cantafio, Maria E Gallo; Gullà, Annamaria; Conforti, Francesco; Morelli, Eugenio; Tomaino, Vera; Rossi, Marco; Negrini, Massimo; Ferrarini, Manlio; Caraglia, Michele; Shammas, Masood A; Munshi, Nikhil C; Anderson, Kenneth C; Neri, Antonino; Tagliaferri, Pierosandro; Tassone, Pierfrancesco

2012-11-15

Deregulated expression of miRNAs has been shown in multiple myeloma (MM). A promising strategy to achieve a therapeutic effect by targeting the miRNA regulatory network is to enforce the expression of miRNAs that act as tumor suppressor genes, such as miR-34a. Here, we investigated the therapeutic potential of synthetic miR-34a against human MM cells in vitro and in vivo. Either transient expression of miR-34a synthetic mimics or lentivirus-based miR-34a-stable enforced expression triggered growth inhibition and apoptosis in MM cells in vitro. Synthetic miR-34a downregulated canonic targets BCL2, CDK6, and NOTCH1 at both the mRNA and protein level. Lentiviral vector-transduced MM xenografts with constitutive miR-34a expression showed high growth inhibition in severe combined immunodeficient (SCID) mice. The anti-MM activity of lipidic-formulated miR-34a was further shown in vivo in two different experimental settings: (i) SCID mice bearing nontransduced MM xenografts; and (ii) SCID-synth-hu mice implanted with synthetic 3-dimensional scaffolds reconstituted with human bone marrow stromal cells and then engrafted with human MM cells. Relevant tumor growth inhibition and survival improvement were observed in mice bearing TP53-mutated MM xenografts treated with miR-34a mimics in the absence of systemic toxicity. Our findings provide a proof-of-principle that formulated synthetic miR-34a has therapeutic activity in preclinical models and support a framework for development of miR-34a-based treatment strategies in MM patients. ©2012 AACR.

Meta-analysis of association between the TP53 Arg72Pro polymorphism and risk of endometriosis based on case-control studies.

Science.gov (United States)

Yan, Yulan; Wu, Renzheng; Li, Shaojing; He, Jinlong

2015-06-01

In the light of the relationship between the TP53 Arg72Pro (rs1042522) polymorphism and the risk of endometriosis remains inclusive or controversial. For better understanding of the effect of TP53 Arg72Pro polymorphism on endometriosis risk, we performed a meta-analysis. The relevant studies were identified through a search of PubMed, Web of Science, EMBASE, Ovid, Springer, China National Knowledge Infrastructure (CNKI), cqvip, Wanfang database, and Chinese Biomedical Literature (CBM) databases up to December, 2014. The association between the TP53 Arg72Pro polymorphism and endometriosis risk was pooled by conducted by odds ratios and 95% confidence intervals. A total of fifteen case-control studies with 2683 cases and 3335 controls were eventually identified. There was significant association between Arg72Pro polymorphism and endometriosis risk in all of the five models in overall populations (C vs. G: OR=1.32, 95%CI=1.14-1.53, p=0.00; CC vs. GG: OR=1.80, 95%CI=1.28-2.53, p=0.001; GC vs. GG: OR=1.52, 95%CI=1.22-1.88, p=0.00; CC vs. OR=1.32, 95%CI=1.05-1.66, p=0.016; CC/GC vs. GG: OR=1.59, 95%CI=1.26-2.00, p=0.00). In the sub-group analysis according to ethnicity, the results suggested that TP53 Arg72Pro polymorphism was not associated with endometriosis risk in Caucasians. However, the significant association was found in Asians and Mixed race (MIX) under the five models. The results of this meta-analysis suggest that the TP53 Arg72Pro polymorphism can increase the risk of endometriosis, especially among Asians and MIX populations. Considering the limited sample size and ethnicities included in the meta-analysis, further larger scaled and well-designed studies are needed to confirm our results. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Characterization and three-dimensional reconstruction of synthetic bone model foams

Energy Technology Data Exchange (ETDEWEB)

Gómez, S. [Interdepartment Research Group for the Applied Scientific Collaboration (IRGASC), Division of Biomaterials and Bioengineering, Technical University of Catalonia (UPC), Avda. Diagonal 647, E-08028 Barcelona (Spain); Vlad, M.D. [Interdepartment Research Group for the Applied Scientific Collaboration (IRGASC), Division of Biomaterials and Bioengineering, Technical University of Catalonia (UPC), Avda. Diagonal 647, E-08028 Barcelona (Spain); Faculty of Medical Bioengineering, “Gr. T. Popa” University of Medicine and Pharmacy, Str. Kogalniceanu 9-13, 700454 Iasi (Romania); López, J. [Interdepartment Research Group for the Applied Scientific Collaboration (IRGASC), Division of Biomaterials and Bioengineering, Technical University of Catalonia (UPC), Avda. Diagonal 647, E-08028 Barcelona (Spain); Navarro, M. [Centre de Biotecnologia Animal i de Teràpia Gènica (CBATEG), Departament de Sanitat i d' Anatomia Animals, Universitat Autònoma de Barcelona, E-08193 Bellaterra, Cerdanyola del Vallès (Spain); Fernández, E., E-mail: enrique.fernandez@upc.edu [Interdepartment Research Group for the Applied Scientific Collaboration (IRGASC), Division of Biomaterials and Bioengineering, Technical University of Catalonia (UPC), Avda. Diagonal 647, E-08028 Barcelona (Spain)

2013-08-01

Sawbones© open-cell foams with different porosity grades are being used as synthetic bone-like models for in vitro mechanical and infiltration experiments. However, a comprehensive characterization of these foams is not available and there is a lack of reliable information about them. For this reason two of these foams (Refs. 1522-505 and -507) have been characterized at the micro architectural level by scanning electron microscopy, computed tomography and image data analysis. BoneJ open software and ImageJ open software were used to obtain the characteristic histomorphometric parameters and the three dimensional virtual models of the foams. The results showed that both foams, while having different macro porosities, appeared undistinguishable at the micro scale. Moreover, the micro structural features resembled those of osteoporotic rather than healthy trabecular bone. It is concluded that Sawbones© foams behave reasonably as synthetic bone-like models. Consequently, their use is recommended for in vitro comparison purposes of both mechanical and infiltration testing performed in real vertebra. Finally, the virtual models obtained, which are available under request, can favour comparisons between future self-similar in vitro experiments and computer simulations. - Highlights: • Sawbones© model foams have been scanned by μ-CT. • Histomorphometric indices and 3D virtual models have been obtained. • The results will be of use to understand biocement vertebra infiltration studies.

Characterization and three-dimensional reconstruction of synthetic bone model foams

International Nuclear Information System (INIS)

Gómez, S.; Vlad, M.D.; López, J.; Navarro, M.; Fernández, E.

2013-01-01

Sawbones© open-cell foams with different porosity grades are being used as synthetic bone-like models for in vitro mechanical and infiltration experiments. However, a comprehensive characterization of these foams is not available and there is a lack of reliable information about them. For this reason two of these foams (Refs. 1522-505 and -507) have been characterized at the micro architectural level by scanning electron microscopy, computed tomography and image data analysis. BoneJ open software and ImageJ open software were used to obtain the characteristic histomorphometric parameters and the three dimensional virtual models of the foams. The results showed that both foams, while having different macro porosities, appeared undistinguishable at the micro scale. Moreover, the micro structural features resembled those of osteoporotic rather than healthy trabecular bone. It is concluded that Sawbones© foams behave reasonably as synthetic bone-like models. Consequently, their use is recommended for in vitro comparison purposes of both mechanical and infiltration testing performed in real vertebra. Finally, the virtual models obtained, which are available under request, can favour comparisons between future self-similar in vitro experiments and computer simulations. - Highlights: • Sawbones© model foams have been scanned by μ-CT. • Histomorphometric indices and 3D virtual models have been obtained. • The results will be of use to understand biocement vertebra infiltration studies

Experimental manipulation of TN:TP ratiossuppress cyanobacterial biovolume and microcystinconcentration in large-scale in situ mesocosms

Science.gov (United States)

Harris, Theodore D.; Wilhelm, Frank M.; Graham, Jennifer L.; Loftin, Keith A.

2014-01-01

A global dataset was compiled to examine relations between the total nitrogen to total phosphorus ratio (TN:TP) and microcystin concentration in lakes and reservoirs. Microcystin concentration decreased as TN:TP ratios increased, suggesting that manipulation of the TN:TP ratio may reduce microcystin concentrations. This relationship was experimentally tested by adding ammonium nitrate to increase the TN:TP ratio in large-scale (70 m3), in situ mesocosms located in a eutrophic reservoir that routinely experiences toxic blooms of cyanobacteria. At a TN:TP ratio >75:1, chlorophytes dominated the phytoplankton community in the mesocosms, while cyanobacterial biovolume was significantly reduced and microcystin was not detected. In contrast, the unmanipulated reservoir was dominated by cyanobacteria, and microcystin was detected. Secchi depths were 1.1 to 1.8 times greater in the mesocosms relative to the reservoir. Cladoceran zooplankton had a larger body size (0.14 mm on average) in the mesocosms compared to conspecifics in the reservoir, which was likely related to the higher quality food. Combined, these empirical and experimental data indicate that although nutrient addition is counterintuitive to current cyanobacteria management practices, increasing the TN:TP ratio by adding nitrogen may be a potential short-term management strategy to reduce cyanobacteria and cyanotoxins when other alternatives (e.g., phosphorus reduction) are not possible. Additional experimental studies with careful controls are needed to define best management practices and identify any potential unintended consequences before nitrogen addition is implemented as a lake and reservoir management practice.

Pemetaan Pusat Pelayanan Terpadu Pemberdayaan Perempuan dan Anak (P2TP2A Provinsi Sumatera Bar

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Hallen Abu Bakar

2017-09-01

Full Text Available The Center of Integrated Service for Women and Children Empowerment (P2TP2A is established by the government based community in order to eliminate the violence towards women and children. It also aims to empower the position of women and children. The purpose of the study is to describe comprehensively the existance of P2TP2A in sub-district, district, city, and province in West Sumatra. Descriptive qualitative research was used where the data taken from questionnaire and in-deepthinterview. The study found that the Center of Integrated Service for Women and Children Empowerment was established by following certain procedure, legality and personnel structure. It also found that the majority of P2TP2A in West Sumatra has insufficient infrastructures. Meanwhile, it is only P2TP2A Limpapeh Rumah Nan Gadang of West Sumatera, and P2TP2A Luhak Nan Tuo Batusangkar has sufficient infrastructures. Many of them were located at the corner of Community Empowerment and Women and Family Planning office (BPMPKB. Every P2TP2A in those district and city have made their programs, but they faced some difficulties in realize them doe to financial problems. The human resources were recruited from SKPD, academician, professional, society figures, LSM who concern on gender meanstreaming. They play the role more on providing the service than giving information and empowerment. The last finding of the study showed that the involvement of local government, Health offices, social services, police, ministry of religion, prosecutors and social services have been effective.

Association of the germline TP53 R337H mutation with breast cancer in southern Brazil

International Nuclear Information System (INIS)

Assumpção, Juliana G; Zeferino, Luiz Carlos; Dufloth, Rozany M; Brandalise, Silvia Regina; Yunes, José Andres; Seidinger, Ana Luíza; Mastellaro, Maria José; Ribeiro, Raul C; Zambetti, Gerard P; Ganti, Ramapriya; Srivastava, Kumar; Shurtleff, Sheila; Pei, Deqing

2008-01-01

The germline TP53-R337H mutation is strongly associated with pediatric adrenocortical tumors (ACT) in southern Brazil; it has low penetrance and limited tissue specificity in most families and therefore is not associated with Li-Fraumeni syndrome. However, other tumor types, mainly breast cancer, have been observed in carriers of several unrelated kindreds, raising the possibility that the R337H mutation may also contribute to breast tumorigenesis in a genetic background-specific context. We conducted a case-control study to determine the prevalence of the R337H mutation by sequencing TP53 exon 10 in 123 women with breast cancer and 223 age- and sex-matched control subjects from southern Brazil. Fisher's test was used to compare the prevalence of the R337H. The R337H mutation was found in three patients but in none of the controls (p = 0.0442). Among the carriers, two had familial history of cancer meeting the Li-Fraumeni-like criteria. Remarkably, tumors in each of these three cases underwent loss of heterozygosity by eliminating the mutant TP53 allele rather than the wild-type allele. Polymorphisms were identified within the TP53 (R72P and Ins16) and MDM2 (SNP309) genes that may further diminish TP53 tumor suppressor activity. These results demonstrate that the R337H mutation can significantly increase the risk of breast cancer in carriers, which likely depends on additional cooperating genetic factors. These findings are also important for understanding how low-penetrant mutant TP53 alleles can differentially influence tumor susceptibility

TP-Space RRT – Kinematic Path Planning of Non-Holonomic Any-Shape Vehicles

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Jose Luis Blanco

2015-05-01

Full Text Available The autonomous navigation of vehicles typically combines two kinds of methods: a path is first planned, and then the robot is driven by a local obstacle-avoidance controller. The present work, which focuses on path planning, proposes an extension to the well-known rapidly-exploring random tree (RRT algorithm to allow its integration with a trajectory parameter-space (TP-space as an efficient method to detect collision-free, kinematically-feasible paths for arbitrarily-shaped vehicles. In contrast to original RRT, this proposal generates navigation trees, with poses as nodes, whose edges are all kinematically-feasible paths, suitable to being accurately followed by vehicles driven by pure reactive algorithms. Initial experiments demonstrate the suitability of the method with an Ackermann-steering vehicle model whose severe kinematic constraints cannot be obviated. An important result that sets this work apart from previous research is the finding that employing several families of potential trajectories to expand the tree, which can be done efficiently under the TP-space formalism, improves the optimality of the planned trajectories. A reference C++ implementation has been released as open-source.

TP53 supports basal-like differentiation of mammary epithelial cells by preventing translocation of deltaNp63 into nucleoli

Science.gov (United States)

Munne, Pauliina M.; Gu, Yuexi; Tumiati, Manuela; Gao, Ping; Koopal, Sonja; Uusivirta, Sanna; Sawicki, Janet; Wei, Gong-Hong; Kuznetsov, Sergey G.

2014-04-01

Multiple observations suggest a cell type-specific role for TP53 in mammary epithelia. We developed an in vitro assay, in which primary mouse mammary epithelial cells (mMECs) progressed from lumenal to basal-like phenotypes based on expression of Krt18 or ΔNp63, respectively. Such transition was markedly delayed in Trp53-/- mMECs suggesting that Trp53 is required for specification of the basal, but not lumenal cells. Evidence from human basal-like cell lines suggests that TP53 may support the activity of ΔNp63 by preventing its translocation from nucleoplasm into nucleoli. In human lumenal cells, activation of TP53 by inhibiting MDM2 or BRCA1 restored the nucleoplasmic expression of ΔNp63. Trp53-/- mMECs eventually lost epithelial features resulting in upregulation of MDM2 and translocation of ΔNp63 into nucleoli. We propose that TP63 may contribute to TP53-mediated oncogenic transformation of epithelial cells and shed light on tissue- and cell type-specific biases observed for TP53-related cancers.

Microstructure and properties of TP2 copper tube with La microalloying by horizontal continuous casting

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Jin-hu Wu

2018-01-01

Full Text Available The TP2 copper tube was prepared with La microalloying by horizontal continuous casting (HCC. The absorptivity of La and its effects on microstructure, tensile and corrosion properties of HCC TP2 copper tube were studied by means of the inductively coupled plasma optical emission spectrometer (ICP-OES, optical microscope (OM, scanning electron microscope (SEM and potentiodynamic polarization measurements. The results show that the absorptivity of La in the HCC TP2 copper tube is about 15% under antivacuum conditions due to the good chemical activities of La. The impurity elements in copper tube such as O, S, Pb and Si can be significantly reduced, and the average columnar dendrite spacing of the copper tube can also be reduced from 2.21 mm to 0.93 mm by adding La. The ultimate tensile strength and the elongation with and without La addition are almost unchanged. However, the annual corrosion rate of the HCC TP2 copper tube is reduced from 10.18 mm•a-1 to 9.37 mm•a-1 by the purification effect of trace La.

TP53 mutations in myelodysplastic syndrome are strongly correlated with aberrations of chromosome 5, and correlate with adverse prognosis.

Science.gov (United States)

Kulasekararaj, Austin G; Smith, Alexander E; Mian, Syed A; Mohamedali, Azim M; Krishnamurthy, Pramila; Lea, Nicholas C; Gäken, Joop; Pennaneach, Coralie; Ireland, Robin; Czepulkowski, Barbara; Pomplun, Sabine; Marsh, Judith C; Mufti, Ghulam J

2013-03-01

This study aimed to determine the incidence/prognostic impact of TP53 mutation in 318 myelodysplastic syndrome (MDS) patients, and to correlate the changes to cytogenetics, single nucleotide polymorphism array karyotyping and clinical outcome. The median age was 65 years (17-89 years) and median follow-up was 45 months [95% confidence interval (CI) 27-62 months]. TP53 mutations occurred in 30 (9.4%) patients, exclusively in isolated del5q (19%) and complex karyotype (CK) with -5/5q-(72%), correlated with International Prognostic Scoring System intermediate-2/high, TP53 protein expression, higher blast count and leukaemic progression. Patients with mutant TP53 had a paucity of mutations in other genes implicated in myeloid malignancies. Median overall survival of patients with TP53 mutation was shorter than wild-type (9 versus 66 months, P disappearance of the mutant clone or emergence of new clones, suggesting an early occurrence of TP53 mutations. A reduction in mutant clone correlated with response to 5-azacitidine, however clones increased in non-responders and persisted at relapse. The adverse impact of TP53 persists after adjustment for cytogenetic risk and is of practical importance in evaluating prognosis. The relatively common occurrence of these mutations in two different prognostic spectrums of MDS, i.e. isolated 5q- and CK with -5/5q-, possibly implies two different mechanistic roles for TP53 protein. © 2013 Crown copyright. This article is published with the permission of the Controller of HMSO and the Queen's Printer for Scotland.

New recurrent deletions in the PPARgamma and TP53 genes are associated with childhood myelodysplastic syndrome

DEFF Research Database (Denmark)

Silveira, Cássia G T; Oliveira, Fábio M; Valera, Elvis T

2009-01-01

Myelodysplastic syndrome (MDS) is a rare hematological malignancy in children. It was performed FISH analysis in 19 pediatric MDS patients to investigate deletions involving the PPARgamma and TP53 genes. Significant losses in the PPARgamma gene and deletions in the tumor suppressor gene TP53 were...

New reaction rate for 16O( p, γ )17F and its influence on the oxygen isotopic ratios in massive AGB stars

NARCIS (Netherlands)

Iliadis, C.; Angulo, C.; Descouvement, P.; Lugaro, M.A.|info:eu-repo/dai/nl/304833975; Mohr, P.

2008-01-01

The 16O(p, γ )17F reaction rate is revisited with special emphasis on the stellar temperature range of T=60-100 MK, important for hot bottom burning in asymptotic giant branch (AGB) stars. We evaluate existing cross-section data that were obtained since 1958 and, if appropriate, correct published

A meta-analysis of the relationship between FGFR3 and TP53 mutations in bladder cancer.

Directory of Open Access Journals (Sweden)

Yann Neuzillet

Full Text Available TP53 and FGFR3 mutations are the most common mutations in bladder cancers. FGFR3 mutations are most frequent in low-grade low-stage tumours, whereas TP53 mutations are most frequent in high-grade high-stage tumours. Several studies have reported FGFR3 and TP53 mutations to be mutually exclusive events, whereas others have reported them to be independent. We carried out a meta-analysis of published findings for FGFR3 and TP53 mutations in bladder cancer (535 tumours, 6 publications and additional unpublished data for 382 tumours. TP53 and FGFR3 mutations were not independent events for all tumours considered together (OR = 0.25 [0.18-0.37], p = 0.0001 or for pT1 tumours alone (OR = 0.47 [0.28-0.79], p = 0.0009. However, if the analysis was restricted to pTa tumours or to muscle-invasive tumours alone, FGFR3 and TP53 mutations were independent events (OR = 0.56 [0.23-1.36] (p = 0.12 and OR = 0.99 [0.37-2.7] (p = 0.35, respectively. After stratification of the tumours by stage and grade, no dependence was detected in the five tumour groups considered (pTaG1 and pTaG2 together, pTaG3, pT1G2, pT1G3, pT2-4. These differences in findings can be attributed to the putative existence of two different pathways of tumour progression in bladder cancer: the CIS pathway, in which FGFR3 mutations are rare, and the Ta pathway, in which FGFR3 mutations are frequent. TP53 mutations occur at the earliest stage of the CIS pathway, whereas they occur would much later in the Ta pathway, at the T1G3 or muscle-invasive stage.

Comparison of Nonlinear Model Results Using Modified Recorded and Synthetic Ground Motions

International Nuclear Information System (INIS)

Spears, Robert E.; Wilkins, J. Kevin

2011-01-01

A study has been performed that compares results of nonlinear model runs using two sets of earthquake ground motion time histories that have been modified to fit the same design response spectra. The time histories include applicable modified recorded earthquake ground motion time histories and synthetic ground motion time histories. The modified recorded earthquake ground motion time histories are modified from time history records that are selected based on consistent magnitude and distance. The synthetic ground motion time histories are generated using appropriate Fourier amplitude spectrums, Arias intensity, and drift correction. All of the time history modification is performed using the same algorithm to fit the design response spectra. The study provides data to demonstrate that properly managed synthetic ground motion time histories are reasonable for use in nonlinear seismic analysis.

Association of the germline TP53 R337H mutation with breast cancer in southern Brazil

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Srivastava Kumar

2008-12-01

Full Text Available Abstract Background The germline TP53-R337H mutation is strongly associated with pediatric adrenocortical tumors (ACT in southern Brazil; it has low penetrance and limited tissue specificity in most families and therefore is not associated with Li-Fraumeni syndrome. However, other tumor types, mainly breast cancer, have been observed in carriers of several unrelated kindreds, raising the possibility that the R337H mutation may also contribute to breast tumorigenesis in a genetic background-specific context. Methods We conducted a case-control study to determine the prevalence of the R337H mutation by sequencing TP53 exon 10 in 123 women with breast cancer and 223 age- and sex-matched control subjects from southern Brazil. Fisher's test was used to compare the prevalence of the R337H. Results The R337H mutation was found in three patients but in none of the controls (p = 0.0442. Among the carriers, two had familial history of cancer meeting the Li-Fraumeni-like criteria. Remarkably, tumors in each of these three cases underwent loss of heterozygosity by eliminating the mutant TP53 allele rather than the wild-type allele. Polymorphisms were identified within the TP53 (R72P and Ins16 and MDM2 (SNP309 genes that may further diminish TP53 tumor suppressor activity. Conclusion These results demonstrate that the R337H mutation can significantly increase the risk of breast cancer in carriers, which likely depends on additional cooperating genetic factors. These findings are also important for understanding how low-penetrant mutant TP53 alleles can differentially influence tumor susceptibility.

A novel ELISA using a recombinant outer membrane protein, rTp0663, as the antigen for serological diagnosis of syphilis.

Science.gov (United States)

Xu, Man; Xie, Yafeng; Jiang, Chuanhao; Xiao, Yongjian; Kuang, Xingxing; Zhao, Feijun; Zeng, Tiebing; Liu, Shuangquan; Liang, Mingxing; Li, Li; Wang, Chuan; Wu, Yimou

2016-02-01

The lack of Treponema pallidum-specific antigens with highly accurate diagnosis makes the diagnosis of syphilis challenging. A soluble recombinant version of a new diagnostic protein Tp0663 has been produced. The serodiagnostic potential of this protein was assessed by screening 3326 serum samples simultaneously evaluated by rapid plasma reagin and T. pallidum particle agglutination tests. Kappa (κ) coefficients were used to compare the concordance between clinical diagnosis and the Tp0663-based ELISA or the ARCHITECT Syphilis TP chemiluminescent immunoassay (Abbott GmbH and Co. KG). Using the results of clinical diagnosis as the gold standard, the sensitivity and specificity of Tp0663 were found to be 98.83% (95% confidence interval (CI) 96.61-99.60%) and 100% (95% CI 99.88-100%), respectively. In comparison, the ARCHITECT Syphilis TP assay was found to have a lower sensitivity (97.27%, 95% CI 94.46-98.67%) and specificity (99.61%, 95% CI 99.32-99.78%). In particular, the ARCHITECT Syphilis TP exhibited a false-positive rate of 0.39%. Moreover, the ELISA was in perfect agreement with the gold standard, with a κ value of 0.99, comparable to that of ARCHITECT Syphilis TP (0.96). These results identified Tp0663 as a novel serodiagnostic candidate with great potential for developing novel tests for the diagnosis of syphilis. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

TP53 p.R337H is a conditional cancer-predisposing mutation: further evidence from a homozygous patient

International Nuclear Information System (INIS)

Giacomazzi, Juliana; Hainaut, Pierre; Ashton-Prolla, Patricia; Selistre, Simone; Duarte, Juliana; Ribeiro, Jorge Pinto; Vieira, Paulo JC; Souza Macedo, Gabriel de; Rossi, Cristina; Czepielewski, Mauro; Netto, Cristina Brinkmann Oliveira

2013-01-01

Adrenocortical carcinomas (ACCs) are among the most common childhood cancers occurring in infants affected with the Li-Fraumeni and Li- Fraumeni-like (LFS/LFL) syndromes, which are caused by dominant germline mutations in the TP53 gene. In Brazil, a particular mutation, occurring in the tetramerisation domain of the gene, p.R337H, is exceedingly common due to a founder effect and is strongly associated with ACC. In this report, we describe the phenotype and long-term clinical follow-up of a female child diagnosed with ACC and homozygous for the TP53 p.R337H founder mutation. At age 11 months, the patient was diagnosed with a virilising anaplastic adrenal cortical tumour, which was completely excised without disturbing the adrenal capsule. Family history was consistent with an LFL tumour pattern, and genotyping identified the TP53 p.R337H mutation in both alleles in genomic DNA from lymphocytes and fibroblasts. Haplotype analysis confirmed the occurrence of the mutation in the same founder haplotype previously described in other Brazilian patients. No other germline or somatic TP53 mutations or rearrangements were identified. At age 9 years, the child was asymptomatic and had no evidence of endocrine derangements. Full body and brain magnetic resonance imaging (MRI) failed to detect any suspicious proliferative lesions, and cardiopulmonary exercise testing results were within the normal reference for the child’s age, ruling out a major exercise capacity deficiency. This is the first clinical and aerobic functional capacity documentation of a patient who carries two mutant TP53 alleles and no wild-type allele. Our results support the hypothesis that TP53 p.R337H, the most common TP53 mutation ever described in any population, is a conditional mutant. Furthermore, our observations over a long period of clinical follow-up suggest that TP53 p.R337H homozygotes do not have a more severe disease phenotype than do heterozygote carriers of the same mutation. Patients with

Generating synthetic wave climates for coastal modelling: a linear mixed modelling approach

Science.gov (United States)

Thomas, C.; Lark, R. M.

2013-12-01

Numerical coastline morphological evolution models require wave climate properties to drive morphological change through time. Wave climate properties (typically wave height, period and direction) may be temporally fixed, culled from real wave buoy data, or allowed to vary in some way defined by a Gaussian or other pdf. However, to examine sensitivity of coastline morphologies to wave climate change, it seems desirable to be able to modify wave climate time series from a current to some new state along a trajectory, but in a way consistent with, or initially conditioned by, the properties of existing data, or to generate fully synthetic data sets with realistic time series properties. For example, mean or significant wave height time series may have underlying periodicities, as revealed in numerous analyses of wave data. Our motivation is to develop a simple methodology to generate synthetic wave climate time series that can change in some stochastic way through time. We wish to use such time series in a coastline evolution model to test sensitivities of coastal landforms to changes in wave climate over decadal and centennial scales. We have worked initially on time series of significant wave height, based on data from a Waverider III buoy located off the coast of Yorkshire, England. The statistical framework for the simulation is the linear mixed model. The target variable, perhaps after transformation (Box-Cox), is modelled as a multivariate Gaussian, the mean modelled as a function of a fixed effect, and two random components, one of which is independently and identically distributed (iid) and the second of which is temporally correlated. The model was fitted to the data by likelihood methods. We considered the option of a periodic mean, the period either fixed (e.g. at 12 months) or estimated from the data. We considered two possible correlation structures for the second random effect. In one the correlation decays exponentially with time. In the second

Assessing the impacts of human activities and climate variations on grassland productivity by partial least squares structural equation modeling (PLS-SEM)

Institute of Scientific and Technical Information of China (English)

SHA Zongyao; XIE Yichun; TAN Xicheng; BAI Yongfei; LI Jonathan; LIU Xuefeng

2017-01-01

The cause-effect associations between geographical phenomena are an important focus in ecological research.Recent studies in structural equation modeling (SEM) demonstrated the potential for analyzing such associations.We applied the variance-based partial least squares SEM (PLS-SEM) and geographically-weighted regression (GWR) modeling to assess the human-climate impact on grassland productivity represented by above-ground biomass (AGB).The human and climate factors and their interaction were taken to explain the AGB variance by a PLS-SEM developed for the grassland ecosystem in Inner Mongolia,China.Results indicated that 65.5％ of the AGB variance could be explained by the human and climate factors and their interaction.The case study showed that the human and climate factors imposed a significant and negative impact on the AGB and that their interaction alleviated to some extent the threat from the intensified human-climate pressure.The alleviation may be attributable to vegetation adaptation to high human-climate stresses,to human adaptation to climate conditions or/and to recent vegetation restoration programs in the highly degraded areas.Furthermore,the AGB response to the human and climate factors modeled by GWR exhibited significant spatial variations.This study demonstrated that the combination of PLS-SEM and GWR model is feasible to investigate the cause-effect relation in socio-ecological systems.

Mutational analysis of the activator of late transcription, Alt , in the lactococcal bacteriophage TP901-1

DEFF Research Database (Denmark)

Pedersen, Margit; Hammer, Karin

2007-01-01

An activator protein, Alt, synthesized during the early state of lytic infection is required for transcription of the late operon in the lactococcal phage TP901-1. In order to identify amino acid residues in the Alt protein required for activation of the TP901-1 late promoter, Plate, hydroxylamine...

Clinical Impact of TP53 Gene Mutations in Diffuse Large B-Cell Lymphoma (DLBCL)

DEFF Research Database (Denmark)

Young, Ken H; Patten, Nancy; Truong, Sim

2009-01-01

Mutations of the TP53 tumor suppressor gene are associated with a poor clinical outcome in DLBCL patients treated with CHOP. The impact of TP53 mutations on clinical outcome of DLBCL patients treated with Rituxan-CHOP has not been comprehensively analyzed. The purpose of this study was to analyze...

Influencia de la soldadura sobre la rotura por tensiones en tubos de acero inoxidable austenitico del tipo 18-11NB(TP347

Directory of Open Access Journals (Sweden)

Gutiérrez de Saiz-Solabarria, S.

2000-06-01

Full Text Available This work has been undertaken to study the stress cracking failure in various 18Cr11Ni [TP347 (18-11Nb, TP 321 (18-11 Ti, TP304 (18-11 and TP316 (18-11-2] types austenitic stainless steel tubes. The material used was produced hot-rolling at 76,2 mm φ (3"φ x 2,54 mm (1/10" thickness. The study was carried out at 593ºC and applied stress of 50 Ton/in2.

Se estudia el efecto de la soldadura sobre la rotura por tensiones en tubos de acero inoxidable austenítico estabilizado con Nb o Ti de los tipos 18-11Nb (TP 347 y 18-11Ti (TP 321 así como sin estabilizar del tipo 18-11 (TP 304 y con Mo del tipo 18-11-2 (TP 316. Los tubos, en todos los casos, son de dimensiones 76,2 mm (3” φ x 2,54 mm (1/10” de espesor y la tensión aplicada (σ de 10 Ton/in2, para una temperatura de servicio de 593ºC.

License - TP Atlas | LSDB Archive [Life Science Database Archive metadata

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Full Text Available switchLanguage; BLAST Search Image Search Home About Archive Update History Data ... might be changed without notice. About This Database Database Description Download License Update History of This Database Site Policy | Contact Us License - TP Atlas | LSDB Archive ...

The Efficacy of Using Synthetic Vision Terrain-Textured Images to Improve Pilot Situation Awareness

Science.gov (United States)

Uenking, Michael D.; Hughes, Monica F.

2002-01-01

The General Aviation Element of the Aviation Safety Program's Synthetic Vision Systems (SVS) Project is developing technology to eliminate low visibility induced General Aviation (GA) accidents. SVS displays present computer generated 3-dimensional imagery of the surrounding terrain on the Primary Flight Display (PFD) to greatly enhance pilot's situation awareness (SA), reducing or eliminating Controlled Flight into Terrain, as well as Low-Visibility Loss of Control accidents. SVS-conducted research is facilitating development of display concepts that provide the pilot with an unobstructed view of the outside terrain, regardless of weather conditions and time of day. A critical component of SVS displays is the appropriate presentation of terrain to the pilot. An experimental study is being conducted at NASA Langley Research Center (LaRC) to explore and quantify the relationship between the realism of the terrain presentation and resulting enhancements of pilot SA and performance. Composed of complementary simulation and flight test efforts, Terrain Portrayal for Head-Down Displays (TP-HDD) experiments will help researchers evaluate critical terrain portrayal concepts. The experimental effort is to provide data to enable design trades that optimize SVS applications, as well as develop requirements and recommendations to facilitate the certification process. In this part of the experiment a fixed based flight simulator was equipped with various types of Head Down flight displays, ranging from conventional round dials (typical of most GA aircraft) to glass cockpit style PFD's. The variations of the PFD included an assortment of texturing and Digital Elevation Model (DEM) resolution combinations. A test matrix of 10 terrain display configurations (in addition to the baseline displays) were evaluated by 27 pilots of various backgrounds and experience levels. Qualitative (questionnaires) and quantitative (pilot performance and physiological) data were collected during

Effect of reciprocating agitation thermal processing (RA-TP) on quality of canned tomato (Solanum lycopersicum) puree.

Science.gov (United States)

Pratap Singh, Anubhav; Singh, Anika; Ramaswamy, Hosahalli S

2017-06-01

Reciprocating agitation thermal processing (RA-TP) is a recent innovation in the field of canning for obtaining high-quality canned food. The objective of this study was to compare RA-TP processing with conventional non-agitated (still) processing with respect to the impact on quality (color, antioxidant capacity, total phenols, carotenoid and lycopene contents) of canned tomato (Solanum lycopersicum) puree. Owing to a 63-81% reduction in process times as compared with still processing, tomato puree with a brighter red color (closer to fresh) was obtained during RA-TP. At 3 Hz reciprocation frequency, the loss of antioxidant, lycopene and carotenoid contents could be reduced to 34, 8 and 8% respectively as compared with 96, 41 and 52% respectively during still processing. In fact, the phenolic content for RA-TP at 3 Hz was 5% higher than in fresh puree. Quality retention generally increased with an increase in frequency, although the differences were less significant at higher reciprocation frequencies (between 2 and 3 Hz). Research findings indicate that RA-TP can be effective to obtain thermally processed foods with high-quality attribute retention. It can also be concluded that a very high reciprocation frequency (>3 Hz) is not necessarily needed and significant quality improvement can be obtained at lower frequencies (∼2 Hz). © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Gravity model development for TOPEX/POSEIDON: Joint gravity models 1 and 2

Science.gov (United States)

Nerem, R. S.; Lerch, F. J.; Marshall, J. A.; Pavlis, E. C.; Putney, B. H.; Tapley, B. D.; Eanes, R. J.; Ries, J. C.; Schutz, B. E.; Shum, C. K.

1994-01-01

The TOPEX/POSEIDON (T/P) prelaunch Joint Gravity Model-1 (JGM-1) and the postlaunch JGM-2 Earth gravitational models have been developed to support precision orbit determination for T/P. Each of these models is complete to degree 70 in spherical harmonics and was computed from a combination of satellite tracking data, satellite altimetry, and surface gravimetry. While improved orbit determination accuracies for T/P have driven the improvements in the models, the models are general in application and also provide an improved geoid for oceanographic computations. The postlaunch model, JGM-2, which includes T/P satellite laser ranging (SLR) and Doppler orbitography and radiopositioning integrated by satellite (DORIS) tracking data, introduces radial orbit errors for T/P that are only 2 cm RMS with the commission errors of the marine geoid for terms to degree 70 being +/- 25 cm. Errors in modeling the nonconservative forces acting on T/P increase the total radial errors to only 3-4 cm root mean square (RMS), a result much better than premission goals. While the orbit accuracy goal for T/P has been far surpassed geoid errors still prevent the absolute determination of the ocean dynamic topography for wavelengths shorter than about 2500 km. Only a dedicated gravitational field satellite mission will likely provide the necessary improvement in the geoid.

FOXP1 and TP63 involvement in the progression of myelodysplastic syndrome with 5q- and additional cytogenetic abnormalities

International Nuclear Information System (INIS)

L’Abbate, Alberto; Tagliafico, Enrico; Minoia, Carla; De Tullio, Giacoma; Guarini, Attilio; Testoni, Nicoletta; Agostinelli, Claudio; Storlazzi, Clelia Tiziana; Lo Cunsolo, Crocifissa; Macrì, Ettore; Iuzzolino, Paolo; Mecucci, Cristina; Doglioni, Claudio; Coco, Michelina; Muscarella, Lucia Anna; Salati, Simona

2014-01-01

The progression of low-risk del(5q) myelodysplastic syndrome to acute myeloid leukemia is increased when associated with mutations of TP53, or with additional chromosomal abnormalities. However, to date the prognostic impact and molecular consequences of these rearrangements were poorly investigated. Single additional alterations to del(5q) by balanced chromosome rearrangements were rarely found in myelodysplasia. In particular, balanced alterations involving TP63 and FOXP1 genes were never reported in the literature. Here we report on a 79-year woman with an aggressive form of myelodysplastic syndrome with del(5q), no TP53 mutation, and a novel complex rearrangement of chromosome 3 in bone marrow cells. Our results revealed that the FOXP1 and TP63 genes were both relocated along chromosome 3. Strikingly, immunohistochemistry analysis showed altered protein levels, disclosing that this rearrangement triggered the expression of FOXP1 and TP63 genes. FOXP1 was also found activated in other patients with myelodysplasia and acute myeloid leukemia, showing that it is an important, recurrent event. We document an apparent role of FOXP1 and TP63, up to now poorly documented, in the progression of MDS in our patient who is lacking mutations in the TP53 tumor suppressor gene normally associated with poor outcome in myelodysplastic syndrome with 5q-. Finally, our results may suggest a possible broader role of FOXP1 in the pathogenesis and progression of myelodysplasia and acute myeloid leukemia

The association of TP53 mutations with the resistance of colorectal carcinoma to the insulin-like growth factor-1 receptor inhibitor picropodophyllin

International Nuclear Information System (INIS)

Wang, Quan; Wei, Feng; Lv, Guoyue; Li, Chunsheng; Liu, Tongjun; Hadjipanayis, Costas G; Zhang, Guikai; Hao, Chunhai; Bellail, Anita C

2013-01-01

There is growing evidence indicating the insulin-like growth factor 1 receptor (IGF-1R) plays a critical role in the progression of human colorectal carcinomas. IGF-1R is an attractive drug target for the treatment of colon cancer. Picropodophyllin (PPP), of the cyclolignan family, has recently been identified as an IGF-1R inhibitor. The aim of this study is to determine the therapeutic response and mechanism after colorectal carcinoma treatment with PPP. Seven colorectal carcinoma cell lines were treated with PPP. Following treatment, cells were analyzed for growth by a cell viability assay, sub-G1 apoptosis by flow cytometry, caspase cleavage and activation of AKT and extracellular signal-regulated kinase (ERK) by western blot analysis. To examine the in vivo therapeutic efficacy of PPP, mice implanted with human colorectal carcinoma xenografts underwent PPP treatment. PPP treatment blocked the phosphorylation of IGF-1R, AKT and ERK and inhibited the growth of TP53 wild-type but not mutated colorectal carcinoma cell lines. The treatment of PPP also induced apoptosis in TP53 wild-type cells as evident by the presence of sub-G1 cells and the cleavage of caspase-9, caspase-3, DNA fragmentation factor-45 (DFF45), poly (ADP-ribose) polymerase (PARP), and X-linked inhibitor of apoptosis protein (XIAP). The loss of BAD phosphorylation in the PPP-treated TP53 wild type cells further suggested that the treatment induced apoptosis through the BAD-mediated mitochondrial pathway. In contrast, PPP treatment failed to induce the phosphorylation of AKT and ERK and caspase cleavage in TP53 mutated colorectal carcinoma cell lines. Finally, PPP treatment suppressed the growth of xenografts derived from TP53 wild type but not mutated colorectal carcinoma cells. We report the association of TP53 mutations with the resistance of treatment of colorectal carcinoma cells in culture and in a xenograft mouse model with the IGF-1R inhibitor PPP. TP53 mutations often occur in colorectal

Extremely high Tp53 mutation load in esophageal squamous cell carcinoma in Golestan Province, Iran.

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Behnoush Abedi-Ardekani

Full Text Available BACKGROUND: Golestan Province in northeastern Iran has one of the highest incidences of esophageal squamous cell carcinoma (ESCC in the world with rates over 50 per 100,000 person-years in both sexes. We have analyzed TP53 mutation patterns in tumors from this high-risk geographic area in search of clues to the mutagenic processes involved in causing ESCC. METHODOLOGY/PRINCIPAL FINDINGS: Biopsies of 119 confirmed ESCC tumor tissue from subjects enrolled in a case-control study conducted in Golestan Province were analyzed by direct sequencing of TP53 exons 2 through 11. Immunohistochemical staining for p53 was carried out using two monoclonal antibodies, DO7 and 1801. A total of 120 TP53 mutations were detected in 107/119 cases (89.9%, including 11 patients with double or triple mutations. The mutation pattern was heterogeneous with infrequent mutations at common TP53 "hotspots" but frequent transversions potentially attributable to environmental carcinogens forming bulky DNA adducts, including 40% at bases known as site of mutagenesis by polycyclic aromatic hydrocarbons (PAHs. Mutations showed different patterns according to the reported temperature of tea consumption, but no variation was observed in relation to ethnicity, tobacco or opium use, and alcoholic beverage consumption or urban versus rural residence. CONCLUSION/SIGNIFICANCE: ESCC tumors in people from Golestan Province show the highest rate of TP53 mutations ever reported in any cancer anywhere. The heterogeneous mutation pattern is highly suggestive of a causative role for multiple environmental carcinogens, including PAHs. The temperature and composition of tea may also influence mutagenesis.

Evaluating the influence of spatial resolution of Landsat predictors on the accuracy of biomass models for large-area estimation across the eastern USA

Science.gov (United States)

Deo, Ram K.; Domke, Grant M.; Russell, Matthew B.; Woodall, Christopher W.; Andersen, Hans-Erik

2018-05-01

Aboveground biomass (AGB) estimates for regional-scale forest planning have become cost-effective with the free access to satellite data from sensors such as Landsat and MODIS. However, the accuracy of AGB predictions based on passive optical data depends on spatial resolution and spatial extent of target area as fine resolution (small pixels) data are associated with smaller coverage and longer repeat cycles compared to coarse resolution data. This study evaluated various spatial resolutions of Landsat-derived predictors on the accuracy of regional AGB models at three different sites in the eastern USA: Maine, Pennsylvania-New Jersey, and South Carolina. We combined national forest inventory data with Landsat-derived predictors at spatial resolutions ranging from 30–1000 m to understand the optimal spatial resolution of optical data for large-area (regional) AGB estimation. Ten generic models were developed using the data collected in 2014, 2015 and 2016, and the predictions were evaluated (i) at the county-level against the estimates of the USFS Forest Inventory and Analysis Program which relied on EVALIDator tool and national forest inventory data from the 2009–2013 cycle and (ii) within a large number of strips (~1 km wide) predicted via LiDAR metrics at 30 m spatial resolution. The county-level estimates by the EVALIDator and Landsat models were highly related (R 2 > 0.66), although the R 2 varied significantly across sites and resolution of predictors. The mean and standard deviation of county-level estimates followed increasing and decreasing trends, respectively, with models of coarser resolution. The Landsat-based total AGB estimates were larger than the LiDAR-based total estimates within the strips, however the mean of AGB predictions by LiDAR were mostly within one-standard deviations of the mean predictions obtained from the Landsat-based model at any of the resolutions. We conclude that satellite data at resolutions up to 1000 m provide

Mapping boreal forest biomass from a SRTM and TanDEM-X based on canopy height model and Landsat spectral indices

Science.gov (United States)

Sadeghi, Yaser; St-Onge, Benoît; Leblon, Brigitte; Prieur, Jean-François; Simard, Marc

2018-06-01

We propose a method for mapping above-ground biomass (AGB) (Mg ha-1) in boreal forests based predominantly on Landsat 8 images and on canopy height models (CHM) generated using interferometric synthetic aperture radar (InSAR) from the Shuttle Radar Topographic Mission (SRTM) and the TanDEM-X mission. The original SRTM digital elevation model (DEM) was corrected by modelling the respective effects of landform and land cover on its errors and then subtracted from a TanDEM-X DSM to produce a SAR CHM. Among all the landform factors, the terrain curvature had the largest effect on SRTM elevation errors, with a r2 of 0.29. The NDSI was the best predictor of the residual SRTM land cover error, with a r2 of 0.30. The final SAR CHM had a RMSE of 2.45 m, with a bias of 0.07 m, compared to a lidar-based CHM. An AGB prediction model was developed based on a combination of the SAR CHM, TanDEM-X coherence, Landsat 8 NDVI, and other vegetation indices of RVI, DVI, GRVI, EVI, LAI, GNDVI, SAVI, GVI, Brightness, Greenness, and Wetness. The best results were obtained using a Random forest regression algorithm, at the stand level, yielding a RMSE of 26 Mg ha-1 (34% of average biomass), with a r2 of 0.62. This method has the potential of creating spatially continuous biomass maps over entire biomes using only spaceborne sensors and requiring only low-intensity calibration.

Dynamics of synthetic drugs transmission model with psychological addicts and general incidence rate

Science.gov (United States)

Ma, Mingju; Liu, Sanyang; Xiang, Hong; Li, Jun

2018-02-01

Synthetic drugs are replacing traditional ones and becoming the main popular ones gradually, which have given rise to serious social issues in recent years. In this paper, a synthetic drugs transmission model with psychological addicts and general contact rate is proposed. The local and global stabilities are decided by the basic reproduction number R0. By analyzing the sensitivity of parameters, we obtain that controlling psychological addiction is better than drugs treatment. These results are verified by numerical simulations.

ESTADO DEL ARTE MPLS-TP CONMUTACIÓN MULTIPROTOCOLO MEDIANTE ETIQUETAS - PERFIL DE TRANSPORTE

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Lois Albert Espinel García

2013-09-01

Full Text Available La creciente demanda en servicios de telecomunicaciones genera la necesidad de desarrollar diferentes modelos de red. En el año 2008, la UIT-T une sinergias con la IETF para desarrollar un protocolo llamado MPLS-TP cuya arquitectura representa el resultado la agregación de la eficiencia en el transporte de paquetes de IP/MPLS con la fiabilidad en el transporte de SONET/SDH. Este trabajo presenta un estado del arte de MPLS-TP donde se plasman los estudios actuales y avances relacionados con ésta tecnología: modelos de arquitectura óptica, modelos de protección en OAM. Además se presenta la estructura, funcionamiento y características que hacen de MPLS-TP una opción para las redes de transporte de siguiente generación. El material de apoyo para el desarrollo de este artículo ha sido obtenido de la base documental de recursos electrónicos con contenido científico de apoyo a la investigación de la Universidad Distrital Francisco José de Caldas.

Stress Rupture and Precipitation Behavior of TP310HCbN(HR3C for Supercritical Boilers

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FANG Xu-dong

2017-06-01

Full Text Available Using persistent experiment method, combined with Gleeble,hardness analysis, SEM, EDS, TEM and other analytical methods, the hot deformation, stress rupture and precipitation behavior of TP310HCbN heat resistance steel was analysed at 650℃ and 700℃, the results show that:the change of the hardness is not obviously under two different stress rupture temperature; with stress rupture time prolongs, TP310HCbN heat-resistant steel intragranular precipitates from granular into rod-shaped, and presence of wormlike NbCrN rich precipitates and dislocation interactions; Taiyuan Iron and Steel production of TP310HCbN heat-resistant steel at 650/700℃-100000h extrapolation lasting strength meet the standard requirements.

TP Atlas: integration and dissemination of advances in Targeted Proteins Research Program (TPRP)-structural biology project phase II in Japan.

Science.gov (United States)

Iwayanagi, Takao; Miyamoto, Sei; Konno, Takeshi; Mizutani, Hisashi; Hirai, Tomohiro; Shigemoto, Yasumasa; Gojobori, Takashi; Sugawara, Hideaki

2012-09-01

The Targeted Proteins Research Program (TPRP) promoted by the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan is the phase II of structural biology project (2007-2011) following the Protein 3000 Project (2002-2006) in Japan. While the phase I Protein 3000 Project put partial emphasis on the construction and maintenance of pipelines for structural analyses, the TPRP is dedicated to revealing the structures and functions of the targeted proteins that have great importance in both basic research and industrial applications. To pursue this objective, 35 Targeted Proteins (TP) Projects selected in the three areas of fundamental biology, medicine and pharmacology, and food and environment are tightly collaborated with 10 Advanced Technology (AT) Projects in the four fields of protein production, structural analyses, chemical library and screening, and information platform. Here, the outlines and achievements of the 35 TP Projects are summarized in the system named TP Atlas. Progress in the diversified areas is described in the modules of Graphical Summary, General Summary, Tabular Summary, and Structure Gallery of the TP Atlas in the standard and unified format. Advances in TP Projects owing to novel technologies stemmed from AT Projects and collaborative research among TP Projects are illustrated as a hallmark of the Program. The TP Atlas can be accessed at http://net.genes.nig.ac.jp/tpatlas/index_e.html .

Synthetic properties of models of globular clusters

Energy Technology Data Exchange (ETDEWEB)

Angeletti, L; Dolcetta, R; Giannone, P. (Rome Univ. (Italy). Osservatorio Astronomico)

1980-05-01

Synthetic and projected properties of models of globular clusters have been computed on the basis of stellar evolution and time changes of the dynamical cluster structure. Clusters with five and eight stellar groups (each group consisting of stars with the same mass) were studied. Mass loss from evolved stars was taken into account. Observational features were obtained at ages of 10-19 x 10/sup 9/ yr. The basic importance of the horizontal- and asymptotic-branch stars was pointed out. A comparison of the results with observed data of M3 is discussed with the purpose of obtaining general indications rather than a specific fit.

Synthetic properties of models of globular clusters

International Nuclear Information System (INIS)

Angeletti, L.; Dolcetta, R.; Giannone, P.

1980-01-01

Synthetic and projected properties of models of globular clusters have been computed on the basis of stellar evolution and time changes of the dynamical cluster structure. Clusters with five and eight stellar groups (each group consisting of stars with the same mass) were studied. Mass loss from evolved stars was taken into account. Observational features were obtained at ages of 10-19 x 10 9 yr. The basic importance of the horizontal- and asymptotic-branch stars was pointed out. A comparison of the results with observed data of M3 is discussed with the purpose of obtaining general indications rather than a specific fit. (orig.)

Contribution of germline TP53 variants and assessment of HER-2 status among young breast cancer patients in Malaysia

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Shao Yan Lau

2017-12-01

Full Text Available Background: Li-Fraumeni Syndrome (LFS is caused by a mutation in the TP53 tumour suppressor gene. This rare hereditary condition predisposes individuals to an increased risk of cancers including breast cancer in women at a relatively young age, which accounts for nearly 25%–30% of all LFS‑associated cancers. Studies have shown that breast tumours in women with a germline TP53 deleterious variants are associated with a human epidermal growth factor receptor 2 (HER2-positive phenotype. Taken together, this study aimed to investigate the contribution of germline TP53 variants and its association with tumour HER-2 status in a cohort of young women with breast cancer. Methods: From 2002 to 2017, 4048 women with breast cancer treated at University Malaya Medical Centre or Sime Darby Medical Centre participated in the Malaysian Breast Cancer Genetics Study. Of which, 87 patients were diagnosed before 30 years of age. All patients were analysed for germline TP53 single nucleotide variants, small insertions or deletions by amplicon‑based targeted sequencing and validated by Sanger sequencing. DNA from patients who tested negative for sequencing were subsequently evaluated for the presence of TP53 exon deletions or duplications by multiplex ligation‑dependent probe amplification. HER-2 status of breast tumours was defined by immunohistochemistry, fluorescence in situ hybridisation and/or silver in situ hybridisation. Results: 5 distinct TP53 variants were detected in 5 individuals. 3 out of 5 TP53 variants were classified as frameshift mutations, one nonsense mutation and one in-frame duplication. Variants in other genes were detected in 17 individuals. No large genomic rearrangements were detected in the remaining 65 sequencing-negative patients. The assessment of HER-2 status will be presented. Conclusions: Our results suggest that alterations in TP53 gene were identified in approximately 5.7% (5/87 of this cohort of young women with breast

Mutations and polymorphisms in TP53 gene--an overview on the role in colorectal cancer

Czech Academy of Sciences Publication Activity Database

Naccarati, Alessio; Poláková, Veronika; Pardini, Barbara; Vodičková, Ludmila; Hemminki, K.; Kumar, R.; Vodička, Pavel (ed.)

2012-01-01

Roč. 27, č. 2 (2012), s. 211-218 ISSN 0267-8357 R&D Projects: GA ČR GP305/09/P194; GA ČR GAP304/10/1286 Grant - others:GA UK(CZ) GA96908/B/2008 Institutional research plan: CEZ:AV0Z50390512 Keywords : TP53 mutations * TP53 polymorphisms * cancer risk Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.500, year: 2012

Evolving cell models for systems and synthetic biology.

Science.gov (United States)

Cao, Hongqing; Romero-Campero, Francisco J; Heeb, Stephan; Cámara, Miguel; Krasnogor, Natalio

2010-03-01

This paper proposes a new methodology for the automated design of cell models for systems and synthetic biology. Our modelling framework is based on P systems, a discrete, stochastic and modular formal modelling language. The automated design of biological models comprising the optimization of the model structure and its stochastic kinetic constants is performed using an evolutionary algorithm. The evolutionary algorithm evolves model structures by combining different modules taken from a predefined module library and then it fine-tunes the associated stochastic kinetic constants. We investigate four alternative objective functions for the fitness calculation within the evolutionary algorithm: (1) equally weighted sum method, (2) normalization method, (3) randomly weighted sum method, and (4) equally weighted product method. The effectiveness of the methodology is tested on four case studies of increasing complexity including negative and positive autoregulation as well as two gene networks implementing a pulse generator and a bandwidth detector. We provide a systematic analysis of the evolutionary algorithm's results as well as of the resulting evolved cell models.

Phylogenetic analysis of human Tp53 gene using computational ...

African Journals Online (AJOL)

The TP53 gene encoding p53 protein is involved in regulating a series of pathways. New discoveries about the function and control of p53 are still in progress and it is hoped to develop better therapeutics and diagnostics by exploiting this system. Evolutionary studies are of prime importance in the field of biological ...

Rhabdomyosarcoma-associated renal cell carcinoma: a link with constitutional Tp53 mutation.

LENUS (Irish Health Repository)

Curry, Sarah

2012-02-01

The 2004 World Health Organization classification includes the new entity "neuroblastoma-associated renal cell carcinoma." The pathogenetic link between these entities is unknown as yet. The patient reported herein developed renal cell carcinoma after anaplastic embryonal rhabdomyosarcoma, a previously unknown association. The 2nd malignancy developed very soon after the 1st one, prompting concern for inherent cancer predisposition rather than a therapy-induced 2nd malignancy. A variety of features raised suspicion for Tp53 mutation, and indeed a pathogenic germline Tp53 mutation was identified in this child, despite a negative family history for Li-Fraumeni syndrome. Consideration of underlying predisposition is advocated in the context of rapid evolution of 2nd childhood malignancy.

TP53 mutation and human papilloma virus status of oral squamous cell carcinomas in young adult patients

NARCIS (Netherlands)

Braakhuis, B.J.M.; Rietbergen, M.M.; Buijze, M.; Snijders, P.J.F.; Bloemena, E.; Brakenhoff, R.H.; Leemans, C.R.

2014-01-01

Objective Little is known about the molecular carcinogenesis of oral squamous cell carcinoma (OSCC) in young adult patients. The aim of this study was to investigate the detailed TP53 mutation and human papilloma virus (HPV) status of OSCC in patients, younger than 45 years. Methods TP53 mutations

Prognostic value of TP53 transcriptional activity on p21 and bax in patients with esophageal squamous cell carcinomas treated by definitive chemoradiotherapy

International Nuclear Information System (INIS)

Michel, Pierre; Magois, Karine; Robert, Valerie; Chiron, Anne; Lepessot, Florence; Bodenant, Corinne; Roque, Isabelle; Seng, Sok H.; Frebourg, Thierry; Paillot, Bernard

2002-01-01

Purpose: The aim of this study was to evaluate biologic factors on survival and clinical response after definitive concomitant chemoradiotherapy (CRT) in patients with esophageal squamous cell carcinoma (ESCC). Methods and Materials: TP53 protein hyperexpression (immunochemistry [IHC]) and functional assay (FA) of TP53, measuring the ability of TP53 to transactivate p21 and bax reporter systems, were performed in patients with ESCC treated by CRT. The impact of parameters studied on survival and clinical response to CRT was assessed. Results: Thirty-eight patients with ESCC were included. TP53 alterations were detected in 84.2% of cases with FA. All TP53 mutations abolished the transactivation of p21 and bax reporter systems. After CRT, complete response rate was 55.3%. The median survival of the population was 17.5 months. Serum albumin (p=0.002), weight loss <10% (p=0.005), and response to treatment (p<0.001) were significantly linked with survival. TP53 alteration in FA was not significantly predictive of response to CRT (p=0.132) nor survival (p=0.154). Conclusions: Our results suggest that wild-type TP53 in ESCC could be associated with good response to definitive CRT. However, the small rate of ESCC with wild-type TP53 suggests that systematic determination of TP53 status is not appropriate for the management of the ESCC population

The Relationship between TP53 Gene Status and Carboxylesterase 2 Expression in Human Colorectal Cancer

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Momoko Ishimine

2018-01-01

Full Text Available Irinotecan (CPT-11 is an anticancer prodrug that is activated by the carboxylesterase CES2 and has been approved for the treatment of many types of solid tumors, including colorectal cancer. Recent studies with cell lines show that CES2 expression is regulated by the tumor suppressor protein p53. However, clinical evidence for this regulatory mechanism in cancer is lacking. In this study, we examined the relationship between TP53 gene status and CES2 expression in human colorectal cancer. Most colorectal cancer specimens (70%; 26 of 37 showed lower CES2 mRNA levels (≥1.5-fold lower than the adjacent normal tissue, and only 30% (12 of 37 showed similar (<1.5-fold lower or higher CES2 mRNA levels. However, TP53 gene sequencing revealed no relationship between CES2 downregulation and TP53 mutational status. Moreover, while colorectal cancer cells expressing wild-type p53 exhibited p53-dependent upregulation of CES2, PRIMA-1MET, a drug that restores the transcriptional activity of mutant p53, failed to upregulate CES2 expression in cells with TP53 missense mutations. These results, taken together, suggest that CES2 mRNA expression is decreased in human colorectal cancer independently of p53.

TP53 alterations in Wilms tumour represent progression events with strong intratumour heterogeneity that are closely linked but not limited to anaplasia

OpenAIRE

Wegert, Jenny; Vokuh, Christian; Ziegler, Barbara; Ernestus, Karen; Leuschner, Ivo; Furtwängler, Rhoikos; Graf, Norbert; Gessler, Manfred

2018-01-01

TP53 mutations have been associated with anaplasia in Wilms tumour, which conveys a high risk for relapse and fatal outcome. Nevertheless, TP53 alterations have been reported in no more than 60% of anaplastic tumours, and recent data have suggested their presence in tumours that do not fulfil the criteria for anaplasia, questioning the clinical utility of TP53 analysis. Therefore, we characterized the TP53 status in 84 fatal cases of Wilms tumour, irrespective of histological subtype. We iden...

TP53 alterations in Wilms tumour represent progression events with strong intratumour heterogeneity that are closely linked but not limited to anaplasia

OpenAIRE

Wegert, Jenny; Vokuhl, Christian; Ziegler, Barbara; Ernestus, Karen; Leuschner, Ivo; Furtwängler, Rhoikos; Graf, Norbert; Gessler, Manfred

2017-01-01

Abstract TP53 mutations have been associated with anaplasia in Wilms tumour, which conveys a high risk for relapse and fatal outcome. Nevertheless, TP53 alterations have been reported in no more than 60% of anaplastic tumours, and recent data have suggested their presence in tumours that do not fulfil the criteria for anaplasia, questioning the clinical utility of TP53 analysis. Therefore, we characterized the TP53 status in 84 fatal cases of Wilms tumour, irrespective of histological subtype...

Accurate, model-based tuning of synthetic gene expression using introns in S. cerevisiae.

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Ido Yofe

2014-06-01

Full Text Available Introns are key regulators of eukaryotic gene expression and present a potentially powerful tool for the design of synthetic eukaryotic gene expression systems. However, intronic control over gene expression is governed by a multitude of complex, incompletely understood, regulatory mechanisms. Despite this lack of detailed mechanistic understanding, here we show how a relatively simple model enables accurate and predictable tuning of synthetic gene expression system in yeast using several predictive intron features such as transcript folding and sequence motifs. Using only natural Saccharomyces cerevisiae introns as regulators, we demonstrate fine and accurate control over gene expression spanning a 100 fold expression range. These results broaden the engineering toolbox of synthetic gene expression systems and provide a framework in which precise and robust tuning of gene expression is accomplished.

TP53 genetic polymorphisms, interactions with lifestyle factors and lung cancer risk: a case control study in a Chinese population

OpenAIRE

Li, Yanli; Chang, Shen-Chih; Niu, Rungui; Liu, Li; Crabtree-Ide, Christina R; Zhao, Baoxing; Shi, Jianping; Han, Xiaoyou; Li, Jiawei; Su, Jia; Cai, Lin; Yu, Shunzhang; Zhang, Zuo-Feng; Mu, Lina

2013-01-01

Abstract Background A pathway-based genotyping analysis suggested rs2078486 was a novel TP53 SNP, but very few studies replicate this association. TP53 rs1042522 is the most commonly studied SNP, but very few studies examined its potential interaction with environmental factors in relation to lung cancer risk. This study aims to examine associations between two TP53 single-nucleotide polymorphisms (SNPs) (rs2078486, rs1042522), their potential interac...

Acute and persistent Mycobacterium tuberculosis infections depend on the thiol peroxidase TpX.

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Yanmin Hu

Full Text Available The macrophage is the natural niche of Mycobacterium tuberculosis infection. In order to combat oxidative and nitrosative stresses and persist in macrophages successfully, M. tuberculosis is endowed with a very efficient antioxidant complex. Amongst these antioxidant enzymes, TpX is the only one in M. tuberculosis with sequence homology to thiol peroxidase. Previous reports have demonstrated that the M. tuberculosis TpX protein functions as a peroxidase in vitro. It is the dominant antioxidant which protects M. tuberculosis against oxidative and nitrosative stresses. The level of the protein increases in oxidative stress. To determine the roles of tpx gene in M. tuberculosis survival and virulence in vivo, we constructed an M. tuberculosis strain lacking the gene. The characteristics of the mutant were examined in an in vitro stationary phase model, in response to stresses; in murine bone marrow derived macrophages and in an acute and an immune resistant model of murine tuberculosis. The tpx mutant became sensitive to H(2O(2 and NO compared to the wild type strain. Enzymatic analysis using bacterial extracts from the WT and the tpx mutant demonstrated that the mutant contains reduced peroxidase activity. As a result of this, the mutant failed to grow and survive in macrophages. The growth deficiency in macrophages became more pronounced after interferon-gamma activation. In contrast, its growth was significantly restored in the macrophages of inducible nitric oxide synthase (iNOS or NOS2 knockout mice. Moreover, the tpx mutant was impaired in its ability to initiate an acute infection and to maintain a persistent infection. Its virulence was attenuated. Our results demonstrated that tpx is required for M. tuberculosis to deal with oxidative and nitrosative stresses, to survive in macrophages and to establish acute and persistent infections in animal tuberculosis models.

New Approaches in Modeling Multiphase Flows and Dispersion in Turbulence, Fractal Methods and Synthetic Turbulence

CERN Document Server

Nicolleau, FCGA; Redondo, J-M

2012-01-01

This book contains a collection of the main contributions from the first five workshops held by Ercoftac Special Interest Group on Synthetic Turbulence Models (SIG42. It is intended as an illustration of the sig's activities and of the latest developments in the field. This volume investigates the use of Kinematic Simulation (KS) and other synthetic turbulence models for the particular application to environmental flows. This volume offers the best syntheses on the research status in KS, which is widely used in various domains, including Lagrangian aspects in turbulence mixing/stirring, partic

Inactivation of human osteosarcoma cells in vitro by 211At-TP-3 monoclonal antibody: Comparison with astatine-211 and external-beam X rays

International Nuclear Information System (INIS)

Larsen, R.H.; Bruland, O.S.; Hoff, P.; Alstad, J.; Lindmo, T.; Rofstad, E.K.

1994-01-01

The potential usefulness of α-particle radioimmunotherapy in the treatment of osteosarcoma was studied in vitro by using the monoclonal antibody TP-3 and cells of three human osteosarcoma cell lines (OHS, SAOS and KPDX) differing in antigen expression. Cell survival curves were established after treatment with (a) 211 At-TP-3 of different specific activities, (b) 211 At-labeled bovine serum albumin (BSA), (c) free 211 At and (d) external-beam X rays. The three osteosarcoma cell lines showed similar survival curves, whether treated with external-beam X rays, 211 At-BSA or free 211 At. The D o 's were lower for free 211 At than for 211 At-BSA. The survival curves for 211 At-TP-3 treatment, on the other hand, differed significantly among the cell lines, suggesting that sensitivity to 211 At-TP-3 treatment was governed by cellular properties other than sensitivity to external-beam X rays. The cellular property most important for sensitivity to 211 At-TP-3 treatment was the antigen expression. Cell inactivation after 211 At-TP-3 treatment increased substantially with increasing specific activity of the 211 At-TP-3. At high specific activities, the cytotoxic effect of 211 At-TP-3 was significantly higher than that of 211 At-BSA. In conclusion, 211 At-TP-3 has the potential to give clinically favorable therapeutic ratios in the treatment of osteosarcoma. 39 refs., 5 figs., 2 tabs

Material problems related to large scale firing of biomass. Steam oxidation of TP 347H FG and X20

Energy Technology Data Exchange (ETDEWEB)

Noergaard Hansson, A.

2009-07-01

TP 347 H and X20 is often used as construction material in biomass-fired boilers. The corrosion rate of the alloys is affected by the metal temperature. In this project, the oxidation behaviour of TP 347H FG and X20 is studied by field-testing, laboratory exposures, and thermodynamic/kinetic modelling. The long term oxidation behaviour of TP 347H FG at ultra supercritical steam conditions was assessed by exposing the steel in 4 test superheater loops in a coal-fired power plant. The steel was exposed for 7720, 22985, 29588, and 57554 h at metal temperatures between 499 and 650 deg. C. In the laboratory furnace, the oxidation behaviour of TP 347H FG, TP 347H CG, and X20 was studied in water vapour containing environments (8 or 46%) in the temperature range 500-700 deg. C. Air, Ar and Ar+7% H{sub 2} were used as carrier gas. The microstructure of the oxide layer and the subjacent alloy was investigated with X-ray diffraction (XRD), reflective light microscopy (RLM), scanning electron microscopy (SEM) equipped with energy dispersive spectroscopy (EDS), and transmission electron microscopy (TEM) equipped with electron diffraction (ED) and EDS. Double-layered oxides developed during steam oxidation of TP 347H FG both during field-testing and during laboratory exposures. TEM investigation suggested that the interior of the alloy grain was oxidised internally, forming particles of metallic Ni/Fe and Fe-Cr spinel. A FeCr{sub 2}O{sub 4} layer developed along the former alloy grain boundaries. Cr{sub 2}O{sub 3} developed in between this layer and the alloy during field-testing, and its formation was promoted by higher temperature. The morphology of the inner layer for the samples oxidised below and above approx. 585 deg. C looked very different in SEM (field-testing). It is suggested that more Cr is incorporated into the oxide layer at higher temperature, gradually transforming the morphology of the inner oxide layer. The alloy beneath the oxide layer was depleted in Cr

Attribute Synthetic Evaluation Model for the CBM Recoverability and Its Application

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Xiao-gang Xia

2015-01-01

Full Text Available The coal-bed methane (CBM recoverability is the basic premise of CBM development practice; in order to effectively evaluate the CBM recoverability, the attribute synthetic evaluation model is established based on the theory and method of attribute mathematics. Firstly, five indexes are chosen to evaluate the recoverability through analyzing the influence factors of CBM, including seam thickness, gas saturation, permeability, reservoir pressure gradient, and hydrogeological conditions. Secondly, the attribute measurement functions of each index are constructed based on the attribute mathematics theory, and the calculation methods of the single index attribute measurement and the synthetic attribute measurement also are provided. Meanwhile, the weight of each index is given with the method of similar number and similar weight; the evaluation results also are determined by the confidence criterion reliability code. At last, according to the application results of the model in some coal target area of Fuxin and Hancheng mine, the evaluation results are basically consistent with the actual situation, which proves that the evaluation model can be used in the CBM recoverability prediction, and an effective method of the CBM recoverability evaluation is also provided.

TP53 codon 72 polymorphism as a risk factor for cardiovascular disease in a Brazilian population

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M.A.C. Smith

2007-11-01

Full Text Available TP53, a tumor suppressor gene, has a critical role in cell cycle, apoptosis and cell senescence and participates in many crucial physiological and pathological processes. Identification of TP53 polymorphism in older people and age-related diseases may provide an understanding of its physiology and pathophysiological role as well as risk factors for complex diseases. TP53 codon 72 (TP53:72 polymorphism was investigated in 383 individuals aged 66 to 97 years in a cohort from a Brazilian Elderly Longitudinal Study. We investigated allele frequency, genotype distribution and allele association with morbidities such as cardiovascular disease, type II diabetes, obesity, neoplasia, low cognitive level (dementia, and depression. We also determined the association of this polymorphism with serum lipid fractions and urea, creatinine, albumin, fasting glucose, and glycated hemoglobin levels. DNA was isolated from blood cells, amplified by PCR using sense 5'-TTGCCGTCCCAAGCAATGGATGA-3' and antisense 5'-TCTGGGAAGGGACAGAAGATGAC-3' primers and digested with the BstUI enzyme. This polymorphism is within exon 4 at nucleotide residue 347. Descriptive statistics, logistic regression analysis and Student t-test using the multiple comparison test were used. Allele frequencies, R (Arg = 0.69 and P (Pro = 0.31, were similar to other populations. Genotype distributions were within Hardy-Weinberg equilibrium. This polymorphism did not show significant association with any age-related disease or serum variables. However, R allele carriers showed lower HDL levels and a higher frequency of cardiovascular disease than P allele subjects. These findings may help to elucidate the physiopathological role of TP53:72 polymorphism in Brazilian elderly people.

Assimilating satellite-based canopy height within an ecosystem model to estimate aboveground forest biomass

Science.gov (United States)

Joetzjer, E.; Pillet, M.; Ciais, P.; Barbier, N.; Chave, J.; Schlund, M.; Maignan, F.; Barichivich, J.; Luyssaert, S.; Hérault, B.; von Poncet, F.; Poulter, B.

2017-07-01

Despite advances in Earth observation and modeling, estimating tropical biomass remains a challenge. Recent work suggests that integrating satellite measurements of canopy height within ecosystem models is a promising approach to infer biomass. We tested the feasibility of this approach to retrieve aboveground biomass (AGB) at three tropical forest sites by assimilating remotely sensed canopy height derived from a texture analysis algorithm applied to the high-resolution Pleiades imager in the Organizing Carbon and Hydrology in Dynamic Ecosystems Canopy (ORCHIDEE-CAN) ecosystem model. While mean AGB could be estimated within 10% of AGB derived from census data in average across sites, canopy height derived from Pleiades product was spatially too smooth, thus unable to accurately resolve large height (and biomass) variations within the site considered. The error budget was evaluated in details, and systematic errors related to the ORCHIDEE-CAN structure contribute as a secondary source of error and could be overcome by using improved allometric equations.

Polarimetric scattering model for estimation of above ground biomass of multilayer vegetation using ALOS-PALSAR quad-pol data

Science.gov (United States)

Sai Bharadwaj, P.; Kumar, Shashi; Kushwaha, S. P. S.; Bijker, Wietske

Forests are important biomes covering a major part of the vegetation on the Earth, and as such account for seventy percent of the carbon present in living beings. The value of a forest's above ground biomass (AGB) is considered as an important parameter for the estimation of global carbon content. In the present study, the quad-pol ALOS-PALSAR data was used for the estimation of AGB for the Dudhwa National Park, India. For this purpose, polarimetric decomposition components and an Extended Water Cloud Model (EWCM) were used. The PolSAR data orientation angle shifts were compensated for before the polarimetric decomposition. The scattering components obtained from the polarimetric decomposition were used in the Water Cloud Model (WCM). The WCM was extended for higher order interactions like double bounce scattering. The parameters of the EWCM were retrieved using the field measurements and the decomposition components. Finally, the relationship between the estimated AGB and measured AGB was assessed. The coefficient of determination (R2) and root mean square error (RMSE) were 0.4341 and 119 t/ha respectively.

Distinct pattern of TP53 mutations in human immunodeficiency virus-related head and neck squamous cell carcinoma.

Science.gov (United States)

Gleber-Netto, Frederico O; Zhao, Mei; Trivedi, Sanchit; Wang, Jiping; Jasser, Samar; McDowell, Christina; Kadara, Humam; Zhang, Jiexin; Wang, Jing; William, William N; Lee, J Jack; Nguyen, Minh Ly; Pai, Sara I; Walline, Heather M; Shin, Dong M; Ferris, Robert L; Carey, Thomas E; Myers, Jeffrey N; Pickering, Curtis R

2018-01-01

Human immunodeficiency virus-infected individuals (HIVIIs) have a higher incidence of head and neck squamous cell carcinoma (HNSCC), and clinical and histopathological differences have been observed in their tumors in comparison with those of HNSCC patients without a human immunodeficiency virus (HIV) infection. The reasons for these differences are not clear, and molecular differences between HIV-related HNSCC and non-HIV-related HNSCC may exist. This study compared the mutational patterns of HIV-related HNSCC and non-HIV-related HNSCC. The DNA of 20 samples of HIV-related HNSCCs and 32 samples of non-HIV-related HNSCCs was sequenced. DNA libraries covering exons of 18 genes frequently mutated in HNSCC (AJUBA, CASP8, CCND1, CDKN2A, EGFR, FAT1, FBXW7, HLA-A, HRAS, KEAP1, NFE2L2, NOTCH1, NOTCH2, NSD1, PIK3CA, TGFBR2, TP53, and TP63) were prepared and sequenced on an Ion Personal Genome Machine sequencer. DNA sequencing data were analyzed with Ion Reporter software. The human papillomavirus (HPV) status of the tumor samples was assessed with in situ hybridization, the MassARRAY HPV multiplex polymerase chain reaction assay, and p16 immunostaining. Mutation calls were compared among the studied groups. HIV-related HNSCC revealed a distinct pattern of mutations in comparison with non-HIV-related HNSCC. TP53 mutation frequencies were significantly lower in HIV-related HNSCC. Mutations in HIV+ patients tended to be TpC>T nucleotide changes for all mutated genes but especially for TP53. HNSCC in HIVIIs presents a distinct pattern of genetic mutations, particularly in the TP53 gene. HIV-related HNSCC may have a distinct biology, and an effect of the HIV virus on the pathogenesis of these tumors should not be ruled out. Cancer 2018;124:84-94. © 2017 American Cancer Society. © 2017 American Cancer Society.

Frequency Response of Synthetic Vocal Fold Models with Linear and Nonlinear Material Properties

Science.gov (United States)

Shaw, Stephanie M.; Thomson, Scott L.; Dromey, Christopher; Smith, Simeon

2012-01-01

Purpose: The purpose of this study was to create synthetic vocal fold models with nonlinear stress-strain properties and to investigate the effect of linear versus nonlinear material properties on fundamental frequency (F[subscript 0]) during anterior-posterior stretching. Method: Three materially linear and 3 materially nonlinear models were…

High-resolution observations of IRAS 08544-4431. Detection of a disk orbiting a post-AGB star and of a slow disk wind

Science.gov (United States)

Bujarrabal, V.; Castro-Carrizo, A.; Winckel, H. Van; Alcolea, J.; Contreras, C. Sánchez; Santander-García, M.; Hillen, M.

2018-06-01

Context. Aims: In order to study the effects of rotating disks in the post-asymptotic giant branch (post-AGB) evolution, we observe a class of binary post-AGB stars that seem to be systematically surrounded by equatorial disks and slow outflows. Although the rotating dynamics had only been well identified in three cases, the study of such structures is thought to be fundamental to the understanding of the formation of disks in various phases of the late evolution of binary stars and the ejection of planetary nebulae from evolved stars. Methods: We present ALMA maps of 12CO and 13CO J = 3-2 lines in the source IRAS 08544-4431, which belongs to the above mentioned class of objects. We analyzed the data by means of nebula models, which account for the expectedly composite source and can reproduce the data. From our modeling, we estimated the main nebula parameters, including the structure and dynamics and the density and temperature distributions. We discuss the uncertainties of the derived values and, in particular, their dependence on the distance. Results: Our observations reveal the presence of an equatorial disk in rotation; a low-velocity outflow is also found, probably formed of gas expelled from the disk. The main characteristics of our observations and modeling of IRAS 08544-4431 are similar to those of better studied objects, confirming our interpretation. The disk rotation indicates a total central mass of about 1.8 M⊙, for a distance of 1100 pc. The disk is found to be relatively extended and has a typical diameter of 4 × 1016 cm. The total nebular mass is 2 × 10-2 M⊙, of which 90% corresponds to the disk. Assuming that the outflow is due to mass loss from the disk, we derive a disk lifetime of 10 000 yr. The disk angular momentum is found to be comparable to that of the binary system at present. Assuming that the disk angular momentum was transferred from the binary system, as expected, the high values of the disk angular momentum in this and other

Solar Magnetic Carpet III: Coronal Modelling of Synthetic Magnetograms

Science.gov (United States)

Meyer, K. A.; Mackay, D. H.; van Ballegooijen, A. A.; Parnell, C. E.

2013-09-01

This article is the third in a series working towards the construction of a realistic, evolving, non-linear force-free coronal-field model for the solar magnetic carpet. Here, we present preliminary results of 3D time-dependent simulations of the small-scale coronal field of the magnetic carpet. Four simulations are considered, each with the same evolving photospheric boundary condition: a 48-hour time series of synthetic magnetograms produced from the model of Meyer et al. ( Solar Phys. 272, 29, 2011). Three simulations include a uniform, overlying coronal magnetic field of differing strength, the fourth simulation includes no overlying field. The build-up, storage, and dissipation of magnetic energy within the simulations is studied. In particular, we study their dependence upon the evolution of the photospheric magnetic field and the strength of the overlying coronal field. We also consider where energy is stored and dissipated within the coronal field. The free magnetic energy built up is found to be more than sufficient to power small-scale, transient phenomena such as nanoflares and X-ray bright points, with the bulk of the free energy found to be stored low down, between 0.5 - 0.8 Mm. The energy dissipated is currently found to be too small to account for the heating of the entire quiet-Sun corona. However, the form and location of energy-dissipation regions qualitatively agree with what is observed on small scales on the Sun. Future MHD modelling using the same synthetic magnetograms may lead to a higher energy release.

Significance of TP53 mutation in Wilms tumors with diffuse anaplasia : A report from the Children's Oncology Group

NARCIS (Netherlands)

Ooms, Ariadne H A G; Gadd, Samantha; Gerhard, Daniela S.; Smith, Malcolm A.; Guidry Auvil, Jaime M.; Meerzaman, Daoud; Chen, Qing Rong; Hsu, Chih Hao; Yan, Chunhua; Nguyen, Cu; Hu, Ying; Ma, Yussanne; Zong, Zusheng; Mungall, Andrew J.; Moore, Richard A.; Marra, Marco A.; Huff, Vicki; Dome, Jeffrey S.; Chi, Yueh Yun; Tian, Jing; Geller, James I.; Mullighan, Charles G.; Ma, Jing; Wheeler, David A.; Hampton, Oliver A.; Walz, Amy L.; Van Den Heuvel-Eibrink, Marry M.; De Krijger, Ronald R.; Ross, Nicole; Gastier-Foster, Julie M.; Perlman, Elizabeth J.

2016-01-01

Purpose: To investigate the role and significance of TP53 mutation in diffusely anaplastic Wilms tumors (DAWTs). Experimental Design: All DAWTs registered on National Wilms Tumor Study-5 (n = 118) with available samples were analyzed for TP53 mutations and copy loss. Integrative genomic analysis was

Mapping the spatial pattern of temperate forest above ground biomass by integrating airborne lidar with Radarsat-2 imagery via geostatistical models

Science.gov (United States)

Li, Wang; Niu, Zheng; Gao, Shuai; Wang, Cheng

2014-11-01

Light Detection and Ranging (LiDAR) and Synthetic Aperture Radar (SAR) are two competitive active remote sensing techniques in forest above ground biomass estimation, which is important for forest management and global climate change study. This study aims to further explore their capabilities in temperate forest above ground biomass (AGB) estimation by emphasizing the spatial auto-correlation of variables obtained from these two remote sensing tools, which is a usually overlooked aspect in remote sensing applications to vegetation studies. Remote sensing variables including airborne LiDAR metrics, backscattering coefficient for different SAR polarizations and their ratio variables for Radarsat-2 imagery were calculated. First, simple linear regression models (SLR) was established between the field-estimated above ground biomass and the remote sensing variables. Pearson's correlation coefficient (R2) was used to find which LiDAR metric showed the most significant correlation with the regression residuals and could be selected as co-variable in regression co-kriging (RCoKrig). Second, regression co-kriging was conducted by choosing the regression residuals as dependent variable and the LiDAR metric (Hmean) with highest R2 as co-variable. Third, above ground biomass over the study area was estimated using SLR model and RCoKrig model, respectively. The results for these two models were validated using the same ground points. Results showed that both of these two methods achieved satisfactory prediction accuracy, while regression co-kriging showed the lower estimation error. It is proved that regression co-kriging model is feasible and effective in mapping the spatial pattern of AGB in the temperate forest using Radarsat-2 data calibrated by airborne LiDAR metrics.

Parametric Study of Synthetic-Jet-Based Flow Control on a Vertical Tail Model

Science.gov (United States)

Monastero, Marianne; Lindstrom, Annika; Beyar, Michael; Amitay, Michael

2015-11-01

Separation control over the rudder of the vertical tail of a commercial airplane using synthetic-jet-based flow control can lead to a reduction in tail size, with an associated decrease in drag and increase in fuel savings. A parametric, experimental study was undertaken using an array of finite span synthetic jets to investigate the sensitivity of the enhanced vertical tail side force to jet parameters, such as jet spanwise spacing and jet momentum coefficient. A generic wind tunnel model was designed and fabricated to fundamentally study the effects of the jet parameters at varying rudder deflection and model sideslip angles. Wind tunnel results obtained from pressure measurements and tuft flow visualization in the Rensselaer Polytechnic Subsonic Wind Tunnel show a decrease in separation severity and increase in model performance in comparison to the baseline, non-actuated case. The sensitivity to various parameters will be presented.

TP53 alterations in Wilms tumour represent progression events with strong intratumour heterogeneity that are closely linked but not limited to anaplasia.

Science.gov (United States)

Wegert, Jenny; Vokuhl, Christian; Ziegler, Barbara; Ernestus, Karen; Leuschner, Ivo; Furtwängler, Rhoikos; Graf, Norbert; Gessler, Manfred

2017-10-01

TP53 mutations have been associated with anaplasia in Wilms tumour, which conveys a high risk for relapse and fatal outcome. Nevertheless, TP53 alterations have been reported in no more than 60% of anaplastic tumours, and recent data have suggested their presence in tumours that do not fulfil the criteria for anaplasia, questioning the clinical utility of TP53 analysis. Therefore, we characterized the TP53 status in 84 fatal cases of Wilms tumour, irrespective of histological subtype. We identified TP53 alterations in at least 90% of fatal cases of anaplastic Wilms tumour, and even more when diffuse anaplasia was present, indicating a very strong if not absolute coupling between anaplasia and deregulation of p53 function. Unfortunately, TP53 mutations do not provide additional predictive value in anaplastic tumours since the same mutation rate was found in a cohort of non-fatal anaplastic tumours. When classified according to tumour stage, patients with stage I diffuse anaplastic tumours still had a high chance of survival (87%), but this rate dropped to 26% for stages II-IV. Thus, volume of anaplasia or possible spread may turn out to be critical parameters. Importantly, among non-anaplastic fatal tumours, 26% had TP53 alterations, indicating that TP53 screening may identify additional cases at risk. Several of these non-anaplastic tumours fulfilled some criteria for anaplasia, for example nuclear unrest, suggesting that such partial phenotypes should be under special scrutiny to enhance detection of high-risk tumours via TP53 screening. A major drawback is that these alterations are secondary changes that occur only later in tumour development, leading to striking intratumour heterogeneity that requires multiple biopsies and analysis guided by histological criteria. In conclusion, we found a very close correlation between histological signs of anaplasia and TP53 alterations. The latter may precede development of anaplasia and thereby provide diagnostic value

Overexpression of RBBP6, alone or combined with mutant TP53, is predictive of poor prognosis in colon cancer.

Directory of Open Access Journals (Sweden)

Jian Chen

Full Text Available Retinoblastoma binding protein 6 (RBBP6 plays an important role in chaperone-mediated ubiquitination and interacts with TP53 in carcinogenesis. However, the clinicopathologic significance of RBBP6 expression in colon cancer is unknown; in particular, the prognostic value of RBBP6 combined with TP53 expression has not been explored. Therefore, quantitative real-time PCR and western blot analyses were performed to detect RBBP6 expression in colon cancer tissues. RBBP6 and TP53 expression were assessed by immunohistochemistry in a tissue microarray format, in which the primary colon cancer tissue was paired with noncancerous tissue. Tissue specimens were obtained from 203 patients. We found that RBBP6 was overexpressed in colon tumorous tissues and was significantly associated with clinical stage, depth of tumor invasion, lymph node metastasis (LNM, distant metastasis, and histologic grade. Further studies revealed that a corresponding correlation between RBBP6 overexpression and mutant TP53 was evident in colon cancer (r = 0.450; P<0.001. RBBP6 expression was an independent prognostic factor for overall survival (OS and disease free survival (DFS. Interestingly, patients with tumors that had both RBBP6 overexpression and mutant TP53 protein accumulation relapsed and died within a significantly short period after surgery (P<0.001. Multivariate analysis showed that patients with LNM and patients with both RBBP6- and TP53-positive tumors had extremely poor OS (HR 6.75; 95% CI 2.63-17.35; P<0.001 and DFS (HR 8.08; 95% CI 2.80-23.30; P<0.001. These clinical findings indicate that the assessment of both RBBP6 and mutant TP53 expression will be helpful in predicting colon cancer prognosis.

Model-Assisted Estimation of Tropical Forest Biomass Change: A Comparison of Approaches

Directory of Open Access Journals (Sweden)

Nikolai Knapp

2018-05-01

Full Text Available Monitoring of changes in forest biomass requires accurate transfer functions between remote sensing-derived changes in canopy height (ΔH and the actual changes in aboveground biomass (ΔAGB. Different approaches can be used to accomplish this task: direct approaches link ΔH directly to ΔAGB, while indirect approaches are based on deriving AGB stock estimates for two points in time and calculating the difference. In some studies, direct approaches led to more accurate estimations, while, in others, indirect approaches led to more accurate estimations. It is unknown how each approach performs under different conditions and over the full range of possible changes. Here, we used a forest model (FORMIND to generate a large dataset (>28,000 ha of natural and disturbed forest stands over time. Remote sensing of forest height was simulated on these stands to derive canopy height models for each time step. Three approaches for estimating ΔAGB were compared: (i the direct approach; (ii the indirect approach and (iii an enhanced direct approach (dir+tex, using ΔH in combination with canopy texture. Total prediction accuracies of the three approaches measured as root mean squared errors (RMSE were RMSEdirect = 18.7 t ha−1, RMSEindirect = 12.6 t ha−1 and RMSEdir+tex = 12.4 t ha−1. Further analyses revealed height-dependent biases in the ΔAGB estimates of the direct approach, which did not occur with the other approaches. Finally, the three approaches were applied on radar-derived (TanDEM-X canopy height changes on Barro Colorado Island (Panama. The study demonstrates the potential of forest modeling for improving the interpretation of changes observed in remote sensing data and for comparing different methodologies.

Development of a data driven process-based model for remote sensing of terrestrial ecosystem productivity, evapotranspiration, and above-ground biomass

Science.gov (United States)

El Masri, Bassil

2011-12-01

Modeling terrestrial ecosystem functions and structure has been a subject of increasing interest because of the importance of the terrestrial carbon cycle in global carbon budget and climate change. In this study, satellite data were used to estimate gross primary production (GPP), evapotranspiration (ET) for two deciduous forests: Morgan Monroe State forest (MMSF) in Indiana and Harvard forest in Massachusetts. Also, above-ground biomass (AGB) was estimated for the MMSF and the Howland forest (mixed forest) in Maine. Surface reflectance and temperature, vegetation indices, soil moisture, tree height and canopy area derived from the Moderate Resolution Imagining Spectroradiometer (MODIS), the Advanced Microwave Scanning Radiometer (AMRS-E), LIDAR, and aerial imagery respectively, were used for this purpose. These variables along with others derived from remotely sensed data were used as inputs variables to process-based models which estimated GPP and ET and to a regression model which estimated AGB. The process-based models were BIOME-BGC and the Penman-Monteith equation. Measured values for the carbon and water fluxes obtained from the Eddy covariance flux tower were compared to the modeled GPP and ET. The data driven methods produced good estimation of GPP and ET with an average root mean square error (RMSE) of 0.17 molC/m2 and 0.40 mm/day, respectively for the MMSF and the Harvard forest. In addition, allometric data for the MMSF were used to develop the regression model relating AGB with stem volume. The performance of the AGB regression model was compared to site measurements using remotely sensed data for the MMSF and the Howland forest where the model AGB RMSE ranged between 2.92--3.30 Kg C/m2. Sensitivity analysis revealed that improvement in maintenance respiration estimation and remotely sensed maximum photosynthetic activity as well as accurate estimate of canopy resistance will result in improved GPP and ET predictions. Moreover, AGB estimates were

Inactivation of TP53 correlates with disease progression and low miR-34a expression in previously treated chronic lymphocytic leukemia patients

DEFF Research Database (Denmark)

Dufour, Annika; Palermo, Giuseppe; Zellmeier, Evelyn

2013-01-01

In chronic lymphocytic leukemia (CLL) patients, disruptions of the TP53 tumor suppressor pathway by 17p13 deletion (del17p), somatic TP53 mutations, or downregulation of microRNA-34a have been associated with a poor prognosis. So far, the impact of the various TP53 defects has not been evaluated ...

Image File - TP Atlas | LSDB Archive [Life Science Database Archive metadata

Lifescience Database Archive (English)

Full Text Available ption of data contents Network diagrams (in PNG format) for each project. One project has one pathway file o...List Contact us TP Atlas Image File Data detail Data name Image File DOI 10.18908/lsdba.nbdc01161-004 Descri

Freedom and Responsibility in Synthetic Genomics: The Synthetic Yeast Project.

Science.gov (United States)

Sliva, Anna; Yang, Huanming; Boeke, Jef D; Mathews, Debra J H

2015-08-01

First introduced in 2011, the Synthetic Yeast Genome (Sc2.0) PROJECT is a large international synthetic genomics project that will culminate in the first eukaryotic cell (Saccharomyces cerevisiae) with a fully synthetic genome. With collaborators from across the globe and from a range of institutions spanning from do-it-yourself biology (DIYbio) to commercial enterprises, it is important that all scientists working on this project are cognizant of the ethical and policy issues associated with this field of research and operate under a common set of principles. In this commentary, we survey the current ethics and regulatory landscape of synthetic biology and present the Sc2.0 Statement of Ethics and Governance to which all members of the project adhere. This statement focuses on four aspects of the Sc2.0 PROJECT: societal benefit, intellectual property, safety, and self-governance. We propose that such project-level agreements are an important, valuable, and flexible model of self-regulation for similar global, large-scale synthetic biology projects in order to maximize the benefits and minimize potential harms. Copyright © 2015 by the Genetics Society of America.

Multivariate synthetic streamflow generation using a hybrid model based on artificial neural networks

Directory of Open Access Journals (Sweden)

J. C. Ochoa-Rivera

2002-01-01

Full Text Available A model for multivariate streamflow generation is presented, based on a multilayer feedforward neural network. The structure of the model results from two components, the neural network (NN deterministic component and a random component which is assumed to be normally distributed. It is from this second component that the model achieves the ability to incorporate effectively the uncertainty associated with hydrological processes, making it valuable as a practical tool for synthetic generation of streamflow series. The NN topology and the corresponding analytical explicit formulation of the model are described in detail. The model is calibrated with a series of monthly inflows to two reservoir sites located in the Tagus River basin (Spain, while validation is performed through estimation of a set of statistics that is relevant for water resources systems planning and management. Among others, drought and storage statistics are computed and compared for both the synthetic and historical series. The performance of the NN-based model was compared to that of a standard autoregressive AR(2 model. Results show that NN represents a promising modelling alternative for simulation purposes, with interesting potential in the context of water resources systems management and optimisation. Keywords: neural networks, perceptron multilayer, error backpropagation, hydrological scenario generation, multivariate time-series..

Assessment of Aboveground Woody Biomass Dynamics Using Terrestrial Laser Scanner and L-Band ALOS PALSAR Data in South African Savanna

Directory of Open Access Journals (Sweden)

Victor Onyango Odipo

2016-11-01

Full Text Available The use of optical remote sensing data for savanna vegetation structure mapping is hindered by sparse and heterogeneous distribution of vegetation canopy, leading to near-similar spectral signatures among lifeforms. An additional challenge to optical sensors is the high cloud cover and unpredictable weather conditions. Longwave microwave data, with its low sensitivity to clouds addresses some of these problems, but many space borne studies are still limited by low quality structural reference data. Terrestrial laser scanning (TLS derived canopy cover and height metrics can improve aboveground biomass (AGB prediction at both plot and landscape level. To date, few studies have explored the strength of TLS for vegetation structural mapping, and particularly few focusing on savannas. In this study, we evaluate the potential of high resolution TLS-derived canopy cover and height metrics to estimate plot-level aboveground biomass, and to extrapolate to a landscape-wide biomass estimation using multi-temporal L-band Synthetic Aperture Radar (SAR within a 9 km2 area savanna in Kruger National Park (KNP. We inventoried 42 field plots in the wet season and computed AGB for each plot using site-specific allometry. Canopy cover, canopy height, and their product were regressed with plot-level AGB over the TLS-footprint, while SAR backscatter was used to model dry season biomass for the years 2007, 2008, 2009, and 2010 for the study area. The results from model validation showed a significant linear relationship between TLS-derived predictors with field biomass, p < 0.05 and adjusted R2 ranging between 0.56 for SAR to 0.93 for the TLS-derived canopy cover and height. Log-transformed AGB yielded lower errors with TLS metrics compared with non-transformed AGB. An assessment of the backscatter based on root mean square error (RMSE showed better AGB prediction with cross-polarized (RMSE = 6.6 t/ha as opposed to co-polarized data (RMSE = 6.7 t/ha, attributed to

Geochemical Characteristics of TP3 Mine Wastes at the Elizabeth Copper Mine Superfund Site, Orange County, Vermont

Science.gov (United States)

Hammarstrom, Jane M.; Piatak, Nadine M.; Seal, Robert R.; Briggs, Paul H.; Meier, Allen L.; Muzik, Timothy L.

2003-01-01

Remediation of the Elizabeth mine Superfund site in the Vermont copper belt poses challenges for balancing environmental restoration goals with issues of historic preservation while adopting cost-effective strategies for site cleanup and long-term maintenance. The waste-rock pile known as TP3, at the headwaters of Copperas Brook, is especially noteworthy in this regard because it is the worst source of surface- and ground-water contamination identified to date, while also being the area of greatest historical significance. The U.S. Geological Survey (USGS) conducted a study of the historic mine-waste piles known as TP3 at the Elizabeth mine Superfund site near South Strafford, Orange County, VT. TP3 is a 12.3-acre (49,780 m2) subarea of the Elizabeth mine site. It is a focus area for historic preservation because it encompasses an early 19th century copperas works as well as waste from late 19th- and 20th century copper mining (Kierstead, 2001). Surface runoff and seeps from TP3 form the headwaters of Copperas Brook. The stream flows down a valley onto flotation tailings from 20th century copper mining operations and enters the West Branch of the Ompompanoosuc River approximately 1 kilometer downstream from the mine site. Shallow drinking water wells down gradient from TP3 exceed drinking water standards for copper and cadmium (Hathaway and others, 2001). The Elizabeth mine was listed as a Superfund site in 2001, mainly because of impacts of acid-mine drainage on the Ompompanoosuc River.

[Cytogenetical comparison of restorers TP-4 and D minghui63 and maintainer D46B of autotetraploid rice].

Science.gov (United States)

Long, Wen-Bo; Luan, Li; Wang, Xing; Liu, Yu-Hua; Tu, Sheng-Bin; Kong, Fan-Lun; He, Tao

2007-04-01

Cytogenetical comparison was made between high seed set restorers TP-4 and D minghui63 and eminent maintainer line D46B of autotetraploid rice. The meiosis observation demonstrated the genomes of our autotetraploid materials were all 2n = 48, the same as those in mitosis observation. Low percentages of univalent and trivalent in metaphase I (MI) of restorers TP-4 and D minghui63 and in metaphase I (MI) of maintainer line D46B of autotetraploid rice were observed. And the percentages of chromosome pairing were all over 99%, showing eminent cytological character. The frequency of TP-4 and D minghui63 in metaphase I (MI) was 2.00/PMC and 2.26/PMC, respectively. However the frequency of D46B was 6.00/PMC, significantly higher than those of TP-4 and D minghui63. It indicated that the maintainer D46B has better chromosome pairing capability in metaphase I (MI). While, the frequency of lagging chromosomes of the maintainer D46B in anaphase I (AI) was 10.62%, significantly lower than that of TP-4 (19.44%) or D minghui63 (23.14%), and it was close to the level of diploid control (7.30%). In telophase I (TI), maintainer D46B exhibited a lower frequency of microkernel, and in telophase II (TII) the frequency of normal quartered microspore of maintainer D46B was not only higher than that of TP-4 or D minghui63 but also than that of diploid control. The percentage of the cell observed chromosome lagging in A1 and the percentage of abnormal cell in TI showed a greatly significant positive correlation. That may demonstrate chromo some separation in anaphase I (AI) and microkernel formation in telophase I (TI) are controlled by the same dominant single gene or the major gene of QTL.

Deletion/duplication mutation screening of TP53 gene in patients with transitional cell carcinoma of urinary bladder using multiplex ligation-dependent probe amplification.

Science.gov (United States)

Bazrafshani, Mohammad Reza R; Nowshadi, Pouriaali A; Shirian, Sadegh; Daneshbod, Yahya; Nabipour, Fatemeh; Mokhtari, Maral; Hosseini, Fatemehsadat; Dehghan, Somayeh; Saeedzadeh, Abolfazl; Mosayebi, Ziba

2016-02-01

Bladder cancer is a molecular disease driven by the accumulation of genetic, epigenetic, and environmental factors. The aim of this study was to detect the deletions/duplication mutations in TP53 gene exons using multiplex ligation-dependent probe amplification (MLPA) method in the patients with transitional cell carcinoma (TCC). The achieved formalin-fixed paraffin-embedded tissues from 60 patients with TCC of bladder were screened for exonal deletions or duplications of every 12 TP53 gene exons using MLPA. The pathological sections were examined by three pathologists and categorized according to the WHO scoring guideline as 18 (30%) grade I, 22 (37%) grade II, 13 (22%) grade III, and 7 (11%) grade IV cases of TCC. None mutation changes of TP53 gene were detected in 24 (40%) of the patients. Furthermore, mutation changes including, 15 (25%) deletion, 17 (28%) duplication, and 4 (7%) both deletion and duplication cases were observed among 60 samples. From 12 exons of TP53 gene, exon 1 was more subjected to exonal deletion. Deletion of exon 1 of TP53 gene has occurred in 11 (35.4%) patients with TCC. In general, most mutations of TP53, either deletion or duplication, were found in exon 1, which was statistically significant. In addition, no relation between the TCC tumor grade and any type of mutation were observed in this research. MLPA is a simple and efficient method to analyze genomic deletions and duplications of all 12 exons of TP53 gene. The finding of this report that most of the mutations of TP53 occur in exon 1 is in contrast to that of the other reports suggesting that exons 5-8 are the most (frequently) mutated exons of TP53 gene. The mutations of exon 1 of TP53 gene may play an important role in the tumorogenesis of TCC. © 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

T/P23, 24, 911 and 92: New grades for advanced coal-fired power plants-Properties and experience

International Nuclear Information System (INIS)

Vaillant, J.C.; Vandenberghe, B.; Hahn, B.; Heuser, H.; Jochum, C.

2008-01-01

After the development of the well-known T/P91 grade in the early 1980s and the long industrial experiences since the early 1990s, it has been necessary to develop new steels to answer the demand of the powergen industry. New (ultra) super critical boilers require materials with advanced creep properties to reach severe steam parameters. For the 2.25% Cr family, grades 23 and 24 are now available to be used instead of the previous grade 22 with many technical and economical advantages. For the 9% Cr steels, new grades such as T/P911 and T/P92 have been developed with higher creep properties than T/P91. Thanks to its large industrial experience in these new grades, Vallourec and Mannesmann Tubes and Boehler Thyssen Schweisstechnik have now worldwide references of use with these new steel grades. In this paper, information on properties, behaviour and workability will be presented with a focus on ·elevated temperature properties and allowable stresses, ·oxidation and maximum service temperature and ·weldability procedures and recommendations

Involvement of phorbol-12-myristate-13-acetate-induced protein 1 in goniothalamin-induced TP53-dependent and -independent apoptosis in hepatocellular carcinoma-derived cells

International Nuclear Information System (INIS)

Kuo, Kung-Kai; Chen, Yi-Ling; Chen, Lih-Ren; Li, Chien-Feng; Lan, Yu-Hsuan; Chang, Fang-Rong; Wu, Yang-Chang; Shiue, Yow-Ling

2011-01-01

The objective was to investigate the upstream apoptotic mechanisms that were triggered by a styrylpyrone derivative, goniothalamin (GTN), in tumor protein p53 (TP53)-positive and -negative hepatocellular carcinoma (HCC)-derived cells. Effects of GTN were evaluated by the flow cytometry, alkaline comet assay, immunocytochemistry, small-hairpin RNA interference, mitochondria/cytosol fractionation, quantitative reverse transcription-polymerase chain reaction, immunoblotting analysis and caspase 3 activity assays in two HCC-derived cell lines. Results indicated that GTN triggered phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1, also known as NOXA)-mediated apoptosis via TP53-dependent and -independent pathways. In TP53-positive SK-Hep1 cells, GTN furthermore induced TP53 transcription-dependent and -independent apoptosis. After GTN treatment, accumulation of reactive oxygen species, formation of DNA double-strand breaks, transactivation of TP53 and/or PMAIP1 gene, translocation of TP53 and/or PMAIP1 proteins to mitochondria, release of cytochrome c from mitochondria, cleavage of caspases and induction of apoptosis in both cell lines were sustained. GTN might represent a novel class of anticancer drug that induces apoptosis in HCC-derived cells through PMAIP1 transactivation regardless of the status of TP53 gene. - Highlights: → Goniothalamin (GTN) induced apoptosis in hepatocellular carcinomas-derived cells. → The apoptosis induced by GTN is PMAIP1-dependent, regardless of TP53 status. → The apoptosis induced by GTN might be TP53 transcription-dependent or -independent. → GTN-induced apoptosis is mitochondria- and caspases-mediated.

Recent (t,p) and (3He,n) studies of elementary excitations in the lead region

International Nuclear Information System (INIS)

Flynn, E.R.

1978-01-01

A number of experiments involving two-nucleon transfer reactions were recently carried out in the region of 208 Pb to explore the limits of the pairing vibration model. ( 3 He,n) studies revealed that the proton pairing elementary excitations give a reasonably simple vibrational picture after corrections for important particle--hole terms. These data are also described accurately by microscopic calculations of the 0 + pairing phonon. (t,p) results on a 204 Hg target reveal a pairing vibrational state in 206 Hg near the predicted energy, after various interactions are taken into account. 14 figures

Calculation of the thermal neutron scattering kernel using the synthetic model. Pt. 2. Zero-order energy transfer kernel

International Nuclear Information System (INIS)

Drozdowicz, K.

1995-01-01

A comprehensive unified description of the application of Granada's Synthetic Model to the slow-neutron scattering by the molecular systems is continued. Detailed formulae for the zero-order energy transfer kernel are presented basing on the general formalism of the model. An explicit analytical formula for the total scattering cross section as a function of the incident neutron energy is also obtained. Expressions of the free gas model for the zero-order scattering kernel and for total scattering kernel are considered as a sub-case of the Synthetic Model. (author). 10 refs

Valproic acid treatment response in vitro is determined by TP53 status in medulloblastoma.

Science.gov (United States)

Mascaro-Cordeiro, Bruna; Oliveira, Indhira Dias; Tesser-Gamba, Francine; Pavon, Lorena Favaro; Saba-Silva, Nasjla; Cavalheiro, Sergio; Dastoli, Patrícia; Toledo, Silvia Regina Caminada

2018-05-22

Histone deacetylate inhibitors (HDACi), as valproic acid (VA), have been reported to enhance efficacy and to prevent drug resistance in some tumors, including medulloblastoma (MB). In the present study, we investigated VA role, combined to cisplatin (CDDP) in cell viability and gene expression of MB cell lines. Dose-response curve determined IC 50 values for each treatment: (1) VA single, (2) CDDP single, and (3) VA and CDDP combined. Cytotoxicity and flow cytometry evaluated cell viability after exposure to treatments. Quantitative PCR evaluated gene expression levels of AKT, CTNNB1, GLI1, KDM6A, KDM6B, NOTCH2, PTCH1, and TERT, before and after treatment. Besides, we performed next-generation sequencing (NGS) for PTCH1, TERT, and TP53 genes. The most effective treatment to reduce viability was combined for D283MED and ONS-76; and CDDP single for DAOY cells (p AKT genes were overexpressed after treatments with VA. D283MED and ONS-76 cells presented variants in TERT and PTCH1, respectively and DAOY cell line presented a TP53 mutation. MB tumors belonging to SHH molecular subgroup, with TP53 MUT , would be the ones that present high risk in relation to VA use during the treatment, while TP53 WT MBs can benefit from VA therapy, both SHH and groups 3 and 4. Our study shows a new perspective about VA action in medulloblastoma cells, raising the possibility that VA may act in different patterns. According to the genetic background of MB cell, VA can stimulate cell cycle arrest and apoptosis or induce resistance to treatment via signaling pathways activation.

Predictive and prognostic impact of TP53 mutations and MDM2 promoter genotype in primary breast cancer patients treated with epirubicin or paclitaxel.

Directory of Open Access Journals (Sweden)

Ranjan Chrisanthar

Full Text Available BACKGROUND: TP53 mutations have been associated with resistance to anthracyclines but not to taxanes in breast cancer patients. The MDM2 promoter single nucleotide polymorphism (SNP T309G increases MDM2 activity and may reduce wild-type p53 protein activity. Here, we explored the predictive and prognostic value of TP53 and CHEK2 mutation status together with MDM2 SNP309 genotype in stage III breast cancer patients receiving paclitaxel or epirubicin monotherapy. EXPERIMENTAL DESIGN: Each patient was randomly assigned to treatment with epirubicin 90 mg/m(2 (n = 109 or paclitaxel 200 mg/m(2 (n = 114 every 3rd week as monotherapy for 4-6 cycles. Patients obtaining a suboptimal response on first-line treatment requiring further chemotherapy received the opposite regimen. Time from last patient inclusion to follow-up censoring was 69 months. Each patient had snap-frozen tumor tissue specimens collected prior to commencing chemotherapy. PRINCIPAL FINDINGS: While TP53 and CHEK2 mutations predicted resistance to epirubicin, MDM2 status did not. Neither TP53/CHEK2 mutations nor MDM2 status was associated with paclitaxel response. Remarkably, TP53 mutations (p = 0.007 but also MDM2 309TG/GG genotype status (p = 0.012 were associated with a poor disease-specific survival among patients having paclitaxel but not patients having epirubicin first-line. The effect of MDM2 status was observed among individuals harbouring wild-type TP53 (p = 0.039 but not among individuals with TP53 mutated tumors (p>0.5. CONCLUSION: TP53 and CHEK2 mutations were associated with lack of response to epirubicin monotherapy. In contrast, TP53 mutations and MDM2 309G allele status conferred poor disease-specific survival among patients treated with primary paclitaxel but not epirubicin monotherapy.

TP53 hotspot mutations are predictive of survival in primary central nervous system lymphoma patients treated with combination chemotherapy

DEFF Research Database (Denmark)

Munch-Petersen, Helga D; Asmar, Fazila; Dimopoulos, Konstantinos

2016-01-01

regimens (high-dose methotrexate/whole brain radiation therapy, 6.0 months, or no therapy, 0.83 months), P hotspot/direct DNA contact mutations. CCT-treated patients with PCNSL harboring a hotspot/direct DNA contact MUT......-TP53 (n = 9) had a significantly worse OS and progression free survival (PFS) compared to patients with non-hotspot/non-direct DNA contact MUT-TP53 or wild-type TP53 (median PFS 4.6 versus 18.2 or 45.7 months), P = 0.041 and P = 0.00076, respectively. Multivariate Cox regression analysis confirmed...... that hotspot/direct DNA contact MUT-TP53 was predictive of poor outcome in CCT-treated PCNSL patients, P = 0.012 and P = 0.008; HR: 1.86 and 1.95, for OS and PFS, respectively. MIR34A, MIR34B/C, and DAPK promoter methylation were detected in 53/93 (57.0 %), 80/84 (95.2 %), and 70/75 (93.3 %) of the PCNSL...

Polimorfismo do gene tp53 no códon 72 em pacientes com suspeita de LMC Codon 72 polymorphism of the TP53 gene in patients suspected to have CML

Directory of Open Access Journals (Sweden)

Camila S. Hamú

2007-12-01

Full Text Available A leucemia mielóide crônica (LMC é uma doença proliferativa do sistema hematopoiético, caracterizada pela expansão clonal de uma célula-tronco primitiva e pluripotente denominada stem cell. Este tipo de leucemia está associado, em 90% dos casos, à translocação t(9;22(q34;q11. Essa alteração cromossômica estrutural codifica para uma proteína quimérica BCR-ABL, que confere às células leucêmicas uma alta resistência à morte, independente do agente indutor desse processo. A proteína p53 é uma reguladora transcricional induzida por danos no DNA, fato que resulta na parada do ciclo celular com conseqüente ativação de mecanismos de reparo ou mesmo na indução à apoptose. As mutações no gene TP53 são as alterações genéticas mais comuns em tumores malignos humanos. O presente estudo teve como objetivo genotipar e determinar a freqüência alélica do polimorfismo do TP53 no códon 72 (arginina - Arg e prolina - Pro, em pacientes com suspeita de LMC, pela Reação em Cadeia da Polimerase. Desta forma, os resultados indicaram que 73,4% (23/30 dos pacientes apresentaram homozigose para arginina (Arg/Arg e 26,6% (7/30 heterozigose (Arg/Pro. Não foi encontrado nenhum paciente homozigoto para prolina (Pro/Pro. Os resultados obtidos sugerem que o polimorfismo do gene TP53 no códon 72 não é um fator de risco importante para a iniciação, promoção e progressão da LMC.Chronic myeloid leukemia (CML is a proliferative disorder of the hematopoietic system characterized by clonal expansion of a primitive and pluripotent stem cell. In this type of leukemia, up to 90% of all cases is associated to a specific chromosomal translocation, t(9;22(q34;q11. The genomic alteration results in a chimeric protein, BCR-ABL, that confers a high resistance leukemia cells to death, independent of the induction mechanism of this process. Protein p53 is a transcriptional factor expressed after DNA damage which ceases cell cycle progression and

Evaluation of synthetic vascular grafts in a mouse carotid grafting model.

Science.gov (United States)

Chan, Alex H P; Tan, Richard P; Michael, Praveesuda L; Lee, Bob S L; Vanags, Laura Z; Ng, Martin K C; Bursill, Christina A; Wise, Steven G

2017-01-01

Current animal models for the evaluation of synthetic grafts are lacking many of the molecular tools and transgenic studies available to other branches of biology. A mouse model of vascular grafting would allow for the study of molecular mechanisms of graft failure, including in the context of clinically relevant disease states. In this study, we comprehensively characterise a sutureless grafting model which facilitates the evaluation of synthetic grafts in the mouse carotid artery. Using conduits electrospun from polycaprolactone (PCL) we show the gradual development of a significant neointima within 28 days, found to be greatest at the anastomoses. Histological analysis showed temporal increases in smooth muscle cell and collagen content within the neointima, demonstrating its maturation. Endothelialisation of the PCL grafts, assessed by scanning electron microscopy (SEM) analysis and CD31 staining, was near complete within 28 days, together replicating two critical aspects of graft performance. To further demonstrate the potential of this mouse model, we used longitudinal non-invasive tracking of bone-marrow mononuclear cells from a transgenic mouse strain with a dual reporter construct encoding both luciferase and green fluorescent protein (GFP). This enabled characterisation of mononuclear cell homing and engraftment to PCL using bioluminescence imaging and histological staining over time (7, 14 and 28 days). We observed peak luminescence at 7 days post-graft implantation that persisted until sacrifice at 28 days. Collectively, we have established and characterised a high-throughput model of grafting that allows for the evaluation of key clinical drivers of graft performance.

Evaluation of synthetic vascular grafts in a mouse carotid grafting model.

Directory of Open Access Journals (Sweden)

Alex H P Chan

Full Text Available Current animal models for the evaluation of synthetic grafts are lacking many of the molecular tools and transgenic studies available to other branches of biology. A mouse model of vascular grafting would allow for the study of molecular mechanisms of graft failure, including in the context of clinically relevant disease states. In this study, we comprehensively characterise a sutureless grafting model which facilitates the evaluation of synthetic grafts in the mouse carotid artery. Using conduits electrospun from polycaprolactone (PCL we show the gradual development of a significant neointima within 28 days, found to be greatest at the anastomoses. Histological analysis showed temporal increases in smooth muscle cell and collagen content within the neointima, demonstrating its maturation. Endothelialisation of the PCL grafts, assessed by scanning electron microscopy (SEM analysis and CD31 staining, was near complete within 28 days, together replicating two critical aspects of graft performance. To further demonstrate the potential of this mouse model, we used longitudinal non-invasive tracking of bone-marrow mononuclear cells from a transgenic mouse strain with a dual reporter construct encoding both luciferase and green fluorescent protein (GFP. This enabled characterisation of mononuclear cell homing and engraftment to PCL using bioluminescence imaging and histological staining over time (7, 14 and 28 days. We observed peak luminescence at 7 days post-graft implantation that persisted until sacrifice at 28 days. Collectively, we have established and characterised a high-throughput model of grafting that allows for the evaluation of key clinical drivers of graft performance.

Integration of TP53, DREAM, MMB-FOXM1 and RB-E2F target gene analyses identifies cell cycle gene regulatory networks.

Science.gov (United States)

Fischer, Martin; Grossmann, Patrick; Padi, Megha; DeCaprio, James A

2016-07-27

Cell cycle (CC) and TP53 regulatory networks are frequently deregulated in cancer. While numerous genome-wide studies of TP53 and CC-regulated genes have been performed, significant variation between studies has made it difficult to assess regulation of any given gene of interest. To overcome the limitation of individual studies, we developed a meta-analysis approach to identify high confidence target genes that reflect their frequency of identification in independent datasets. Gene regulatory networks were generated by comparing differential expression of TP53 and CC-regulated genes with chromatin immunoprecipitation studies for TP53, RB1, E2F, DREAM, B-MYB, FOXM1 and MuvB. RNA-seq data from p21-null cells revealed that gene downregulation by TP53 generally requires p21 (CDKN1A). Genes downregulated by TP53 were also identified as CC genes bound by the DREAM complex. The transcription factors RB, E2F1 and E2F7 bind to a subset of DREAM target genes that function in G1/S of the CC while B-MYB, FOXM1 and MuvB control G2/M gene expression. Our approach yields high confidence ranked target gene maps for TP53, DREAM, MMB-FOXM1 and RB-E2F and enables prediction and distinction of CC regulation. A web-based atlas at www.targetgenereg.org enables assessing the regulation of any human gene of interest. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Identification of operator sites of the CI repressor of phage TP901-1: evolutionary link to other phages

International Nuclear Information System (INIS)

Johansen, Annette H.; Broendsted, Lone; Hammer, Karin

2003-01-01

The repressor encoded by the cI gene of the temperate Lactococcus lactis subsp. cremoris bacteriophage TP901-1 has been purified. Gel-retardation and footprinting analyses identified three palindromic operator sites (O R , O L , and O D ). The operator site O R is located between the two divergent early promoters P R and P L , O L overlaps the transcriptional start of the lytic P L promoter, and O D is located downstream of the mor gene, the first gene in the lytic gene cluster. The function of O L was verified by mutational analysis. Binding was found to be specific and cooperative. Multimeric forms of the repressor were observed, thus indicating that the repressor may bind simultaneously to all three operator sites. Inverted repeats with homology to the operator sites of TP901-1 were identified in phage genomes encoding repressors homologous to CI of TP901-1. Interestingly, the locations of these repeats on the phage genomes correspond to those found in TP901-1, indicating that the same system of cooperative repression of early phage promoters has been inherited by modular evolution

STARDUST FROM ASYMPTOTIC GIANT BRANCH STARS

International Nuclear Information System (INIS)

Gail, H.-P.; Zhukovska, S. V.; Hoppe, P.; Trieloff, M.

2009-01-01

The formation of dust in the outflows of low- and intermediate-mass stars on the first giant branch and asymptotic giant branch (AGB) is studied and the relative contributions of stars of different initial masses and metallicities to the interstellar medium (ISM) at the instant of solar system formation are derived. These predictions are compared with the characteristics of the parent stars of presolar dust grains found in primitive meteorites and interplanetary dust particles (IDPs) inferred from their isotopic compositions. For this purpose, model calculations for dust condensation in stellar outflows are combined with synthetic models of stellar evolution on the first giant branch and AGB and an evolution model of the Milky Way for the solar neighborhood. The dust components considered are olivine, pyroxene, carbon, SiC, and iron. The corresponding dust production rates are derived for the solar vicinity. From these rates and taking into account dust destruction by supernova shocks in the ISM, the contributions to the inventory of presolar dust grains in the solar system are derived for stars of different initial masses and metallicities. It is shown that stars on the first giant branch and the early AGB are not expected to form dust, in accord with astronomical observations. Dust formation is concentrated in the last phase of evolution, the thermally pulsing AGB. Due to the limited lifetime of dust grains in the ISM only parent stars from a narrow range of metallicities are expected to contribute to the population of presolar dust grains. Silicate and silicon carbide dust grains are predicted to come from parent stars with metallicities not less than about Z ∼ 0.008 (0.6 x solar). This metallicity limit is higher than that inferred from presolar SiC grain isotope data. The population of presolar carbon dust grains is predicted to originate from a wider range of metallicities, down to Z ∼ 0.004. Masses of AGB stars that produce C-rich dust are in the range �

Neutron spectra and cross sections for ice and clathrate generated from the synthetic spectrum and synthetic model for molecular solids

International Nuclear Information System (INIS)

Petriw, S; Cantargi, F; Granada, R

2006-01-01

We present here a Synthetic Model for Molecular Solids, aimed at the description of the interaction of thermal neutrons with this kind of systems.Simple representations of the molecular dynamical modes are used, in order to produce a fair description of neutron scattering kernels and cross sections with a minimum set of input data. Using those spectra, we have generated thermal libraries for M C N P [es

A model for improving microbial biofuel production using a synthetic feedback loop

Energy Technology Data Exchange (ETDEWEB)

Dunlop, Mary; Keasling, Jay; Mukhopadhyay, Aindrila

2011-07-14

Cells use feedback to implement a diverse range of regulatory functions. Building synthetic feedback control systems may yield insight into the roles that feedback can play in regulation since it can be introduced independently of native regulation, and alternative control architectures can be compared. We propose a model for microbial biofuel production where a synthetic control system is used to increase cell viability and biofuel yields. Although microbes can be engineered to produce biofuels, the fuels are often toxic to cell growth, creating a negative feedback loop that limits biofuel production. These toxic effects may be mitigated by expressing efflux pumps that export biofuel from the cell. We developed a model for cell growth and biofuel production and used it to compare several genetic control strategies for their ability to improve biofuel yields. We show that controlling efflux pump expression directly with a biofuel-responsive promoter is a straight forward way of improving biofuel production. In addition, a feed forward loop controller is shown to be versatile at dealing with uncertainty in biofuel production rates.

Baseline results from the UK SIGNIFY study: a whole-body MRI screening study in TP53 mutation carriers and matched controls.

Science.gov (United States)

Saya, Sibel; Killick, Emma; Thomas, Sarah; Taylor, Natalie; Bancroft, Elizabeth K; Rothwell, Jeanette; Benafif, Sarah; Dias, Alexander; Mikropoulos, Christos; Pope, Jenny; Chamberlain, Anthony; Gunapala, Ranga; Izatt, Louise; Side, Lucy; Walker, Lisa; Tomkins, Susan; Cook, Jackie; Barwell, Julian; Wiles, Vicki; Limb, Lauren; Eccles, Diana; Leach, Martin O; Shanley, Susan; Gilbert, Fiona J; Hanson, Helen; Gallagher, David; Rajashanker, Bala; Whitehouse, Richard W; Koh, Dow-Mu; Sohaib, S Aslam; Evans, D Gareth; Eeles, Rosalind A

2017-07-01

In the United Kingdom, current screening guidelines for TP53 germline mutation carriers solely recommends annual breast MRI, despite the wide spectrum of malignancies typically seen in this group. This study sought to investigate the role of one-off non-contrast whole-body MRI (WB MRI) in the screening of asymptomatic TP53 mutation carriers. 44 TP53 mutation carriers and 44 population controls were recruited. Scans were read by radiologists blinded to participant carrier status. The incidence of malignancies diagnosed in TP53 mutation carriers against general population controls was calculated. The incidences of non-malignant relevant disease and irrelevant disease were measured, as well as the number of investigations required to determine relevance of findings. In TP53 mutation carriers, 6 of 44 (13.6, 95% CI 5.2-27.4%) participants were diagnosed with cancer during the study, all of which would be considered life threatening if untreated. Two were found to have two primary cancers. Two participants with cancer had abnormalities on the MRI which were initially thought to be benign (a pericardial cyst and a uterine fibroid) but transpired to be sarcomas. No controls were diagnosed with cancer. Fifteen carriers (34.1, 95% CI 20.5-49.9%) and seven controls (15.9, 95% CI 6.7-30.1%) underwent further investigations following the WB MRI for abnormalities that transpired to be benign (p = 0.049). The cancer detection rate in this group justifies a minimum baseline non-contrast WB MRI in germline TP53 mutation carriers. This should be adopted into national guidelines for management of adult TP53 mutation carriers in addition to the current practice of contrast enhanced breast MRI imaging.

Synergistic Synthetic Biology: Units in Concert

Science.gov (United States)

Trosset, Jean-Yves; Carbonell, Pablo

2013-01-01

Synthetic biology aims at translating the methods and strategies from engineering into biology in order to streamline the design and construction of biological devices through standardized parts. Modular synthetic biology devices are designed by means of an adequate elimination of cross-talk that makes circuits orthogonal and specific. To that end, synthetic constructs need to be adequately optimized through in silico modeling by choosing the right complement of genetic parts and by experimental tuning through directed evolution and craftsmanship. In this review, we consider an additional and complementary tool available to the synthetic biologist for innovative design and successful construction of desired circuit functionalities: biological synergies. Synergy is a prevalent emergent property in biological systems that arises from the concerted action of multiple factors producing an amplification or cancelation effect compared with individual actions alone. Synergies appear in domains as diverse as those involved in chemical and protein activity, polypharmacology, and metabolic pathway complementarity. In conventional synthetic biology designs, synergistic cross-talk between parts and modules is generally attenuated in order to verify their orthogonality. Synergistic interactions, however, can induce emergent behavior that might prove useful for synthetic biology applications, like in functional circuit design, multi-drug treatment, or in sensing and delivery devices. Synergistic design principles are therefore complementary to those coming from orthogonal design and may provide added value to synthetic biology applications. The appropriate modeling, characterization, and design of synergies between biological parts and units will allow the discovery of yet unforeseeable, novel synthetic biology applications. PMID:25022769

Synergistic Synthetic Biology: Units in Concert

International Nuclear Information System (INIS)

Trosset, Jean-Yves; Carbonell, Pablo

2013-01-01

Synthetic biology aims at translating the methods and strategies from engineering into biology in order to streamline the design and construction of biological devices through standardized parts. Modular synthetic biology devices are designed by means of an adequate elimination of cross-talk that makes circuits orthogonal and specific. To that end, synthetic constructs need to be adequately optimized through in silico modeling by choosing the right complement of genetic parts and by experimental tuning through directed evolution and craftsmanship. In this review, we consider an additional and complementary tool available to the synthetic biologist for innovative design and successful construction of desired circuit functionalities: biological synergies. Synergy is a prevalent emergent property in biological systems that arises from the concerted action of multiple factors producing an amplification or cancelation effect compared with individual actions alone. Synergies appear in domains as diverse as those involved in chemical and protein activity, polypharmacology, and metabolic pathway complementarity. In conventional synthetic biology designs, synergistic cross-talk between parts and modules is generally attenuated in order to verify their orthogonality. Synergistic interactions, however, can induce emergent behavior that might prove useful for synthetic biology applications, like in functional circuit design, multi-drug treatment, or in sensing and delivery devices. Synergistic design principles are therefore complementary to those coming from orthogonal design and may provide added value to synthetic biology applications. The appropriate modeling, characterization, and design of synergies between biological parts and units will allow the discovery of yet unforeseeable, novel synthetic biology applications.

Gene-gene interaction between MSX1 and TP63 in Asian case-parent trios with nonsyndromic cleft lip with or without cleft palate.

Science.gov (United States)

Liu, Dongjing; Schwender, Holger; Wang, Mengying; Wang, Hong; Wang, Ping; Zhu, Hongping; Zhou, Zhibo; Li, Jing; Wu, Tao; Beaty, Terri H

2018-03-01

Small ubiquitin-like modification, also known as sumoylation, is a crucial post-translational regulatory mechanisms involved in development of the lip and palate. Recent studies reported two sumoylation target genes, MSX1 and TP63, to have achieved genome-wide level significance in tests of association with nonsyndromic clefts. Here, we performed a candidate gene analysis considering gene-gene and gene-environment interaction for SUMO1, MSX1, and TP63 to further explore the etiology of nonsyndromic cleft lip with or without cleft palate (NSCL/P). A total of 130 single-nucleotide polymorphisms (SNPs) in or near SUMO1, MSX1, and TP63 was analyzed among 1,038 Asian NSCL/P trios ascertained through an international consortium. Conditional logistic regression models were used to explore gene-gene (G × G) and gene-environment (G × E) interaction involving maternal environmental tobacco smoke and multivitamin supplementation. Bonferroni correction was used for G × E analysis and permutation tests were used for G × G analysis. While transmission disequilibrium tests and gene-environment interaction analysis showed no significant results, we did find signals of gene-gene interaction between SNPs near MSX1 and TP63. Three pairwise interactions yielded significant p values in permutation tests (rs884690 and rs9290890 with p = 9.34 × 10 -5 and empirical p = 1.00 × 10 -4 , rs1022136 and rs4687098 with p = 2.41 × 10 -4 and empirical p = 2.95 × 10 -4 , rs6819546 and rs9681004 with p = 5.15 × 10 -4 and empirical p = 3.02 × 10 -4 ). Gene-gene interaction between MSX1 and TP63 may influence the risk of NSCL/P in Asian populations. Our study provided additional understanding of the genetic etiology of NSCL/P and underlined the importance of considering gene-gene interaction in the etiology of this common craniofacial malformation. © 2018 Wiley Periodicals, Inc.

Expression of TpNRAMP5, a metal transporter from Polish wheat (Triticum polonicum L.), enhances the accumulation of Cd, Co and Mn in transgenic Arabidopsis plants.

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Peng, Fan; Wang, Chao; Zhu, Jianshu; Zeng, Jian; Kang, Houyang; Fan, Xing; Sha, Lina; Zhang, Haiqin; Zhou, Yonghong; Wang, Yi

2018-06-01

TpRNAMP5 is mainly expressed in the plasma membrane of roots and basal stems. It functions as a metal transporter for Cd, Mn and Co accumulation. Numerous natural resistance-associated macrophage proteins (NRAMPs) have been functionally identified in various plant species, including Arabidopsis, rice, soybean and tobacco, but no information is available on NRAMP genes in wheat. In this study, we isolated a TpNRAMP5 from dwarf Polish wheat (DPW, Triticum polonicum L.), a species with high tolerance to Cd and Zn. Expression pattern analysis revealed that TpNRAMP5 is mainly expressed in roots and basal stems of DPW. TpNRAMP5 was localized at the plasma membrane of Arabidopsis leaf protoplast. Expression of TpNRAMP5 in yeast significantly increased yeast sensitivity to Cd and Co, but not Zn, and enhanced Cd and Co concentrations. Expression of TpNRAMP5 in Arabidopsis significantly increased Cd, Co and Mn concentrations in roots, shoots and whole plants, but had no effect on Fe and Zn concentrations. These results indicate that TpNRAMP5 is a metal transporter enhancing the accumulation of Cd, Co and Mn, but not Zn and Fe. Genetic manipulation of TpNRAMP5 can be applied in the future to limit the transfer of Cd from soil to wheat grains, thereby protecting human health.

Development of a Novel Tetravalent Synthetic Peptide That Binds to Phosphatidic Acid.

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Rina Ogawa

Full Text Available We employed a multivalent peptide-library screening technique to identify a peptide motif that binds to phosphatidic acid (PA, but not to other phospholipids such as phosphatidylcholine (PC, phosphatidylethanolamine (PE, and phosphatidylserine (PS. A tetravalent peptide with the sequence motif of MARWHRHHH, designated as PAB-TP (phosphatidic acid-binding tetravalent peptide, was shown to bind as low as 1 mol% of PA in the bilayer membrane composed of PC and cholesterol. Kinetic analysis of the interaction between PAB-TP and the membranes containing 10 mol% of PA showed that PAB-TP associated with PA with a low dissociation constant of KD = 38 ± 5 nM. Coexistence of cholesterol or PE with PA in the membrane enhanced the PAB-TP binding to PA by increasing the ionization of the phosphomonoester head group as well as by changing the microenvironment of PA molecules in the membrane. Amino acid replacement analysis demonstrated that the tryptophan residue at position 4 of PAB-TP was involved in the interaction with PA. Furthermore, a series of amino acid substitutions at positions 5 to 9 of PAB-TP revealed the involvement of consecutive histidine and arginine residues in recognition of the phosphomonoester head group of PA. Our results demonstrate that the recognition of PA by PAB-TP is achieved by a combination of hydrophobic, electrostatic and hydrogen-bond interactions, and that the tetravalent structure of PAB-TP contributes to the high affinity binding to PA in the membrane. The novel PA-binding tetravalent peptide PAB-TP will provide insight into the molecular mechanism underlying the recognition of PA by PA-binding proteins that are involved in various cellular events.

Molecular dynamics modeling the synthetic and biological polymers interactions pre-studied via docking

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Tsvetkov, Vladimir B.; Serbin, Alexander V.

2014-06-01

In previous works we reported the design, synthesis and in vitro evaluations of synthetic anionic polymers modified by alicyclic pendant groups (hydrophobic anchors), as a novel class of inhibitors of the human immunodeficiency virus type 1 ( HIV-1) entry into human cells. Recently, these synthetic polymers interactions with key mediator of HIV-1 entry-fusion, the tri-helix core of the first heptad repeat regions [ HR1]3 of viral envelope protein gp41, were pre-studied via docking in terms of newly formulated algorithm for stepwise approximation from fragments of polymeric backbone and side-group models toward real polymeric chains. In the present article the docking results were verified under molecular dynamics ( MD) modeling. In contrast with limited capabilities of the docking, the MD allowed of using much more large models of the polymeric ligands, considering flexibility of both ligand and target simultaneously. Among the synthesized polymers the dinorbornen anchors containing alternating copolymers of maleic acid were selected as the most representative ligands (possessing the top anti-HIV activity in vitro in correlation with the highest binding energy in the docking). To verify the probability of binding of the polymers with the [HR1]3 in the sites defined via docking, various starting positions of polymer chains were tried. The MD simulations confirmed the main docking-predicted priority for binding sites, and possibilities for axial and belting modes of the ligands-target interactions. Some newly MD-discovered aspects of the ligand's backbone and anchor units dynamic cooperation in binding the viral target clarify mechanisms of the synthetic polymers anti-HIV activity and drug resistance prevention.

Altered vocal fold kinematics in synthetic self-oscillating models that employ adipose tissue as a lateral boundary condition.

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Saidi, Hiba; Erath, Byron D.

2015-11-01

The vocal folds play a major role in human communication by initiating voiced sound production. During voiced speech, the vocal folds are set into sustained vibrations. Synthetic self-oscillating vocal fold models are regularly employed to gain insight into flow-structure interactions governing the phonation process. Commonly, a fixed boundary condition is applied to the lateral, anterior, and posterior sides of the synthetic vocal fold models. However, physiological observations reveal the presence of adipose tissue on the lateral surface between the thyroid cartilage and the vocal folds. The goal of this study is to investigate the influence of including this substrate layer of adipose tissue on the dynamics of phonation. For a more realistic representation of the human vocal folds, synthetic multi-layer vocal fold models have been fabricated and tested while including a soft lateral layer representative of adipose tissue. Phonation parameters have been collected and are compared to those of the standard vocal fold models. Results show that vocal fold kinematics are affected by adding the adipose tissue layer as a new boundary condition.

Novel variant in the TP63 gene associated to ankyloblepharon-ectodermal dysplasia-cleft lip/palate (AEC) syndrome.

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Gonzalez, Francisco; Loidi, Lourdes; Abalo-Lojo, Jose M

2017-01-01

Ankyloblepharon-ectodermal dysplasia-cleft lip/palate (AEC) syndrome is a disorder resulting from anomalous embryonic development of ectodermal tissues. There is evidence that AEC syndrome is caused by mutations in the TP63 gene, which encodes the p63 protein. This is an important regulatory protein involved in epidermal proliferation and differentiation. Genome sequencing was performed in DNA from peripheral blood leukocytes of a newborn with AEC syndrome and her parents. Variants were searched in all coding exons and intron-exon boundaries of the TP63 gene. A heterozygous missense variant (NM_003722.4:c.1063G>C (p.Asp355His) was found in the newborn patient. No variants were found in either of the parents. We identified a previously unreported variant in TP63 gene which seems to be involved in the somatic malformations found in the AEC syndrome. The absence of this variant in both parents suggests that the variant appeared de novo.

CK2 phospho-dependent binding of R2TP complex to TEL2 is essential for mTOR and SMG1 stability.

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Horejsí, Zuzana; Takai, Hiroyuki; Adelman, Carrie A; Collis, Spencer J; Flynn, Helen; Maslen, Sarah; Skehel, J Mark; de Lange, Titia; Boulton, Simon J

2010-09-24

TEL2 interacts with and is essential for the stability of all phosphatidylinositol 3-kinase-related kinases (PIKKs), but its mechanism of action remains unclear. Here, we show that TEL2 is constitutively phosphorylated on conserved serines 487 and 491 by casein kinase 2 (CK2). Proteomic analyses establish that the CK2 phosphosite of TEL2 confers binding to the R2TP/prefoldin-like complex, which possesses chaperon/prefoldin activities required during protein complex assembly. The PIH1D1 subunit of the R2TP complex binds directly to the CK2 phosphosite of TEL2 in vitro and is required for the TEL2-R2TP/prefoldin-like complex interaction in vivo. Although the CK2 phosphosite mutant of TEL2 retains association with the PIKKs and HSP90 in cells, failure to interact with the R2TP/prefoldin-like complex results in instability of the PIKKs, principally mTOR and SMG1. We propose that TEL2 acts as a scaffold to coordinate the activities of R2TP/prefoldin-like and HSP90 chaperone complexes during the assembly of the PIKKs. Copyright © 2010 Elsevier Inc. All rights reserved.

Incorporating Canopy Cover for Airborne-Derived Assessments of Forest Biomass in the Tropical Forests of Cambodia.

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Singh, Minerva; Evans, Damian; Coomes, David A; Friess, Daniel A; Suy Tan, Boun; Samean Nin, Chan

2016-01-01

This research examines the role of canopy cover in influencing above ground biomass (AGB) dynamics of an open canopied forest and evaluates the efficacy of individual-based and plot-scale height metrics in predicting AGB variation in the tropical forests of Angkor Thom, Cambodia. The AGB was modeled by including canopy cover from aerial imagery alongside with the two different canopy vertical height metrics derived from LiDAR; the plot average of maximum tree height (Max_CH) of individual trees, and the top of the canopy height (TCH). Two different statistical approaches, log-log ordinary least squares (OLS) and support vector regression (SVR), were used to model AGB variation in the study area. Ten different AGB models were developed using different combinations of airborne predictor variables. It was discovered that the inclusion of canopy cover estimates considerably improved the performance of AGB models for our study area. The most robust model was log-log OLS model comprising of canopy cover only (r = 0.87; RMSE = 42.8 Mg/ha). Other models that approximated field AGB closely included both Max_CH and canopy cover (r = 0.86, RMSE = 44.2 Mg/ha for SVR; and, r = 0.84, RMSE = 47.7 Mg/ha for log-log OLS). Hence, canopy cover should be included when modeling the AGB of open-canopied tropical forests.

Synthetic Sediments and Stochastic Groundwater Hydrology

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Wilson, J. L.

2002-12-01

For over twenty years the groundwater community has pursued the somewhat elusive goal of describing the effects of aquifer heterogeneity on subsurface flow and chemical transport. While small perturbation stochastic moment methods have significantly advanced theoretical understanding, why is it that stochastic applications use instead simulations of flow and transport through multiple realizations of synthetic geology? Allan Gutjahr was a principle proponent of the Fast Fourier Transform method for the synthetic generation of aquifer properties and recently explored new, more geologically sound, synthetic methods based on multi-scale Markov random fields. Focusing on sedimentary aquifers, how has the state-of-the-art of synthetic generation changed and what new developments can be expected, for example, to deal with issues like conceptual model uncertainty, the differences between measurement and modeling scales, and subgrid scale variability? What will it take to get stochastic methods, whether based on moments, multiple realizations, or some other approach, into widespread application?

Quasi-Similarity Model of Synthetic Jets

Czech Academy of Sciences Publication Activity Database

Tesař, Václav; Kordík, Jozef

2009-01-01

Roč. 149, č. 2 (2009), s. 255-265 ISSN 0924-4247 R&D Projects: GA AV ČR IAA200760705; GA ČR GA101/07/1499 Institutional research plan: CEZ:AV0Z20760514 Keywords : jets * synthetic jets * similarity solution Subject RIV: BK - Fluid Dynamics Impact factor: 1.674, year: 2009 http://www.sciencedirect.com

Radiosensitivity and TP 53, EGFR amplification and LOH10 analysis of primary glioma cell cultures

International Nuclear Information System (INIS)

Gerlach, B.; Harder, A.H.; Slotman, B.J.; Sminia, P.; Hulsebos, T.J.M.; Leenstra, S.; Peter Vandertop, W.; Hartmann, K.A.

2002-01-01

Aim: Determination of in-vitro radiosensitivity and genetic alterations of cell cultures derived from human glioma biopsy tissue and established glioma cell lines. Material and Methods: Fresh brain tumor specimens of six patients were processed to early passage cell cultures. In addition the cell lines D 384 and Gli 6 were used. Cell cultures were irradiated with doses from 2 to 10 Gy. Following irradiation, cell survival was determined by clonogenic assay and survival curves were generated. The surviving fractions after 2 Gy (SF2) and 4 Gy (SF4) were used as radiosensitivity parameters. Genetic analysis included determination of the mutational and loss of heterozygosity (LOH) status of TP 53 (exons 5-8), the LOH 10- and epidermal growth factor receptor gene (EGFR) amplification status. Results: The SF2 and SF4 values ranged from 0.54 to 0.88 (mean: 0.70) and from 0.13 to 0.52 (mean: 0.32), respectively. Genetic alterations were found in the Gli 6 cell line and in two primary cell cultures. The genetic profile of Gli 6 showed LOH but no TP 53 mutation, complete LOH 10 and no EGFR amplification. The VU 15 cell culture showed TP 53 mutation but no LOH 10 or EGFR amplification, while VU 24 showed incomplete LOH 10, EGFR amplification and no TP 53 mutation. In the other four cell cultures and D 384 cell line no genetic alterations were diagnosed. Histopathological classification of glioblastoma multiforme and/or genetic alterations resulted in lower radiosensitivity. Conclusion: In this small series of early passage glioma cell cultures low radiosensitivity and alterations in cell regulatory genes were seen. Further testing of biological behavior in larger series of patient-derived material is ongoing. (orig.)

Synthetic biology between challenges and risks: suggestions for a model of governance and a regulatory framework, based on fundamental rights.

Science.gov (United States)

Colussi, Ilaria Anna

2013-01-01

This paper deals with the emerging synthetic biology, its challenges and risks, and tries to design a model for the governance and regulation of the field. The model is called of "prudent vigilance" (inspired by the report about synthetic biology, drafted by the U.S. Presidential Commission on Bioethics, 2010), and it entails (a) an ongoing and periodically revised process of assessment and management of all the risks and concerns, and (b) the adoption of policies - taken through "hard law" and "soft law" sources - that are based on the principle of proportionality (among benefits and risks), on a reasonable balancing between different interests and rights at stake, and are oriented by a constitutional frame, which is represented by the protection of fundamental human rights emerging in the field of synthetic biology (right to life, right to health, dignity, freedom of scientific research, right to environment). After the theoretical explanation of the model, its operability is "checked", by considering its application with reference to only one specific risk brought up by synthetic biology - biosecurity risk, i.e. the risk of bioterrorism.

Benzo[a]pyrene, Aflatoxine B1 and Acetaldehyde Mutational Patterns in TP53 Gene Using a Functional Assay: Relevance to Human Cancer Aetiology

Science.gov (United States)

Paget, Vincent; Lechevrel, Mathilde; André, Véronique; Le Goff, Jérémie; Pottier, Didier; Billet, Sylvain; Garçon, Guillaume; Shirali, Pirouz; Sichel, François

2012-01-01

Mutations in the TP53 gene are the most common alterations in human tumours. TP53 mutational patterns have sometimes been linked to carcinogen exposure. In hepatocellular carcinoma, a specific G>T transversion on codon 249 is classically described as a fingerprint of aflatoxin B1 exposure. Likewise G>T transversions in codons 157 and 158 have been related to tobacco exposure in human lung cancers. However, controversies remain about the interpretation of TP53 mutational pattern in tumours as the fingerprint of genotoxin exposure. By using a functional assay, the Functional Analysis of Separated Alleles in Yeast (FASAY), the present study depicts the mutational pattern of TP53 in normal human fibroblasts after in vitro exposure to well-known carcinogens: benzo[a]pyrene, aflatoxin B1 and acetaldehyde. These in vitro patterns of mutations were then compared to those found in human tumours by using the IARC database of TP53 mutations. The results show that the TP53 mutational patterns found in human tumours can be only partly ascribed to genotoxin exposure. A complex interplay between the functional impact of the mutations on p53 phenotype and the cancer natural history may affect these patterns. However, our results strongly support that genotoxins exposure plays a major role in the aetiology of the considered cancers. PMID:22319594

Analysis of the complete DNA sequence of the temperate bacteriophage TP901-1: Evolution, structure, and genome organization of lactococcal bacteriophages

DEFF Research Database (Denmark)

Brøndsted, Lone; Østergaard, Solvej; Pedersen, Margit

2001-01-01

A complete analysis of the entire genome of the temperate lactococcal bacteriophage TP901-1 has been performed and the function of 21 of 56 TP901-1-encoded ORFs has been assigned. This knowledge has been used to propose 10 functional modules each responsible for specific functions during...

TP53 mutation and human papilloma virus status of oral squamous cell carcinomas in young adult patients.

Science.gov (United States)

Braakhuis, B J M; Rietbergen, M M; Buijze, M; Snijders, P J F; Bloemena, E; Brakenhoff, R H; Leemans, C R

2014-09-01

Little is known about the molecular carcinogenesis of oral squamous cell carcinoma (OSCC) in young adult patients. The aim of this study was to investigate the detailed TP53 mutation and human papilloma virus (HPV) status of OSCC in patients, younger than 45 years. TP53 mutations were determined with direct sequencing on paraffin-embedded carcinoma tissue from 31 young patients and compared with two older age OSCC reference groups: one from the same institute (N = 87) and an independent one (N = 675). Biologically active tumour HPV was detected by p16-immunohistochemistry followed by a HPV-DNA GP5 + /6 + -PCR. HPV16 was present in one OSCC (3%). TP53 mutations were found in 14 (45%) OSCC: five were missense and nine resulted in a truncated protein. Six of these latter were insertions or deletions of one or more nucleotides leading to frameshift, one was at a splice site and two resulted in a stop codon. The percentage of truncating mutations (64% of all mutations) was higher than that observed in the institute's reference group (44%, P = 0.23) and in the independent reference group (24%, P = 0.002). This study shows that TP53 mutations are common in OSCC of young adult patients; infection with biologically active HPV is rare. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Molecular Characterization of TP53 Gene in Human Populations Exposed to Low-Dose Ionizing Radiation

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Igor Brasil-Costa

2013-01-01

Full Text Available Ionizing radiation, such as that emitted by uranium, may cause mutations and consequently lead to neoplasia in human cells. The TP53 gene acts to maintain genomic integrity and constitutes an important biomarker of susceptibility. The present study investigated the main alterations observed in exons 4, 5, 6, 7, and 8 of the TP53 gene and adjacent introns in Amazonian populations exposed to radioactivity. Samples were collected from 163 individuals. Occurrence of the following alterations was observed: (i a missense exchange in exon 4 (Arg72Pro; (ii 2 synonymous exchanges, 1 in exon 5 (His179His, and another in exon 6 (Arg213Arg; (iii 4 intronic exchanges, 3 in intron 7 (C → T at position 13.436; C → T at position 13.491; T → G at position 13.511 and 1 in intron 8 (T → G at position 13.958. Alteration of codon 72 was found to be an important risk factor for cancer development (P=0.024; OR=6.48; CI: 1.29–32.64 when adjusted for age and smoking. Thus, TP53 gene may be an important biomarker for carcinogenesis susceptibility in human populations exposed to ionizing radiation.

Long-term durum wheat monoculture: modelling and future projection

Directory of Open Access Journals (Sweden)

Ettore Bernardoni

2012-03-01

Full Text Available The potential effects of future climate change on grain production of a winter durum wheat cropping system were investigated. Based on future climate change projections, derived from a statistical downscaling process applied to the HadCM3 general circulation model and referred to two IPCC scenarios (A2 and B1, the response on yield and aboveground biomass (AGB and the variation in total organic carbon (TOC were explored. The software used in this work is an hybrid dynamic simulation model able to simulate, under different pedoclimatic conditions, the processes involved in cropping system such as crop growth and development, water and nitrogen balance. It implements different approaches in order to ensure accurate simulation of the mainprocess related to soil-crop-atmosphere continuum.The model was calibrated using soil data, crop yield, AGB and phenology coming from a long-term experiment, located in Apulia region. The calibration was performed using data collected in the period 1978–1990; validation was carried out on the 1991–2009 data. Phenology simulation was sufficiently accurate, showing some limitation only in predicting the physiological maturity. Yields and AGBs were predicted with an acceptable accuracy during both calibration and validation. CRM resulted always close to optimum value, EF in every case scored positive value, the value of index r2 was good, although in some cases values lower than 0.6 were calculated. Slope of the linear regression equation between measured and simulated values was always close to 1, indicating an overall good performance of the model. Both future climate scenarios led to a general increase in yields but a slightly decrease in AGB values. Data showed variations in the total production and yield among the different periods due to the climate variation. TOC evolution suggests that the combination of temperature and precipitation is the main factor affecting TOC variation under future scenarios

Nuclear reactions in AGB nucleosynthesis: the 19F(α, p22Ne at energies of astrophysical relevance

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D’Agata G.

2017-01-01

Full Text Available The abundance of 19F in the universe is strictly related to standard and extra-mixing processes taking place inside AGB-stars, that are considered to be the most important sites for its production. Nevertheless the way in which it is destroyed is far from being well understood. For this reason we studied the 19F(α,p22Ne reaction, that is supposed to be the main destruction channel in the Helium-rich part of the star. In this experiment, the reaction has been studied in the energy range of relevance for astrophysics (0÷1 MeV via the Trojan Horse Method (THM, using the three-body reaction 6Li(19F,p22Ned.

Oropharyngeal Squamous Cell Carcinoma Treated With Radiotherapy or Radiochemotherapy: Prognostic Role of TP53 and HPV Status

International Nuclear Information System (INIS)

Fallai, Carlo; Perrone, Federica; Licitra, Lisa; Pilotti, Silvana; Locati, Laura; Bossi, Paolo; Orlandi, Ester; Palazzi, Mauro; Olmi, Patrizia

2009-01-01

Purpose: To study the prognostic value of the TP53 mutation and human papilloma virus (HPV) status in oropharyngeal squamous cell carcinoma (OPSCC). Methods and materials: The TP53 mutation and HPV status were analyzed in 78 cases of locoregionally advanced OPSCC. The possible correlation of these factors with locoregiownal control, relapse-free survival, disease-specific survival, and overall survival (OS) was also investigated. Results: Of these 78 cases, 22 had disruptive and 22 had non-disruptive (silent) TP53 mutations; the remaining 34 cases had wild-type (WT) TP53. HPV 16 DNA was found in 9 cases (11%), but all HPV-positive (HPV+) cases carried a functional p53 protein, except for 1 case that had a silent mutation. HPV+ patients fared better than HPV-negative (HPV-) patients in terms of all survival parameters, with highly statistically significant differences between the groups. Specifically, no distant metastases were observed in the HPV+ patients, whereas they occurred in 17% of the HPV- patients. However, no difference was observed between the WT TP53 and mutation group, even when this was analyzed in terms of disruptive and non-disruptive mutations. Regardless, treatment with chemotherapy nearly doubled the 5-year OS rates, both in the mutation (42% vs. 22%) and WT (30 vs. 16%) group, but only the mutation group showed improvement in all survival parameters. In addition, the second tumor-free 5-year survival rate was 72% in HPV- cases, but no second tumors were observed in HPV+ and WT p53 cases. Conclusions: Patients with HPV+ OPSCC have an excellent prognosis after radiochemotherapy, but cisplatin-based chemotherapy may not confer a satisfactory outcome, especially in WT cases, thereby justifying the additional or alternative use of taxanes and epidermal growth factor receptors inhibitors. Uncommon distant metastases and second tumors in the HPV+ group may be cause for clinicians to review the follow-up policies in these patients.

Transcriptional dissection of melanoma identifies a high-risk subtype underlying TP53 family genes and epigenome deregulation

Science.gov (United States)

Badal, Brateil; Solovyov, Alexander; Di Cecilia, Serena; Chan, Joseph Minhow; Chang, Li-Wei; Iqbal, Ramiz; Aydin, Iraz T.; Rajan, Geena S.; Chen, Chen; Abbate, Franco; Arora, Kshitij S.; Tanne, Antoine; Gruber, Stephen B.; Johnson, Timothy M.; Fullen, Douglas R.; Phelps, Robert; Bhardwaj, Nina; Bernstein, Emily; Ting, David T.; Brunner, Georg; Schadt, Eric E.; Greenbaum, Benjamin D.; Celebi, Julide Tok

2017-01-01

BACKGROUND. Melanoma is a heterogeneous malignancy. We set out to identify the molecular underpinnings of high-risk melanomas, those that are likely to progress rapidly, metastasize, and result in poor outcomes. METHODS. We examined transcriptome changes from benign states to early-, intermediate-, and late-stage tumors using a set of 78 treatment-naive melanocytic tumors consisting of primary melanomas of the skin and benign melanocytic lesions. We utilized a next-generation sequencing platform that enabled a comprehensive analysis of protein-coding and -noncoding RNA transcripts. RESULTS. Gene expression changes unequivocally discriminated between benign and malignant states, and a dual epigenetic and immune signature emerged defining this transition. To our knowledge, we discovered previously unrecognized melanoma subtypes. A high-risk primary melanoma subset was distinguished by a 122-epigenetic gene signature (“epigenetic” cluster) and TP53 family gene deregulation (TP53, TP63, and TP73). This subtype associated with poor overall survival and showed enrichment of cell cycle genes. Noncoding repetitive element transcripts (LINEs, SINEs, and ERVs) that can result in immunostimulatory signals recapitulating a state of “viral mimicry” were significantly repressed. The high-risk subtype and its poor predictive characteristics were validated in several independent cohorts. Additionally, primary melanomas distinguished by specific immune signatures (“immune” clusters) were identified. CONCLUSION. The TP53 family of genes and genes regulating the epigenetic machinery demonstrate strong prognostic and biological relevance during progression of early disease. Gene expression profiling of protein-coding and -noncoding RNA transcripts may be a better predictor for disease course in melanoma. This study outlines the transcriptional interplay of the cancer cell’s epigenome with the immune milieu with potential for future therapeutic targeting. FUNDING

BRCA1 and TP53 Gene-Mutations: Family Predisposition and Radioecological Risk of Developing Breast Cancer.

Science.gov (United States)

Apsalikov, Bakytbek; Manambaeva, Zukhra; Ospanov, Erlan; Massabayeva, Meruyert; Zhabagin, Kuantkan; Zhagiparova, Zhanar; Maximov, Vladymir; Voropaeva, Elena; Apsalikov, Kazbek; Belikhina, Tatiana; Abdrahmanov, Ramil; Cherepkova, Elena; Tanatarov, Sayat; Massadykov, Adilzhan; Urazalina, Naylia

2016-01-01

Frequencies of polymorphisms of genes BRCA1 and TP53 in breast cancer (BC) patients with a BC family history and radiation history were assessed and compared in the Semey region of Kazakhstan. The study included 60 women directly irradiated by the activities of the Semipalatinsk test site with a calculated effective equivalent dose of 500 mSv and their first generation descendants (group BC+Her+Exp); 65 women with family BC and absence of radiological history - the effective equivalent dose due to anthropogenic sources not exceeding 50 mSv (group BC+Her-Exp). The comparison group consisted of 65 women patients with breast cancer without family and radiological history (BC-Her-Exp). The control group comprised 60 women without breast cancer and without family and radiological history (nonBC). We carried out the genotyping of the polymorphisms c.2311T>C, c.4308T>C and 5382insC of the BRCA1 gene and rs1042522 of the TP53 gene. The frequency of the polymorphism c.2311T>C was significantly higher in patients of the group BC+Her+Exp than in healthy women, and of the polymorphism 5382insC in BC+Her+Exp compared to all other groups. The frequency of the rs1042522 polymorphism of TP53 was significantly higher in all groups of patients with breast cancer compared with the control group. Differences between groups of women with breast cancer were significant only in BC+Her+Exp vs. BC+Her-Exp. Combinations of polymorphisms of the genes BRCA1 and TP53 predominated in women with a family and radiological history.

Inference for multivariate regression model based on multiply imputed synthetic data generated via posterior predictive sampling

Science.gov (United States)

Moura, Ricardo; Sinha, Bimal; Coelho, Carlos A.

2017-06-01

The recent popularity of the use of synthetic data as a Statistical Disclosure Control technique has enabled the development of several methods of generating and analyzing such data, but almost always relying in asymptotic distributions and in consequence being not adequate for small sample datasets. Thus, a likelihood-based exact inference procedure is derived for the matrix of regression coefficients of the multivariate regression model, for multiply imputed synthetic data generated via Posterior Predictive Sampling. Since it is based in exact distributions this procedure may even be used in small sample datasets. Simulation studies compare the results obtained from the proposed exact inferential procedure with the results obtained from an adaptation of Reiters combination rule to multiply imputed synthetic datasets and an application to the 2000 Current Population Survey is discussed.

The AGB star nucleosynthesis in the light of the recent {sup 17}O(p,α){sup 14}N and {sup 18}O(p,α){sup 15}N reaction rate determinations

Energy Technology Data Exchange (ETDEWEB)

Palmerini, S.; Sergi, M. L.; La Cognata, M.; Pizzone, R. G. [INFN-Laboratori Nazionali del Sud, Catania (Italy); Lamia, L. [Dipartimento di Fisica e Astronomia, Universitá degli Studi di Catania (Italy); Spitaleri, C. [INFN-Laboratori Nazionali del Sud, Catania, Italy and Dipartimento di Fisica e Astronomia, Universitá degli Studi di Catania (Italy)

2015-02-24

Presolar grains form in the cold and dusty envelopes of Asymptotic Giant Branch (AGB) stars. These solides, once that have been ejected by stellar winds, come to us as inclusions in meteorites providing invaluable benchmarks and constraints for our knowledge of low temeperature H-burning in stars. The Trojan Horse Method (THM) has been used to investigate the low-energy cross sections of the {sup 17}O(p,α){sup 14}N and {sup 18}O(p,α){sup 15}N reactions. Moreover, the strength of the 65 keV resonance in the {sup 17}O(p,α){sup 14}N reaction, measured by means of the THM, has been used to renormalize the corresponding resonance strength in the {sup 17}O+p radiative capture channel. The new estimates of the reaction rates have been introduced into calculations of AGB star nucleosynthesis and the results have been compared with geochemical analysis of 'presolar' grains to determine their impact on astrophysical environments.

Investigation of steam oxidation behaviour of TP347H FG Part 2: Exposure at 91 bar

DEFF Research Database (Denmark)

Jianmin, J; Montgomery, Melanie; Larsen, OH

2005-01-01

Tube specimens of TP347FG were exposed in a test superheater loop in a biomass plant in Denmark. The specimens were exposed to surface metal temperatures in the range of 455-568C, steam pressure of 91 bar and exposure duration of 3500 and 8700 hours. The oxide thickness and morphology was investi......Tube specimens of TP347FG were exposed in a test superheater loop in a biomass plant in Denmark. The specimens were exposed to surface metal temperatures in the range of 455-568C, steam pressure of 91 bar and exposure duration of 3500 and 8700 hours. The oxide thickness and morphology...

Biology of the temperate Streptococcus thermophilus bacteriophage TP-J34 and physical characterization of the phage genome

International Nuclear Information System (INIS)

Neve, Horst; Freudenberg, Wiebke; Diestel-Feddersen, Frederike; Ehlert, Regina; Heller, Knut J.

2003-01-01

The temperate Streptococcus thermophilus bacteriophage TP-J34 was identified in the lysogenic host strain J34. The majority of phage particles produced upon induction was defective and noninfectious, consisting of DNA-filled heads lacking tails. A physical map (45.6 kb) was established. Analysis of minor restriction bands of the DNA isolated from phage particles as well as the analysis of the protein pattern indicated that phage TP-J34 is a pac-type phage. This was confirmed by immunoelectron microscopy using antisera raised against virulent cos- and pac-type S. thermophilus phages. The lysogenic host J34 but not its noninducible derivate J34-12 contained phage DNA in the nonintegrated state and exhibited autolysis at elevated temperatures. Prophage-carrying strains grew homogeneously while 16 of 20 prophage-cured derivatives aggregated and sedimented rapidly. When phage TP-J34 was propagated lytically on a prophage-cured host strain, a 2.7-kb site-specific deletion occurred in the phage genome. This deletion was also identified in the prophage DNAs of relysogenized strains

Assessment of Above-Ground Biomass of Borneo Forests through a New Data-Fusion Approach Combining Two Pan-Tropical Biomass Maps

Directory of Open Access Journals (Sweden)

Andreas Langner

2015-08-01

Full Text Available This study investigates how two existing pan-tropical above-ground biomass (AGB maps (Saatchi 2011, Baccini 2012 can be combined to derive forest ecosystem specific carbon estimates. Several data-fusion models which combine these AGB maps according to their local correlations with independent datasets such as the spectral bands of SPOT VEGETATION imagery are analyzed. Indeed these spectral bands convey information about vegetation type and structure which can be related to biomass values. Our study area is the island of Borneo. The data-fusion models are evaluated against a reference AGB map available for two forest concessions in Sabah. The highest accuracy was achieved by a model which combines the AGB maps according to the mean of the local correlation coefficients calculated over different kernel sizes. Combining the resulting AGB map with a new Borneo land cover map (whose overall accuracy has been estimated at 86.5% leads to average AGB estimates of 279.8 t/ha and 233.1 t/ha for forests and degraded forests respectively. Lowland dipterocarp and mangrove forests have the highest and lowest AGB values (305.8 t/ha and 136.5 t/ha respectively. The AGB of all natural forests amounts to 10.8 Gt mainly stemming from lowland dipterocarp (66.4%, upper dipterocarp (10.9% and peat swamp forests (10.2%. Degraded forests account for another 2.1 Gt of AGB. One main advantage of our approach is that, once the best fitting data-fusion model is selected, no further AGB reference dataset is required for implementing the data-fusion process. Furthermore, the local harmonization of AGB datasets leads to more spatially precise maps. This approach can easily be extended to other areas in Southeast Asia which are dominated by lowland dipterocarp forest, and can be repeated when newer or more accurate AGB maps become available.

The Tp0684 (MglB-2 Lipoprotein of Treponema pallidum: A Glucose-Binding Protein with Divergent Topology.

Directory of Open Access Journals (Sweden)

Chad A Brautigam

Full Text Available Treponema pallidum, the bacterium that causes syphilis, is an obligate human parasite. As such, it must acquire energy, in the form of carbon sources, from the host. There is ample evidence that the principal source of energy for this spirochete is D-glucose acquired from its environment, likely via an ABC transporter. Further, there is genetic evidence of a D-glucose chemotaxis system in T. pallidum. Both of these processes may be dependent on a single lipidated chemoreceptor: Tp0684, also called TpMglB-2 for its sequence homology to MglB of Escherichia coli. To broaden our understanding of this potentially vital protein, we determined a 2.05-Å X-ray crystal structure of a soluble form of the recombinant protein. Like its namesake, TpMglB-2 adopts a bilobed fold that is similar to that of the ligand-binding proteins (LBPs of other ABC transporters. However, the protein has an unusual, circularly permuted topology. This feature prompted a series of biophysical studies that examined whether the protein's topological distinctiveness affected its putative chemoreceptor functions. Differential scanning fluorimetry and isothermal titration calorimetry were used to confirm that the protein bound D-glucose in a cleft between its two lobes. Additionally, analytical ultracentrifugation was employed to reveal that D-glucose binding is accompanied by a significant conformational change. TpMglB-2 thus appears to be fully functional in vitro, and given the probable central importance of the protein to T. pallidum's physiology, our results have implications for the viability and pathogenicity of this obligate human pathogen.

The Tp0684 (MglB-2) Lipoprotein of Treponema pallidum: A Glucose-Binding Protein with Divergent Topology.

Science.gov (United States)

Brautigam, Chad A; Deka, Ranjit K; Liu, Wei Z; Norgard, Michael V

2016-01-01

Treponema pallidum, the bacterium that causes syphilis, is an obligate human parasite. As such, it must acquire energy, in the form of carbon sources, from the host. There is ample evidence that the principal source of energy for this spirochete is D-glucose acquired from its environment, likely via an ABC transporter. Further, there is genetic evidence of a D-glucose chemotaxis system in T. pallidum. Both of these processes may be dependent on a single lipidated chemoreceptor: Tp0684, also called TpMglB-2 for its sequence homology to MglB of Escherichia coli. To broaden our understanding of this potentially vital protein, we determined a 2.05-Å X-ray crystal structure of a soluble form of the recombinant protein. Like its namesake, TpMglB-2 adopts a bilobed fold that is similar to that of the ligand-binding proteins (LBPs) of other ABC transporters. However, the protein has an unusual, circularly permuted topology. This feature prompted a series of biophysical studies that examined whether the protein's topological distinctiveness affected its putative chemoreceptor functions. Differential scanning fluorimetry and isothermal titration calorimetry were used to confirm that the protein bound D-glucose in a cleft between its two lobes. Additionally, analytical ultracentrifugation was employed to reveal that D-glucose binding is accompanied by a significant conformational change. TpMglB-2 thus appears to be fully functional in vitro, and given the probable central importance of the protein to T. pallidum's physiology, our results have implications for the viability and pathogenicity of this obligate human pathogen.

The prognostic values of the expression of Vimentin, TP53, and Podoplanin in patients with cervical cancer.

Science.gov (United States)

Lin, Jiaying; Lu, Jiaqi; Wang, Chao; Xue, Xiaohong

2017-01-01

Epithelial-mesenchymal transition (EMT), TP53, and Podoplanin have been implicated in the tumorigenesis and metastasis of human cancers. Nevertheless, the clinical significance of these markers in cancer patients is still not clear. In this study, we sought to determine the prognostic values of Vimentin, TP53, and Podoplanin in patients with cervical cancer. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis were performed to determine the messenger RNA and protein expression levels of Vimentin, TP53, and Podoplanin, respectively, in cervical squamous cell carcinoma and adjacent normal cervical tissues. Additionally, the expression levels of Podoplanin were also measured in 130 cervical cancer patients (FIGO stages Ib1-IIa2) using immunohistochemistry (IHC) staining. The mRNA expression levels of Vimentin, TP53, and Podoplanin were considerably elevated in cervical cancer tissues, compared with those in the adjacent normal cervical tissues. Additionally, the protein expression levels of Vimentin were closely correlated with the age of onset (P = 0.007), lymph node metastasis (P = 0.007), lymphatic invasion (P = 0.024), disease recurrence (P < 0.001), and the clinical prognosis of patients with cervical cancer (P < 0.001). Our multivariate analysis also suggests that Vimentin is an independent marker for survival in cervical cancer patients. Furthermore, the expression levels of Vimentin are negatively correlated with the proliferation marker Ki67 expression. Our data show that Vimentin can serve as an independent prognostic marker for cervical cancer patients with primary surgery. Registration number ChiCTR-TRC-06000236 Registered 15 December 2006.

Natural - synthetic - artificial!

DEFF Research Database (Denmark)

Nielsen, Peter E

2010-01-01

The terms "natural," "synthetic" and "artificial" are discussed in relation to synthetic and artificial chromosomes and genomes, synthetic and artificial cells and artificial life.......The terms "natural," "synthetic" and "artificial" are discussed in relation to synthetic and artificial chromosomes and genomes, synthetic and artificial cells and artificial life....

Peak-Temperature (Tp) estimates with Raman micro-spectroscopy on carbonaceous material (RSCM) as a tool for distinguishing tectometamorphic regimes in the Tauern Window (Eastern Alps, Austria)

Science.gov (United States)

Scharf, A.; Ziemann, M. A.; Handy, M. R.

2012-04-01

Raman micro-spectroscopy of CM in 201 samples from the eastern part of the Tauern Window reveal the overprinting of HP subduction metamorphism, post-nappe HT metamorphism and late orogenic crustal attenuation during exhumation. The following patterns of our CM data lend insight into this evolution, especially when considered in the context of the distribution of mineral parageneses, radiometric ages and structures in the Tauern Window: (1) a continuous increase in Tp (330-500°C) across nappe boundaries between two oceanic units (Valais, Piemont) in the NE part of the Tauern Window indicates that temperatures equilibrated after accretion and nappe stacking. The Tp gradient preserved in this area is ca. 10°C/km; (2) a higher Tp gradient (20-25°C/km) in the footwall of a major top-SE extensional shear zone affecting the same units at the E end of the Tauern Window reveals that the previously equilibrated Tp gradient was attenuated during doming and exhumation; (3) identical Tp estimates (500°C) -within error and for a given calibration (ref. below) - are recorded at the top and bottom of a moderately E-dipping basement nappe (Storz Nappe) within a foreland-dipping duplex (the Venediger Nappe Complex, VNC) forming the basement core of the Tauern Window. The Tp value at the top of this nappe occurs at the base of the attenuated Tp gradient described in (2), whereas the Tp at the bottom of the nappe is typical for high Tp values (530-640°C) in the core of the duplex that is exposed in a post-nappe dome (Hochalm) in the SE part of the Tauern Window. We intepret Tp values in the central part of the Tauern Window (530°C) that contain relict HP assemblages and are unaffected by doming as the maximum temperature of subduction-related metamorphism. Existing radiometric data in the area as well as from related units in other parts of the Tauern Window indicate that the thermal peak of HP metamorphism occurred at 38-40 Ma (Kurz et al. 2008, refs therein), followed by HT

A synthetic study on constaining a 2D density-dependent saltwater intrusion model using electrical imaging data

DEFF Research Database (Denmark)

Antonsson, Arni Valur; Nguyen, Frederic; Engesgaard, Peter Knudegaard

of the synthetic model, basically a salinity distribution in the coastal aquifer, was converted to resistivity distribution by assuming a certain petrophysical relation between water salinity and electrical conductivity. The obtained resistivity distribution was then used when electrical data acquisition...... was simulated. By applying an advanced inversion approach, electrical images of resistivity were obtained and based on the assumed petrophysical model the salinity distribution was derived. A number of different intrusion simulations were conducted with the aim of assessing the applicability of the method under....... Compared to conventional methods, which only give (few) point information, electrical images can give data over large spatial distances but that can be of great value for groundwater modeling purposes. The aim of this study is to investigate in a synthetic way, the applicability of using electrical images...

THE RGB AND AGB STAR NUCLEOSYNTHESIS IN LIGHT OF THE RECENT {sup 17}O(p, {alpha}){sup 14}N AND {sup 18}O(p, {alpha}){sup 15}N REACTION-RATE DETERMINATIONS

Energy Technology Data Exchange (ETDEWEB)

Palmerini, S.; Sergi, M. L.; La Cognata, M.; Pizzone, R. G.; Spitaleri, C. [INFN-Laboratori Nazionali del Sud, Catania (Italy); Lamia, L. [Dipartimento di Fisica e Astronomia, Universita di Catania, Catania (Italy)

2013-02-20

In recent years, the Trojan Horse Method (THM) has been used to investigate the low-energy cross sections of proton-induced reactions on A = 17 and A = 18 oxygen isotopes, overcoming extrapolation procedures and enhancement effects due to electron screening. In particular, the strengths of the 20 keV and 65 keV resonances in the {sup 18}O(p, {alpha}){sup 15}N and {sup 17}O(p, {alpha}){sup 14}N reactions, respectively, have been extracted, as well as the contribution of the tail of the broad 656 keV resonance in the {sup 18}O(p, {alpha}){sup 15}N reaction inside the Gamow window. The strength of the 65 keV resonance in the {sup 17}O(p, {alpha}){sup 14}N reaction, measured by means of the THM, has been used to renormalize the corresponding resonance strength in the {sup 17}O + p radiative capture channel. As a result, more accurate reaction rates for the {sup 18}O(p, {alpha}){sup 15}N, {sup 17}O(p, {alpha}){sup 14}N, and {sup 17}O(p, {gamma}){sup 18}F processes have been deduced, devoid of systematic errors due to extrapolation or the electron screening effect. Such rates have been introduced into state-of-the-art red giant branch and asymptotic giant branch (AGB) models for proton-capture nucleosynthesis coupled with extra-mixing episodes. The predicted abundances have been compared with isotopic compositions provided by geochemical analysis of presolar grains. As a result, an improved agreement is found between the models and the isotopic mix of oxide grains of AGB origins, whose composition is the signature of low-temperature proton-capture nucleosynthesis. The low {sup 14}N/{sup 15}N found in SiC grains cannot be explained by the revised nuclear reaction rates and remains a serious problem that has not been satisfactorily addressed.

A Canine Arthroscopic Anterior Cruciate Ligament Reconstruction Model for Study of Synthetic Augmentation of Tendon Allografts.

Science.gov (United States)

Cook, James L; Smith, Pat; Stannard, James P; Pfeiffer, Ferris; Kuroki, Keiichi; Bozynski, Chantelle C; Cook, Cristi

2017-09-01

Novel graft types, fixation methods, and means for augmenting anterior cruciate ligament (ACL) reconstructions require preclinical validation prior to safe and effective clinical application. The objective of this study was to describe and validate a translational canine model for all-inside arthroscopic complete ACL reconstruction using a quadriceps tendon allograft with internal brace (QTIB). With institutional approval, adult research hounds underwent complete transection of the native ACL followed by all-inside ACL reconstruction using the novel QTIB construct with suspensory fixation ( n  = 10). Contralateral knees were used as nonoperated controls ( n  = 10). Dogs were assessed over a 6-month period using functional, diagnostic imaging, gross, biomechanical, and histologic outcome measures required for preclinical animal models. Study results suggest that the novel QTIB construct used for complete ACL reconstruction can provide sustained knee stability and function without the development of premature osteoarthritis in a rigorous and valid preclinical model. The unique configuration of the QTIB construct-the combination of a tendon allograft with a synthetic suture tape internal brace-allowed for an effective biologic-synthetic load-sharing ACL construct. It prevented early failure, allowed for direct, four-zone graft-to-bone healing, and functional graft remodeling while avoiding problems noted with use of all-synthetic grafts. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Programming languages for synthetic biology.

Science.gov (United States)

Umesh, P; Naveen, F; Rao, Chanchala Uma Maheswara; Nair, Achuthsankar S

2010-12-01

In the backdrop of accelerated efforts for creating synthetic organisms, the nature and scope of an ideal programming language for scripting synthetic organism in-silico has been receiving increasing attention. A few programming languages for synthetic biology capable of defining, constructing, networking, editing and delivering genome scale models of cellular processes have been recently attempted. All these represent important points in a spectrum of possibilities. This paper introduces Kera, a state of the art programming language for synthetic biology which is arguably ahead of similar languages or tools such as GEC, Antimony and GenoCAD. Kera is a full-fledged object oriented programming language which is tempered by biopart rule library named Samhita which captures the knowledge regarding the interaction of genome components and catalytic molecules. Prominent feature of the language are demonstrated through a toy example and the road map for the future development of Kera is also presented.

The evaluation of different forest structural indices to predict the stand aboveground biomass of even-aged Scotch pine (Pinus sylvestris L.) forests in Kunduz, Northern Turkey.

Science.gov (United States)

Ercanli, İlker; Kahriman, Aydın

2015-03-01

We assessed the effect of stand structural diversity, including the Shannon, improved Shannon, Simpson, McIntosh, Margelef, and Berger-Parker indices, on stand aboveground biomass (AGB) and developed statistical prediction models for the stand AGB values, including stand structural diversity indices and some stand attributes. The AGB prediction model, including only stand attributes, accounted for 85 % of the total variance in AGB (R (2)) with an Akaike's information criterion (AIC) of 807.2407, Bayesian information criterion (BIC) of 809.5397, Schwarz Bayesian criterion (SBC) of 818.0426, and root mean square error (RMSE) of 38.529 Mg. After inclusion of the stand structural diversity into the model structure, considerable improvement was observed in statistical accuracy, including 97.5 % of the total variance in AGB, with an AIC of 614.1819, BIC of 617.1242, SBC of 633.0853, and RMSE of 15.8153 Mg. The predictive fitting results indicate that some indices describing the stand structural diversity can be employed as significant independent variables to predict the AGB production of the Scotch pine stand. Further, including the stand diversity indices in the AGB prediction model with the stand attributes provided important predictive contributions in estimating the total variance in AGB.

DNA methylation patterns of candidate genes regulated by thymine DNA glycosylase in patients with TP53 germline mutations

Energy Technology Data Exchange (ETDEWEB)

Fortes, F.P. [CIPE, Laboratrio de Oncogentica Molecular, A.C. Camargo Cancer Center, São Paulo, SP (Brazil); Kuasne, H. [CIPE, Laboratrio NeoGene, A.C. Camargo Cancer Center, São Paulo, SP (Brazil); Departamento de Urologia, Faculdade de Medicina, Universidade Estadual Paulista, Botucatu, SP (Brazil); Marchi, F.A. [CIPE, Laboratrio NeoGene, A.C. Camargo Cancer Center, São Paulo, SP (Brazil); Programa Inter-Institucional em Bioinformtica, Instituto de Matemtica e Estatstica, Universidade So Paulo, So Paulo, SP (Brazil); Miranda, P.M. [CIPE, Laboratrio NeoGene, A.C. Camargo Cancer Center, São Paulo, SP (Brazil); Rogatto, S.R. [CIPE, Laboratrio NeoGene, A.C. Camargo Cancer Center, São Paulo, SP (Brazil); Departamento de Urologia, Faculdade de Medicina, Universidade Estadual Paulista, Botucatu, SP (Brazil); Achatz, M.I. [CIPE, Laboratrio de Oncogentica Molecular, A.C. Camargo Cancer Center, São Paulo, SP (Brazil); Departamento de Oncogentica, A.C. Camargo Cancer Center, So Paulo, SP (Brazil)

2015-04-28

Li-Fraumeni syndrome (LFS) is a rare, autosomal dominant, hereditary cancer predisposition disorder. In Brazil, the p.R337H TP53 founder mutation causes the variant form of LFS, Li-Fraumeni-like syndrome. The occurrence of cancer and age of disease onset are known to vary, even in patients carrying the same mutation, and several mechanisms such as genetic and epigenetic alterations may be involved in this variability. However, the extent of involvement of such events has not been clarified. It is well established that p53 regulates several pathways, including the thymine DNA glycosylase (TDG) pathway, which regulates the DNA methylation of several genes. This study aimed to identify the DNA methylation pattern of genes potentially related to the TDG pathway (CDKN2A, FOXA1, HOXD8, OCT4, SOX2, and SOX17) in 30 patients with germline TP53mutations, 10 patients with wild-type TP53, and 10 healthy individuals. We also evaluated TDG expression in patients with adrenocortical tumors (ADR) with and without the p.R337H TP53 mutation. Gene methylation patterns of peripheral blood DNA samples assessed by pyrosequencing revealed no significant differences between the three groups. However, increased TDG expression was observed by quantitative reverse transcription PCR in p.R337H carriers with ADR. Considering the rarity of this phenotype and the relevance of these findings, further studies using a larger sample set are necessary to confirm our results.

Origin of the solar system s-process abundances

International Nuclear Information System (INIS)

Malaney, R.A.; Boothroyd, A.I.

1987-01-01

In the search for the origin of the solar system s-process abundances much attention has been focused on the intershell zones of thermally pulsing asymptotic giant branch (AGB) stars. It has recently been suggested that, relative to the poor fits obtained from intermediate-mass AGB models, low-mass AGB models may result in much better fits to the observed solar system abundances. This suggestion was motivated by the high intershell base temperatures indicated by recent low-mass AGB calculations. Using new data, presented for the peak intershell base temperature in such stars, the s-process enhancements occurring in the intershell zones of low-mass AGB stars are calculated. A nonsolar distribution of s-process abundances is reported for all realistic AGB models studied. Other possible astrophysical sites for the origin of the solar system s-process abundances are discussed. 35 references

Tundra plant above-ground biomass and shrub dominance mapped across the North Slope of Alaska

Science.gov (United States)

Berner, Logan T.; Jantz, Patrick; Tape, Ken D.; Goetz, Scott J.

2018-03-01

Arctic tundra is becoming greener and shrubbier due to recent warming. This is impacting climate feedbacks and wildlife, yet the spatial distribution of plant biomass in tundra ecosystems is uncertain. In this study, we mapped plant and shrub above-ground biomass (AGB; kg m-2) and shrub dominance (%; shrub AGB/plant AGB) across the North Slope of Alaska by linking biomass harvests at 28 field sites with 30 m resolution Landsat satellite imagery. We first developed regression models (p plant AGB (r 2 = 0.79) and shrub AGB (r 2 = 0.82) based on the normalized difference vegetation index (NDVI) derived from imagery acquired by Landsat 5 and 7. We then predicted regional plant and shrub AGB by combining these regression models with a regional Landsat NDVI mosaic built from 1721 summer scenes acquired between 2007 and 2016. Our approach employed a Monte Carlo uncertainty analysis that propagated sampling and sensor calibration errors. We estimated that plant AGB averaged 0.74 (0.60, 0.88) kg m-2 (95% CI) and totaled 112 (91, 135) Tg across the region, with shrub AGB accounting for ~43% of regional plant AGB. The new maps capture landscape variation in plant AGB visible in high resolution satellite and aerial imagery, notably shrubby riparian corridors. Modeled shrub AGB was strongly correlated with field measurements of shrub canopy height at 25 sites (rs  = 0.88) and with a regional map of shrub cover (rs  = 0.76). Modeled plant AGB and shrub dominance were higher in shrub tundra than graminoid tundra and increased between areas with the coldest and warmest summer air temperatures, underscoring the fact that future warming has the potential to greatly increase plant AGB and shrub dominance in this region. These new biomass maps provide a unique source of ecological information for a region undergoing rapid environmental change.

Vínculos observacionais para o processo-S em estrelas gigantes de Bário

Science.gov (United States)

Smiljanic, R. H. S.; Porto de Mello, G. F.; da Silva, L.

2003-08-01

Estrelas de bário são gigantes vermelhas de tipo GK que apresentam excessos atmosféricos dos elementos do processo-s. Tais excessos são esperados em estrelas na fase de pulsos térmicos do AGB (TP-AGB). As estrelas de bário são, no entanto, menos massivas e menos luminosas que as estrelas do AGB, assim, não poderiam ter se auto-enriquecido. Seu enriquecimento teria origem em uma estrela companheira, inicialmente mais massiva, que evolui pelo TP-AGB, se auto-enriquece com os elementos do processo-s e transfere material contaminado para a atmosfera da atual estrela de bário. A companheira evolui então para anã branca deixando de ser observada diretamente. As estrelas de bário são, portanto, úteis como testes observacionais para teorias de nucleossíntese pelo processo-s, convecção e perda de massa. Análises detalhadas de abundância com dados de alta qualidade para estes objetos são ainda escassas na literatura. Neste trabalho construímos modelos de atmosferas e, procedendo a uma análise diferencial, determinamos parâmetros atmosféricos e evolutivos de uma amostra de dez gigantes de bário e quatro normais. Determinamos seus padrões de abundância para Na, Mg, Al, Si, Ca, Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Sr, Y, Zr, Ba, La, Ce, Nd, Sm, Eu e Gd, concluindo que algumas estrelas classificadas na literatura como gigantes de bário são na verdade gigantes normais. Comparamos dois padrões médios de abundância, para estrelas com grandes excessos e estrelas com excessos moderados, com modelos teóricos de enriquecimento pelo processo-s. Os dois grupos de estrelas são ajustados pelos mesmos parâmetros de exposição de nêutrons. Tal resultado sugere que a ocorrência do fenômeno de bário com diferentes intensidades não se deve a diferentes exposições de nêutrons. Discutimos ainda efeitos nucleossintéticos, ligados ao processo-s, sugeridos na literatura para os elementos Cu, Mn, V e Sc.

Analysis of the collar-whisker structure of temperate lactococcal bacteriophage TP901-1

DEFF Research Database (Denmark)

Vegge, Christina Skovgaard; Neve, Horst; Brøndsted, Lone

2006-01-01

Proteins homologous to the protein NPS (neck passage structure) are widespread among lactococcal phages. We investigated the hypothesis that NPS is involved in the infection of phage TP901-1 by analysis of an NPS mutant. NPS was determined to form a collar-whisker complex but was shown to be none...

Synthetic and Empirical Capsicum Annuum Image Dataset

NARCIS (Netherlands)

Barth, R.

2016-01-01

This dataset consists of per-pixel annotated synthetic (10500) and empirical images (50) of Capsicum annuum, also known as sweet or bell pepper, situated in a commercial greenhouse. Furthermore, the source models to generate the synthetic images are included. The aim of the datasets are to

Wall modeled large eddy simulations of complex high Reynolds number flows with synthetic inlet turbulence

International Nuclear Information System (INIS)

Patil, Sunil; Tafti, Danesh

2012-01-01

Highlights: ► Large eddy simulation. ► Wall layer modeling. ► Synthetic inlet turbulence. ► Swirl flows. - Abstract: Large eddy simulations of complex high Reynolds number flows are carried out with the near wall region being modeled with a zonal two layer model. A novel formulation for solving the turbulent boundary layer equation for the effective tangential velocity in a generalized co-ordinate system is presented and applied in the near wall zonal treatment. This formulation reduces the computational time in the inner layer significantly compared to the conventional two layer formulations present in the literature and is most suitable for complex geometries involving body fitted structured and unstructured meshes. The cost effectiveness and accuracy of the proposed wall model, used with the synthetic eddy method (SEM) to generate inlet turbulence, is investigated in turbulent channel flow, flow over a backward facing step, and confined swirling flows at moderately high Reynolds numbers. Predictions are compared with available DNS, experimental LDV data, as well as wall resolved LES. In all cases, there is at least an order of magnitude reduction in computational cost with no significant loss in prediction accuracy.

Monitoring coastal marshes biomass with CASI: a comparison of parametric and non-parametric models

Science.gov (United States)

Mo, Y.; Kearney, M.

2017-12-01

Coastal marshes are important carbon sinks that face multiple natural and anthropogenic stresses. Optical remote sensing is a powerful tool for closely monitoring the biomass of coastal marshes. However, application of hyperspectral sensors on assessing the biomass of diverse coastal marsh ecosystems is limited. This study samples spectral and biophysical data from coastal freshwater, intermediate, brackish, and saline marshes in Louisiana, and develops parametric and non-parametric models for using the Compact Airborne Spectrographic Imager (CASI) to retrieve the marshes' biomass. Linear models and random forest models are developed from simulated CASI data (48 bands, 380-1050 nm, bandwidth 14 nm). Linear models are also developed using narrowband vegetation indices computed from all possible band combinations from the blue, red, and near infrared wavelengths. It is found that the linear models derived from the optimal narrowband vegetation indices provide strong predictions for the marshes' Leaf Area Index (LAI; R2 > 0.74 for ARVI), but not for their Aboveground Green Biomass (AGB; R2 > 0.25). The linear models derived from the simulated CASI data strongly predict the marshes' LAI (R2 = 0.93) and AGB (R2 = 0.71) and have 27 and 30 bands/variables in the final models through stepwise regression, respectively. The random forest models derived from the simulated CASI data also strongly predict the marshes' LAI and AGB (R2 = 0.91 and 0.84, respectively), where the most important variables for predicting LAI are near infrared bands at 784 and 756 nm and for predicting ABG are red bands at 684 and 670 nm. In sum, the random forest model is preferable for assessing coastal marsh biomass using CASI data as it offers high R2 for both LAI and AGB. The superior performance of the random forest model is likely to due to that it fully utilizes the full-spectrum data and makes no assumption of the approximate normality of the sampling population. This study offers solutions

Synthetic Domain Theory and Models of Linear Abadi & Plotkin Logic

DEFF Research Database (Denmark)

Møgelberg, Rasmus Ejlers; Birkedal, Lars; Rosolini, Guiseppe

2008-01-01

Plotkin suggested using a polymorphic dual intuitionistic/linear type theory (PILLY) as a metalanguage for parametric polymorphism and recursion. In recent work the first two authors and R.L. Petersen have defined a notion of parametric LAPL-structure, which are models of PILLY, in which one can...... reason using parametricity and, for example, solve a large class of domain equations, as suggested by Plotkin.In this paper, we show how an interpretation of a strict version of Bierman, Pitts and Russo's language Lily into synthetic domain theory presented by Simpson and Rosolini gives rise...... to a parametric LAPL-structure. This adds to the evidence that the notion of LAPL-structure is a general notion, suitable for treating many different parametric models, and it provides formal proofs of consequences of parametricity expected to hold for the interpretation. Finally, we show how these results...

TinkerCell: modular CAD tool for synthetic biology

Science.gov (United States)

Chandran, Deepak; Bergmann, Frank T; Sauro, Herbert M

2009-01-01

Background Synthetic biology brings together concepts and techniques from engineering and biology. In this field, computer-aided design (CAD) is necessary in order to bridge the gap between computational modeling and biological data. Using a CAD application, it would be possible to construct models using available biological "parts" and directly generate the DNA sequence that represents the model, thus increasing the efficiency of design and construction of synthetic networks. Results An application named TinkerCell has been developed in order to serve as a CAD tool for synthetic biology. TinkerCell is a visual modeling tool that supports a hierarchy of biological parts. Each part in this hierarchy consists of a set of attributes that define the part, such as sequence or rate constants. Models that are constructed using these parts can be analyzed using various third-party C and Python programs that are hosted by TinkerCell via an extensive C and Python application programming interface (API). TinkerCell supports the notion of a module, which are networks with interfaces. Such modules can be connected to each other, forming larger modular networks. TinkerCell is a free and open-source project under the Berkeley Software Distribution license. Downloads, documentation, and tutorials are available at . Conclusion An ideal CAD application for engineering biological systems would provide features such as: building and simulating networks, analyzing robustness of networks, and searching databases for components that meet the design criteria. At the current state of synthetic biology, there are no established methods for measuring robustness or identifying components that fit a design. The same is true for databases of biological parts. TinkerCell's flexible modeling framework allows it to cope with changes in the field. Such changes may involve the way parts are characterized or the way synthetic networks are modeled and analyzed computationally. TinkerCell can readily

TinkerCell: modular CAD tool for synthetic biology

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Bergmann Frank T

2009-10-01

Full Text Available Abstract Background Synthetic biology brings together concepts and techniques from engineering and biology. In this field, computer-aided design (CAD is necessary in order to bridge the gap between computational modeling and biological data. Using a CAD application, it would be possible to construct models using available biological "parts" and directly generate the DNA sequence that represents the model, thus increasing the efficiency of design and construction of synthetic networks. Results An application named TinkerCell has been developed in order to serve as a CAD tool for synthetic biology. TinkerCell is a visual modeling tool that supports a hierarchy of biological parts. Each part in this hierarchy consists of a set of attributes that define the part, such as sequence or rate constants. Models that are constructed using these parts can be analyzed using various third-party C and Python programs that are hosted by TinkerCell via an extensive C and Python application programming interface (API. TinkerCell supports the notion of a module, which are networks with interfaces. Such modules can be connected to each other, forming larger modular networks. TinkerCell is a free and open-source project under the Berkeley Software Distribution license. Downloads, documentation, and tutorials are available at http://www.tinkercell.com. Conclusion An ideal CAD application for engineering biological systems would provide features such as: building and simulating networks, analyzing robustness of networks, and searching databases for components that meet the design criteria. At the current state of synthetic biology, there are no established methods for measuring robustness or identifying components that fit a design. The same is true for databases of biological parts. TinkerCell's flexible modeling framework allows it to cope with changes in the field. Such changes may involve the way parts are characterized or the way synthetic networks are modeled

Evaluation of Above Ground Biomass Estimation Accuracy for Alpine Meadow Based on MODIS Vegetation Indices

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Meng Bao-Ping

2017-01-01

Full Text Available Animal husbandry is the main agricultural type over the Tibetan Plateau, above ground biomass (AGB is very important to monitor the productivity for administration of grassland resources and grazing balance. The MODIS vegetation indices have been successfully used in numerous studies on grassland AGB estimation in the Tibetan Plateau area. However, there are considerable differences of AGB estimation models both in the form of the models and the accuracy of estimation. In this study, field measurements of AGB data at Sangke Town, Gansu Province, China in four years (2013-2016 and MODIS indices (NDVI and EVI are combined to construct AGB estimation models of alpine meadow grassland. The field measured AGB are also used to evaluate feasibility of models developed for large scale in applying to small area. The results show that (1 the differences in biomass were relatively large among the 5 sample areas of alpine meadow grassland in the study area during 2013-2016, with the maximum and minimum biomass values of 3,963 kg DW/ha and 745.5 kg DW/ha, respectively, and mean value of 1,907.7 kg DW/ha; the mean of EVI value range (0.42-0.60 are slightly smaller than the NDVI’s (0.59-0.75; (2 the optimum estimation model of grassland AGB in the study area is the exponential model based on MODIS EVI, with root mean square error of 656.6 kg DW/ha and relative estimation errors (REE of 36.3%; (3 the estimation errors of grassland AGB models previously constructed at different spatial scales (the Tibetan Plateau, the Gannan Prefecture, and Xiahe County are higher than those directly constructed based on the small area of this study by 9.5%–31.7%, with the increase of the modeling study area scales, the REE increasing as well. This study presents an improved monitoring algorithm of alpine natural grassland AGB estimation and provides a clear direction for future improvement of the grassland AGB estimation and grassland productivity from remote sensing

Philosophy of Systems and Synthetic Biology

DEFF Research Database (Denmark)

Green, Sara

2017-01-01

This entry aims to clarify how systems and synthetic biology contribute to and extend discussions within philosophy of science. Unlike fields such as developmental biology or molecular biology, systems and synthetic biology are not easily demarcated by a focus on a specific subject area or level...... of organization. Rather, they are characterized by the development and application of mathematical, computational, and synthetic modeling strategies in response to complex problems and challenges within the life sciences. Proponents of systems and synthetic biology often stress the necessity of a perspective...... that goes beyond the scope of molecular biology and genetic engineering, respectively. With the emphasis on systems and interaction networks, the approaches explicitly engage in one of the oldest philosophical discussions on the relationship between parts and wholes, or between reductionism and holism...

Association of polymorphism in TP53 gene with susceptibility and radiation sensitivity of non-small-cell-lung cancer in Chinese population

International Nuclear Information System (INIS)

Shao Guoguang; Liu Linlin; Xu Chuanjie

2005-01-01

Objective: To study the association of polymorphism in TP53 gene with the susceptibility and radiation sensitivity of non-small-cell-lung cancer (NSCLC) of the population in the North of China. Methods: Using RFLP-PCR assays, TP53 genotypes were detected by amplifying DNA fragments with sequence specific primers and digested by FnuD II enzyme in 88 patients with NSCLC as well as 112 healthy controls. Results: The C/C allele frequency was significantly higher in NSCLC patients than that in the healthy controls (χ 2 =5.65, P=0.017). The C/C genotype frequency was significantly higher in NSCLC patients than that of the healthy controls (χ 2 =9.33, P=0.0023). The risk of C/C homozygotes in NSCLC patients was about 2.7 times against G/G homozygotes with odds ratio of 2.43(95% CI=1.32-4.51). Conclusion: In the population in the North of China, TP53 C/C genotype is closely associated with the susceptibility of NSCLC. There is no significant relationship between the polymorphism in TP53 gene and radiation sensitivity in NSCLC. (authors)

Frequency of Somatic TP53 Mutations in Combination with Known Pathogenic Mutations in Colon Adenocarcinoma, Non–Small Cell Lung Carcinoma, and Gliomas as Identified by Next-Generation Sequencing

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Zahra Shajani-Yi

2018-03-01

Full Text Available The tumor suppressor gene TP53 is the most frequently mutated gene in human cancer. It encodes p53, a DNA-binding transcription factor that regulates multiple genes involved in DNA repair, metabolism, cell cycle arrest, apoptosis, and senescence. TP53 is associated with human cancer by mutations that lead to a loss of wild-type p53 function as well as mutations that confer alternate oncogenic functions that enable them to promote invasion, metastasis, proliferation, and cell survival. Identifying the discrete TP53 mutations in tumor cells may help direct therapies that are more effective. In this study, we identified the frequency of individual TP53 mutations in patients with colon adenocarcinoma (48%, non–small cell lung carcinoma (NSCLC (36%, and glioma/glioblastoma (28% at our institution using next-generation sequencing. We also identified the occurrence of somatic mutations in numerous actionable genes including BRAF, EGFR, KRAS, IDH1, and PIK3CA that occurred concurrently with these TP53 mutations. Of the 480 tumors examined that contained one or more mutations in the TP53 gene, 219 were colon adenocarcinomas, 215 were NSCLCs, and 46 were gliomas/glioblastomas. Among the patients positive for TP53 mutations diagnosed with colon adenocarcinoma, 50% also showed at least one mutation in pathogenic genes of which 14% were BRAF, 33% were KRAS, and 3% were NRAS. Forty-seven percent of NSCLC patients harboring TP53 mutations also had a mutation in at least one actionable pathogenic variant with the following frequencies: BRAF: 4%, EGFR: 10%, KRAS: 28%, and PIK3CA: 4%. Fifty-two percent of patients diagnosed with glioma/glioblastoma with a positive TP53 mutation had at least one concurrent mutation in a known pathogenic gene of which 9% were CDKN2A, 41% were IDH1, and 11% were PIK3CA.

Nuclear Test Depth Determination with Synthetic Modelling: Global Analysis from PNEs to DPRK-2016

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Rozhkov, Mikhail; Stachnik, Joshua; Baker, Ben; Epiphansky, Alexey; Bobrov, Dmitry

2016-04-01

Seismic event depth determination is critical for the event screening process at the International Data Center, CTBTO. A thorough determination of the event depth can be conducted mostly through additional special analysis because the IDC's Event Definition Criteria is based, in particular, on depth estimation uncertainties. This causes a large number of events in the Reviewed Event Bulletin to have depth constrained to the surface making the depth screening criterion not applicable. Further it may result in a heavier workload to manually distinguish between subsurface and deeper crustal events. Since the shape of the first few seconds of signal of very shallow events is very sensitive to the depth phases, cross correlation between observed and theoretic seismograms can provide a basis for the event depth estimation, and so an expansion to the screening process. We applied this approach mostly to events at teleseismic and partially regional distances. The approach was found efficient for the seismic event screening process, with certain caveats related mostly to poorly defined source and receiver crustal models which can shift the depth estimate. An adjustable teleseismic attenuation model (t*) for synthetics was used since this characteristic is not known for most of the rays we studied. We studied a wide set of historical records of nuclear explosions, including so called Peaceful Nuclear Explosions (PNE) with presumably known depths, and recent DPRK nuclear tests. The teleseismic synthetic approach is based on the stationary phase approximation with hudson96 program, and the regional modelling was done with the generalized ray technique by Vlastislav Cerveny modified to account for the complex source topography. The software prototype is designed to be used for the Expert Technical Analysis at the IDC. With this, the design effectively reuses the NDC-in-a-Box code and can be comfortably utilized by the NDC users. The package uses Geotool as a front-end for data

Carbon-enhanced metal-poor stars in SDSS/Segue. II. Comparison of CEMP-star frequencies with binary population-synthesis models

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Lee, Young Sun [Department of Astronomy, New Mexico State University, Las Cruces, NM 88003 (United States); Suda, Takuma [National Astronomical Observatory of Japan, Osawa 2-21-1, Mitaka, Tokyo 181-8588 (Japan); Beers, Timothy C. [National Optical Astronomy Observatory, Tucson, AZ 85719 (United States); Stancliffe, Richard J., E-mail: yslee@nmsu.edu [Argelander-Institut für Astronomie, Auf dem Hügel 71, D-53121 Bonn (Germany)

2014-06-20

We present a comparison of the frequencies of carbon-enhanced metal-poor (CEMP) giant and main-sequence turnoff (MSTO) stars with predictions from binary population-synthesis models involving asymptotic giant-branch (AGB) mass transfer. The giant and MSTO stars are selected from the Sloan Digital Sky Survey and the Sloan Extension for Galactic Understanding and Exploration. We consider two initial mass functions (IMFs)—a Salpeter IMF, and a mass function with a characteristic mass of 10 M {sub ☉}. For giant stars, the comparison indicates a good agreement between the observed CEMP frequencies and the AGB binary model using a Salpeter IMF for [Fe/H] > – 1.5, and a characteristic mass of 10 M {sub ☉} for [Fe/H] < – 2.5. This result suggests that the IMF shifted from high- to low-mass dominated in the early history of the Milky Way, which appears to have occurred at a 'chemical time' between [Fe/H] =–2.5 and [Fe/H] =–1.5. The CEMP frequency for the turnoff stars with [Fe/H] < – 3.0 is much higher than the AGB model prediction from the high-mass IMF, supporting the previous assertion that one or more additional mechanisms, not associated with AGB stars, are required for the production of carbon-rich material below [Fe/H] =–3.0. We also discuss possible effects of first dredge-up and extra mixing in red giants and internal mixing in turnoff stars on the derived CEMP frequencies.

A comparative analysis of extended water cloud model and backscatter modelling for above-ground biomass assessment in Corbett Tiger Reserve

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Kumar, Yogesh; Singh, Sarnam; Chatterjee, R. S.; Trivedi, Mukul

2016-04-01

Forest biomass acts as a backbone in regulating the climate by storing carbon within itself. Thus the assessment of forest biomass is crucial in understanding the dynamics of the environment. Traditionally the destructive methods were adopted for the assessment of biomass which were further advanced to the non-destructive methods. The allometric equations developed by destructive methods were further used in non-destructive methods for the assessment, but they were mostly applied for woody/commercial timber species. However now days Remote Sensing data are primarily used for the biomass geospatial pattern assessment. The Optical Remote Sensing data (Landsat8, LISS III, etc.) are being used very successfully for the estimation of above ground biomass (AGB). However optical data is not suitable for all atmospheric/environmental conditions, because it can't penetrate through clouds and haze. Thus Radar data is one of the alternate possible ways to acquire data in all-weather conditions irrespective of weather and light. The paper examines the potential of ALOS PALSAR L-band dual polarisation data for the estimation of AGB in the Corbett Tiger Reserve (CTR) covering an area of 889 km2. The main focus of this study is to explore the accuracy of Polarimetric Scattering Model (Extended Water Cloud Model (EWCM) with respect to Backscatter model in the assessment of AGB. The parameters of the EWCM were estimated using the decomposition components (Raney Decomposition) and the plot level information. The above ground biomass in the CTR ranges from 9.6 t/ha to 322.6 t/ha.

Plant synthetic biology.

Science.gov (United States)

Liu, Wusheng; Stewart, C Neal

2015-05-01

Plant synthetic biology is an emerging field that combines engineering principles with plant biology toward the design and production of new devices. This emerging field should play an important role in future agriculture for traditional crop improvement, but also in enabling novel bioproduction in plants. In this review we discuss the design cycles of synthetic biology as well as key engineering principles, genetic parts, and computational tools that can be utilized in plant synthetic biology. Some pioneering examples are offered as a demonstration of how synthetic biology can be used to modify plants for specific purposes. These include synthetic sensors, synthetic metabolic pathways, and synthetic genomes. We also speculate about the future of synthetic biology of plants. Copyright © 2015 Elsevier Ltd. All rights reserved.

a Study of the AGB in Local Group Bulge Populations

Science.gov (United States)

Rich, R.

1994-01-01

We propose to survey the bolometric luminosities, colors, and space distribution of the most luminous asymptotic giant branch (AGB) stars in the bulges of M31, M32, and M33. We seek to discover whether the bulges of these galaxies are relatively young, of order 10 Gyr rather than 15 Gyr. We will use WFPC2 and the R, I, and F1042M (1 micron) filters. Knowing that F1042M falls on the first continuum point of M giants, we have shown that we can use 1.04 micron fluxes to reliably calculate bolometric magnitudes for these very red stars. Color information from R and I will permit (1) comparison with Galactic bulge M giants, (2) an estimate of the spread of abundance and (3) increase the accuracy of the bolometric magnitudes. Frames with the damaged HST show signs of resolution to within 3" of the M31 nucleus; Red images with the aberrated HST show a red star cluster associated with the nucleus. Ground-based studies of M32 find an intermediate-age population from spectroscopy and infrared photometry. The repaired HST should resolve stars close to the nuclei of these galaxies. We will measure bolometric luminosity functions to determine if the populations are intermediate age, and attempt to measure the abundance range for stars near the nuclei of these galaxies. If metals have been lost due to winds, theory predicts that we should see a substantial spread of abundances even near the nucleus.

Identification of colorectal cancer patients with tumors carrying the TP53 mutation on the codon 72 proline allele that benefited most from 5-fluorouracil (5-FU) based postoperative chemotherapy

International Nuclear Information System (INIS)

Godai, Ten-i; Sakuma, Yuji; Tsuchiya, Eiju; Kameda, Yoichi; Akaike, Makoto; Miyagi, Yohei; Suda, Tetsuji; Sugano, Nobuhiro; Tsuchida, Kazuhito; Shiozawa, Manabu; Sekiguchi, Hironobu; Sekiyama, Akiko; Yoshihara, Mitsuyo; Matsukuma, Shoichi

2009-01-01

Although postoperative chemotherapy is widely accepted as the standard modality for Dukes' stage C or earlier stage colorectal cancer (CRC) patients, biomarkers to predict those who may benefit from the therapy have not been identified. Previous in vitro and clinical investigations reported that CRC patients with wild-type p53 gene (TP53)-tumors benefit from 5-fluorouracil (5-FU) based chemotherapy, while those with mutated TP53-tumors do not. However, these studies evaluated the mutation-status of TP53 by immunohistochemistry with or without single-strand conformation polymorphism, and the mutation frequency was different from study to study. In addition, the polymorphic status at p53 codon 72, which results in arginine or proline residues (R72P) and is thought to influence the function of the protein significantly, was not examined. To evaluate the significance of the TP53 mutation as a molecular marker to predict the prognosis of CRC patients, especially those who received postoperative chemotherapy, we examined the mutation by direct sequencing from fresh CRC tumors and evaluated the R72P polymorphism of the mutated TP53 by a combined mutant allele- and polymorphic allele-specific polymerase chain reaction (PCR). The TP53 mutation occurred in 147 (70%) of 211 Japanese CRC tumors. The mutation was observed in 93 (63%) tumors on the R72 allele and in 54 (37%) tumors on the P72 allele. Although the alterations to TP53 have no prognostic significance for CRC patients overall, we found that Dukes' stage C CRC patients who did not receive postoperative chemotherapy and carried the mutated TP53-R72 showed significantly longer survival times than those with the mutated TP53-P72 when evaluated by overall survival (p = 0.012). Using a combined mutant allele- and polymorphic allele-specific PCR, we defined the codon 72 polymorphic status of the TP53 mutated allele in Japanese CRC patients. We raised a possibility that Dukes' stage C colorectal cancer

MicroRNA‑663b mediates TAM resistance in breast cancer by modulating TP73 expression.

Science.gov (United States)

Jiang, Hua; Cheng, Lin; Hu, Pan; Liu, Renbin

2018-05-23

Breast cancer is the second leading cause of cancer‑associated mortalities in women. Tamoxifen (TAM) is an endocrine therapy commonly used in the treatment of patients with breast cancer expressing estrogen receptor α. However, treatment often ends in failure due to the emergence of drug resistance. MicroRNAs (miRNAs), a family of small non‑coding RNAs, serve critical roles in the regulation of gene expression and cell events. To date, whether miRNA‑663b could mediate TAM resistance in breast cancer remains unknown. Therefore, the aim of the present study was to investigate the role of miRNA‑663b in TAM resistance in breast cancer. The results demonstrated that miRNA‑663b was upregulated in breast cancer with TAM resistance. Tumor protein 73 (TP73) was a direct target of miRNA‑663b, and was negatively regulated by miRNA‑663b in MCF‑7 cells. Furthermore, it was identified that downregulation of miRNA‑663b inhibited cell proliferation ability and promoted cell apoptosis, resulting in enhanced TAM sensitivity. In addition, these findings suggested that TP73 silencing may have eliminated the effects of miRNA‑663b inhibitor on breast cancer cells. In conclusion, the present study verified a novel molecular link between miRNA‑663b and TP73, and indicated that miRNA‑663b may be a critical therapeutic target in breast cancer.

Effects of external stresses on hot corrosion behavior of stainless steel TP347HFG

International Nuclear Information System (INIS)

Fu, Jiapeng; Zhou, Qulan; Li, Na; Liu, Zhuhan; Liu, Taisheng

2016-01-01

Highlights: • Hot corrosion tests of TP347HFG under different stresses were conducted. • The corrosion resistance was strengthened by the exertion of tensile stresses. • External stresses promoted faster formation of the protective Cr_2O_3 layer. • Specimens under critical stress 40 MPa condition present the best resistance. - Abstract: Hot corrosion experiments of alloy TP347HFG under different stresses were conducted. Corroded specimens were examined by means of corrosion products, morphology and compositional changes in corrosion scales. The corrosion behavior was strongly associated with the formation of oxides layers. The corrosion resistance was strengthened by the external stress. It seemed that the exertion of stresses caused many micro cracks and defects, which acted as faster and easier diffusion paths for Cr atoms to diffuse to the surface, and thus, promote faster formation of the protective Cr_2O_3 oxide layer. Critical stress 40 MPa was found, specimens under which present the best resistance.

Synthetic biology analysed tools for discussion and evaluation

CERN Document Server

2016-01-01

Synthetic biology is a dynamic, young, ambitious, attractive, and heterogeneous scientific discipline. It is constantly developing and changing, which makes societal evaluation of this emerging new science a challenging task, prone to misunderstandings. Synthetic biology is difficult to capture, and confusion arises not only regarding which part of synthetic biology the discussion is about, but also with respect to the underlying concepts in use. This book offers a useful toolbox to approach this complex and fragmented field. It provides a biological access to the discussion using a 'layer' model that describes the connectivity of synthetic or semisynthetic organisms and cells to the realm of natural organisms derived by evolution. Instead of directly reviewing the field as a whole, firstly our book addresses the characteristic features of synthetic biology that are relevant to the societal discussion. Some of these features apply only to parts of synthetic biology, whereas others are relevant to synthetic bi...

Semi-empirical modelling for forest above ground biomass estimation using hybrid and fully PolSAR data

Science.gov (United States)

Tomar, Kiledar S.; Kumar, Shashi; Tolpekin, Valentyn A.; Joshi, Sushil K.

2016-05-01

Forests act as sink of carbon and as a result maintains carbon cycle in atmosphere. Deforestation leads to imbalance in global carbon cycle and changes in climate. Hence estimation of forest biophysical parameter like biomass becomes a necessity. PolSAR has the ability to discriminate the share of scattering element like surface, double bounce and volume scattering in a single SAR resolution cell. Studies have shown that volume scattering is a significant parameter for forest biophysical characterization which mainly occurred from vegetation due to randomly oriented structures. This random orientation of forest structure causes shift in orientation angle of polarization ellipse which ultimately disturbs the radar signature and shows overestimation of volume scattering and underestimation of double bounce scattering after decomposition of fully PolSAR data. Hybrid polarimetry has the advantage of zero POA shift due to rotational symmetry followed by the circular transmission of electromagnetic waves. The prime objective of this study was to extract the potential of Hybrid PolSAR and fully PolSAR data for AGB estimation using Extended Water Cloud model. Validation was performed using field biomass. The study site chosen was Barkot Forest, Uttarakhand, India. To obtain the decomposition components, m-alpha and Yamaguchi decomposition modelling for Hybrid and fully PolSAR data were implied respectively. The RGB composite image for both the decomposition techniques has generated. The contribution of all scattering from each plot for m-alpha and Yamaguchi decomposition modelling were extracted. The R2 value for modelled AGB and field biomass from Hybrid PolSAR and fully PolSAR data were found 0.5127 and 0.4625 respectively. The RMSE for Hybrid and fully PolSAR between modelled AGB and field biomass were 63.156 (t ha-1) and 73.424 (t ha-1) respectively. On the basis of RMSE and R2 value, this study suggests Hybrid PolSAR decomposition modelling to retrieve scattering

Allometric Equations for Aboveground and Belowground Biomass Estimations in an Evergreen Forest in Vietnam.

Science.gov (United States)

Nam, Vu Thanh; van Kuijk, Marijke; Anten, Niels P R

2016-01-01

Allometric regression models are widely used to estimate tropical forest biomass, but balancing model accuracy with efficiency of implementation remains a major challenge. In addition, while numerous models exist for aboveground mass, very few exist for roots. We developed allometric equations for aboveground biomass (AGB) and root biomass (RB) based on 300 (of 45 species) and 40 (of 25 species) sample trees respectively, in an evergreen forest in Vietnam. The biomass estimations from these local models were compared to regional and pan-tropical models. For AGB we also compared local models that distinguish functional types to an aggregated model, to assess the degree of specificity needed in local models. Besides diameter at breast height (DBH) and tree height (H), wood density (WD) was found to be an important parameter in AGB models. Existing pan-tropical models resulted in up to 27% higher estimates of AGB, and overestimated RB by nearly 150%, indicating the greater accuracy of local models at the plot level. Our functional group aggregated local model which combined data for all species, was as accurate in estimating AGB as functional type specific models, indicating that a local aggregated model is the best choice for predicting plot level AGB in tropical forests. Finally our study presents the first allometric biomass models for aboveground and root biomass in forests in Vietnam.

Allometric Equations for Aboveground and Belowground Biomass Estimations in an Evergreen Forest in Vietnam.

Directory of Open Access Journals (Sweden)

Vu Thanh Nam

Full Text Available Allometric regression models are widely used to estimate tropical forest biomass, but balancing model accuracy with efficiency of implementation remains a major challenge. In addition, while numerous models exist for aboveground mass, very few exist for roots. We developed allometric equations for aboveground biomass (AGB and root biomass (RB based on 300 (of 45 species and 40 (of 25 species sample trees respectively, in an evergreen forest in Vietnam. The biomass estimations from these local models were compared to regional and pan-tropical models. For AGB we also compared local models that distinguish functional types to an aggregated model, to assess the degree of specificity needed in local models. Besides diameter at breast height (DBH and tree height (H, wood density (WD was found to be an important parameter in AGB models. Existing pan-tropical models resulted in up to 27% higher estimates of AGB, and overestimated RB by nearly 150%, indicating the greater accuracy of local models at the plot level. Our functional group aggregated local model which combined data for all species, was as accurate in estimating AGB as functional type specific models, indicating that a local aggregated model is the best choice for predicting plot level AGB in tropical forests. Finally our study presents the first allometric biomass models for aboveground and root biomass in forests in Vietnam.

Estimating above-ground biomass on mountain meadows and pastures through remote sensing

Science.gov (United States)

Barrachina, M.; Cristóbal, J.; Tulla, A. F.

2015-06-01

Extensive stock-breeding systems developed in mountain areas like the Pyrenees are crucial for local farming economies and depend largely on above-ground biomass (AGB) in the form of grass produced on meadows and pastureland. In this study, a multiple linear regression analysis technique based on in-situ biomass collection and vegetation and wetness indices derived from Landsat-5 TM data is successfully applied in a mountainous Pyrenees area to model AGB. Temporal thoroughness of the data is ensured by using a large series of images. Results of on-site AGB collection show the importance for AGB models to capture the high interannual and intraseasonal variability that results from both meteorological conditions and farming practices. AGB models yield best results at midsummer and end of summer before mowing operations by farmers, with a mean R2, RMSE and PE for 2008 and 2009 midsummer of 0.76, 95 g m-2 and 27%, respectively; and with a mean R2, RMSE and PE for 2008 and 2009 end of summer of 0.74, 128 g m-2 and 36%, respectively. Although vegetation indices are a priori more related with biomass production, wetness indices play an important role in modeling AGB, being statistically selected more frequently (more than 50%) than other traditional vegetation indexes (around 27%) such as NDVI. This suggests that middle infrared bands are crucial descriptors of AGB. The methodology applied in this work compares favorably with other works in the literature, yielding better results than those works in mountain areas, owing to the ability of the proposed methodology to capture natural and anthropogenic variations in AGB which are the key to increasing AGB modeling accuracy.

Geostatistical estimation of forest biomass in interior Alaska combining Landsat-derived tree cover, sampled airborne lidar and field observations

Science.gov (United States)

Babcock, Chad; Finley, Andrew O.; Andersen, Hans-Erik; Pattison, Robert; Cook, Bruce D.; Morton, Douglas C.; Alonzo, Michael; Nelson, Ross; Gregoire, Timothy; Ene, Liviu; Gobakken, Terje; Næsset, Erik

2018-06-01

The goal of this research was to develop and examine the performance of a geostatistical coregionalization modeling approach for combining field inventory measurements, strip samples of airborne lidar and Landsat-based remote sensing data products to predict aboveground biomass (AGB) in interior Alaska's Tanana Valley. The proposed modeling strategy facilitates pixel-level mapping of AGB density predictions across the entire spatial domain. Additionally, the coregionalization framework allows for statistically sound estimation of total AGB for arbitrary areal units within the study area---a key advance to support diverse management objectives in interior Alaska. This research focuses on appropriate characterization of prediction uncertainty in the form of posterior predictive coverage intervals and standard deviations. Using the framework detailed here, it is possible to quantify estimation uncertainty for any spatial extent, ranging from pixel-level predictions of AGB density to estimates of AGB stocks for the full domain. The lidar-informed coregionalization models consistently outperformed their counterpart lidar-free models in terms of point-level predictive performance and total AGB precision. Additionally, the inclusion of Landsat-derived forest cover as a covariate further improved estimation precision in regions with lower lidar sampling intensity. Our findings also demonstrate that model-based approaches that do not explicitly account for residual spatial dependence can grossly underestimate uncertainty, resulting in falsely precise estimates of AGB. On the other hand, in a geostatistical setting, residual spatial structure can be modeled within a Bayesian hierarchical framework to obtain statistically defensible assessments of uncertainty for AGB estimates.

Association of TP53 and MDM2 polymorphisms with survival in bladder cancer patients treated with chemoradiotherapy

International Nuclear Information System (INIS)

Shinohara, Asano; Sakano, Shigeru; Hinoda, Yuji; Nishijima, Jun; Kawai, Yoshihisa; Misumi, Taku; Nagao, Kazuhiro; Hara, Takahiko; Matsuyama, Hideyasu

2009-01-01

Platinum-based chemoradiotherapy (CRT) as bladder conservation therapy has shown promising results for muscle-invasive bladder cancer. However, CRT might diminish survival as a result of the delay in cystectomy for some patients with non-responding bladder tumors. Because the p53 tumor suppression pathway, including its MDM2 counterpart, is important in chemotherapy- and radiotherapy-associated effects, functional polymorphisms in the TP53 and MDM2 genes could influence the response to treatment and the prognosis following CRT. We investigated associations between two such polymorphisms, and p53 overexpression, and response or survival in bladder cancer patients treated with CRT. The study group comprised 96 patients who underwent CRT for transitional cell carcinoma of the bladder. Single nucleotide polymorphisms (SNPs) in TP53 (codon 72, arginine>proline) and MDM2 (SNP3O9, T>G) were genotyped using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP), and nuclear expression levels of p53 were examined using immunohistochemistry. None of the genotypes or p53 overexpression was significantly associated with response to CRT. However, patients with MDM2 T/G+G/G genotypes had improved cancer-specific survival rates after CRT (P=0.009). In multivariate analysis, the MDM2 T/G+G/G genotypes, and more than two of total variant alleles in TP53 and MDM2, were independently associated with improved cancer-specific survival (P=0.031 and P=0.015, respectively). In addition, MDM2 genotypes were significantly associated with cystectomy-free survival (P=0.030). These results suggest that the TP53 and MDM2 genotypes might be useful prognostic factors following CRT in bladder cancer, helping patient selection for bladder conservation therapy. (author)

Synthetic Cannabinoids

Directory of Open Access Journals (Sweden)

Aslihan Okan Ibiloglu

2017-09-01

Full Text Available Synthetic cannabinoids which is a subgroup of cannabinoids are commonly used for recreational drug use throughout the whole world. Although both marijuana and synthetic cannabinoids stimulate the same receptors, cannabinoid receptor 1 (CB1 and cannabinoid receptor 2 (CB2, studies have shown that synthetic cannabinoids are much more potent than marijuana. The longer use of synthetic cannabinoids can cause severe physical and psychological symptoms that might even result in death, similar to many known illicit drugs. Main treatment options mostly involve symptom management and supportive care. The aim of this article is to discuss clinical and pharmacological properties of the increasingly used synthetic cannabinoids. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2017; 9(3.000: 317-328

Src kinases in chondrosarcoma chemoresistance and migration: dasatinib sensitises to doxorubicin in TP53 mutant cells

Science.gov (United States)

van Oosterwijk, J G; van Ruler, M A J H; Briaire-de Bruijn, I H; Herpers, B; Gelderblom, H; van de Water, B; Bovée, J V M G

2013-01-01

Background: Chondrosarcomas are malignant cartilage-forming tumours of bone. Because of their resistance to conventional chemotherapy and radiotherapy, currently no treatment strategies exist for unresectable and metastatic chondrosarcoma. Previously, PI3K/AKT/GSK3β and Src kinase pathways were shown to be activated in chondrosarcoma cell lines. Our aim was to investigate the role of these kinases in chemoresistance and migration in chondrosarcoma in relation to TP53 mutation status. Methods: We used five conventional and three dedifferentiated chondrosarcoma cell lines and investigated the effect of PI3K/AKT/GSK3β pathway inhibition (enzastaurin) and Src pathway inhibition (dasatinib) in chemoresistance using WST assay and live cell imaging with AnnexinV staining. Immunohistochemistry on tissue microarrays (TMAs) containing 157 cartilaginous tumours was performed for Src family members. Migration assays were performed with the RTCA xCelligence System. Results: Src inhibition was found to overcome chemoresistance, to induce apoptosis and to inhibit migration. Cell lines with TP53 mutations responded better to combination therapy than wild-type cell lines (P=0.002). Tissue microarray immunohistochemistry confirmed active Src (pSrc) signalling, with Fyn being most abundantly expressed (76.1%). Conclusion: These results strongly indicate Src family kinases, in particular Fyn, as a potential target for the treatment of inoperable and metastatic chondrosarcomas, and to sensitise for doxorubicin especially in the presence of TP53 mutations. PMID:23922104

Surface characterisation of synthetic coal chars made from model compounds

Energy Technology Data Exchange (ETDEWEB)

Arenillas, A.; Pevida, C.; Rubiera, F.; Palacios, J.M.; Navarrete, R.; Denoyel, R.; Rouquerol, J.; Pis, J.J. [Instituto Nacional del Carbon, CSIC, Oviedo (Spain)

2004-07-01

Knowledge of surface properties is essential for understanding the reaction mechanisms involved in several coal conversion processes. However, due to the complexity and heterogeneity of coal this is rather difficult and the use of known model compounds could be a valuable tool. Single model compounds have been widely used, but they give a quite simplified picture. In this work a mixture of model compounds in a phenol-formaldehyde matrix was cured in order to create cross-linked structures. The obtained synthetic coal was pyrolysed in a fixed bed reactor, under helium atmosphere. The surface composition of the chars was evaluated by XPS, adsorption gravimetry of water vapour, temperature-programmed desorption and potentiometric titration. Texture was characterised by N{sub 2} and CO{sub 2} adsorption isotherms at 77 and 273 K, respectively, and immersion calorimetry in benzene. The results obtained from the different techniques were contrasted in order to give an overview of the surface properties (chemical and physical) of the samples studied. Chars obtained under the same operating conditions from a high volatile bituminous coal were used as a reference.

SYNTHETIC EDUCATIONAL ENVIRONMENT – A FOOTPACE TO NEW EDUCATION

Directory of Open Access Journals (Sweden)

Olga P. Pinchuk

2017-09-01

Full Text Available The article studies the problems of introducing a synthetic learning environment in the practice of education. The modern views on the essence of the learning environment and its new forms based on information and communication technologies are analyzed. Particular attention is paid to a range of issues that are united in the English-language publications as a "synthetic environment", which is considered in two aspects – artificial environment and synthetic as is formed due to the synthesis of the real physical world and the results of simulation and modeling. There are considered issues of trends in usage of game-based learning and modeling as cognitive technologies, as well as of social networks as a synthetic environment of social development. Conclusions are drawn: synthetic learning environment becomes an independent subject of learning through the expansion of its content and didactic power, transformation of the individual as a recipient of knowledge into the synthesizing element of the educational process in the metaverse.

Temperate phages TP901-1 and phi LC3, belonging to the P335 species, apparently use different pathways for DNA injection in Lactococcus lactis subsp cremoris 3107

DEFF Research Database (Denmark)

Breum, Solvej Østergaard; Neve, Horst; Heller, Knut J.

2007-01-01

Five mutants of Lactococcus lactis subsp. cremoris 3107 resistant to phage TP901-1 were obtained after treatment with ethyl methanesulfonate. Two of the mutants were also resistant to phage phi LC3. The remaining three mutants were as sensitive as 3107. Mutants E46 and E100 did not adsorb the two...... phages. Mutants E119, E121 and E126 adsorbed phage phi LC3 as well as 3107 but phage TP901-1 with significantly reduced efficiency. All, except E46, could be lysogenized with phage TP901-BC1034, a derivative of TP901-1 harboring an erythromycin-resistance marker. However, the lysogenization frequency......-1. As such impairment was not seen when infecting E119, E121 and E126 with phi LC3, we conclude that TP901-1 and phi LC3 either are differently triggered by their receptor or utilize different pathways of injection....

Major prognostic value of complex karyotype in addition to TP53 and IGHV mutational status in first-line chronic lymphocytic leukemia.

Science.gov (United States)

Le Bris, Yannick; Struski, Stéphanie; Guièze, Romain; Rouvellat, Caroline; Prade, Naïs; Troussard, Xavier; Tournilhac, Olivier; Béné, Marie C; Delabesse, Eric; Ysebaert, Loïc

2017-12-01

Chronic lymphocytic leukemia (CLL) is a lymphoproliferative disorder of remarkable heterogeneity as demonstrated by cytogenetics and molecular analyses. Complex karyotype (CK), TP53 deletions and/or mutations (TP53 disruption), IGVH mutational status, and, more recently, recurrent somatic mutations have been identified as prognostic markers in CLL. On a cohort of 110 patients with CLL treated with first-line fludarabin, cyclophosphamide, and rituximab treatment compared with 33 untreated (watch and wait) patients with CLL, we report more frequent complex karyotypes (34 vs 15%; P = .05), unmutated IGHV (70 vs 21%; P < .0001), ATM deletion (25 vs 6%, P = .02), and NOTCH mutation (3 vs 17%, P = .04). Among treated patients, 39 relapsed during the follow-up period. These patients were characterized before treatment by a higher incidence of trisomy 12 (38 vs 11%, P < .001) and TP53 disruption (31 vs 4%, P = .0002). A significantly shorter 5-year overall survival was found for treated patients with CK (72.4 vs 85.8%; P = .007), unmutated IGHV (70 vs 100%; P = .04), or TP53 disruption (55.7 vs 82.7%; P < .0001). Three risk groups were defined based on the status of TP53 disruption or unmutated IGVH, which differed significantly in terms of 5-year overall survival. Moreover, the presence of CK impacted pejoratively 5-year overall survival and progression-free survival in all these 3 groups. Conventional karyotyping therefore appears to be of value, CK being an additional factor, undetectable in classical FISH, in patients with CLL at the stage when therapy becomes required. Copyright © 2016 John Wiley & Sons, Ltd.

Model prodrugs for the intestinal peptide transporter. a synthetic approach for coupling of hydroxy-containing compounds to dieptides

DEFF Research Database (Denmark)

Friedrichsen, G; Nielsen, Carsten Uhd; Steffansen, Bente

2001-01-01

The human peptide transporter, hPepT1, situated in the small intestine, may be exploited to increase absorption of drugs or model drugs by attaching them to a dipeptide, which is recognised by hPepT1. A synthetic protocol for this kind of model prodrugs was developed, in which model drugs...

Importance of TP53 and RB in the repair of potentially lethal damage and induction of color junctions after exposure to ionizing radiation

NARCIS (Netherlands)

Franken, N. A. P.; van Bree, C.; ten Cate, R.; van Oven, C. H.; Haveman, J.

2002-01-01

Repair of potentially lethal damage (PLD) was investigated in cells with functional G(1)-phase arrest with wild-type TP53 and wild-type RB and in cells in which G(1)-phase arrest was abrogated by inactivation of TP53 or RB. Confluent cultures of cells were plated for clonogenic survival assay either

Improved object optimal synthetic description, modeling, learning, and discrimination by GEOGINE computational kernel

Science.gov (United States)

Fiorini, Rodolfo A.; Dacquino, Gianfranco

2005-03-01

GEOGINE (GEOmetrical enGINE), a state-of-the-art OMG (Ontological Model Generator) based on n-D Tensor Invariants for n-Dimensional shape/texture optimal synthetic representation, description and learning, was presented in previous conferences elsewhere recently. Improved computational algorithms based on the computational invariant theory of finite groups in Euclidean space and a demo application is presented. Progressive model automatic generation is discussed. GEOGINE can be used as an efficient computational kernel for fast reliable application development and delivery in advanced biomedical engineering, biometric, intelligent computing, target recognition, content image retrieval, data mining technological areas mainly. Ontology can be regarded as a logical theory accounting for the intended meaning of a formal dictionary, i.e., its ontological commitment to a particular conceptualization of the world object. According to this approach, "n-D Tensor Calculus" can be considered a "Formal Language" to reliably compute optimized "n-Dimensional Tensor Invariants" as specific object "invariant parameter and attribute words" for automated n-Dimensional shape/texture optimal synthetic object description by incremental model generation. The class of those "invariant parameter and attribute words" can be thought as a specific "Formal Vocabulary" learned from a "Generalized Formal Dictionary" of the "Computational Tensor Invariants" language. Even object chromatic attributes can be effectively and reliably computed from object geometric parameters into robust colour shape invariant characteristics. As a matter of fact, any highly sophisticated application needing effective, robust object geometric/colour invariant attribute capture and parameterization features, for reliable automated object learning and discrimination can deeply benefit from GEOGINE progressive automated model generation computational kernel performance. Main operational advantages over previous

The Neuronal Ischemic Tolerance Is Conditioned by the Tp53 Arg72Pro Polymorphism.

Science.gov (United States)

Ramos-Araque, Maria E; Rodriguez, Cristina; Vecino, Rebeca; Cortijo Garcia, Elisa; de Lera Alfonso, Mercedes; Sanchez Barba, Mercedes; Colàs-Campàs, Laura; Purroy, Francisco; Arenillas, Juan F; Almeida, Angeles; Delgado-Esteban, Maria

2018-04-23

Cerebral preconditioning (PC) confers endogenous brain protection after stroke. Ischemic stroke patients with a prior transient ischemic attack (TIA) may potentially be in a preconditioned state. Although PC has been associated with the activation of pro-survival signals, the mechanism by which preconditioning confers neuroprotection is not yet fully clarified. Recently, we have described that PC-mediated neuroprotection against ischemic insult is promoted by p53 destabilization, which is mediated by its main regulator MDM2. Moreover, we have previously described that the human Tp53 Arg72Pro single nucleotide polymorphism (SNP) controls susceptibility to ischemia-induced neuronal apoptosis and governs the functional outcome of patients after stroke. Here, we studied the contribution of the human Tp53 Arg72Pro SNP on PC-induced neuroprotection after ischemia. Our results showed that cortical neurons expressing the Pro72-p53 variant exhibited higher PC-mediated neuroprotection as compared with Arg72-p53 neurons. PC prevented ischemia-induced nuclear and cytosolic p53 stabilization in Pro72-p53 neurons. However, PC failed to prevent mitochondrial p53 stabilization, which occurs in Arg72-p53 neurons after ischemia. Furthermore, PC promoted neuroprotection against ischemia by controlling the p53/active caspase-3 pathway in Pro72-p53, but not in Arg72-p53 neurons. Finally, we found that good prognosis associated to TIA within 1 month prior to ischemic stroke was restricted to patients harboring the Pro72 allele. Our findings demonstrate that the Tp53 Arg72Pro SNP controls PC-promoted neuroprotection against a subsequent ischemic insult by modulating mitochondrial p53 stabilization and then modulates TIA-induced ischemic tolerance.

Generation of synthetic Kinect depth images based on empirical noise model

DEFF Research Database (Denmark)

Iversen, Thorbjørn Mosekjær; Kraft, Dirk

2017-01-01

The development, training and evaluation of computer vision algorithms rely on the availability of a large number of images. The acquisition of these images can be time-consuming if they are recorded using real sensors. An alternative is to rely on synthetic images which can be rapidly generated....... This Letter describes a novel method for the simulation of Kinect v1 depth images. The method is based on an existing empirical noise model from the literature. The authors show that their relatively simple method is able to provide depth images which have a high similarity with real depth images....

The Herschel Planetary Nebula Survey (HerPlaNS): A Comprehensive Dusty Photoionization Model of NGC6781.

Science.gov (United States)

Otsuka, Masaaki; Ueta, Toshiya; van Hoof, Peter A M; Sahai, Raghvendra; Aleman, Isabel; Zijlstra, Albert A; Chu, You-Hua; Villaver, Eva; Leal-Ferreira, Marcelo L; Kastner, Joel; Szczerba, Ryszard; Exter, Katrina M

2017-08-01

We perform a comprehensive analysis of the planetary nebula (PN) NGC 6781 to investigate the physical conditions of each of its ionized, atomic, and molecular gas and dust components and the object's evolution, based on panchromatic observational data ranging from UV to radio. Empirical nebular elemental abundances, compared with theoretical predictions via nucleosynthesis models of asymptotic giant branch (AGB) stars, indicate that the progenitor is a solar-metallicity, 2.25-3.0 M ⊙ initial-mass star. We derive the best-fit distance of 0.46 kpc by fitting the stellar luminosity (as a function of the distance and effective temperature of the central star) with the adopted post-AGB evolutionary tracks. Our excitation energy diagram analysis indicates high-excitation temperatures in the photodissociation region (PDR) beyond the ionized part of the nebula, suggesting extra heating by shock interactions between the slow AGB wind and the fast PN wind. Through iterative fitting using the Cloudy code with empirically derived constraints, we find the best-fit dusty photoionization model of the object that would inclusively reproduce all of the adopted panchromatic observational data. The estimated total gas mass (0.41 M ⊙ ) corresponds to the mass ejected during the last AGB thermal pulse event predicted for a 2.5 M ⊙ initial-mass star. A significant fraction of the total mass (about 70%) is found to exist in the PDR, demonstrating the critical importance of the PDR in PNe that are generally recognized as the hallmark of ionized/H + regions.

Active aeroelastic control aspects of an aircraft wing by using synthetic jet actuators : Modeling, simulations, experiments

NARCIS (Netherlands)

Donnell, K.O.; Schober, S.; Stolk, M.; Marzocca, P.; De Breuker, R.; Abdalla, M.; Nicolini, E.; Gürdal, Z.

2007-01-01

This paper discusses modeling, simulations and experimental aspects of active aeroelastic control on aircraft wings by using Synthetic Jet Actuators (SJAs). SJAs, a particular class of zero-net mass-flux actuators, have shown very promising results in numerous aeronautical applications, such as

Asymptotic analysis soot model and experiment for a directed injection engine

Science.gov (United States)

Liu, Yongfeng; Pei, Pucheng; Xiong, Qinghui; Lu, Yong

2012-09-01

The existing soot models are either too complex and can not be applied to the internal combustion engine, or too simple to make calculation errors. Exploring the soot model becomes the pursuit of the goal of many researchers within the error range in the current computer speed. On the basis of the latest experimental results, TP (temperature phases) model is presented as a new soot model to carry out optimization calculation for a high-pressure common rail diesel engine. Temperature and excess air factor are the most important two parameters in this model. When zone temperature T0.6, only the soot precursors—polycyclic aromatic hydrocarbons(PAH) is created and there is no soot emission. When zone temperature T ⩾ 1 500 K and excess air factor Φinjection time, variation of rail pressure and variation of speed among TP models. The experimental results indicate that the TP model can carry out optimization and computational fluid dynamics can be a tool to calculate for a high-pressure common rail directed injection diesel engine. The TP model result is closer than the use of the original KIVA-3V results of soot model accuracy by about 50% and TP model gives a new method for engine researchers.

Long-period variables in the Magellanic Clouds: Supergiants, AGB stars, supernova precursors, planetary nebula precursors, and enrichment of the interstellar medium

International Nuclear Information System (INIS)

Wood, P.; Bessell, M.S.; Fox, M.W.

1983-01-01

Infrared JHK magnitudes and low-dispersion red spectra have been obtained for 90 long-period variables (LPVs) in the Small and Large Magellanic Clouds. The LPVs fall into two distinct groups, core helium (or carbon) burning supergiants and stars on the asymptotic giant branch (AGB). The supergiants have small pulsation amplitudes in K ( or approx. =5 M/sub sun/ produce supernovae while less massive stars produce planetary nebulae with nebula masses from approx.0.1--2.1 M/sub sun/. The coreburning red supergiants appear highly overluminous for their pulsation mass, indicating that they have lost up to half their mass since the main-sequence phase

Human Papillomavirus 16 Infection and TP53 Mutation: Two Distinct Pathogeneses for Oropharyngeal Squamous Cell Carcinoma in an Eastern Chinese Population

OpenAIRE

Wang, Zhen; Xia, Rong-Hui; Ye, Dong-Xia; Li, Jiang

2016-01-01

Objectives To investigate the clinicopathological characteristics, human papillomavirus (HPV) infection, p53 expression, and TP53 mutations in oropharyngeal squamous cell carcinoma (OPSCC) and determine their utility as prognostic predictors in a primarily eastern Chinese population. Methods The HPV infection status was tested via p16INK4A immunohistochemistry and validated using PCR, reverse blot hybridization and in situ hybridization (ISH) in 188 OPSCC samples. p53 expression levels and TP...

Identification of DNA-binding sites for the activator involved in late transcription of the temperate lactococcal phage TP901-1

DEFF Research Database (Denmark)

Pedersen, Margit; Kilstrup, Mogens; Hammer, Karin

2006-01-01

Alt, encoded by the lactococcal phage TP901-1, is needed for late transcription. We identify Alt as a DNA-binding protein, and footprint analysis shows that Alt binds to a region containing four imperfect direct repeats (ALT boxes) located -76 to -32 relative to the P-late transcriptional start...... site. The importance of the ALT boxes was confirmed by deletion of one or two ALT boxes and by introducing mutations in ALT boxes 1 and 4. Alt is proposed to act as a tetramer or higher multimer activating transcription of TP901-1 late genes by binding to the four ALT boxes, and bending of the DNA may...... be important for transcriptional activation of P-late. Furthermore, our results suggest that DNA replication may be required for late transcription in TP901-1. Additionally, we identify gp28 of the related lactococcal phage Tuc2009 as an activator and show that the activators required for late transcription...

TP53 germline mutation testing in 180 families suspected of Li-Fraumeni syndrome: mutation detection rate and relative frequency of cancers in different familial phenotypes

NARCIS (Netherlands)

Ruijs, M.W.G.; Verhoef, S.; Rookus, M.A.; Pruntel, R.; van der Hout, A.H.; Hogervorst, F.B.L.; Kluijt, I.; Sijmons, R.H.; Aalfs, C.M.; Wagner, A.; Ausems, M.G.E.M.; Hoogerbrugge, N.; van Asperen, C.J.; Gómez García, E.B.; Meijers-Heijboer, H.; ten Kate, L.P.; Menko, F.H.; van 't Veer, L.J.

2010-01-01

Background Li-Fraumeni syndrome (LFS) is a rare autosomal dominant cancer predisposition syndrome. Most families fulfilling the classical diagnostic criteria harbour TP53 germline mutations. However, TP53 germline mutations may also occur in less obvious phenotypes. As a result, different criteria

Stereoscopy in cinematographic synthetic imagery

Science.gov (United States)

Eisenmann, Jonathan; Parent, Rick

2009-02-01

In this paper we present experiments and results pertaining to the perception of depth in stereoscopic viewing of synthetic imagery. In computer animation, typical synthetic imagery is highly textured and uses stylized illumination of abstracted material models by abstracted light source models. While there have been numerous studies concerning stereoscopic capabilities, conventions for staging and cinematography in stereoscopic movies have not yet been well-established. Our long-term goal is to measure the effectiveness of various cinematography techniques on the human visual system in a theatrical viewing environment. We would like to identify the elements of stereoscopic cinema that are important in terms of enhancing the viewer's understanding of a scene as well as providing guidelines for the cinematographer relating to storytelling. In these experiments we isolated stereoscopic effects by eliminating as many other visual cues as is reasonable. In particular, we aim to empirically determine what types of movement in synthetic imagery affect the perceptual depth sensing capabilities of our viewers. Using synthetic imagery, we created several viewing scenarios in which the viewer is asked to locate a target object's depth in a simple environment. The scenarios were specifically designed to compare the effectiveness of stereo viewing, camera movement, and object motion in aiding depth perception. Data were collected showing the error between the choice of the user and the actual depth value, and patterns were identified that relate the test variables to the viewer's perceptual depth accuracy in our theatrical viewing environment.

Elastic properties of synthetic materials for soft tissue modeling

International Nuclear Information System (INIS)

Mansy, H A; Grahe, J R; Sandler, R H

2008-01-01

Mechanical models of soft tissue are useful for studying vibro-acoustic phenomena. They may be used for validating mathematical models and for testing new equipment and techniques. The objective of this study was to measure density and visco-elastic properties of synthetic materials that can be used to build such models. Samples of nine different materials were tested under dynamic (0.5 Hz) compressive loading conditions. The modulus of elasticity of the materials was varied, whenever possible, by adding a softener during manufacturing. The modulus was measured over a nine month period to quantify the effect of ageing and softener loss on material properties. Results showed that a wide range of the compression elasticity modulus (10 to 1400 kPa) and phase (3.5 0 -16.7 0 ) between stress and strain were possible. Some materials tended to exude softener over time, resulting in a weight loss and elastic properties change. While the weight loss under normal conditions was minimal in all materials (<3% over nine months), loss under accelerated weight-loss conditions can reach 59%. In the latter case an elasticity modulus increase of up to 500% was measured. Key advantages and limitations of candidate materials were identified and discussed

[From synthetic biology to synthetic humankind].

Science.gov (United States)

Nouvel, Pascal

2015-01-01

In this paper, we propose an historical survey of the expression "synthetic biology" in order to identify its main philosophical components. The result of the analysis is then used to investigate the meaning of the notion of "synthetic man". It is shown that both notions share a common philosophical background that can be summed up by the short but meaningful assertion: "biology is technology". The analysis allows us to distinguish two notions that are often confused in transhumanist literature: the notion of synthetic man and the notion of renewed man. The consequences of this crucial distinction are discussed. Copyright © 2015 Académie des sciences. Published by Elsevier SAS. All rights reserved.

s-PROCESSING IN AGB STARS REVISITED. II. ENHANCED {sup 13}C PRODUCTION THROUGH MHD-INDUCED MIXING

Energy Technology Data Exchange (ETDEWEB)

Trippella, O.; Busso, M.; Palmerini, S.; Maiorca, E. [Department of Physics, University of Perugia, and INFN, Section of Perugia, via A. Pascoli, I-06123 Perugia (Italy); Nucci, M. C., E-mail: oscar.trippella@fisica.unipg.it [Department of Mathematics and Informatics, University of Perugia, via Vanvitelli, I-06123 Perugia and INFN, Section of Perugia, via A. Pascoli, I-06123 Perugia (Italy)

2016-02-20

Slow neutron captures are responsible for the production of about 50% of elements heavier than iron, mainly occurring during the asymptotic giant branch phase of low-mass stars (1 ≲ M/M{sub ⊙} ≲ 3), where the main neutron source is the {sup 13}C(α, n){sup 16}O reaction. This last reaction is activated from locally produced {sup 13}C, formed by partial mixing of hydrogen into the He-rich layers. We present here the first attempt to describe a physical mechanism for the formation of the {sup 13}C reservoir, studying the mass circulation induced by magnetic buoyancy without adding new free parameters to those already involved in stellar modeling. Our approach represents the application to the stellar layers relevant for s-processing of recent exact analytical 2D and 3D models for magneto-hydrodynamic processes at the base of convective envelopes in evolved stars in order to promote downflows of envelope material for mass conservation during the occurrence of a dredge-up phenomenon. We find that the proton penetration is characterized by small concentrations, but is extended over a large fractional mass of the He-layers, thus producing {sup 13}C reservoirs of several 10{sup −3} M{sub ⊙}. The ensuing {sup 13}C-enriched zone has an almost flat profile, while only a limited production of {sup 14}N occurs. In order to verify the effects of our new findings we show how the abundances of the main s-component nuclei can be accounted for in solar proportions and how our large {sup 13}C-reservoir allows us to solve a few so far unexplained features in the abundance distribution of post-AGB objects.

Association of the germline TP53 R72P and MDM2 SNP309 variants with breast cancer survival in specific breast tumor subgroups

NARCIS (Netherlands)

van den Broek, Alexandra J.; Broeks, Annegien; Horlings, Hugo M.; Canisius, Sander V. M.; Braaf, Linde M.; Langerød, Anita; van't Veer, Laura J.; Schmidt, Marjanka K.

2011-01-01

The tumor suppressor gene TP53 and its regulator MDM2 are both important players in the DNA-damage repair "TP53 response pathway". Common germline polymorphisms in these genes may affect outcome in patients with tumors characterized by additional somatic changes in the same or a related pathway. To

Identical TP53 mutations in pelvic carcinosarcomas and associated serous tubal intraepithelial carcinomas provide evidence of their clonal relationship.

Science.gov (United States)

Ardighieri, Laura; Mori, Luigi; Conzadori, Sara; Bugatti, Mattia; Falchetti, Marcella; Donzelli, Carla Maria; Ravaggi, Antonella; Odicino, Franco E; Facchetti, Fabio

2016-07-01

Pelvic carcinosarcomas (PCSs) are rare aggressive biphasic tumors that localize in the ovary, fallopian tube, or peritoneum and present frequently as bilateral disease. We undertook a morphological, p53 immunohistochemical and TP53 gene mutational analysis study in a single institution cohort of 16 PCSs in order to investigate the nature of bilateral tumors and to shed light on their origin and pathogenesis. Of the 16 patients, 10 presented with bilateral disease, 6 with a carcinosarcoma in both adnexa, and the remaining cases with a carcinosarcoma in one adnexum and a carcinoma in the opposite. The carcinoma component showed high-grade serous features in 13/16 of cases (81 %). In 10 patients (63 %), a serous tubal intraepithelial carcinoma (STIC) was found, in one case bilateral, making a total of 11 STICs. STIC was found only in cases with a carcinoma component with high-grade serous features. All 10 bilateral tumors and all 11 PCS-associated STICs showed a similar p53 immunostaining pattern. At mutation analysis of the TP53 gene, all five bilateral PCS contained an identical mutation in both localizations. Furthermore, a TP53 mutation was found in 8 of 10 STICs, with an identical mutation in the associated PCS. The finding of similar p53 immunostaining in all bilateral cases and identical TP53 mutations in most PCS-associated STIC provides evidence for a clonal relation between these neoplastic lesions, supporting a metastatic nature of bilateral PCS and suggesting that they have an extraovarian origin in a STIC.

The puzzle of the CNO isotope ratios in asymptotic giant branch carbon stars

Science.gov (United States)

Abia, C.; Hedrosa, R. P.; Domínguez, I.; Straniero, O.

2017-03-01

Context. The abundance ratios of the main isotopes of carbon, nitrogen and oxygen are modified by the CNO-cycle in the stellar interiors. When the different dredge-up events mix the burning material with the envelope, valuable information on the nucleosynthesis and mixing processes can be extracted by measuring these isotope ratios. Aims: Previous determinations of the oxygen isotopic ratios in asymptotic giant branch (AGB) carbon stars were at odds with the existing theoretical predictions. We aim to redetermine the oxygen ratios in these stars using new spectral analysis tools and further develop discussions on the carbon and nitrogen isotopic ratios in order to elucidate this problem. Methods: Oxygen isotopic ratios were derived from spectra in the K-band in a sample of galactic AGB carbon stars of different spectral types and near solar metallicity. Synthetic spectra calculated in local thermodynamic equillibrium (LTE) with spherical carbon-rich atmosphere models and updated molecular line lists were used. The CNO isotope ratios derived in a homogeneous way, were compared with theoretical predictions for low-mass (1.5-3 M⊙) AGB stars computed with the FUNS code assuming extra mixing both during the RGB and AGB phases. Results: For most of the stars the 16O/17O/18O ratios derived are in good agreement with theoretical predictions confirming that, for AGB stars, are established using the values reached after the first dredge-up (FDU) according to the initial stellar mass. This fact, as far as the oxygen isotopic ratios are concerned, leaves little space for the operation of any extra mixing mechanism during the AGB phase. Nevertheless, for a few stars with large 16O/17O/18O, the operation of such a mechanism might be required, although their observed 12C/13C and 14N/15N ratios would be difficult to reconcile within this scenario. Furthermore, J-type stars tend to have lower 16O/17O ratios than the normal carbon stars, as already indicated in previous studies

Optimization of Soil Hydraulic Model Parameters Using Synthetic Aperture Radar Data: An Integrated Multidisciplinary Approach

DEFF Research Database (Denmark)

Pauwels, Valentijn; Balenzano, Anna; Satalino, Giuseppe

2009-01-01

It is widely recognized that Synthetic Aperture Radar (SAR) data are a very valuable source of information for the modeling of the interactions between the land surface and the atmosphere. During the last couple of decades, most of the research on the use of SAR data in hydrologic applications has...... that no direct relationships between the remote-sensing observations, more specifically radar backscatter values, and the parameter values can be derived. However, land surface models can provide these relationships. The objective of this paper is to retrieve a number of soil physical model parameters through...

Time Series of Tropical-Forest Structure from TanDEM-X, Transformed to Time Series of Biomass by MODIS

Science.gov (United States)

Treuhaft, R. N.; Baccini, A.; Goncalves, F. G.; Lei, Y.; Keller, M.; Walker, W. S.

2017-12-01

Tropical forests account for about 50% of the world's forested biomass, and play a critical role in the control of atmospheric carbon dioxide. Large-scale (1000's of km) changes in forest structure and biomass bear on global carbon source-sink dynamics, while small-scale (phase-height observation, we show forest phase-height time series from the TanDEM-X radar interferometer at X-band (3 cm), taken with monthly and sub-hectare temporal and spatial resolution, respectively. The measurements were taken with more than 30 TanDEM-X passes over Tapajós National Forest in the Brazilian Amazon between 2011 and 2014. The transformation of phase-height rates into aboveground biomass (AGB) rates is based on the idea that the change in AGB due to a change in phase-height depends on the plot's AGB. Plots with higher AGB will produce more AGB for a given increase in height or phase-height. Postulating a power-law dependence of plot-level mass density on physical height, we previously found that the best conversion factors for transforming phase-height rate to AGB rate were indeed dependent on AGB. For 78 plots, we demonstrated AGB rates from InSAR phase-height rates using AGB from field measurements. For regional modeling of the Amazon Basin, field measurements of AGB, to specify the conversion factors, is impractical. Conversion factors from InSAR phase-height rate to AGB rate in this talk will be based on AGB derived from the Moderate Resolution Imaging Spectroradiometer (MODIS). AGB measurement from MODIS is based on the spectral reflectance of 7 bands from the visible to short wave infrared, and auxiliary metrics describing the variance in reflectance. The mapping of MODIS reflectance to AGB is enabled by training a machine learning algorithm with lidar-derived AGB data, which are in turn trained by field measurements for small areas. The performance of TanDEM-X AGB rate from MODIS-derived conversion factors will be compared to that derived from field-based conversion

TP53, STK11 and EGFR Mutations Predict Tumor Immune Profile and the Response to anti-PD-1 in Lung Adenocarcinoma.

Science.gov (United States)

Biton, Jerome; Mansuet-Lupo, Audrey; Pécuchet, Nicolas; Alifano, Marco; Ouakrim, Hanane; Arrondeau, Jennifer; Boudou-Rouquette, Pascaline; Goldwasser, Francois; Leroy, Karen; Goc, Jeremy; Wislez, Marie; Germain, Claire; Laurent-Puig, Pierre; Dieu-Nosjean, Marie-Caroline; Cremer, Isabelle; Herbst, Ronald; Blons, Hélène F; Damotte, Diane

2018-05-15

By unlocking anti-tumor immunity, antibodies targeting programmed cell death 1 (PD-1) exhibit impressive clinical results in non-small cell lung cancer, underlining the strong interactions between tumor and immune cells. However, factors that can robustly predict long-lasting responses are still needed. We performed in depth immune profiling of lung adenocarcinoma using an integrative analysis based on immunohistochemistry, flow-cytometry and transcriptomic data. Tumor mutational status was investigated using next-generation sequencing. The response to PD-1 blockers was analyzed from a prospective cohort according to tumor mutational profiles and to PD-L1 expression, and a public clinical database was used to validate the results obtained. We showed that distinct combinations of STK11 , EGFR and TP53 mutations, were major determinants of the tumor immune profile (TIP) and of the expression of PD-L1 by malignant cells. Indeed, the presence of TP53 mutations without co-occurring STK11 or EGFR alterations ( TP53 -mut/ STK11 - EGFR -WT), independently of KRAS mutations, identified the group of tumors with the highest CD8 T cell density and PD-L1 expression. In this tumor subtype, pathways related to T cell chemotaxis, immune cell cytotoxicity, and antigen processing were up-regulated. Finally, a prolonged progression-free survival (PFS: HR=0.32; 95% CI, 0.16-0.63, p <0.001) was observed in anti-PD-1 treated patients harboring TP53 -mut/ STK11 - EGFR -WT tumors. This clinical benefit was even more remarkable in patients with associated strong PD-L1 expression. Our study reveals that different combinations of TP53 , EGFR and STK11 mutations , together with PD-L1 expression by tumor cells, represent robust parameters to identify best responders to PD-1 blockade. Copyright ©2018, American Association for Cancer Research.

Generation of synthetic influent data for performing (micro) pollutant wastewater treatment modelling studies

DEFF Research Database (Denmark)

Snip, L. J. P.; Aymerich, I.; Flores-Alsina, X.

2015-01-01

The use of Activated Sludge Models (ASM) (Henze et al., 2000) is constantly growing and both industry and academia are increasingly applying these tools when performing wastewater treatment plant (WWTP) engineering studies. Besides describing the behaviour of traditional pollutants such as organic...... carbon (C), nitrogen(N) and phosphorus(P), ASM models have been successfully upgraded to predict the fate of different types of micro-pollutants (Benedetti et al., 2013). Indeed, the potential adverse effects of micro-pollutants in aquatic environments have been an object of intensive research during...... (Gernaey et al., 2011). This is an important point since realistic data representing the influent wastewater dynamics are crucial to accomplish any WWTP modelling project (Rieger et al., 2012). For this reason, model-based influent generators/synthetic data are an alternative that has recently gained...

A methodology to annotate systems biology markup language models with the synthetic biology open language.

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Roehner, Nicholas; Myers, Chris J

2014-02-21

Recently, we have begun to witness the potential of synthetic biology, noted here in the form of bacteria and yeast that have been genetically engineered to produce biofuels, manufacture drug precursors, and even invade tumor cells. The success of these projects, however, has often failed in translation and application to new projects, a problem exacerbated by a lack of engineering standards that combine descriptions of the structure and function of DNA. To address this need, this paper describes a methodology to connect the systems biology markup language (SBML) to the synthetic biology open language (SBOL), existing standards that describe biochemical models and DNA components, respectively. Our methodology involves first annotating SBML model elements such as species and reactions with SBOL DNA components. A graph is then constructed from the model, with vertices corresponding to elements within the model and edges corresponding to the cause-and-effect relationships between these elements. Lastly, the graph is traversed to assemble the annotating DNA components into a composite DNA component, which is used to annotate the model itself and can be referenced by other composite models and DNA components. In this way, our methodology can be used to build up a hierarchical library of models annotated with DNA components. Such a library is a useful input to any future genetic technology mapping algorithm that would automate the process of composing DNA components to satisfy a behavioral specification. Our methodology for SBML-to-SBOL annotation is implemented in the latest version of our genetic design automation (GDA) software tool, iBioSim.

A hierarchical stress release model for synthetic seismicity

Science.gov (United States)

Bebbington, Mark

1997-06-01

We construct a stochastic dynamic model for synthetic seismicity involving stochastic stress input, release, and transfer in an environment of heterogeneous strength and interacting segments. The model is not fault-specific, having a number of adjustable parameters with physical interpretation, namely, stress relaxation, stress transfer, stress dissipation, segment structure, strength, and strength heterogeneity, which affect the seismicity in various ways. Local parameters are chosen to be consistent with large historical events, other parameters to reproduce bulk seismicity statistics for the fault as a whole. The one-dimensional fault is divided into a number of segments, each comprising a varying number of nodes. Stress input occurs at each node in a simple random process, representing the slow buildup due to tectonic plate movements. Events are initiated, subject to a stochastic hazard function, when the stress on a node exceeds the local strength. An event begins with the transfer of excess stress to neighboring nodes, which may in turn transfer their excess stress to the next neighbor. If the event grows to include the entire segment, then most of the stress on the segment is transferred to neighboring segments (or dissipated) in a characteristic event. These large events may themselves spread to other segments. We use the Middle America Trench to demonstrate that this model, using simple stochastic stress input and triggering mechanisms, can produce behavior consistent with the historical record over five units of magnitude. We also investigate the effects of perturbing various parameters in order to show how the model might be tailored to a specific fault structure. The strength of the model lies in this ability to reproduce the behavior of a general linear fault system through the choice of a relatively small number of parameters. It remains to develop a procedure for estimating the internal state of the model from the historical observations in order to

Numerical modeling of the radiative transfer in a turbid medium using the synthetic iteration.

Science.gov (United States)

Budak, Vladimir P; Kaloshin, Gennady A; Shagalov, Oleg V; Zheltov, Victor S

2015-07-27

In this paper we propose the fast, but the accurate algorithm for numerical modeling of light fields in the turbid media slab. For the numerical solution of the radiative transfer equation (RTE) it is required its discretization based on the elimination of the solution anisotropic part and the replacement of the scattering integral by a finite sum. The solution regular part is determined numerically. A good choice of the method of the solution anisotropic part elimination determines the high convergence of the algorithm in the mean square metric. The method of synthetic iterations can be used to improve the convergence in the uniform metric. A significant increase in the solution accuracy with the use of synthetic iterations allows applying the two-stream approximation for the regular part determination. This approach permits to generalize the proposed method in the case of an arbitrary 3D geometry of the medium.

Modelling biogas production of solid waste: application of the BGP model to a synthetic landfill

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Rodrigo-Ilarri, Javier; Segura-Sobrino, Francisco

2013-04-01

Production of biogas as a result of the decomposition of organic matter included on solid waste landfills is still an issue to be understood. Reports on this matter are rarely included on the engineering construction projects of solid waste landfills despite it can be an issue of critical importance while operating the landfill and after its closure. This paper presents an application of BGP (Bio-Gas-Production) model to a synthetic landfill. The evolution in time of the concentrations of the different chemical compounds of biogas is studied. Results obtained show the impact on the air quality of different management alternatives which are usually performed in real landfills.

An analytical model for the evolution of the coldest component of the Boomerang Nebula

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