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Sample records for dna combining intrinsic

  1. Intrinsically bent DNA in replication origins and gene promoters.

    Science.gov (United States)

    Gimenes, F; Takeda, K I; Fiorini, A; Gouveia, F S; Fernandez, M A

    2008-06-24

    Intrinsically bent DNA is an alternative conformation of the DNA molecule caused by the presence of dA/dT tracts, 2 to 6 bp long, in a helical turn phase DNA or with multiple intervals of 10 to 11 bp. Other than flexibility, intrinsic bending sites induce DNA curvature in particular chromosome regions such as replication origins and promoters. Intrinsically bent DNA sites are important in initiating DNA replication, and are sometimes found near to regions associated with the nuclear matrix. Many methods have been developed to localize bent sites, for example, circular permutation, computational analysis, and atomic force microscopy. This review discusses intrinsically bent DNA sites associated with replication origins and gene promoter regions in prokaryote and eukaryote cells. We also describe methods for identifying bent DNA sites for circular permutation and computational analysis.

  2. The Intrinsic Fragility of DNA (Nobel Lecture).

    Science.gov (United States)

    Lindahl, Tomas

    2016-07-18

    Our cells contain common molecules, such as water or oxygen, that can damage DNA. In his studies Tomas Lindahl has shown how specific repair enzymes remove and replace damaged parts of DNA in a process of vital importance. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Sequence periodicity in nucleosomal DNA and intrinsic curvature.

    Science.gov (United States)

    Nair, T Murlidharan

    2010-05-17

    Most eukaryotic DNA contained in the nucleus is packaged by wrapping DNA around histone octamers. Histones are ubiquitous and bind most regions of chromosomal DNA. In order to achieve smooth wrapping of the DNA around the histone octamer, the DNA duplex should be able to deform and should possess intrinsic curvature. The deformability of DNA is a result of the non-parallelness of base pair stacks. The stacking interaction between base pairs is sequence dependent. The higher the stacking energy the more rigid the DNA helix, thus it is natural to expect that sequences that are involved in wrapping around the histone octamer should be unstacked and possess intrinsic curvature. Intrinsic curvature has been shown to be dictated by the periodic recurrence of certain dinucleotides. Several genome-wide studies directed towards mapping of nucleosome positions have revealed periodicity associated with certain stretches of sequences. In the current study, these sequences have been analyzed with a view to understand their sequence-dependent structures. Higher order DNA structures and the distribution of molecular bend loci associated with 146 base nucleosome core DNA sequence from C. elegans and chicken have been analyzed using the theoretical model for DNA curvature. The curvature dispersion calculated by cyclically permuting the sequences revealed that the molecular bend loci were delocalized throughout the nucleosome core region and had varying degrees of intrinsic curvature. The higher order structures associated with nucleosomes of C.elegans and chicken calculated from the sequences revealed heterogeneity with respect to the deviation of the DNA axis. The results points to the possibility of context dependent curvature of varying degrees to be associated with nucleosomal DNA.

  4. Intrinsic flexibility of B-DNA: the experimental TRX scale.

    Science.gov (United States)

    Heddi, Brahim; Oguey, Christophe; Lavelle, Christophe; Foloppe, Nicolas; Hartmann, Brigitte

    2010-01-01

    B-DNA flexibility, crucial for DNA-protein recognition, is sequence dependent. Free DNA in solution would in principle be the best reference state to uncover the relation between base sequences and their intrinsic flexibility; however, this has long been hampered by a lack of suitable experimental data. We investigated this relationship by compiling and analyzing a large dataset of NMR (31)P chemical shifts in solution. These measurements reflect the BI BII equilibrium in DNA, intimately correlated to helicoidal descriptors of the curvature, winding and groove dimensions. Comparing the ten complementary DNA dinucleotide steps indicates that some steps are much more flexible than others. This malleability is primarily controlled at the dinucleotide level, modulated by the tetranucleotide environment. Our analyses provide an experimental scale called TRX that quantifies the intrinsic flexibility of the ten dinucleotide steps in terms of Twist, Roll, and X-disp (base pair displacement). Applying the TRX scale to DNA sequences optimized for nucleosome formation reveals a 10 base-pair periodic alternation of stiff and flexible regions. Thus, DNA flexibility captured by the TRX scale is relevant to nucleosome formation, suggesting that this scale may be of general interest to better understand protein-DNA recognition.

  5. Combined intrinsic elastocaloric and electrocaloric properties of ferroelectrics

    Science.gov (United States)

    Khassaf, H.; Patel, T.; Alpay, S. P.

    2017-04-01

    In multiferroic materials, adiabatic temperature changes can be obtained by the combined application of electric, stress, and magnetic fields. These external stimuli provide additional channels of entropy variations resulting in a multi-caloric response. In ferroelectric (FE) materials, caloric responses can be obtained with the application of electric and mechanical fields. Here, we compute the intrinsic elastocaloric and stress-mediated electrocaloric behavior of prototypical FE materials using the Landau-Devonshire theory of phase transformations with appropriate electrical and electro-mechanical boundary conditions. We show that an elastocaloric adiabatic temperature variation of 12.7 °C can be obtained in PbTiO3 with the application of uniaxial tensile stress of 500 MPa near its Curie point. This is 59% higher than its pure intrinsic electrocaloric response for an electric field difference of 100 kV/cm. Moreover, external stresses allow the maximum electro-elastocaloric response to be tuned towards room temperature. Our calculations show that relaxor FEs should exhibit large adiabatic temperature variations in relatively broad temperature ranges. These findings indicate that caloric responses in ferroic materials can be deterministically controlled and enhanced by utilizing a variety of external stimuli.

  6. Intrinsic Dynamics Analysis of a DNA Octahedron by Elastic Network Model

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    Guang Hu

    2017-01-01

    Full Text Available DNA is a fundamental component of living systems where it plays a crucial role at both functional and structural level. The programmable properties of DNA make it an interesting building block for the construction of nanostructures. However, molecular mechanisms for the arrangement of these well-defined DNA assemblies are not fully understood. In this paper, the intrinsic dynamics of a DNA octahedron has been investigated by using two types of Elastic Network Models (ENMs. The application of ENMs to DNA nanocages include the analysis of the intrinsic flexibilities of DNA double-helices and hinge sites through the calculation of the square fluctuations, as well as the intrinsic collective dynamics in terms of cross-collective map calculation coupled with global motions analysis. The dynamics profiles derived from ENMs have then been evaluated and compared with previous classical molecular dynamics simulation trajectories. The results presented here revealed that ENMs can provide useful insights into the intrinsic dynamics of large DNA nanocages and represent a useful tool in the field of structural DNA nanotechnology.

  7. Intrinsic bent DNA sites in the chromosomal replication origin of Xylella fastidiosa 9a5c

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    F. Gimenes

    2008-04-01

    Full Text Available The features of the nucleotide sequences in both replication and promoter regions have been investigated in many organisms. Intrinsically bent DNA sites associated with transcription have been described in several prokaryotic organisms. The aim of the present study was to investigate intrinsic bent DNA sites in the segment that holds the chromosomal replication origin, oriC, of Xylella fastidiosa 9a5c. Electrophoretic behavior analyses, as well as in silico analyses of both the 2-D projection and helical parameters, were performed. The chromosomal segment analyzed contains the initial sequence of the rpmH gene, an intergenic region, the dnaA gene, the oriC sequence, and the 5' partial sequence of the dnaN gene. The analysis revealed fragments with reduced electrophoretic mobility, which indicates the presence of curved DNA segments. The analysis of the helical parameter ENDS ratio revealed three bent DNA sites (b1, b2, and b3 located in the rpmH-dnaA intergenic region, the dnaA gene, and the oriC 5' end, respectively. The chromosomal segment of X. fastidiosa analyzed here is rich in phased AT tracts and in CAnT motifs. The 2-D projection indicated a segment whose structure was determined by the cumulative effect of all bent DNA sites. Further, the in silico analysis of the three different bacterial oriC sequences indicated similar negative roll and twist >34.00° values. The DnaA box sequences, and other motifs in them, may be associated with the intrinsic DNA curvature.

  8. RPA and Rad51 constitute a cell intrinsic mechanism to protect the cytosol from self DNA.

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    Wolf, Christine; Rapp, Alexander; Berndt, Nicole; Staroske, Wolfgang; Schuster, Max; Dobrick-Mattheuer, Manuela; Kretschmer, Stefanie; König, Nadja; Kurth, Thomas; Wieczorek, Dagmar; Kast, Karin; Cardoso, M Cristina; Günther, Claudia; Lee-Kirsch, Min Ae

    2016-05-27

    Immune recognition of cytosolic DNA represents a central antiviral defence mechanism. Within the host, short single-stranded DNA (ssDNA) continuously arises during the repair of DNA damage induced by endogenous and environmental genotoxic stress. Here we show that short ssDNA traverses the nuclear membrane, but is drawn into the nucleus by binding to the DNA replication and repair factors RPA and Rad51. Knockdown of RPA and Rad51 enhances cytosolic leakage of ssDNA resulting in cGAS-dependent type I IFN activation. Mutations in the exonuclease TREX1 cause type I IFN-dependent autoinflammation and autoimmunity. We demonstrate that TREX1 is anchored within the outer nuclear membrane to ensure immediate degradation of ssDNA leaking into the cytosol. In TREX1-deficient fibroblasts, accumulating ssDNA causes exhaustion of RPA and Rad51 resulting in replication stress and activation of p53 and type I IFN. Thus, the ssDNA-binding capacity of RPA and Rad51 constitutes a cell intrinsic mechanism to protect the cytosol from self DNA.

  9. Motor memory is encoded as a gain-field combination of intrinsic and extrinsic action representations.

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    Brayanov, Jordan B; Press, Daniel Z; Smith, Maurice A

    2012-10-24

    Actions can be planned in either an intrinsic (body-based) reference frame or an extrinsic (world-based) frame, and understanding how the internal representations associated with these frames contribute to the learning of motor actions is a key issue in motor control. We studied the internal representation of this learning in human subjects by analyzing generalization patterns across an array of different movement directions and workspaces after training a visuomotor rotation in a single movement direction in one workspace. This provided a dense sampling of the generalization function across intrinsic and extrinsic reference frames, which allowed us to dissociate intrinsic and extrinsic representations and determine the manner in which they contributed to the motor memory for a trained action. A first experiment showed that the generalization pattern reflected a memory that was intermediate between intrinsic and extrinsic representations. A second experiment showed that this intermediate representation could not arise from separate intrinsic and extrinsic learning. Instead, we find that the representation of learning is based on a gain-field combination of local representations in intrinsic and extrinsic coordinates. This gain-field representation generalizes between actions by effectively computing similarity based on the (Mahalanobis) distance across intrinsic and extrinsic coordinates and is in line with neural recordings showing mixed intrinsic-extrinsic representations in motor and parietal cortices.

  10. Simulation Assisted Analysis of the Intrinsic Stiffness for Short DNA Molecules Imaged with Scanning Atomic Force Microscopy.

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    Haowei Wang

    Full Text Available Studying the mechanical properties of short segments of dsDNA can provide insight into various biophysical phenomena, from DNA looping to the organization of nucleosomes. Scanning atomic force microscopy (AFM is able to acquire images of single DNA molecules with near-basepair resolution. From many images, one may use equilibrium statistical mechanics to quantify the intrinsic stiffness (or persistence length of the DNA. However, this approach is highly dependent upon both the correct microscopic polymer model and a correct image analysis of DNA contours. These complications have led to significant debate over the flexibility of dsDNA at short length scales. We first show how to extract accurate measures of DNA contour lengths by calibrating to DNA traces of simulated AFM data. After this calibration, we show that DNA adsorbed on an aminopropyl-mica surface behaves as a worm-like chain (WLC for contour lengths as small as ~20 nm. We also show that a DNA binding protein can modify the mechanics of the DNA from that of a WLC.

  11. DNA Profiling of Convicted Offender Samples for the Combined DNA Index System

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    Millard, Julie T

    2011-01-01

    The cornerstone of forensic chemistry is that a perpetrator inevitably leaves trace evidence at a crime scene. One important type of evidence is DNA, which has been instrumental in both the implication and exoneration of thousands of suspects in a wide range of crimes. The Combined DNA Index System (CODIS), a network of DNA databases, provides…

  12. Acceleration of vascularized bone tissue-engineered constructs in a large animal model combining intrinsic and extrinsic vascularization.

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    Weigand, Annika; Beier, Justus P; Hess, Andreas; Gerber, Thomas; Arkudas, Andreas; Horch, Raymund E; Boos, Anja M

    2015-05-01

    During the last decades, a range of excellent and promising strategies in Bone Tissue Engineering have been developed. However, the remaining major problem is the lack of vascularization. In this study, extrinsic and intrinsic vascularization strategies were combined for acceleration of vascularization. For optimal biomechanical stability of the defect site and simplifying future transition into clinical application, a primary stable and approved nanostructured bone substitute in clinically relevant size was used. An arteriovenous (AV) loop was microsurgically created in sheep and implanted, together with the bone substitute, in either perforated titanium chambers (intrinsic/extrinsic) for different time intervals of up to 18 weeks or isolated Teflon(®) chambers (intrinsic) for 18 weeks. Over time, magnetic resonance imaging and micro-computed tomography (CT) analyses illustrate the dense vascularization arising from the AV loop. The bone substitute was completely interspersed with newly formed tissue after 12 weeks of intrinsic/extrinsic vascularization and after 18 weeks of intrinsic/extrinsic and intrinsic vascularization. Successful matrix change from an inorganic to an organic scaffold could be demonstrated in vascularized areas with scanning electron microscopy and energy dispersive X-ray spectroscopy. Using the intrinsic vascularization method only, the degradation of the scaffold and osteoclastic activity was significantly lower after 18 weeks, compared with 12 and 18 weeks in the combined intrinsic-extrinsic model. Immunohistochemical staining revealed an increase in bone tissue formation over time, without a difference between intrinsic/extrinsic and intrinsic vascularization after 18 weeks. This study presents the combination of extrinsic and intrinsic vascularization strategies for the generation of an axially vascularized bone substitute in clinically relevant size using a large animal model. The additional extrinsic vascularization promotes tissue

  13. Combined Model of Intrinsic and Extrinsic Variability for Computational Network Design with Application to Synthetic Biology

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    Toni, Tina; Tidor, Bruce

    2013-01-01

    Biological systems are inherently variable, with their dynamics influenced by intrinsic and extrinsic sources. These systems are often only partially characterized, with large uncertainties about specific sources of extrinsic variability and biochemical properties. Moreover, it is not yet well understood how different sources of variability combine and affect biological systems in concert. To successfully design biomedical therapies or synthetic circuits with robust performance, it is crucial to account for uncertainty and effects of variability. Here we introduce an efficient modeling and simulation framework to study systems that are simultaneously subject to multiple sources of variability, and apply it to make design decisions on small genetic networks that play a role of basic design elements of synthetic circuits. Specifically, the framework was used to explore the effect of transcriptional and post-transcriptional autoregulation on fluctuations in protein expression in simple genetic networks. We found that autoregulation could either suppress or increase the output variability, depending on specific noise sources and network parameters. We showed that transcriptional autoregulation was more successful than post-transcriptional in suppressing variability across a wide range of intrinsic and extrinsic magnitudes and sources. We derived the following design principles to guide the design of circuits that best suppress variability: (i) high protein cooperativity and low miRNA cooperativity, (ii) imperfect complementarity between miRNA and mRNA was preferred to perfect complementarity, and (iii) correlated expression of mRNA and miRNA – for example, on the same transcript – was best for suppression of protein variability. Results further showed that correlations in kinetic parameters between cells affected the ability to suppress variability, and that variability in transient states did not necessarily follow the same principles as variability in the steady

  14. Phylogenetic relationships of the Gomphales based on nuc-25S-rDNA, mit-12S-rDNA, and mit-atp6-DNA combined sequences

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    Admir J. Giachini; Kentaro Hosaka; Eduardo Nouhra; Joseph Spatafora; James M. Trappe

    2010-01-01

    Phylogenetic relationships among Geastrales, Gomphales, Hysterangiales, and Phallales were estimated via combined sequences: nuclear large subunit ribosomal DNA (nuc-25S-rDNA), mitochondrial small subunit ribosomal DNA (mit-12S-rDNA), and mitochondrial atp6 DNA (mit-atp6-DNA). Eighty-one taxa comprising 19 genera and 58 species...

  15. DNA origami scaffold for studying intrinsically disordered proteins of the nuclear pore complex

    NARCIS (Netherlands)

    Ketterer, Philip; Ananth, Adithya N; Laman Trip, Diederik S; Mishra, Ankur; Bertosin, Eva; Ganji, Mahipal; van der Torre, Jaco; Onck, Patrick; Dietz, Hendrik; Dekker, Cees

    2018-01-01

    The nuclear pore complex (NPC) is the gatekeeper for nuclear transport in eukaryotic cells. A key component of the NPC is the central shaft lined with intrinsically disordered proteins (IDPs) known as FG-Nups, which control the selective molecular traffic. Here, we present an approach to realize

  16. DNA origami scaffold for studying intrinsically disordered proteins of the nuclear pore complex

    NARCIS (Netherlands)

    Ketterer, Philip; Ananth, A.N.; Laman Trip, J.D.S.; Mishra, Ankur; Bertosin, Eva; Ganji, M.; van der Torre, J.; Onck, Patrick; Dietz, Hendrik; Dekker, C.

    2018-01-01

    The nuclear pore complex (NPC) is the gatekeeper for nuclear transport in eukaryotic cells. A key component of the NPC is the central shaft lined with intrinsically disordered proteins (IDPs) known as FG-Nups, which control the selective molecular traffic. Here, we present an approach to realize

  17. Effect of Temperature on the Intrinsic Flexibility of DNA and Its Interaction with Architectural Proteins

    NARCIS (Netherlands)

    Driessen, R.P.C.; Sitter, G.; Moolenaar, G.F.; Wuite, G.J.L.; Goosen, N.; Dame, R.T.

    2014-01-01

    The helical structure of double-stranded DNA is destabilized by increasing temperature. Above a critical temperature (the melting temperature), the two strands in duplex DNA become fully separated. Below this temperature, the structural effects are localized. Using tethered particle motion in a

  18. Electrochemical DNA biosensors based on platinum nanoparticles combined carbon nanotubes

    International Nuclear Information System (INIS)

    Zhu Ningning; Chang Zhu; He Pingang; Fang Yuzhi

    2005-01-01

    Platinum nanoparticles were used in combination with multi-walled carbon nanotubes (MWCNTs) for fabricating sensitivity-enhanced electrochemical DNA biosensor. Multi-walled carbon nanotubes and platinum nanoparticles were dispersed in Nafion, which were used to fabricate the modification of the glassy carbon electrode (GCE) surface. Oligonucleotides with amino groups at the 5' end were covalently linked onto carboxylic groups of MWCNTs on the electrode. The hybridization events were monitored by differential pulse voltammetry (DPV) measurement of the intercalated daunomycin. Due to the ability of carbon nanotubes to promote electron-transfer reactions, the high catalytic activities of platinum nanoparticles for chemical reactions, the sensitivity of presented electrochemical DNA biosensors was remarkably improved. The detection limit of the method for target DNA was 1.0 x 10 -11 mol l -1

  19. The intrinsic role of nanoconfinement in chemical equilibrium: evidence from DNA hybridization.

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    Rubinovich, Leonid; Polak, Micha

    2013-05-08

    Recently we predicted that when a reaction involving a small number of molecules occurs in a nanometric-scale domain entirely segregated from the surrounding media, the nanoconfinement can shift the position of equilibrium toward products via reactant-product reduced mixing. In this Letter, we demonstrate how most-recently reported single-molecule fluorescence measurements of partial hybridization of ssDNA confined within nanofabricated chambers provide the first experimental confirmation of this entropic nanoconfinement effect. Thus, focusing separately on each occupancy-specific equilibrium constant, quantitatively reveals extra stabilization of the product upon decreasing the chamber occupancy or size. Namely, the DNA hybridization under nanoconfined conditions is significantly favored over the identical reaction occurring in bulk media with the same reactant concentrations. This effect, now directly verified for DNA, can be relevant to actual biological processes, as well as to diverse reactions occurring within molecular capsules, nanotubes, and other functional nanospaces.

  20. Novel Bacterial Topoisomerase Inhibitors Exploit Asp83 and the Intrinsic Flexibility of the DNA Gyrase Binding Site

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    Sebastian Franco-Ulloa

    2018-02-01

    Full Text Available DNA gyrases are enzymes that control the topology of DNA in bacteria cells. This is a vital function for bacteria. For this reason, DNA gyrases are targeted by widely used antibiotics such as quinolones. Recently, structural and biochemical investigations identified a new class of DNA gyrase inhibitors called NBTIs (i.e., novel bacterial topoisomerase inhibitors. NBTIs are particularly promising because they are active against multi-drug resistant bacteria, an alarming clinical issue. Structural data recently demonstrated that these NBTIs bind tightly to a newly identified pocket at the dimer interface of the DNA–protein complex. In the present study, we used molecular dynamics (MD simulations and docking calculations to shed new light on the binding of NBTIs to this site. Interestingly, our MD simulations demonstrate the intrinsic flexibility of this binding site, which allows the pocket to adapt its conformation and form optimal interactions with the ligand. In particular, we examined two ligands, AM8085 and AM8191, which induced a repositioning of a key aspartate (Asp83B, whose side chain can rotate within the binding site. The conformational rearrangement of Asp83B allows the formation of a newly identified H-bond interaction with an NH on the bound NBTI, which seems important for the binding of NBTIs having such functionality. We validated these findings through docking calculations using an extended set of cognate oxabicyclooctane-linked NBTIs derivatives (~150, in total, screened against multiple target conformations. The newly identified H-bond interaction significantly improves the docking enrichment. These insights could be helpful for future virtual screening campaigns against DNA gyrase.

  1. Intrinsically active nanobody-modified polymeric micelles for tumor-targeted combination therapy

    NARCIS (Netherlands)

    Talelli, M.; Oliveira, S.; Rijcken, C.J.; Pieters, E.H.; Etrych, T.; Ulbrich, K.; van Nostrum, C.F.; Storm, Gerrit; Hennink, W.E.; Lammers, Twan Gerardus Gertudis Maria

    2013-01-01

    Various different passively and actively targeted nanomedicines have been designed and evaluated over the years, in particular for the treatment of cancer. Reasoning that the potential of ligand-modified nanomedicines can be substantially improved if intrinsically active targeting moieties are used,

  2. Activation of the intrinsic-apoptotic pathway in LNCaP prostate cancer cells by genistein- topotecan combination treatments

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    Vanessa Hörmann

    2013-03-01

    Full Text Available ABSTRACTBackground: Prostate cancer is the second most common cancer in American men. The development of alternative preventative and/or treatment options utilizing a combination of phytochemicals and chemotherapeutic drugs could be an attractive alternative compared to conventional carcinoma treatments. Genistein isoflavone is the primary dietary phytochemical found in soy and has demonstrated anti-tumor activities in LNCaP prostate cancer cells. Topotecan Hydrochloride (Hycamtin is an FDA-approved chemotherapy for secondary treatment of lung, ovarian and cervical cancers. The purpose of this study was to detail the potential activation of the intrinsic apoptotic pathway in LNCaP prostate cancer cells through genistein-topotecan combination treatments.Methods: LNCaP cells were cultured in complete RPMI medium in a monolayer (70-80% confluency at 37ºC and 5% CO2. Treatment consisted of single and combination groups of genistein and topotecan for 24 hours. The treated cells were assayed for i growth inhibition through trypan blue exclusion assay and microphotography , ii classification of cellular death through acridine/ ethidium bromide fluorescent staining, and iii activation of the intrinsic apoptotic pathway through Jc-1: mitochondrial membrane potential assay, cytochrome c release and Bcl-2 protein expression.Results: The overall data indicated that genistein-topotecan combination was significantly more efficacious in reducing the prostate carcinoma’s viability compared to the single treatment options. In all treatment groups, cell death occurred primarily through the activation of the intrinsic apoptotic pathway.Conclusion: The combination of topotecan and genistein has the potential to lead to treatment options with equal therapeutic efficiency as traditional chemo- and radiation therapies, but lower cell cytotoxicity and fewer side effects in patients.

  3. A Programmable DNA Origami Platform for Organizing Intrinsically Disordered Nucleoporins within Nanopore Confinement.

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    Fisher, Patrick D Ellis; Shen, Qi; Akpinar, Bernice; Davis, Luke K; Chung, Kenny Kwok Hin; Baddeley, David; Šarić, Anđela; Melia, Thomas J; Hoogenboom, Bart W; Lin, Chenxiang; Lusk, C Patrick

    2018-02-27

    Nuclear pore complexes (NPCs) form gateways that control molecular exchange between the nucleus and the cytoplasm. They impose a diffusion barrier to macromolecules and enable the selective transport of nuclear transport receptors with bound cargo. The underlying mechanisms that establish these permeability properties remain to be fully elucidated but require unstructured nuclear pore proteins rich in Phe-Gly (FG)-repeat domains of different types, such as FxFG and GLFG. While physical modeling and in vitro approaches have provided a framework for explaining how the FG network contributes to the barrier and transport properties of the NPC, it remains unknown whether the number and/or the spatial positioning of different FG-domains along a cylindrical, ∼40 nm diameter transport channel contributes to their collective properties and function. To begin to answer these questions, we have used DNA origami to build a cylinder that mimics the dimensions of the central transport channel and can house a specified number of FG-domains at specific positions with easily tunable design parameters, such as grafting density and topology. We find the overall morphology of the FG-domain assemblies to be dependent on their chemical composition, determined by the type and density of FG-repeat, and on their architectural confinement provided by the DNA cylinder, largely consistent with here presented molecular dynamics simulations based on a coarse-grained polymer model. In addition, high-speed atomic force microscopy reveals local and reversible FG-domain condensation that transiently occludes the lumen of the DNA central channel mimics, suggestive of how the NPC might establish its permeability properties.

  4. Combining short- and long-range fluorescence reporters with simulations to explore the intramolecular dynamics of an intrinsically disordered protein

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    Zosel, Franziska; Haenni, Dominik; Soranno, Andrea; Nettels, Daniel; Schuler, Benjamin

    2017-10-01

    Intrinsically disordered proteins (IDPs) are increasingly recognized as a class of molecules that can exert essential biological functions even in the absence of a well-defined three-dimensional structure. Understanding the conformational distributions and dynamics of these highly flexible proteins is thus essential for explaining the molecular mechanisms underlying their function. Single-molecule fluorescence spectroscopy in combination with Förster resonance energy transfer (FRET) is a powerful tool for probing intramolecular distances and the rapid long-range distance dynamics in IDPs. To complement the information from FRET, we combine it with photoinduced electron transfer (PET) quenching to monitor local loop-closure kinetics at the same time and in the same molecule. Here we employed this combination to investigate the intrinsically disordered N-terminal domain of HIV-1 integrase. The results show that both long-range dynamics and loop closure kinetics on the sub-microsecond time scale can be obtained reliably from a single set of measurements by the analysis with a comprehensive model of the underlying photon statistics including both FRET and PET. A more detailed molecular interpretation of the results is enabled by direct comparison with a recent extensive atomistic molecular dynamics simulation of integrase. The simulations are in good agreement with experiment and can explain the deviation from simple models of chain dynamics by the formation of persistent local secondary structure. The results illustrate the power of a close combination of single-molecule spectroscopy and simulations for advancing our understanding of the dynamics and detailed mechanisms in unfolded and intrinsically disordered proteins.

  5. Human Immunodeficiency Virus-Type 1 LTR DNA contains an intrinsic gene producing antisense RNA and protein products

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    Hsiao Chiu-Bin

    2006-11-01

    Full Text Available Abstract Background While viruses have long been shown to capitalize on their limited genomic size by utilizing both strands of DNA or complementary DNA/RNA intermediates to code for viral proteins, it has been assumed that human retroviruses have all their major proteins translated only from the plus or sense strand of RNA, despite their requirement for a dsDNA proviral intermediate. Several studies, however, have suggested the presence of antisense transcription for both HIV-1 and HTLV-1. More recently an antisense transcript responsible for the HTLV-1 bZIP factor (HBZ protein has been described. In this study we investigated the possibility of an antisense gene contained within the human immunodeficiency virus type 1 (HIV-1 long terminal repeat (LTR. Results Inspection of published sequences revealed a potential transcription initiator element (INR situated downstream of, and in reverse orientation to, the usual HIV-1 promoter and transcription start site. This antisense initiator (HIVaINR suggested the possibility of an antisense gene responsible for RNA and protein production. We show that antisense transcripts are generated, in vitro and in vivo, originating from the TAR DNA of the HIV-1 LTR. To test the possibility that protein(s could be translated from this novel HIV-1 antisense RNA, recombinant HIV antisense gene-FLAG vectors were designed. Recombinant protein(s were produced and isolated utilizing carboxy-terminal FLAG epitope (DYKDDDDK sequences. In addition, affinity-purified antisera to an internal peptide derived from the HIV antisense protein (HAP sequences identified HAPs from HIV+ human peripheral blood lymphocytes. Conclusion HIV-1 contains an antisense gene in the U3-R regions of the LTR responsible for both an antisense RNA transcript and proteins. This antisense transcript has tremendous potential for intrinsic RNA regulation because of its overlap with the beginning of all HIV-1 sense RNA transcripts by 25 nucleotides. The

  6. Specific solvent effect on lumazine photophysics: A combined fluorescence and intrinsic reaction coordinate analysis

    Energy Technology Data Exchange (ETDEWEB)

    Moyon, N. Shaemningwar; Gashnga, Pynsakhiat Miki; Phukan, Smritakshi; Mitra, Sivaprasad, E-mail: smitra@nehu.ac.in

    2013-06-27

    Highlights: • Correlation of lumazine photophysics with multiparametric Kamlet–Taft equation. • Solvent basicity (β) contributes maximum towards the hydrogen bonding (HB) effect. • HB interaction occurs at N1 and N3 proton in S{sub 0} and S{sub 1} state, respectively. • IRC calculation for different tautomerization processes both in S{sub 0} and S{sub 1} states. • Process related to riboflavin biosynthesis is thermodynamically feasible. - Abstract: The photophysical properties and tautomerization behavior of neutral lumazine were studied by fluorescence spectroscopy and density functional theory calculation. A quantitative estimation of the contributions from different solvatochromic parameters, like solvent polarizibility (π{sup ∗}), hydrogen bond donation (α) and hydrogen bond accepting (β) ability of the solvent, was made using linear free energy relationships based on the Kamlet–Taft equation. The analysis reveals that the hydrogen bond acceptance ability of the solvent is the most important parameter characterizing the excited state behavior of lumazine. Theoretical calculations result predict an extensive charge redistribution of lumazine upon excitation corresponding to the N3 and N1 proton dissociation sites by solvents in the ground and excited states, respectively. Comparison of S{sub 0} and S{sub 1} state potential energy curves constructed for several water mediated tautomerization processes by intrinsic reaction coordinate analysis of lumazine-H{sub 2}O cluster shows that (3,2) and (1,8) hydrogen migrations are the most favorable processes upon excitation.

  7. DNA Immobilization and Hybridization Detection by the Intrinsic Molecular Charge Using Capacitive Field-Effect Sensors Modified with a Charged Weak Polyelectrolyte Layer.

    Science.gov (United States)

    Bronder, Thomas S; Poghossian, Arshak; Scheja, Sabrina; Wu, Chunsheng; Keusgen, Michael; Mewes, Dieter; Schöning, Michael J

    2015-09-16

    Miniaturized setup, compatibility with advanced micro- and nanotechnologies, and ability to detect biomolecules by their intrinsic molecular charge favor the semiconductor field-effect platform as one of the most attractive approaches for the development of label-free DNA chips. In this work, a capacitive field-effect EIS (electrolyte-insulator-semiconductor) sensor covered with a layer-by-layer prepared, positively charged weak polyelectrolyte layer of PAH (poly(allylamine hydrochloride)) was used for the label-free electrical detection of DNA (deoxyribonucleic acid) immobilization and hybridization. The negatively charged probe single-stranded DNA (ssDNA) molecules were electrostatically adsorbed onto the positively charged PAH layer, resulting in a preferentially flat orientation of the ssDNA molecules within the Debye length, thus yielding a reduced charge-screening effect and a higher sensor signal. Each sensor-surface modification step (PAH adsorption, probe ssDNA immobilization, hybridization with complementary target DNA (cDNA), reducing an unspecific adsorption by a blocking agent, incubation with noncomplementary DNA (ncDNA) solution) was monitored by means of capacitance-voltage and constant-capacitance measurements. In addition, the surface morphology of the PAH layer was studied by atomic force microscopy and contact-angle measurements. High hybridization signals of 34 and 43 mV were recorded in low-ionic strength solutions of 10 and 1 mM, respectively. In contrast, a small signal of 4 mV was recorded in the case of unspecific adsorption of fully mismatched ncDNA. The density of probe ssDNA and dsDNA molecules as well as the hybridization efficiency was estimated using the experimentally measured DNA immobilization and hybridization signals and a simplified double-layer capacitor model. The results of field-effect experiments were supported by fluorescence measurements, verifying the DNA-immobilization and hybridization event.

  8. The merits of DNA content and cell kinetic parameters for the assessment of intrinsic cellular radiosensitivity to photon and high-LET neutron irradiation

    International Nuclear Information System (INIS)

    Theron, C.S.; Serafin, A.; Bohm, L.; Slabbert, J.P.

    1997-01-01

    Differences of the intrinsic cellular radiosensitivity between tumours make the selection of patients for specific radiation schedules very difficult. The reasons for these variations are still unclear, but are thought to be due to genomic and cellular characteristics. Radiosensitivities vary between cell cycle stages, with S-phase cells being most radioresistant and G2/M phase cells most radiosensitive. It is also well established that most tumour cells have an abnormal ploidy. DNA content and cellular proliferation kinetics therefore could influence the intrinsic radiosensitivity. This prompted us to assess the merits of these parameters as predictors of radiation response. (authors)

  9. Combined Cognitive-Psychological-Physical Intervention Induces Reorganization of Intrinsic Functional Brain Architecture in Older Adults

    Directory of Open Access Journals (Sweden)

    Zhiwei Zheng

    2015-01-01

    Full Text Available Mounting evidence suggests that enriched mental, physical, and socially stimulating activities are beneficial for counteracting age-related decreases in brain function and cognition in older adults. Here, we used functional magnetic resonance imaging (fMRI to demonstrate the functional plasticity of brain activity in response to a combined cognitive-psychological-physical intervention and investigated the contribution of the intervention-related brain changes to individual performance in healthy older adults. The intervention was composed of a 6-week program of combined activities including cognitive training, Tai Chi exercise, and group counseling. The results showed improved cognitive performance and reorganized regional homogeneity of spontaneous fluctuations in the blood oxygen level-dependent (BOLD signals in the superior and middle temporal gyri, and the posterior lobe of the cerebellum, in the participants who attended the intervention. Intriguingly, the intervention-induced changes in the coherence of local spontaneous activity correlated with the improvements in individual cognitive performance. Taken together with our previous findings of enhanced resting-state functional connectivity between the medial prefrontal cortex and medial temporal lobe regions following a combined intervention program in older adults, we conclude that the functional plasticity of the aging brain is a rather complex process, and an effective cognitive-psychological-physical intervention is helpful for maintaining a healthy brain and comprehensive cognition during old age.

  10. Altered temporal features of intrinsic connectivity networks in boys with combined type of attention deficit hyperactivity disorder

    International Nuclear Information System (INIS)

    Wang, Xun-Heng; Li, Lihua

    2015-01-01

    Highlights: • Temporal patterns within ICNs provide new way to investigate ADHD brains. • ADHD exhibits enhanced temporal activities within and between ICNs. • Network-wise ALFF influences functional connectivity between ICNs. • Univariate patterns within ICNs are correlated to behavior scores. - Abstract: Purpose: Investigating the altered temporal features within and between intrinsic connectivity networks (ICNs) for boys with attention-deficit/hyperactivity disorder (ADHD); and analyzing the relationships between altered temporal features within ICNs and behavior scores. Materials and methods: A cohort of boys with combined type of ADHD and a cohort of age-matched healthy boys were recruited from ADHD-200 Consortium. All resting-state fMRI datasets were preprocessed and normalized into standard brain space. Using general linear regression, 20 ICNs were taken as spatial templates to analyze the time-courses of ICNs for each subject. Amplitude of low frequency fluctuations (ALFFs) were computed as univariate temporal features within ICNs. Pearson correlation coefficients and node strengths were computed as bivariate temporal features between ICNs. Additional correlation analysis was performed between temporal features of ICNs and behavior scores. Results: ADHD exhibited more activated network-wise ALFF than normal controls in attention and default mode-related network. Enhanced functional connectivities between ICNs were found in ADHD. The network-wise ALFF within ICNs might influence the functional connectivity between ICNs. The temporal pattern within posterior default mode network (pDMN) was positively correlated to inattentive scores. The subcortical network, fusiform-related DMN and attention-related networks were negatively correlated to Intelligence Quotient (IQ) scores. Conclusion: The temporal low frequency oscillations of ICNs in boys with ADHD were more activated than normal controls during resting state; the temporal features within ICNs could

  11. Altered temporal features of intrinsic connectivity networks in boys with combined type of attention deficit hyperactivity disorder

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Xun-Heng, E-mail: xhwang@hdu.edu.cn [College of Life Information Science and Instrument Engineering, Hangzhou Dianzi University, Hangzhou 310018 (China); School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096 (China); Li, Lihua [College of Life Information Science and Instrument Engineering, Hangzhou Dianzi University, Hangzhou 310018 (China)

    2015-05-15

    Highlights: • Temporal patterns within ICNs provide new way to investigate ADHD brains. • ADHD exhibits enhanced temporal activities within and between ICNs. • Network-wise ALFF influences functional connectivity between ICNs. • Univariate patterns within ICNs are correlated to behavior scores. - Abstract: Purpose: Investigating the altered temporal features within and between intrinsic connectivity networks (ICNs) for boys with attention-deficit/hyperactivity disorder (ADHD); and analyzing the relationships between altered temporal features within ICNs and behavior scores. Materials and methods: A cohort of boys with combined type of ADHD and a cohort of age-matched healthy boys were recruited from ADHD-200 Consortium. All resting-state fMRI datasets were preprocessed and normalized into standard brain space. Using general linear regression, 20 ICNs were taken as spatial templates to analyze the time-courses of ICNs for each subject. Amplitude of low frequency fluctuations (ALFFs) were computed as univariate temporal features within ICNs. Pearson correlation coefficients and node strengths were computed as bivariate temporal features between ICNs. Additional correlation analysis was performed between temporal features of ICNs and behavior scores. Results: ADHD exhibited more activated network-wise ALFF than normal controls in attention and default mode-related network. Enhanced functional connectivities between ICNs were found in ADHD. The network-wise ALFF within ICNs might influence the functional connectivity between ICNs. The temporal pattern within posterior default mode network (pDMN) was positively correlated to inattentive scores. The subcortical network, fusiform-related DMN and attention-related networks were negatively correlated to Intelligence Quotient (IQ) scores. Conclusion: The temporal low frequency oscillations of ICNs in boys with ADHD were more activated than normal controls during resting state; the temporal features within ICNs could

  12. Determination of chromium combined with DNA, RNA and protein in chromium-rich brewer's yeast

    International Nuclear Information System (INIS)

    Ding Wenjun; Qian Qinfang; Hou Xiaolin; Feng Weiyue; Chai Zhifang

    2000-01-01

    The contents of chromium in the DNA, RNA and protein fractions separated from chromium-rich and normal brewer's yeast were determined with the neutron activation analysis in order to study the combination of Cr with DNA, RNA and protein in chromium-rich brewer's yeast. The results showed that the extracting rats and concentrations of DNA, RNA and protein had no significant difference in two types of yeast, but the chromium contents of DNA, RNA and protein in the chromium-rich yeast were significantly higher than those in the normal. In addition, the content of chromium in DNA was much higher than that in RNA and protein, which indicated that the inorganic chromium compounds entered into the yeast cell, during the yeast cultivation in the culture medium containing chromium were converted into organic chromium compounds combined with DNA, RNA and protein

  13. Editing of misaligned 3'-termini by an intrinsic 3'-5' exonuclease activity residing in the PHP domain of a family X DNA polymerase.

    Science.gov (United States)

    Baños, Benito; Lázaro, José M; Villar, Laurentino; Salas, Margarita; de Vega, Miguel

    2008-10-01

    Bacillus subtilis gene yshC encodes a family X DNA polymerase (PolX(Bs)), whose biochemical features suggest that it plays a role during DNA repair processes. Here, we show that, in addition to the polymerization activity, PolX(Bs) possesses an intrinsic 3'-5' exonuclease activity specialized in resecting unannealed 3'-termini in a gapped DNA substrate. Biochemical analysis of a PolX(Bs) deletion mutant lacking the C-terminal polymerase histidinol phosphatase (PHP) domain, present in most of the bacterial/archaeal PolXs, as well as of this separately expressed protein region, allow us to state that the 3'-5' exonuclease activity of PolX(Bs) resides in its PHP domain. Furthermore, site-directed mutagenesis of PolX(Bs) His339 and His341 residues, evolutionary conserved in the PHP superfamily members, demonstrated that the predicted metal binding site is directly involved in catalysis of the exonucleolytic reaction. The implications of the unannealed 3'-termini resection by the 3'-5' exonuclease activity of PolX(Bs) in the DNA repair context are discussed.

  14. Peptidomics combined with cDNA library unravel the diversity of centipede venom

    DEFF Research Database (Denmark)

    Rong, Mingqiang; Yang, Shilong; Wen, Bo

    2015-01-01

    of centipede venom. In the present study, we use peptidomics combined with cDNA library to uncover the diversity of centipede Scolopendra subspinipes mutilans L. Koch. 192 peptides were identified by LC-MS/MS and 79 precursors were deduced by cDNA library. Surprisingly, the signal peptides of centipede toxins...

  15. Population genetic data for six non-combined DNA index system ...

    African Journals Online (AJOL)

    The respective values for the combined power of exclusion in these populations were 0.94 and 0.99. The allele frequency data generated can be used for estimating DNA profile frequencies for the studied populations residing in South Africa. Key words: Allele frequencies, MiniSTR, DNA typing, population data, South Africa ...

  16. Mapping the structural and dynamical features of multiple p53 DNA binding domains: insights into loop 1 intrinsic dynamics.

    Directory of Open Access Journals (Sweden)

    Suryani Lukman

    Full Text Available The transcription factor p53 regulates cellular integrity in response to stress. p53 is mutated in more than half of cancerous cells, with a majority of the mutations localized to the DNA binding domain (DBD. In order to map the structural and dynamical features of the DBD, we carried out multiple copy molecular dynamics simulations (totaling 0.8 μs. Simulations show the loop 1 to be the most dynamic element among the DNA-contacting loops (loops 1-3. Loop 1 occupies two major conformational states: extended and recessed; the former but not the latter displays correlations in atomic fluctuations with those of loop 2 (~24 Å apart. Since loop 1 binds to the major groove whereas loop 2 binds to the minor groove of DNA, our results begin to provide some insight into the possible mechanism underpinning the cooperative nature of DBD binding to DNA. We propose (1 a novel mechanism underlying the dynamics of loop 1 and the possible tread-milling of p53 on DNA and (2 possible mutations on loop 1 residues to restore the transcriptional activity of an oncogenic mutation at a distant site.

  17. Replication origins oriGNAI3 and oriB of the mammalian AMPD2 locus nested in a region of straight DNA flanked by intrinsically bent DNA sites.

    Science.gov (United States)

    Balani, Valério Américo; de Lima Neto, Quirino Alves; Takeda, Karen Izumi; Gimenes, Fabrícia; Fiorini, Adriana; Debatisse, Michelle; Fernandez, Maria Aparecida

    2010-11-01

    The aim of this work was to determine whether intrinsically bent DNA sites are present at, or close to, the mammalian replication origins oriGNAI3 and oriB in the Chinese hamster AMPD2 locus. Using an electrophoretic mobility shift assay and in silico analysis, we located four intrinsically bent DNA sites (b1 to b4) in a fragment that contains the oriGNAI3 and one site (b5) proximal to oriB. The helical parameters show that each bent DNA site is curved in a left-handed superhelical writhe. A 2D projection of 3D fragment trajectories revealed that oriGNAI3 is located in a relatively straight segment flanked by bent sites b1 and b2, which map in previously identified Scaffold/Matrix Attachment Region. Sites b3 and b4 are located approximately 2 kb downstream and force the fragment into a strong closed loop structure. The b5 site is also located in an S/MAR that is found just downstream of oriB.

  18. A combined HM-PCR/SNuPE method for high sensitive detection of rare DNA methylation

    Directory of Open Access Journals (Sweden)

    Tierling Sascha

    2010-06-01

    Full Text Available Abstract Background DNA methylation changes are widely used as early molecular markers in cancer detection. Sensitive detection and classification of rare methylation changes in DNA extracted from circulating body fluids or complex tissue samples is crucial for the understanding of tumor etiology, clinical diagnosis and treatment. In this paper, we describe a combined method to monitor the presence of methylated tumor DNA in an excess of unmethylated background DNA of non-tumorous cells. The method combines heavy methyl-PCR, which favors preferential amplification of methylated marker sequence from bisulfite-treated DNA with a methylation-specific single nucleotide primer extension monitored by ion-pair, reversed-phase, high-performance liquid chromatography separation. Results This combined method allows detection of 14 pg (that is, four to five genomic copies of methylated chromosomal DNA in a 2000-fold excess (that is, 50 ng of unmethylated chromosomal background, with an analytical sensitivity of > 90%. We outline a detailed protocol for the combined assay on two examples of known cancer markers (SEPT9 and TMEFF2 and discuss general aspects of assay design and data interpretation. Finally, we provide an application example for rapid testing on tumor methylation in plasma DNA derived from a small cohort of patients with colorectal cancer. Conclusion The method allows unambiguous detection of rare DNA methylation, for example in body fluid or DNA isolates from cells or tissues, with very high sensitivity and accuracy. The application combines standard technologies and can easily be adapted to any target region of interest. It does not require costly reagents and can be used for routine screening of many samples.

  19. Combining crystallography and EPR: crystal and solution structures of the multidomain cochaperone DnaJ

    Energy Technology Data Exchange (ETDEWEB)

    Barends, Thomas R. M., E-mail: thomas.barends@mpimf-heidelberg.mpg.de [MPI for Medical Research, Heidelberg (Germany); Brosi, Richard W. W. [Freie Universitat Berlin, Berlin (Germany); Steinmetz, Andrea; Scherer, Anna; Hartmann, Elisabeth; Eschenbach, Jessica; Lorenz, Thorsten [MPI for Medical Research, Heidelberg (Germany); Seidel, Ralf [MPI for Molecular Physiology, Dortmund (Germany); Shoeman, Robert L.; Zimmermann, Sabine [MPI for Medical Research, Heidelberg (Germany); Bittl, Robert [Freie Universitat Berlin, Berlin (Germany); Schlichting, Ilme; Reinstein, Jochen [MPI for Medical Research, Heidelberg (Germany)

    2013-08-01

    The crystal structure of the N-terminal part of T. thermophilus DnaJ unexpectedly showed an ordered GF domain and guided the design of a construct enabling the first structure determination of a complete DnaJ cochaperone molecule. By combining the crystal structures with spin-labelling EPR and cross-linking in solution, a dynamic view of this flexible molecule was developed. Hsp70 chaperones assist in a large variety of protein-folding processes in the cell. Crucial for these activities is the regulation of Hsp70 by Hsp40 cochaperones. DnaJ, the bacterial homologue of Hsp40, stimulates ATP hydrolysis by DnaK (Hsp70) and thus mediates capture of substrate protein, but is also known to possess chaperone activity of its own. The first structure of a complete functional dimeric DnaJ was determined and the mobility of its individual domains in solution was investigated. Crystal structures of the complete molecular cochaperone DnaJ from Thermus thermophilus comprising the J, GF and C-terminal domains and of the J and GF domains alone showed an ordered GF domain interacting with the J domain. Structure-based EPR spin-labelling studies as well as cross-linking results showed the existence of multiple states of DnaJ in solution with different arrangements of the various domains, which has implications for the function of DnaJ.

  20. Combining bleach and mild predigestion improves ancient DNA recovery from bones

    DEFF Research Database (Denmark)

    Boessenkool, Sanne; Hanghøj, Kristian Ebbesen; Nistelberger, Heidi M.

    2017-01-01

    library characteristics, such as DNA damage profiles or the composition of microbial communities, are little affected by the pre-extraction protocols. Application of the combined protocol presented in this study will facilitate the genetic analysis of an increasing number of ancient remains...... aimed to improve ancient DNA recovery before library amplification have recently been developed. Here, we test the effects of combining two of such protocols, a bleach wash and a predigestion step, on 12 bone samples of Atlantic cod and domestic horse aged 750-1350 cal. years before present. Using high...

  1. A detrimental effect of a combined chemotherapy-radiotherapy approach in children with diffuse intrinsic brain stem gliomas?

    International Nuclear Information System (INIS)

    Freeman, Carolyn R.; Kepner, Jim; Kun, Larry E.; Sanford, Robert A.; Kadota, Richard; Mandell, Lynda; Friedman, Henry

    2000-01-01

    Purpose: To compare the proportion of patients that survive at least 1 year following treatment with hyperfractionated radiotherapy (HRT) to a dose of 70.2 Gy on Pediatric Oncology Group (POG) study no. 8495 with that of patients treated with similar radiotherapy plus cisplatinum given by continuous infusion on weeks 1, 3, and 5 of radiotherapy on POG no. 9239. Methods and Materials: The eligibility criteria for the two studies were identical and included age 3 to 21 years, previously untreated tumor involving the brain stem of which two-thirds was in the pons, history less than 6 months, and clinical findings typical for diffuse intrinsic brain stem glioma, including cranial nerve deficits, long tract signs, and ataxia. The outcome of 57 patients who were treated at the 70.2 Gy dose level of POG no. 8495 between May 1986 and February 1988 was compared with that of 64 patients treated with identical radiotherapy plus cisplatinum on POG no. 9239 between June 1992 and March 1996. Results: The number of patients accrued to POG no. 9239 was determined to guarantee that the probability was at least 0.80 of correctly detecting that the 1-year survival rate exceeded that of patients on POG no. 8495 by 0.2. However, the z value for this test was -1.564, giving a p value of 0.9411. That is, there is almost sufficient evidence to conclude that survival for patients receiving HRT plus cisplatinum on POG no. 9239 was worse than that for patients receiving the same radiotherapy alone on POG no. 8495. Conclusion: The finding that patients who received cisplatinum given as a radiosensitizing agent concurrent with HRT fared less well than those receiving the same dose of HRT alone was unexpected and is clearly a cause for concern as many current protocols for patients with diffuse intrinsic brain stem gliomas call for use of chemotherapeutic and/or biological agents given concurrent with radiotherapy

  2. Rapid detection of Listeria monocytogenes in foods, by a combination of PCR and DNA probe.

    Science.gov (United States)

    Ingianni, A; Floris, M; Palomba, P; Madeddu, M A; Quartuccio, M; Pompei, R

    2001-10-01

    Listeria monocytogenes is a frequent contaminant of water and foods. Its rapid detection is needed before some foods can be prepared for marketing. In this work L. monocytogenes has been searched for in foods, by a combination of polymerase chain reaction (PCR) and a DNA probe. Both PCR and the probe were prepared for recognizing a specific region of the internalin gene, which is responsible for the production of one of the most important pathogenic factors of Listeria. The combined use of PCR and the DNA probe was used for the detection of L. monocytogenes in over 180 environmental and food samples. Several detection methods were compared in this study, namely conventional culture methods; direct PCR; PCR after an enrichment step; a DNA probe alone; a DNA probe after enrichment and another commercially available gene-probe. Finally PCR and the DNA probe were used in series on all the samples collected. When the DNA probe was associated with the PCR, specific and accurate detection of listeria in the samples could be obtained in about a working-day. The present molecular method showed some advantages in terms of rapidity and specificity in comparison to the other aforementioned tests. In addition, it resulted as being easy to handle, even for non-specialized personnel in small diagnostic microbiology laboratories. Copyright 2001 Academic Press.

  3. A combined method for DNA analysis and radiocarbon dating from a single sample.

    Science.gov (United States)

    Korlević, Petra; Talamo, Sahra; Meyer, Matthias

    2018-03-07

    Current protocols for ancient DNA and radiocarbon analysis of ancient bones and teeth call for multiple destructive samplings of a given specimen, thereby increasing the extent of undesirable damage to precious archaeological material. Here we present a method that makes it possible to obtain both ancient DNA sequences and radiocarbon dates from the same sample material. This is achieved by releasing DNA from the bone matrix through incubation with either EDTA or phosphate buffer prior to complete demineralization and collagen extraction utilizing the acid-base-acid-gelatinization and ultrafiltration procedure established in most radiocarbon dating laboratories. Using a set of 12 bones of different ages and preservation conditions we demonstrate that on average 89% of the DNA can be released from sample powder with minimal, or 38% without any, detectable collagen loss. We also detect no skews in radiocarbon dates compared to untreated samples. Given the different material demands for radiocarbon dating (500 mg of bone/dentine) and DNA analysis (10-100 mg), combined DNA and collagen extraction not only streamlines the sampling process but also drastically increases the amount of DNA that can be recovered from limited sample material.

  4. Intrinsic Motivation.

    Science.gov (United States)

    Deci, Edward L.

    The paper draws together a wide variety of research which relates to the topic of intrinsic motivation; intrinsically motivated activities are defined as those which a person does for no apparent reward except the activity itself or the feelings which result from the activity. Most of this research was not originally reported within the framework…

  5. Imaging of DNA and Protein by SFM and Combined SFM-TIRF Microscopy.

    Science.gov (United States)

    Grosbart, Małgorzata; Ristić, Dejan; Sánchez, Humberto; Wyman, Claire

    2018-01-01

    Direct imaging is invaluable for understanding the mechanism of complex genome transactions where proteins work together to organize, transcribe, replicate and repair DNA. Scanning (or atomic) force microscopy is an ideal tool for this, providing 3D information on molecular structure at nm resolution from defined components. This is a convenient and practical addition to in vitro studies as readily obtainable amounts of purified proteins and DNA are required. The images reveal structural details on the size and location of DNA bound proteins as well as protein-induced arrangement of the DNA, which are directly correlated in the same complexes. In addition, even from static images, the different forms observed and their relative distributions can be used to deduce the variety and stability of different complexes that are necessarily involved in dynamic processes. Recently available instruments that combine fluorescence with topographic imaging allow the identification of specific molecular components in complex assemblies, which broadens the applications and increases the information obtained from direct imaging of molecular complexes. We describe here basic methods for preparing samples of proteins, DNA and complexes of the two for topographic imaging and quantitative analysis. We also describe special considerations for combined fluorescence and topographic imaging of molecular complexes.

  6. Combination phenylbutyrate/gemcitabine therapy effectively inhibits in vitro and in vivo growth of NSCLC by intrinsic apoptotic pathways

    Directory of Open Access Journals (Sweden)

    Schniewind Bodo

    2006-11-01

    Full Text Available Abstract Background Standard chemotherapy protocols in NSCLC are of limited clinical benefit. Histone deacetylase (HDAC inhibitors represent a new strategy in human cancer therapy. In this study the combination of the HDAC inhibitor phenylbutyrate (PB and the nucleoside analogue gemcitabine (GEM was evaluated and the mechanisms underlying increased cell death were analyzed. Methods Dose escalation studies evaluating the cytotoxicity of PB (0.01–100 mM, GEM (0.01–100 μg/ml and a combination of the two were performed on two NSCLC cell lines (BEN and KNS62. Apoptotic cell death was quantified. The involvement of caspase-dependent cell death and MAP-kinase activation was analyzed. Additionally, mitochondrial damage was determined. In an orthotopic animal model the combined effect of PB and GEM on therapy was analyzed. Results Applied as a single drug both GEM and PB revealed limited potential to induce apoptosis in KNS62 and Ben cells. Combination therapy was 50–80% (p = 0.012 more effective than either agent alone. On the caspase level, combination therapy significantly increased cleavage of the pro-forms compared to single chemotherapy. The broad spectrum caspase-inhibitor zVAD was able to inhibit caspase cleavage completely, but reduced the frequency of apoptotic cells only by 30%. Combination therapy significantly increased changes in MTP and the release of cyto-c, AIF and Smac/Diabolo into the cytoplasm. Furthermore, the inhibitors of apoptosis c-IAP1 and c-IAP2 were downregulated and it was shown that in combination therapy JNK activation contributed significantly to induction of apoptosis. The size of the primary tumors growing orthotopically in SCID mice treated for 4 weeks with GEM and PB was significantly reduced (2.2–2.7 fold compared to GEM therapy alone. The Ki-67 (KNS62: p = 0.015; Ben: p = 0.093 and topoisomerase IIα (KNS62: p = 0.008; Ben: p = 0.064 proliferation indices were clearly reduced in tumors treated by combination

  7. MUTYH mediates the toxicity of combined DNA 6-thioguanine and UVA radiation

    Science.gov (United States)

    De Luca, Gabriele; Leopardi, Paola; Mancuso, Maria Teresa; Casorelli, Ida; Pichierri, Pietro; Karran, Peter; Bignami, Margherita

    2015-01-01

    The therapeutic thiopurines, including the immunosuppressant azathioprine (Aza) cause the accumulation of the UVA photosensitizer 6-thioguanine (6-TG) in the DNA of the patients' cells. DNA 6-TG and UVA are synergistically cytotoxic and their interaction causes oxidative damage. The MUTYH DNA glycosylase participates in the base excision repair of oxidized DNA bases. Using Mutyh-nullmouse fibroblasts (MEFs) we examined whether MUTYH provides protection against the lethal effects of combined DNA 6-TG/UVA. Surprisingly, Mutyh-null MEFs were more resistant than wild-type MEFs, despite accumulating higher levels of DNA 8-oxo-7,8-dihydroguanine (8-oxoG). Their enhanced 6-TG/UVA resistance reflected the absence of the MUTYH protein and MEFs expressing enzymatically-dead human variants were as sensitive as wild-type cells. Consistent with their enhanced resistance, Mutyh-null cells sustained fewer DNA strand breaks and lower levels of chromosomal damage after 6-TG/UVA. Although 6-TG/UVA treatment caused early checkpoint activation irrespective of the MUTYH status, Mutyh-null cells failed to arrest in S-phase at late time points. MUTYH-dependent toxicity was also apparent in vivo. Mutyh−/−mice survived better than wild-type during a 12-month chronicexposure to Aza/UVA treatments that significantly increased levels of skin DNA 8-oxoG. Two squamous cell skin carcinomas arose in Aza/UVA treated Mutyh−/− mice whereas similarly treated wild-type animals remained tumor-free. PMID:25638157

  8. Flow cytometric detection of micronuclei by combined staining of DNA and membranes

    International Nuclear Information System (INIS)

    Wessels, J.M.; Nuesse, M.

    1995-01-01

    A new staining method is presented for flow cytometric measurement of micronuclei (MN) in cell cultures and human lymphocytes using membrane-specific fluorescent dyes in addition to DNA staining. Several combinations of fluorescent membrane and DNA dyes were studied for a better discrimination of MN from debris in a suspension of nuclei and micronuclei. For staining of membranes, the lipophilic dyes 2-hydroxyethyl-7,12,17-tris(methoxyethyl)porphycene (HEPn) and 1,6-diphenyl-1,3,5-hexatriene (DPH) were used in combination with ethidium bromide (EB), proflavine (PF), and Hoechst 33258 (HO). Due to their spectral properties, HO or EB combined with HEPn were not as suitable for the discrimination of MN from debris as was HEPn in combination with PF. With HEPn in combination with PF, however, additional noise was found at low fluorescence intensities, probably due to free fluorescent dye molecules in the solution. The optimal simultaneous staining of membranes and DNA was obtained using a combination of DPH and EB. The induction of MN in Chinese hamster and mouse NIH-3T3 cells by UV-B illumination was studied with this new staining technique. UV-B illumination (280-360 nm) induced MN in both cell lines. Chinese hamster cells were found to be more sensitive to these wavelengths. Illumination with wavelengths above 360 nm did not induce MN in either cell line. The results obtained from human lymphocytes using the combination of EB or DPH were comparable to the results obtained with the combination of EB and HO. 23 refs., 7 figs

  9. Intrinsic and extrinsic mortality reunited

    DEFF Research Database (Denmark)

    Koopman, Jacob J E; Wensink, Maarten J; Rozing, Maarten P

    2015-01-01

    Intrinsic and extrinsic mortality are often separated in order to understand and measure aging. Intrinsic mortality is assumed to be a result of aging and to increase over age, whereas extrinsic mortality is assumed to be a result of environmental hazards and be constant over age. However......, allegedly intrinsic and extrinsic mortality have an exponentially increasing age pattern in common. Theories of aging assert that a combination of intrinsic and extrinsic stressors underlies the increasing risk of death. Epidemiological and biological data support that the control of intrinsic as well...... as extrinsic stressors can alleviate the aging process. We argue that aging and death can be better explained by the interaction of intrinsic and extrinsic stressors than by classifying mortality itself as being either intrinsic or extrinsic. Recognition of the tight interaction between intrinsic and extrinsic...

  10. In vitro DNA binding studies of lenalidomide using spectroscopic in combination with molecular docking techniques

    Science.gov (United States)

    Xu, Liang; Hu, Yan-Xi; Li, Yan-Cheng; Zhang, Li; Ai, Hai-Xin; Liu, Yu-Feng; Liu, Hong-Sheng

    2018-02-01

    In the present work, the binding interaction between lenalidomide (LEN) and calf thymus DNA (ct-DNA) was systematically studied by using fluorescence, ultraviolet-visible (UV-vis) absorption, circular dichroism (CD) spectroscopies under imitated physiological conditions (pH = 7.4) coupled with molecular docking. It was found that LEN was bound to ct-DNA with high binding affinity (Ka = 2.308 × 105 M-1 at 283 K) through groove binding as evidenced by a slight decrease in the absorption intensity in combination with CD spectra. Thermodynamic parameters (ΔG 0 and ΔS interaction. Furthermore, competitive binding experiments with ethidium bromide and 4‧, 6-dia-midino-2-phenylindoleas probes showed that LEN could preferentially bind in the minor groove of double-stranded DNA. The average lifetime of LEN was calculated to be 7.645 ns. The φ of LEN was measured as 0.09 and non-radiation energy transfer between LEN and DNA had occurred. The results of the molecular docking were consistent with the experimental results. This study explored the potential applicability of the spectroscopic properties of LEN and also investigated its interactions with relevant biological targets. In addition, it will provide some theoretical references for the deep research of simultaneous administration of LEN with other drugs.

  11. Augmentation of French grunt diet description using combined visual and DNA-based analyses

    Science.gov (United States)

    Hargrove, John S.; Parkyn, Daryl C.; Murie, Debra J.; Demopoulos, Amanda W.J.; Austin, James D.

    2012-01-01

    Trophic linkages within a coral-reef ecosystem may be difficult to discern in fish species that reside on, but do not forage on, coral reefs. Furthermore, dietary analysis of fish can be difficult in situations where prey is thoroughly macerated, resulting in many visually unrecognisable food items. The present study examined whether the inclusion of a DNA-based method could improve the identification of prey consumed by French grunt, Haemulon flavolineatum, a reef fish that possesses pharyngeal teeth and forages on soft-bodied prey items. Visual analysis indicated that crustaceans were most abundant numerically (38.9%), followed by sipunculans (31.0%) and polychaete worms (5.2%), with a substantial number of unidentified prey (12.7%). For the subset of prey with both visual and molecular data, there was a marked reduction in the number of unidentified sipunculans (visual – 31.1%, combined &ndash 4.4%), unidentified crustaceans (visual &ndash 15.6%, combined &ndash 6.7%), and unidentified taxa (visual &ndash 11.1%, combined &ndash 0.0%). Utilising results from both methodologies resulted in an increased number of prey placed at the family level (visual &ndash 6, combined &ndash 33) and species level (visual &ndash 0, combined &ndash 4). Although more costly than visual analysis alone, our study demonstrated the feasibility of DNA-based identification of visually unidentifiable prey in the stomach contents of fish.

  12. DNA repair in human cells exposed to combinations of carcinogenic agents

    International Nuclear Information System (INIS)

    Setlow, R.B.; Ahmed, F.E.

    1980-01-01

    Normal human and XP 2 fibroblasts were treated with uv plus uv-mimetic chemicals. The uv dose used was sufficient to saturate the uv excision repair system. Excision repair after combined treatments was estimated by unscheduled DNA synthesis, BrdUrd photolysis, and the loss of sites sensitive to a uv specific endonuclease. Since the repair of damage from uv and its mimetics is coordinately controlled we expected that there would be similar rate-limiting steps in the repair of uv and chemical damage and that after a combined treatment the total amount of repair would be the same as from uv or the chemicals separately. The expectation was not fulfilled. In normal cells repair after a combined treatment was additive whereas in XP cells repair after a combined treatment was usually less than after either agent separately. The chemicals tested were AAAF, DMBA-epoxide, 4NQO, and ICR-170

  13. Microdosimetry calculations for monoenergetic electrons using Geant4-DNA combined with a weighted track sampling algorithm.

    Science.gov (United States)

    Famulari, Gabriel; Pater, Piotr; Enger, Shirin A

    2017-07-07

    The aim of this study was to calculate microdosimetric distributions for low energy electrons simulated using the Monte Carlo track structure code Geant4-DNA. Tracks for monoenergetic electrons with kinetic energies ranging from 100 eV to 1 MeV were simulated in an infinite spherical water phantom using the Geant4-DNA extension included in Geant4 toolkit version 10.2 (patch 02). The microdosimetric distributions were obtained through random sampling of transfer points and overlaying scoring volumes within the associated volume of the tracks. Relative frequency distributions of energy deposition f(>E)/f(>0) and dose mean lineal energy ([Formula: see text]) values were calculated in nanometer-sized spherical and cylindrical targets. The effects of scoring volume and scoring techniques were examined. The results were compared with published data generated using MOCA8B and KURBUC. Geant4-DNA produces a lower frequency of higher energy deposits than MOCA8B. The [Formula: see text] values calculated with Geant4-DNA are smaller than those calculated using MOCA8B and KURBUC. The differences are mainly due to the lower ionization and excitation cross sections of Geant4-DNA for low energy electrons. To a lesser extent, discrepancies can also be attributed to the implementation in this study of a new and fast scoring technique that differs from that used in previous studies. For the same mean chord length ([Formula: see text]), the [Formula: see text] calculated in cylindrical volumes are larger than those calculated in spherical volumes. The discrepancies due to cross sections and scoring geometries increase with decreasing scoring site dimensions. A new set of [Formula: see text] values has been presented for monoenergetic electrons using a fast track sampling algorithm and the most recent physics models implemented in Geant4-DNA. This dataset can be combined with primary electron spectra to predict the radiation quality of photon and electron beams.

  14. Postradiation DNA repair in mammalian cells under the combined effect of hyperthermia and 8-bromocaffeine and actinomycin D

    International Nuclear Information System (INIS)

    Rezvaya, S.P.; Khanson, K.P.

    1981-01-01

    A study was made of the influence of postirradiation hyperthermia combined with chemical inhibitirors of DNA repa on rejoining the singlestranded DNA breaks induced by X-irradiation (50 Gy) of LL, cells. Separation of single- and double-stranded DNA fragments on a column with hydroxyapatite has revealed that elevation of the postradiation incubation temperature up to 41 deg C does not influence the degree of repair of single-stranded breaks. No repair is detected at 43 deg C. 8-Bromocaffeine and actinomycin combined with the elevated temperature (41 deg C) remove the inhibitory effect of the preparations on the postradiation repair of DNA [ru

  15. An integrated strategy combining DNA walking and NGS to detect GMOs.

    Science.gov (United States)

    Fraiture, Marie-Alice; Herman, Philippe; Papazova, Nina; De Loose, Marc; Deforce, Dieter; Ruttink, Tom; Roosens, Nancy H

    2017-10-01

    Recently, we developed a DNA walking system for the detection and characterization of a broad spectrum of GMOs in routine analysis of food/feed matrices. Here, we present a new version with improved throughput and sensitivity by coupling the DNA walking system to Pacific Bioscience® Next-generation sequencing technology. The performance of the new strategy was thoroughly assessed through several assays. First, we tested its detection and identification capability on grains with high or low GMO content. Second, the potential impacts of food processing were investigated using rice noodle samples. Finally, GMO mixtures and a real-life sample were analyzed to illustrate the applicability of the proposed strategy in routine GMO analysis. In all tested samples, the presence of multiple GMOs was unambiguously proven by the characterization of transgene flanking regions and the combinations of elements that are typical for transgene constructs. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  16. GANN: Genetic algorithm neural networks for the detection of conserved combinations of features in DNA

    Directory of Open Access Journals (Sweden)

    Beiko Robert G

    2005-02-01

    Full Text Available Abstract Background The multitude of motif detection algorithms developed to date have largely focused on the detection of patterns in primary sequence. Since sequence-dependent DNA structure and flexibility may also play a role in protein-DNA interactions, the simultaneous exploration of sequence- and structure-based hypotheses about the composition of binding sites and the ordering of features in a regulatory region should be considered as well. The consideration of structural features requires the development of new detection tools that can deal with data types other than primary sequence. Results GANN (available at http://bioinformatics.org.au/gann is a machine learning tool for the detection of conserved features in DNA. The software suite contains programs to extract different regions of genomic DNA from flat files and convert these sequences to indices that reflect sequence and structural composition or the presence of specific protein binding sites. The machine learning component allows the classification of different types of sequences based on subsamples of these indices, and can identify the best combinations of indices and machine learning architecture for sequence discrimination. Another key feature of GANN is the replicated splitting of data into training and test sets, and the implementation of negative controls. In validation experiments, GANN successfully merged important sequence and structural features to yield good predictive models for synthetic and real regulatory regions. Conclusion GANN is a flexible tool that can search through large sets of sequence and structural feature combinations to identify those that best characterize a set of sequences.

  17. Combined Triplex/Duplex Invasion of Double-Stranded DNA by "Tail-Clamp" Peptide Nucleic Acid

    DEFF Research Database (Denmark)

    Bentin, Thomas; Larsen, H. J.; Nielsen, Peter E.

    2003-01-01

    as determined by T-m measurements. Binding to double-stranded (ds) DNA occurred by combined triplex and duplex invasion as analyzed by permanganate probing. Furthermore, C-50 measurements revealed that tail-clamp PNAs consistently bound the dsDNA target more efficiently, and kinetics experiments revealed...

  18. Impact of arsenic/phosphorus substitution on the intrinsic conformational properties of the phosphodiester backbone of DNA investigated using ab initio quantum mechanical calculations.

    Science.gov (United States)

    Denning, Elizabeth J; Mackerell, Alexander D

    2011-04-20

    Deoxyribonucleic acid (DNA) is composed of five major elements carbon, hydrogen, nitrogen, oxygen, and phosphorus. The substitution of any of these elements in DNA would be anticipated to have major biological implications. However, recent studies have suggested that the substitution of arsenic into DNA (As-DNA) in bacteria may be possible. To help evaluate this possibility, ab initio quantum mechanical calculations are used to show that arsenodiester and phosphodiester linkages have similar geometric and conformational properties. Based on these results, it is suggested that the As-DNA will have similar conformational properties to phosphorus-based DNA, including the maintenance of base stacking.

  19. Combined sequencing of mRNA and DNA from human embryonic stem cells

    Directory of Open Access Journals (Sweden)

    Florian Mertes

    2016-06-01

    Full Text Available Combined transcriptome and whole genome sequencing of the same ultra-low input sample down to single cells is a rapidly evolving approach for the analysis of rare cells. Besides stem cells, rare cells originating from tissues like tumor or biopsies, circulating tumor cells and cells from early embryonic development are under investigation. Herein we describe a universal method applicable for the analysis of minute amounts of sample material (150 to 200 cells derived from sub-colony structures from human embryonic stem cells. The protocol comprises the combined isolation and separate amplification of poly(A mRNA and whole genome DNA followed by next generation sequencing. Here we present a detailed description of the method developed and an overview of the results obtained for RNA and whole genome sequencing of human embryonic stem cells, sequencing data is available in the Gene Expression Omnibus (GEO database under accession number GSE69471.

  20. Intrinsic Instability of Cs2In(I)M(III)X6 (M = Bi, Sb; X = Halogen) Double Perovskites: A Combined Density Functional Theory and Experimental Study.

    Science.gov (United States)

    Xiao, Zewen; Du, Ke-Zhao; Meng, Weiwei; Wang, Jianbo; Mitzi, David B; Yan, Yanfa

    2017-05-03

    Recently, there has been substantial interest in developing double-B-cation halide perovskites, which hold the potential to overcome the toxicity and instability issues inherent within emerging lead halide-based solar absorber materials. Among all double perovskites investigated, In(I)-based Cs 2 InBiCl 6 and Cs 2 InSbCl 6 have been proposed as promising thin-film photovoltaic absorber candidates, with computational examination predicting suitable materials properties, including direct bandgap and small effective masses for both electrons and holes. In this study, we report the intrinsic instability of Cs 2 In(I)M(III)X 6 (M = Bi, Sb; X = halogen) double perovskites by a combination of density functional theory and experimental study. Our results suggest that the In(I)-based double perovskites are unstable against oxidation into In(III)-based compounds. Further, the results show the need to consider reduction-oxidation (redox) chemistry when predicting stability of new prospective electronic materials, especially when less common oxidation states are involved.

  1. DNA repair in mammalian cells exposed to combinations of carcinogenic agents

    International Nuclear Information System (INIS)

    Setlow, R.B.; Ahmed, F.E.

    1979-01-01

    Cells defective in one or more aspects of repair are killed and often mutagenized more readily than normal cells by DNA damaging agents, and humans whose cells are deficient in repair are at an increased carcinogenic risk compared to normal individuals. The excision repair of uv induced pyrimidine dimers is a well studied system, but the details of the steps in this repair system are far from being understood in human cells. We know that there are a number of chemicals that mimic uv in that normal human cells repair DNA damage from both these agents and from uv by a long patch excision repair system, and that xeroderma pigmentosum cells defective in repair of uv are also defective in the repair of damage from these chemicals. The chemicals we have investigated are AAAF, 4-NQO, DMBA-epoxide, and ICR-170. We describe experiments, using several techniques, in which DNA excision repair is measured after treatment of various human cell strains with combinations of uv and these agents. If two agents have a common rate limiting step then, at doses high enough to saturate the repair system, one would expect the observed repair after a treatment with a combination of agents to be equal to that from one agent alone. Such is not the case for normal human or excision-deficient XP cells. In the former repair is additive and in the latter repair is usually appreciably less than that observed with either agent alone. Models that attempt to explain these surprising results involve complexes of enzymes and cofactors

  2. A combined approach of hollow microneedles and nanocarriers for skin immunization with plasmid DNA encoding ovalbumin

    Directory of Open Access Journals (Sweden)

    Pamornpathomkul B

    2017-01-01

    Full Text Available Boonnada Pamornpathomkul,1 Adisak Wongkajornsilp,2 Wanida Laiwattanapaisal,3 Theerasak Rojanarata,1 Praneet Opanasopit,1 Tanasait Ngawhirunpat1 1Department of Pharmaceutical Technology, Faculty of Pharmacy, Pharmaceutical Development of Green Innovations Group, Silpakorn University, Nakhon Pathom, 2Department of Pharmacology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 3Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, Thailand Abstract: The aim of this study was to investigate the use of different types of microneedles (MNs and nanocarriers for in vitro skin permeation and in vivo immunization of plasmid DNA encoding ovalbumin (pOVA. In vitro skin permeation studies indicated that hollow MNs had a superior enhancing effect on skin permeation compared with solid MN patches, electroporation (EP patches, the combination of MN and EP patches, and untreated skin. Upon using hollow MNs combined with nanocarriers for pOVA delivery, the skin permeation was higher than for the delivery of naked pOVA, as evidenced by the increased amount of pOVA in Franz diffusion cells and immunoglobulin G (IgG antibody responses. When the hollow MNs were used for the delivery of nanocarrier:pOVA complexes into the skin of mice, they induced a stronger IgG immune response than conventional subcutaneous (SC injections. In addition, immunization of mice with the hollow MNs did not induce signs of skin infection or pinpoint bleeding. Accordingly, the hollow MNs combined with a nanocarrier delivery system is a promising approach for delivering pOVA complexes to the skin for promoting successful immunization. Keywords: hollow microneedle, solid microneedle, electroporation, plasmid DNA encoding ovalbumin, skin immunization, nanocarrier

  3. Combined histochemical staining, RNA amplification, regional, and single cell cDNA analysis within the hippocampus.

    Science.gov (United States)

    Ginsberg, Stephen D; Che, Shaoli

    2004-08-01

    The use of five histochemical stains (cresyl violet, thionin, hematoxylin & eosin, silver stain, and acridine orange) was evaluated in combination with an expression profiling paradigm that included regional and single cell analyses within the hippocampus of post-mortem human brains and adult mice. Adjacent serial sections of human and mouse hippocampus were labeled by histochemistry or neurofilament immunocytochemistry. These tissue sections were used as starting material for regional and single cell microdissection followed by a newly developed RNA amplification procedure (terminal continuation (TC) RNA amplification) and subsequent hybridization to custom-designed cDNA arrays. Results indicated equivalent levels of global hybridization signal intensity and relative expression levels for individual genes for hippocampi stained by cresyl violet, thionin, and hematoxylin & eosin, and neurofilament immunocytochemistry. Moreover, no significant differences existed between the Nissl stains and neurofilament immunocytochemistry for individual CA1 neurons obtained via laser capture microdissection. In contrast, a marked decrement was observed in adjacent hippocampal sections stained for silver stain and acridine orange, both at the level of the regional dissection and at the CA1 neuron population level. Observations made on the cDNA array platform were validated by real-time qPCR using primers directed against beta-actin and glyceraldehyde-3 phosphate dehydrogenase. Thus, this report demonstrated the utility of using specific Nissl stains, but not stains that bind RNA species directly, in both human and mouse brain tissues at the regional and cellular level for state-of-the-art molecular fingerprinting studies.

  4. Combining use of a panel of ssDNA aptamers in the detection of Staphylococcus aureus.

    Science.gov (United States)

    Cao, Xiaoxiao; Li, Shaohua; Chen, Liucun; Ding, Hongmei; Xu, Hua; Huang, Yanping; Li, Jie; Liu, Nongle; Cao, Weihong; Zhu, Yanjun; Shen, Beifen; Shao, Ningsheng

    2009-08-01

    In this article, a panel of ssDNA aptamers specific to Staphylococcus aureus was obtained by a whole bacterium-based SELEX procedure and applied to probing S. aureus. After several rounds of selection with S. aureus as the target and Streptococcus and S. epidermidis as counter targets, the highly enriched oligonucleic acid pool was sequenced and then grouped under different families on the basis of the homology of the primary sequence and the similarity of the secondary structure. Eleven sequences from different families were selected for further characterization by confocal imaging and flow cytometry analysis. Results showed that five aptamers demonstrated high specificity and affinity to S. aureus individually. The five aptamers recognize different molecular targets by competitive experiment. Combining these five aptamers had a much better effect than the individual aptamer in the recognition of different S. aureus strains. In addition, the combined aptamers can probe single S. aureus in pyogenic fluids. Our work demonstrates that a set of aptamers specific to one bacterium can be used in combination for the identification of the bacterium instead of a single aptamer.

  5. Combined effect of radiation and environmental contaminants on DNA repair mechanisms

    International Nuclear Information System (INIS)

    Altmann, H.

    1975-11-01

    Investigations on the influence of various environmental contamination agents on DNA repair (in combination with irradiation) were reviewed. The agents tested were: detergents (Tween 80, Nonidel P40, Cremophor), aflatoxin B 1 , furocumarines, drugs (indometacin, cyclophosphamide, vincristine, vinblastine, procarbacine), fluorides, irradiated food constituents, food additives (saccharin), metal ions (Cd, Hg), pesticides (2,4,5-trichlorophenoxyethanol) and infective agents (mycoplasmas). Most of the tests were carried out in vitro with γ-irradiated mouse spleen cells. The detergents and aflatoxin were tested also on E. coli, and irradiated glucose solutions were tested in vivo on Swiss albino mice injected with Salmonella typhimurium TA 1530. Most of the tested agents showed some kind of inhibitory or mutagenic effect. The experiments and results are explained briefly with references to earlier investigations

  6. Dynamics of relationship between the presence of Coxiella burnetii DNA, antibodies, and intrinsic variables in cow milk and bulk tank milk from Danish dairy cattle

    DEFF Research Database (Denmark)

    Angen, Øystein; Ståhl, Marie; Agerholm, J. S.

    2011-01-01

    protein concentration in milk. The antibody levels in bulk tank milk and prevalence levels of C. burnetii DNA and antibodies in individual cow milk samples were correlated. A significant correlation was also found between the quantification cycle values of the cow samples (weighted according to milk yield......Milk samples of 12 Danish dairy herds were collected 3 times during an 11-mo period and tested for Coxiella burnetii DNA by real-time PCR, detecting the IS1111 element, and for the presence of antibodies against the bacterium by ELISA. On average, 25% of 1,514 samples were seropositive and 32% were...... positive for C. burnetii DNA. Among the 485 DNA-positive samples, quantification cycle values ranging from 15.8 to 37.8 were found. Test sensitivity did not increase after DNA extraction from the cream fraction compared with full milk. The relationship between antibody levels and bacterial shedding...

  7. Determination of chromium combined with DNA, RNA and proteins in chromium-rich brewer's yeast by NAA

    International Nuclear Information System (INIS)

    Ding, W.J.; Qian, Q.F.; Hou, X.L.; Feng, W.Y.; Chai, Z.F.

    2000-01-01

    The content of chromium in the DNA, RNA and protein fractions separated from chromium-rich and normal brewer's yeast was determined by neutron activation analysis (NAA). Our results show that the extracted relative amounts and concentrations of DNA, RNA and proteins have no significant difference for two types of yeast, but the chromium content in DNA, RNA and proteins fractions extracted from the chromium-rich yeast are substantially higher than those from the normal. In addition, the concentration of chromium in DNA is much higher than that in RNA and proteins. It is evident that the inorganic chromium compounds can enter the yeast cell during the yeast cultivation in the chromium-containing culture medium and are converted into organic chromium species, which are combined with DNA, RNA and proteins. (author)

  8. Branched-DNA signal amplification combined with paper chromatography hybridization assay and used in hepatitis B virus DNA detection

    International Nuclear Information System (INIS)

    Fu, F.Z.; Liu, L.X.; Wang, W.Q.; Sun, S. H.; Liu, L.B.

    2002-01-01

    Nucleic acids detection method is vital to the clinical pathogen diagnosis. The established method can be classified into target direct amplification and signal amplification format according to the target DNA or RNA being directly amplified or not. Those methods have advantages and disadvantages respectively in the clinical application. In the United States of American, branched-DNA as a strong signal amplifier is broadly used in the quantification of the nucleic acids. To gain satisfied sensitivity, some expensive label molecular and instruments should be adopted. Personnel should be special trained to perform. Hence, those can't be widely carried out in the Third World. To avoid those disadvantages, we used the branched-DNA amplifier in the paper chromatography hybridization assay. Methods: Branched DNA signal amplifier and series of probes complementary to the nucleic acid sequence of hepatitis B virus (HBV) have been synthesized. HBV-DNA or it's capture probe were immobilized on the high flow nitrocellulose strip. Having loaded at one end of the strip in turn, probes or HBV-DNA in the hybridization solution migrate to the opposite end of the strip by capillary forces and hybridizes to the immobilized DNA. The branched-DNA signal amplifier and probe labeled with biotin or 32P were then loaded. Through streptavidin-alkaline phosphatase (SA-AP) conjugate and NBT/BCIP ( the specific chromogenic substrate of AP) or autoradiography, the result can be visualized by color reaction or image production on the X-ray film. Results: The sensitivity of this HBV-DNA detection method used probe labeled with biotin and 32P are 1ng and 10pg. The method using the probe labeled with biotin is simple and rapid (2h) without depending on special instruments, it also avoids the pollution of EtBr which can lead to tumor. And the method using the probe labeled with 32P is simple and sensitive, with the exception of long time autoradiography and the inconvenient isotopic disposal

  9. Editing of misaligned 3′-termini by an intrinsic 3′–5′ exonuclease activity residing in the PHP domain of a family X DNA polymerase

    Science.gov (United States)

    Baños, Benito; Lázaro, José M.; Villar, Laurentino; de Vega, Miguel

    2008-01-01

    Bacillus subtilis gene yshC encodes a family X DNA polymerase (PolXBs), whose biochemical features suggest that it plays a role during DNA repair processes. Here, we show that, in addition to the polymerization activity, PolXBs possesses an intrinsic 3′–5′ exonuclease activity specialized in resecting unannealed 3′-termini in a gapped DNA substrate. Biochemical analysis of a PolXBs deletion mutant lacking the C-terminal polymerase histidinol phosphatase (PHP) domain, present in most of the bacterial/archaeal PolXs, as well as of this separately expressed protein region, allow us to state that the 3′–5′ exonuclease activity of PolXBs resides in its PHP domain. Furthermore, site-directed mutagenesis of PolXBs His339 and His341 residues, evolutionary conserved in the PHP superfamily members, demonstrated that the predicted metal binding site is directly involved in catalysis of the exonucleolytic reaction. The implications of the unannealed 3′-termini resection by the 3′–5′ exonuclease activity of PolXBs in the DNA repair context are discussed. PMID:18776221

  10. Exogenous DNA internalisation by sperm cells is improved by combining lipofection and restriction enzyme mediated integration.

    Science.gov (United States)

    Churchil, R R; Gupta, J; Singh, A; Sharma, D

    2011-06-01

    1. Three types of exogenous DNA inserts, i.e. complete linearised pVIVO2-GFP/LacZ vector (9620 bp), the LacZ gene (5317 bp) and the GFP gene (2152 bp) were used to transfect chicken spermatozoa through simple incubation of sperm cells with insert. 2. PCR assay, Dot Blot hybridisation and Southern hybridisation showed the successful internalisation of exogenous DNA by chicken sperm cells. 3. Lipofection and Restriction Enzyme Mediated Integration (REMI) were used to improve the rate of internalisation of exogenous DNA by sperm cells. 4. Results from dot blot as well as Southern hybridisation were semi-quantified and improved exogenous DNA uptake by sperm cells through lipofection and REMI. Stronger signals were observed from hybridisation of LacZ as well as GFP specific probe with the DNA from lipofected exogenous DNA transfected sperm DNA in comparison with those transfected with nude exogenous DNA.

  11. Intrinsic and extrinsic mortality reunited.

    Science.gov (United States)

    Koopman, Jacob J E; Wensink, Maarten J; Rozing, Maarten P; van Bodegom, David; Westendorp, Rudi G J

    2015-07-01

    Intrinsic and extrinsic mortality are often separated in order to understand and measure aging. Intrinsic mortality is assumed to be a result of aging and to increase over age, whereas extrinsic mortality is assumed to be a result of environmental hazards and be constant over age. However, allegedly intrinsic and extrinsic mortality have an exponentially increasing age pattern in common. Theories of aging assert that a combination of intrinsic and extrinsic stressors underlies the increasing risk of death. Epidemiological and biological data support that the control of intrinsic as well as extrinsic stressors can alleviate the aging process. We argue that aging and death can be better explained by the interaction of intrinsic and extrinsic stressors than by classifying mortality itself as being either intrinsic or extrinsic. Recognition of the tight interaction between intrinsic and extrinsic stressors in the causation of aging leads to the recognition that aging is not inevitable, but malleable through the environment. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Identifying cis-regulatory modules by combining comparative and compositional analysis of DNA.

    Science.gov (United States)

    Pierstorff, Nora; Bergman, Casey M; Wiehe, Thomas

    2006-12-01

    Predicting cis-regulatory modules (CRMs) in higher eukaryotes is a challenging computational task. Commonly used methods to predict CRMs based on the signal of transcription factor binding sites (TFBS) are limited by prior information about transcription factor specificity. More general methods that bypass the reliance on TFBS models are needed for comprehensive CRM prediction. We have developed a method to predict CRMs called CisPlusFinder that identifies high density regions of perfect local ungapped sequences (PLUSs) based on multiple species conservation. By assuming that PLUSs contain core TFBS motifs that are locally overrepresented, the method attempts to capture the expected features of CRM structure and evolution. Applied to a benchmark dataset of CRMs involved in early Drosophila development, CisPlusFinder predicts more annotated CRMs than all other methods tested. Using the REDfly database, we find that some 'false positive' predictions in the benchmark dataset correspond to recently annotated CRMs. Our work demonstrates that CRM prediction methods that combine comparative genomic data with statistical properties of DNA may achieve reasonable performance when applied genome-wide in the absence of an a priori set of known TFBS motifs. The program CisPlusFinder can be downloaded at http://jakob.genetik.uni-koeln.de/bioinformatik/people/nora/nora.html. All software is licensed under the Lesser GNU Public License (LGPL).

  13. G+C content dominates intrinsic nucleosome occupancy

    Directory of Open Access Journals (Sweden)

    Hughes Timothy R

    2009-12-01

    Full Text Available Abstract Background The relative preference of nucleosomes to form on individual DNA sequences plays a major role in genome packaging. A wide variety of DNA sequence features are believed to influence nucleosome formation, including periodic dinucleotide signals, poly-A stretches and other short motifs, and sequence properties that influence DNA structure, including base content. It was recently shown by Kaplan et al. that a probabilistic model using composition of all 5-mers within a nucleosome-sized tiling window accurately predicts intrinsic nucleosome occupancy across an entire genome in vitro. However, the model is complicated, and it is not clear which specific DNA sequence properties are most important for intrinsic nucleosome-forming preferences. Results We find that a simple linear combination of only 14 simple DNA sequence attributes (G+C content, two transformations of dinucleotide composition, and the frequency of eleven 4-bp sequences explains nucleosome occupancy in vitro and in vivo in a manner comparable to the Kaplan model. G+C content and frequency of AAAA are the most important features. G+C content is dominant, alone explaining ~50% of the variation in nucleosome occupancy in vitro. Conclusions Our findings provide a dramatically simplified means to predict and understand intrinsic nucleosome occupancy. G+C content may dominate because it both reduces frequency of poly-A-like stretches and correlates with many other DNA structural characteristics. Since G+C content is enriched or depleted at many types of features in diverse eukaryotic genomes, our results suggest that variation in nucleotide composition may have a widespread and direct influence on chromatin structure.

  14. Highly sensitive detection of human IgG using a novel bio-barcode assay combined with DNA chip technology

    International Nuclear Information System (INIS)

    Liu, Zhenbao; Zhou, Bo; Wang, Haiqing; Lu, Feng; Liu, Tianjun; Song, Cunxian; Leng, Xigang

    2013-01-01

    A simple and ultrasensitive detection of human IgG based on signal amplification using a novel bio-barcode assay and DNA chip technology was developed. The sensing platform was a sandwich system made up of antibody-modified magnetic microparticles (Ab-MMPs)/human IgG/Cy3-labeled single-stranded DNA and antibody-modified gold nanoparticles (Cy3-ssDNA-Ab-AuNPs). The MMPs (2.5 μm in diameter) modified with mouse anti-human IgG monoclonal-antibodies could capture human IgG and further be separated and enriched via a magnetic field. The AuNPs (13 nm in diameter) conjugated with goat anti-human IgG polyclonal-antibodies and Cy3-ssDNA could further combine with the human IgG/Ab-MMP complex. The Cy3-ssDNA on AuNPs was then released by TCEP to hybridize with the DNA chip, thus generating a detectable signal by the fluorescence intensity of Cy3. In order to improve detection sensitivity, a three-level cascaded signal amplification was developed: (1) The MMP enrichment as the first-level; (2) Large quantities of Cy3-ssDNA on AuNPs as the second-level; (3) The Cy3-ssDNA conjugate with DNA chip as the third-level. The highly sensitive technique showed an increased response of the fluorescence intensity to the increased concentration of human IgG through a detection range from 1 pg mL −1 to 10 ng mL −1 . This sensing technique could not only improve the detection sensitivity for the low concentration of human IgG but also present a robust and efficient signal amplification model. The detection method has good stability, specificity, and reproducibility and could be applied in the detection of human IgG in the real samples

  15. Highly sensitive detection of human IgG using a novel bio-barcode assay combined with DNA chip technology

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Zhenbao [Central South University, School of Pharmaceutical Sciences (China); Zhou, Bo, E-mail: zhoubo1771@163.com [The Affiliated Zhongda Hospital of Southeast University, Department of Gerontology (China); Wang, Haiqing; Lu, Feng; Liu, Tianjun; Song, Cunxian; Leng, Xigang, E-mail: lengxigyky@163.com [Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College (China)

    2013-09-15

    A simple and ultrasensitive detection of human IgG based on signal amplification using a novel bio-barcode assay and DNA chip technology was developed. The sensing platform was a sandwich system made up of antibody-modified magnetic microparticles (Ab-MMPs)/human IgG/Cy3-labeled single-stranded DNA and antibody-modified gold nanoparticles (Cy3-ssDNA-Ab-AuNPs). The MMPs (2.5 {mu}m in diameter) modified with mouse anti-human IgG monoclonal-antibodies could capture human IgG and further be separated and enriched via a magnetic field. The AuNPs (13 nm in diameter) conjugated with goat anti-human IgG polyclonal-antibodies and Cy3-ssDNA could further combine with the human IgG/Ab-MMP complex. The Cy3-ssDNA on AuNPs was then released by TCEP to hybridize with the DNA chip, thus generating a detectable signal by the fluorescence intensity of Cy3. In order to improve detection sensitivity, a three-level cascaded signal amplification was developed: (1) The MMP enrichment as the first-level; (2) Large quantities of Cy3-ssDNA on AuNPs as the second-level; (3) The Cy3-ssDNA conjugate with DNA chip as the third-level. The highly sensitive technique showed an increased response of the fluorescence intensity to the increased concentration of human IgG through a detection range from 1 pg mL{sup -1} to 10 ng mL{sup -1}. This sensing technique could not only improve the detection sensitivity for the low concentration of human IgG but also present a robust and efficient signal amplification model. The detection method has good stability, specificity, and reproducibility and could be applied in the detection of human IgG in the real samples.

  16. Highly sensitive detection of human IgG using a novel bio-barcode assay combined with DNA chip technology

    Science.gov (United States)

    Liu, Zhenbao; Zhou, Bo; Wang, Haiqing; Lu, Feng; Liu, Tianjun; Song, Cunxian; Leng, Xigang

    2013-09-01

    A simple and ultrasensitive detection of human IgG based on signal amplification using a novel bio-barcode assay and DNA chip technology was developed. The sensing platform was a sandwich system made up of antibody-modified magnetic microparticles (Ab-MMPs)/human IgG/Cy3-labeled single-stranded DNA and antibody-modified gold nanoparticles (Cy3-ssDNA-Ab-AuNPs). The MMPs (2.5 μm in diameter) modified with mouse anti-human IgG monoclonal-antibodies could capture human IgG and further be separated and enriched via a magnetic field. The AuNPs (13 nm in diameter) conjugated with goat anti-human IgG polyclonal-antibodies and Cy3-ssDNA could further combine with the human IgG/Ab-MMP complex. The Cy3-ssDNA on AuNPs was then released by TCEP to hybridize with the DNA chip, thus generating a detectable signal by the fluorescence intensity of Cy3. In order to improve detection sensitivity, a three-level cascaded signal amplification was developed: (1) The MMP enrichment as the first-level; (2) Large quantities of Cy3-ssDNA on AuNPs as the second-level; (3) The Cy3-ssDNA conjugate with DNA chip as the third-level. The highly sensitive technique showed an increased response of the fluorescence intensity to the increased concentration of human IgG through a detection range from 1 pg mL-1 to 10 ng mL-1. This sensing technique could not only improve the detection sensitivity for the low concentration of human IgG but also present a robust and efficient signal amplification model. The detection method has good stability, specificity, and reproducibility and could be applied in the detection of human IgG in the real samples.

  17. Intrinsic superspin Hall current

    Science.gov (United States)

    Linder, Jacob; Amundsen, Morten; Risinggârd, Vetle

    2017-09-01

    We discover an intrinsic superspin Hall current: an injected charge supercurrent in a Josephson junction containing heavy normal metals and a ferromagnet generates a transverse spin supercurrent. There is no accompanying dissipation of energy, in contrast to the conventional spin Hall effect. The physical origin of the effect is an antisymmetric spin density induced among transverse modes ky near the interface of the superconductor arising due to the coexistence of p -wave and conventional s -wave superconducting correlations with a belonging phase mismatch. Our predictions can be tested in hybrid structures including thin heavy metal layers combined with strong ferromagnets and ordinary s -wave superconductors.

  18. Combining ligation reaction and capillary gel electrophoresis to obtain reliable long DNA probes.

    Science.gov (United States)

    García-Cañas, Virginia; Mondello, Monica; Cifuentes, Alejandro

    2011-05-01

    New DNA amplification methods are continuously developed for sensitive detection and quantification of specific DNA target sequences for, e.g. clinical, environmental or food applications. These new applications often require the use of long DNA oligonucleotides as probes for target sequences hybridization. Depending on the molecular technique, the length of DNA probes ranges from 40 to 450 nucleotides, solid-phase chemical synthesis being the strategy generally used for their production. However, the fidelity of chemical synthesis of DNA decreases for larger DNA probes. Defects in the oligonucleotide sequence result in the loss of hybridization efficiency, affecting the sensitivity and selectivity of the amplification method. In this work, an enzymatic procedure has been developed as an alternative to solid-phase chemical synthesis for the production of long oligonucleotides. The enzymatic procedure for probe production was based on ligation of short DNA sequences. Long DNA probes were obtained from smaller oligonucleotides together with a short sequence that acts as bridge stabilizing the molecular complex for DNA ligation. The ligation reactions were monitored by capillary gel electrophoresis with laser-induced fluorescence detection (CGE-LIF) using a bare fused-silica capillary. The capillary gel electrophoresis-LIF method demonstrated to be very useful and informative for the characterization of the ligation reaction, providing important information about the nature of some impurities, as well as for the fine optimization of the ligation conditions (i.e. ligation cycles, oligonucleotide and enzyme concentration). As a result, the yield and quality of the ligation product were highly improved. The in-lab prepared DNA probes were used in a novel multiplex ligation-dependent genome amplification (MLGA) method for the detection of genetically modified maize in samples. The great possibilities of the whole approach were demonstrated by the specific and sensitive

  19. Anonymous letters? DNA and fingerprints technologies combined to solve a case.

    Science.gov (United States)

    Barbaro, A; Cormaci, P; Teatino, A; La Marca, A; Barbaro, A

    2004-12-02

    Two brothers, living in two different cities, received two different anonymous letters. We performed latent prints development and DNA research on the letters and also on a glass used by a cousin suspected to be the letters' sender.

  20. Evaluation of forensic DNA mixture evidence: protocol for evaluation, interpretation, and statistical calculations using the combined probability of inclusion.

    Science.gov (United States)

    Bieber, Frederick R; Buckleton, John S; Budowle, Bruce; Butler, John M; Coble, Michael D

    2016-08-31

    The evaluation and interpretation of forensic DNA mixture evidence faces greater interpretational challenges due to increasingly complex mixture evidence. Such challenges include: casework involving low quantity or degraded evidence leading to allele and locus dropout; allele sharing of contributors leading to allele stacking; and differentiation of PCR stutter artifacts from true alleles. There is variation in statistical approaches used to evaluate the strength of the evidence when inclusion of a specific known individual(s) is determined, and the approaches used must be supportable. There are concerns that methods utilized for interpretation of complex forensic DNA mixtures may not be implemented properly in some casework. Similar questions are being raised in a number of U.S. jurisdictions, leading to some confusion about mixture interpretation for current and previous casework. Key elements necessary for the interpretation and statistical evaluation of forensic DNA mixtures are described. Given the most common method for statistical evaluation of DNA mixtures in many parts of the world, including the USA, is the Combined Probability of Inclusion/Exclusion (CPI/CPE). Exposition and elucidation of this method and a protocol for use is the focus of this article. Formulae and other supporting materials are provided. Guidance and details of a DNA mixture interpretation protocol is provided for application of the CPI/CPE method in the analysis of more complex forensic DNA mixtures. This description, in turn, should help reduce the variability of interpretation with application of this methodology and thereby improve the quality of DNA mixture interpretation throughout the forensic community.

  1. Modified method for combined DNA and RNA isolation from peanut and other oil seeds.

    Science.gov (United States)

    Dang, Phat M; Chen, Charles Y

    2013-02-01

    Isolation of good quality RNA and DNA from seeds is difficult due to high levels of polysaccharides, polyphenols, and lipids that can degrade or co-precipitate with nucleic acids. Standard RNA extraction methods utilizing guanidinium-phenol-chloroform extraction has not shown to be successful. RNA isolation from plant seeds is a prerequisite for many seed specific gene expression studies and DNA is necessary in marker-assisted selection and other genetic studies. We describe a modified method to isolate both RNA and DNA from the same seed tissue and have been successful with several oil seeds including peanut, soybean, sunflower, canola, and oil radish. An additional LiCl precipitation step was added to isolate both RNA and DNA from the same seed tissues. High quality nucleic acids were observed based on A(260)/A(280) and A(260)/A(230) ratios above 2.0 and distinct bands on gel-electrophoresis. RNA was shown to be suitable for reverse transcriptase polymerase chain reaction based on actin or 60S ribosomal primer amplification and DNA was shown to have a single band on gel-electrophoresis analysis. This result shows that RNA and DNA isolated using this method can be appropriate for molecular studies in peanut and other oil containing seeds.

  2. Two-photon fluorescence and fluorescence imaging of two styryl heterocyclic dyes combined with DNA.

    Science.gov (United States)

    Gao, Chao; Liu, Shu-yao; Zhang, Xian; Liu, Ying-kai; Qiao, Cong-de; Liu, Zhao-e

    2016-03-05

    Two new styryl heterocyclic two-photon (TP) materials, 4-[4-(N-methyl)styrene]-imidazo [4,5-f][1,10] phenanthroline-benzene iodated salt (probe-1) and 4,4-[4-(N-methyl)styrene]-benzene iodated salt (probe-2) were successfully synthesized and studied as potential fluorescent probes of DNA detection. The linear and nonlinear photophysical properties of two compounds in different solvents were investigated. The absorption, one- and two-photon fluorescent spectra of the free dye and dye-DNA complex were also examined to evaluate their photophysical properties. The binding constants of dye-DNA were obtained according to Scatchard equation with good values. The results showed that two probes could be used as fluorescent DNA probes by two-photon excitation, and TP fluorescent properties of probe-1 are superior to that of probe-2. The fluorescent method date indicated that the mechanisms of dye-DNA complex interaction may be groove binding for probe-1 and electrostatic interaction for probe-2, respectively. The MTT assay experiments showed two probes are low toxicity. Moreover, the TP fluorescence imaging of DNA detection in living cells at 800 nm indicated that the ability to locate in cell nuclei of probe-1 is better than that of probe-2. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Combining Electro-Osmotic Flow and FTA® Paper for DNA Analysis on Microfluidic Devices

    Directory of Open Access Journals (Sweden)

    Ryan Wimbles

    2016-07-01

    Full Text Available FTA® paper can be used to protect a variety of biological samples prior to analysis, facilitating ease-of-transport to laboratories or long-term archive storage. The use of FTA® paper as a solid phase eradicates the need to elute the nucleic acids from the matrix prior to DNA amplification, enabling both DNA purification and polymerase chain reaction (PCR-based DNA amplification to be performed in a single chamber on the microfluidic device. A disc of FTA® paper, containing a biological sample, was placed within the microfluidic device on top of wax-encapsulated DNA amplification reagents. The disc containing the biological sample was then cleaned up using Tris-EDTA (TE buffer, which was passed over the disc, via electro-osmotic flow, in order to remove any potential inhibitors of downstream processes. DNA amplification was successfully performed (from buccal cells, whole blood and semen using a Peltier thermal cycling system, whereupon the stored PCR reagents were released during the initial denaturing step due to the wax barrier melting between the FTA® disc and PCR reagents. Such a system offers advantages in terms of a simple sample introduction interface and the ability to process archived samples in an integrated microfluidic environment with minimal risk of contamination.

  4. Combined immunotherapy of breast cancer with EGF and VEGF vaccines from DNA shuffling in a mouse model.

    Science.gov (United States)

    Jin, Dong; Yu, Xin; Chen, Bing; Li, Zhitao; Ding, Jia; Zhao, Xiuyun; Qi, Gaofu

    2017-06-01

    Development of EGF and VEGF vaccines with high antigenicity for combined immunotherapy of EGF-EGFR signaling-dependent epithelial tumors such as breast cancer. EGF genes from mouse, human and chicken were randomly assembled to chimeric genes by DNA shuffling, then a chimeric EGF was selected out by PCR, SDS-PAGE and immunization for combined immunotherapy of breast cancer with a previously constructed chimeric VEGF vaccine from shuffling. Combined vaccination with chimeric EGF and VEGF from shuffling could induce high titer of antibodies against EGF and VEGF to inhibit tumor growth and angiogenesis, and improve the survival rate of mice with breast cancer. Combined vaccination with EGF and VEGF from shuffling showed better immunotherapy on EGF-EGFR signaling-dependent epithelial tumors such as breast cancer than the single-agent EGF vaccination.

  5. The combination of gold nanorods and nanoparticles with DNA nanodevices for logic gates construction

    International Nuclear Information System (INIS)

    Yao, Dongbao; Song, Tingjie; Xiao, Shiyan; Huang, Fujian; Liang, Haojun; Zheng, Bin

    2015-01-01

    In this work, two DNA nanodevices were constructed utilizing a DNA strand displacement reaction. With the assistance of gold nanoparticles (AuNPs) and gold nanorods (AuNRs), the autonomous reactions can be reflected from the aggregation states of nanoparticles. By sequence design and the two non-overlapping double hump-like UV–vis spectral peaks of AuNPs and AuNRs, two logic gates with multiple inputs and outputs were successfully run with expected outcomes. This method not only shows how to achieve computing with multiple logic calculations but also has great potential for multiple targets detection. (paper)

  6. Combined analysis of DNA methylome and transcriptome reveal novel candidate genes with susceptibility to bovine Staphylococcus aureus subclinical mastitis.

    Science.gov (United States)

    Song, Minyan; He, Yanghua; Zhou, Huangkai; Zhang, Yi; Li, Xizhi; Yu, Ying

    2016-07-14

    Subclinical mastitis is a widely spread disease of lactating cows. Its major pathogen is Staphylococcus aureus (S. aureus). In this study, we performed genome-wide integrative analysis of DNA methylation and transcriptional expression to identify candidate genes and pathways relevant to bovine S. aureus subclinical mastitis. The genome-scale DNA methylation profiles of peripheral blood lymphocytes in cows with S. aureus subclinical mastitis (SA group) and healthy controls (CK) were generated by methylated DNA immunoprecipitation combined with microarrays. We identified 1078 differentially methylated genes in SA cows compared with the controls. By integrating DNA methylation and transcriptome data, 58 differentially methylated genes were shared with differently expressed genes, in which 20.7% distinctly hypermethylated genes showed down-regulated expression in SA versus CK, whereas 14.3% dramatically hypomethylated genes showed up-regulated expression. Integrated pathway analysis suggested that these genes were related to inflammation, ErbB signalling pathway and mismatch repair. Further functional analysis revealed that three genes, NRG1, MST1 and NAT9, were strongly correlated with the progression of S. aureus subclinical mastitis and could be used as powerful biomarkers for the improvement of bovine mastitis resistance. Our studies lay the groundwork for epigenetic modification and mechanistic studies on susceptibility of bovine mastitis.

  7. Combination of gefitinib and DNA methylation inhibitor decitabine exerts synergistic anti-cancer activity in colon cancer cells.

    Directory of Open Access Journals (Sweden)

    Yun-feng Lou

    Full Text Available Despite recent advances in the treatment of human colon cancer, the chemotherapy efficacy against colon cancer is still unsatisfactory. In the present study, effects of concomitant inhibition of the epidermal growth factor receptor (EGFR and DNA methyltransferase were examined in human colon cancer cells. We demonstrated that decitabine (a DNA methyltransferase inhibitor synergized with gefitinib (an EGFR inhibitor to reduce cell viability and colony formation in SW1116 and LOVO cells. However, the combination of the two compounds displayed minimal toxicity to NCM460 cells, a normal human colon mucosal epithelial cell line. The combination was also more effective at inhibiting the AKT/mTOR/S6 kinase pathway. In addition, the combination of decitabine with gefitinib markedly inhibited colon cancer cell migration. Furthermore, gefitinib synergistically enhanced decitabine-induced cytotoxicity was primarily due to apoptosis as shown by Annexin V labeling that was attenuated by z-VAD-fmk, a pan caspase inhibitor. Concomitantly, cell apoptosis resulting from the co-treatment of gefitinib and decitabine was accompanied by induction of BAX, cleaved caspase 3 and cleaved PARP, along with reduction of Bcl-2 compared to treatment with either drug alone. Interestingly, combined treatment with these two drugs increased the expression of XIAP-associated factor 1 (XAF1 which play an important role in cell apoptosis. Moreover, small interfering RNA (siRNA depletion of XAF1 significantly attenuated colon cancer cells apoptosis induced by the combination of the two drugs. Our findings suggested that gefitinib in combination with decitabine exerted enhanced cell apoptosis in colon cancer cells were involved in mitochondrial-mediated pathway and induction of XAF1 expression. In conclusion, based on the observations from our study, we suggested that the combined administration of these two drugs might be considered as a novel therapeutic regimen for treating colon

  8. Intrinsic determinants of Aβ(12-24 pH-dependent self-assembly revealed by combined computational and experimental studies.

    Directory of Open Access Journals (Sweden)

    Weixin Xu

    Full Text Available The propensity of amyloid-β (Aβ peptide to self-assemble into highly ordered amyloid structures lies at the core of their accumulation in the brain during Alzheimer's disease. By using all-atom explicit solvent replica exchange molecular dynamics simulations, we elucidated at the atomic level the intrinsic determinants of the pH-dependent dimerization of the central hydrophobic segment Aβ(12-24 and related these with the propensity to form amyloid fibrils measured by experimental tools such as atomic force microscopy and fluorescence. The process of Aβ(12-24 dimerization was evaluated in terms of free energy landscape, side-chain two-dimensional contact probability maps, β-sheet registries, potential mean force as a function of inter-chain distances, secondary structure development and radial solvation distributions. We showed that dimerization is a key event in Aβ(12-24 amyloid formation; it is highly prompted in the order of pH 5.0>2.9>>8.4 and determines further amyloid growth. The dimerization is governed by a dynamic interplay of hydrophobic, electrostatic and solvation interactions permitting some variability of β-sheets at each pH. These results provide atomistic insight into the complex process of molecular recognition detrimental for amyloid growth and pave the way for better understanding of the molecular basis of amyloid diseases.

  9. DNA bases assembled on the Au(110)/electrolyte interface: A combined experimental and theoretical study

    DEFF Research Database (Denmark)

    Salvatore, Princia; Nazmutdinov, Renat R.; Ulstrup, Jens

    2015-01-01

    Among the low-index single-crystal gold surfaces, the Au(110) surface is the most active toward molecular adsorption and the one with fewest electrochemical adsorption data reported. Cyclic voltammetry (CV), electrochemically controlled scanning tunneling microscopy (EC-STM), and density functional......, accompanied by a pair of strong voltammetry peaks in the double-layer region in acid solutions. Adsorption of the DNA bases gives featureless voltammograms with lower double-layer capacitance, suggesting that all the bases are chemisorbed on the Au(110) surface. Further investigation of the surface structures...... of the adlayers of the four DNA bases by EC-STM disclosed lifting of the Au(110) reconstruction, specific molecular packing in dense monolayers, and pH dependence of the A and G adsorption. DFT computations based on a cluster model for the Au(110) surface were performed to investigate the adsorption energy...

  10. MAXIMIZATION OF DNA DAMAGE TO MGMT(+ EGFR(+ GBM CELLS USING OPTIMAL COMBINATION OF TEMOZOLOMIDE-ANTI EGFR MONOCLONAL ANTIBODY NIMOTUZUMAB

    Directory of Open Access Journals (Sweden)

    M. A. M. Inggas

    2015-09-01

    Full Text Available Background: Glioblastoma multiforme (GBM is the most aggressive primary brain tumor in adultswith dismal prognosis due to the unavailability of an effective therapy. Up to now, there had been no definitive studies published on EGFR inhibition therapy as a chemosensitizer for GBM therapy using Temozolomide (TMZ. This study aims to reveal the most effective method and timing to administer TMZ-anti EGFR targeted therapy which causes maximal DNA damage on GBM cells.Methods: Various regimens of anti EGFR monoclonal antibody Nimotuzumab (NMZ was administered in different combinations with TMZ, performed on U87MG MGMT(+ EGFR(+ cells. The effectiveness of the combinations were evaluated by measuring yH2AX levels which reflects the degree of DNA damage. One-way Anova and LSD tests were performed to determine the effects of each treatment with p<0.05. Results and discussion: the mean SD of yH2AX of each treatment was: 11,90±1,25 for the control group; 29.33±1.91 for NMZ alone; 28.13±1.58 for TMZ alone; 41.53±3.51 for concurrent use; 35.67 ±2.65 for NMZ after 24 hours TMZ; 31.87±2.94 for NMZ after 48 hours TMZ; 39.57±4.2 for TMZ after 24 hours NMZ; and 35.93 ±3.56 for TMZ after 48 hours NMZ. The administration of TMZ concurrent with or after 24 hours NMZ gives the highest amount of DNA damage to GBM cells. Conclusion: The administration of Nimotuzumab targeted therapy up to 24 hours before Temozolomide chemotherapy has been proven to be effective in maximizing the amount of DNA damage done to GBM cells in vitro. 

  11. Combining use of a panel of ssDNA aptamers in the detection of Staphylococcus aureus

    OpenAIRE

    Cao, Xiaoxiao; Li, Shaohua; Chen, Liucun; Ding, Hongmei; Xu, Hua; Huang, Yanping; Li, Jie; Liu, Nongle; Cao, Weihong; Zhu, Yanjun; Shen, Beifen; Shao, Ningsheng

    2009-01-01

    In this article, a panel of ssDNA aptamers specific to Staphylococcus aureus was obtained by a whole bacterium-based SELEX procedure and applied to probing S. aureus. After several rounds of selection with S. aureus as the target and Streptococcus and S. epidermidis as counter targets, the highly enriched oligonucleic acid pool was sequenced and then grouped under different families on the basis of the homology of the primary sequence and the similarity of the secondary structure. Eleven sequ...

  12. Mitochondrial DNA deletion in a patient with combined features of Leigh and Pearson syndromes

    Energy Technology Data Exchange (ETDEWEB)

    Blok, R.B.; Thorburn, D.R.; Danks, D.M. [Royal Children`s Hospital, Melbourne (Australia)] [and others

    1994-09-01

    We describe a heteroplasmic 4237 bp mitochondrial DNA (mtDNA) deletion in an 11 year old girl who has suffered from progressive illness since birth. She has some features of Leigh syndrome (global developmental delay with regression, brainstem dysfunction and lactic acidosis), together with other features suggestive of Pearson syndrome (history of pancytopenia and failure to thrive). The deletion was present at a level greater than 50% in skeletal muscle, but barely detectable in skin fibroblasts following Southern blot analysis, and only observed in blood following PCR analysis. The deletion spanned nt 9498 to nt 13734, and was flanked by a 12 bp direct repeat. Genes for cytochrome c oxidase subunit III, NADH dehydrogenase subunits 3, 4L, 4 and 5, and tRNAs for glycine, arginine, histidine, serine({sup AGY}) and leucine({sup CUN}) were deleted. Southern blotting also revealed an altered Apa I restriction site which was shown by sequence analysis to be caused by G{r_arrow}A nucleotide substitution at nt 1462 in the 12S rRNA gene. This was presumed to be a polymorphism. No abnormalities of mitochondrial ultrastructure, distribution or of respiratory chain enzyme complexes I-IV in skeletal muscle were observed. Mitochondrial disorders with clinical features overlapping more than one syndrome have been reported previously. This case further demonstrates the difficulty in correlating observed clinical features with a specific mitochondrial DNA mutation.

  13. Formulation and in vitro/in vivo evaluation of combining DNA repair and immune enhancing nutritional supplements.

    Science.gov (United States)

    Pero, R W; Amiri, A; Sheng, Y; Welther, M; Rich, M

    2005-04-01

    Combining nutritional supplements to achieve synergistic benefit is a common practice in the nutraceutical industry. However, establishing added health benefit from a combination of natural ingredients is often assumed, untested and without regard to the principle of metabolic competition between the active components. Here, we report on the combination of a cat's claw water extract (C-Med-100, carboxy alkyl esters = active ingredients) + medicinal mushroom extracts (Cordyceps sinensis, Grifola blazei, Grifolafrondosa, Trametes versicolor and Ganoderma lucidum, polysaccharides = active ingredients) + nicotinamide + zinc into a formulation designed to optimize different modes of immunostimulatory action, and yet that would avoid metabolic antioxidant competition yielding less than expected efficacious effects. Isobole curve analyses of these two active classes of ingredients determined by growth inhibition of HL-60 human leukemic cells in vitro confirmed they were indeed synergistic when in combination, and not metabolically competitive. Furthermore, an in vivo study showed significant health benefit for 14 subjects treated for 4 weeks with the unique C-Med-100/mushroom extract formulation in that they had reduced pain, reduced fatigue, weight loss and a reduced presence of DNA damage in peripheral blood assessed by (8-OH) guanine DNA adducts and elevation in serum protein thiols. Because this broad-based panel of clinical parameters indicating clinical efficacy has never been demonstrated before for either of the active ingredients evaluated alone in humans, these data were taken as strong evidence that the combination of C-Med-100 + mushroom extracts + nicotinamide + zinc gave additive or synergistic effects to health benefit, and thus supported no efficacious limits from metabolic competition regarding this particular formulation.

  14. Molecular recognition of DNA-protein complexes: A straightforward method combining scanning force and fluorescence microscopy

    NARCIS (Netherlands)

    H. Sanchez (Humberto); R. Kanaar (Roland); C. Wyman (Claire)

    2010-01-01

    textabstractCombining scanning force and fluorescent microscopy allows simultaneous identification of labeled biomolecules and analysis of their nanometer level architectural arrangement. Fluorescent polystyrene nano-spheres were used as reliable objects for alignment of optical and topographic

  15. Radioprotective effects saffron and its combination with green tea against γ-radiation-induced DNA damage in Swiss albino mice

    International Nuclear Information System (INIS)

    Koul, Apurva; Abraham, Suresh K.

    2016-01-01

    Protective effects of aqueous extract of saffron (dried stigmas of Crocus sativus L.) alone and its combination with green tea against γ-radiation-induced genotoxicity and oxidative stress were investigated in Swiss albino mice. Saffron (40 mg/kg bw) alone and in combination with green tea (40 mg/kg bw) were orally administered to mice for six consecutive days, followed by exposure to γ-radiation (2.25 Gy) on 6 th day after final feeding. Antigenotoxic effect of saffron was assayed using micronucleus test in bone marrow cells which showed a significant decrease in the number of micronucleated PCEs in saffron alone and its combination with green tea pre-treated animals when compared with the radiation alone treated animals. Saffron alone and its combination with green tea pre-treated animals showed a significant decrease in lipid peroxidation levels with a significant increase in the activity of antioxidant defense system enzymes, viz. acetylcholine esterase, glutathione-S-transferase, catalase, glutathione peroxidase, glutathione reductase and non-enzymatic antioxidant (GSH), when compared with the radiation alone treated animals. Our results suggested that saffron in combination with green tea exhibits radioprotective effects against γ-radiation induced DNA damage and oxidative stress in Swiss albino mice. (author)

  16. Combined DNA, toxicological and heavy metal analyses provides an auditing toolkit to improve pharmacovigilance of traditional Chinese medicine (TCM)

    Science.gov (United States)

    Coghlan, Megan L.; Maker, Garth; Crighton, Elly; Haile, James; Murray, Dáithí C.; White, Nicole E.; Byard, Roger W.; Bellgard, Matthew I.; Mullaney, Ian; Trengove, Robert; Allcock, Richard J. N.; Nash, Christine; Hoban, Claire; Jarrett, Kevin; Edwards, Ross; Musgrave, Ian F.; Bunce, Michael

    2015-12-01

    Globally, there has been an increase in the use of herbal remedies including traditional Chinese medicine (TCM). There is a perception that products are natural, safe and effectively regulated, however, regulatory agencies are hampered by a lack of a toolkit to audit ingredient lists, adulterants and constituent active compounds. Here, for the first time, a multidisciplinary approach to assessing the molecular content of 26 TCMs is described. Next generation DNA sequencing is combined with toxicological and heavy metal screening by separation techniques and mass spectrometry (MS) to provide a comprehensive audit. Genetic analysis revealed that 50% of samples contained DNA of undeclared plant or animal taxa, including an endangered species of Panthera (snow leopard). In 50% of the TCMs, an undeclared pharmaceutical agent was detected including warfarin, dexamethasone, diclofenac, cyproheptadine and paracetamol. Mass spectrometry revealed heavy metals including arsenic, lead and cadmium, one with a level of arsenic >10 times the acceptable limit. The study showed 92% of the TCMs examined were found to have some form of contamination and/or substitution. This study demonstrates that a combination of molecular methodologies can provide an effective means by which to audit complementary and alternative medicines.

  17. Strong intrinsic motivation

    OpenAIRE

    Dessi, Roberta; Rustichini, Aldo

    2015-01-01

    A large literature in psychology, and more recently in economics, has argued that monetary rewards can reduce intrinsic motivation. We investigate whether the negative impact persists when intrinsic motivation is strong, and test this hypothesis experimentally focusing on the motivation to undertake interesting and challenging tasks, informative about individual ability. We find that this type of task can generate strong intrinsic motivation, that is impervious to the effect of monetary incen...

  18. Novel synthetic approach to asymmetric monocationic trimethine cyanine dyes derived from N-ethyl quinolinum moiety. Combined fluorescent and ICD probes for AT-DNA labelling

    Energy Technology Data Exchange (ETDEWEB)

    Kurutos, Atanas [Department of Pharmaceutical and Applied Organic Chemistry, Faculty of Chemistry, University of Sofia, 1164 Sofia (Bulgaria); Crnolatac, Ivo; Orehovec, Iva [Laboratory for Study of Interactions of Biomacromolecules, Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička c. 54, 10000 Zagreb (Croatia); Gadjev, Nikolai [Department of Pharmaceutical and Applied Organic Chemistry, Faculty of Chemistry, University of Sofia, 1164 Sofia (Bulgaria); Piantanida, Ivo, E-mail: pianta@irb.hr [Laboratory for Study of Interactions of Biomacromolecules, Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička c. 54, 10000 Zagreb (Croatia); Deligeorgiev, Todor, E-mail: ohtak@chem.uni-sofia.bg [Department of Pharmaceutical and Applied Organic Chemistry, Faculty of Chemistry, University of Sofia, 1164 Sofia (Bulgaria)

    2016-06-15

    Two asymmetric monocationic trimethine cyanine dyes were obtained via condensation reaction between 2-methylbenzothialolium salts containing various (aliphatic and benzyl) substituents on the nitrogen atom of the benzothiazolic chromophore, and 1-ethyl−4-(2-(phenylamine)vinyl)quinolin−1-ium iodide, by a novel improved method at room temperature under mild conditions. Both compounds bind non-covalently to double stranded DNA and RNA by micromolar affinity, but give highly selective fluorescent response>650 nm for only AT-DNA sequences at excess of DNA over dye, combined with equally AT-DNA selective ICD response at dye/DNA crowded conditions (r{sub [dye]/[AT-DNA]}>0.2)-namely ICD bands (attributed to dye-dimer formation) allow determination of AT-DNA at submicromolar concentrations. Selectivity was attributed to particular steric properties of AT-DNA minor groove in respect to other studied ds-DNA/RNA. Comparison of aliphatic- and benzyl- dye showed that only aliphatic- derivative revealed ICD band upon binding to AU-RNA major groove and short AT-sequences in mixed sequence (ct-)DNA.

  19. Cations form sequence selective motifs within DNA grooves via a combination of cation-pi and ion-dipole/hydrogen bond interactions.

    Science.gov (United States)

    Stewart, Mikaela; Dunlap, Tori; Dourlain, Elizabeth; Grant, Bryce; McFail-Isom, Lori

    2013-01-01

    The fine conformational subtleties of DNA structure modulate many fundamental cellular processes including gene activation/repression, cellular division, and DNA repair. Most of these cellular processes rely on the conformational heterogeneity of specific DNA sequences. Factors including those structural characteristics inherent in the particular base sequence as well as those induced through interaction with solvent components combine to produce fine DNA structural variation including helical flexibility and conformation. Cation-pi interactions between solvent cations or their first hydration shell waters and the faces of DNA bases form sequence selectively and contribute to DNA structural heterogeneity. In this paper, we detect and characterize the binding patterns found in cation-pi interactions between solvent cations and DNA bases in a set of high resolution x-ray crystal structures. Specifically, we found that monovalent cations (Tl⁺) and the polarized first hydration shell waters of divalent cations (Mg²⁺, Ca²⁺) form cation-pi interactions with DNA bases stabilizing unstacked conformations. When these cation-pi interactions are combined with electrostatic interactions a pattern of specific binding motifs is formed within the grooves.

  20. Classification of Breast Cancer Subtypes by combining Gene Expression and DNA Methylation Data

    Directory of Open Access Journals (Sweden)

    List Markus

    2014-06-01

    Full Text Available Selecting the most promising treatment strategy for breast cancer crucially depends on determining the correct subtype. In recent years, gene expression profiling has been investigated as an alternative to histochemical methods. Since databases like TCGA provide easy and unrestricted access to gene expression data for hundreds of patients, the challenge is to extract a minimal optimal set of genes with good prognostic properties from a large bulk of genes making a moderate contribution to classification. Several studies have successfully applied machine learning algorithms to solve this so-called gene selection problem. However, more diverse data from other OMICS technologies are available, including methylation. We hypothesize that combining methylation and gene expression data could already lead to a largely improved classification model, since the resulting model will reflect differences not only on the transcriptomic, but also on an epigenetic level. We compared so-called random forest derived classification models based on gene expression and methylation data alone, to a model based on the combined features and to a model based on the gold standard PAM50. We obtained bootstrap errors of 10-20% and classification error of 1-50%, depending on breast cancer subtype and model. The gene expression model was clearly superior to the methylation model, which was also reflected in the combined model, which mainly selected features from gene expression data. However, the methylation model was able to identify unique features not considered as relevant by the gene expression model, which might provide deeper insights into breast cancer subtype differentiation on an epigenetic level.

  1. Classification of Breast Cancer Subtypes by combining Gene Expression and DNA Methylation Data

    DEFF Research Database (Denmark)

    List, Markus; Hauschild, Anne-Christin; Tan, Qihua

    2014-01-01

    expression data for hundreds of patients, the challenge is to extract a minimal optimal set of genes with good prognostic properties from a large bulk of genes making a moderate contribution to classification. Several studies have successfully applied machine learning algorithms to solve this so-called gene...... on the transcriptomic, but also on an epigenetic level. We compared so-called random forest derived classification models based on gene expression and methylation data alone, to a model based on the combined features and to a model based on the gold standard PAM50. We obtained bootstrap errors of 10...

  2. Chromosome damage induced by DNA topoisomerase II inhibitors combined with g-radiation in vitro

    Directory of Open Access Journals (Sweden)

    Maria Cristina P. Araújo

    1998-09-01

    Full Text Available Combined radiation and antineoplastic drug treatment have important applications in cancer therapy. In the present work, an evaluation was made of two known topoisomerase II inhibitors, doxorubicin (DXR and mitoxantrone (MXN, with g-radiation. The effects of DXR or MXN on g-radiation-induced chromosome aberrations in Chinese hamster ovary (CHO cells were analyzed. Two concentrations of each drug, 0.5 and 1.0 µg/ml DXR, and 0.02 and 0.04 µg/ml MXN, were applied in combination with two doses of g-radiation (20 and 40 cGy. A significant potentiating effect on chromosomal aberrations was observed in CHO cells exposed to 1.0 µg/ml DXR plus 40 cGy. In the other tests, the combination of g-radiation with DXR or MXN gave approximately additive effects. Reduced mitotic indices reflected higher toxicity of the drugs when combined with radiation.A associação de radiação ionizante com drogas antineoplásicas tem importante aplicação na terapia do câncer. No presente trabalho, foram avaliados os efeitos de dois inibidores de topoisomerase II, doxorubicina (DXR e mitoxantrona (MXN, sobre as aberrações cromossômicas induzidas pelas radiações-g em células do ovário de hamster chinês (CHO. Foram usadas as concentrações 0,5 e 1,0 mg/ml de DXR e 0,02 e 0,04 mg/ml de MXN, combinadas com duas doses de radiações gama (20 e 40 cGy. Um significativo efeito potenciador das aberrações cromossômicas foi observado em células CHO tratadas com 1,0 mg/ml de DXR e expostas a 40 cGy de radiação. Nos outros testes, a combinação da radiação-g com a DXR ou MXN apresentou um efeito próximo ao aditivo. A redução dos índices mitóticos refletiu a alta citotoxicidade das drogas quando combinadas às radiações-g.

  3. Nuclear and cpDNA sequences combined provide strong inference of higher phylogenetic relationships in the phlox family (Polemoniaceae).

    Science.gov (United States)

    Johnson, Leigh A; Chan, Lauren M; Weese, Terri L; Busby, Lisa D; McMurry, Samuel

    2008-09-01

    Members of the phlox family (Polemoniaceae) serve as useful models for studying various evolutionary and biological processes. Despite its biological importance, no family-wide phylogenetic estimate based on multiple DNA regions with complete generic sampling is available. Here, we analyze one nuclear and five chloroplast DNA sequence regions (nuclear ITS, chloroplast matK, trnL intron plus trnL-trnF intergeneric spacer, and the trnS-trnG, trnD-trnT, and psbM-trnD intergenic spacers) using parsimony and Bayesian methods, as well as assessments of congruence and long branch attraction, to explore phylogenetic relationships among 84 ingroup species representing all currently recognized Polemoniaceae genera. Relationships inferred from the ITS and concatenated chloroplast regions are similar overall. A combined analysis provides strong support for the monophyly of Polemoniaceae and subfamilies Acanthogilioideae, Cobaeoideae, and Polemonioideae. Relationships among subfamilies, and thus for the precise root of Polemoniaceae, remain poorly supported. Within the largest subfamily, Polemonioideae, four clades corresponding to tribes Polemonieae, Phlocideae, Gilieae, and Loeselieae receive strong support. The monogeneric Polemonieae appears sister to Phlocideae. Relationships within Polemonieae, Phlocideae, and Gilieae are mostly consistent between analyses and data permutations. Many relationships within Loeselieae remain uncertain. Overall, inferred phylogenetic relationships support a higher-level classification for Polemoniaceae proposed in 2000.

  4. Potential DNA barcodes for Melilotus species based on five single loci and their combinations.

    Directory of Open Access Journals (Sweden)

    Fan Wu

    Full Text Available Melilotus, an annual or biennial herb, belongs to the tribe Trifolieae (Leguminosae and consists of 19 species. As an important green manure crop, diverse Melilotus species have different values as feed and medicine. To identify different Melilotus species, we examined the efficiency of five candidate regions as barcodes, including the internal transcribed spacer (ITS and two chloroplast loci, rbcL and matK, and two non-coding loci, trnH-psbA and trnL-F. In total, 198 individuals from 98 accessions representing 18 Melilotus species were sequenced for these five potential barcodes. Based on inter-specific divergence, we analysed sequences and confirmed that each candidate barcode was able to identify some of the 18 species. The resolution of a single barcode and its combinations ranged from 33.33% to 88.89%. Analysis of pairwise distances showed that matK+rbcL+trnL-F+trnH-psbA+ITS (MRTPI had the greatest value and rbcL the least. Barcode gap values and similarity value analyses confirmed these trends. The results indicated that an ITS region, successfully identifying 13 of 18 species, was the most appropriate single barcode and that the combination of all five potential barcodes identified 16 of the 18 species. We conclude that MRTPI is the most effective tool for Melilotus species identification. Taking full advantage of the barcode system, a clear taxonomic relationship can be applied to identify Melilotus species and enhance their practical production.

  5. [Combined use of irradiation and DNA tumor vaccine to treat canine oral malignant melanoma: a pilot study].

    Science.gov (United States)

    Herzog, A; Buchholz, J; Ruess-Melzer, K; Lang, J; Kaser-Hotz, B

    2013-02-01

    Melanoma is the most common oral tumor in dogs, characterized by rapid growth, local invasion, and high metastatic rate. The goal of this study was to evaluate the combination of radiation therapy and DNA tumor vaccine. We hypothesized, that the concurrent use would not increase toxicity. Nine dogs with oral melanoma were treated with 4 fractions of 8 Gray at 7-day intervals. The vaccine was given 4 times every 14 days, beginning at the first radiation fraction. Local acute radiation toxicities were assessed according to the VRTOG toxicity scoring scheme over a time period of 7 weeks. In none of the evaluated dogs, mucositis, dermatitis and conjunctivitis exceeded grade 2. In 3 dogs mild fever, lethargy, and local swelling at the injection site were seen after vaccine application. In conclusion, the concurrent administration of radiation therapy and vaccine was well tolerated in all dogs.

  6. The influence of combined treatment of Cd, and γ-irradiation on DNA damage and repair in lymphoid tissues of mice

    International Nuclear Information System (INIS)

    Privezentsev, K.V.; Sirota, N.P.; Gaziev, A.I.

    1996-01-01

    The effect of combined treatment of Cd and γ-irradiation on DNA damage and repair was studied in lymphoid tissues of mice using single-cell gel assay. Single i.p. injection of CdCl 2 (1 mg Cd/kg body wt), 2 h prior to irradiation resulted in increasing of DNA lesions in peripheral blood lymphocytes (PBL) when compared to non-injected animals. However, the same treatment, 48 h prior to irradiation is shown to decrease DNA damage in PBL and splenocytes in comparison with untreated mice. In thymocytes maximal protective effect of Cd was determined when mice were irradiated in 24 h after injection. The protective effect observed is due to decreasing of initial level of DNA damage in thymocytes as well as acceleration of DNA repair in PBL and splenocytes. 28 refs.; 2 figs

  7. DNA: Structure and function

    DEFF Research Database (Denmark)

    Sinden, Richard R.; E. Pearson, Christopher; N. Potaman, Vladimir

    1998-01-01

    This chapter discusses the structure and function of DNA. DNA occupies a critical role in cells, because it is the source of all intrinsic genetic information. Chemically, DNA is a very stable molecule, a characteristic important for a macromolecule that may have to persist in an intact form...

  8. Combination of pentafluorophenylhydrazine derivatization and isotope dilution LC-MS/MS techniques for the quantification of apurinic/apyrimidinic sites in cellular DNA.

    Science.gov (United States)

    Li, Jie; Leung, Elvis M K; Choi, Martin M F; Chan, Wan

    2013-05-01

    Apurinic/apyrimidinic (AP) sites are common DNA lesions arising from spontaneous hydrolysis of the N-glycosidic bond and base-excision repair mechanisms of the modified bases. Due to the strong association of AP site formation with physically/chemically induced DNA damage, quantifying AP sites provides important information for risk assessment of exposure to genotoxins and oxidative stress. However, rigorous quantification of AP sites in DNA has been hampered by technical problems relating to the sensitivity and selectivity of existing analytical methods. We have developed a new isotope dilution liquid chromatography-coupled tandem mass spectrometry (LC-MS/MS) method for the rigorous quantification of AP sites in genomic DNA. The method entails enzymatic digestion of AP site-containing DNA by endo- and exonucleases, derivatization with pentafluorophenylhydrazine (PFPH), addition of an isotopically labeled PFPH derivative as internal standard, and quantification by LC-MS/MS. The combination of PFPH derivatization with LC-MS/MS analysis on a triple quadrupole mass spectrometer allows for sensitive and selective quantification of AP sites in DNA at a detection limit of 6.5 fmol, corresponding to 4 AP sites/10(9) nt in 5 μg of DNA, which is at least ten times more sensitive than existing analytical methods. The protocol was validated by AP site-containing oligonucleotides and applied in quantifying methyl methanesulfonate-induced formation of AP sites in cellular DNA.

  9. Intrinsic-density functionals

    International Nuclear Information System (INIS)

    Engel, J.

    2007-01-01

    The Hohenberg-Kohn theorem and Kohn-Sham procedure are extended to functionals of the localized intrinsic density of a self-bound system such as a nucleus. After defining the intrinsic-density functional, we modify the usual Kohn-Sham procedure slightly to evaluate the mean-field approximation to the functional, and carefully describe the construction of the leading corrections for a system of fermions in one dimension with a spin-degeneracy equal to the number of particles N. Despite the fact that the corrections are complicated and nonlocal, we are able to construct a local Skyrme-like intrinsic-density functional that, while different from the exact functional, shares with it a minimum value equal to the exact ground-state energy at the exact ground-state intrinsic density, to next-to-leading order in 1/N. We briefly discuss implications for real Skyrme functionals

  10. Combination is the dominant free radical process initiated in DNA by ionizing radiation: an overview based on solid-state EPR studies

    International Nuclear Information System (INIS)

    Bernhard, W.A.; Mroczka, N.; Barnes, J.

    1994-01-01

    An overview of the early processes initiated in DNA by ionizing radiation is given from the perspective of studies done by solid-state EPR with the focus on radical combination. Comparisons with free radical formation and trapping in crystalline pyrimidines (1-methylcytosine, thymine, 1-methylthymine, 1-methyluracil, and cytosine monohydrate) provide insight into the processes occurring in DNA. Between 25 and 50% of low LET ionizations in fully hydrated DNA at 4 K lead to trapped free radicals, the remaining unobserved radicals are assumed to have combined. The majority of the radicals trapped in DNA at 4 K (G ∼ 0.3 μmol/J) are believed to be in clusters. Based on the value of G, it is argued that the range of holes and bound electrons in DNA at 4 K are, in the main, limited to within the cluster diameter, ∼ 4 nm. Proton transfer across hydrogen bonds promotes radical trapping and inhibits combination but is thermally reversible. Warming to room temperature mobilizes the reversibly trapped radicals and gives additional combination (50-80% of those trapped at 4 K). The yield of free radicals, after anneal, is sufficient to account for the yield of single-strand breaks produced by direct effects. (Author)

  11. Intrinsic Time Quantum Geometrodynamics

    OpenAIRE

    Ita III, Eyo Eyo; Soo, Chopin; Yu, Hoi-Lai

    2015-01-01

    Quantum Geometrodynamics with intrinsic time development and momentric variables is presented. An underlying SU(3) group structure at each spatial point regulates the theory. The intrinsic time behavior of the theory is analyzed, together with its ground state and primordial quantum fluctuations. Cotton-York potential dominates at early times when the universe was small; the ground state naturally resolves Penrose's Weyl Curvature Hypothesis, and thermodynamic and gravitational `arrows of tim...

  12. Synergy of irofulven in combination with other DNA damaging agents: synergistic interaction with altretamine, alkylating, and platinum-derived agents in the MV522 lung tumor model.

    Science.gov (United States)

    Kelner, Michael J; McMorris, Trevor C; Rojas, Rafael J; Estes, Leita A; Suthipinijtham, Pharnuk

    2008-12-01

    Irofulven (MGI 114, NSC 683863) is a semisynthetic derivative of illudin S, a natural product present in the Omphalotus illudins (Jack O'Lantern) mushroom. This novel agent produces DNA damage, that in contrast to other agents, is predominately ignored by the global genome repair pathway of the nucleotide excision repair (NER)(2) system. The aim of this study was to determine the antitumor activity of irofulven when administered in combination with 44 different DNA damaging agents, whose damage is in general detected and repaired by the genome repair pathway. The human lung carcinoma MV522 cell line and its corresponding xenograft model were used to evaluate the activity of irofulven in combination with different DNA damaging agents. Two main classes of DNA damaging agents, platinum-derived agents, and select bifunctional alkylating agents, demonstrated in vivo synergistic or super-additive interaction with irofulven. DNA helicase inhibiting agents also demonstrated synergy in vitro, but an enhanced interaction with irofulven could not be demonstrated in vivo. There was no detectable synergistic activity between irofulven and agents capable of inducing DNA cleavage or intercalating into DNA. These results indicate that the antitumor activity of irofulven is enhanced when combined with platinum-derived agents, altretamine, and select alkylating agents such as melphalan or chlorambucil. A common factor between these agents appears to be the production of intrastrand DNA crosslinks. The synergistic interaction between irofulven and other agents may stem from the nucleotide excision repair system being selectively overwhelmed at two distinct points in the pathway, resulting in prolonged stalling of transcription forks, and subsequent initiation of apoptosis.

  13. Revealing the uncultivated majority: combining DNA stable-isotope probing, multiple displacement amplification and metagenomic analyses of uncultivated Methylocystis in acidic peatlands.

    Science.gov (United States)

    Chen, Yin; Dumont, Marc G; Neufeld, Josh D; Bodrossy, Levente; Stralis-Pavese, Nancy; McNamara, Niall P; Ostle, Nick; Briones, Maria J I; Murrell, J Colin

    2008-10-01

    Peatlands represent an enormous carbon reservoir and have a potential impact on the global climate because of the active methanogenesis and methanotrophy in these soils. Uncultivated methanotrophs from seven European peatlands were studied using a combination of molecular methods. Screening for methanotroph diversity using a particulate methane monooxygenase-based diagnostic gene array revealed that Methylocystis-related species were dominant in six of the seven peatlands studied. The abundance and methane oxidation activity of Methylocystis spp. were further confirmed by DNA stable-isotope probing analysis of a sample taken from the Moor House peatland (England). After ultracentrifugation, (13)C-labelled DNA, containing genomic DNA of these Methylocystis spp., was separated from (12)C DNA and subjected to multiple displacement amplification (MDA) to generate sufficient DNA for the preparation of a fosmid metagenomic library. Potential bias of MDA was detected by fingerprint analysis of 16S rRNA using denaturing gradient gel electrophoresis for low-template amplification (0.01 ng template). Sufficient template (1-5 ng) was used in MDA to circumvent this bias and chimeric artefacts were minimized by using an enzymatic treatment of MDA-generated DNA with S1 nuclease and DNA polymerase I. Screening of the metagenomic library revealed one fosmid containing methanol dehydrogenase and two fosmids containing 16S rRNA genes from these Methylocystis-related species as well as one fosmid containing a 16S rRNA gene related to that of Methylocella/Methylocapsa. Sequencing of the 14 kb methanol dehydrogenase-containing fosmid allowed the assembly of a gene cluster encoding polypeptides involved in bacterial methanol utilization (mxaFJGIRSAC). This combination of DNA stable-isotope probing, MDA and metagenomics provided access to genomic information of a relatively large DNA fragment of these thus far uncultivated, predominant and active methanotrophs in peatland soil.

  14. [Applylication of new type combined fragments: nrDNA ITS+ nad 1-intron 2 for identification of Dendrobium species of Fengdous].

    Science.gov (United States)

    Geng, Li-xia; Zheng, Rui; Ren, Jie; Niu, Zhi-tao; Sun, Yu-long; Xue, Qing-yun; Liu, Wei; Ding, Xiao-yu

    2015-08-01

    In this study, 17 kinds of Dendrobium species of Fengdous including 39 individuals were collected from 4 provinces. Mitochondrial gene sequences co I, nad 5, nad 1-intron 2 and chloroplast gene sequences rbcL, matK amd psbA-trnH were amplified from these materials, as well as nrDNA ITS. Furthermore, suitable sequences for identification of Dendrobium species of Fengdous were screened by K-2-P and P-distance. The results showed that during the mentioned 7 sequences, nrDNA ITS, nad 1-intron 2 and psbA-trnH which had a high degree of variability could be used to identify Dendrobium species of Fengdous. However, single fragment could not be used to distinguish D. moniliforme and D. huoshanense. Moreover, compared to other combined fragments, new type combined fragments nrDNA ITS+nad 1-intron 2 was more effective in identifying the original plants of Dendrobium species and could be used to identify D. huoshanense and D. moniliforme. Besides, according to the UPGMA tree constructed with nrDNA ITS+nad 1-intron 2, 3 inspected Dendrobium plants were identified as D. huoshanense, D. moniliforme and D. officinale, respectively. This study identified Dendrobium species of Fengdous by combined fragments nrDNA ITS+nad 1-intron 2 for the first time, which provided a more effective basis for identification of Dendrobium species. And this study will be helpful for regulating the market of Fengdous.

  15. Activity of levofloxacin alone and in combination with a DnaK inhibitor against gram-negative rods, including levofloxacin-resistant strains.

    Science.gov (United States)

    Credito, Kim; Lin, Gengrong; Koeth, Laura; Sturgess, Michael A; Appelbaum, Peter C

    2009-02-01

    Synergy time-kill testing of levofloxacin alone and in combination with CHP-105, a representative DnaK inhibitor, against 50 gram-negative rods demonstrated that 34 of the 50 strains tested showed significant synergy between levofloxacin and CHP-105 after 12 h and 24 h. Fourteen of these 34 organisms were quinolone resistant (levofloxacin MICs of > or =4 microg/ml).

  16. Individual and combined effects of ochratoxin A and citrinin on viability and DNA fragmentation in cultured Vero cells and on chromosome aberrations in mice bone marrow cells

    International Nuclear Information System (INIS)

    Bouslimi, Amel; Bouaziz, Chayma; Ayed-Boussema, Imen; Hassen, Wafa; Bacha, Hassen

    2008-01-01

    Ochratoxin A (OTA) and citrinin (CTN) are two common contaminant mycotoxins which can occur jointly in a wide range of food commodities. Both mycotoxins have several toxic effects but share a significant nephrotoxic and carcinogenic potential since OTA and CTN were reported to be responsible for naturally occurring human and animal kidney diseases and tumors. Considering the concomitant production of OTA and CTN, it is very likely that humans and animals are always exposed to the mixture rather than to individual compounds. Therefore, the aim of the present study was to investigate, in vivo and in vitro, whether DNA damage is enhanced by combination of both mycotoxins as compared to their effect separately. To this end, we have assessed their effects individually or combined on cell proliferation and DNA fragmentation in cultured Vero cells and in vivo by monitoring the induction of chromosome aberrations. Our results clearly showed that cultured renal cells respond to OTA and CTN exposure by a moderate and weak inhibition of cell proliferation, respectively. However, when combined, they exert a significant increase in inhibition of cell viability. Similar results were found for the investigated genotoxicity endpoints (DNA fragmentation and chromosome aberrations). Altogether, our study showed that OTA and CTN combination effects are clearly synergistic. The synergistic induction of DNA damage observed with OTA and CTN taken concomitantly could be relevant to explain the molecular basis of the renal diseases and tumorogenesis induced by naturally occurring mycotoxins

  17. Rapid, highly sensitive and highly specific gene detection by combining enzymatic amplification and DNA chip detection simultaneously

    Directory of Open Access Journals (Sweden)

    Koji Hashimoto

    2016-05-01

    Full Text Available We have developed a novel gene detection method based on the loop-mediated isothermal amplification (LAMP reaction and the DNA dissociation reaction on the same DNA chip surface to achieve a lower detection limit, broader dynamic range and faster detection time than are attainable with a conventional DNA chip. Both FAM- and thiol-labeled DNA probe bound to the complementary sequence accompanying Dabcyl was immobilized on the gold surface via Au/thiol bond. The LAMP reaction was carried out on the DNA probe fixed gold surface. At first, Dabcyl molecules quenched the FAM fluorescence. According to the LAMP reaction, the complementary sequence with Dabcyl was competitively reacted with the amplified targeted sequence. As a result, the FAM fluorescence increased owing to dissociation of the complementary sequence from the DNA probe. The simultaneous reaction of LAMP and DNA chip detection was achieved, and 103 copies of the targeted gene were detected within an hour by measuring fluorescence intensity of the DNA probe. Keywords: Biosensor, DNA chip, Loop-mediated isothermal amplification (LAMP, Fluorescence detection, Gold substrate, Au/thiol bond

  18. A radioisotope dilution assay for unlabelled vitamin B12-intrinsic factor complex employing the binding intrinsic factor antibody: probable evidence for two types of binding antibody

    International Nuclear Information System (INIS)

    Jacob, E.; O'Brien, H.A.W.; Mollin, D.L.

    1977-01-01

    A new radioisotope dilution assay for vitamin B 12 -intrinsic factor complex is described. The method is based on the use of the binding type intrinsic antibody (the binding reagent), which when combined with the intrinsic factor-vitamin B 12 complex (labelled ligand), is quantitatively adsorbed onto zirconium phosphate gel pH 6.25. The new assay has been shown to provide a measure of intrinsic factor comparable with other intrinsic factor assays, but it has the important advantage of being able to measure the unlabelled vitamin B 12 -intrinsic factor complex (unlabelled ligand), and will, therefore, be valuable in the study of physiological events in the gastrointestinal tract. During the study, it was found that there is some evidence for at least two types of binding intrinsic factor antibody: One which combines preferentially with the intrinsic factor-vitamin B 12 complex and one which combines equally well with this complex or with free intrinsic factor. (author)

  19. Intrinsic contractures of the hand.

    Science.gov (United States)

    Paksima, Nader; Besh, Basil R

    2012-02-01

    Contractures of the intrinsic muscles of the fingers disrupt the delicate and complex balance of intrinsic and extrinsic muscles, which allows the hand to be so versatile and functional. The loss of muscle function primarily affects the interphalangeal joints but also may affect etacarpophalangeal joints. The resulting clinical picture is often termed, intrinsic contracture or intrinsic-plus hand. Disruption of the balance between intrinsic and extrinsic muscles has many causes and may be secondary to changes within the intrinsic musculature or the tendon unit. This article reviews diagnosis, etiology, and treatment algorithms in the management of intrinsic contractures of the fingers. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. Study on effect of artemisinin combined with 60Co γ-ray on DNA damage in HeLa and SiHa cells

    International Nuclear Information System (INIS)

    Feng Yang; Zhou Yuanyuan; Yang Wei; Chen Qiu; Li Ming; Zhang Shuyu; Zhu Wei; Cao Jianping; Zhang Xuguang

    2011-01-01

    Objective: To investigate the effect of Artemisinin combined with 60 Co γ-ray on DNA damage in HeLa and SiHa cells of human cervical cancer. Methods: Cell growth kinetics was evaluated by MTT assay to determine the most appropriate drug concentration. Effects of Artemisinin combined with 60 Co γ-ray on DNA damage in HeLa and SiHa cells were detected by single cell gel electrophoresis. Results: With the concentration increased during the effect of Artemisinin, the HeLa and SiHa cells had higher inhibition on cell proliferation. The SCGE showed that:the comet cell analysis indexes (the comet cells ratio, Tail Length, Olive Tail Moment and Tail DNA%) there was no statistic difference in between the artemisinin group and the control group (P>0.05). With radiation in the same dose, the comet cell analysis indexes of Hela cells treated with both artermisinin and exposed to radiation were higher than that only exposed to radiation group(P 0.05). Conclusion: Artemisinin can not induce DNA damage in both HeLa and SiHa cells, but it can make irradiated HeLa cells DNA damage to be aggravated and enhance HeLa cells' radiation sensitivity. However, Artemisinin has no radiosensitizing effect on SiHa cells. (authors)

  1. Predicting Intrinsic Motivation

    Science.gov (United States)

    Martens, Rob; Kirschner, Paul A.

    2004-01-01

    Intrinsic motivation can be predicted from participants' perceptions of the social environment and the task environment (Ryan & Deci, 2000)in terms of control, relatedness and competence. To determine the degree of independence of these factors 251 students in higher vocational education (physiotherapy and hotel management) indicated the…

  2. A dual amplification strategy for DNA detection combining bio-barcode assay and metal-enhanced fluorescence modality.

    Science.gov (United States)

    Zhou, Zhenpeng; Li, Tian; Huang, Hongduan; Chen, Yang; Liu, Feng; Huang, Chengzhi; Li, Na

    2014-11-11

    Silver-enhanced fluorescence was coupled with a bio-barcode assay to facilitate a dual amplification assay to demonstrate a non-enzymatic approach for simple and sensitive detection of DNA. In the assay design, magnetic nanoparticles seeded with silver nanoparticles were modified with the capture DNA, and silver nanoparticles were modified with the binding of ssDNA and the fluorescently labeled barcode dsDNA. Upon introduction of the target DNA, a sandwich structure was formed because of the hybridization reaction. By simple magnetic separation, silver-enhanced fluorescence of barcode DNAs could be readily measured without the need of a further step to liberate barcode DNAs from silver nanoparticles, endowing the method with simplicity and high sensitivity with a detection limit of 1 pM.

  3. Combination of methylated-DNA precipitation and methylation-sensitive restriction enzymes (COMPARE-MS) for the rapid, sensitive and quantitative detection of DNA methylation.

    Science.gov (United States)

    Yegnasubramanian, Srinivasan; Lin, Xiaohui; Haffner, Michael C; DeMarzo, Angelo M; Nelson, William G

    2006-02-09

    Hypermethylation of CpG island (CGI) sequences is a nearly universal somatic genome alteration in cancer. Rapid and sensitive detection of DNA hypermethylation would aid in cancer diagnosis and risk stratification. We present a novel technique, called COMPARE-MS, that can rapidly and quantitatively detect CGI hypermethylation with high sensitivity and specificity in hundreds of samples simultaneously. To quantitate CGI hypermethylation, COMPARE-MS uses real-time PCR of DNA that was first digested by methylation-sensitive restriction enzymes and then precipitated by methyl-binding domain polypeptides immobilized on a magnetic solid matrix. We show that COMPARE-MS could detect five genome equivalents of methylated CGIs in a 1000- to 10,000-fold excess of unmethylated DNA. COMPARE-MS was used to rapidly quantitate hypermethylation at multiple CGIs in >155 prostate tissues, including benign and malignant prostate specimens, and prostate cell lines. This analysis showed that GSTP1, MDR1 and PTGS2 CGI hypermethylation as determined by COMPARE-MS could differentiate between malignant and benign prostate with sensitivities >95% and specificities approaching 100%. This novel technology could significantly improve our ability to detect CGI hypermethylation.

  4. New flexible origination technology based on electron-beam lithography and its integration into security devices in combination with covert features based on DNA authentication

    Science.gov (United States)

    Drinkwater, John K.; Ryzi, Zbynek; Outwater, Chris S.

    2002-04-01

    Embossed diffractive optically variable devices are becoming increasingly familiar security items on plastic cards, banknotes, security documents and on branded goods and media to protect against counterfeit, protect copyright and to evidence tamper. Equally as this devices become both more widely available there is a pressing requirement for security technology upgrades to keep ahead of technology advances available to potential counterfeiters. This paper describes a new generation electron beam DOVID origination technology particularly suitable for high security applications. Covert marking of security devices is provided using the DNA matrix by creating and verifying unique DNA sequences. This integration of this into practical security features in combination with covert features based on DNA matrix authentication and other more straightforwardly authenticable features to provide multi- technology security solutions will be described.

  5. Curcumin stably interacts with DNA hairpin through minor groove binding and demonstrates enhanced cytotoxicity in combination with FdU nucleotides.

    Science.gov (United States)

    Ghosh, Supratim; Mallick, Sumana; Das, Upasana; Verma, Ajay; Pal, Uttam; Chatterjee, Sabyasachi; Nandy, Abhishek; Saha, Krishna D; Maiti, Nakul Chandra; Baishya, Bikash; Suresh Kumar, G; Gmeiner, William H

    2018-03-01

    We report, based on biophysical studies and molecular mechanical calculations that curcumin binds DNA hairpin in the minor groove adjacent to the loop region forming a stable complex. UV-Vis and fluorescence spectroscopy indicated interaction of curcumin with DNA hairpin. In this novel binding motif, two ɣ H of curcumin heptadiene chain are closely positioned to the A 16 -H8 and A 17 -H8, while G 12 -H8 is located in the close proximity of curcumin α H. Molecular dynamics (MD) simulations suggest, the complex is stabilized by noncovalent forces including; π-π stacking, H-bonding and hydrophobic interactions. Nuclear magnetic resonance (NMR) spectroscopy in combination with molecular dynamics simulations indicated curcumin is bound in the minor groove, while circular dichroism (CD) spectra suggested minute enhancement in base stacking and a little change in DNA helicity, without significant conformational change of DNA hairpin structure. The DNA:curcumin complex formed with FdU nucleotides rather than Thymidine, demonstrated enhanced cytotoxicity towards oral cancer cells relative to the only FdU substituted hairpin. Fluorescence co-localization demonstrated stability of the complex in biologically relevant conditions, including its cellular uptake. Acridine orange/EtBr staining further confirmed the enhanced cytotoxic effects of the complex, suggesting apoptosis as mode of cell death. Thus, curcumin can be noncovalently complexed to small DNA hairpin for cellular delivery and the complex showed increased cytotoxicity in combination with FdU nucleotides, demonstrating its potential for advanced cancer therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Concepts of intrinsic safety

    International Nuclear Information System (INIS)

    Anon.

    1985-01-01

    A newly introduced Japanese reactor concept, ISER (Intrinsically Safe and Economical Reactor), is intended to be a reference intrinsically safe light water reactor. ISER is designed similarly to PIUS but with greater economy in mind such that any utility in any country can choose it for its power system. Social assimilation and acceptability in the Asia Pacific Region including the United States are the keys to the ISER with the hope of dramatic reductions of social costs due to safeguards, reliability, financiability, and infrastructure building, particularly in the third world, as well as reactor safety itself. In this respect and others, the ISER proposal is different from other vendor-proposed reactor concepts and is unique

  7. Nuclear/Nucleolar morphometry and DNA image cytometry as a combined diagnostic tool in pathology of prostatic carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Kavantzas, N.; Agapitos, E.; Lazaris, A. C.; Pavlopulos, P.M.; Sofikitis, N.; Davaris, P. [National University of Athens, Dept. of Pathology, Medical School, Athens (Greece)

    2001-12-01

    Paraffin tissue sections from 50 patients with prostate adenocarcinoma were used to study nuclear and nucleolar morphometric features by image analysis. The results were compared to DNA ploidy and Gleason grade. In the examined histological samples nuclear and nucleolar areas were positively interrelated. It was also noticed that the higher the percentage of nucleolated nuclei, the bigger the nuclear and nucleolar areas. The morphometric characteristics did not differ significantly among the four grades of the examined specimens. In well-differentiated carcinomas the DNA index was lower than in the rest at a statistically significant level. Hypodiploid carcinomas were found to possess significantly bigger nuclear areas than any other DNA index group. Morphonuclear evidence of anaplasia and DNA aneuploidy may be used as diagnostic tools in prostate cancer in addition to Gleason grade.

  8. Nuclear/Nucleolar morphometry and DNA image cytometry as a combined diagnostic tool in pathology of prostatic carcinoma

    International Nuclear Information System (INIS)

    Kavantzas, N.; Agapitos, E.; Lazaris, A. C.; Pavlopulos, P.M.; Sofikitis, N.; Davaris, P.

    2001-01-01

    Paraffin tissue sections from 50 patients with prostate adenocarcinoma were used to study nuclear and nucleolar morphometric features by image analysis. The results were compared to DNA ploidy and Gleason grade. In the examined histological samples nuclear and nucleolar areas were positively interrelated. It was also noticed that the higher the percentage of nucleolated nuclei, the bigger the nuclear and nucleolar areas. The morphometric characteristics did not differ significantly among the four grades of the examined specimens. In well-differentiated carcinomas the DNA index was lower than in the rest at a statistically significant level. Hypodiploid carcinomas were found to possess significantly bigger nuclear areas than any other DNA index group. Morphonuclear evidence of anaplasia and DNA aneuploidy may be used as diagnostic tools in prostate cancer in addition to Gleason grade

  9. 5-Azacytidine combined with 2,4-D improves somatic embryogenesis of Acca sellowiana (O. Berg) Burret by means of changes in global DNA methylation levels.

    Science.gov (United States)

    Fraga, Hugo P F; Vieira, Leila N; Caprestano, Clarissa A; Steinmacher, Douglas A; Micke, Gustavo A; Spudeit, Daniel A; Pescador, Rosete; Guerra, Miguel P

    2012-12-01

    DNA methylation is an epigenetic regulatory mechanism of gene expression which can be associated with developmental phases and in vitro morphogenetic competence in plants. The present work evaluated the effects of 5-azacytidine (AzaC) and 2,4-dichlorophenoxyacetic acid (2,4-D) on Acca sellowiana somatic embryogenesis (SE) and global DNA methylation levels by high-performance liquid chromatography mass spectrometry (HPLC/MS/MS). 2,4-D-free treatments revealed no somatic embryo formation in both accessions tested. Treatments supplemented with 2,4-D pulse plus AzaC in the culture medium resulted in increased embryo formation. In AzaC-free treatment, HPLC/MS/MS analysis showed a gradual increase in methylation levels in cultures of both accessions tested during SE induction. Treatment with AzaC and 2,4-D-free resulted in a marked decrease in methylation for both accessions, ranging from 37.6 to 20.8 %. In treatment with 2,4-D and AzaC combined, the 85 accession showed increasing global methylation levels. Otherwise, the 101X458 accession, in the same treatment, showed a decrease between 10 and 20 days, followed by an increase after 30 days (39.5, 36.2 and 41.6 %). These results indicate that 2,4-D pulse combined with AzaC improves SE induction. However, the conversion phase showed that although positively influencing SE induction, AzaC had a dysregulatory effect on the stage of autotrophic plant formation, resulting in significantly lower conversion rates. The results suggest that DNA methylation dramatically influences SE in Acca sellowiana, and global DNA methylation dynamics are related to morphogenetic response. 5-Azacytidine combined with 2,4-D increases the number of Acca sellowiana somatic embryos. Global DNA methylation is directly affected by these compounds.

  10. Combined quantum-mechanics/molecular-mechanics dynamics simulation of A-DNA double strands irradiated by ultra-low-energy carbon ions

    Energy Technology Data Exchange (ETDEWEB)

    Ngaojampa, C.; Nimmanpipug, P. [Computer Simulation and Modeling Laboratory (CSML), Department of Chemistry and Center for Innovation Chemistry, Faculty of Science, Chiang Mai University, Chiang Mai 50200 (Thailand); Yu, L.D., E-mail: yuld@fnrf.science.cmu.ac.t [Plasma and Beam Physics Research Facility, Department of Physics and Materials Science, Faculty of Science, Chiang Mai University, Chiang Mai 50200 (Thailand); Thailand Center of Excellence in Physics, Commission on Higher Education, 328 Si Ayutthaya Road, Bangkok 10400 (Thailand); Anuntalabhochai, S. [Molecular Biology Laboratory, Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai 50200 (Thailand); Lee, V.S., E-mail: vannajan@gmail.co [Computer Simulation and Modeling Laboratory (CSML), Department of Chemistry and Center for Innovation Chemistry, Faculty of Science, Chiang Mai University, Chiang Mai 50200 (Thailand); Thailand Center of Excellence in Physics, Commission on Higher Education, 328 Si Ayutthaya Road, Bangkok 10400 (Thailand)

    2011-02-15

    In order to promote understanding of the fundamentals of ultra-low-energy ion interaction with DNA, molecular dynamics simulations using combined quantum-mechanics/molecular-mechanics of poly-AT and poly-GC A-DNA double strands irradiated by <200 eV carbon ions were performed to investigate the molecular implications of mutation bias. The simulations were focused on the responses of the DNA backbones and nitrogenous bases to irradiation. Analyses of the root mean square displacements of the backbones and non-hydrogen atoms of base rings of the simulated DNA structure after irradiation revealed a potential preference of DNA double strand separation, dependent on the irradiating energy. The results show that for the backbones, the large difference in the displacement between poly-GC and poly-AT in the initial time period could be the reason for the backbone breakage; for the nitrogenous base pairs, A-T is 30% more sensitive or vulnerable to ion irradiation than G-C, demonstrating a preferential, instead of random, effect of irradiation-induced mutation.

  11. One simple DNA extraction device and its combination with modified visual loop-mediated isothermal amplification for rapid on-field detection of genetically modified organisms.

    Science.gov (United States)

    Zhang, Miao; Liu, Yinan; Chen, Lili; Quan, Sheng; Jiang, Shimeng; Zhang, Dabing; Yang, Litao

    2013-01-02

    Quickness, simplicity, and effectiveness are the three major criteria for establishing a good molecular diagnosis method in many fields. Herein we report a novel detection system for genetically modified organisms (GMOs), which can be utilized to perform both on-field quick screening and routine laboratory diagnosis. In this system, a newly designed inexpensive DNA extraction device was used in combination with a modified visual loop-mediated isothermal amplification (vLAMP) assay. The main parts of the DNA extraction device included a silica gel membrane filtration column and a modified syringe. The DNA extraction device could be easily operated without using other laboratory instruments, making it applicable to an on-field GMO test. High-quality genomic DNA (gDNA) suitable for polymerase chain reaction (PCR) and isothermal amplification could be quickly isolated from plant tissues using this device within 15 min. In the modified vLAMP assay, a microcrystalline wax encapsulated detection bead containing SYBR green fluorescent dye was introduced to avoid dye inhibition and cross-contaminations from post-LAMP operation. The system was successfully applied and validated in screening and identification of GM rice, soybean, and maize samples collected from both field testing and the Grain Inspection, Packers, and Stockyards Administration (GIPSA) proficiency test program, which demonstrated that it was well-adapted to both on-field testing and/or routine laboratory analysis of GMOs.

  12. Combined quantum-mechanics/molecular-mechanics dynamics simulation of A-DNA double strands irradiated by ultra-low-energy carbon ions

    International Nuclear Information System (INIS)

    Ngaojampa, C.; Nimmanpipug, P.; Yu, L.D.; Anuntalabhochai, S.; Lee, V.S.

    2011-01-01

    In order to promote understanding of the fundamentals of ultra-low-energy ion interaction with DNA, molecular dynamics simulations using combined quantum-mechanics/molecular-mechanics of poly-AT and poly-GC A-DNA double strands irradiated by <200 eV carbon ions were performed to investigate the molecular implications of mutation bias. The simulations were focused on the responses of the DNA backbones and nitrogenous bases to irradiation. Analyses of the root mean square displacements of the backbones and non-hydrogen atoms of base rings of the simulated DNA structure after irradiation revealed a potential preference of DNA double strand separation, dependent on the irradiating energy. The results show that for the backbones, the large difference in the displacement between poly-GC and poly-AT in the initial time period could be the reason for the backbone breakage; for the nitrogenous base pairs, A-T is 30% more sensitive or vulnerable to ion irradiation than G-C, demonstrating a preferential, instead of random, effect of irradiation-induced mutation.

  13. Activity of Levofloxacin Alone and in Combination with a DnaK Inhibitor against Gram-Negative Rods, Including Levofloxacin-Resistant Strains▿

    Science.gov (United States)

    Credito, Kim; Lin, Gengrong; Koeth, Laura; Sturgess, Michael A.; Appelbaum, Peter C.

    2009-01-01

    Synergy time-kill testing of levofloxacin alone and in combination with CHP-105, a representative DnaK inhibitor, against 50 gram-negative rods demonstrated that 34 of the 50 strains tested showed significant synergy between levofloxacin and CHP-105 after 12 h and 24 h. Fourteen of these 34 organisms were quinolone resistant (levofloxacin MICs of ≥4 μg/ml). PMID:19015359

  14. The synergistic effect of combined immunization with a DNA vaccine and chimeric yellow fever/dengue virus leads to strong protection against dengue.

    Directory of Open Access Journals (Sweden)

    Adriana S Azevedo

    Full Text Available The dengue envelope glycoprotein (E is the major component of virion surface and its ectodomain is composed of domains I, II and III. This protein is the main target for the development of a dengue vaccine with induction of neutralizing antibodies. In the present work, we tested two different vaccination strategies, with combined immunizations in a prime/booster regimen or simultaneous inoculation with a DNA vaccine (pE1D2 and a chimeric yellow fever/dengue 2 virus (YF17D-D2. The pE1D2 DNA vaccine encodes the ectodomain of the envelope DENV2 protein fused to t-PA signal peptide, while the YF17D-D2 was constructed by replacing the prM and E genes from the 17D yellow fever vaccine virus by those from DENV2. Balb/c mice were inoculated with these two vaccines by different prime/booster or simultaneous immunization protocols and most of them induced a synergistic effect on the elicited immune response, mainly in neutralizing antibody production. Furthermore, combined immunization remarkably increased protection against a lethal dose of DENV2, when compared to each vaccine administered alone. Results also revealed that immunization with the DNA vaccine, regardless of the combination with the chimeric virus, induced a robust cell immune response, with production of IFN-γ by CD8+ T lymphocytes.

  15. Intrinsic molecular subtypes of glioma are prognostic and predict benefit from adjuvant procarbazine, lomustine, and vincristine chemotherapy in combination with other prognostic factors in anaplastic oligodendroglial brain tumors: a report from EORTC study 26951

    NARCIS (Netherlands)

    Erdem-Eraslan, L.; Gravendeel, L.A.; Rooi, J. de; Eilers, P.H.; Idbaih, A.; Spliet, W.G.; Dunnen, W. den; Teepen, J.L.; Wesseling, P.; Sillevis Smitt, P.A.; Kros, J.M.; Gorlia, T.; Bent, M.J. van den; French, P.J.

    2013-01-01

    PURPOSE: Intrinsic glioma subtypes (IGSs) are molecularly similar tumors that can be identified based on unsupervised gene expression analysis. Here, we have evaluated the clinical relevance of these subtypes within European Organisation for Research and Treatment of Cancer (EORTC) 26951, a

  16. Cell-killing efficiency and number of platinum atoms binding to DNA, RNA and protein molecules of HeLa cells treated with combinations of hyperthermia and carboplatin

    International Nuclear Information System (INIS)

    Akaboshi, M.; Kawai, K.; Tanaka, Y.; Takada, J.; Sumino, T.

    1999-01-01

    The effect of hyperthermia on the cell killing efficiency of Pt atoms binding to DNA, RNA and protein molecules of HeLa cells treated with cis-diamine(1,1-cyclobutanedicarboxylato)platinum(II) (CBDCA) was examined. HeLa S-3 cells were treated with 195m Pt-radiolabeled CBDCA for 60 minutes at various temperatures, and the relationship between the lethal effect and the number of Pt atoms binding to DNA, RNA and proteins was examined. The mean lethal concentration (D 0 ) of carboplatin for a 60 min-treatment at 0, 25, 37, 40, 42 and 44 deg C was 671.2, 201.5, 67.3, 33.4, 20.2 and 15.6 μM, respectively. By using identically treated cells, the number of Pt-atoms combined with DNA, RNA and protein molecules were determined in the subcellular fractions. Thus, the D 0 's given as the drug concentrations were replaced with the number of Pt-atoms combined in each fraction. Then, the cell-killing efficiency of the Pt atom was expressed as the reciprocal of the number of Pt-atoms combined and was calculated for each molecule. The efficiency for DNA molecules was 0.699, 1.42, 2.65, 4.84, 7.74 and 8.28x10 4 nucleotides, respectively, for the conditions described above. From 0 to 44 deg C, the cell-killing efficiency of Pt atoms increased by a factor of 11.9. (author)

  17. Inhibition of the synthesis of polyamines and DNA in activated lymphocytes by a combination of alpha-methylornithine and methylglyoxal bis(guanylhydrazone).

    Science.gov (United States)

    Morris, D R; Jorstad, C M; Seyfried, C E

    1977-09-01

    The cancer chemotherapeutic drug, methylglyoxal bis(guanylhydrazone), inhibits the synthesis of spermidine and spermine, but allows continued putrescine production in small lymphocytes stimulated by concanavalin A. DNA replication in these cells is inhibited 50% while the synthesis of protein and RNA continues normally. When excess putrescine accumulation in the presence of methylglyoxal bis(guanylhydrazone) was inhibited with alpha-methylornithine, a competitive inhibitor of ornithine decarboxylase, the inhibition of DNA replication was accentuated, with still no effect on protein or RNA synthesis. No inhibition of DNA synthesis by the combination of alpha-methylornithine and methylglyoxal bis(guanylhydrazone) was observed when the inhibitors were added after accumulation of cellular polyamines. In addition, inhibition was reversed by exogenous putrescine, spermidine, or spermine. We conclude that putrescine can fulfill in part the role normally played by spermidine and spermine in DNA replication, and that blocking putrescine synthesis in the presence of methylglyoxal bis(guanylhydrazone) amplifies the polyamine requirement. The implications of this with regard to polyamine synthesis as a site of chemotherapy are discussed.

  18. ITS2 barcoding DNA region combined with high resolution melting (HRM) analysis of Hyoscyami Semen, the mature seed of Hyoscyamus niger.

    Science.gov (United States)

    Xiong, Chao; Hu, Zhi-Gang; Tu, Yuan; Liu, He-Gang; Wang, Ping; Zhao, Ming-Ming; SHIi, Yu-Hua; Wu, Lan; Sun, Wei; Chen, Shi-Lin

    2016-12-01

    Hyoscyami Semen, the mature dried seed of Hyoscyamus niger L., has long been used as a traditional Chinese medicine to treat human diseases. Hyoscyami Semen is found in local markets in China. In markets, sellers and buyers commonly inadvertently mix the seeds of H. niger with the seeds of related species such as Hygrophila salicifolia (Vahl) Nees, Astragalus complanatus R. Br., Cuscuta australis R. Br., Cuscuta chinensis Lam., and Impatiens balsamina L. because of their similar morphologies or similar names. Thus, developing a reliable method for discriminating H. niger seeds from its adulterants is necessary to reduce confusion and ensure the safe use of Hyoscyami Semen. The present study was designed to evaluate the efficiency of high-resolution melting analysis combined with DNA barcoding (Bar-HRM) with internal transcribed spacer 2 to discriminate H. niger. Our results show that Bar-HRM successfully identified the adulterants and detected the proportion of H. niger DNA extract within an admixture. In particular, HRM detected H. niger DNA extract in A. complanatus DNA extract at concentrations as low as 1%. In conclusion, the Bar-HRM method developed in the present study for authenticating H. niger is rapid and cost-effective. It can be used in the future to guarantee the purity of Hyoscyami Semen for the clinical use. Copyright © 2016 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

  19. Membrane Destruction and DNA Binding of Staphylococcus aureus Cells Induced by Carvacrol and Its Combined Effect with a Pulsed Electric Field.

    Science.gov (United States)

    Wang, Lang-Hong; Wang, Man-Sheng; Zeng, Xin-An; Zhang, Zhi-Hong; Gong, De-Ming; Huang, Yan-Bo

    2016-08-17

    Carvacrol (5-isopropyl-2-methylphenol, CAR) is an antibacterial ingredient that occurs naturally in the leaves of the plant Origanum vulgare. The antimicrobial mechanism of CAR against Staphylococcus aureus ATCC 43300 was investigated in the study. Analysis of the membrane fatty acids by gas chromatography-mass spectrometry (GC-MS) showed that exposure to CAR at low concentrations induced a marked increase in the level of unbranched fatty acids (from 34.90 ± 1.77% to 62.37 ± 4.26%). Moreover, CAR at higher levels severely damaged the integrity and morphologies of the S. aureus cell membrane. The DNA-binding properties of CAR were also investigated using fluorescence, circular dichroism, molecular modeling, and atomic-force microscopy. The results showed that CAR bound to DNA via the minor-groove mode, mildly perturbed the DNA secondary structure, and induced DNA molecules to be aggregated. Furthermore, a combination of CAR with a pulsed-electric field was found to exhibit strong synergistic effects on S. aureus.

  20. Comparative evaluation of the QIAsymphony RGQ system with the easyMAG/R-gene combination for the quantitation of cytomegalovirus DNA load in whole blood

    Directory of Open Access Journals (Sweden)

    Pillet Sylvie

    2012-10-01

    Full Text Available Abstract Background The detection of cytomegalovirus (CMV DNA in blood is a key feature of the virological surveillance of immunocompromised patients. Methods The QIAsymphony RGQ system (QIAGEN S.A.S., France combines the extraction/distribution steps on QIAsymphony SP/AS instruments with amplification on a Rotor-Gene Q RT-PCR machine. This system was compared to a strategy combining an extraction step on the NUCLISENS easyMAG platform (bioMérieux with the CMV R-gene kit (Argene on 100 whole blood specimens collected from immunocompromised patients of the University Hospital of Saint-Etienne, France. Results The overall agreement between the two strategies was 86% (kappa coefficient of 0.67; the 14 discrepant results corresponded to low DNA loads. The 62 samples found positive with both tests were correlated (Pearson r coefficient of 0.70, P 10 copies/ml with the easyMAG/Argene strategy (P 10 copies/ml. The inter-run and intra-run variability was consistently lower with the QIAGEN platform. Conclusions These results validate the performance of the QIAsymphony RGQ system for the routine quantitation of CMV DNA. This fully-automated platform reduces the hands-on time and improves standardization, traceability and quality control assessment.

  1. Effects of GST Polymorphism on Ameliorative Effect of Curcumin and Carvacrol against DNA Damage Induced by Combined Treatment of Malathion and Parathion

    Directory of Open Access Journals (Sweden)

    Neeraj Kumar

    2016-04-01

    Full Text Available Background: Organophosphorus pesticides has been widely used in agriculture fields to control various crop insects and their extensive use pose human life at threat because of their adverse effects on human health. In this study, we checked the effects of GST polymorphism on ameliorative effect of curcumin and carvacrol against DNA damages. Methods: Comet assay was used to assess the DNA damage and results were expressed as Tail moment. Heparinised fresh blood from healthy individuals was treated with combined concentration of malathion and parathion (i.e. 30 µg/ml of malathion and 2.5 µg/ml of parathion in presence of combination of curcumin and carvacrol (25 µg/ml curcumin + 2.5 µg/ml carvacrol and 50 µg/ml curcumin + 5.0 µg/ml carvacrol in order to observe the ameliorative role of curcumin and carvacrol. Multiplex PCR was performed for GSTM1 and GSTT1 genotyping. Results: Curcumin in combination with carvacrol (i.e. 25 µg/ml curcumin + 2.5 µg/ml carvacrol and 50 µg/ml curcumin + 5.0 µg/ml carvacrol significantly reduced the DNA damage caused by combined action of malathion and parathion which supports their antigenotoxic property. No significant relationship of GSTT1 and GSTM1 polymorphism with genotoxicity of both the pesticides and antigenotoxic potential of curcumin and carvacrol was observed. Conclusion: Malathion and parathion were genotoxic in human PBL. Curcumin and carvacrol had an antigenotoxic effect against the malathion and parathion while there was not any significant effect of GSTT1 and GSTM1 polymorphism on genotoxicity of these pesticides and antigenotoxicity of curcumin and carvacrol.

  2. On using intrinsic spectral analysis for low-resource languages

    CSIR Research Space (South Africa)

    Sahraeian, R

    2014-05-01

    Full Text Available for a phone recognition task on the Afrikaans language show that a combination of the intrinsic subspace and extrinsic subspaces provides us with improved performance compared to conventional features....

  3. Lesion-induced DNA weak structural changes detected by pulsed EPR spectroscopy combined with site-directed spin labelling.

    Science.gov (United States)

    Sicoli, Giuseppe; Mathis, Gérald; Aci-Sèche, Samia; Saint-Pierre, Christine; Boulard, Yves; Gasparutto, Didier; Gambarelli, Serge

    2009-06-01

    Double electron-electron resonance (DEER) was applied to determine nanometre spin-spin distances on DNA duplexes that contain selected structural alterations. The present approach to evaluate the structural features of DNA damages is thus related to the interspin distance changes, as well as to the flexibility of the overall structure deduced from the distance distribution. A set of site-directed nitroxide-labelled double-stranded DNA fragments containing defined lesions, namely an 8-oxoguanine, an abasic site or abasic site analogues, a nick, a gap and a bulge structure were prepared and then analysed by the DEER spectroscopic technique. New insights into the application of 4-pulse DEER sequence are also provided, in particular with respect to the spin probes' positions and the rigidity of selected systems. The lesion-induced conformational changes observed, which were supported by molecular dynamics studies, confirm the results obtained by other, more conventional, spectroscopic techniques. Thus, the experimental approaches described herein provide an efficient method for probing lesion-induced structural changes of nucleic acids.

  4. Combination of ICP-MS, capillary electrophoresis, and their hyphenation for probing Ru(III) metallodrug-DNA interactions.

    Science.gov (United States)

    Foteeva, Lidia S; Matczuk, Magdalena; Pawlak, Katarzyna; Aleksenko, Svetlana S; Nosenko, Sergey V; Karandashev, Vasily K; Jarosz, Maciej; Timerbaev, Andrei R

    2017-03-01

    Determination of the DNA-binding reactivity and affinity is an important part of a successful program for the selection of metallodrug candidates. For such assaying, a range of complementary analytical techniques was proposed and tested here using one of few anticancer metal-based drugs that are currently in clinical trials, indazolium trans-[tetrachloridobis(1H-indazole)ruthenate(III), and a DNA oligonucleotide. A high reactivity of the Ru drug was confirmed in affinity capillary electrophoresis (CE) mode, where adduct formation takes place in situ (i.e., in the capillary filled with an oligonucleotide-containing electrolyte). To further characterize the binding kinetics, a drug-oligonucleotide mixture was incubated for a different period of time, followed by ultrafiltration separation into two different in molecular weight fractions (>3 and ICP-MS), revealing that at least two DNA adducts exist at equilibrium conditions. Using standalone ICP-MS, dominant equilibrium amount of the bound ruthenium was found to occur in a fraction of 5-10 kDa, which includes the oligonucleotide (ca. 6 kDa). Importantly, in all three assays, the drug was used for the first time in in-vitro studies, not in the intact form but as its active species released from the transferrin adduct at simulated cancer cytosolic conditions. This circumstance makes the established analytical platform promising to provide a detailed view on metallodrug targeting, including other possible biomolecules and ex vivo samples.

  5. Targeting DNA Replication Stress for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Jun Zhang

    2016-08-01

    Full Text Available The human cellular genome is under constant stress from extrinsic and intrinsic factors, which can lead to DNA damage and defective replication. In normal cells, DNA damage response (DDR mediated by various checkpoints will either activate the DNA repair system or induce cellular apoptosis/senescence, therefore maintaining overall genomic integrity. Cancer cells, however, due to constitutive growth signaling and defective DDR, may exhibit “replication stress” —a phenomenon unique to cancer cells that is described as the perturbation of error-free DNA replication and slow-down of DNA synthesis. Although replication stress has been proven to induce genomic instability and tumorigenesis, recent studies have counterintuitively shown that enhancing replicative stress through further loosening of the remaining checkpoints in cancer cells to induce their catastrophic failure of proliferation may provide an alternative therapeutic approach. In this review, we discuss the rationale to enhance replicative stress in cancer cells, past approaches using traditional radiation and chemotherapy, and emerging approaches targeting the signaling cascades induced by DNA damage. We also summarize current clinical trials exploring these strategies and propose future research directions including the use of combination therapies, and the identification of potential new targets and biomarkers to track and predict treatment responses to targeting DNA replication stress.

  6. Intrinsic Chevrolets at the SSC

    International Nuclear Information System (INIS)

    Brodsky, S.J.; Collins, J.C.; Ellis, S.D.; Gunion, J.F.; Mueller, A.H.

    1984-01-01

    The possibility of the production at high energy of heavy quarks, supersymmetric particles and other large mass colored systems via the intrinsic twist-six components in the proton wave function is discussed. While the existing data do not rule out the possible relevance of intrinsic charm production at present energies, the extrapolation of such intrinsic contributions to very high masses and energies suggests that they will not play an important role at the SSC

  7. Enhanced antitumor effects by combining an IL-12/anti-DNA fusion protein with avelumab, an anti-PD-L1 antibody.

    Science.gov (United States)

    Fallon, Jonathan K; Vandeveer, Amanda J; Schlom, Jeffrey; Greiner, John W

    2017-03-28

    The combined therapeutic potential of an immunocytokine designed to deliver IL-12 to the necrotic regions of solid tumors with an anti-PD-L1 antibody that disrupts the immunosuppressive PD-1/PD-L1 axis yielded a combinatorial benefit in multiple murine tumor models. The murine version of the immunocytokine, NHS-muIL12, consists of an antibody (NHS76) recognizing DNA/DNA-histone complexes, fused with two molecules of murine IL-12 (NHS-muIL12). By its recognition of exposed DNA, NHS-muIL12 targets IL-12 to the necrotic portions of tumors; it has a longer plasma half-life and better antitumor efficacy against murine tumors than recombinant murine IL-12. It is shown here that NHS-muIL12, in an IFN-γ‒dependent mechanism, upregulates mPD-L1 expression on mouse tumors, which could be construed as an immunosuppressive action. Yet concurrent therapy with NHS-muIL12 and an anti-PD-L1 antibody resulted in additive/synergistic antitumor effects in PD-L1‒expressing subcutaneously transplanted tumors (MC38, MB49) and in an intravesical bladder tumor model (MB49). Antitumor efficacy correlated with (a) with a higher frequency of tumor antigen-specific splenic CD8+ T cells and (b) enhanced T cell activation over a wide range of NHS-muIL12 concentrations. These findings suggest that combining NHS-muIL12 and an anti-PD-L1 antibody enhances T cell activation and T cell effector functions within the tumor microenvironment, significantly improving overall tumor regression. These results should provide the rationale to examine the combination of these agents in clinical studies.

  8. Study on the effect of artesunate combined with irradiation on DNA damage of HeLa and Siha cells of human cervical cancer

    International Nuclear Information System (INIS)

    Zhou Yuanyuan; Feng Yang; Zhu Wei; Ni Qianying; Geng Chong; Chen Guanglie; Luo Judong; Fan Sanjun; Cao Jianping; Zhang Xuguang

    2011-01-01

    In order to investigate the effect of artesunate combined with irradiation on DNA damage of HeLa and Siha cells of human cervical cancer, HeLa and Siha cells were cultured in vitro and exposed to different concentration of artesunate for 24 h and MTT assay was used to observe the inhibitory effect of different concentration of artesunate on the proliferation of HeLa and Siha cells. The cells were divided into 2 groups as the irradiated group and the union treatment group. Here it was set up four absorbed doses of 60 Co γ-irradiation in each group with 0, 2, 4 and 6 Gy, and the DNA damage were detected by single cell gel electrophoresis assay. MTT analysis showed that the inhibition of artesunate on HeLa and Siha cells of cervical cancer was in concentration-dependent manners. Single cell gel electrophoresis showed that the DNA damage of HeLa cells treated with artesunate was more serious than that treated only with irradiation (P<0.05), but had no such effect on Siha cells. Artesunate can increase the radio-sensitivity of HeLa cells cervical cancer with p53 mutant, but has no such effect on wide type p53 cells. (authors)

  9. Use of vibrational spectroscopy to study protein and DNA structure, hydration, and binding of biomolecules: A combined theoretical and experimental approach

    DEFF Research Database (Denmark)

    Jalkanen, Karl J.; Jürgensen, Vibeke Würtz; Claussen, Anetta

    2006-01-01

    and experimental approach. The systems we have studied systematically are the amino acids (L-alanine, L-tryptophan, and L-histidine), peptides (N-acetyl L-alanine N'-methyl amide, N-acetyl L-tryptophan N'-methyl amide, N-acetyl L-histidine N'-methyl amide, L-alanyl L-alanine, tri-L-serine, N-acetyl L-alanine L......+disp, RHF, MP2, and DFT methodologies for the modeling studies with the goal of interpreting the experimentally measured vibrational spectra for these molecules to the greatest extent possible and to use this combined approach to understand the structure, function, and electronic properties......We report on our work with vibrational absorption, vibrational circular dichroism, Raman scattering, Raman optical activity, and surface-enhanced Raman spectroscopy to study protein and DNA structure, hydration, and the binding of ligands, drugs, pesticides, or herbicides via a combined theoretical...

  10. DNA replication and cancer

    DEFF Research Database (Denmark)

    Boyer, Anne-Sophie; Walter, David; Sørensen, Claus Storgaard

    2016-01-01

    A dividing cell has to duplicate its DNA precisely once during the cell cycle to preserve genome integrity avoiding the accumulation of genetic aberrations that promote diseases such as cancer. A large number of endogenous impacts can challenge DNA replication and cells harbor a battery of pathways...... causing DNA replication stress and genome instability. Further, we describe cellular and systemic responses to these insults with a focus on DNA replication restart pathways. Finally, we discuss the therapeutic potential of exploiting intrinsic replicative stress in cancer cells for targeted therapy....

  11. Inhibition of DNA and protein synthesis in UV-irradiated mouse skin by 2-difluoromethylornithine, methylglyoxal bis(guanylhydrazone), and their combination

    Energy Technology Data Exchange (ETDEWEB)

    Kaepyaho, K.; Lauharanta, J.; Jaenne, J.

    1983-08-01

    Exposure of mouse skin to UVB irradiation greatly enhanced the biosynthesis and accumulation of putrescine and spermidine before or concomitantly with stimulation of epidermal macromolecular (DNA and protein) synthesis. Topical treatment of UV-exposed skin with 2 inhibitors of polyamine biosynthesis, 2-difluoromethylornithine (DFMO) and methylglyoxal bis(guanylhydrazone) (MGBG) prevented the enhanced epidermal accumulation of polyamines, especially spermidine, and also inhibited the incorporation of radioactive precursors into DNA and protein. When applied in combination, these 2 antimetabolites of polyamines produced an inhibition of macromolecular synthesis that was at least additive: (/sup 3/H)thymidine incorporation decreased by 80% and (/sup 14/C)leucine incorporation by 44% as compared with the UVB-irradiated control mice. A slight decrease in the ratio of (/sup 3/H)histidine/(/sup 14/C)leucine incorporation indicated that protein synthesis of the differentiating cell layers was also affected by the inhibitors. The effects of the combined DFMO and MGBG treatment were partially reversed by concomitant topical application of spermidine.

  12. Inhibition of DNA and protein synthesis in UV-irradiated mouse skin by 2-difluoromethylornithine, methylglyoxal bis(guanylhydrazone), and their combination

    International Nuclear Information System (INIS)

    Kaepyaho, K.; Lauharanta, J.; Jaenne, J.

    1983-01-01

    Exposure of mouse skin to UVB irradiation greatly enhanced the biosynthesis and accumulation of putrescine and spermidine before or concomitantly with stimulation of epidermal macromolecular (DNA and protein) synthesis. Topical treatment of UV-exposed skin with 2 inhibitors of polyamine biosynthesis, 2-difluoromethylornithine (DFMO) and methylglyoxal bis(guanylhydrazone) (MGBG) prevented the enhanced epidermal accumulation of polyamines, especially spermidine, and also inhibited the incorporation of radioactive precursors into DNA and protein. When applied in combination, these 2 antimetabolites of polyamines produced an inhibition of macromolecular synthesis that was at least additive: [ 3 H]thymidine incorporation decreased by 80% and [ 14 C]leucine incorporation by 44% as compared with the UVB-irradiated control mice. A slight decrease in the ratio of [ 3 H]histidine/[ 14 C]leucine incorporation indicated that protein synthesis of the differentiating cell layers was also affected by the inhibitors. The effects of the combined DFMO and MGBG treatment were partially reversed by concomitant topical application of spermidine

  13. DNA biosensor combining single-wavelength colorimetry and a digital lock-in amplifier within a smartphone.

    Science.gov (United States)

    Wu, Tzu-Heng; Chang, Chia-Chen; Vaillant, Julien; Bruyant, Aurélien; Lin, Chii-Wann

    2016-11-15

    Smartphone camera based gold nanoparticle colorimetry (SCB-AuNP colorimetry) has shown good potential for point-of-care applications. However, due to the use of a camera as a photo-detector, there are major limitations to this technique such as a low bit resolution (∼8 bits mainstream) and a low data acquisition rate. These issues have limited the ultimate sensitivity of smartphone based colorimetry as well as the possibility to integrate efficiently a more sensitive approach such as detection based on a lock-in amplifier (LIA). In this paper, we improve the metrological performance of the smartphone to overcome existing issues by adding the LIA capability to AuNP sensing. In this work, instead of using the camera as a photo-detector, the audio jack is used as a photo-detector reader and function generator for driving a laser diode in order to achieve a smartphone based digital lock-in amplifier AuNP colorimetric (SBLIA-AuNP colorimetry) system. A full investigation on the SBLIA design, parameters and performance is comprehensively provided. It is found that the SBLIA can reduce most of the noise and provides a detection noise-to-signal ratio down to -63 dB, which is much better than the -49 dB of the state-of-the-art SCB based method. A DNA detection experiment is demonstrated to reveal the efficacy of the proposed metrological method. The results are compared to UV-visible spectrometry, which is the gold standard for colorimetric measurement. Based on our results, the SBLIA-AuNP colorimetric system has a detection limit of 0.77 nM on short strand DNA detection, which is 5.7 times better than the 4.36 nM limit of a commercial UV-visible spectrometer. Judging from the results, we believe that the sensitive SBLIA would be further extended to other optical diagnostic tools in the near future.

  14. A universal protocol for the combined isolation of metabolites, DNA, long RNAs, small RNAs, and proteins from plants and microorganisms

    Czech Academy of Sciences Publication Activity Database

    Valledor, Luis; Escandón, M.; Meijón, M.; Nukarinen, E.; Jesús Cañal, M.; Weckwerth, W.

    2014-01-01

    Roč. 79, č. 1 (2014), s. 173-180 ISSN 0960-7412 R&D Projects: GA MŠk(CZ) EE2.3.20.0256 Institutional support: RVO:67179843 Keywords : systems biology * combined isolation * RNA * small RNA * proteins * metabolites * Chlamydomonas reinhardtii * Arabidopsis thaliana * Populus sp. * Pinus sp. * technical advance Subject RIV: EI - Biotechnology ; Bionics Impact factor: 5.972, year: 2014

  15. Self-perception of intrinsic and extrinsic motivation.

    Science.gov (United States)

    Calder, B J; Staw, B M

    1975-04-01

    Self-perception theory predicts that intrinsic and extrinsic motivation do not combine additively but rather interact. To test this predicted interaction, intrinsic and extrinsic motivation were both manipulated as independent variables. The results revealed a significant interaction for task satisfaction and a trend for the interaction on a behavioral measure. These results are discussed in terms of a general approach to the self-perception of motivation.

  16. On-Chip Evaluation of DNA Methylation with Electrochemical Combined Bisulfite Restriction Analysis Utilizing a Carbon Film Containing a Nanocrystalline Structure.

    Science.gov (United States)

    Kurita, Ryoji; Yanagisawa, Hiroyuki; Kamata, Tomoyuki; Kato, Dai; Niwa, Osamu

    2017-06-06

    This paper reports an on-chip electrochemical assessment of the DNA methylation status in genomic DNA on a conductive nanocarbon film electrode realized with combined bisulfite restriction analysis (COBRA). The film electrode consists of sp 2 and sp 3 hybrid bonds and is fabricated with an unbalanced magnetron (UBM) sputtering method. First, we studied the effect of the sp 2 /sp 3 ratio of the UBM nanocarbon film electrode with p-aminophenol, which is a major electro-active product of the labeling enzyme from p-aminophenol phosphate. The signal current for p-aminophenol increases as the sp 2 content in the UBM nanocarbon film electrode increases because of the π-π interaction between aromatic p-aminophenol and the graphene-like sp 2 structure. Furthermore, the capacitative current at the UBM nanocarbon film electrode was successfully reduced by about 1 order of magnitude thanks to the angstrom-level surface flatness. Therefore, a high signal-to-noise ratio was achieved compared with that of conventional electrodes. Then, after performing an ELISA-like hybridization assay with a restriction enzyme, we undertook an electrochemical evaluation of the cytosine methylation status in DNA by measuring the oxidation current derived from p-aminophenol. When the target cytosine in the analyte sequence is methylated (unmethylated), the restriction enzyme of HpyCH4IV is able (unable) to cleave the sequence, that is, the detection probe cannot (can) hybridize. We succeeded in estimating the methylation ratio at a site-specific CpG site from the peak current of a cyclic voltammogram obtained from a PCR product solution ranging from 0.01 to 1 nM.

  17. Combining real-time PCR and next-generation DNA sequencing to provide quantitative comparisons of fungal aerosol populations

    Science.gov (United States)

    Dannemiller, Karen C.; Lang-Yona, Naama; Yamamoto, Naomichi; Rudich, Yinon; Peccia, Jordan

    2014-02-01

    We examined fungal communities associated with the PM10 mass of Rehovot, Israel outdoor air samples collected in the spring and fall seasons. Fungal communities were described by 454 pyrosequencing of the internal transcribed spacer (ITS) region of the fungal ribosomal RNA encoding gene. To allow for a more quantitative comparison of fungal exposure in humans, the relative abundance values of specific taxa were transformed to absolute concentrations through multiplying these values by the sample's total fungal spore concentration (derived from universal fungal qPCR). Next, the sequencing-based absolute concentrations for Alternaria alternata, Cladosporium cladosporioides, Epicoccum nigrum, and Penicillium/Aspergillus spp. were compared to taxon-specific qPCR concentrations for A. alternata, C. cladosporioides, E. nigrum, and Penicillium/Aspergillus spp. derived from the same spring and fall aerosol samples. Results of these comparisons showed that the absolute concentration values generated from pyrosequencing were strongly associated with the concentration values derived from taxon-specific qPCR (for all four species, p 0.70). The correlation coefficients were greater for species present in higher concentrations. Our microbial aerosol population analyses demonstrated that fungal diversity (number of fungal operational taxonomic units) was higher in the spring compared to the fall (p = 0.02), and principal coordinate analysis showed distinct seasonal differences in taxa distribution (ANOSIM p = 0.004). Among genera containing allergenic and/or pathogenic species, the absolute concentrations of Alternaria, Aspergillus, Fusarium, and Cladosporium were greater in the fall, while Cryptococcus, Penicillium, and Ulocladium concentrations were greater in the spring. The transformation of pyrosequencing fungal population relative abundance data to absolute concentrations can improve next-generation DNA sequencing-based quantitative aerosol exposure assessment.

  18. Intrinsically Passive Handling and Grasping

    NARCIS (Netherlands)

    Stramigioli, Stefano; Scherpen, Jacquelien M.A.; Khodabandehloo, Koorosh

    2000-01-01

    The paper presents a control philosophy called Intrinsically Passive Control, which has the feature to properly behave during interaction with any passive objects. The controlled robot will never become unstable due to the physical structure of the controller.

  19. Evaluation of chlorpyrifos effects, alone and combined with lipopolysaccharide stress, on DNA integrity and immune responses of the three-spined stickleback, Gasterosteus aculeatus.

    Science.gov (United States)

    Marchand, Adrien; Porcher, Jean-Marc; Turies, Cyril; Chadili, Edith; Palluel, Olivier; Baudoin, Patrick; Betoulle, Stéphane; Bado-Nilles, Anne

    2017-11-01

    Organism immune defences might be weakened by pollutants, largely detected in aquatic ecosystems, leading to the facilitation for opportunistic pathogens to infect organisms. In this context, destabilization of fish non-specific immune parameters and erythrocyte DNA integrity was tested, on a model fish species, the three-spined stickleback (Gasterosteus aculeatus), after exposure to chlorpyrifos (CPF). Alone, pesticide exposure induced a genotoxic potential (chlorpyrifos at 1.75 and 0.88µg/L) in addition to a decrease in phagocytosis capacity and a stimulation of respiratory burst. Then, to mimic pathogenic infection, fish exposure to chlorpyrifos was combined with lipopolysaccharides (LPS) stress. In this second experiment, an increase of DNA damage was observed in fish exposed to a lower concentration of chlorpyrifos and LPS. Moreover, at the higher concentration of chlorpyrifos, an early destabilization of innate immunity was observed as suggested by the absence of an increase of lysosomal presence in fish injected with LPS. This study highlighted the usefulness of stress on stress responses to better understand the impact of contaminants on the organism's health. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Droplet digital PCR combined with minisequencing, a new approach to analyze fetal DNA from maternal blood: application to the non-invasive prenatal diagnosis of achondroplasia.

    Science.gov (United States)

    Orhant, Lucie; Anselem, Olivia; Fradin, Mélanie; Becker, Pierre Hadrien; Beugnet, Caroline; Deburgrave, Nathalie; Tafuri, Gilles; Letourneur, Franck; Goffinet, François; Allach El Khattabi, Laïla; Leturcq, France; Bienvenu, Thierry; Tsatsaris, Vassilis; Nectoux, Juliette

    2016-05-01

    Achondroplasia is generally detected by abnormal prenatal ultrasound findings in the third trimester of pregnancy and then confirmed by molecular genetic testing of fetal genomic DNA obtained by aspiration of amniotic fluid. This invasive procedure presents a small but significant risk for both the fetus and mother. Therefore, non-invasive procedures using cell-free fetal DNA in maternal plasma have been developed for the detection of the fetal achondroplasia mutations. To determine whether the fetus carries the de novo mis-sense genetic mutation at nucleotide 1138 in FGFR3 gene involved in >99% of achondroplasia cases, we developed two independent methods: digital-droplet PCR combined with minisequencing, which are very sensitive methods allowing detection of rare alleles. We collected 26 plasmatic samples from women carrying fetus at risk of achondroplasia and diagnosed to date a total of five affected fetuses in maternal blood. The sensitivity and specificity of our test are respectively 100% [95% confidence interval, 56.6-100%] and 100% [95% confidence interval, 84.5-100%]. This novel, original strategy for non-invasive prenatal diagnosis of achondroplasia is suitable for implementation in routine clinical testing and allows considering extending the applications of these technologies in non-invasive prenatal diagnosis of many other monogenic diseases. © 2016 John Wiley & Sons, Ltd. © 2016 John Wiley & Sons, Ltd.

  1. Direct identification of antibiotic resistance genes on single plasmid molecules using CRISPR/Cas9 in combination with optical DNA mapping

    Science.gov (United States)

    Müller, Vilhelm; Rajer, Fredrika; Frykholm, Karolin; Nyberg, Lena K.; Quaderi, Saair; Fritzsche, Joachim; Kristiansson, Erik; Ambjörnsson, Tobias; Sandegren, Linus; Westerlund, Fredrik

    2016-12-01

    Bacterial plasmids are extensively involved in the rapid global spread of antibiotic resistance. We here present an assay, based on optical DNA mapping of single plasmids in nanofluidic channels, which provides detailed information about the plasmids present in a bacterial isolate. In a single experiment, we obtain the number of different plasmids in the sample, the size of each plasmid, an optical barcode that can be used to identify and trace the plasmid of interest and information about which plasmid that carries a specific resistance gene. Gene identification is done using CRISPR/Cas9 loaded with a guide-RNA (gRNA) complementary to the gene of interest that linearizes the circular plasmids at a specific location that is identified using the optical DNA maps. We demonstrate the principle on clinically relevant extended spectrum beta-lactamase (ESBL) producing isolates. We discuss how the gRNA sequence can be varied to obtain the desired information. The gRNA can either be very specific to identify a homogeneous group of genes or general to detect several groups of genes at the same time. Finally, we demonstrate an example where we use a combination of two gRNA sequences to identify carbapenemase-encoding genes in two previously not characterized clinical bacterial samples.

  2. Rapid classification of turmeric based on DNA fingerprint by near-infrared spectroscopy combined with moving window partial least squares-discrimination analysis

    International Nuclear Information System (INIS)

    Kasemsumran, Sumaporn; Suttiwijitpukdee, Nattaporn; Keeratinijakal, Vichein

    2017-01-01

    In this research, near-infrared (NIR) spectroscopy in combination with moving window partial least squares-discrimination analysis (MWPLS-DA) was utilized to discriminate the variety of turmeric based on DNA markers, which correlated to the quantity of curcuminoid. Curcuminoid was used as a marker compound in variety identification due to the most pharmacological properties of turmeric possessed from it. MWPLS-DA optimized informative NIR spectral regions for the fitting and prediction to {-1/1}-coded turmeric varieties, indicating variables in the development of latent variables in discrimination analysis. Consequently, MWPLS-DA benefited in the selection of combined informative NIR spectral regions of 1100 – 1260, 1300 – 1500 and 1880 – 2500 nm for classification modeling of turmeric variety with 148 calibration samples, and yielded the results better than that obtained from a partial least squares-discrimination analysis (PLS-DA) model built by using the whole NIR spectral region. An effective and rapid strategy of using NIR in combination with MWPLS-DA provided the best variety identification results of 100% in both specificity and total accuracy for 48 test samples. (author)

  3. Triploblastic relationships with emphasis on the acoelomates and the position of Gnathostomulida, Cycliophora, Plathelminthes, and Chaetognatha: a combined approach of 18S rDNA sequences and morphology.

    Science.gov (United States)

    Giribet, G; Distel, D L; Polz, M; Sterrer, W; Wheeler, W C

    2000-09-01

    Triploblastic relationships were examined in the light of molecular and morphological evidence. Representatives for all triploblastic "phyla" (except Loricifera) were represented by both sources of phylogenetic data. The 18S ribosomal (rDNA) sequence data for 145 terminal taxa and 276 morphological characters coded for 36 supraspecific taxa were combined in a total evidence regime to determine the most consistent picture of triploblastic relationships for these data. Only triploblastic taxa are used to avoid rooting with distant outgroups, which seems to happen because of the extreme distance that separates diploblastic from triploblastic taxa according to the 18S rDNA data. Multiple phylogenetic analyses performed with variable analysis parameters yield largely inconsistent results for certain groups such as Chaetognatha, Acoela, and Nemertodermatida. A normalized incongruence length metric is used to assay the relative merit of the multiple analyses. The combined analysis having the least character incongruence yields the following scheme of relationships of four main clades: (1) Deuterostomia [((Echinodermata + Enteropneusta) (Cephalochordata (Urochordata + Vertebrata)))]; (2) Ecdysozoa [(((Priapulida + Kinorhyncha) (Nematoda + Nematomorpha)) ((Onychophora + Tardigrada) Arthropoda))]; (3) Trochozoa [((Phoronida + Brachiopoda) (Entoprocta (Nemertea (Sipuncula (Mollusca (Pogonophora (Echiura + Annelida)))))))]; and (4) Platyzoa [((Gnathostomulida (Cycliophora + Syndermata)) (Gastrotricha + Plathelminthes))]. Chaetognatha, Nemertodermatida, and Bryozoa cannot be assigned to any one of these four groups. For the first time, a data analysis recognizes a clade of acoelomates, the Platyzoa (sensu Cavalier-Smith, Biol. Rev. 73:203-266, 1998). Other relationships that corroborate some morphological analyses are the existence of a clade that groups Gnathostomulida + Syndermata (= Gnathifera), which is expanded to include the enigmatic phylum Cycliophora, as sister group

  4. The DNA-encoded nucleosome organization of a eukaryotic genome.

    Science.gov (United States)

    Kaplan, Noam; Moore, Irene K; Fondufe-Mittendorf, Yvonne; Gossett, Andrea J; Tillo, Desiree; Field, Yair; LeProust, Emily M; Hughes, Timothy R; Lieb, Jason D; Widom, Jonathan; Segal, Eran

    2009-03-19

    Nucleosome organization is critical for gene regulation. In living cells this organization is determined by multiple factors, including the action of chromatin remodellers, competition with site-specific DNA-binding proteins, and the DNA sequence preferences of the nucleosomes themselves. However, it has been difficult to estimate the relative importance of each of these mechanisms in vivo, because in vivo nucleosome maps reflect the combined action of all influencing factors. Here we determine the importance of nucleosome DNA sequence preferences experimentally by measuring the genome-wide occupancy of nucleosomes assembled on purified yeast genomic DNA. The resulting map, in which nucleosome occupancy is governed only by the intrinsic sequence preferences of nucleosomes, is similar to in vivo nucleosome maps generated in three different growth conditions. In vitro, nucleosome depletion is evident at many transcription factor binding sites and around gene start and end sites, indicating that nucleosome depletion at these sites in vivo is partly encoded in the genome. We confirm these results with a micrococcal nuclease-independent experiment that measures the relative affinity of nucleosomes for approximately 40,000 double-stranded 150-base-pair oligonucleotides. Using our in vitro data, we devise a computational model of nucleosome sequence preferences that is significantly correlated with in vivo nucleosome occupancy in Caenorhabditis elegans. Our results indicate that the intrinsic DNA sequence preferences of nucleosomes have a central role in determining the organization of nucleosomes in vivo.

  5. HIV DNA Is Frequently Present within Pathologic Tissues Evaluated at Autopsy from Combined Antiretroviral Therapy-Treated Patients with Undetectable Viral Loads.

    Science.gov (United States)

    Lamers, Susanna L; Rose, Rebecca; Maidji, Ekaterina; Agsalda-Garcia, Melissa; Nolan, David J; Fogel, Gary B; Salemi, Marco; Garcia, Debra L; Bracci, Paige; Yong, William; Commins, Deborah; Said, Jonathan; Khanlou, Negar; Hinkin, Charles H; Sueiras, Miguel Valdes; Mathisen, Glenn; Donovan, Suzanne; Shiramizu, Bruce; Stoddart, Cheryl A; McGrath, Michael S; Singer, Elyse J

    2016-10-15

    HIV infection treatment strategies have historically defined effectiveness through measuring patient plasma HIV RNA. While combined antiretroviral therapy (cART) can reduce plasma viral load (pVL) to undetectable levels, the degree that HIV is eliminated from other anatomical sites remains unclear. We investigated the HIV DNA levels in 229 varied autopsy tissues from 20 HIV-positive (HIV(+)) cART-treated study participants with low or undetectable plasma VL and cerebrospinal fluid (CSF) VL prior to death who were enrolled in the National Neurological AIDS Bank (NNAB) longitudinal study and autopsy cohort. Extensive medical histories were obtained for each participant. Autopsy specimens, including at least six brain and nonbrain tissues per participant, were reviewed by study pathologists. HIV DNA, measured in tissues by quantitative and droplet digital PCR, was identified in 48/87 brain tissues and 82/142 nonbrain tissues at levels >200 HIV copies/million cell equivalents. No participant was found to be completely free of tissue HIV. Parallel sequencing studies from some tissues recovered intact HIV DNA and RNA. Abnormal histological findings were identified in all participants, especially in brain, spleen, lung, lymph node, liver, aorta, and kidney. All brain tissues demonstrated some degree of pathology. Ninety-five percent of participants had some degree of atherosclerosis, and 75% of participants died with cancer. This study assists in characterizing the anatomical locations of HIV, in particular, macrophage-rich tissues, such as the central nervous system (CNS) and testis. Additional studies are needed to determine if the HIV recovered from tissues promotes the pathogenesis of inflammatory diseases, such as HIV-associated neurocognitive disorders, cancer, and atherosclerosis. It is well-known that combined antiretroviral therapy (cART) can reduce plasma HIV to undetectable levels; however, cART cannot completely clear HIV infection. An ongoing question is

  6. Innate and intrinsic antiviral immunity in skin.

    Science.gov (United States)

    Kawamura, Tatsuyoshi; Ogawa, Youichi; Aoki, Rui; Shimada, Shinji

    2014-09-01

    As the body's most exposed interface with the environment, the skin is constantly challenged by potentially pathogenic microbes, including viruses. To sense the invading viruses, various types of cells resident in the skin express many different pattern-recognition receptors (PRRs) such as C-type lectin receptors (CLRs), Toll-like receptors (TLRs), nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs), retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) and cytosolic DNA sensors, that can detect the pathogen-associated molecular patterns (PAMPs) of the viruses. The detection of viral PAMPs initiates two major innate immune signaling cascades: the first involves the activation of the downstream transcription factors, such as interferon regulatory factors (IRFs), nuclear factor kappa B (NF-κB) and activator protein 1 (AP-1), which cooperate to induce the transcription of type I interferons and pro-inflammatory cytokines. The second signaling pathway involves the caspase-1-mediated processing of IL-1β and IL-18 through the formation of an inflammasome complex. Cutaneous innate immunity including the production of the innate cytokines constitutes the first line of host defence that limits the virus dissemination from the skin, and also plays an important role in the activation of adaptive immune response, which represents the second line of defence. More recently, the third immunity "intrinsic immunity" has emerged, that provides an immediate and direct antiviral defense mediated by host intrinsic restriction factors. This review focuses on the recent advances regarding the antiviral immune systems, highlighting the innate and intrinsic immunity against the viral infections in the skin, and describes how viral components are recognized by cutaneous immune systems. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  7. Intrinsic radiation resistance in human chondrosarcoma cells

    International Nuclear Information System (INIS)

    Moussavi-Harami, Farid; Mollano, Anthony; Martin, James A.; Ayoob, Andrew; Domann, Frederick E.; Gitelis, Steven; Buckwalter, Joseph A.

    2006-01-01

    Human chondrosarcomas rarely respond to radiation treatment, limiting the options for eradication of these tumors. The basis of radiation resistance in chondrosarcomas remains obscure. In normal cells radiation induces DNA damage that leads to growth arrest or death. However, cells that lack cell cycle control mechanisms needed for these responses show intrinsic radiation resistance. In previous work, we identified immortalized human chondrosarcoma cell lines that lacked p16 ink4a , one of the major tumor suppressor proteins that regulate the cell cycle. We hypothesized that the absence of p16 ink4a contributes to the intrinsic radiation resistance of chondrosarcomas and that restoring p16 ink4a expression would increase their radiation sensitivity. To test this we determined the effects of ectopic p16 ink4a expression on chondrosarcoma cell resistance to low-dose γ-irradiation (1-5 Gy). p16 ink4a expression significantly increased radiation sensitivity in clonogenic assays. Apoptosis did not increase significantly with radiation and was unaffected by p16 ink4a transduction of chondrosarcoma cells, indicating that mitotic catastrophe, rather than programmed cell death, was the predominant radiation effect. These results support the hypothesis that p16 ink4a plays a role in the radiation resistance of chondrosarcoma cell lines and suggests that restoring p16 expression will improve the radiation sensitivity of human chondrosarcomas

  8. Separating intrinsic from extrinsic fluctuations in dynamic biological systems.

    Science.gov (United States)

    Hilfinger, Andreas; Paulsson, Johan

    2011-07-19

    From molecules in cells to organisms in ecosystems, biological populations fluctuate due to the intrinsic randomness of individual events and the extrinsic influence of changing environments. The combined effect is often too complex for effective analysis, and many studies therefore make simplifying assumptions, for example ignoring either intrinsic or extrinsic effects to reduce the number of model assumptions. Here we mathematically demonstrate how two identical and independent reporters embedded in a shared fluctuating environment can be used to identify intrinsic and extrinsic noise terms, but also how these contributions are qualitatively and quantitatively different from what has been previously reported. Furthermore, we show for which classes of biological systems the noise contributions identified by dual-reporter methods correspond to the noise contributions predicted by correct stochastic models of either intrinsic or extrinsic mechanisms. We find that for broad classes of systems, the extrinsic noise from the dual-reporter method can be rigorously analyzed using models that ignore intrinsic stochasticity. In contrast, the intrinsic noise can be rigorously analyzed using models that ignore extrinsic stochasticity only under very special conditions that rarely hold in biology. Testing whether the conditions are met is rarely possible and the dual-reporter method may thus produce flawed conclusions about the properties of the system, particularly about the intrinsic noise. Our results contribute toward establishing a rigorous framework to analyze dynamically fluctuating biological systems.

  9. VELOCITY EVOLUTION AND THE INTRINSIC COLOR OF TYPE Ia SUPERNOVAE

    International Nuclear Information System (INIS)

    Foley, Ryan J.; Sanders, Nathan E.; Kirshner, Robert P.

    2011-01-01

    To understand how best to use observations of Type Ia supernovae (SNe Ia) to obtain precise and accurate distances, we investigate the relations between spectra of SNe Ia and their intrinsic colors. Using a sample of 1630 optical spectra of 255 SNe, based primarily on data from the CfA Supernova Program, we examine how the velocity evolution and line strengths of Si II λ6355 and Ca II H and K are related to the B – V color at peak brightness. We find that the maximum-light velocity of Si II λ6355 and Ca II H and K and the maximum-light pseudo-equivalent width of Si II λ6355 are correlated with intrinsic color, with intrinsic color having a linear relation with the Si II λ6355 measurements. Ca II H and K does not have a linear relation with intrinsic color, but lower-velocity SNe tend to be intrinsically bluer. Combining the spectroscopic measurements does not improve intrinsic color inference. The intrinsic color scatter is larger for higher-velocity SNe Ia—even after removing a linear trend with velocity—indicating that lower-velocity SNe Ia are more 'standard crayons'. Employing information derived from SN Ia spectra has the potential to improve the measurements of extragalactic distances and the cosmological properties inferred from them.

  10. cGAS Conducts Micronuclei DNA Surveillance.

    Science.gov (United States)

    de Oliveira Mann, Carina C; Kranzusch, Philip J

    2017-10-01

    DNA damage elicits a potent proinflammatory immune response. A collection of four papers now reveals that micronuclear DNA is a new cell intrinsic immunostimulatory molecule, and that accumulation of the immune sensor cyclic GMP-AMP synthase (cGAS) in micronuclei leads to a cell-cycle-dependent proinflammatory response following DNA damage. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. The DNA damage response during mitosis

    NARCIS (Netherlands)

    Heijink, Anne Margriet; Krajewska, Malgorzata; van Vugt, Marcel A. T. M.

    2013-01-01

    Cells are equipped with a cell-intrinsic signaling network called the DNA damage response (DDR). This signaling network recognizes DNA lesions and initiates various downstream pathways to coordinate a cell cycle arrest with the repair of the damaged DNA. Alternatively, the DDR can mediate clearance

  12. Combined virus-like particle and fusion protein-encoding DNA vaccination of cotton rats induces protection against respiratory syncytial virus without causing vaccine-enhanced disease

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Hye Suk; Lee, Young-Tae; Kim, Ki-Hye; Park, Soojin; Kwon, Young-Man; Lee, Youri; Ko, Eun-Ju; Jung, Yu-Jin [Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA (United States); Lee, Jong Seok [Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA (United States); National Institute of Biological Resources, Incheon (Korea, Republic of); Kim, Yu-Jin [Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA (United States); Lee, Yu-Na; Kim, Min-Chul [Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA (United States); Animal and Plant Quarantine Agency, Gyeonggi-do, Gimcheon, Gyeongsangbukdo (Korea, Republic of); Cho, Minkyoung [Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA (United States); Kang, Sang-Moo, E-mail: skang24@gsu.edu [Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA (United States)

    2016-07-15

    A safe and effective vaccine against respiratory syncytial virus (RSV) should confer protection without causing vaccine-enhanced disease. Here, using a cotton rat model, we investigated the protective efficacy and safety of an RSV combination vaccine composed of F-encoding plasmid DNA and virus-like particles containing RSV fusion (F) and attachment (G) glycoproteins (FFG-VLP). Cotton rats with FFG-VLP vaccination controlled lung viral replication below the detection limit, and effectively induced neutralizing activity and antibody-secreting cell responses. In comparison with formalin inactivated RSV (FI-RSV) causing severe RSV disease after challenge, FFG-VLP vaccination did not cause weight loss, airway hyper-responsiveness, IL-4 cytokines, histopathology, and infiltrates of proinflammatory cells such as eosinophils. FFG-VLP was even more effective in preventing RSV-induced pulmonary inflammation than live RSV infections. This study provides evidence that FFG-VLP can be developed into a safe and effective RSV vaccine candidate. - Highlights: • Combined RSV FFG VLP vaccine is effective in inducing F specific responses. • FFG VLP vaccine confers RSV neutralizing activity and viral control in cotton rats. • Cotton rats with RSV FFG VLP vaccination do not show vaccine-enhanced disease. • Cotton rats with FFG VLP vaccine induce F specific antibody secreting cell responses. • Cotton rats with FFG VLP do not induce lung cellular infiltrates and Th2 cytokine.

  13. Combined virus-like particle and fusion protein-encoding DNA vaccination of cotton rats induces protection against respiratory syncytial virus without causing vaccine-enhanced disease

    International Nuclear Information System (INIS)

    Hwang, Hye Suk; Lee, Young-Tae; Kim, Ki-Hye; Park, Soojin; Kwon, Young-Man; Lee, Youri; Ko, Eun-Ju; Jung, Yu-Jin; Lee, Jong Seok; Kim, Yu-Jin; Lee, Yu-Na; Kim, Min-Chul; Cho, Minkyoung; Kang, Sang-Moo

    2016-01-01

    A safe and effective vaccine against respiratory syncytial virus (RSV) should confer protection without causing vaccine-enhanced disease. Here, using a cotton rat model, we investigated the protective efficacy and safety of an RSV combination vaccine composed of F-encoding plasmid DNA and virus-like particles containing RSV fusion (F) and attachment (G) glycoproteins (FFG-VLP). Cotton rats with FFG-VLP vaccination controlled lung viral replication below the detection limit, and effectively induced neutralizing activity and antibody-secreting cell responses. In comparison with formalin inactivated RSV (FI-RSV) causing severe RSV disease after challenge, FFG-VLP vaccination did not cause weight loss, airway hyper-responsiveness, IL-4 cytokines, histopathology, and infiltrates of proinflammatory cells such as eosinophils. FFG-VLP was even more effective in preventing RSV-induced pulmonary inflammation than live RSV infections. This study provides evidence that FFG-VLP can be developed into a safe and effective RSV vaccine candidate. - Highlights: • Combined RSV FFG VLP vaccine is effective in inducing F specific responses. • FFG VLP vaccine confers RSV neutralizing activity and viral control in cotton rats. • Cotton rats with RSV FFG VLP vaccination do not show vaccine-enhanced disease. • Cotton rats with FFG VLP vaccine induce F specific antibody secreting cell responses. • Cotton rats with FFG VLP do not induce lung cellular infiltrates and Th2 cytokine.

  14. Absence of DNA damage after 60-Hz electromagnetic field exposure combined with ionizing radiation, hydrogen peroxide, or c-Myc overexpression.

    Science.gov (United States)

    Jin, Yeung Bae; Choi, Seo-Hyun; Lee, Jae Seon; Kim, Jae-Kyung; Lee, Ju-Woon; Hong, Seung-Cheol; Myung, Sung Ho; Lee, Yun-Sil

    2014-03-01

    The principal objective of this study was to assess the DNA damage in a normal cell line system after exposure to 60 Hz of extremely low frequency magnetic field (ELF-MF) and particularly in combination with various external factors, via comet assays. NIH3T3 mouse fibroblast cells, WI-38 human lung fibroblast cells, L132 human lung epithelial cells, and MCF10A human mammary gland epithelial cells were exposed for 4 or 16 h to a 60-Hz, 1 mT uniform magnetic field in the presence or absence of ionizing radiation (IR, 1 Gy), H(2)O(2) (50 μM), or c-Myc oncogenic activation. The results obtained showed no significant differences between the cells exposed to ELF-MF alone and the unexposed cells. Moreover, no synergistic or additive effects were observed after 4 or 16 h of pre-exposure to 1 mT ELF-MF or simultaneous exposure to ELF-MF combined with IR, H(2)O(2), or c-Myc activation.

  15. Predicted sub-populations in a marine shrimp proteome as revealed by combined EST and cDNA data from multiple Penaeus species

    Directory of Open Access Journals (Sweden)

    Kotewong Rattanawadee

    2010-11-01

    Full Text Available Abstract Background Many species of marine shrimp in the Family Penaeidae, viz. Penaeus (Litopenaeus vannamei, Penaeus monodon, Penaeus (Fenneropenaeus chinensis, and Penaeus (Marsupenaeus japonicus, are animals of economic importance in the aquaculture industry. Yet information about their DNA and protein sequences is lacking. In order to predict their collective proteome, we combined over 270,000 available EST and cDNA sequences from the 4 shrimp species with all protein sequences of Drosophila melanogaster and Caenorhabditis elegans. EST data from 4 other crustaceans, the crab Carcinus maenas, the lobster Homarus americanus (Decapoda, the water flea Daphnia pulex, and the brine shrimp Artemia franciscana were also used. Findings Similarity searches from EST collections of the 4 shrimp species matched 64% of the protein sequences of the fruit fly, but only 45% of nematode proteins, indicating that the shrimp proteome content is more similar to that of an insect than a nematode. Combined results with 4 additional non-shrimp crustaceans increased matching to 78% of fruit fly and 56% of nematode proteins, suggesting that present shrimp EST collections still lack sequences for many conserved crustacean proteins. Analysis of matching data revealed the presence of 4 EST groups from shrimp, namely sequences for proteins that are both fruit fly-like and nematode-like, fruit fly-like only, nematode-like only, and non-matching. Gene ontology profiles of proteins for the 3 matching EST groups were analyzed. For non-matching ESTs, a small fraction matched protein sequences from other species in the UniProt database, including other crustacean-specific proteins. Conclusions Shrimp ESTs indicated that the shrimp proteome is comprised of sub-populations of proteins similar to those common to both insect and nematode models, those present specifically in either model, or neither. Combining small EST collections from related species to compensate for their

  16. Combined Analyses of Chloroplast DNA Haplotypes and Microsatellite Markers Reveal New Insights Into the Origin and Dissemination Route of Cultivated Pears Native to East Asia

    Directory of Open Access Journals (Sweden)

    Xiaoyan Yue

    2018-05-01

    originated from the interspecific hybridization of wild Pyrus ussuriensis with cultivated Pyrus pyrifolia. The combination of uniparental DNA sequences and nuclear markers give us a better understanding of origins and genetic relationships for Asian pear groups and will be beneficial for the future improvement of Asian pear cultivars.

  17. Ancient DNA

    DEFF Research Database (Denmark)

    Willerslev, Eske; Cooper, Alan

    2004-01-01

    ancient DNA, palaeontology, palaeoecology, archaeology, population genetics, DNA damage and repair......ancient DNA, palaeontology, palaeoecology, archaeology, population genetics, DNA damage and repair...

  18. Intrinsic Motivation in Physical Education

    Science.gov (United States)

    Davies, Benjamin; Nambiar, Nathan; Hemphill, Caroline; Devietti, Elizabeth; Massengale, Alexandra; McCredie, Patrick

    2015-01-01

    This article describes ways in which educators can use Harter's perceived competence motivation theory, the achievement goal theory, and self-determination theory to develop students' intrinsic motivation to maintain physical fitness, as demonstrated by the Sound Body Sound Mind curriculum and proven effective by the 2013 University of…

  19. Acoustic resonance spectroscopy intrinsic seals

    International Nuclear Information System (INIS)

    Olinger, C.T.; Burr, T.; Vnuk, D.R.

    1994-01-01

    We have begun to quantify the ability of acoustic resonance spectroscopy (ARS) to detect the removal and replacement of the lid of a simulated special nuclear materials drum. Conceptually, the acoustic spectrum of a container establishcs a baseline fingerprint, which we refer to as an intrinsic seal, for the container. Simply removing and replacing the lid changes some of the resonant frequencies because it is impossible to exactly duplicate all of the stress patterns between the lid and container. Preliminary qualitative results suggested that the ARS intrinsic seal could discriminate between cases where a lid has or has not been removed. The present work is directed at quantifying the utility of the ARS intrinsic seal technique, including the technique's sensitivity to ''nuisance'' effects, such as temperature swings, movement of the container, and placement of the transducers. These early quantitative tests support the potential of the ARS intrinsic seal application, but also reveal a possible sensitivity to nuisance effects that could limit environments or conditions under which the technique is effective

  20. A novel quantitative assay of mitophagy: Combining high content fluorescence microscopy and mitochondrial DNA load to quantify mitophagy and identify novel pharmacological tools against pathogenic heteroplasmic mtDNA.

    Science.gov (United States)

    Diot, Alan; Hinks-Roberts, Alex; Lodge, Tiffany; Liao, Chunyan; Dombi, Eszter; Morten, Karl; Brady, Stefen; Fratter, Carl; Carver, Janet; Muir, Rebecca; Davis, Ryan; Green, Charlotte J; Johnston, Iain; Hilton-Jones, David; Sue, Carolyn; Mortiboys, Heather; Poulton, Joanna

    2015-10-01

    Mitophagy is a cellular mechanism for the recycling of mitochondrial fragments. This process is able to improve mitochondrial DNA (mtDNA) quality in heteroplasmic mtDNA disease, in which mutant mtDNA co-exists with normal mtDNA. In disorders where the load of mutant mtDNA determines disease severity it is likely to be an important determinant of disease progression. Measuring mitophagy is technically demanding. We used pharmacological modulators of autophagy to validate two techniques for quantifying mitophagy. First we used the IN Cell 1000 analyzer to quantify mitochondrial co-localisation with LC3-II positive autophagosomes. Unlike conventional fluorescence and electron microscopy, this high-throughput system is sufficiently sensitive to detect transient low frequency autophagosomes. Secondly, because mitophagy preferentially removes pathogenic heteroplasmic mtDNA mutants, we developed a heteroplasmy assay based on loss of m.3243A>G mtDNA, during culture conditions requiring oxidative metabolism ("energetic stress"). The effects of the pharmacological modulators on these two measures were consistent, confirming that the high throughput imaging output (autophagosomes co-localising with mitochondria) reflects mitochondrial quality control. To further validate these methods, we performed a more detailed study using metformin, the most commonly prescribed antidiabetic drug that is still sometimes used in Maternally Inherited Diabetes and Deafness (MIDD). This confirmed our initial findings and revealed that metformin inhibits mitophagy at clinically relevant concentrations, suggesting that it may have novel therapeutic uses. Copyright © 2015. Published by Elsevier Ltd.

  1. Programmable chemical controllers made from DNA

    Science.gov (United States)

    Chen, Yuan-Jyue; Dalchau, Neil; Srinivas, Niranjan; Phillips, Andrew; Cardelli, Luca; Soloveichik, David; Seelig, Georg

    2013-10-01

    Biological organisms use complex molecular networks to navigate their environment and regulate their internal state. The development of synthetic systems with similar capabilities could lead to applications such as smart therapeutics or fabrication methods based on self-organization. To achieve this, molecular control circuits need to be engineered to perform integrated sensing, computation and actuation. Here we report a DNA-based technology for implementing the computational core of such controllers. We use the formalism of chemical reaction networks as a 'programming language' and our DNA architecture can, in principle, implement any behaviour that can be mathematically expressed as such. Unlike logic circuits, our formulation naturally allows complex signal processing of intrinsically analogue biological and chemical inputs. Controller components can be derived from biologically synthesized (plasmid) DNA, which reduces errors associated with chemically synthesized DNA. We implement several building-block reaction types and then combine them into a network that realizes, at the molecular level, an algorithm used in distributed control systems for achieving consensus between multiple agents.

  2. Intrinsic terminators in Mycoplasma hyopneumoniae transcription.

    Science.gov (United States)

    Fritsch, Tiago Ebert; Siqueira, Franciele Maboni; Schrank, Irene Silveira

    2015-04-08

    Mycoplasma hyopneumoniae, an important pathogen of swine, exhibits a low guanine and cytosine (GC) content genome. M. hyopneumoniae genome is organised in long transcriptional units and promoter sequences have been mapped upstream of all transcription units. These analysis provided insights into the gene organisation and transcription initiation at the genome scale. However, the presence of transcriptional terminator sequences in the M. hyopneumoniae genome is poorly understood. In silico analyses demonstrated the presence of putative terminators in 82% of the 33 monocistronic units (mCs) and in 74% of the 116 polycistronic units (pCs) considering different classes of terminators. The functional activity of 23 intrinsic terminators was confirmed by RT-PCR and qPCR. Analysis of all terminators found by three software algorithms, combined with experimental results, allowed us to propose a pattern of RNA hairpin formation during the termination process and to predict the location of terminators in the M. hyopneumoniae genome sequence. The stem-loop structures of intrinsic terminators of mycoplasma diverge from the pattern of terminators found in other bacteria due the low content of guanine and cytosine. In M. hyopneumoniae, transcription can end after a transcriptional unit and before its terminator sequence and can also continue past the terminator sequence with RNA polymerases gradually releasing the RNA.

  3. Combining combing and secondary ion mass spectrometry to study DNA on chips using 13C and 15N labeling [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Armelle Cabin-Flaman

    2016-06-01

    Full Text Available Dynamic secondary ion mass spectrometry (D-SIMS imaging of combed DNA – the combing, imaging by SIMS or CIS method – has been developed previously using a standard NanoSIMS 50 to reveal, on the 50 nm scale, individual DNA fibers labeled with different, non-radioactive isotopes in vivo and to quantify these isotopes. This makes CIS especially suitable for determining the times, places and rates of DNA synthesis as well as the detection of the fine-scale re-arrangements of DNA and of molecules associated with combed DNA fibers. Here, we show how CIS may be extended to 13C-labeling via the detection and quantification of the 13C14N- recombinant ion and the use of the 13C:12C ratio, we discuss how CIS might permit three successive labels, and we suggest ideas that might be explored using CIS.

  4. Intrinsic and Extrinsic Aspects on Campylobacter jejuni Biofilms

    Directory of Open Access Journals (Sweden)

    Roberta T. Melo

    2017-07-01

    Full Text Available Biofilm represents a way of life that allows greater survival of microorganisms in hostile habitats. Campylobacter jejuni is able to form biofilms in vitro and on surfaces at several points in the poultry production chain. Genetic determinants related to their formation are expressed differently between strains and external conditions are decisive in this respect. Our approach combines phylogenetic analysis and the presence of seven specific genes linked to biofilm formation in association with traditional microbiology techniques, using Mueller Hinton and chicken juice as substrates in order to quantify, classify, determine the composition and morphology of the biomass of simple and mixed biofilms of 30 C. jejuni strains. It also evaluates the inhibition of its formation by biocides commonly used in industry and also by zinc oxide nanoparticles. Genetic analysis showed high heterogeneity with the identification of 23 pulsotypes. Despite the diversity, the presence of flaA, cadF, luxS, dnaJ, htrA, cbrA, and sodB genes in all strains shows the high potential for biofilm formation. This ability was only expressed in chicken juice, where they presented phenotype of a strong biofilm producer, with a mean count of 7.37 log CFU/mL and an ultrastructure characteristic of mature biofilm. The composition of simple and mixed biofilms was predominantly composed by proteins. The exceptions were found in mixed biofilms with Pseudomonas aeruginosa, which includes a carbohydrate-rich matrix, lower ability to sessile form in chicken juice and compact architecture of the biofilm, this aspects are intrinsic to this species. Hypochlorite, chlorhexidine, and peracetic acid were more effective in controlling viable cells of C. jejuni in biofilm, but the existence of tolerant strains indicates exposure to sublethal concentrations and development of adaptation mechanisms. This study shows that in chicken juice C. jejuni presents greater potential in producing mature

  5. Intrinsic charm and charmed particle production at Serpukhov energies

    International Nuclear Information System (INIS)

    Zmushko, V.V.

    1995-01-01

    This paper presents a study of the charmed particle production by protons on nuclei in the framework of two-component model at the Serpukhov energies. This model combines the leading-twist QCD and intrinsic charm contributions. It is shown that both contributions are comparable at 70 GeV energy of a proton, which makes possible the testing of the intrinsic charm predictions: the asymmetry between the leading and non-leading charm production and the A dependence of charm production. The asymmetry for D-bar/D mesons and Λ c + /Λ c - baryons and the cross section ratios for different nuclei are estimated [ru

  6. Finding intrinsic rewards by embodied evolution and constrained reinforcement learning.

    Science.gov (United States)

    Uchibe, Eiji; Doya, Kenji

    2008-12-01

    Understanding the design principle of reward functions is a substantial challenge both in artificial intelligence and neuroscience. Successful acquisition of a task usually requires not only rewards for goals, but also for intermediate states to promote effective exploration. This paper proposes a method for designing 'intrinsic' rewards of autonomous agents by combining constrained policy gradient reinforcement learning and embodied evolution. To validate the method, we use Cyber Rodent robots, in which collision avoidance, recharging from battery packs, and 'mating' by software reproduction are three major 'extrinsic' rewards. We show in hardware experiments that the robots can find appropriate 'intrinsic' rewards for the vision of battery packs and other robots to promote approach behaviors.

  7. Combined effects of DNA methyltransferase 1 and 3A polymorphisms and urinary total arsenic levels on the risk for clear cell renal cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Shu-Mei [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan (China); Huang, Chao-Yuan [Department of Urology, National Taiwan University Hospital, College of Medicine National Taiwan University, Taipei, Taiwan (China); Shiue, Horng-Sheng [Department of Chinese Medicine, Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Taoyuan, Taiwan (China); Pu, Yeong-Shiau [Department of Urology, National Taiwan University Hospital, College of Medicine National Taiwan University, Taipei, Taiwan (China); Hsieh, Yi-Hsun; Chen, Wei-Jen [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan (China); Lin, Ying-Chin [Department of Family Medicine, Shung Ho Hospital, Taipei Medical University, Taipei, Taiwan (China); Department of Health Examination, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan (China); Division of Family Medicine, School of Medicine, Taipei Medical University, Taipei, Taiwan (China); Hsueh, Yu-Mei, E-mail: ymhsueh@tmu.edu.tw [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan (China); Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China)

    2016-08-15

    Our previous study showed that high urinary total arsenic levels were associated with higher odds ratio (OR) for renal cell carcinoma (RCC). Single nucleotide polymorphisms (SNPs) of DNA methyltransferases (DNMTs) might influence DNMT enzyme activity associated with tumorigenesis. In this study, we investigated the association of five SNPs from DNMT1 (rs8101626 and rs2228611), DNMT3A (rs34048824 and rs1550117), and DNMT3B (rs1569686) with the risk of clear cell renal cell carcinoma (ccRCC). We also examined the combined effects of DNMT genotypes and urinary arsenic levels on ccRCC risk. We conducted a hospital-based case-control study, which included 293 subjects with ccRCC and 293 age- and gender-matched controls. The urinary arsenic species were determined by a high performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. Genotypes were investigated using polymerase chain reaction and restriction fragment length polymorphism analyses. We observed that the DNMT1 rs8101626 G/G genotype was significantly associated with reduced odds ratio (OR) of ccRCC [OR = 0.38, 95% confidence interval (CI) 0.14–0.99]. Subjects with concurrent DNMT1 rs8101626 A/A + A/G and DNMT3A rs34048824 T/T + T/C genotypes had significantly higher OR for ccRCC [OR = 2.88, 95% CI 1.44–5.77]. Participants with the high-risk genotype of DNMT1 rs8101626 and DNMT3A rs34048824 with concurrently high urinary total arsenic levels had even higher OR of ccRCC in a dose-response manner. This is the first study to evaluate variant DNMT1 rs8101626 and DNMT3A rs34048824 genotypes that modify the arsenic-related ccRCC risk in a geographic area without significant arsenic exposure in Taiwan. - Highlights: • High urinary total arsenic level or polymorphism of DNMT1 increased the OR of ccRCC. • High risk genotypes of combination of DNMT1 and DNMT3A increased the OR of ccRCC. • A joint effect of urinary total arsenic level and DNMTs genotypes may affect ccRCC.

  8. Nanotechnology Applications for Diffuse Intrinsic Pontine Glioma.

    Science.gov (United States)

    Bredlau, Amy Lee; Dixit, Suraj; Chen, Chao; Broome, Ann-Marie

    2017-01-01

    Diffuse intrinsic pontine gliomas (DIPGs) are invariably fatal tumors found in the pons of elementary school aged children. These tumors are grade II-IV gliomas, with a median survival of less than 1 year from diagnosis when treated with standard of care (SOC) therapy. Nanotechnology may offer therapeutic options for the treatment of DIPGs. Multiple nanoparticle formulations are currently being investigated for the treatment of DIPGs. Nanoparticles based upon stable elements, polymer nanoparticles, and organic nanoparticles are under development for the treatment of brain tumors, including DIPGs. Targeting of nanoparticles is now possible as delivery techniques that address the difficulty in crossing the blood brain barrier (BBB) are developed. Theranostic nanoparticles, a combination of therapeutics and diagnostic nanoparticles, improve imaging of the cancerous tissue while delivering therapy to the local region. However, additional time and attention should be directed to developing a nanoparticle delivery system for treatment of the uniformly fatal pediatric disease of DIPG.

  9. Profiles of Intrinsic and Extrinsic Motivations in Elementary School: A Longitudinal Analysis

    Science.gov (United States)

    Corpus, Jennifer Henderlong; Wormington, Stephanie V.

    2014-01-01

    The authors used a person-centered, longitudinal approach to identify and evaluate naturally occurring combinations of intrinsic and extrinsic motivations among 490 third- through fifth-grade students. Cluster analysis revealed 3 groups, characterized by high levels of both motivations ("high quantity"): high intrinsic motivation but low…

  10. INTRINSIC AND EXTRINSIC MOTIVATION - AN INVESTIGATION OF PERFORMANCE CORRELATION

    Directory of Open Access Journals (Sweden)

    Abrudan Maria-Madela

    2011-07-01

    Full Text Available A series of research untaken in the last decade have revealed some interesting aspects regarding the effects of different types of motivation on performance. Among the researchers who have shown interest in this field we can number: Richard Ryan, Edward Deci, Sam Glucksberg, Dan Ariely, Robert Eisenhower, Linda Shanock, analysts from London School of Economics, and others. Their findings suggest that extrinsic incentives may have a negative impact on overall performance, but a general agreement in this respect has not been reached. In this paper we intend to shed some light upon the relationship between intrinsic and extrinsic motivation and performance. Experts define intrinsic motivation as being the execution of a task or activity because of the inherent satisfaction arising from it rather than due to some separate outcome. In contrast with intrinsic motivation, we speak of extrinsic motivation whenever an activity is done in order to attain some separable outcome. With the purpose of contributing to the clarification of the links between concepts, we initiated and conducted an explanatory research. The research is based on the analysis of the relations between the results obtained by third year students and their predominant type of motivation. For this, we formulated and tested four work hypotheses using a combination of quantitative methods (investigation and qualitative methods (focus group. After the validation of the questionnaires, the respondents were divided into four categories: intrinsically motivated, extrinsically motivated, both intrinsically and extrinsically motivated and unmotivated. To analyze the collected data, we made use of Excel and SPSS. Some of the primary conclusions of the research are as follows: as the average increases, the percent of individuals having both extrinsic and intrinsic motivation is decreasing; the highest percentage of unmotivated students is concentrated in the highest average category; Female

  11. Quantifying intrinsic and extrinsic variability in stochastic gene expression models.

    Science.gov (United States)

    Singh, Abhyudai; Soltani, Mohammad

    2013-01-01

    Genetically identical cell populations exhibit considerable intercellular variation in the level of a given protein or mRNA. Both intrinsic and extrinsic sources of noise drive this variability in gene expression. More specifically, extrinsic noise is the expression variability that arises from cell-to-cell differences in cell-specific factors such as enzyme levels, cell size and cell cycle stage. In contrast, intrinsic noise is the expression variability that is not accounted for by extrinsic noise, and typically arises from the inherent stochastic nature of biochemical processes. Two-color reporter experiments are employed to decompose expression variability into its intrinsic and extrinsic noise components. Analytical formulas for intrinsic and extrinsic noise are derived for a class of stochastic gene expression models, where variations in cell-specific factors cause fluctuations in model parameters, in particular, transcription and/or translation rate fluctuations. Assuming mRNA production occurs in random bursts, transcription rate is represented by either the burst frequency (how often the bursts occur) or the burst size (number of mRNAs produced in each burst). Our analysis shows that fluctuations in the transcription burst frequency enhance extrinsic noise but do not affect the intrinsic noise. On the contrary, fluctuations in the transcription burst size or mRNA translation rate dramatically increase both intrinsic and extrinsic noise components. Interestingly, simultaneous fluctuations in transcription and translation rates arising from randomness in ATP abundance can decrease intrinsic noise measured in a two-color reporter assay. Finally, we discuss how these formulas can be combined with single-cell gene expression data from two-color reporter experiments for estimating model parameters.

  12. Intrinsic stability of technical superconductors

    International Nuclear Information System (INIS)

    Veringa, H.J.

    1981-10-01

    For the operation of technical superconductors under high current density conditions, the superconducting wires composing high current cables should be intrinsically stabilized. In this report the various important stability criteria are derived and investigated on their validity. An experimental set up is made to check the occurrence of magnetic instabilities if the different applicable criteria are violated. It is found that the observed instabilities can be predicted on the basis of the model given in this report. Production of high current cables based upon composites made by the ECN technique seems to be possible. (Auth.)

  13. Nuclear Filtering of Intrinsic Charm

    International Nuclear Information System (INIS)

    Kopeliovich, B. Z.; Potashnikova, I. K.; Schmidt, Ivan

    2010-01-01

    Nuclei are transparent for a heavy intrinsic charm (IC) component of the beam hadrons, what leads to an enhanced nuclear dependence of open charm production at large Feynman x F . Indeed, such an effect is supported by data from the SELEX experiment published recently [1]. Our calculations reproduce well the data, providing strong support for the presence of IC in hadrons in amount less than 1%. Moreover, we performed an analysis of nuclear effects in J/Ψ production and found at large x F a similar, albeit weaker effect, which does not contradict data.

  14. A combined approach of DNA probe and RFLP for family and species identification of larval stages of commercially important aquatic species: A study on the surfclam Spisula solidissima

    Digital Repository Service at National Institute of Oceanography (India)

    Achuthankutty, C.T.

    fragment length polymorphism (RFLP) analysis. An oilgonucleotide sequence designed from the 18S ribosomal RNA gene (nucleotide position 259-276) provided a sensitive probe for the Family Mactridae, to which S. solidissima belongs. DNA of unknown larvae...

  15. David Ross, Ideal Utilitarianism, and the Intrinsic Value of Acts

    Directory of Open Access Journals (Sweden)

    Francesco Orsi

    2012-01-01

    Full Text Available The denial of the intrinsic value of acts apart from both motives and consequences lies at the heart of Ross’s deontology and his opposition to ideal utilitarianism. Moreover, the claim that acts can have intrinsic value is a staple element of early and contemporary attempts to “consequentialise” all of morality. I first show why Ross’s denial is relevant both for his philosophy and for current debates. Then I consider and reject as inconclusive some of Ross’s explicit and implicit motivations for his claim, stemming from his philosophy of action, his axiology, and his concept of intrinsic value, or a combination of these. I also criticize Ross’s later view that all right acts somehow produce some good, but that the value of some of these goods is explained by the prior rightness of the act. In the course of the discussion, the idea that acts can have intrinsic value apart from motives and consequences gains credibility both from the weaknesses in Ross’s arguments and from some putative examples. So, finally, I distinguish two attitudes in the history of ideal utilitarianism towards the necessity or not to give a detailed account of the intrinsic value of acts, and suggest that a Why Bother attitude is more promising than a Constructive one.

  16. Photovoltaic device comprising compositionally graded intrinsic photoactive layer

    Science.gov (United States)

    Hoffbauer, Mark A; Williamson, Todd L

    2013-04-30

    Photovoltaic devices and methods of making photovoltaic devices comprising at least one compositionally graded photoactive layer, said method comprising providing a substrate; growing onto the substrate a uniform intrinsic photoactive layer having one surface disposed upon the substrate and an opposing second surface, said intrinsic photoactive layer consisting essentially of In.sub.1-xA.sub.xN,; wherein: i. 0.ltoreq.x.ltoreq.1; ii. A is gallium, aluminum, or combinations thereof; and iii. x is at least 0 on one surface of the intrinsic photoactive layer and is compositionally graded throughout the layer to reach a value of 1 or less on the opposing second surface of the layer; wherein said intrinsic photoactive layer is isothermally grown by means of energetic neutral atom beam lithography and epitaxy at a temperature of 600.degree. C. or less using neutral nitrogen atoms having a kinetic energy of from about 1.0 eV to about 5.0 eV, and wherein the intrinsic photoactive layer is grown at a rate of from about 5 nm/min to about 100 nm/min.

  17. Symmetries of collective models in intrinsic frame

    International Nuclear Information System (INIS)

    Gozdz, A.; Pedrak, A.; Szulerecka, A.; Dobrowolski, A.; Dudek, J.

    2013-01-01

    In the paper a very general definition of intrinsic frame, by means of group theoretical methods, is introduced. It allows to analyze nuclear properties which are invariant in respect to the group which defines the intrinsic frame. For example, nuclear shape is a well determined feature in the intrinsic frame defined by the Euclidean group. It is shown that using of intrinsic frame gives an opportunity to consider intrinsic nuclear symmetries which are independent of symmetries observed in the laboratory frame. An importance of the notion of partial symmetries is emphasized. (author)

  18. Evaluation of Genetic DNA damage in the agricultural workers exposed to combined action of pesticides in Jonia area of Barpeta district of Assam

    OpenAIRE

    Dr. Ranjit Hazarika; Purbajyoti Deka

    2017-01-01

    Abstract— The use of pesticide is increasing day by day and it causes a serious concern to the human health, especially some pesticides causes’ deleterious effect causing Cancer. Genotoxicity test has a special significance because it is one of the tests for cancer research and risk assessment. The sprayer has more risk because they directly cause in contact with pesticides. Pesticides may affect the DNA of the body cells of the sprayer and known to cause DNA damage. In this case control stud...

  19. Polo-like Kinase 1 as a potential therapeutic target in Diffuse Intrinsic Pontine Glioma

    International Nuclear Information System (INIS)

    Amani, Vladimir; Prince, Eric W; Alimova, Irina; Balakrishnan, Ilango; Birks, Diane; Donson, Andrew M.; Harris, Peter; Levy, Jean M. Mulcahy; Handler, Michael; Foreman, Nicholas K.; Venkataraman, Sujatha; Vibhakar, Rajeev

    2016-01-01

    Diffuse intrinsic pontine gliomas (DIPGs) are highly aggressive, fatal, childhood tumors that arise in the brainstem. DIPGs have no effective treatment, and their location and diffuse nature render them inoperable. Radiation therapy remains the only standard of care for this devastating disease. New therapeutic targets are needed to develop novel therapy for DIPG. We examined the expression of PLK1 mRNA in DIPG tumor samples through microarray analysis and found it to be up regulated versus normal pons. Using the DIPG tumor cells, we inhibited PLK1 using a clinically relevant specific inhibitor BI 6727 and evaluated the effects on, proliferation, apoptosis, induction of DNA damage and radio sensitization of the DIPG tumor cells. Treatment of DIPG cell lines with BI 6727, a new generation, highly selective inhibitor of PLK1, resulted in decreased cell proliferation and a marked increase in cellular apoptosis. Cell cycle analysis showed a significant arrest in G2-M phase and a substantial increase in cell death. Treatment also resulted in an increased γH2AX expression, indicating induction of DNA damage. PLK1 inhibition resulted in radiosensitization of DIPG cells. These findings suggest that targeting PLK1 with small-molecule inhibitors, in combination with radiation therapy, will hold a novel strategy in the treatment of DIPG that warrants further investigation

  20. Intrinsic cylindrical and spherical waves

    International Nuclear Information System (INIS)

    Ludlow, I K

    2008-01-01

    Intrinsic waveforms associated with cylindrical and spherical Bessel functions are obtained by eliminating the factors responsible for the inverse radius and inverse square radius laws of wave power per unit area of wavefront. The resulting expressions are Riccati-Bessel functions for both cases and these can be written in terms of amplitude and phase functions of order v and wave variable z. When z is real, it is shown that a spatial phase angle of the intrinsic wave can be defined and this, together with its amplitude function, is systematically investigated for a range of fixed orders and varying z. The derivatives of Riccati-Bessel functions are also examined. All the component functions exhibit different behaviour in the near field depending on the order being less than, equal to or greater than 1/2. Plots of the phase angle can be used to display the locations of the zeros of the general Riccati-Bessel functions and lead to new relations concerning the ordering of the real zeros of Bessel functions and the occurrence of multiple zeros when the argument of the Bessel function is fixed

  1. Intrinsic irreversibility in quantum theory

    International Nuclear Information System (INIS)

    Prigogine, I.; Petrosky, T.Y.

    1987-01-01

    Quantum theory has a dual structure: while solutions of the Schroedinger equation evolve in a deterministic and time reversible way, measurement introduces irreversibility and stochasticity. This presents a contrast to Bohr-Sommerfeld-Einstein theory, in which transitions between quantum states are associated with spontaneous and induced transitions, defined in terms of stochastic processes. A new form of quantum theory is presented here, which contains an intrinsic form of irreversibility, independent of observation. This new form applies to situations corresponding to a continuous spectrum and to quantum states with finite life time. The usual non-commutative algebra associated to quantum theory is replaced by more general algebra, in which operators are also non-distributive. Our approach leads to a number of predictions, which hopefully may be verified or refuted in the next years. (orig.)

  2. Intrinsic rotation with gyrokinetic models

    International Nuclear Information System (INIS)

    Parra, Felix I.; Barnes, Michael; Catto, Peter J.; Calvo, Iván

    2012-01-01

    The generation of intrinsic rotation by turbulence and neoclassical effects in tokamaks is considered. To obtain the complex dependences observed in experiments, it is necessary to have a model of the radial flux of momentum that redistributes the momentum within the tokamak in the absence of a preexisting velocity. When the lowest order gyrokinetic formulation is used, a symmetry of the model precludes this possibility, making small effects in the gyroradius over scale length expansion necessary. These effects that are usually small become important for momentum transport because the symmetry of the lowest order gyrokinetic formulation leads to the cancellation of the lowest order momentum flux. The accuracy to which the gyrokinetic equation needs to be obtained to retain all the physically relevant effects is discussed.

  3. Signatures of DNA target selectivity by ETS transcription factors.

    Science.gov (United States)

    Poon, Gregory M K; Kim, Hye Mi

    2017-05-27

    The ETS family of transcription factors is a functionally heterogeneous group of gene regulators that share a structurally conserved, eponymous DNA-binding domain. DNA target specificity derives from combinatorial interactions with other proteins as well as intrinsic heterogeneity among ETS domains. Emerging evidence suggests molecular hydration as a fundamental feature that defines the intrinsic heterogeneity in DNA target selection and susceptibility to epigenetic DNA modification. This perspective invokes novel hypotheses in the regulation of ETS proteins in physiologic osmotic stress, their pioneering potential in heterochromatin, and the effects of passive and pharmacologic DNA demethylation on ETS regulation.

  4. Experiences matter: Positive emotions facilitate intrinsic motivation

    OpenAIRE

    Løvoll, Helga Synnevåg; Røysamb, Espen; Vittersø, Joar

    2017-01-01

    This paper has two major aims. First, to investigate how positive emotions and intrinsic motivation affect each other over time. Second, to test the effect of positive emotions and intrinsic motivation on subsequent educational choices. Through two ordinary study semesters, 64 sport students in Norway reported on their intrinsic motivation for outdoor activities (twice) as well as positive emotions after two three-day outdoor events (four times). Next autumn, students study choice was collect...

  5. Experiences matter: Positive emotions facilitate intrinsic motivation

    OpenAIRE

    Løvoll, Helga Synnevåg; Røysamb, Espen; Vittersø, Joar

    2017-01-01

    https://doi.org/10.1080/23311908.2017.1340083 This paper has two major aims. First, to investigate how positive emotions and intrinsic motivation affect each other over time. Second, to test the effect of positive emotions and intrinsic motivation on subsequent educational choices. Through two ordinary study semesters, 64 sport students in Norway reported on their intrinsic motivation for outdoor activities (twice) as well as positive emotions after two three-day outdoor e...

  6. Intrinsic and extrinsic geometry of random surfaces

    International Nuclear Information System (INIS)

    Jonsson, T.

    1992-01-01

    We prove that the extrinsic Hausdorff dimension is always greater than or equal to the intrinsic Hausdorff dimension in models of triangulated random surfaces with action which is quadratic in the separation of vertices. We furthermore derive a few naive scaling relations which relate the intrinsic Hausdorff dimension to other critical exponents. These relations suggest that the intrinsic Hausdorff dimension is infinite if the susceptibility does not diverge at the critical point. (orig.)

  7. A DNA probe combination for improved detection of MLL/11q23 breakpoints by double-color interphase-FISH in acute leukemias.

    NARCIS (Netherlands)

    Bergh, A. von; Emanuel, B.; Zelderen-Bhola, S. van; Smetsers, A.F.C.M.; Soest, R. van; Stul, M.; Vranckx, H.; Schuuring, E.; Hagemeijer, A.; Kluin, P.

    2000-01-01

    Reciprocal translocations involving the MLL gene on chromosome band 11q23 have been observed in both acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). In AML, identification of MLL breakpoints is an important prognostic factor. Breakpoints are clustered in an 8 kb DNA fragment

  8. Incentives and intrinsic motivation in healthcare

    Directory of Open Access Journals (Sweden)

    Mikel Berdud

    2016-11-01

    Conclusions: The conclusions could act as a guide to support the optimal design of incentive policies and schemes within health organisations when healthcare professionals are intrinsically motivated.

  9. An RNA origami octahedron with intrinsic siRNAs for potent gene knockdown

    DEFF Research Database (Denmark)

    Høiberg, Hans Christian; Sparvath, Steffen Møller; Andersen, Veronica Liv

    2018-01-01

    The fields of DNA and RNA nanotechnology have established nucleic acids as valuable building blocks for functional nanodevices with applications in nanomedicine. Here, a simple method for designing and assembling a three‐dimensional (3D) scaffolded RNA origami wireframe structure with intrinsic...

  10. Molecules in the mud: Combining ancient DNA and lipid biomarkers to reconstruct vegetation response to climate variability during the Last Interglacial and the Holocene on Baffin Island, Arctic Canada

    Science.gov (United States)

    Crump, S. E.; Sepúlveda, J.; Bunce, M.; Miller, G. H.

    2017-12-01

    Modern ecological studies are revealing that the "greening" of the Arctic, resulting from a poleward shift in woody vegetation ranges, is already underway. The increasing abundance of shrubs in tundra ecosystems plays an important role in the global climate system through multiple positive feedbacks, yet uncertainty in future predictions of terrestrial vegetation means that climate models are likely not capturing these feedbacks accurately. Recently developed molecular techniques for reconstructing past vegetation and climate allow for a closer look at the paleo-record in order to improve our understanding of tundra community responses to climate variability; our current research focus is to apply these tools to both Last Interglacial and Holocene warm times. Here we present initial results from a small lake on southern Baffin Island spanning the last 7.2 ka. We reconstruct climate with both bulk geochemical and biomarker proxies, primarily using biogenic silica and branched glycerol dialkyl glycerol tetraethers (brGDGTs) as temperature indicators. We assess shifts in plant community using multivariate analysis of sedimentary ancient DNA (sedaDNA) metabarcoding data. This combination of approaches reveals that the vegetation community has responded sensitively to early Holocene warmth, Neoglacial cooling, and possibly modern anthropogenic warming. To our knowledge, this represents the first combination of a quantitative, biomarker-based climate reconstruction with a sedaDNA-based paleoecological reconstruction, and offers a glimpse at the potential of these molecular techniques used in tandem.

  11. Protein intrinsic disorder in plants.

    Science.gov (United States)

    Pazos, Florencio; Pietrosemoli, Natalia; García-Martín, Juan A; Solano, Roberto

    2013-09-12

    To some extent contradicting the classical paradigm of the relationship between protein 3D structure and function, now it is clear that large portions of the proteomes, especially in higher organisms, lack a fixed structure and still perform very important functions. Proteins completely or partially unstructured in their native (functional) form are involved in key cellular processes underlain by complex networks of protein interactions. The intrinsic conformational flexibility of these disordered proteins allows them to bind multiple partners in transient interactions of high specificity and low affinity. In concordance, in plants this type of proteins has been found in processes requiring these complex and versatile interaction networks. These include transcription factor networks, where disordered proteins act as integrators of different signals or link different transcription factor subnetworks due to their ability to interact (in many cases simultaneously) with different partners. Similarly, they also serve as signal integrators in signaling cascades, such as those related to response to external stimuli. Disordered proteins have also been found in plants in many stress-response processes, acting as protein chaperones or protecting other cellular components and structures. In plants, it is especially important to have complex and versatile networks able to quickly and efficiently respond to changing environmental conditions since these organisms cannot escape and have no other choice than adapting to them. Consequently, protein disorder can play an especially important role in plants, providing them with a fast mechanism to obtain complex, interconnected and versatile molecular networks.

  12. Geochemical indicators of intrinsic bioremediation

    International Nuclear Information System (INIS)

    Borden, R.C.; Gomez, C.A.; Becker, M.T.

    1995-01-01

    A detailed field investigation has been completed at a gasoline-contaminated aquifer near Rocky Point, NC, to examine possible indicators of intrinsic bioremediation and identify factors that may significantly influence the rae and extent of bioremediation. The dissolved plume of benzene, toluene, ethylbenzene, and xylene (BTEX) in ground water is naturally degrading. Toluene and o-xylene are most rapidly degraded followed by m-, p-xylene, and benzene. Ethylbenzene appears to degrade very slowly under anaerobic conditions present in the center of the plume. The rate and extent of biodegradation appears to be strongly influenced by the type and quantity of electron acceptors present in the aquifer. At the upgradient edge of the plume, nitrate, ferric iron, and oxygen are used as terminal electron acceptors during hydrocarbon biodegradation. The equivalent of 40 to 50 mg/l of hydrocarbon is degraded based on the increase in dissolved CO 2 relative to background ground water. Immediately downgradient of the source area, sulfate and iron are the dominant electron acceptors. Toluene and o-xylene are rapidly removed in this region. Once the available oxygen, nitrate, and sulfate are consumed, biodegradation is limited and appears to be controlled by mixing and aerobic biodegradation at the plume fringes

  13. Protein intrinsic disorder in plants

    Directory of Open Access Journals (Sweden)

    Florencio ePazos

    2013-09-01

    Full Text Available To some extent contradicting the classical paradigm of the relationship between protein 3D structure and function, now it is clear that large portions of the proteomes, especially in higher organisms, lack a fixed structure and still perform very important functions. Proteins completely or partially unstructured in their native (functional form are involved in key cellular processes underlain by complex networks of protein interactions. The intrinsic conformational flexibility of these disordered proteins allows them to bind multiple partners in transient interactions of high specificity and low affinity. In concordance, in plants this type of proteins has been found in processes requiring these complex and versatile interaction networks. These include transcription factor networks, where disordered proteins act as integrators of different signals or link different transcription factor subnetworks due to their ability to interact (in many cases simultaneously with different partners. Similarly, they also serve as signal integrators in signalling cascades, such as those related to response to external stimuli. Disordered proteins have also been found in plants in many stress-response processes, acting as protein chaperones or protecting other cellular components and structures. In plants, it is especially important to have complex and versatile networks able to quickly and efficiently respond to changing environmental conditions since these organisms can not escape and have no other choice than adapting to them. Consequently, protein disorder can play an especially important role in plants, providing them with a fast mechanism to obtain complex, interconnected and versatile molecular networks.

  14. Intrinsically Survivable Structural Composite Materials

    National Research Council Canada - National Science Library

    Anderson, D

    2000-01-01

    Spherical nanoscale particles were incorporated into an aerospace epoxy resin. When properly dispersed with a combination of mechanical and ultrasonic mixing, the fracture toughness could be made twice that of the control resin...

  15. Intrinsic bioremediation of landfills interim report

    Energy Technology Data Exchange (ETDEWEB)

    Brigmon, R.L. [Westinghouse Savannah River Company, Aiken, SC (United States); Fliermans, C.B.

    1997-07-14

    Intrinsic bioremediation is a risk management option that relies on natural biological and physical processes to contain the spread of contamination from a source. Evidence is presented in this report that intrinsic bioremediation is occurring at the Sanitary Landfill is fundamental to support incorportion into a Corrective Action Plan (CAP).

  16. Expressing intrinsic volumes as rotational integrals

    DEFF Research Database (Denmark)

    Auneau, Jeremy Michel; Jensen, Eva Bjørn Vedel

    2010-01-01

    A new rotational formula of Crofton type is derived for intrinsic volumes of a compact subset of positive reach. The formula provides a functional defined on the section of X with a j-dimensional linear subspace with rotational average equal to the intrinsic volumes of X. Simplified forms of the ...

  17. Differential scanning microcalorimetry of intrinsically disordered proteins.

    Science.gov (United States)

    Permyakov, Sergei E

    2012-01-01

    Ultrasensitive differential scanning calorimetry (DSC) is an indispensable thermophysical technique enabling to get direct information on enthalpies accompanying heating/cooling of dilute biopolymer solutions. The thermal dependence of protein heat capacity extracted from DSC data is a valuable source of information on intrinsic disorder level of a protein. Application details and limitations of DSC technique in exploration of protein intrinsic disorder are described.

  18. Intrinsic bioremediation of landfills interim report

    International Nuclear Information System (INIS)

    Brigmon, R.L.; Fliermans, C.B.

    1997-01-01

    Intrinsic bioremediation is a risk management option that relies on natural biological and physical processes to contain the spread of contamination from a source. Evidence is presented in this report that intrinsic bioremediation is occurring at the Sanitary Landfill is fundamental to support incorportion into a Corrective Action Plan (CAP)

  19. Isolate extended state in the DNA molecular transistor with surface interaction

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Le, E-mail: wang_le917@gs.zzu.edu.cn; Qin, Zhi-Jie

    2016-02-01

    The field effect characteristic of a DNA molecular device is investigated in a tight binding model with binary disorder and side site correlation. Using the transfer-matrix method and Landauer–Büttiker theory, we find that the system has isolated extended state that is irrespective of the DNA sequence and can be modulated by the gate voltage. When the gate voltage reaches some proper value, the isolated extended state appears at the Fermi level of the system and the long range charge transport is greatly enhanced. We attribute this phenomenon to the combination of the external field, the surface interaction, and the intrinsic disorder of DNA. The result is a generic feature of the nanowire with binary disorder and surface interaction.

  20. A DNA sequence element that advances replication origin activation time in Saccharomyces cerevisiae.

    Science.gov (United States)

    Pohl, Thomas J; Kolor, Katherine; Fangman, Walton L; Brewer, Bonita J; Raghuraman, M K

    2013-11-06

    Eukaryotic origins of DNA replication undergo activation at various times in S-phase, allowing the genome to be duplicated in a temporally staggered fashion. In the budding yeast Saccharomyces cerevisiae, the activation times of individual origins are not intrinsic to those origins but are instead governed by surrounding sequences. Currently, there are two examples of DNA sequences that are known to advance origin activation time, centromeres and forkhead transcription factor binding sites. By combining deletion and linker scanning mutational analysis with two-dimensional gel electrophoresis to measure fork direction in the context of a two-origin plasmid, we have identified and characterized a 19- to 23-bp and a larger 584-bp DNA sequence that are capable of advancing origin activation time.

  1. Genetic architecture of intrinsic antibiotic susceptibility.

    Directory of Open Access Journals (Sweden)

    Hany S Girgis

    2009-05-01

    Full Text Available Antibiotic exposure rapidly selects for more resistant bacterial strains, and both a drug's chemical structure and a bacterium's cellular network affect the types of mutations acquired.To better characterize the genetic determinants of antibiotic susceptibility, we exposed a transposon-mutagenized library of Escherichia coli to each of 17 antibiotics that encompass a wide range of drug classes and mechanisms of action. Propagating the library for multiple generations with drug concentrations that moderately inhibited the growth of the isogenic parental strain caused the abundance of strains with even minor fitness advantages or disadvantages to change measurably and reproducibly. Using a microarray-based genetic footprinting strategy, we then determined the quantitative contribution of each gene to E. coli's intrinsic antibiotic susceptibility. We found both loci whose removal increased general antibiotic tolerance as well as pathways whose down-regulation increased tolerance to specific drugs and drug classes. The beneficial mutations identified span multiple pathways, and we identified pairs of mutations that individually provide only minor decreases in antibiotic susceptibility but that combine to provide higher tolerance.Our results illustrate that a wide-range of mutations can modulate the activity of many cellular resistance processes and demonstrate that E. coli has a large mutational target size for increasing antibiotic tolerance. Furthermore, the work suggests that clinical levels of antibiotic resistance might develop through the sequential accumulation of chromosomal mutations of small individual effect.

  2. Eukaryotic DNA Replicases

    KAUST Repository

    Zaher, Manal S.; Oke, Muse; Hamdan, Samir

    2014-01-01

    The current model of the eukaryotic DNA replication fork includes three replicative DNA polymerases, polymerase α/primase complex (Pol α), polymerase δ (Pol δ), and polymerase ε (Pol ε). The primase synthesizes 8–12 nucleotide RNA primers that are extended by the DNA polymerization activity of Pol α into 30–35 nucleotide RNA-DNA primers. Replication factor C (RFC) opens the polymerase clamp-like processivity factor, proliferating cell nuclear antigen (PCNA), and loads it onto the primer-template. Pol δ utilizes PCNA to mediate highly processive DNA synthesis, while Pol ε has intrinsic high processivity that is modestly stimulated by PCNA. Pol ε replicates the leading strand and Pol δ replicates the lagging strand in a division of labor that is not strict. The three polymerases are comprised of multiple subunits and share unifying features in their large catalytic and B subunits. The remaining subunits are evolutionarily not related and perform diverse functions. The catalytic subunits are members of family B, which are distinguished by their larger sizes due to inserts in their N- and C-terminal regions. The sizes of these inserts vary among the three polymerases, and their functions remain largely unknown. Strikingly, the quaternary structures of Pol α, Pol δ, and Pol ε are arranged similarly. The catalytic subunits adopt a globular structure that is linked via its conserved C-terminal region to the B subunit. The remaining subunits are linked to the catalytic and B subunits in a highly flexible manner.

  3. Eukaryotic DNA Replicases

    KAUST Repository

    Zaher, Manal S.

    2014-11-21

    The current model of the eukaryotic DNA replication fork includes three replicative DNA polymerases, polymerase α/primase complex (Pol α), polymerase δ (Pol δ), and polymerase ε (Pol ε). The primase synthesizes 8–12 nucleotide RNA primers that are extended by the DNA polymerization activity of Pol α into 30–35 nucleotide RNA-DNA primers. Replication factor C (RFC) opens the polymerase clamp-like processivity factor, proliferating cell nuclear antigen (PCNA), and loads it onto the primer-template. Pol δ utilizes PCNA to mediate highly processive DNA synthesis, while Pol ε has intrinsic high processivity that is modestly stimulated by PCNA. Pol ε replicates the leading strand and Pol δ replicates the lagging strand in a division of labor that is not strict. The three polymerases are comprised of multiple subunits and share unifying features in their large catalytic and B subunits. The remaining subunits are evolutionarily not related and perform diverse functions. The catalytic subunits are members of family B, which are distinguished by their larger sizes due to inserts in their N- and C-terminal regions. The sizes of these inserts vary among the three polymerases, and their functions remain largely unknown. Strikingly, the quaternary structures of Pol α, Pol δ, and Pol ε are arranged similarly. The catalytic subunits adopt a globular structure that is linked via its conserved C-terminal region to the B subunit. The remaining subunits are linked to the catalytic and B subunits in a highly flexible manner.

  4. Human DNA polymerase alpha uses a combination of positive and negative selectivity to polymerize purine dNTPs with high fidelity

    Czech Academy of Sciences Publication Activity Database

    Beckman, J.; Kincaid, K.; Hocek, Michal; Spratt, T.; Engels, J.; Cosstick, R.; Kuchta, R. D.

    2007-01-01

    Roč. 46, č. 2 (2007), s. 448-460 ISSN 0006-2960 R&D Projects: GA MŠk LC512 Grant - others:NIH(US) GM54194; NIH(US) TW007372-01; Army Research Office(US) W911NF-05-1-0172; DFG(DE) SFB 579 Institutional research plan: CEZ:AV0Z40550506 Keywords : DNA polymerase * nucleoside triphosphates * modified nucleobases Subject RIV: CC - Organic Chemistry Impact factor: 3.368, year: 2007

  5. Transport of Intrinsic Plutonium Colloids in Saturated Porous Media

    Science.gov (United States)

    Zhou, D.; Abdel-Fattah, A.; Boukhalfa, H.; Ware, S. D.; Tarimala, S.; Keller, A. A.

    2011-12-01

    column at a flow rate of ~ 6 mL/hr. Despite that the Pu intrinsic colloids are positively charged while the alluvium grain surfaces are negatively charged under the current experimental conditions, about 30% of the Pu colloids population transported through the column and broke through earlier than trillium. Our previous experiments in the same column have shown a highly unretarded transport of the negatively charged pseudo Pu colloids (Pu sorbed onto smectite colloids) and complete retardation of the dissolved Pu. The enhanced transport of Pu colloids was explained by the effective pore volume concept. Combining the results of these two experiments, it is concluded that the intrinsic Pu colloids transported in the column by adsorbing onto the background clay colloids due to electrostatic repulsion.

  6. The role of DNA dependent protein kinase in synapsis of DNA ends.

    Science.gov (United States)

    Weterings, Eric; Verkaik, Nicole S; Brüggenwirth, Hennie T; Hoeijmakers, Jan H J; van Gent, Dik C

    2003-12-15

    DNA dependent protein kinase (DNA-PK) plays a central role in the non-homologous end-joining pathway of DNA double strand break repair. Its catalytic subunit (DNA-PK(CS)) functions as a serine/threonine protein kinase. We show that DNA-PK forms a stable complex at DNA termini that blocks the action of exonucleases and ligases. The DNA termini become accessible after autophosphorylation of DNA-PK(CS), which we demonstrate to require synapsis of DNA ends. Interestingly, the presence of DNA-PK prevents ligation of the two synapsed termini, but allows ligation to another DNA molecule. This alteration of the ligation route is independent of the type of ligase that we used, indicating that the intrinsic architecture of the DNA-PK complex itself is not able to support ligation of the synapsed DNA termini. We present a working model in which DNA-PK creates a stable molecular bridge between two DNA ends that is remodeled after DNA-PK autophosphorylation in such a way that the extreme termini become accessible without disrupting synapsis. We infer that joining of synapsed DNA termini would require an additional protein factor.

  7. Intrinsic brightness temperatures of blazar jets at 15 GHz

    Directory of Open Access Journals (Sweden)

    Hovatta Talvikki

    2013-12-01

    Full Text Available We have developed a new Bayesian Markov Chain Monte Carlo method to deconvolve light curves of blazars into individual flares, including proper estimation of the fit errors. We use the method to fit 15GHzlight curves obtained within the OVRO 40-m blazar monitoring program where a large number of AGN have been monitored since 2008 in support of the Fermi Gamma-Ray Space Telescope mission. The time scales obtained from the fitted models are used to calculate the variability brightness temperature of the sources. Additionally, we have calculated brightness temperatures of a sample of these objects using Very Long Baseline Array data from the MOJAVE survey. Combining these two data sets enables us to study the intrinsic brightness temperature distribution in these blazars at 15 GHz. Our preliminary results indicate that the mean intrinsic brightness temperature in a sample of 14 sources is near the equipartition brightness temperature of ~ 1011K.

  8. Rapid and simple method by combining FTA™ card DNA extraction with two set multiplex PCR for simultaneous detection of non-O157 Shiga toxin-producing Escherichia coli strains and virulence genes in food samples.

    Science.gov (United States)

    Kim, S A; Park, S H; Lee, S I; Ricke, S C

    2017-12-01

    The aim of this research was to optimize two multiplex polymerase chain reaction (PCR) assays that could simultaneously detect six non-O157 Shiga toxin-producing Escherichia coli (STEC) as well as the three virulence genes. We also investigated the potential of combining the FTA™ card-based DNA extraction with the multiplex PCR assays. Two multiplex PCR assays were optimized using six primer pairs for each non-O157 STEC serogroup and three primer pairs for virulence genes respectively. Each STEC strain specific primer pair only amplified 155, 238, 321, 438, 587 and 750 bp product for O26, O45, O103, O111, O121 and O145 respectively. Three virulence genes were successfully multiplexed: 375 bp for eae, 655 bp for stx1 and 477 bp for stx2. When two multiplex PCR assays were validated with ground beef samples, distinctive bands were also successfully produced. Since the two multiplex PCR examined here can be conducted under the same PCR conditions, the six non-O157 STEC and their virulence genes could be concurrently detected with one run on the thermocycler. In addition, all bands clearly appeared to be amplified by FTA card DNA extraction in the multiplex PCR assay from the ground beef sample, suggesting that an FTA card could be a viable sampling approach for rapid and simple DNA extraction to reduce time and labour and therefore may have practical use for the food industry. Two multiplex polymerase chain reaction (PCR) assays were optimized for discrimination of six non-O157 Shiga toxin-producing Escherichia coli (STEC) and identification of their major virulence genes within a single reaction, simultaneously. This study also determined the successful ability of the FTA™ card as an alternative to commercial DNA extraction method for conducting multiplex STEC PCR assays. The FTA™ card combined with multiplex PCR holds promise for the food industry by offering a simple and rapid DNA sample method for reducing time, cost and labour for detection of STEC in

  9. Defining intrinsic vs. extrinsic atopic dermatitis.

    Science.gov (United States)

    Karimkhani, Chante; Silverberg, Jonathan I; Dellavalle, Robert P

    2015-06-16

    Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin condition characterized by eczematous lesions, i.e. ill-demarcated erythematous patches and plaques. AD is commonly associated with elevated immunoglobulin E (IgE) and atopic disorders, such as asthma, hay fever, and food allergies. Rackemann and Mallory were some of the first to distinguish between asthma based on the presence ("extrinsic") or absence ("intrinsic") of allergy. This distinction has subsequently been applied to AD based on the presence ("extrinsic") or absence ("intrinsic") of increased IgE and atopic disease. Although the distinction between intrinsic and extrinsic AD is widely used, it remains controversial.

  10. Algebraic description of intrinsic modes in nuclei

    International Nuclear Information System (INIS)

    Leviatan, A.

    1989-01-01

    We present a procedure for extracting normal modes in algebraic number-conserving systems of interacting bosons relevant for collective states in even-even nuclei. The Hamiltonian is resolved into intrinsic (bandhead related) and collective (in-band related) parts. Shape parameters are introduced through non-spherical boson bases. Intrinsic modes decoupled from the spurious modes are obtained from the intinsic part of the Hamiltonian in the limit of large number of bosons. Intrinsic states are constructed and serve to evaluate electromagnetic transition rates. The method is illustrated for systems with one type of boson as well as with proton-neutron bosons. 28 refs., 1 fig

  11. Intrinsic neuromodulation: altering neuronal circuits from within.

    Science.gov (United States)

    Katz, P S; Frost, W N

    1996-02-01

    There are two sources of neuromodulation for neuronal circuits: extrinsic inputs and intrinsic components of the circuits themselves. Extrinsic neuromodulation is known to be pervasive in nervous systems, but intrinsic neuromodulation is less recognized, despite the fact that it has now been demonstrated in sensory and neuromuscular circuits and in central pattern generators. By its nature, intrinsic neuromodulation produces local changes in neuronal computation, whereas extrinsic neuromodulation can cause global changes, often affecting many circuits simultaneously. Studies in a number of systems are defining the different properties of these two forms of neuromodulation.

  12. Intrinsic Tunneling in Phase Separated Manganites

    Science.gov (United States)

    Singh-Bhalla, G.; Selcuk, S.; Dhakal, T.; Biswas, A.; Hebard, A. F.

    2009-02-01

    We present evidence of direct electron tunneling across intrinsic insulating regions in submicrometer wide bridges of the phase-separated ferromagnet (La,Pr,Ca)MnO3. Upon cooling below the Curie temperature, a predominantly ferromagnetic supercooled state persists where tunneling across the intrinsic tunnel barriers (ITBs) results in metastable, temperature-independent, high-resistance plateaus over a large range of temperatures. Upon application of a magnetic field, our data reveal that the ITBs are extinguished resulting in sharp, colossal, low-field resistance drops. Our results compare well to theoretical predictions of magnetic domain walls coinciding with the intrinsic insulating phase.

  13. Extrinsic wrist ligaments: prevalence of injury by magnetic resonance imaging and association with intrinsic ligament tears.

    Science.gov (United States)

    Taneja, Atul K; Bredella, Miriam A; Chang, Connie Y; Joseph Simeone, F; Kattapuram, Susan V; Torriani, Martin

    2013-01-01

    The objective of this study was to determine the prevalence of extrinsic wrist ligament injury by magnetic resonance imaging and its association with intrinsic ligament tears. We reviewed conventional magnetic resonance images performed over a 5-year period from adult patients in the setting of wrist trauma. Two musculoskeletal radiologists examined the integrity of wrist ligaments and presence of bone abnormalities. In a cohort of 75 subjects, extrinsic ligament injury was present in 75%, with radiolunotriquetral being most frequently affected (45%). Intrinsic ligament injury was present in 60%. Almost half of subjects had combined intrinsic and extrinsic ligament injury. Bone abnormalities were seen in 69%. The rate of extrinsic injury was higher in subjects with bone injury (P = 0.008). There is high prevalence of extrinsic ligament injury in the setting of wrist trauma, especially in the presence of bone abnormalities, with combined injury of intrinsic and extrinsic ligaments in about half of cases.

  14. Comparative investigations of sodium arsenite, arsenic trioxide and cadmium sulphate in combination with gamma-radiation on apoptosis, micronuclei induction and DNA damage in a human lymphoblastoid cell line

    International Nuclear Information System (INIS)

    Hornhardt, Sabine; Gomolka, Maria; Walsh, Linda; Jung, Thomas

    2006-01-01

    In the field of radiation protection the combined exposure to radiation and other toxic agents is recognised as an important research area. To elucidate the basic mechanisms of simultaneous exposure, the interaction of the carcinogens and environmental toxicants cadmium and two arsenic compounds, arsenite and arsenic trioxide, in combination with gamma-radiation in human lymphoblastoid cells (TK6) were investigated. Gamma-radiation induced significant genotoxic effects such as micronuclei formation, DNA damage and apoptosis, whereas arsenic and cadmium had no significant effect on these indicators of cellular damage at non-toxic concentrations. However, in combination with gamma-radiation arsenic trioxide induced a more than additive apoptotic rate compared to the sum of the single effects. Here, the level of apoptotic cells was increased, in a dose-dependent way, up to two-fold compared to the irradiated control cells. Arsenite did not induce a significant additive effect at any of the concentrations or radiation doses tested. On the other hand, arsenic trioxide was less effective than arsenite in the induction of DNA protein cross-links. These data indicate that the two arsenic compounds interact through different pathways in the cell. Cadmium sulphate, like arsenite, had no significant effect on apoptosis in combination with gamma-radiation at low concentrations and, at high concentrations, even reduced the radiation-induced apoptosis. An additive effect on micronuclei induction was observed with 1 μM cadmium sulphate with an increase of up to 80% compared to the irradiated control cells. Toxic concentrations of cadmium and arsenic trioxide seemed to reduce micronuclei induction. The results presented here indicate that relatively low concentrations of arsenic and cadmium, close to those occurring in nature, may interfere with radiation effects. Differences in action of the two arsenic compounds were identified

  15. The Intrinsic Dynamics of Psychological Process

    NARCIS (Netherlands)

    Vallacher, Robin R.; van Geert, Paul; Nowak, Andrzej

    2015-01-01

    Psychological processes unfold on various timescales in accord with internally generated patterns. The intrinsic dynamism of psychological process is difficult to investigate using traditional methods emphasizing cause–effect relations, however, and therefore is rarely incorporated into social

  16. Original Paper Detecting Nosocomial Intrinsic Infections through ...

    African Journals Online (AJOL)

    2011-04-20

    Apr 20, 2011 ... surgical procedures as precursory to intrinsic infections and that bacterial pathogens found on wounds and endogenous ... University Teaching Hospital, Idi Araba, Lagos, ..... confirm reason for selective decontamination of the.

  17. Deuterium NMR, induced and intrinsic cholesteric lyomesophases

    International Nuclear Information System (INIS)

    Alcantara, M.R.

    1982-01-01

    Induced and intrinsic cholesteric lyotropic mesophases were studied. Induced cholesteric lyomesophases based on potassium laurate (KL) system, with small amounts of cholesterol added, were studied by deuterium NMR and by polarizing microscopy. Order profiles obtained from deuterium NMR of KL perdenderated chains in both induced cholesteric and normal mesophases were compared. The intrinsic cholesteric lyotropic mesophases were based on the amphiphile potassium N-lauroyl serinate (KLNS) in the resolved levo form. The study of the type I intrinsic cholesteric mesophase was made by optical microscopy under polarized light and the type II intrinsic cholesteric lyomesophase was characterized by deuterium NMR. The new texture was explained by the use of the theory of disclinations developed for thermotropic liquid crystals, specially for cholesteric type. (M.J.C.) [pt

  18. Intrinsic and extrinsic motivation for smoking cessation.

    Science.gov (United States)

    Curry, S; Wagner, E H; Grothaus, L C

    1990-06-01

    An intrinsic-extrinsic model of motivation for smoking cessation was evaluated with 2 samples (ns = 1.217 and 151) of smokers who requested self-help materials for smoking cessation. Exploratory and confirmatory principal components analysis on a 36-item Reasons for Quitting (RFQ) scale supported the intrinsic-extrinsic motivation distinction. A 4-factor model, with 2 intrinsic dimensions (concerns about health and desire for self-control) and 2 extrinsic dimensions (immediate reinforcement and social influence), was defined by 20 of the 36 RFQ items. The 20-item measure demonstrated moderate to high levels of internal consistency and convergent and discriminant validity. Logistic regression analyses indicated that smokers with higher levels of intrinsic relative to extrinsic motivation were more likely to achieve abstinence from smoking.

  19. Intrinsic endometriosis of ureter: a case report

    International Nuclear Information System (INIS)

    Hong, Myung Sun; Kim, Ho Chul; Yun, Ku Sup; Choi, Chul Soon; Bae, Sang Hoon; Kim, Sung Yong; Shin, Hyung Sik

    1995-01-01

    Endometriosis is a rare cause of an ureteral obstruction. We report a case of intrinsic ureteral endometriosis resulting in severe hydroureteronephrosis. The diagnosis of ureteral endometriosis may be considered in women with flank pain and ureteric obstruction within true pelvis

  20. Intrinsic endometriosis of ureter: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Myung Sun; Kim, Ho Chul; Yun, Ku Sup; Choi, Chul Soon; Bae, Sang Hoon; Kim, Sung Yong; Shin, Hyung Sik [College of Medicine, Hallym University, Seoul (Korea, Republic of)

    1995-07-15

    Endometriosis is a rare cause of an ureteral obstruction. We report a case of intrinsic ureteral endometriosis resulting in severe hydroureteronephrosis. The diagnosis of ureteral endometriosis may be considered in women with flank pain and ureteric obstruction within true pelvis.

  1. Candidate DNA Barcode Tags Combined With High Resolution Melting (Bar-HRM Curve Analysis for Authentication of Senna alexandrina Mill. With Validation in Crude Drugs

    Directory of Open Access Journals (Sweden)

    Priyanka Mishra

    2018-03-01

    Full Text Available Senna alexandrina (Fabaceae is a globally recognized medicinal plant for its laxative properties as well as the only source of sennosides, and is highly exported bulk herb from India. Its major procurement is exclusively from limited cultivation, which leads to risks of deliberate or unintended adulteration. The market raw materials are in powdered or finished product form, which lead to difficulties in authentication. Here, DNA barcode tags based on chloroplast genes (rbcL and matK and intergenic spacers (psbA-trnH and ITS were developed for S. alexandrina along with the allied species. The ability and performance of the ITS1 region to discriminate among the Senna species resulted in the present proposal of the ITS1 tags as successful barcode. Further, these tags were coupled with high-resolution melting (HRM curve analysis in a real-time PCR genotyping method to derive Bar-HRM (Barcoding-HRM assays. Suitable HRM primer sets were designed through SNP detection and mutation scanning in genomic signatures of Senna species. The melting profiles of S. alexandrina and S. italica subsp. micrantha were almost identical and the remaining five species were clearly separated so that they can be differentiated by HRM method. The sensitivity of the method was utilized to authenticate market samples [Herbal Sample Assays (HSAs]. HSA01 (S. alexandrina crude drug sample from Bangalore and HSA06 (S. alexandrina crude drug sample from Tuticorin, Tamil Nadu, India were found to be highly contaminated with S. italica subsp. micrantha. Species admixture samples mixed in varying percentage was identified sensitively with detection of contamination as low as 1%. The melting profiles of PCR amplicons are clearly distinct, which enables the authentic differentiation of species by the HRM method. This study reveals that DNA barcoding coupled with HRM is an efficient molecular tool to authenticate Senna herbal products in the market for quality control in the drug

  2. Candidate DNA Barcode Tags Combined With High Resolution Melting (Bar-HRM) Curve Analysis for Authentication of Senna alexandrina Mill. With Validation in Crude Drugs.

    Science.gov (United States)

    Mishra, Priyanka; Shukla, Ashutosh K; Sundaresan, Velusamy

    2018-01-01

    Senna alexandrina (Fabaceae) is a globally recognized medicinal plant for its laxative properties as well as the only source of sennosides, and is highly exported bulk herb from India. Its major procurement is exclusively from limited cultivation, which leads to risks of deliberate or unintended adulteration. The market raw materials are in powdered or finished product form, which lead to difficulties in authentication. Here, DNA barcode tags based on chloroplast genes ( rbcL and matK ) and intergenic spacers ( psbA-trnH and ITS ) were developed for S. alexandrina along with the allied species. The ability and performance of the ITS1 region to discriminate among the Senna species resulted in the present proposal of the ITS1 tags as successful barcode. Further, these tags were coupled with high-resolution melting (HRM) curve analysis in a real-time PCR genotyping method to derive Bar-HRM (Barcoding-HRM) assays. Suitable HRM primer sets were designed through SNP detection and mutation scanning in genomic signatures of Senna species. The melting profiles of S. alexandrina and S . italica subsp. micrantha were almost identical and the remaining five species were clearly separated so that they can be differentiated by HRM method. The sensitivity of the method was utilized to authenticate market samples [Herbal Sample Assays (HSAs)]. HSA01 ( S. alexandrina crude drug sample from Bangalore) and HSA06 ( S. alexandrina crude drug sample from Tuticorin, Tamil Nadu, India) were found to be highly contaminated with S . italica subsp. micrantha . Species admixture samples mixed in varying percentage was identified sensitively with detection of contamination as low as 1%. The melting profiles of PCR amplicons are clearly distinct, which enables the authentic differentiation of species by the HRM method. This study reveals that DNA barcoding coupled with HRM is an efficient molecular tool to authenticate Senna herbal products in the market for quality control in the drug supply

  3. Combining a nanosensor and ELISA for measurement of tyrosyl-dna phosphodiesterase 1 (tdp1) activity and protein amount in cell and tissue extract

    DEFF Research Database (Denmark)

    Jakobsen, Ann-Katrine; Stougaard, Magnus

    2015-01-01

    be combined with ELISA measurement into one assay facilitating measurement of both the enzymatic activity and the protein amount of TDP1. We show that the combined assay can be used for measurements both in cell line-based studies and for measurement in clinical tissue samples. Due to all measurements being...... performed in the exact same aliquot of cell or tissue extract, the combined assay allows the use of minimal amount of cells or tissue and without additional incubation steps compared to the normal ELISA procedure. Measuring protein amount and activity within the same portion of extract also minimizes...... the risk of variation being introduced when comparing amount to activity. Since the assay only uses small amounts of extract, it requires no advanced equipment besides a plate reader, and can work in whole-cell or tissue extract. We expect that it could be useful for analysis of posttranslational...

  4. Management Control, Intrinsic Motivation and Creativity

    OpenAIRE

    Gregersen, Mikkel Godt

    2017-01-01

    This thesis consists of a cape and three papers. The overall research question is: How can intrinsic motivation and management control coexist in a creative environment and how can coordination be possible in such a context? The cape ties together the research done in the three papers. It is divided into six sections. The first section introduces the concepts of intrinsic motivation, creativity and management control. This is followed by a section on management control in a ...

  5. N-terminal segments modulate the α-helical propensities of the intrinsically disordered basic regions of bZIP proteins.

    Science.gov (United States)

    Das, Rahul K; Crick, Scott L; Pappu, Rohit V

    2012-02-17

    Basic region leucine zippers (bZIPs) are modular transcription factors that play key roles in eukaryotic gene regulation. The basic regions of bZIPs (bZIP-bRs) are necessary and sufficient for DNA binding and specificity. Bioinformatic predictions and spectroscopic studies suggest that unbound monomeric bZIP-bRs are uniformly disordered as isolated domains. Here, we test this assumption through a comparative characterization of conformational ensembles for 15 different bZIP-bRs using a combination of atomistic simulations and circular dichroism measurements. We find that bZIP-bRs have quantifiable preferences for α-helical conformations in their unbound monomeric forms. This helicity varies from one bZIP-bR to another despite a significant sequence similarity of the DNA binding motifs (DBMs). Our analysis reveals that intramolecular interactions between DBMs and eight-residue segments directly N-terminal to DBMs are the primary modulators of bZIP-bR helicities. We test the accuracy of this inference by designing chimeras of bZIP-bRs to have either increased or decreased overall helicities. Our results yield quantitative insights regarding the relationship between sequence and the degree of intrinsic disorder within bZIP-bRs, and might have general implications for other intrinsically disordered proteins. Understanding how natural sequence variations lead to modulation of disorder is likely to be important for understanding the evolution of specificity in molecular recognition through intrinsically disordered regions (IDRs). Copyright © 2011 Elsevier Ltd. All rights reserved.

  6. Refining the intrinsic chimera flap: a review.

    Science.gov (United States)

    Agarwal, Jayant P; Agarwal, Shailesh; Adler, Neta; Gottlieb, Lawrence J

    2009-10-01

    Reconstruction of complex tissue deficiencies in which each missing component is in a different spatial relationship to each other can be particularly challenging, especially in patients with limited recipient vessels. The chimera flap design is uniquely suited to reconstruct these deformities. Chimera flaps have been previously defined in many ways with 2 main categories: prefabricated or intrinsic. Herein we attempt to clarify the definition of a true intrinsic chimeric flap and provide examples of how these constructs provide a method for reconstruction of complex defects. The versatility of the intrinsic chimera flap and its procurement from 7 different vascular systems is described. A clarification of the definition of a true intrinsic chimera flap is described. In addition, construction of flaps from the lateral femoral circumflex, deep circumflex iliac, inferior gluteal, peroneal, subscapular, thoracodorsal, and radial arterial systems is described to showcase the versatility of these chimera flaps. A true intrinsic chimera flap must consist of more than a single tissue type. Each of the tissue components receives its blood flow from separate vascular branches or perforators that are connected to a single vascular source. These vascular branches must be of appropriate length to allow for insetting with 3-dimensional spatial freedom. There are a multitude of sites from which true intrinsic chimera flaps may be harvested.

  7. Incentives and intrinsic motivation in healthcare.

    Science.gov (United States)

    Berdud, Mikel; Cabasés, Juan M; Nieto, Jorge

    It has been established in the literature that workers within public organisations are intrinsically motivated. This paper is an empirical study of the healthcare sector using methods of qualitative analysis research, which aims to answer the following hypotheses: 1) doctors are intrinsically motivated; 2) economic incentives and control policies may undermine doctors' intrinsic motivation; and 3) well-designed incentives may encourage doctors' intrinsic motivation. We conducted semi-structured interviews à-la-Bewley with 16 doctors from Navarre's Healthcare Service (Servicio Navarro de Salud-Osasunbidea), Spain. The questions were based on current theories of intrinsic motivation and incentives to test the hypotheses. Interviewees were allowed to respond openly without time constraints. Relevant information was selected, quantified and analysed by using the qualitative concepts of saturation and codification. The results seem to confirm the hypotheses. Evidence supporting hypotheses 1 and 2 was gathered from all interviewees, as well as indications of the validity of hypothesis 3 based on interviewees' proposals of incentives. The conclusions could act as a guide to support the optimal design of incentive policies and schemes within health organisations when healthcare professionals are intrinsically motivated. Copyright © 2016 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.

  8. The intrinsic resistome of bacterial pathogens.

    Science.gov (United States)

    Olivares, Jorge; Bernardini, Alejandra; Garcia-Leon, Guillermo; Corona, Fernando; B Sanchez, Maria; Martinez, Jose L

    2013-01-01

    Intrinsically resistant bacteria have emerged as a relevant health problem in the last years. Those bacterial species, several of them with an environmental origin, present naturally low-level susceptibility to several drugs. It has been proposed that intrinsic resistance is mainly the consequence of the impermeability of cellular envelopes, the activity of multidrug efflux pumps or the lack of appropriate targets for a given family of drugs. However, recently published articles indicate that the characteristic phenotype of susceptibility to antibiotics of a given bacterial species depends on the concerted activity of several elements, what has been named as intrinsic resistome. These determinants comprise not just classical resistance genes. Other elements, several of them involved in basic bacterial metabolic processes, are of relevance for the intrinsic resistance of bacterial pathogens. In the present review we analyze recent publications on the intrinsic resistomes of Escherichia coli and Pseudomonas aeruginosa. We present as well information on the role that global regulators of bacterial metabolism, as Crc from P. aeruginosa, may have on modulating bacterial susceptibility to antibiotics. Finally, we discuss the possibility of searching inhibitors of the intrinsic resistome in the aim of improving the activity of drugs currently in use for clinical practice.

  9. The intrinsic resistome of bacterial pathogens

    Directory of Open Access Journals (Sweden)

    Jorge Andrés Olivares Pacheco

    2013-04-01

    Full Text Available Intrinsically resistant bacteria have emerged as a relevant health problem in the last years. Those bacterial species, several of them with an environmental origin, present naturally a low-level susceptibility to several drugs. It has been proposed that intrinsic resistance is mainly the consequence of the impermeability of cellular envelopes, the activity of multidrug efflux pumps or the lack of appropriate targets for a given family of drugs. However, recently published articles indicate that the characteristic phenotype of susceptibility to antibiotics of a given bacterial species depends on the concerted activity of several elements, what has been named as intrinsic resistome. These determinants comprise not just classical resistance genes. Other elements, several of them involved in basic bacterial metabolic processes, are of relevance for the intrinsic resistance of bacterial pathogens. In the present review we analyse recent publications on the intrinsic resistomes of Escherichia coli and Pseudomonas aeruginosa. We present as well information on the role that global regulators of bacterial metabolism, as Crc from P. aeruginosa, may have on modulating bacterial susceptibility to antibiotics. Finally, we discuss the possibility of searching inhibitors of the intrinsic resistome in the aim of improving the activity of drugs currently in use for clinical practice.

  10. Intrinsic work function of molecular films

    International Nuclear Information System (INIS)

    Ivančo, Ján

    2012-01-01

    The electronic properties of molecular films are analysed with the consideration of the molecular orientation. The study demonstrates that surfaces of electroactive oligomeric molecular films can be classified—analogously to the elemental surfaces—by their intrinsic work functions. The intrinsic work function of molecular films is correlated with their ionisation energies; again, the behaviour is analogous to the correlation existing between the first ionisation energy of elements and the work function of the corresponding elemental surfaces. The proposed intrinsic work-function concept suggests that the mechanism for the energy-level alignment at the interfaces associated with molecular films is virtually controlled by work functions of materials brought into the contact. - Highlights: ► Molecular films exhibit their own (intrinsic) work function. ► Intrinsic work function is correlated with ionisation energy of molecular films. ► Intrinsic work function determines dipole at interface with a particular surface. ► Surface vacuum-level change upon film growth does not relate to interfacial dipole.

  11. TRX-LOGOS - a graphical tool to demonstrate DNA information content dependent upon backbone dynamics in addition to base sequence.

    Science.gov (United States)

    Fortin, Connor H; Schulze, Katharina V; Babbitt, Gregory A

    2015-01-01

    It is now widely-accepted that DNA sequences defining DNA-protein interactions functionally depend upon local biophysical features of DNA backbone that are important in defining sites of binding interaction in the genome (e.g. DNA shape, charge and intrinsic dynamics). However, these physical features of DNA polymer are not directly apparent when analyzing and viewing Shannon information content calculated at single nucleobases in a traditional sequence logo plot. Thus, sequence logos plots are severely limited in that they convey no explicit information regarding the structural dynamics of DNA backbone, a feature often critical to binding specificity. We present TRX-LOGOS, an R software package and Perl wrapper code that interfaces the JASPAR database for computational regulatory genomics. TRX-LOGOS extends the traditional sequence logo plot to include Shannon information content calculated with regard to the dinucleotide-based BI-BII conformation shifts in phosphate linkages on the DNA backbone, thereby adding a visual measure of intrinsic DNA flexibility that can be critical for many DNA-protein interactions. TRX-LOGOS is available as an R graphics module offered at both SourceForge and as a download supplement at this journal. To demonstrate the general utility of TRX logo plots, we first calculated the information content for 416 Saccharomyces cerevisiae transcription factor binding sites functionally confirmed in the Yeastract database and matched to previously published yeast genomic alignments. We discovered that flanking regions contain significantly elevated information content at phosphate linkages than can be observed at nucleobases. We also examined broader transcription factor classifications defined by the JASPAR database, and discovered that many general signatures of transcription factor binding are locally more information rich at the level of DNA backbone dynamics than nucleobase sequence. We used TRX-logos in combination with MEGA 6.0 software

  12. The effects of X-irradiation, N-ethyl-N-nitrosourea or combined treatment on O6-alkylguanine-DNA alkyltransferase activity in fetal rat brain and liver and the induction of CNS tumours

    International Nuclear Information System (INIS)

    Stammberger, I.; Nice, L.; Schmahl, W.

    1990-01-01

    Wistar rats were treated in utero on day 16 of gestation either by X-irradiation, N-ethyl-N-nitrosourea (ENU), or both in combination. The O 6 -alkylguanine-DNA alkyltransferase (AT) activity of the fetal brain and liver was analyzed and long-term observations were made to reveal any relationship between the O 6 -ethylguanine repair capability and tumour incidence in the organs of the offspring. The AT activity in the brain was affected to the same extent in the fetuses as in the dams. There was a 60.9% decrease in AT activity in fetuses 24 h after ENU treatment. This correlates with a significant increase in the incidence of brain tumours in the treated offspring (44.1%) compared to control animals. The inductive effect of X-irradiation on AT activity corresponded in turn with a reduction of the incidence of tumours after the combined treatment. In the liver of the rat fetuses, there was generally no effect of treatment on AT activity in contrast to the results obtained for the dams, where an increased AT activity was observed. There were no tumours of the liver observed in the offspring after either treatment alone or after combined treatment. It is suggested that the combined treatment of rat fetuses could significantly reduce the incidence of brain tumours in adult life. (author)

  13. The effects of X-irradiation, N-ethyl-N-nitrosourea or combined treatment on O sup 6 -alkylguanine-DNA alkyltransferase activity in fetal rat brain and liver and the induction of CNS tumours

    Energy Technology Data Exchange (ETDEWEB)

    Stammberger, I.; Nice, L. (Muenchen Univ. (Germany, F.R.). Walter-Straub-Institut fuer Pharmakologie und Toxikologie); Schmahl, W. (Gesellschaft fuer Strahlen- und Umweltforschung mbH Muenchen, Neuherberg (Germany, F.R.). Inst. fuer Pathologie)

    1990-02-01

    Wistar rats were treated in utero on day 16 of gestation either by X-irradiation, N-ethyl-N-nitrosourea (ENU), or both in combination. The O{sup 6}-alkylguanine-DNA alkyltransferase (AT) activity of the fetal brain and liver was analyzed and long-term observations were made to reveal any relationship between the O{sup 6}-ethylguanine repair capability and tumour incidence in the organs of the offspring. The AT activity in the brain was affected to the same extent in the fetuses as in the dams. There was a 60.9% decrease in AT activity in fetuses 24 h after ENU treatment. This correlates with a significant increase in the incidence of brain tumours in the treated offspring (44.1%) compared to control animals. The inductive effect of X-irradiation on AT activity corresponded in turn with a reduction of the incidence of tumours after the combined treatment. In the liver of the rat fetuses, there was generally no effect of treatment on AT activity in contrast to the results obtained for the dams, where an increased AT activity was observed. There were no tumours of the liver observed in the offspring after either treatment alone or after combined treatment. It is suggested that the combined treatment of rat fetuses could significantly reduce the incidence of brain tumours in adult life. (author).

  14. DNA-Controlled Assembly of Soft Nanoparticles

    DEFF Research Database (Denmark)

    Vogel, Stefan

    2015-01-01

    This book covers the emerging topic of DNA nanotechnology and DNA supramolecular chemistry in its broader sense. By taking DNA out of its biological role, this biomolecule has become a very versatile building block in materials chemistry, supramolecular chemistry and bio-nanotechnology. Many nove......-covalent systems, DNA origami, DNA based switches, DNA machines, and alternative structures and templates. This broad coverage is very appealing since it combines both the synthesis of modified DNA as well as designer concepts to successfully plan and make DNA nanostructures....

  15. Phylogenetics of tribe Orchideae (Orchidaceae: Orchidoideae) based on combined DNA matrices: inferences regarding timing of diversification and evolution of pollination syndromes.

    Science.gov (United States)

    Inda, Luis A; Pimentel, Manuel; Chase, Mark W

    2012-07-01

    Tribe Orchideae (Orchidaceae: Orchidoideae) comprises around 62 mostly terrestrial genera, which are well represented in the Northern Temperate Zone and less frequently in tropical areas of both the Old and New Worlds. Phylogenetic relationships within this tribe have been studied previously using only nuclear ribosomal DNA (nuclear ribosomal internal transcribed spacer, nrITS). However, different parts of the phylogenetic tree in these analyses were weakly supported, and integrating information from different plant genomes is clearly necessary in orchids, where reticulate evolution events are putatively common. The aims of this study were to: (1) obtain a well-supported and dated phylogenetic hypothesis for tribe Orchideae, (ii) assess appropriateness of recent nomenclatural changes in this tribe in the last decade, (3) detect possible examples of reticulate evolution and (4) analyse in a temporal context evolutionary trends for subtribe Orchidinae with special emphasis on pollination systems. The analyses included 118 samples, belonging to 103 species and 25 genera, for three DNA regions (nrITS, mitochondrial cox1 intron and plastid rpl16 intron). Bayesian and maximum-parsimony methods were used to construct a well-supported and dated tree. Evolutionary trends in the subtribe were analysed using Bayesian and maximum-likelihood methods of character evolution. The dated phylogenetic tree strongly supported the recently recircumscribed generic concepts of Bateman and collaborators. Moreover, it was found that Orchidinae have diversified in the Mediterranean basin during the last 15 million years, and one potential example of reticulate evolution in the subtribe was identified. In Orchidinae, pollination systems have shifted on numerous occasions during the last 23 million years. The results indicate that ancestral Orchidinae were hymenopteran-pollinated, food-deceptive plants and that these traits have been dominant throughout the evolutionary history of the

  16. DNA replication stress restricts ribosomal DNA copy number

    Science.gov (United States)

    Salim, Devika; Bradford, William D.; Freeland, Amy; Cady, Gillian; Wang, Jianmin

    2017-01-01

    Ribosomal RNAs (rRNAs) in budding yeast are encoded by ~100–200 repeats of a 9.1kb sequence arranged in tandem on chromosome XII, the ribosomal DNA (rDNA) locus. Copy number of rDNA repeat units in eukaryotic cells is maintained far in excess of the requirement for ribosome biogenesis. Despite the importance of the repeats for both ribosomal and non-ribosomal functions, it is currently not known how “normal” copy number is determined or maintained. To identify essential genes involved in the maintenance of rDNA copy number, we developed a droplet digital PCR based assay to measure rDNA copy number in yeast and used it to screen a yeast conditional temperature-sensitive mutant collection of essential genes. Our screen revealed that low rDNA copy number is associated with compromised DNA replication. Further, subculturing yeast under two separate conditions of DNA replication stress selected for a contraction of the rDNA array independent of the replication fork blocking protein, Fob1. Interestingly, cells with a contracted array grew better than their counterparts with normal copy number under conditions of DNA replication stress. Our data indicate that DNA replication stresses select for a smaller rDNA array. We speculate that this liberates scarce replication factors for use by the rest of the genome, which in turn helps cells complete DNA replication and continue to propagate. Interestingly, tumors from mini chromosome maintenance 2 (MCM2)-deficient mice also show a loss of rDNA repeats. Our data suggest that a reduction in rDNA copy number may indicate a history of DNA replication stress, and that rDNA array size could serve as a diagnostic marker for replication stress. Taken together, these data begin to suggest the selective pressures that combine to yield a “normal” rDNA copy number. PMID:28915237

  17. DNA replication stress restricts ribosomal DNA copy number.

    Science.gov (United States)

    Salim, Devika; Bradford, William D; Freeland, Amy; Cady, Gillian; Wang, Jianmin; Pruitt, Steven C; Gerton, Jennifer L

    2017-09-01

    Ribosomal RNAs (rRNAs) in budding yeast are encoded by ~100-200 repeats of a 9.1kb sequence arranged in tandem on chromosome XII, the ribosomal DNA (rDNA) locus. Copy number of rDNA repeat units in eukaryotic cells is maintained far in excess of the requirement for ribosome biogenesis. Despite the importance of the repeats for both ribosomal and non-ribosomal functions, it is currently not known how "normal" copy number is determined or maintained. To identify essential genes involved in the maintenance of rDNA copy number, we developed a droplet digital PCR based assay to measure rDNA copy number in yeast and used it to screen a yeast conditional temperature-sensitive mutant collection of essential genes. Our screen revealed that low rDNA copy number is associated with compromised DNA replication. Further, subculturing yeast under two separate conditions of DNA replication stress selected for a contraction of the rDNA array independent of the replication fork blocking protein, Fob1. Interestingly, cells with a contracted array grew better than their counterparts with normal copy number under conditions of DNA replication stress. Our data indicate that DNA replication stresses select for a smaller rDNA array. We speculate that this liberates scarce replication factors for use by the rest of the genome, which in turn helps cells complete DNA replication and continue to propagate. Interestingly, tumors from mini chromosome maintenance 2 (MCM2)-deficient mice also show a loss of rDNA repeats. Our data suggest that a reduction in rDNA copy number may indicate a history of DNA replication stress, and that rDNA array size could serve as a diagnostic marker for replication stress. Taken together, these data begin to suggest the selective pressures that combine to yield a "normal" rDNA copy number.

  18. DNA replication stress restricts ribosomal DNA copy number.

    Directory of Open Access Journals (Sweden)

    Devika Salim

    2017-09-01

    Full Text Available Ribosomal RNAs (rRNAs in budding yeast are encoded by ~100-200 repeats of a 9.1kb sequence arranged in tandem on chromosome XII, the ribosomal DNA (rDNA locus. Copy number of rDNA repeat units in eukaryotic cells is maintained far in excess of the requirement for ribosome biogenesis. Despite the importance of the repeats for both ribosomal and non-ribosomal functions, it is currently not known how "normal" copy number is determined or maintained. To identify essential genes involved in the maintenance of rDNA copy number, we developed a droplet digital PCR based assay to measure rDNA copy number in yeast and used it to screen a yeast conditional temperature-sensitive mutant collection of essential genes. Our screen revealed that low rDNA copy number is associated with compromised DNA replication. Further, subculturing yeast under two separate conditions of DNA replication stress selected for a contraction of the rDNA array independent of the replication fork blocking protein, Fob1. Interestingly, cells with a contracted array grew better than their counterparts with normal copy number under conditions of DNA replication stress. Our data indicate that DNA replication stresses select for a smaller rDNA array. We speculate that this liberates scarce replication factors for use by the rest of the genome, which in turn helps cells complete DNA replication and continue to propagate. Interestingly, tumors from mini chromosome maintenance 2 (MCM2-deficient mice also show a loss of rDNA repeats. Our data suggest that a reduction in rDNA copy number may indicate a history of DNA replication stress, and that rDNA array size could serve as a diagnostic marker for replication stress. Taken together, these data begin to suggest the selective pressures that combine to yield a "normal" rDNA copy number.

  19. Stochastic synchronization of neuronal populations with intrinsic and extrinsic noise.

    KAUST Repository

    Bressloff, Paul C

    2011-05-03

    We extend the theory of noise-induced phase synchronization to the case of a neural master equation describing the stochastic dynamics of an ensemble of uncoupled neuronal population oscillators with intrinsic and extrinsic noise. The master equation formulation of stochastic neurodynamics represents the state of each population by the number of currently active neurons, and the state transitions are chosen so that deterministic Wilson-Cowan rate equations are recovered in the mean-field limit. We apply phase reduction and averaging methods to a corresponding Langevin approximation of the master equation in order to determine how intrinsic noise disrupts synchronization of the population oscillators driven by a common extrinsic noise source. We illustrate our analysis by considering one of the simplest networks known to generate limit cycle oscillations at the population level, namely, a pair of mutually coupled excitatory (E) and inhibitory (I) subpopulations. We show how the combination of intrinsic independent noise and extrinsic common noise can lead to clustering of the population oscillators due to the multiplicative nature of both noise sources under the Langevin approximation. Finally, we show how a similar analysis can be carried out for another simple population model that exhibits limit cycle oscillations in the deterministic limit, namely, a recurrent excitatory network with synaptic depression; inclusion of synaptic depression into the neural master equation now generates a stochastic hybrid system.

  20. Development of species-specific rDNA probes for Giardia by multiple fluorescent in situ hybridization combined with immunocytochemical identification of cyst wall antigens.

    Science.gov (United States)

    Erlandsen, Stanley L; Jarroll, Edward; Wallis, Peter; van Keulen, Harry

    2005-08-01

    In this study, we describe the development of fluorescent oligonucleotide probes to variable regions in the small subunit of 16S rRNA in three distinct Giardia species. Sense and antisense probes (17-22 mer) to variable regions 1, 3, and 8 were labeled with digoxygenin or selected fluorochomes (FluorX, Cy3, or Cy5). Optimal results were obtained with fluorochome-labeled oligonucleotides for detection of rRNA in Giardia cysts. Specificity of fluorescent in situ hybridization (FISH) was shown using RNase digestion and high stringency to diminish the hybridization signal, and oligonucleotide probes for rRNA in Giardia lamblia, Giardia muris, and Giardia ardeae were shown to specifically stain rRNA only within cysts or trophozoites of those species. The fluorescent oligonucleotide specific for rRNA in human isolates of Giardia was positive for ten different strains. A method for simultaneous FISH detection of cysts using fluorescent antibody (genotype marker) and two oligonucleotide probes (species marker) permitted visualization of G. lamblia and G. muris cysts in the same preparation. Testing of an environmental water sample revealed the presence of FISH-positive G. lamblia cysts with a specific rDNA probe for rRNA, while negative cysts were presumed to be of animal or bird origin.

  1. Function and regulation of plant major intrinsic proteins

    DEFF Research Database (Denmark)

    Popovic, Milan

    ;1 in Arabidopsis. That led to the discovery that tip4;1 is gametophytic lethal- gene essential for normal seed set. ICP-MS analyses of the elemental composition of tip4;1 heterozygous T-DNA insert mutant plants and 35S::TIP4;1 over-expression plants indicate that AtTIP4;1 has a role in arsenic distribution...... inorganic forms of arsenic in the environment, can be taken up by plants and thus enter the food chain. Once inside the root cells, As(V) is reduced to As(III) which is then extruded to the soil solution or bound to phytochelatins (PCs) and transported to the vacuole in an effort to accomplish...... detoxification. Plant Noduline 26-like Intrinsic Proteins (NIPs) can channel As(III) and consequently influence the detoxification process. The role of the Tonoplast Intrinsic Proteins (TIPs) in As(III) detoxification remains to be clarified, yet TIPs could have an impact on As(III) accumulation in plant cell...

  2. DNA damage-induced inflammation and nuclear architecture.

    Science.gov (United States)

    Stratigi, Kalliopi; Chatzidoukaki, Ourania; Garinis, George A

    2017-07-01

    Nuclear architecture and the chromatin state affect most-if not all- DNA-dependent transactions, including the ability of cells to sense DNA lesions and restore damaged DNA back to its native form. Recent evidence points to functional links between DNA damage sensors, DNA repair mechanisms and the innate immune responses. The latter raises the question of how such seemingly disparate processes operate within the intrinsically complex nuclear landscape and the chromatin environment. Here, we discuss how DNA damage-induced immune responses operate within chromatin and the distinct sub-nuclear compartments highlighting their relevance to chronic inflammation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. The Intrinsic Far-infrared Continua of Type-1 Quasars

    Energy Technology Data Exchange (ETDEWEB)

    Lyu, Jianwei; Rieke, George H., E-mail: jianwei@email.arizona.edu [Steward Observatory, University of Arizona, 933 North Cherry Avenue, Tucson, AZ 85721 (United States)

    2017-06-01

    The range of currently proposed active galactic nucleus (AGN) far-infrared templates results in uncertainties in retrieving host galaxy information from infrared observations and also undermines constraints on the outer part of the AGN torus. We discuss how to test and reconcile these templates. Physically, the fraction of the intrinsic AGN IR-processed luminosity compared with that from the central engine should be consistent with the dust-covering factor. In addition, besides reproducing the composite spectral energy distributions (SEDs) of quasars, a correct AGN IR template combined with an accurate library of star-forming galaxy templates should be able to reproduce the IR properties of the host galaxies, such as the luminosity-dependent SED shapes and aromatic feature strengths. We develop tests based on these expected behaviors and find that the shape of the AGN intrinsic far-IR emission drops off rapidly starting at ∼20 μ m and can be matched by an Elvis et al.-like template with a minor modification. Despite the variations in the near- to mid-IR bands, AGNs in quasars and Seyfert galaxies have remarkably similar intrinsic far-IR SEDs at λ ∼ 20–100 μ m, suggesting a similar emission character of the outermost region of the circumnuclear torus. The variations of the intrinsic AGN IR SEDs among the type-1 quasar population can be explained by the changing relative strengths of four major dust components with similar characteristic temperatures, and there is evidence for compact AGN-heated dusty structures at sub-kiloparsec scales in the far-IR.

  4. Ecological Divergence and the Origins of Intrinsic Postmating Isolation with Gene Flow

    Directory of Open Access Journals (Sweden)

    Aneil F. Agrawal

    2011-01-01

    Full Text Available The evolution of intrinsic postmating isolation has received much attention, both historically and in recent studies of speciation genes. Intrinsic isolation often stems from between-locus genetic incompatibilities, where alleles that function well within species are incompatible with one another when brought together in the genome of a hybrid. It can be difficult for such incompatibilities to originate when populations diverge with gene flow, because deleterious genotypic combinations will be created and then purged by selection. However, it has been argued that if genes underlying incompatibilities are themselves subject to divergent selection, then they might overcome gene flow to diverge between populations, resulting in the origin of incompatibilities. Nonetheless, there has been little explicit mathematical exploration of such scenarios for the origin of intrinsic incompatibilities during ecological speciation with gene flow. Here we explore theoretical models for the origin of intrinsic isolation where genes subject to divergent natural selection also affect intrinsic isolation, either directly or via linkage disequilibrium with other loci. Such genes indeed overcome gene flow, diverge between populations, and thus result in the evolution of intrinsic isolation. We also examine barriers to neutral gene flow. Surprisingly, we find that intrinsic isolation sometimes weakens this barrier, by impeding differentiation via ecologically based divergent selection.

  5. Potential New Therapies for Pediatric Diffuse Intrinsic Pontine Glioma

    Directory of Open Access Journals (Sweden)

    Wenyong Long

    2017-07-01

    Full Text Available Diffuse intrinsic pontine glioma (DIPG is an extensively invasive malignancy with infiltration into other regions of the brainstem. Although large numbers of specific targeted therapies have been tested, no significant progress has been made in treating these high-grade gliomas. Therefore, the identification of new therapeutic approaches is of great importance for the development of more effective treatments. This article reviews the conventional therapies and new potential therapeutic approaches for DIPG, including epigenetic therapy, immunotherapy, and the combination of stem cells with nanoparticle delivery systems.

  6. A new method for species identification via protein-coding and non-coding DNA barcodes by combining machine learning with bioinformatic methods.

    Directory of Open Access Journals (Sweden)

    Ai-bing Zhang

    Full Text Available Species identification via DNA barcodes is contributing greatly to current bioinventory efforts. The initial, and widely accepted, proposal was to use the protein-coding cytochrome c oxidase subunit I (COI region as the standard barcode for animals, but recently non-coding internal transcribed spacer (ITS genes have been proposed as candidate barcodes for both animals and plants. However, achieving a robust alignment for non-coding regions can be problematic. Here we propose two new methods (DV-RBF and FJ-RBF to address this issue for species assignment by both coding and non-coding sequences that take advantage of the power of machine learning and bioinformatics. We demonstrate the value of the new methods with four empirical datasets, two representing typical protein-coding COI barcode datasets (neotropical bats and marine fish and two representing non-coding ITS barcodes (rust fungi and brown algae. Using two random sub-sampling approaches, we demonstrate that the new methods significantly outperformed existing Neighbor-joining (NJ and Maximum likelihood (ML methods for both coding and non-coding barcodes when there was complete species coverage in the reference dataset. The new methods also out-performed NJ and ML methods for non-coding sequences in circumstances of potentially incomplete species coverage, although then the NJ and ML methods performed slightly better than the new methods for protein-coding barcodes. A 100% success rate of species identification was achieved with the two new methods for 4,122 bat queries and 5,134 fish queries using COI barcodes, with 95% confidence intervals (CI of 99.75-100%. The new methods also obtained a 96.29% success rate (95%CI: 91.62-98.40% for 484 rust fungi queries and a 98.50% success rate (95%CI: 96.60-99.37% for 1094 brown algae queries, both using ITS barcodes.

  7. A new method for species identification via protein-coding and non-coding DNA barcodes by combining machine learning with bioinformatic methods.

    Science.gov (United States)

    Zhang, Ai-bing; Feng, Jie; Ward, Robert D; Wan, Ping; Gao, Qiang; Wu, Jun; Zhao, Wei-zhong

    2012-01-01

    Species identification via DNA barcodes is contributing greatly to current bioinventory efforts. The initial, and widely accepted, proposal was to use the protein-coding cytochrome c oxidase subunit I (COI) region as the standard barcode for animals, but recently non-coding internal transcribed spacer (ITS) genes have been proposed as candidate barcodes for both animals and plants. However, achieving a robust alignment for non-coding regions can be problematic. Here we propose two new methods (DV-RBF and FJ-RBF) to address this issue for species assignment by both coding and non-coding sequences that take advantage of the power of machine learning and bioinformatics. We demonstrate the value of the new methods with four empirical datasets, two representing typical protein-coding COI barcode datasets (neotropical bats and marine fish) and two representing non-coding ITS barcodes (rust fungi and brown algae). Using two random sub-sampling approaches, we demonstrate that the new methods significantly outperformed existing Neighbor-joining (NJ) and Maximum likelihood (ML) methods for both coding and non-coding barcodes when there was complete species coverage in the reference dataset. The new methods also out-performed NJ and ML methods for non-coding sequences in circumstances of potentially incomplete species coverage, although then the NJ and ML methods performed slightly better than the new methods for protein-coding barcodes. A 100% success rate of species identification was achieved with the two new methods for 4,122 bat queries and 5,134 fish queries using COI barcodes, with 95% confidence intervals (CI) of 99.75-100%. The new methods also obtained a 96.29% success rate (95%CI: 91.62-98.40%) for 484 rust fungi queries and a 98.50% success rate (95%CI: 96.60-99.37%) for 1094 brown algae queries, both using ITS barcodes.

  8. Intrinsic and Extrinsic Neuromodulation of Olfactory Processing.

    Science.gov (United States)

    Lizbinski, Kristyn M; Dacks, Andrew M

    2017-01-01

    Neuromodulation is a ubiquitous feature of neural systems, allowing flexible, context specific control over network dynamics. Neuromodulation was first described in invertebrate motor systems and early work established a basic dichotomy for neuromodulation as having either an intrinsic origin (i.e., neurons that participate in network coding) or an extrinsic origin (i.e., neurons from independent networks). In this conceptual dichotomy, intrinsic sources of neuromodulation provide a "memory" by adjusting network dynamics based upon previous and ongoing activation of the network itself, while extrinsic neuromodulators provide the context of ongoing activity of other neural networks. Although this dichotomy has been thoroughly considered in motor systems, it has received far less attention in sensory systems. In this review, we discuss intrinsic and extrinsic modulation in the context of olfactory processing in invertebrate and vertebrate model systems. We begin by discussing presynaptic modulation of olfactory sensory neurons by local interneurons (LNs) as a mechanism for gain control based on ongoing network activation. We then discuss the cell-class specific effects of serotonergic centrifugal neurons on olfactory processing. Finally, we briefly discuss the integration of intrinsic and extrinsic neuromodulation (metamodulation) as an effective mechanism for exerting global control over olfactory network dynamics. The heterogeneous nature of neuromodulation is a recurring theme throughout this review as the effects of both intrinsic and extrinsic modulation are generally non-uniform.

  9. Hidden Structural Codes in Protein Intrinsic Disorder.

    Science.gov (United States)

    Borkosky, Silvia S; Camporeale, Gabriela; Chemes, Lucía B; Risso, Marikena; Noval, María Gabriela; Sánchez, Ignacio E; Alonso, Leonardo G; de Prat Gay, Gonzalo

    2017-10-17

    Intrinsic disorder is a major structural category in biology, accounting for more than 30% of coding regions across the domains of life, yet consists of conformational ensembles in equilibrium, a major challenge in protein chemistry. Anciently evolved papillomavirus genomes constitute an unparalleled case for sequence to structure-function correlation in cases in which there are no folded structures. E7, the major transforming oncoprotein of human papillomaviruses, is a paradigmatic example among the intrinsically disordered proteins. Analysis of a large number of sequences of the same viral protein allowed for the identification of a handful of residues with absolute conservation, scattered along the sequence of its N-terminal intrinsically disordered domain, which intriguingly are mostly leucine residues. Mutation of these led to a pronounced increase in both α-helix and β-sheet structural content, reflected by drastic effects on equilibrium propensities and oligomerization kinetics, and uncovers the existence of local structural elements that oppose canonical folding. These folding relays suggest the existence of yet undefined hidden structural codes behind intrinsic disorder in this model protein. Thus, evolution pinpoints conformational hot spots that could have not been identified by direct experimental methods for analyzing or perturbing the equilibrium of an intrinsically disordered protein ensemble.

  10. Intrinsic-extrinsic factors in sport motivation.

    Science.gov (United States)

    Pedersen, Darhl M

    2002-10-01

    Participants were 83 students (36 men and 47 women). 10 intrinsic-extrinsic factors involved in sport motivation were obtained. The factors were generated from items obtained from the participants rather than items from the experimenter. This was done to avoid the possible influence of preconceptions on the part of the experimenter regarding what the final dimensions may be. Obtained motivational factors were Social Reinforcement, Fringe Benefits, Fame and Fortune, External Forces, Proving Oneself, Social Benefits, Mental Enrichment, Expression of Self, Sense of Accomplishment, and Self-enhancement. Each factor was referred to an intrinsic-extrinsic dimension to describe its relative position on that dimension. The order of the factors as listed indicates increasing intrinsic motivation. i.e., the first four factors were rated in the extrinsic range, whereas the remaining six were rated to be in the intrinsic range. Next, the participants rated the extent to which each of the various factors was involved in their decision to participate in sport activities. The pattern of use of the motivational factors was the same for both sexes except that men indicated greater use of the Fringe Benefits factor. Overall, the more intrinsic a sport motivation factor was rated, the more likely it was to be rated as a factor in actual sport participation.

  11. Modeling DNA

    Science.gov (United States)

    Robertson, Carol

    2016-01-01

    Deoxyribonucleic acid (DNA) is life's most amazing molecule. It carries the genetic instructions that almost every organism needs to develop and reproduce. In the human genome alone, there are some three billion DNA base pairs. The most difficult part of teaching DNA structure, however, may be getting students to visualize something as small as a…

  12. The interactive roles of mastery climate and performance climate in predicting intrinsic motivation.

    Science.gov (United States)

    Buch, R; Nerstad, C G L; Säfvenbom, R

    2017-02-01

    This study examined the interplay between perceived mastery and performance climates in predicting increased intrinsic motivation. The results of a two-wave longitudinal study comprising of 141 individuals from three military academies revealed a positive relationship between a perceived mastery climate and increased intrinsic motivation only for individuals who perceived a low performance climate. This finding suggests a positive relationship between a perceived mastery climate and increased intrinsic motivation only when combined with low perceptions of a performance climate. Hence, introducing a performance climate in addition to a mastery climate can be an undermining motivational strategy, as it attenuates the positive relationship between a mastery climate and increased intrinsic motivation. Implications for future research and practice are discussed. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Genome-Wide Prediction of Intrinsic Disorder; Sequence Alignment of Intrinsically Disordered Proteins

    Science.gov (United States)

    Midic, Uros

    2012-01-01

    Intrinsic disorder (ID) is defined as a lack of stable tertiary and/or secondary structure under physiological conditions in vitro. Intrinsically disordered proteins (IDPs) are highly abundant in nature. IDPs possess a number of crucial biological functions, being involved in regulation, recognition, signaling and control, e.g. their functional…

  14. Flavor Structure of Intrinsic Nucleon Sea

    International Nuclear Information System (INIS)

    Peng, Jen-Chieh; Chang, Wen-Chen; Cheng, Hai-Yang; Liu, Keh-Fei

    2015-01-01

    The concept of intrinsic charm suggested by Brodsky et al. is extended to lighter quarks. Extraction of the intrinsic ū, d-macron, and s-macron seas is obtained from an analysis of the d-macron − ū, s + s-macron, and ū + d-macron − s −s-macron distributions. The connection between the intrinsic/extrinsic seas and the connected/disconnected seas in lattice QCD is also examined. It is shown that the connected and disconnected components for the ū(x) + d-macron(x) sea can be separated. The striking x-dependence of the [s(x) + s-macron(x)]/[ū(x) + d-macron(x)] ratio is interpreted as an interplay between the connected and disconnected seas. (author)

  15. Management Control, Intrinsic Motivation and Creativity

    DEFF Research Database (Denmark)

    Godt Gregersen, Mikkel

    This thesis consists of a cape and three papers. The overall research question is: How can intrinsic motivation and management control coexist in a creative environment and how can coordination be possible in such a context? The cape ties together the research done in the three papers....... It is divided into six sections. The first section introduces the concepts of intrinsic motivation, creativity and management control. This is followed by a section on management control in a creative context. These two sections frame the thesis and introduce the setting in which the research has been done...... of the conclusion is that intrinsic motivation and management control can coexist under the conditions that all three basic needs, i.e. autonomy, competence and relatedness, are supported. This can happen when control takes point of departure in the individual employee. The second part of the conclusion...

  16. Multiple structure-intrinsic disorder interactions regulate and coordinate Hox protein function

    Science.gov (United States)

    Bondos, Sarah

    During animal development, Hox transcription factors determine fate of developing tissues to generate diverse organs and appendages. Hox proteins are famous for their bizarre mutant phenotypes, such as replacing antennae with legs. Clearly, the functions of individual Hox proteins must be distinct and reliable in vivo, or the organism risks malformation or death. However, within the Hox protein family, the DNA-binding homeodomains are highly conserved and the amino acids that contact DNA are nearly invariant. These observations raise the question: How do different Hox proteins correctly identify their distinct target genes using a common DNA binding domain? One possible means to modulate DNA binding is through the influence of the non-homeodomain protein regions, which differ significantly among Hox proteins. However genetic approaches never detected intra-protein interactions, and early biochemical attempts were hindered because the special features of ``intrinsically disordered'' sequences were not appreciated. We propose the first-ever structural model of a Hox protein to explain how specific contacts between distant, intrinsically disordered regions of the protein and the homeodomain regulate DNA binding and coordinate this activity with other Hox molecular functions.

  17. A model of intrinsic symmetry breaking

    International Nuclear Information System (INIS)

    Ge, Li; Li, Sheng; George, Thomas F.; Sun, Xin

    2013-01-01

    Different from the symmetry breaking associated with a phase transition, which occurs when the controlling parameter is manipulated across a critical point, the symmetry breaking presented in this Letter does not need parameter manipulation. Instead, the system itself suddenly undergoes symmetry breaking at a certain time during its evolution, which is intrinsic symmetry breaking. Through a polymer model, it is revealed that the origin of the intrinsic symmetry breaking is nonlinearity, which produces instability at the instance when the evolution crosses an inflexion point, where this instability breaks the original symmetry

  18. Intrinsic viscosity of a suspension of cubes

    KAUST Repository

    Mallavajula, Rajesh K.

    2013-11-06

    We report on the viscosity of a dilute suspension of cube-shaped particles. Irrespective of the particle size, size distribution, and surface chemistry, we find empirically that cubes manifest an intrinsic viscosity [η]=3.1±0.2, which is substantially higher than the well-known value for spheres, [η]=2.5. The orientation-dependent intrinsic viscosity of cubic particles is determined theoretically using a finite-element solution of the Stokes equations. For isotropically oriented cubes, these calculations show [η]=3.1, in excellent agreement with our experimental observations. © 2013 American Physical Society.

  19. Identification of Inhibitors of Biological Interactions Involving Intrinsically Disordered Proteins

    Directory of Open Access Journals (Sweden)

    Daniela Marasco

    2015-04-01

    Full Text Available Protein–protein interactions involving disordered partners have unique features and represent prominent targets in drug discovery processes. Intrinsically Disordered Proteins (IDPs are involved in cellular regulation, signaling and control: they bind to multiple partners and these high-specificity/low-affinity interactions play crucial roles in many human diseases. Disordered regions, terminal tails and flexible linkers are particularly abundant in DNA-binding proteins and play crucial roles in the affinity and specificity of DNA recognizing processes. Protein complexes involving IDPs are short-lived and typically involve short amino acid stretches bearing few “hot spots”, thus the identification of molecules able to modulate them can produce important lead compounds: in this scenario peptides and/or peptidomimetics, deriving from structure-based, combinatorial or protein dissection approaches, can play a key role as hit compounds. Here, we propose a panoramic review of the structural features of IDPs and how they regulate molecular recognition mechanisms focusing attention on recently reported drug-design strategies in the field of IDPs.

  20. Fanconi anemia complementation group A (FANCA) protein has intrinsic affinity for nucleic acids with preference for single-stranded forms.

    Science.gov (United States)

    Yuan, Fenghua; Qian, Liangyue; Zhao, Xinliang; Liu, Jesse Y; Song, Limin; D'Urso, Gennaro; Jain, Chaitanya; Zhang, Yanbin

    2012-02-10

    The Fanconi anemia complementation group A (FANCA) gene is one of 15 disease-causing genes and has been found to be mutated in ∼60% of Fanconi anemia patients. Using purified protein, we report that human FANCA has intrinsic affinity for nucleic acids. FANCA binds to both single-stranded (ssDNA) and double-stranded (dsDNA) DNAs; however, its affinity for ssDNA is significantly higher than for dsDNA in an electrophoretic mobility shift assay. FANCA also binds to RNA with an intriguingly higher affinity than its DNA counterpart. FANCA requires a certain length of nucleic acids for optimal binding. Using DNA and RNA ladders, we determined that the minimum number of nucleotides required for FANCA recognition is ∼30 for both DNA and RNA. By testing the affinity between FANCA and a variety of DNA structures, we found that a 5'-flap or 5'-tail on DNA facilitates its interaction with FANCA. A patient-derived FANCA truncation mutant (Q772X) has diminished affinity for both DNA and RNA. In contrast, the complementing C-terminal fragment of Q772X, C772-1455, retains the differentiated nucleic acid-binding activity (RNA > ssDNA > dsDNA), indicating that the nucleic acid-binding domain of FANCA is located primarily at its C terminus, where most disease-causing mutations are found.

  1. Fanconi Anemia Complementation Group A (FANCA) Protein Has Intrinsic Affinity for Nucleic Acids with Preference for Single-stranded Forms*

    Science.gov (United States)

    Yuan, Fenghua; Qian, Liangyue; Zhao, Xinliang; Liu, Jesse Y.; Song, Limin; D'Urso, Gennaro; Jain, Chaitanya; Zhang, Yanbin

    2012-01-01

    The Fanconi anemia complementation group A (FANCA) gene is one of 15 disease-causing genes and has been found to be mutated in ∼60% of Fanconi anemia patients. Using purified protein, we report that human FANCA has intrinsic affinity for nucleic acids. FANCA binds to both single-stranded (ssDNA) and double-stranded (dsDNA) DNAs; however, its affinity for ssDNA is significantly higher than for dsDNA in an electrophoretic mobility shift assay. FANCA also binds to RNA with an intriguingly higher affinity than its DNA counterpart. FANCA requires a certain length of nucleic acids for optimal binding. Using DNA and RNA ladders, we determined that the minimum number of nucleotides required for FANCA recognition is ∼30 for both DNA and RNA. By testing the affinity between FANCA and a variety of DNA structures, we found that a 5′-flap or 5′-tail on DNA facilitates its interaction with FANCA. A patient-derived FANCA truncation mutant (Q772X) has diminished affinity for both DNA and RNA. In contrast, the complementing C-terminal fragment of Q772X, C772–1455, retains the differentiated nucleic acid-binding activity (RNA > ssDNA > dsDNA), indicating that the nucleic acid-binding domain of FANCA is located primarily at its C terminus, where most disease-causing mutations are found. PMID:22194614

  2. Studying DNA looping by single-molecule FRET.

    Science.gov (United States)

    Le, Tung T; Kim, Harold D

    2014-06-28

    Bending of double-stranded DNA (dsDNA) is associated with many important biological processes such as DNA-protein recognition and DNA packaging into nucleosomes. Thermodynamics of dsDNA bending has been studied by a method called cyclization which relies on DNA ligase to covalently join short sticky ends of a dsDNA. However, ligation efficiency can be affected by many factors that are not related to dsDNA looping such as the DNA structure surrounding the joined sticky ends, and ligase can also affect the apparent looping rate through mechanisms such as nonspecific binding. Here, we show how to measure dsDNA looping kinetics without ligase by detecting transient DNA loop formation by FRET (Fluorescence Resonance Energy Transfer). dsDNA molecules are constructed using a simple PCR-based protocol with a FRET pair and a biotin linker. The looping probability density known as the J factor is extracted from the looping rate and the annealing rate between two disconnected sticky ends. By testing two dsDNAs with different intrinsic curvatures, we show that the J factor is sensitive to the intrinsic shape of the dsDNA.

  3. Intrinsic Scene Decomposition from RGB-D Images

    KAUST Repository

    Hachama, Mohammed; Ghanem, Bernard; Wonka, Peter

    2015-01-01

    In this paper, we address the problem of computing an intrinsic decomposition of the colors of a surface into an albedo and a shading term. The surface is reconstructed from a single or multiple RGB-D images of a static scene obtained from different views. We thereby extend and improve existing works in the area of intrinsic image decomposition. In a variational framework, we formulate the problem as a minimization of an energy composed of two terms: a data term and a regularity term. The first term is related to the image formation process and expresses the relation between the albedo, the surface normals, and the incident illumination. We use an affine shading model, a combination of a Lambertian model, and an ambient lighting term. This model is relevant for Lambertian surfaces. When available, multiple views can be used to handle view-dependent non-Lambertian reflections. The second term contains an efficient combination of l2 and l1-regularizers on the illumination vector field and albedo respectively. Unlike most previous approaches, especially Retinex-like techniques, these terms do not depend on the image gradient or texture, thus reducing the mixing shading/reflectance artifacts and leading to better results. The obtained non-linear optimization problem is efficiently solved using a cyclic block coordinate descent algorithm. Our method outperforms a range of state-of-the-art algorithms on a popular benchmark dataset.

  4. Intrinsic Scene Decomposition from RGB-D Images

    KAUST Repository

    Hachama, Mohammed

    2015-12-07

    In this paper, we address the problem of computing an intrinsic decomposition of the colors of a surface into an albedo and a shading term. The surface is reconstructed from a single or multiple RGB-D images of a static scene obtained from different views. We thereby extend and improve existing works in the area of intrinsic image decomposition. In a variational framework, we formulate the problem as a minimization of an energy composed of two terms: a data term and a regularity term. The first term is related to the image formation process and expresses the relation between the albedo, the surface normals, and the incident illumination. We use an affine shading model, a combination of a Lambertian model, and an ambient lighting term. This model is relevant for Lambertian surfaces. When available, multiple views can be used to handle view-dependent non-Lambertian reflections. The second term contains an efficient combination of l2 and l1-regularizers on the illumination vector field and albedo respectively. Unlike most previous approaches, especially Retinex-like techniques, these terms do not depend on the image gradient or texture, thus reducing the mixing shading/reflectance artifacts and leading to better results. The obtained non-linear optimization problem is efficiently solved using a cyclic block coordinate descent algorithm. Our method outperforms a range of state-of-the-art algorithms on a popular benchmark dataset.

  5. Dynamic heterogeneity and DNA methylation in embryonic stem cells.

    KAUST Repository

    Singer, Zakary S

    2014-07-01

    Cell populations can be strikingly heterogeneous, composed of multiple cellular states, each exhibiting stochastic noise in its gene expression. A major challenge is to disentangle these two types of variability and to understand the dynamic processes and mechanisms that control them. Embryonic stem cells (ESCs) provide an ideal model system to address this issue because they exhibit heterogeneous and dynamic expression of functionally important regulatory factors. We analyzed gene expression in individual ESCs using single-molecule RNA-FISH and quantitative time-lapse movies. These data discriminated stochastic switching between two coherent (correlated) gene expression states and burst-like transcriptional noise. We further showed that the "2i" signaling pathway inhibitors modulate both types of variation. Finally, we found that DNA methylation plays a key role in maintaining these metastable states. Together, these results show how ESC gene expression states and dynamics arise from a combination of intrinsic noise, coherent cellular states, and epigenetic regulation.

  6. Close linkage of the locus for X chromosome-linked severe combined immunodeficiency to polymorphic DNA markers in Xq11-q13

    International Nuclear Information System (INIS)

    de Saint Basile, G.; Arveiler, B.; Oberle, I.

    1987-01-01

    The gene for X chromosome-linked severe combined immunodeficiency (SCID), a disease characterized by a block in early T-cell differentiation, has been mapped to the region Xq11-q13 by linkage analysis with restriction fragment length polymorphisms. High logarithm of odds (lod) scores were obtained with the marker 19.2 (DXS3) and with the marker cpX73 (DXS159) that showed complete cosegregation with the disease locus in the informative families analyzed. Other significant linkages were obtained with several markers from Xq11 to q22. With the help of a recently developed genetic map of the region, it was possible to perform multipoint linkage analysis, and the most likely genetic order is DXS1-(SCID, DXS159)-DXYS1-DXYS12-DXS3, with a maximum multipoint logarithm of odds score of 11.0. The results demonstrate that the SCID locus (gene symbol IMD4) is not closely linked to the locus of Bruton's agammaglobulinemia (a defect in B-cell maturation). They also provide a way for a better estimation of risk for carrier and antenatal diagnosis

  7. Biosensors for DNA sequence detection

    Science.gov (United States)

    Vercoutere, Wenonah; Akeson, Mark

    2002-01-01

    DNA biosensors are being developed as alternatives to conventional DNA microarrays. These devices couple signal transduction directly to sequence recognition. Some of the most sensitive and functional technologies use fibre optics or electrochemical sensors in combination with DNA hybridization. In a shift from sequence recognition by hybridization, two emerging single-molecule techniques read sequence composition using zero-mode waveguides or electrical impedance in nanoscale pores.

  8. Organisational Learning and Employees' Intrinsic Motivation

    Science.gov (United States)

    Remedios, Richard; Boreham, Nick

    2004-01-01

    This study examined the effects of organisational learning initiatives on employee motivation. Four initiatives consistent with theories of organisational learning were a priori ranked in terms of concepts that underpin intrinsic-motivation theory. Eighteen employees in a UK petrochemical company were interviewed to ascertain their experiences of…

  9. Intrinsic Diophantine approximation on general polynomial surfaces

    DEFF Research Database (Denmark)

    Tiljeset, Morten Hein

    2017-01-01

    We study the Hausdorff measure and dimension of the set of intrinsically simultaneously -approximable points on a curve, surface, etc, given as a graph of integer polynomials. We obtain complete answers to these questions for algebraically “nice” manifolds. This generalizes earlier work done...

  10. Sex Differences, Positive Feedback and Intrinsic Motivation.

    Science.gov (United States)

    Deci, Edward L.; And Others

    The paper presents two experiments which test the "change in feelings of competence and self-determination" proposition of cognitive evaluation theory. This proposition states that when a person receives feedback about his performance on an intrinsically motivated activity this information will affect his sense of competence and…

  11. Intrinsic and Extrinsic Motivation among Collegiate Instrumentalists

    Science.gov (United States)

    Diaz, Frank M.

    2010-01-01

    The purpose of this study was to gather and compare information on measures of intrinsic and extrinsic motivation among instrumentalists enrolled in collegiate ensembles. A survey instrument was developed to gather information concerning demographic data and responses to questions on motivational preference. Participants were undergraduate and…

  12. Intrinsic intensity fluctuations in random lasers

    International Nuclear Information System (INIS)

    Molen, Karen L. van der; Mosk, Allard P.; Lagendijk, Ad

    2006-01-01

    We present a quantitative experimental and theoretical study of intensity fluctuations in the emitted light of a random laser that has different realizations of disorder for every pump pulse. A model that clarifies these intrinsic fluctuations is developed. We describe the output versus input power graphs of the random laser with an effective spontaneous emission factor (β factor)

  13. Intrinsic Motivation, Organizational Justice, and Creativity

    Science.gov (United States)

    Hannam, Kalli; Narayan, Anupama

    2015-01-01

    For employees to generate creative ideas that are not only original, but also useful to their company, they must interact with their workplace environment to determine organizational needs. Therefore, it is important to consider aspects of the individual as well as their environment when studying creativity. Intrinsic motivation, a predictor of…

  14. Intrinsically conductive polymer thin film piezoresistors

    DEFF Research Database (Denmark)

    Lillemose, Michael; Spieser, Martin; Christiansen, N.O.

    2008-01-01

    We report on the piezoresistive effect in the intrinsically conductive polymer, polyaniline. A process recipe for indirect patterning of thin film polyaniline has been developed. Using a specially designed chip, the polyaniline thin films have been characterised with respect to resistivity...

  15. LEADERSHIP STYLE AND EMPLOYEES' INTRINSIC JOB ...

    African Journals Online (AJOL)

    This study investigates the impact of leadership style on employees' intrinsic ... of many factors including motivation, leadership, job satisfaction, workers' alienation and ... Factors associated with job satisfaction include incentive to work, reward of ... advancement/promotion, recognition and self-actualization cannot be met ...

  16. Discovery of Intrinsic Primitives on Triangle Meshes

    KAUST Repository

    Solomon, Justin

    2011-04-01

    The discovery of meaningful parts of a shape is required for many geometry processing applications, such as parameterization, shape correspondence, and animation. It is natural to consider primitives such as spheres, cylinders and cones as the building blocks of shapes, and thus to discover parts by fitting such primitives to a given surface. This approach, however, will break down if primitive parts have undergone almost-isometric deformations, as is the case, for example, for articulated human models. We suggest that parts can be discovered instead by finding intrinsic primitives, which we define as parts that posses an approximate intrinsic symmetry. We employ the recently-developed method of computing discrete approximate Killing vector fields (AKVFs) to discover intrinsic primitives by investigating the relationship between the AKVFs of a composite object and the AKVFs of its parts. We show how to leverage this relationship with a standard clustering method to extract k intrinsic primitives and remaining asymmetric parts of a shape for a given k. We demonstrate the value of this approach for identifying the prominent symmetry generators of the parts of a given shape. Additionally, we show how our method can be modified slightly to segment an entire surface without marking asymmetric connecting regions and compare this approach to state-of-the-art methods using the Princeton Segmentation Benchmark. © 2011 The Author(s).

  17. Intrinsic Risk Factors of Falls in Elderly

    Directory of Open Access Journals (Sweden)

    Yasmin Amatullah

    2016-09-01

    Full Text Available Background: Falls are common geriatric problems. The risk factors of falls are the intrinsic and extrinsic risk factors. Studies on falls are scarcely conducted in Indonesia, especially in Bandung. Therefore, this study was conducted to identify the intrinsic risk factors of falls among elderly. Methods: A descriptive study was carried out from August to October 2013 at the Geriatric Clinic of Dr. Hasan Sadikin General Hospital Bandung. Fifty three participants were selected according to the inclusion and exclusion criteria using consecutive sampling. The determined variables in this study were classification of the risk of falls, demographic profile, history of falls, disease, and medications. After the selection, the participants were tested by Timed up-and-go test (TUGT. Moreover, an interview and analysis of medical records were carried out to discover the risk factors of falls. The collected data were analyzed and presented in the form of percentages shown in tables. Results: From 53 patients, women (35.66% were considered to have higher risk of fall than men (18.34%. The majority of patients (66% with the risk of fall were from the age group 60–74 years. The major diseases suffered by patients were hypertension, osteoarthritis and diabetes mellitus. Drugs that were widely used were antihypertensive drugs; analgesic and antipyretic drugs and antidiabetic drugs. Conclusions: There are various intrinsic risk factors of falls in elderly and each of the elderly has more than one intrinsic risk factor of falls.

  18. The proofreading 3'→5' exonuclease activity of DNA polymerases: a kinetic barrier to translesion DNA synthesis

    International Nuclear Information System (INIS)

    Khare, Vineeta; Eckert, Kristin A.

    2002-01-01

    The 3'→5' exonuclease activity intrinsic to several DNA polymerases plays a primary role in genetic stability; it acts as a first line of defense in correcting DNA polymerase errors. A mismatched basepair at the primer terminus is the preferred substrate for the exonuclease activity over a correct basepair. The efficiency of the exonuclease as a proofreading activity for mispairs containing a DNA lesion varies, however, being dependent upon both the DNA polymerase/exonuclease and the type of DNA lesion. The exonuclease activities intrinsic to the T4 polymerase (family B) and DNA polymerase γ (family A) proofread DNA mispairs opposite endogenous DNA lesions, including alkylation, oxidation, and abasic adducts. However, the exonuclease of the Klenow polymerase cannot discriminate between correct and incorrect bases opposite alkylation and oxidative lesions. DNA damage alters the dynamics of the intramolecular partitioning of DNA substrates between the 3'→5' exonuclease and polymerase activities. Enzymatic idling at lesions occurs when an exonuclease activity efficiently removes the same base that is preferentially incorporated by the DNA polymerase activity. Thus, the exonuclease activity can also act as a kinetic barrier to translesion synthesis (TLS) by preventing the stable incorporation of bases opposite DNA lesions. Understanding the downstream consequences of exonuclease activity at DNA lesions is necessary for elucidating the mechanisms of translesion synthesis and damage-induced cytotoxicity

  19. The dynamic multisite interactions between two intrinsically disordered proteins

    KAUST Repository

    Wu, Shaowen

    2017-05-11

    Protein interactions involving intrinsically disordered proteins (IDPs) comprise a variety of binding modes, from the well characterized folding upon binding to dynamic fuzzy complex. To date, most studies concern the binding of an IDP to a structured protein, while the Interaction between two IDPs is poorly understood. In this study, we combined NMR, smFRET, and molecular dynamics (MD) simulation to characterize the interaction between two IDPs, the C-terminal domain (CTD) of protein 4.1G and the nuclear mitotic apparatus (NuMA) protein. It is revealed that CTD and NuMA form a fuzzy complex with remaining structural disorder. Multiple binding sites on both proteins were identified by MD and mutagenesis studies. Our study provides an atomic scenario in which two IDPs bearing multiple binding sites interact with each other in dynamic equilibrium. The combined approach employed here could be widely applicable for investigating IDPs and their dynamic interactions.

  20. Combining Push Pull Tracer Tests and Microbial DNA and mRNA Analysis to Assess In-Situ Groundwater Nitrate Transformations

    Science.gov (United States)

    Henson, W.; Graham, W. D.; Huang, L.; Ogram, A.

    2015-12-01

    Nitrogen transformation mechanisms in the Upper Floridan Aquifer (UFA) are still poorly understood because of karst aquifer complexity and spatiotemporal variability in nitrate and carbon loading. Transformation rates have not been directly measured in the aquifer. This study quantifies nitrate-nitrogen transformation potential in the UFA using single well push-pull tracer injection (PPT) experiments combined with microbial characterization of extracted water via qPCR and RT-qPCR of selected nitrate reduction genes. Tracer tests with chloride and nitrate ± carbon were executed in two wells representing anoxic and oxic geochemical end members in a spring groundwater contributing area. A significant increase in number of microbes with carbon addition suggests stimulated growth. Increases in the activities of denitrification genes (nirK and nirS) as measured by RT-qPCR were not observed. However, only microbes suspended in the tracer were obtained, ignoring effects of aquifer material biofilms. Increases in nrfA mRNA and ammonia concentrations were observed, supporting Dissimilatory Reduction of Nitrate to Ammonia (DNRA) as a reduction mechanism. In the oxic aquifer, zero order nitrate loss rates ranged from 32 to 89 nmol /L*hr with no added carbon and 90 to 240 nmol /L*hr with carbon. In the anoxic aquifer, rates ranged from 18 to 95 nmol /L*hr with no added carbon and 34 to 207 nmol /L*hr with carbon. These loss rates are low; 13 orders of magnitude less than the loads applied in the contributing area each year, however they do indicate that losses can occur in oxic and anoxic aquifers with and without carbon. These rates may include, ammonia adsorption, uptake, or denitrification in aquifer material biofilms. Rates with and without carbon addition for both aquifers were similar, suggesting aquifer redox state and carbon availability alone are insufficient to predict response to nutrient additions without characterization of microbial response. Surprisingly, these

  1. DNA Camouflage

    Science.gov (United States)

    2016-01-08

    1 DNA Camouflage Supplementary Information Bijan Zakeri1,2*, Timothy K. Lu1,2*, Peter A. Carr2,3* 1Department of Electrical Engineering and...ll.mit.edu). Distribution A: Public Release   2 Supplementary Figure 1 DNA camouflage with the 2-state device. (a) In the presence of Cre, DSD-2[α...10 1 + Cre 1 500 1,000 length (bp) chromatogram alignment template − Cre   4 Supplementary Figure 3 DNA camouflage with a switchable

  2. Identifying the neural substrates of intrinsic motivation during task performance.

    Science.gov (United States)

    Lee, Woogul; Reeve, Johnmarshall

    2017-10-01

    Intrinsic motivation is the inherent tendency to seek out novelty and challenge, to explore and investigate, and to stretch and extend one's capacities. When people imagine performing intrinsically motivating tasks, they show heightened anterior insular cortex (AIC) activity. To fully explain the neural system of intrinsic motivation, however, requires assessing neural activity while people actually perform intrinsically motivating tasks (i.e., while answering curiosity-inducing questions or solving competence-enabling anagrams). Using event-related functional magnetic resonance imaging, we found that the neural system of intrinsic motivation involves not only AIC activity, but also striatum activity and, further, AIC-striatum functional interactions. These findings suggest that subjective feelings of intrinsic satisfaction (associated with AIC activations), reward processing (associated with striatum activations), and their interactions underlie the actual experience of intrinsic motivation. These neural findings are consistent with the conceptualization of intrinsic motivation as the pursuit and satisfaction of subjective feelings (interest and enjoyment) as intrinsic rewards.

  3. Bimanual motor coordination controlled by cooperative interactions in intrinsic and extrinsic coordinates.

    Science.gov (United States)

    Sakurada, Takeshi; Ito, Koji; Gomi, Hiroaki

    2016-01-01

    Although strong motor coordination in intrinsic muscle coordinates has frequently been reported for bimanual movements, coordination in extrinsic visual coordinates is also crucial in various bimanual tasks. To explore the bimanual coordination mechanisms in terms of the frame of reference, here we characterized implicit bilateral interactions in visuomotor tasks. Visual perturbations (finger-cursor gain change) were applied while participants performed a rhythmic tracking task with both index fingers under an in-phase or anti-phase relationship in extrinsic coordinates. When they corrected the right finger's amplitude, the left finger's amplitude unintentionally also changed [motor interference (MI)], despite the instruction to keep its amplitude constant. Notably, we observed two specificities: one was large MI and low relative-phase variability (PV) under the intrinsic in-phase condition, and the other was large MI and high PV under the extrinsic in-phase condition. Additionally, using a multiple-interaction model, we successfully decomposed MI into intrinsic components caused by motor correction and extrinsic components caused by visual-cursor mismatch of the right finger's movements. This analysis revealed that the central nervous system facilitates MI by combining intrinsic and extrinsic components in the condition with in-phases in both intrinsic and extrinsic coordinates, and that under-additivity of the effects is explained by the brain's preference for the intrinsic interaction over extrinsic interaction. In contrast, the PV was significantly correlated with the intrinsic component, suggesting that the intrinsic interaction dominantly contributed to bimanual movement stabilization. The inconsistent features of MI and PV suggest that the central nervous system regulates multiple levels of bilateral interactions for various bimanual tasks. © 2015 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and

  4. Recollection and unitization in associating actors with extrinsic and intrinsic motions.

    Science.gov (United States)

    Kersten, Alan W; Earles, Julie L; Berger, Johanna D

    2015-04-01

    Four experiments provide evidence for a distinction between 2 different kinds of motion representations. Extrinsic motions involve the path of an object with respect to an external frame of reference. Intrinsic motions involve the relative motions of the parts of an object. This research suggests that intrinsic motions are represented conjointly with information about the identities of the actors who perform them, whereas extrinsic motions are represented separately from identity information. Experiment 1 demonstrated that participants remembered which actor had performed a particular intrinsic motion better than they remembered which actor had performed a particular extrinsic motion. Experiment 2 replicated this effect with incidental encoding of actor information, suggesting that encoding intrinsic motions leads one to automatically encode identity information. The results of Experiments 3 and 4 were fit by Yonelinas's (1999) source-memory model to quantify the contributions of familiarity and recollection to memory for the actors who carried out the intrinsic and extrinsic motions. Successful performance with extrinsic motion items in Experiment 3 required participants to remember in which scene contexts an actor had appeared, whereas successful performance in Experiment 4 required participants to remember the exact path taken by an actor in each scene. In both experiments, discrimination of old and new combinations of actors and extrinsic motions relied strongly on recollection, suggesting independent but associated representations of actors and extrinsic motions. In contrast, participants discriminated old and new combinations of actors and intrinsic motions primarily on the basis of familiarity, suggesting unitized representations of actors and intrinsic motions. (c) 2015 APA, all rights reserved).

  5. [Single-molecule detection and characterization of DNA replication based on DNA origami].

    Science.gov (United States)

    Wang, Qi; Fan, Youjie; Li, Bin

    2014-08-01

    To investigate single-molecule detection and characterization of DNA replication. Single-stranded DNA (ssDNA) as the template of DNA replication was attached to DNA origami by a hybridization reaction based on the complementary base-pairing principle. DNA replication catalyzed by E.coli DNA polymerase I Klenow Fragment (KF) was detected using atomic force microscopy (AFM). The height variations between the ssDNA and the double-stranded DNA (dsDNA), the distribution of KF during DNA replication and biotin-streptavidin (BA) complexes on the DNA strand after replication were detected. Agarose gel electrophoresis was employed to analyze the changes in the DNA after replication. The designed ssDNA could be anchored on the target positions of over 50% of the DNA origami. The KF was capable of binding to the ssDNA fixed on DNA origami and performing its catalytic activities, and was finally dissociated from the DNA after replication. The height of DNA strand increased by about 0.7 nm after replication. The addition of streptavidin also resulted in an DNA height increase to about 4.9 nm due to the formation of BA complexes on the biotinylated dsDNA. The resulting dsDNA and BA complex were subsequently confirmed by agarose gel electrophoresis. The combination of AFM and DNA origami allows detection and characterization of DNA replication at the single molecule level, and this approach provides better insights into the mechanism of DNA polymerase and the factors affecting DNA replication.

  6. DNA-damage response associated with occupational exposure, age and chronic inflammation in workers in the automotive industry.

    Science.gov (United States)

    Savina, Natalya V; Smal, Marharyta P; Kuzhir, Tatyana D; Ershova-Pavlova, Alla A; Goncharova, Roza I

    2012-10-09

    The evaluation of genome integrity in populations occupationally exposed to combine industrial factors is of medical importance. In the present study, the DNA-damage response was estimated by means of the alkaline comet assay in a sizeable cohort of volunteers recruited among workers in the automotive industry. For this purpose, freshly collected lymphocytes were treated with hydrogen peroxide (100μM, 1min, 4°C) in vitro, and the levels of basal and H(2)O(2)-induced DNA damage, and the kinetics and efficiency of DNA repair were measured during a 180-min interval after exposure. The parameters studied in the total cohort of workers were in a range of values prescribed for healthy adult residents of Belarus. Based on the 95th percentiles, individuals possessing enhanced cellular sensitivity to DNA damage were present in different groups, but the frequency was significantly higher among elderly persons and among individuals with chronic inflammatory diseases. The results indicate that the inter-individual variations in DNA-damage response should be taken into account to estimate adequately the environmental genotoxic effects and to identify individuals with an enhanced DNA-damage response due to the influence of some external factors or intrinsic properties of the organism. Underling mechanisms need to be further explored. © 2012 Elsevier B.V. All rights reserved.

  7. Tomato protoplast DNA transformation : physical linkage and recombination of exogenous DNA sequences

    NARCIS (Netherlands)

    Jongsma, Maarten; Koornneef, Maarten; Zabel, Pim; Hille, Jacques

    1987-01-01

    Tomato protoplasts have been transformed with plasmid DNA's, containing a chimeric kanamycin resistance gene and putative tomato origins of replication. A calcium phosphate-DNA mediated transformation procedure was employed in combination with either polyethylene glycol or polyvinyl alcohol. There

  8. DNA glue

    DEFF Research Database (Denmark)

    Filichev, Vyacheslav V; Astakhova, Irina V.; Malakhov, Andrei D.

    2008-01-01

    Significant alterations in thermal stability of parallel DNA triplexes and antiparallel duplexes were observed upon changing the attachment of ethynylpyrenes from para to ortho in the structure of phenylmethylglycerol inserted as a bulge into DNA (TINA). Insertions of two ortho-TINAs as a pseudo...

  9. Hyperstretching DNA

    NARCIS (Netherlands)

    Schakenraad, Koen; Biebricher, Andreas S.; Sebregts, Maarten; Ten Bensel, Brian; Peterman, Erwin J.G.; Wuite, Gijs J L; Heller, Iddo; Storm, Cornelis; Van Der Schoot, Paul

    2017-01-01

    The three-dimensional structure of DNA is highly susceptible to changes by mechanical and biochemical cues in vivo and in vitro. In particular, large increases in base pair spacing compared to regular B-DNA are effected by mechanical (over)stretching and by intercalation of compounds that are widely

  10. Microwave oscillator based on an intrinsic BSCCO-type Josephson junction

    DEFF Research Database (Denmark)

    Pedersen, Niels Falsig; Madsen, Søren Peder

    2005-01-01

    . The resulting model is a set of coupled nonlinear partial differential equations. By direct numerical simulations we have demonstrated that the qualitative behavior of the combined intrinsic Josephson junction and cavity system can be understood on the basis of general concepts of nonlinear oscillators...

  11. Functions of intrinsic disorder in transmembrane proteins

    DEFF Research Database (Denmark)

    Kjaergaard, Magnus; Kragelund, Birthe B.

    2017-01-01

    Intrinsic disorder is common in integral membrane proteins, particularly in the intracellular domains. Despite this observation, these domains are not always recognized as being disordered. In this review, we will discuss the biological functions of intrinsically disordered regions of membrane...... receptors. The functions of the disordered regions are many and varied. We will discuss selected examples including: (1) Organization of receptors, kinases, phosphatases and second messenger sources into signaling complexes. (2) Modulation of the membrane-embedded domain function by ball-and-chain like...... mechanisms. (3) Trafficking of membrane proteins. (4) Transient membrane associations. (5) Post-translational modifications most notably phosphorylation and (6) disorder-linked isoform dependent function. We finish the review by discussing the future challenges facing the membrane protein community regarding...

  12. Extrinsic and intrinsic curvatures in thermodynamic geometry

    Energy Technology Data Exchange (ETDEWEB)

    Hosseini Mansoori, Seyed Ali, E-mail: shossein@bu.edu [Department of Physics, Boston University, 590 Commonwealth Ave., Boston, MA 02215 (United States); Department of Physics, Isfahan University of Technology, Isfahan 84156-83111 (Iran, Islamic Republic of); Mirza, Behrouz, E-mail: b.mirza@cc.iut.ac.ir [Department of Physics, Isfahan University of Technology, Isfahan 84156-83111 (Iran, Islamic Republic of); Sharifian, Elham, E-mail: e.sharifian@ph.iut.ac.ir [Department of Physics, Isfahan University of Technology, Isfahan 84156-83111 (Iran, Islamic Republic of)

    2016-08-10

    We investigate the intrinsic and extrinsic curvatures of a certain hypersurface in thermodynamic geometry of a physical system and show that they contain useful thermodynamic information. For an anti-Reissner–Nordström-(A)de Sitter black hole (Phantom), the extrinsic curvature of a constant Q hypersurface has the same sign as the heat capacity around the phase transition points. The intrinsic curvature of the hypersurface can also be divergent at the critical points but has no information about the sign of the heat capacity. Our study explains the consistent relationship holding between the thermodynamic geometry of the KN-AdS black holes and those of the RN (J-zero hypersurface) and Kerr black holes (Q-zero hypersurface) ones [1]. This approach can easily be generalized to an arbitrary thermodynamic system.

  13. Extrinsic and intrinsic curvatures in thermodynamic geometry

    International Nuclear Information System (INIS)

    Hosseini Mansoori, Seyed Ali; Mirza, Behrouz; Sharifian, Elham

    2016-01-01

    We investigate the intrinsic and extrinsic curvatures of a certain hypersurface in thermodynamic geometry of a physical system and show that they contain useful thermodynamic information. For an anti-Reissner–Nordström-(A)de Sitter black hole (Phantom), the extrinsic curvature of a constant Q hypersurface has the same sign as the heat capacity around the phase transition points. The intrinsic curvature of the hypersurface can also be divergent at the critical points but has no information about the sign of the heat capacity. Our study explains the consistent relationship holding between the thermodynamic geometry of the KN-AdS black holes and those of the RN (J-zero hypersurface) and Kerr black holes (Q-zero hypersurface) ones [1]. This approach can easily be generalized to an arbitrary thermodynamic system.

  14. Does Aerobic Exercise Influence Intrinsic Brain Activity?

    DEFF Research Database (Denmark)

    Flodin, Pär; Jonasson, Lars S; Riklund, Katrin

    2017-01-01

    exercise group or an active control group. Both groups recieved supervised training, 3 days a week for 6 months. Multimodal brain imaging data was acquired before and after the intervention, including 10 min of resting state brain functional magnetic resonance imaging (rs-fMRI) and arterial spin labeling......Previous studies have indicated that aerobic exercise could reduce age related decline in cognition and brain functioning. Here we investigated the effects of aerobic exercise on intrinsic brain activity. Sixty sedentary healthy males and females (64-78 years) were randomized into either an aerobic...... group improved more. Contrary to our hypothesis, we did not observe any significant group by time interactions with regard to any measure of intrinsic activity. To further probe putative relationships between fitness and brain activity, we performed post hoc analyses disregarding group belongings...

  15. Survey of intrinsic states of light nuclei

    International Nuclear Information System (INIS)

    Brink, D.M.

    1975-01-01

    The resonating group method and the generator coordinate method are two closely related theories of nuclear structure which can be used to construct wave functions describing cluster structures. In both cases the form of the intrinsic state implies a selection of those degrees of freedom which are regarded as being important for the problem under consideration. The form of the intrinsic state also corresponds to a particular truncation of the shell model space. In the resonating group method the effect of the Pauli principle leads to forbidden or redundant states of relative motion of clusters. An improved understanding of the role of forbidden states in the theory has led to important advances in the phenomenological description of cluster structures in nuclei. 3 tables, 2 figures

  16. Excitonic terahertz photoconductivity in intrinsic semiconductor nanowires

    Science.gov (United States)

    Yan, Jie-Yun

    2018-06-01

    Excitonic terahertz photoconductivity in intrinsic semiconductor nanowires is studied. Based on the excitonic theory, the numerical method to calculate the photoconductivity spectrum in the nanowires is developed, which can simulate optical pump terahertz-probe spectroscopy measurements on real nanowires and thereby calculate the typical photoconductivity spectrum. With the help of the energetic structure deduced from the calculated linear absorption spectrum, the numerically observed shift of the resonant peak in the photoconductivity spectrum is found to result from the dominant exciton transition between excited or continuum states to the ground state, and the quantitative analysis is in good agreement with the quantum plasmon model. Besides, the dependence of the photoconductivity on the polarization of the terahertz field is also discussed. The numerical method and supporting theoretical analysis provide a new tool for experimentalists to understand the terahertz photoconductivity in intrinsic semiconductor nanowires at low temperatures or for nanowires subjected to below bandgap photoexcitation, where excitonic effects dominate.

  17. Process development and tooling design for intrinsic hybrid composites

    Science.gov (United States)

    Riemer, M.; Müller, R.; Drossel, W. G.; Landgrebe, D.

    2017-09-01

    Hybrid parts, which combine the advantages of different material classes, are moving into the focus of lightweight applications. This development is amplified by their high potential for usage in the field of crash relevant structures. By the current state of the art, hybrid parts are mainly made in separate, subsequent forming and joining processes. By using the concept of an intrinsic hybrid, the shaping of the part and the joining of the different materials are performed in a single process step for shortening the overall processing time and thereby the manufacturing costs. The investigated hybrid part is made from continuous fibre reinforced plastic (FRP), in which a metallic reinforcement structure is integrated. The connection between these layered components is realized by a combination of adhesive bonding and a geometrical form fit. The form fit elements are intrinsically generated during the forming process. This contribution regards the development of the forming process and the design of the forming tool for the single step production of a hybrid part. To this end a forming tool, which combines the thermo-forming and the metal forming process, is developed. The main challenge by designing the tool is the temperature management of the tool elements for the variothermal forming process. The process parameters are determined in basic tests and finite element (FE) simulation studies. On the basis of these investigations a control concept for the steering of the motion axes and the tool temperature is developed. Forming tests are carried out with the developed tool and the manufactured parts are analysed by computer assisted tomography (CT) scans.

  18. Structural design of intrinsically fluorescent oxysterols

    DEFF Research Database (Denmark)

    Nåbo, Lina J; Modzel, Maciej; Krishnan, Kathiresan

    2018-01-01

    Oxysterols are oxidized derivatives of cholesterol with many important biological functions. Trafficking of oxysterols in and between cells is not well studied, largely due to the lack of appropriate oxysterol analogs. Intrinsically fluorescent oxysterols present a new route towards direct...... observation of intracellular oxysterol trafficking by fluorescence microscopy. We characterize the fluorescence properties of the existing fluorescent 25-hydroxycholesterol analog 25-hydroxycholestatrienol, and propose a new probe with an extended conjugated system. The location of both probes inside...

  19. Intrinsic defects in ZnO varistors

    International Nuclear Information System (INIS)

    Mahan, G.D.

    1983-01-01

    Theoretical calculations are presented for equilibrium concentrations of zinc and oxygen vacancies in ZnO. Results are presented at the sintering temperature, and also at room temperature. Theoretical calculations of reaction constants show that the intrinsic donor is the oxygen vacancy, rather than the zinc interstitial. The depletion of vacancies in the surface region, as the ZnO is cooled from the sintering temperature, is also calculated. Homojunction effects which are caused by such depletion are shown to be small

  20. Intrinsic and extrinsic effects on image memorability.

    Science.gov (United States)

    Bylinskii, Zoya; Isola, Phillip; Bainbridge, Constance; Torralba, Antonio; Oliva, Aude

    2015-11-01

    Previous studies have identified that images carry the attribute of memorability, a predictive value of whether a novel image will be later remembered or forgotten. Here we investigate the interplay between intrinsic and extrinsic factors that affect image memorability. First, we find that intrinsic differences in memorability exist at a finer-grained scale than previously documented. Second, we test two extrinsic factors: image context and observer behavior. Building on prior findings that images that are distinct with respect to their context are better remembered, we propose an information-theoretic model of image distinctiveness. Our model can automatically predict how changes in context change the memorability of natural images. In addition to context, we study a second extrinsic factor: where an observer looks while memorizing an image. It turns out that eye movements provide additional information that can predict whether or not an image will be remembered, on a trial-by-trial basis. Together, by considering both intrinsic and extrinsic effects on memorability, we arrive at a more complete and fine-grained model of image memorability than previously available. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Moral Distress, Workplace Health, and Intrinsic Harm.

    Science.gov (United States)

    Weber, Elijah

    2016-05-01

    Moral distress is now being recognized as a frequent experience for many health care providers, and there's good evidence that it has a negative impact on the health care work environment. However, contemporary discussions of moral distress have several problems. First, they tend to rely on inadequate characterizations of moral distress. As a result, subsequent investigations regarding the frequency and consequences of moral distress often proceed without a clear understanding of the phenomenon being discussed, and thereby risk substantially misrepresenting the nature, frequency, and possible consequences of moral distress. These discussions also minimize the intrinsically harmful aspects of moral distress. This is a serious omission. Moral distress doesn't just have a negative impact on the health care work environment; it also directly harms the one who experiences it. In this paper, I claim that these problems can be addressed by first clarifying our understanding of moral distress, and then identifying what makes moral distress intrinsically harmful. I begin by identifying three common mistakes that characterizations of moral distress tend to make, and explaining why these mistakes are problematic. Next, I offer an account of moral distress that avoids these mistakes. Then, I defend the claim that moral distress is intrinsically harmful to the subject who experiences it. I conclude by explaining how acknowledging this aspect of moral distress should reshape our discussions about how best to deal with this phenomenon. © 2015 John Wiley & Sons Ltd.

  2. Strand Displacement by DNA Polymerase III Occurs through a τ-ψ-χ Link to Single-stranded DNA-binding Protein Coating the Lagging Strand Template*

    OpenAIRE

    Yuan, Quan; McHenry, Charles S.

    2009-01-01

    In addition to the well characterized processive replication reaction catalyzed by the DNA polymerase III holoenzyme on single-stranded DNA templates, the enzyme possesses an intrinsic strand displacement activity on flapped templates. The strand displacement activity is distinguished from the single-stranded DNA-templated reaction by a high dependence upon single-stranded DNA binding protein and an inability of γ-complex to support the reaction in the absence of τ. However, if γ-complex is p...

  3. DNA binding studies of tartrazine food additive.

    Science.gov (United States)

    Kashanian, Soheila; Zeidali, Sahar Heidary

    2011-07-01

    The interaction of native calf thymus DNA with tartrazine in 10 mM Tris-HCl aqueous solution at neutral pH 7.4 was investigated. Tartrazine is a nitrous derivative and may cause allergic reactions, with a potential of toxicological risk. Also, tartrazine induces oxidative stress and DNA damage. Its DNA binding properties were studied by UV-vis and circular dichroism spectra, competitive binding with Hoechst 33258, and viscosity measurements. Tartrazine molecules bind to DNA via groove mode as illustrated by hyperchromism in the UV absorption band of tartrazine, decrease in Hoechst-DNA solution fluorescence, unchanged viscosity of DNA, and conformational changes such as conversion from B-like to C-like in the circular dichroism spectra of DNA. The binding constants (K(b)) of DNA with tartrazine were calculated at different temperatures. Enthalpy and entropy changes were calculated to be +37 and +213 kJ mol(-1), respectively, according to the Van't Hoff equation, which indicated that the reaction is predominantly entropically driven. Also, tartrazine does not cleave plasmid DNA. Tartrazine interacts with calf thymus DNA via a groove interaction mode with an intrinsic binding constant of 3.75 × 10(4) M(-1).

  4. Intrinsic bioremediation of diesel-contaminated cold groundwater in bedrock

    International Nuclear Information System (INIS)

    Cross, K.M.; Biggar, K.W.; Guigard, S.E.

    2006-01-01

    Natural attenuation refers to the natural process by which contaminants in groundwater or soil are reduced through a combination of physico-chemical processes and biodegradation by indigenous organisms. The physico chemical processes include advection, dilution, dispersion, sorption, volatilization and abiotic transformation. This study evaluated the historical contaminant and geochemical evidence of natural attenuation at a well site where groundwater had been contaminated by a diesel fuel leak in 1982. In particular, evidence of intrinsic bioremediation was evaluated. Evidence of microbial activity was determined by most probably number (MPN) and commercial biological activity reaction tests. Groundwater samples from the site were incubated in a laboratory under aerobic and anaerobic conditions with electron acceptor and nutrient amendment to assess microbial activity. Mineralization of carbon 14-dodecane was measured to determine aerobic biodegradation rates. Anaerobic biodegradation rates were calculated from the depletion of total extractable hydrocarbon over 717 days. Nutrient addition increased the anaerobic first-order biodegradation rate from 0.0005 to 0.0016 per day. It was suggested controlled nutrient addition can improve the current slow rates of intrinsic bioremediation. 33 refs., 9 tabs., 5 figs

  5. PDA: Pooled DNA analyzer

    Directory of Open Access Journals (Sweden)

    Lin Chin-Yu

    2006-04-01

    Full Text Available Abstract Background Association mapping using abundant single nucleotide polymorphisms is a powerful tool for identifying disease susceptibility genes for complex traits and exploring possible genetic diversity. Genotyping large numbers of SNPs individually is performed routinely but is cost prohibitive for large-scale genetic studies. DNA pooling is a reliable and cost-saving alternative genotyping method. However, no software has been developed for complete pooled-DNA analyses, including data standardization, allele frequency estimation, and single/multipoint DNA pooling association tests. This motivated the development of the software, 'PDA' (Pooled DNA Analyzer, to analyze pooled DNA data. Results We develop the software, PDA, for the analysis of pooled-DNA data. PDA is originally implemented with the MATLAB® language, but it can also be executed on a Windows system without installing the MATLAB®. PDA provides estimates of the coefficient of preferential amplification and allele frequency. PDA considers an extended single-point association test, which can compare allele frequencies between two DNA pools constructed under different experimental conditions. Moreover, PDA also provides novel chromosome-wide multipoint association tests based on p-value combinations and a sliding-window concept. This new multipoint testing procedure overcomes a computational bottleneck of conventional haplotype-oriented multipoint methods in DNA pooling analyses and can handle data sets having a large pool size and/or large numbers of polymorphic markers. All of the PDA functions are illustrated in the four bona fide examples. Conclusion PDA is simple to operate and does not require that users have a strong statistical background. The software is available at http://www.ibms.sinica.edu.tw/%7Ecsjfann/first%20flow/pda.htm.

  6. Noninvasive monitoring of the genetic evolution of EGFR-mutant non-small-cell lung cancer by analyzing circulating tumor DNA during combination chemotherapy with gefitinib and pemetrexed or S-1

    Directory of Open Access Journals (Sweden)

    Nakahara Y

    2016-08-01

    . Four patients underwent gefitinib plus pemetrexed therapy, and five patients underwent gefitinib and S-1 therapy. The median number of cycles delivered was five, and the median progression-free survival was 5.7 months. Efficacy outcomes did not differ between treatments. After the combination therapy, plasma T790M status changed to positive in two patients. Hepatocyte growth factor level did not significantly change through the combination therapy.Conclusion: The usefulness of monitoring the genetic evolution of EGFR-driven tumors using noninvasive procedures was demonstrated. Since continuation of EGFR-TKI therapy with cytotoxic agents has an acceptable tolerability and a possibility of inducing T790M mutation, the combination therapy may be useful for EGFR-mutant NSCLC resistant to EGFR-TKI therapy without T790M mutation. Keywords: circulating tumor DNA, epidermal growth factor receptor, gefitinib, S-1, pemetrexed

  7. DNA probes

    International Nuclear Information System (INIS)

    Castelino, J.

    1992-01-01

    The creation of DNA probes for detection of specific nucleotide segments differs from ligand detection in that it is a chemical rather than an immunological reaction. Complementary DNA or RNA is used in place of the antibody and is labelled with 32 P. So far, DNA probes have been successfully employed in the diagnosis of inherited disorders, infectious diseases, and for identification of human oncogenes. The latest approach to the diagnosis of communicable and parasitic infections is based on the use of deoxyribonucleic acid (DNA) probes. The genetic information of all cells is encoded by DNA and DNA probe approach to identification of pathogens is unique because the focus of the method is the nucleic acid content of the organism rather than the products that the nucleic acid encodes. Since every properly classified species has some unique nucleotide sequences that distinguish it from every other species, each organism's genetic composition is in essence a finger print that can be used for its identification. In addition to this specificity, DNA probes offer other advantages in that pathogens may be identified directly in clinical specimens

  8. DNA probes

    Energy Technology Data Exchange (ETDEWEB)

    Castelino, J

    1993-12-31

    The creation of DNA probes for detection of specific nucleotide segments differs from ligand detection in that it is a chemical rather than an immunological reaction. Complementary DNA or RNA is used in place of the antibody and is labelled with {sup 32}P. So far, DNA probes have been successfully employed in the diagnosis of inherited disorders, infectious diseases, and for identification of human oncogenes. The latest approach to the diagnosis of communicable and parasitic infections is based on the use of deoxyribonucleic acid (DNA) probes. The genetic information of all cells is encoded by DNA and DNA probe approach to identification of pathogens is unique because the focus of the method is the nucleic acid content of the organism rather than the products that the nucleic acid encodes. Since every properly classified species has some unique nucleotide sequences that distinguish it from every other species, each organism`s genetic composition is in essence a finger print that can be used for its identification. In addition to this specificity, DNA probes offer other advantages in that pathogens may be identified directly in clinical specimens 10 figs, 2 tabs

  9. High frequencies of chromatid aberrations produced during G/sub 2/ in human lymphocytes by very low doses (0. 025-0. 4 Gy) of X-rays in combination with inhibitors of DNA synthesis

    Energy Technology Data Exchange (ETDEWEB)

    Andersson, H.C.; Kihlman, B.A. (Uppsala Univ. (Sweden). Dept. of Genetics)

    1984-09-01

    Whole-blood cultures of human lymphocytes were exposed in the G/sub 2/-phase (3.5 h before harvesting) to various doses of X-rays and post-treated for 3 h with inhibitors of DNA synthesis. The inhibitors used were 2'-deoxyadenosine (dAdo), hydroxyurea (HU) and 1-..beta..-D-arabinofuranosylcytosine (ara-C). To prevent deamination of dAdo by adenosine deaminase (ADA), the dAdo treatments were carried out in the presence of the ADA inhibitor coformycin. HU and ara-C were used either alone or in combination. After the 3-h inhibitor treatments, the cultures were harvested and slides prepared and analyzed for chromatid aberrations in metaphase. When the inhibitors were used at concentrations high enough to cause marked chromosome damage by themselves, very low doses of X-rays (0.025-0.2 Gy) were sufficient to produce a dramatic increase in the frequency of chromatid aberrations. High frequencies of chromatid aberrations were also obtained when cultures that had received moderate doses of X-rays (0.4-0.8 Gy) were post-treated with low inhibitor concentrations that produce no or only a few aberrations by themselves.

  10. Crowding out intrinsic motivation in the public sector

    OpenAIRE

    Georgellis, Y; Iossa, E; Tabvuma, V

    2011-01-01

    Employing intrinsically motivated individuals has been proposed as a means of improving public sector performance. In this article, we investigate whether intrinsic motivation affects the sorting of employees between the private and the public sectors, paying particular attention to whether extrinsic rewards crowd out intrinsic motivation. Using British longitudinal data, we find that individuals are attracted to the public sector by the intrinsic rather than the extrinsic rewards that the se...

  11. Intrinsic white-light emission from layered hybrid perovskites.

    Science.gov (United States)

    Dohner, Emma R; Jaffe, Adam; Bradshaw, Liam R; Karunadasa, Hemamala I

    2014-09-24

    We report on the second family of layered perovskite white-light emitters with improved photoluminescence quantum efficiencies (PLQEs). Upon near-ultraviolet excitation, two new Pb-Cl and Pb-Br perovskites emit broadband "cold" and "warm" white light, respectively, with high color rendition. Emission from large, single crystals indicates an origin from the bulk material and not surface defect sites. The Pb-Br perovskite has a PLQE of 9%, which is undiminished after 3 months of continuous irradiation. Our mechanistic studies indicate that the emission has contributions from strong electron-phonon coupling in a deformable lattice and from a distribution of intrinsic trap states. These hybrids provide a tunable platform for combining the facile processability of organic materials with the structural definition of crystalline, inorganic solids.

  12. Intrinsic Motivation: An Overlooked Component for Student Success

    Science.gov (United States)

    Augustyniak, Robert A.; Ables, Adrienne Z.; Guilford, Philip; Lujan, Heidi L.; Cortright, Ronald N.; DiCarlo, Stephen E.

    2016-01-01

    Intrinsic motivation to learn involves engaging in learning opportunities because they are seen as enjoyable, interesting, or relevant to meeting one's core psychological needs. As a result, intrinsic motivation is associated with high levels of effort and task performance. Students with greater levels of intrinsic motivation demonstrate strong…

  13. Personalizing Sample Databases with Facebook Information to Increase Intrinsic Motivation

    Science.gov (United States)

    Marzo, Asier; Ardaiz, Oscar; Sanz de Acedo, María Teresa; Sanz de Acedo, María Luisa

    2017-01-01

    Motivation is fundamental for students to achieve successful and complete learning. Motivation can be extrinsic, i.e., driven by external rewards, or intrinsic, i.e., driven by internal factors. Intrinsic motivation is the most effective and must be inspired by the task at hand. Here, a novel strategy is presented to increase intrinsic motivation…

  14. Individualistic vs. Competitive Participation: The Effect on Intrinsic Motivation.

    Science.gov (United States)

    Jones, Brent M.; And Others

    Studies investigating intrinsic motivation and competition have supported the view that competition decreases intrinsic motivation. More recent studies suggest that the specific outcome of a competition (a win or a loss) differentially affects intrinsic motivation by highlighting the informational rather than the controlling aspect of the reward…

  15. Elements of the Competitive Situation That Affect Intrinsic Motivation.

    Science.gov (United States)

    Reeve, Johnmarshall; Deci, Edward L.

    1996-01-01

    Explores the effects of three elements of the competitive situation (competitive set, competitive outcome, and interpersonal context) on intrinsic motivation in a sample of college students (n=100). Competitive outcome and interpersonal context affected intrinsic motivation: winning increased intrinsic motivation, while pressured interpersonal…

  16. The value of nature: Economic, intrinsic, or both?

    Science.gov (United States)

    There has been a long standing argument that ecosystems have intrinsic value and therefore there is no need to put a price tag on Mother Nature. The concept of intrinsic value reflects the perspective that nature has value in its own right, independent of human uses. Intrinsic va...

  17. Plant DNA barcodes can accurately estimate species richness in poorly known floras.

    Directory of Open Access Journals (Sweden)

    Craig Costion

    Full Text Available BACKGROUND: Widespread uptake of DNA barcoding technology for vascular plants has been slow due to the relatively poor resolution of species discrimination (∼70% and low sequencing and amplification success of one of the two official barcoding loci, matK. Studies to date have mostly focused on finding a solution to these intrinsic limitations of the markers, rather than posing questions that can maximize the utility of DNA barcodes for plants with the current technology. METHODOLOGY/PRINCIPAL FINDINGS: Here we test the ability of plant DNA barcodes using the two official barcoding loci, rbcLa and matK, plus an alternative barcoding locus, trnH-psbA, to estimate the species diversity of trees in a tropical rainforest plot. Species discrimination accuracy was similar to findings from previous studies but species richness estimation accuracy proved higher, up to 89%. All combinations which included the trnH-psbA locus performed better at both species discrimination and richness estimation than matK, which showed little enhanced species discriminatory power when concatenated with rbcLa. The utility of the trnH-psbA locus is limited however, by the occurrence of intraspecific variation observed in some angiosperm families to occur as an inversion that obscures the monophyly of species. CONCLUSIONS/SIGNIFICANCE: We demonstrate for the first time, using a case study, the potential of plant DNA barcodes for the rapid estimation of species richness in taxonomically poorly known areas or cryptic populations revealing a powerful new tool for rapid biodiversity assessment. The combination of the rbcLa and trnH-psbA loci performed better for this purpose than any two-locus combination that included matK. We show that although DNA barcodes fail to discriminate all species of plants, new perspectives and methods on biodiversity value and quantification may overshadow some of these shortcomings by applying barcode data in new ways.

  18. Plant DNA barcodes can accurately estimate species richness in poorly known floras.

    Science.gov (United States)

    Costion, Craig; Ford, Andrew; Cross, Hugh; Crayn, Darren; Harrington, Mark; Lowe, Andrew

    2011-01-01

    Widespread uptake of DNA barcoding technology for vascular plants has been slow due to the relatively poor resolution of species discrimination (∼70%) and low sequencing and amplification success of one of the two official barcoding loci, matK. Studies to date have mostly focused on finding a solution to these intrinsic limitations of the markers, rather than posing questions that can maximize the utility of DNA barcodes for plants with the current technology. Here we test the ability of plant DNA barcodes using the two official barcoding loci, rbcLa and matK, plus an alternative barcoding locus, trnH-psbA, to estimate the species diversity of trees in a tropical rainforest plot. Species discrimination accuracy was similar to findings from previous studies but species richness estimation accuracy proved higher, up to 89%. All combinations which included the trnH-psbA locus performed better at both species discrimination and richness estimation than matK, which showed little enhanced species discriminatory power when concatenated with rbcLa. The utility of the trnH-psbA locus is limited however, by the occurrence of intraspecific variation observed in some angiosperm families to occur as an inversion that obscures the monophyly of species. We demonstrate for the first time, using a case study, the potential of plant DNA barcodes for the rapid estimation of species richness in taxonomically poorly known areas or cryptic populations revealing a powerful new tool for rapid biodiversity assessment. The combination of the rbcLa and trnH-psbA loci performed better for this purpose than any two-locus combination that included matK. We show that although DNA barcodes fail to discriminate all species of plants, new perspectives and methods on biodiversity value and quantification may overshadow some of these shortcomings by applying barcode data in new ways.

  19. DNA methylation

    DEFF Research Database (Denmark)

    Williams, Kristine; Christensen, Jesper; Helin, Kristian

    2012-01-01

    DNA methylation is involved in key cellular processes, including X-chromosome inactivation, imprinting and transcriptional silencing of specific genes and repetitive elements. DNA methylation patterns are frequently perturbed in human diseases such as imprinting disorders and cancer. The recent...... discovery that the three members of the TET protein family can convert 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC) has provided a potential mechanism leading to DNA demethylation. Moreover, the demonstration that TET2 is frequently mutated in haematopoietic tumours suggests that the TET...... proteins are important regulators of cellular identity. Here, we review the current knowledge regarding the function of the TET proteins, and discuss various mechanisms by which they contribute to transcriptional control. We propose that the TET proteins have an important role in regulating DNA methylation...

  20. DNA data

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Raw DNA chromatogram data produced by the ABI 373, 377, 3130 and 3730 automated sequencing machines in ABI format. These are from fish (primarily Sebastes spp.,...

  1. DNA nanotechnology

    Science.gov (United States)

    Seeman, Nadrian C.; Sleiman, Hanadi F.

    2018-01-01

    DNA is the molecule that stores and transmits genetic information in biological systems. The field of DNA nanotechnology takes this molecule out of its biological context and uses its information to assemble structural motifs and then to connect them together. This field has had a remarkable impact on nanoscience and nanotechnology, and has been revolutionary in our ability to control molecular self-assembly. In this Review, we summarize the approaches used to assemble DNA nanostructures and examine their emerging applications in areas such as biophysics, diagnostics, nanoparticle and protein assembly, biomolecule structure determination, drug delivery and synthetic biology. The introduction of orthogonal interactions into DNA nanostructures is discussed, and finally, a perspective on the future directions of this field is presented.

  2. Whole genome DNA methylation: beyond genes silencing

    OpenAIRE

    Tirado-Magallanes, Roberto; Rebbani, Khadija; Lim, Ricky; Pradhan, Sriharsa; Benoukraf, Touati

    2016-01-01

    The combination of DNA bisulfite treatment with high-throughput sequencing technologies has enabled investigation of genome-wide DNA methylation at near base pair level resolution, far beyond that of the kilobase-long canonical CpG islands that initially revealed the biological relevance of this covalent DNA modification. The latest high-resolution studies have revealed a role for very punctual DNA methylation in chromatin plasticity, gene regulation and splicing. Here, we aim to outline the ...

  3. Relationship between intrinsic radiation sensitivity and metastatic potential

    International Nuclear Information System (INIS)

    Lewis, Anne M.; Mei, Su; Doty, Jay; Chen Yi; Pardo, Francisco S.

    1996-01-01

    Purpose: Prior studies emphasized genetic modulation of tumorigenicity, and experimental metastatic potential in cells transfected with oncogenes. Whether the intrinsic radiation sensitivity of cells might correlate with parallel changes in metastatic potential is unknown. Methods and Materials: Rat embryo cells (REC) were transfected with the following oncogenes, and where appropriate, with corresponding selection markers: pCMV neopEJ6.6ras, pEJ6.6ras/v-myc, pE1a, and pEJ6-.6ras/E1a. Individual transfectant clones and corresponding pooled cellular populations were propagated in selective medium. In vitro cellular radiation sensitivity was determined via clonogenic assays, a minimum of three, by standard techniques and individual SF 2 and MID parameters determined. Tumorigenicity was defined as the number of tumors forming following the injection of 1 x 10 5 - 1 x 10 6 cells into the axillary pouch of three different strains of immune-deficient mice. Animals were killed once resultant tumors reached a maximum size of 1.5-2.0 cm in maximum diameter. For determination of experimental metastatic potential, between 1 x 10 5 -1 x 10 6 cells were injected into the tail veins of litter-matched sibling mice in parallel to the tumorigenicity studies. Results: Radiobiologic studies indicate similar levels of radiation sensitivity among REC, mock-transfected REC, E1a, and combined E1a/ras transfectants. pEJ6.6ras, and combined ras/myc transfected pooled cellular populations demonstrated increases in radiation resistance when compared to the pooled radiobiologic data from untransfected and mock-transfected corresponding pooled cellular populations (p 2 , MID). Rat embryo cells, E1a, and mock-transfectants were relatively radiation sensitive and nontumorigenic. pE1a/ras was tumorigenic but demonstrated relatively low experimental metastatic potential. Ras, and ras/myc transfectants, demonstrated similar levels of experimental metastatic potential on lung colonization assays

  4. Linear Association Between Cellular DNA and Epstein-Barr Virus DNA in a Human Lymphoblastoid Cell Line

    Science.gov (United States)

    Adams, Alice; Lindahl, Tomas; Klein, George

    1973-01-01

    High-molecular-weight DNA from cell line Raji (derived from Burkitt's lymphoma), which contains 50-60 copies of Epstein-Barr virus DNA per cell, was fractionated in neutral solution by several cycles of CsCl gradient centrifugation in fixed-angle rotors. Under the fractionation conditions used, intact Epstein-Barr virus DNA from virus particles can be separated from the less-dense cellular DNA. In contrast, a large proportion of the intrinsic Epstein-Barr virus DNA component of Raji cells remains associated with cellular DNA, as determined by nucleic acid hybridization. This interaction, which is resistant to Pronase and phenol treatment, is not the result of aggregation. When the molecular weight of Raji DNA is reduced by hydrodynamic shear, the amount of virus DNA associated with cell DNA decreases. However, some virus DNA still remains bound to fragments of cellular DNA after shearing. The association is completely destroyed in alkaline solution. Molecular weight analysis of Raji DNA after denaturation showed that the alkali-induced release of Epstein-Barr virus DNA was specific and not the result of random single-strand breaks. These data indicate that Epstein-Barr virus DNA is linearly integrated into Raji cell DNA by alkali-labile bonds. PMID:4355371

  5. Experimental demonstration of an up-down asymmetry effect on intrinsic rotation in the TCV tokamak

    International Nuclear Information System (INIS)

    Camenen, Y; Peeters, A G; Casson, F J; Hornsby, W A; Snodin, A P; Szepesi, G; Bortolon, A; Duval, B P; Federspiel, L; Karpushov, A N; Piras, F; Sauter, O

    2010-01-01

    A new mechanism has recently been proposed that generates a radial flux of parallel momentum in toroidal plasmas. Namely, by considering up-down asymmetric flux surfaces, the symmetry following the magnetic field can be broken and an additional contribution to the turbulent momentum flux arises, potentially changing the intrinsic rotation profile. These predictions are tested with specific experiments on TCV. The intrinsic toroidal rotation is observed to change by roughly a factor of two when changing the up-down asymmetry of the plasma. More precisely, the toroidal rotation gradient changes in the outer part of the plasma, where the flux surface asymmetry is the highest. The experiments were performed for all combinations of the toroidal magnetic field and plasma current directions, that affect the sign of the predicted up-down asymmetry flux. In each case the variation of the intrinsic rotation profile with the up-down asymmetry is observed in the direction predicted by the theory.

  6. Radiation response and regulation of apoptosis induced by a combination of TRAIL and CHX in cells lacking mitochondrial DNA: A role for NF-κB-STAT3-directed gene expression

    International Nuclear Information System (INIS)

    Ivanov, Vladimir N.; Ghandhi, Shanaz A.; Zhou, Hongning; Huang, Sarah X.; Chai, Yunfei; Amundson, Sally A.; Hei, Tom K.

    2011-01-01

    Mitochondrial DNA depleted (ρ 0 ) human skin fibroblasts (HSF) with suppressed oxidative phosphorylation were characterized by significant changes in the expression of 2100 nuclear genes, encoding numerous protein classes, in NF-κB and STAT3 signaling pathways, and by decreased activity of mitochondrial death pathway, compared to the parental ρ + HSF. In contrast, the extrinsic TRAIL/TRAIL-Receptor mediated death pathway remained highly active, and exogenous TRAIL in a combination with cycloheximide (CHX) induced higher levels of apoptosis in ρ 0 cells compared to ρ + HSF. Global gene expression analysis using microarray and qRT-PCR demonstrated that mRNA expression levels of many growth factors and their adaptor proteins (FGF13, HGF, IGFBP4, IGFBP6, and IGFL2), cytokines (IL6, ΙL17Β, ΙL18, ΙL19, and ΙL28Β) and cytokine receptors (IL1R1, IL21R, and IL31RA) were substantially decreased after mitochondrial DNA depletion. Some of these genes were targets of NF-κB and STAT3, and their protein products could regulate the STAT3 signaling pathway. Alpha-irradiation further induced expression of several NF-κB/STAT3 target genes, including IL1A, IL1B, IL6, PTGS2/COX2 and MMP12, in ρ + HSF, but this response was substantially decreased in ρ 0 HSF. Suppression of the IKK-NF-κB pathway by the small molecular inhibitor BMS-345541 and of the JAK2-STAT3 pathway by AG490 dramatically increased TRAIL-induced apoptosis in the control and irradiated ρ + HSF. Inhibitory antibodies against IL6, the main activator of JAK2-STAT3 pathway, added into the cell media, also increased TRAIL-induced apoptosis in HSF, especially after alpha-irradiation. Collectively, our results indicated that NF-κB activation was partially lost in ρ 0 HSF resulting in downregulation of the basal or radiation-induced expression of numerous NF-κB targets, further suppressing IL6-JAK2-STAT3 that in concert with NF-κB regulated protection against TRAIL-induced apoptosis.

  7. DNA expressions - A formal notation for DNA

    NARCIS (Netherlands)

    Vliet, Rudy van

    2015-01-01

    We describe a formal notation for DNA molecules that may contain nicks and gaps. The resulting DNA expressions denote formal DNA molecules. Different DNA expressions may denote the same molecule. Such DNA expressions are called equivalent. We examine which DNA expressions are minimal, which

  8. Intrinsic and extrinsic neuromodulation of motor circuits.

    Science.gov (United States)

    Katz, P S

    1995-12-01

    Neuromodulation of motor circuits by extrinsic inputs provides enormous flexibility in the production of behavior. Recent work has shown that neurons intrinsic to central pattern-generating circuits can evoke neuromodulatory effects in addition to their neurotransmitting actions. Modulatory neurons often elicit a multitude of different effects attributable to actions at different receptors and/or through the release of co-transmitters. Differences in neuromodulation between species can account for differences in behavior. Modulation of neuromodulation may provide an additional level of flexibility to motor circuits.

  9. Symplectic Structure of Intrinsic Time Gravity

    Directory of Open Access Journals (Sweden)

    Eyo Eyo Ita

    2016-08-01

    Full Text Available The Poisson structure of intrinsic time gravity is analysed. With the starting point comprising a unimodular three-metric with traceless momentum, a trace-induced anomaly results upon quantization. This leads to a revision of the choice of momentum variable to the (mixed index traceless momentric. This latter choice unitarily implements the fundamental commutation relations, which now take on the form of an affine algebra with SU(3 Lie algebra amongst the momentric variables. The resulting relations unitarily implement tracelessness upon quantization. The associated Poisson brackets and Hamiltonian dynamics are studied.

  10. Intrinsic bioremediation potential of a chronically polluted marine coastal area.

    Science.gov (United States)

    Catania, Valentina; Santisi, Santina; Signa, Geraldina; Vizzini, Salvatrice; Mazzola, Antonio; Cappello, Simone; Yakimov, Michail M; Quatrini, Paola

    2015-10-15

    A microbiological survey of the Priolo Bay (eastern coast of Sicily, Ionian Sea), a chronically polluted marine coastal area, was carried out in order to discern its intrinsic bioremediation potential. Microbiological analysis, 16S rDNA-based DGGE fingerprinting and PLFAs analysis were performed on seawater and sediment samples from six stations on two transects. Higher diversity and variability among stations was detected by DGGE in sediment than in water samples although seawater revealed higher diversity of culturable hydrocarbon-degrading bacteria. The most polluted sediment hosted higher total bacterial diversity and higher abundance and diversity of culturable HC degraders. Alkane- and PAH-degrading bacteria were isolated from all stations and assigned to Alcanivorax, Marinobacter, Thalassospira, Alteromonas and Oleibacter (first isolation from the Mediterranean area). High total microbial diversity associated to a large selection of HC degraders is believed to contribute to natural attenuation of the area, provided that new contaminant contributions are avoided. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Normal-Mode Analysis of Circular DNA at the Base-Pair Level. 2. Large-Scale Configurational Transformation of a Naturally Curved Molecule.

    Science.gov (United States)

    Matsumoto, Atsushi; Tobias, Irwin; Olson, Wilma K

    2005-01-01

    Fine structural and energetic details embedded in the DNA base sequence, such as intrinsic curvature, are important to the packaging and processing of the genetic material. Here we investigate the internal dynamics of a 200 bp closed circular molecule with natural curvature using a newly developed normal-mode treatment of DNA in terms of neighboring base-pair "step" parameters. The intrinsic curvature of the DNA is described by a 10 bp repeating pattern of bending distortions at successive base-pair steps. We vary the degree of intrinsic curvature and the superhelical stress on the molecule and consider the normal-mode fluctuations of both the circle and the stable figure-8 configuration under conditions where the energies of the two states are similar. To extract the properties due solely to curvature, we ignore other important features of the double helix, such as the extensibility of the chain, the anisotropy of local bending, and the coupling of step parameters. We compare the computed normal modes of the curved DNA model with the corresponding dynamical features of a covalently closed duplex of the same chain length constructed from naturally straight DNA and with the theoretically predicted dynamical properties of a naturally circular, inextensible elastic rod, i.e., an O-ring. The cyclic molecules with intrinsic curvature are found to be more deformable under superhelical stress than rings formed from naturally straight DNA. As superhelical stress is accumulated in the DNA, the frequency, i.e., energy, of the dominant bending mode decreases in value, and if the imposed stress is sufficiently large, a global configurational rearrangement of the circle to the figure-8 form takes place. We combine energy minimization with normal-mode calculations of the two states to decipher the configurational pathway between the two states. We also describe and make use of a general analytical treatment of the thermal fluctuations of an elastic rod to characterize the

  12. Iron and intrinsic deep level states in Ga2O3

    Science.gov (United States)

    Ingebrigtsen, M. E.; Varley, J. B.; Kuznetsov, A. Yu.; Svensson, B. G.; Alfieri, G.; Mihaila, A.; Badstübner, U.; Vines, L.

    2018-01-01

    Using a combination of deep level transient spectroscopy, secondary ion mass spectrometry, proton irradiation, and hybrid functional calculations, we identify two similar deep levels that are associated with Fe impurities and intrinsic defects in bulk crystals and molecular beam epitaxy and hydride vapor phase epitaxi-grown epilayers of β-Ga2O3. First, our results indicate that FeGa, and not an intrinsic defect, acts as the deep acceptor responsible for the often dominating E2 level at ˜0.78 eV below the conduction band minimum. Second, by provoking additional intrinsic defect generation via proton irradiation, we identified the emergence of a new level, labeled as E2*, having the ionization energy very close to that of E2, but exhibiting an order of magnitude larger capture cross section. Importantly, the properties of E2* are found to be consistent with its intrinsic origin. As such, contradictory opinions of a long standing literature debate on either extrinsic or intrinsic origin of the deep acceptor in question converge accounting for possible contributions from E2 and E2* in different experimental conditions.

  13. Extrinsic versus intrinsic factors in the decline and extinction of Australian marsupials.

    Science.gov (United States)

    Fisher, Diana O; Blomberg, Simon P; Owens, Ian P F

    2003-09-07

    Recent attempts to explain the susceptibility of vertebrates to declines worldwide have largely focused on intrinsic factors such as body size, reproductive potential, ecological specialization, geographical range and phylogenetic longevity. Here, we use a database of 145 Australian marsupial species to test the effects of both intrinsic and extrinsic factors in a multivariate comparative approach. We model five intrinsic (body size, habitat specialization, diet, reproductive rate and range size) and four extrinsic (climate and range overlap with introduced foxes, sheep and rabbits) factors. We use quantitative measures of geographical range contraction as indices of decline. We also develop a new modelling approach of phylogenetically independent contrasts combined with imputation of missing values to deal simultaneously with phylogenetic structuring and missing data. One extrinsic variable-geographical range overlap with sheep-was the only consistent predictor of declines. Habitat specialization was independently but less consistently associated with declines. This suggests that extrinsic factors largely determine interspecific variation in extinction risk among Australian marsupials, and that the intrinsic factors that are consistently associated with extinction risk in other vertebrates are less important in this group. We conclude that recent anthropogenic changes have been profound enough to affect species on a continent-wide scale, regardless of their intrinsic biology.

  14. Distinct molecular signatures of mild extrinsic and intrinsic atopic dermatitis

    DEFF Research Database (Denmark)

    Martel, Britta Cathrina; Litman, Thomas; Hald, Andreas

    2016-01-01

    Atopic dermatitis (AD) is a common inflammatory skin disease with underlying defects in epidermal function and immune responses. In this study, we used microarray analysis to investigate differences in gene expression in lesional skin from patients with mild extrinsic or intrinsic AD compared...... with mild extrinsic and intrinsic AD similar to previous reports for severe AD. Interestingly, expression of genes involved in inflammatory responses in intrinsic AD resembled that of psoriasis more than that of extrinsic AD. Overall, differences in expression of inflammation-associated genes found among...... patients with mild intrinsic and extrinsic AD correlated with previous findings for patients with severe intrinsic and extrinsic AD....

  15. What Is Mitochondrial DNA?

    Science.gov (United States)

    ... DNA What is mitochondrial DNA? What is mitochondrial DNA? Although most DNA is packaged in chromosomes within ... proteins. For more information about mitochondria and mitochondrial DNA: Molecular Expressions, a web site from the Florida ...

  16. Abundance of intrinsic structural disorder in the histone H1 subtypes.

    Science.gov (United States)

    Kowalski, Andrzej

    2015-12-01

    The intrinsically disordered proteins consist of partially structured regions linked to the unstructured stretches, which consequently form the transient and dynamic conformational ensembles. They undergo disorder to order transition upon binding their partners. Intrinsic disorder is attributed to histones H1, perceived as assemblers of chromatin structure and the regulators of DNA and proteins activity. In this work, the comparison of intrinsic disorder abundance in the histone H1 subtypes was performed both by the analysis of their amino acid composition and by the prediction of disordered stretches, as well as by identifying molecular recognition features (MoRFs) and ANCHOR protein binding regions (APBR) that are responsible for recognition and binding. Both human and model organisms-animals, plants, fungi and protists-have H1 histone subtypes with the properties typical of disordered state. They possess a significantly higher content of hydrophilic and charged amino acid residues, arranged in the long regions, covering over half of the whole amino acid residues in chain. Almost complete disorder corresponds to histone H1 terminal domains, including MoRFs and ANCHOR. Those motifs were also identified in a more ordered histone H1 globular domain. Compared to the control (globular and fibrous) proteins, H1 histones demonstrate the increased folding rate and a higher proportion of low-complexity segments. The results of this work indicate that intrinsic disorder is an inherent structural property of histone H1 subtypes and it is essential for establishing a protein conformation which defines functional outcomes affecting on DNA- and/or partner protein-dependent cell processes. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. The Neuroscience of Growth Mindset and Intrinsic Motivation.

    Science.gov (United States)

    Ng, Betsy

    2018-01-26

    Our actions can be triggered by intentions, incentives or intrinsic values. Recent neuroscientific research has yielded some results about the growth mindset and intrinsic motivation. With the advances in neuroscience and motivational studies, there is a global need to utilize this information to inform educational practice and research. Yet, little is known about the neuroscientific interplay between growth mindset and intrinsic motivation. This paper attempts to draw on the theories of growth mindset and intrinsic motivation, together with contemporary ideas in neuroscience, outline the potential for neuroscientific research in education. It aims to shed light on the relationship between growth mindset and intrinsic motivation in terms of supporting a growth mindset to facilitate intrinsic motivation through neural responses. Recent empirical research from the educational neuroscience perspective that provides insights into the interplay between growth mindset and intrinsic motivation will also be discussed.

  18. The Neuroscience of Growth Mindset and Intrinsic Motivation

    Directory of Open Access Journals (Sweden)

    Betsy Ng

    2018-01-01

    Full Text Available Our actions can be triggered by intentions, incentives or intrinsic values. Recent neuroscientific research has yielded some results about the growth mindset and intrinsic motivation. With the advances in neuroscience and motivational studies, there is a global need to utilize this information to inform educational practice and research. Yet, little is known about the neuroscientific interplay between growth mindset and intrinsic motivation. This paper attempts to draw on the theories of growth mindset and intrinsic motivation, together with contemporary ideas in neuroscience, outline the potential for neuroscientific research in education. It aims to shed light on the relationship between growth mindset and intrinsic motivation in terms of supporting a growth mindset to facilitate intrinsic motivation through neural responses. Recent empirical research from the educational neuroscience perspective that provides insights into the interplay between growth mindset and intrinsic motivation will also be discussed.

  19. A tonoplast intrinsic protein in Gardenia jasminoides

    Science.gov (United States)

    Gao, Lan; Li, Hao-Ming

    2017-08-01

    Physiological and molecular studies proved that plasma membrane intrinsic proteins (PIPs) and tonoplast intrinsic proteins (TIPs) subfamily of aquaporins play key functions in plant water homeostasis. Five specialized subgroups (TIP1-5) of TIPs have been found in higher plants, in which the TIP1 and TIP2 isoforms are the largest arbitrary groups. TIPs have high water-transport activity than PIPs, some TIPs can transport other small molecule such as urea, ammonia, hydrogen peroxide, and carbon dioxide. In this work, the structure of the putative tonoplast aquaporin from Gardenia jasminoides (GjTIP) was analyzed. Its transcript level has increased during fruit maturation. A phylogenetic analysis indicates that the protein belongs to TIP1 subfamily. A three-dimensional model structure of GjTIP was built based on crystal structure of an ammonia-permeable AtTIP2-1 from Arabidopsis thaliana. The model structure displayed as a homo-tetramer, each monomer has six trans-membrane and two half-membrane-spanning α helices. The data suggests that the GjTIP has tendency to be a mixed function aquaporin, might involve in water, urea and hydrogen peroxide transport, and the gating machanism founded in some AQPs involving pH and phosphorylation response have not been proved in GjTIP.

  20. Intrinsic position uncertainty impairs overt search performance.

    Science.gov (United States)

    Semizer, Yelda; Michel, Melchi M

    2017-08-01

    Uncertainty regarding the position of the search target is a fundamental component of visual search. However, due to perceptual limitations of the human visual system, this uncertainty can arise from intrinsic, as well as extrinsic, sources. The current study sought to characterize the role of intrinsic position uncertainty (IPU) in overt visual search and to determine whether it significantly limits human search performance. After completing a preliminary detection experiment to characterize sensitivity as a function of visual field position, observers completed a search task that required localizing a Gabor target within a field of synthetic luminance noise. The search experiment included two clutter conditions designed to modulate the effect of IPU across search displays of varying set size. In the Cluttered condition, the display was tiled uniformly with feature clutter to maximize the effects of IPU. In the Uncluttered condition, the clutter at irrelevant locations was removed to attenuate the effects of IPU. Finally, we derived an IPU-constrained ideal searcher model, limited by the IPU measured in human observers. Ideal searchers were simulated based on the detection sensitivity and fixation sequences measured for individual human observers. The IPU-constrained ideal searcher predicted performance trends similar to those exhibited by the human observers. In the Uncluttered condition, performance decreased steeply as a function of increasing set size. However, in the Cluttered condition, the effect of IPU dominated and performance was approximately constant as a function of set size. Our findings suggest that IPU substantially limits overt search performance, especially in crowded displays.

  1. Human dignity: intrinsic or relative value?

    Science.gov (United States)

    Thiel, Marie-Jo

    2010-09-01

    Is human dignity an intrinsic value? Or is it a relative value, depending on the perception or assessment of quality of life? History had delineated some of its key features, but the advent of human rights and the Holocaust put special emphasis on this notion, particularly in the field of bioethics. But if modern medicine regards human dignity as crucial, it tends to support this notion while assessing and measuring it. The quality of life becomes the gauge for measuring human dignity, starting from a distinction between a viable and a non-viable existence, which may eventually lead to assisted death, or to letting die. This article argues that the concept of quality of life is of great relevant for medical practice, but on the condition of not being used as a standard to measure the dignity of the individual. Rather, the quality of life should be regarded as an imperative posed by human dignity, which is necessarily intrinsic. If the quality of life measures dignity, humankind is divided into two categories: lives worthy of living, and lives unworthy of living, and society becomes a jungle. Raising the quality of life as a requirement of the inherent human dignity does not solve automatically all problems and does not eliminate a feeling of unworthiness. But it ensures its 'human' value: the equal respect for every human being.

  2. Intrinsic electromagnetic solitary vortices in magnetized plasma

    International Nuclear Information System (INIS)

    Liu, J.; Horton, W.

    1986-01-01

    Several Rossby type vortex solutions constructed for electromagnetic perturbations in magnetized plasma encounter the difficulty that the perturbed magnetic field and the parallel current are not continuous on the boundary between two regions. We find that fourth order differential equations must be solved to remove this discontinuity. Special solutions for two types of boundary value problems for the fourth order partial differential equations are presented. By applying these solutions to different nonlinear equations in magnetized plasma, the intrinsic electromagnetic solitary drift-Alfven vortex (along with solitary Alfven vortex) and the intrinsic electromagnetic solitary electron vortex (along with short-wavelength drift vortex) are constructed. While still keeping a localized dipole structure, these new vortices have more complicated radial structures in the inner and outer regions than the usual Rossby wave vortex. The new type of vortices guarantees the continuity of the perturbed magnetic field deltaB/sub perpendicular/ and the parallel current j/sub parallel/ on the boundary between inner and outer regions of the vortex. The allowed regions of propagation speeds for these vortices are analyzed, and we find that the complementary relation between the vortex propagating speeds and the corresponding phase velocities of the linear modes no longer exists

  3. The neglected intrinsic resistome of bacterial pathogens.

    Directory of Open Access Journals (Sweden)

    Alicia Fajardo

    Full Text Available Bacteria with intrinsic resistance to antibiotics are a worrisome health problem. It is widely believed that intrinsic antibiotic resistance of bacterial pathogens is mainly the consequence of cellular impermeability and activity of efflux pumps. However, the analysis of transposon-tagged Pseudomonas aeruginosa mutants presented in this article shows that this phenotype emerges from the action of numerous proteins from all functional categories. Mutations in some genes make P. aeruginosa more susceptible to antibiotics and thereby represent new targets. Mutations in other genes make P. aeruginosa more resistant and therefore define novel mechanisms for mutation-driven acquisition of antibiotic resistance, opening a new research field based in the prediction of resistance before it emerges in clinical environments. Antibiotics are not just weapons against bacterial competitors, but also natural signalling molecules. Our results demonstrate that antibiotic resistance genes are not merely protective shields and offer a more comprehensive view of the role of antibiotic resistance genes in the clinic and in nature.

  4. DNA-based watermarks using the DNA-Crypt algorithm

    Science.gov (United States)

    Heider, Dominik; Barnekow, Angelika

    2007-01-01

    Background The aim of this paper is to demonstrate the application of watermarks based on DNA sequences to identify the unauthorized use of genetically modified organisms (GMOs) protected by patents. Predicted mutations in the genome can be corrected by the DNA-Crypt program leaving the encrypted information intact. Existing DNA cryptographic and steganographic algorithms use synthetic DNA sequences to store binary information however, although these sequences can be used for authentication, they may change the target DNA sequence when introduced into living organisms. Results The DNA-Crypt algorithm and image steganography are based on the same watermark-hiding principle, namely using the least significant base in case of DNA-Crypt and the least significant bit in case of the image steganography. It can be combined with binary encryption algorithms like AES, RSA or Blowfish. DNA-Crypt is able to correct mutations in the target DNA with several mutation correction codes such as the Hamming-code or the WDH-code. Mutations which can occur infrequently may destroy the encrypted information, however an integrated fuzzy controller decides on a set of heuristics based on three input dimensions, and recommends whether or not to use a correction code. These three input dimensions are the length of the sequence, the individual mutation rate and the stability over time, which is represented by the number of generations. In silico experiments using the Ypt7 in Saccharomyces cerevisiae shows that the DNA watermarks produced by DNA-Crypt do not alter the translation of mRNA into protein. Conclusion The program is able to store watermarks in living organisms and can maintain the original information by correcting mutations itself. Pairwise or multiple sequence alignments show that DNA-Crypt produces few mismatches between the sequences similar to all steganographic algorithms. PMID:17535434

  5. DNA-based watermarks using the DNA-Crypt algorithm

    Directory of Open Access Journals (Sweden)

    Barnekow Angelika

    2007-05-01

    Full Text Available Abstract Background The aim of this paper is to demonstrate the application of watermarks based on DNA sequences to identify the unauthorized use of genetically modified organisms (GMOs protected by patents. Predicted mutations in the genome can be corrected by the DNA-Crypt program leaving the encrypted information intact. Existing DNA cryptographic and steganographic algorithms use synthetic DNA sequences to store binary information however, although these sequences can be used for authentication, they may change the target DNA sequence when introduced into living organisms. Results The DNA-Crypt algorithm and image steganography are based on the same watermark-hiding principle, namely using the least significant base in case of DNA-Crypt and the least significant bit in case of the image steganography. It can be combined with binary encryption algorithms like AES, RSA or Blowfish. DNA-Crypt is able to correct mutations in the target DNA with several mutation correction codes such as the Hamming-code or the WDH-code. Mutations which can occur infrequently may destroy the encrypted information, however an integrated fuzzy controller decides on a set of heuristics based on three input dimensions, and recommends whether or not to use a correction code. These three input dimensions are the length of the sequence, the individual mutation rate and the stability over time, which is represented by the number of generations. In silico experiments using the Ypt7 in Saccharomyces cerevisiae shows that the DNA watermarks produced by DNA-Crypt do not alter the translation of mRNA into protein. Conclusion The program is able to store watermarks in living organisms and can maintain the original information by correcting mutations itself. Pairwise or multiple sequence alignments show that DNA-Crypt produces few mismatches between the sequences similar to all steganographic algorithms.

  6. DNA-based watermarks using the DNA-Crypt algorithm.

    Science.gov (United States)

    Heider, Dominik; Barnekow, Angelika

    2007-05-29

    The aim of this paper is to demonstrate the application of watermarks based on DNA sequences to identify the unauthorized use of genetically modified organisms (GMOs) protected by patents. Predicted mutations in the genome can be corrected by the DNA-Crypt program leaving the encrypted information intact. Existing DNA cryptographic and steganographic algorithms use synthetic DNA sequences to store binary information however, although these sequences can be used for authentication, they may change the target DNA sequence when introduced into living organisms. The DNA-Crypt algorithm and image steganography are based on the same watermark-hiding principle, namely using the least significant base in case of DNA-Crypt and the least significant bit in case of the image steganography. It can be combined with binary encryption algorithms like AES, RSA or Blowfish. DNA-Crypt is able to correct mutations in the target DNA with several mutation correction codes such as the Hamming-code or the WDH-code. Mutations which can occur infrequently may destroy the encrypted information, however an integrated fuzzy controller decides on a set of heuristics based on three input dimensions, and recommends whether or not to use a correction code. These three input dimensions are the length of the sequence, the individual mutation rate and the stability over time, which is represented by the number of generations. In silico experiments using the Ypt7 in Saccharomyces cerevisiae shows that the DNA watermarks produced by DNA-Crypt do not alter the translation of mRNA into protein. The program is able to store watermarks in living organisms and can maintain the original information by correcting mutations itself. Pairwise or multiple sequence alignments show that DNA-Crypt produces few mismatches between the sequences similar to all steganographic algorithms.

  7. Risk assessment of DNA-reactive carcinogens in food.

    Science.gov (United States)

    Jeffrey, A M; Williams, G M

    2005-09-01

    Risk assessment of DNA-reactive carcinogens in food requires knowledge of the extent of DNA damage in the target organ which results from the competition between DNA adduct formation and repair. Estimates of DNA adduct levels can be made by direct measurement or indirectly as a consequence of their presence, for example, by tumor formation in animal models or exposed populations epidemiologically. Food-borne DNA-reactive carcinogens are present from a variety of sources. They are generally not intrinsically DNA-reactive but require bioactivation to DNA-reactive metabolites a process which may be modulated by the compound itself or the presence of other xenobiotics. A single DNA reactant may form several distinct DNA adducts each undergoing different rates of repair. Some DNA reactants may be photochemically activated or produce reactive oxygen species and thus indirect oxidative DNA damage. The levels of DNA adducts arising from exposures influenced by variations in the doses, the frequency with which an individual is exposed, and rates of DNA repair for specific adducts. Each adduct has a characteristic efficiency with which it induces mutations. Based on experience with the well-studied DNA-reactive food carcinogen aflatoxin B(1) (AFB(1)), a limit of 20 ppb or approximately 30 microg/day has been set and is considered a tolerable daily intake (TDI). Since AFB(1) is considered a potent carcinogen, doses of carcinogens is made.

  8. Intrinsically secure fast reactors with dense cores

    International Nuclear Information System (INIS)

    Slessarev, Igor

    2007-01-01

    Secure safety, resistance to weapons material proliferation and problems of long-lived wastes remain the most important 'painful points' of nuclear power. Many innovative reactor concepts have been developed aimed at a radical enhancement of safety. The promising potential of innovative nuclear reactors allows for shifting accents in current reactor safety 'strategy' to reveal this worth. Such strategy is elaborated focusing on the priority for intrinsically secure safety features as well as on sure protection being provided by the first barrier of defence. Concerning the potential of fast reactors (i.e. sodium cooled, lead-cooled, etc.), there are no doubts that they are able to possess many favourable intrinsically secure safety features and to lay the proper foundation for a new reactor generation. However, some of their neutronic characteristics have to be radically improved. Among intrinsically secure safety properties, the following core parameters are significantly important: reactivity margin values, reactivity feed-back and coolant void effects. Ways of designing intrinsically secure safety features in fast reactors (titled hereafter as Intrinsically Secure Fast Reactors - ISFR) can be found in the frame of current reactor technologies by radical enhancement of core neutron economy and by optimization of core compositions. Simultaneously, respecting resistance to proliferation, by using non-enriched fuel feed as well as a core breeding gain close to zero, are considered as the important features (long-lived waste problems will be considered in a separate paper). This implies using the following reactor design options as well as closed fuel cycles with natural U as the reactor feed: ·Ultra-plate 'dense cores' of the ordinary (monolithic) type with negative total coolant void effects. ·Modular type cores. Multiple dense modules can be embedded in the common reflector for achieving the desired NPP total power. The modules can be used also independently (as

  9. What's in a name? : Why these proteins are intrinsically disordered: Why these proteins are intrinsically disordered

    NARCIS (Netherlands)

    Dunker, A Keith; Babu, M Madan; Barbar, Elisar; Blackledge, Martin; Bondos, Sarah E; Dosztányi, Zsuzsanna; Dyson, H Jane; Forman-Kay, Julie; Fuxreiter, Monika; Gsponer, Jörg; Han, Kyou-Hoon; Jones, David T; Longhi, Sonia; Metallo, Steven J; Nishikawa, Ken; Nussinov, Ruth; Obradovic, Zoran; Pappu, Rohit V; Rost, Burkhard; Selenko, Philipp; Subramaniam, Vinod; Sussman, Joel L; Tompa, Peter; Uversky, Vladimir N

    2013-01-01

    "What's in a name? That which we call a rose By any other name would smell as sweet." From "Romeo and Juliet", William Shakespeare (1594) This article opens a series of publications on disambiguation of the basic terms used in the field of intrinsically disordered proteins. We start from the

  10. An Analysis of Intrinsic and Extrinsic Hand Muscle EMG for Improved Pattern Recognition Control.

    Science.gov (United States)

    Adewuyi, Adenike A; Hargrove, Levi J; Kuiken, Todd A

    2016-04-01

    Pattern recognition control combined with surface electromyography (EMG) from the extrinsic hand muscles has shown great promise for control of multiple prosthetic functions for transradial amputees. There is, however, a need to adapt this control method when implemented for partial-hand amputees, who possess both a functional wrist and information-rich residual intrinsic hand muscles. We demonstrate that combining EMG data from both intrinsic and extrinsic hand muscles to classify hand grasps and finger motions allows up to 19 classes of hand grasps and individual finger motions to be decoded, with an accuracy of 96% for non-amputees and 85% for partial-hand amputees. We evaluated real-time pattern recognition control of three hand motions in seven different wrist positions. We found that a system trained with both intrinsic and extrinsic muscle EMG data, collected while statically and dynamically varying wrist position increased completion rates from 73% to 96% for partial-hand amputees and from 88% to 100% for non-amputees when compared to a system trained with only extrinsic muscle EMG data collected in a neutral wrist position. Our study shows that incorporating intrinsic muscle EMG data and wrist motion can significantly improve the robustness of pattern recognition control for application to partial-hand prosthetic control.

  11. Quantification and presence of human ancient DNA in burial place ...

    African Journals Online (AJOL)

    Quantification and presence of human ancient DNA in burial place remains of Turkey using real time polymerase chain reaction. ... A published real-time PCR assay, which allows for the combined analysis of nuclear or ancient DNA and mitochondrial DNA, was modified. This approach can be used for recovering DNA from ...

  12. Ancient DNA from marine mammals

    DEFF Research Database (Denmark)

    Foote, Andrew David; Hofreiter, Michael; Morin, Philip A.

    2012-01-01

    such as bone, tooth, baleen, skin, fur, whiskers and scrimshaw using ancient DNA (aDNA) approaches provide an oppor- tunity for investigating such changes over evolutionary and ecological timescales. Here, we review the application of aDNA techniques to the study of marine mammals. Most of the studies have...... focused on detecting changes in genetic diversity following periods of exploitation and environmental change. To date, these studies have shown that even small sample sizes can provide useful information on historical genetic diversity. Ancient DNA has also been used in investigations of changes...... in distribution and range of marine mammal species; we review these studies and discuss the limitations of such ‘presence only’ studies. Combining aDNA data with stable isotopes can provide further insights into changes in ecology and we review past studies and suggest future potential applications. We also...

  13. Intrinsically disordered proteins as molecular shields†

    Science.gov (United States)

    Chakrabortee, Sohini; Tripathi, Rashmi; Watson, Matthew; Kaminski Schierle, Gabriele S.; Kurniawan, Davy P.; Kaminski, Clemens F.; Wise, Michael J.; Tunnacliffe, Alan

    2017-01-01

    The broad family of LEA proteins are intrinsically disordered proteins (IDPs) with several potential roles in desiccation tolerance, or anhydrobiosis, one of which is to limit desiccation-induced aggregation of cellular proteins. We show here that this activity, termed molecular shield function, is distinct from that of a classical molecular chaperone, such as HSP70 – while HSP70 reduces aggregation of citrate synthase (CS) on heating, two LEA proteins, a nematode group 3 protein, AavLEA1, and a plant group 1 protein, Em, do not; conversely, the LEA proteins reduce CS aggregation on desiccation, while HSP70 lacks this ability. There are also differences in interaction with client proteins – HSP70 can be co-immunoprecipitated with a polyglutamine-containing client, consistent with tight complex formation, whereas the LEA proteins can not, although a loose interaction is observed by Förster resonance energy transfer. In a further exploration of molecular shield function, we demonstrate that synthetic polysaccharides, like LEA proteins, are able to reduce desiccation-induced aggregation of a water-soluble proteome, consistent with a steric interference model of anti-aggregation activity. If molecular shields operate by reducing intermolecular cohesion rates, they should not protect against intramolecular protein damage. This was tested using the monomeric red fluorescent protein, mCherry, which does not undergo aggregation on drying, but the absorbance and emission spectra of its intrinsic fluorophore are dramatically reduced, indicative of intramolecular conformational changes. As expected, these changes are not prevented by AavLEA1, except for a slight protection at high molar ratios, and an AavLEA1-mCherry fusion protein is damaged to the same extent as mCherry alone. A recent hypothesis proposed that proteomes from desiccation-tolerant species contain a higher degree of disorder than intolerant examples, and that this might provide greater intrinsic stability

  14. Intrinsically disordered proteins as molecular shields.

    Science.gov (United States)

    Chakrabortee, Sohini; Tripathi, Rashmi; Watson, Matthew; Schierle, Gabriele S Kaminski; Kurniawan, Davy P; Kaminski, Clemens F; Wise, Michael J; Tunnacliffe, Alan

    2012-01-01

    The broad family of LEA proteins are intrinsically disordered proteins (IDPs) with several potential roles in desiccation tolerance, or anhydrobiosis, one of which is to limit desiccation-induced aggregation of cellular proteins. We show here that this activity, termed molecular shield function, is distinct from that of a classical molecular chaperone, such as HSP70 - while HSP70 reduces aggregation of citrate synthase (CS) on heating, two LEA proteins, a nematode group 3 protein, AavLEA1, and a plant group 1 protein, Em, do not; conversely, the LEA proteins reduce CS aggregation on desiccation, while HSP70 lacks this ability. There are also differences in interaction with client proteins - HSP70 can be co-immunoprecipitated with a polyglutamine-containing client, consistent with tight complex formation, whereas the LEA proteins can not, although a loose interaction is observed by Förster resonance energy transfer. In a further exploration of molecular shield function, we demonstrate that synthetic polysaccharides, like LEA proteins, are able to reduce desiccation-induced aggregation of a water-soluble proteome, consistent with a steric interference model of anti-aggregation activity. If molecular shields operate by reducing intermolecular cohesion rates, they should not protect against intramolecular protein damage. This was tested using the monomeric red fluorescent protein, mCherry, which does not undergo aggregation on drying, but the absorbance and emission spectra of its intrinsic fluorophore are dramatically reduced, indicative of intramolecular conformational changes. As expected, these changes are not prevented by AavLEA1, except for a slight protection at high molar ratios, and an AavLEA1-mCherry fusion protein is damaged to the same extent as mCherry alone. A recent hypothesis proposed that proteomes from desiccation-tolerant species contain a higher degree of disorder than intolerant examples, and that this might provide greater intrinsic stability

  15. Structural organization of DNA in chlorella viruses.

    Directory of Open Access Journals (Sweden)

    Timo Wulfmeyer

    Full Text Available Chlorella viruses have icosahedral capsids with an internal membrane enclosing their large dsDNA genomes and associated proteins. Their genomes are packaged in the particles with a predicted DNA density of ca. 0.2 bp nm(-3. Occasionally infection of an algal cell by an individual particle fails and the viral DNA is dynamically ejected from the capsid. This shows that the release of the DNA generates a force, which can aid in the transfer of the genome into the host in a successful infection. Imaging of ejected viral DNA indicates that it is intimately associated with proteins in a periodic fashion. The bulk of the protein particles detected by atomic force microscopy have a size of ∼60 kDa and two proteins (A278L and A282L of about this size are among 6 basic putative DNA binding proteins found in a proteomic analysis of DNA binding proteins packaged in the virion. A combination of fluorescence images of ejected DNA and a bioinformatics analysis of the DNA reveal periodic patterns in the viral DNA. The periodic distribution of GC rich regions in the genome provides potential binding sites for basic proteins. This DNA/protein aggregation could be responsible for the periodic concentration of fluorescently labeled DNA observed in ejected viral DNA. Collectively the data indicate that the large chlorella viruses have a DNA packaging strategy that differs from bacteriophages; it involves proteins and share similarities to that of chromatin structure in eukaryotes.

  16. DNA: Polymer and molecular code

    Science.gov (United States)

    Shivashankar, G. V.

    1999-10-01

    The thesis work focusses upon two aspects of DNA, the polymer and the molecular code. Our approach was to bring single molecule micromanipulation methods to the study of DNA. It included a home built optical microscope combined with an atomic force microscope and an optical tweezer. This combined approach led to a novel method to graft a single DNA molecule onto a force cantilever using the optical tweezer and local heating. With this method, a force versus extension assay of double stranded DNA was realized. The resolution was about 10 picoN. To improve on this force measurement resolution, a simple light backscattering technique was developed and used to probe the DNA polymer flexibility and its fluctuations. It combined the optical tweezer to trap a DNA tethered bead and the laser backscattering to detect the beads Brownian fluctuations. With this technique the resolution was about 0.1 picoN with a millisecond access time, and the whole entropic part of the DNA force-extension was measured. With this experimental strategy, we measured the polymerization of the protein RecA on an isolated double stranded DNA. We observed the progressive decoration of RecA on the l DNA molecule, which results in the extension of l , due to unwinding of the double helix. The dynamics of polymerization, the resulting change in the DNA entropic elasticity and the role of ATP hydrolysis were the main parts of the study. A simple model for RecA assembly on DNA was proposed. This work presents a first step in the study of genetic recombination. Recently we have started a study of equilibrium binding which utilizes fluorescence polarization methods to probe the polymerization of RecA on single stranded DNA. In addition to the study of material properties of DNA and DNA-RecA, we have developed experiments for which the code of the DNA is central. We studied one aspect of DNA as a molecular code, using different techniques. In particular the programmatic use of template specificity makes

  17. Polymers of intrinsic microporosity with dinaphthyl and thianthrene segments

    KAUST Repository

    Du, Naiying; Robertson, Gilles P.; Pinnau, Ingo; Guiver, Michael D.

    2010-01-01

    Novel intrinsically microporous homopolymers and copolymers derived from PIM-1 monomers (5,5,6,6-tetrahydroxy-3,3,3,3-tetramethylspirobisindane and 2,3,5,6-tetrafluoroterephthalonitrile) with two additional monomers- tetrahydroxydinaphthyl and tetrafluorotetraoxide thianthrene-are reported as potential materials for membrane-based gas separations. The resulting copolymers prevent efficient space packing of the stiff polymer chains and consequently exhibit analogous behavior to that of PIM-1, the most widely reported polymer in this class of materials. In addition, the copolymerization provides high molecular weight copolymers and low polydispersity if the polymerization reactions were conducted at elevated temperature for an extended period of time. Detailed structural characterization of the new monomers and polymers was determined by 1H and 19F nuclear magnetic resonance spectroscopy (NMR). The thermal properties were detected by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). Polymer free volume was calculated from the polymer density and specific van der Waals volume. Under the same testing conditions, the homopolymer containing thianthrene units and most of the analogous copolymers have an excellent combination of properties with good film-forming characteristics. The gas transport properties show higher selectivity for gas pairs such as O 2/N2, CO2/N2, and H 2/N2 with a corresponding decrease in permeability compared to PIM-1. This work also demonstrates that significant improvements in properties may be obtained through copolymers of intrinsic microporosity (CoPIM)s. Furthermore, this work extends the spectrum of high molecular weight soluble PIMs beyond those reported previously. © 2010 American Chemical Society.

  18. Polymers of intrinsic microporosity with dinaphthyl and thianthrene segments

    KAUST Repository

    Du, Naiying

    2010-10-26

    Novel intrinsically microporous homopolymers and copolymers derived from PIM-1 monomers (5,5,6,6-tetrahydroxy-3,3,3,3-tetramethylspirobisindane and 2,3,5,6-tetrafluoroterephthalonitrile) with two additional monomers- tetrahydroxydinaphthyl and tetrafluorotetraoxide thianthrene-are reported as potential materials for membrane-based gas separations. The resulting copolymers prevent efficient space packing of the stiff polymer chains and consequently exhibit analogous behavior to that of PIM-1, the most widely reported polymer in this class of materials. In addition, the copolymerization provides high molecular weight copolymers and low polydispersity if the polymerization reactions were conducted at elevated temperature for an extended period of time. Detailed structural characterization of the new monomers and polymers was determined by 1H and 19F nuclear magnetic resonance spectroscopy (NMR). The thermal properties were detected by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). Polymer free volume was calculated from the polymer density and specific van der Waals volume. Under the same testing conditions, the homopolymer containing thianthrene units and most of the analogous copolymers have an excellent combination of properties with good film-forming characteristics. The gas transport properties show higher selectivity for gas pairs such as O 2/N2, CO2/N2, and H 2/N2 with a corresponding decrease in permeability compared to PIM-1. This work also demonstrates that significant improvements in properties may be obtained through copolymers of intrinsic microporosity (CoPIM)s. Furthermore, this work extends the spectrum of high molecular weight soluble PIMs beyond those reported previously. © 2010 American Chemical Society.

  19. Partner-Mediated Polymorphism of an Intrinsically Disordered Protein.

    Science.gov (United States)

    Bignon, Christophe; Troilo, Francesca; Gianni, Stefano; Longhi, Sonia

    2017-11-29

    Intrinsically disordered proteins (IDPs) recognize their partners through molecular recognition elements (MoREs). The MoRE of the C-terminal intrinsically disordered domain of the measles virus nucleoprotein (N TAIL ) is partly pre-configured as an α-helix in the free form and undergoes α-helical folding upon binding to the X domain (XD) of the viral phosphoprotein. Beyond XD, N TAIL also binds the major inducible heat shock protein 70 (hsp70). So far, no structural information is available for the N TAIL /hsp70 complex. Using mutational studies combined with a protein complementation assay based on green fluorescent protein reconstitution, we have investigated both N TAIL /XD and N TAIL /hsp70 interactions. Although the same N TAIL region binds the two partners, the binding mechanisms are different. Hsp70 binding is much more tolerant of MoRE substitutions than XD, and the majority of substitutions lead to an increased N TAIL /hsp70 interaction strength. Furthermore, while an increased and a decreased α-helicity of the MoRE lead to enhanced and reduced interaction strength with XD, respectively, the impact on hsp70 binding is negligible, suggesting that the MoRE does not adopt an α-helical conformation once bound to hsp70. Here, by showing that the α-helical conformation sampled by the free form of the MoRE does not systematically commit it to adopt an α-helical conformation in the bound form, we provide an example of partner-mediated polymorphism of an IDP and of the relative insensitiveness of the bound structure to the pre-recognition state. The present results therefore contribute to shed light on the molecular mechanisms by which IDPs recognize different partners. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. IMPACT OF BARYONIC PHYSICS ON INTRINSIC ALIGNMENTS

    Energy Technology Data Exchange (ETDEWEB)

    Tenneti, Ananth; Gnedin, Nickolay Y. [Particle Astrophysics Center, Fermi National Accelerator Laboratory, Batavia, IL 60510 (United States); Feng, Yu, E-mail: vat@andrew.cmu.edu [Berkeley Center for Cosmological Physics, Department of Physics, University of California Berkeley, Berkeley, CA 94720 (United States)

    2017-01-10

    We explore the effects of specific assumptions in the subgrid models of star formation and stellar and active galactic nucleus feedback on intrinsic alignments of galaxies in cosmological simulations of the “MassiveBlack-II” family. Using smaller-volume simulations, we explore the parameter space of the subgrid star formation and feedback model and find remarkable robustness of the observable statistical measures to the details of subgrid physics. The one observational probe most sensitive to modeling details is the distribution of misalignment angles. We hypothesize that the amount of angular momentum carried away by the galactic wind is the primary physical quantity that controls the orientation of the stellar distribution. Our results are also consistent with a similar study by the EAGLE simulation team.

  1. Intrinsic Orbital Angular Momentum States of Neutrons

    Science.gov (United States)

    Cappelletti, Ronald L.; Jach, Terrence; Vinson, John

    2018-03-01

    It has been shown that single-particle wave functions, of both photons and electrons, can be created with a phase vortex, i.e., an intrinsic orbital angular momentum (OAM). A recent experiment has claimed similar success using neutrons [C. W. Clark et al., Nature, 525, 504 (2015), 10.1038/nature15265]. We show that their results are insufficient to unambiguously demonstrate OAM, and they can be fully explained as phase contrast interference patterns. Furthermore, given the small transverse coherence length of the neutrons in the original experiment, the probability that any neutron was placed in an OAM state is vanishingly small. We highlight the importance of the relative size of the coherence length, which presents a unique challenge for neutron experiments compared to electron or photon work, and we suggest improvements for the creation of neutron OAM states.

  2. Intrinsic magnetic torque at low magnetic induction

    International Nuclear Information System (INIS)

    Doria, M.M.; Oliveira, I.G. de.

    1993-01-01

    Using anisotropic London theory the intrinsic magnetic torque for extreme type II uniaxial superconductors for any value of the magnetic induction is obtained. It is considered the vortex lines straight and take into account the contribution of the supercurrents flowing inside the vortex core within the London theory. It is shown that the interline and intra line free energies give opposite torque contributions, the first drives the magnetic induction parallel to the superconductor's axis of symmetry and the second orthogonal to it. At high magnetic induction torque expression obtained generalizes V. Kogan's formula since it has no free parameters other than the anisotropy γ = m 1 /m 3 and the Ginzburg-Landau parameter κ. At low magnetic induction it is proposed a way to observe vortex chains effects in the total torque based on the fact that London theory is linear and the energy to make a single vortex line in space is independent of the magnetic induction. (author)

  3. Intrinsic factors associated with pregnancy falls.

    Science.gov (United States)

    Wu, Xuefang; Yeoh, Han T

    2014-10-01

    Approximately 25% to 27% of women sustain a fall during pregnancy, and falls are associated with serious injuries and can affect pregnancy outcomes. The objective of the current study was to identify intrinsic factors associated with pregnancy that may contribute to women's increased risk of falls. A literature search (Medline and Pubmed) identified articles published between January 1980 and June 2013 that measured associations between pregnancy and fall risks, using an existing fall accident investigation framework. The results indicated that physiological, biomechanical, and psychological changes associated with pregnancy may influence the initiation, detection, and recovery phases of falls and increase the risk of falls in this population. Considering the logistic difficulties and ethnic concerns in recruiting pregnant women to participate in this investigation of fall risk factors, identification of these factors could establish effective fall prevention and intervention programs for pregnant women and improve birth outcomes. [Workplace Health Saf 2014;62(10):403-408.]. Copyright 2014, SLACK Incorporated.

  4. Intrinsic thermal expansion of crystal defects

    International Nuclear Information System (INIS)

    Ganne, J.-P.

    1981-02-01

    Although the phenomenon of thermal expansion has long been known, the intrinsic thermal expansion coefficient (ITEC) βsub(d) of a point defect, derived from its formation volume vsub(d), has never been measured directly. The differential dilatometer by interferometry built by ASTY and GILDER is described. It has allowed βsub(d) to be measured for several defects. Vacancies and small interstitial loops were produced in aluminium by low temperature (20 K) fast neutron irradiation followed by an anneal up to the beginning of stage III (160 K). The very high value of the measured ratio βsub(d)/β 0 (12+-4) is comparable with a lattice statics calculated (42) value (11.5 0 [fr

  5. Quantum synchronization effects in intrinsic Josephson junctions

    International Nuclear Information System (INIS)

    Machida, M.; Kano, T.; Yamada, S.; Okumura, M.; Imamura, T.; Koyama, T.

    2008-01-01

    We investigate quantum dynamics of the superconducting phase in intrinsic Josephson junctions of layered high-T c superconductors motivated by a recent experimental observation for the switching rate enhancement in the low temperature quantum regime. We pay attention to only the capacitive coupling between neighboring junctions and perform large-scale simulations for the Schroedinger equation derived from the Hamiltonian considering the capacitive coupling alone. The simulation focuses on an issue whether the switching of a junction induces those of the other junctions or not. The results reveal that the superconducting phase dynamics show synchronous behavior with increasing the quantum character, e.g., decreasing the junction plane area and effectively the temperature. This is qualitatively consistent with the experimental result

  6. Intrinsic Dynamics of Quantum-Dash Lasers

    KAUST Repository

    Chen, Cheng; Djie, Hery Susanto; Hwang, James C. M.; Koch, Thomas L.; Lester, Luke F.; Ooi, Boon S.; Wang, Yang

    2011-01-01

    Temperature-dependent intrinsic modulation response of InAs/InAlGaAs quantum-dash lasers was investigated by using pulse optical injection modulation to minimize the effects of parasitics and self-heating. Compared to typical quantum-well lasers, the quantum-dash lasers were found to have comparable differential gain but approximately twice the gain compression factor, probably due to carrier heating by free-carrier absorption, as opposed to stimulated transition. Therefore, the narrower modulation bandwidth of the quantum-dash lasers than that of quantum-well lasers was attributed to their higher gain compression factor. In addition, as expected, quantum-dash lasers with relatively long and uniform dashes exhibit higher temperature stability than quantum-well lasers. However, the lasers with relatively short and nonuniform dashes exhibit stronger temperature dependence, probably due to their higher surface-to-volume ratio and nonuniform dash sizes. © 2011 IEEE.

  7. Intrinsically Safe and Economical Reactor (ISER)

    International Nuclear Information System (INIS)

    Wakabayashi, Hiroaki; Asahi, Yoshiro

    1991-01-01

    The Intrinsically Safe and Economical Reactor (ISER) is designed based on the principle of a process inherent ultimate safe reactor, PIUS, a so-called inherently safe reactor (ISR). ISER has been developed joingly by the members of the Kanagawa Institute of Technology, the University of Tokyo, the Japan Atomic Energy Research Institute (JAERI) and several industrial firms in Japan. This paper describes the requirements for the next generation of power reactor, the safety design philosphy of ISR and ISER, the controllability of ISER and the results of analyses of some of the design-based accidents (DBA) of ISER, namely station blackout, accidents in which the pressurizer relief valve becomes jammed and stuck in open position and tube breaks in the steam generator. It is concluded that the ISER can ensure a wide range of contraollabitily and fuel integrity for all the analysed DBAs. (orig.)

  8. Mechanisms of Intrinsic Tumor Resistance to Immunotherapy

    Directory of Open Access Journals (Sweden)

    John Rieth

    2018-05-01

    Full Text Available An increased understanding of the interactions between the immune system and tumors has opened the door to immunotherapy for cancer patients. Despite some success with checkpoint inhibitors including ipilimumab, pembrolizumab, and nivolumab, most cancer patients remain unresponsive to such immunotherapy, likely due to intrinsic tumor resistance. The mechanisms most likely involve reducing the quantity and/or quality of antitumor lymphocytes, which ultimately are driven by any number of developments: tumor mutations and adaptations, reduced neoantigen generation or expression, indoleamine 2,3-dioxygenase (IDO overexpression, loss of phosphatase and tensin homologue (PTEN expression, and overexpression of the Wnt–β-catenin pathway. Current work in immunotherapy continues to identify various tumor resistance mechanisms; future work is needed to develop adjuvant treatments that target those mechanisms, in order to improve the efficacy of immunotherapy and to expand its scope.

  9. Intrinsic densitometry: In-plant evaluation

    International Nuclear Information System (INIS)

    Nishida, K.; Kurosawa, A.; Masui, J.; Hsue, S.T.

    1994-11-01

    A measurement of the plutonium concentration in a sample is always necessary for nuclear material control and accounting. This report describes the testing of the intrinsic densitometry (ID) technique for implant applications. The authors found that the ID method can determine the plutonium concentrations to between 2 and 3% at concentrations of 100 g/l to 200 g/l with quartz cells and a measurement time of 3600 s. The precision can be improved to 1 to 2% with a higher counting rate. The authors also found that nitric acid concentration and the impurity level of uranium in the product plutonium solution do not affect the concentration measurement. When this technique is applied to plutonium solutions in stainless steel pipes, they found that similar precision in plutonium concentration can be achieved using a high-count-rate detector. The precision, however, is reduced with aged plutonium solutions

  10. Intrinsic thermoelectric power of group VB metals

    Directory of Open Access Journals (Sweden)

    Gunadhor Singh Okram

    2012-03-01

    Full Text Available We have reinvestigated the thermopower of group VB metals in polycrystalline forms in the temperature range of 6-300K, taking into account the critical nature of the sample surface and heat treatment especially for niobium. Strikingly small magnitude, negative sign, phonon drag dip and superconductivity not reported previously were observed in surface-cleaned single crystalline Nb. However, while thermopower magnitudes are small, mixed signs were found in the polycrystalline V, Nb and Ta samples. These properties were therefore interpreted as their intrinsic properties and were briefly discussed taking into account of the existing theory by fitting also the data that give the Fermi energies of 10.94 eV, 5.08 eV and 1.86eV, respectively.

  11. Major Intrinsic Proteins in Biomimetic Membranes

    DEFF Research Database (Denmark)

    Helix Nielsen, Claus

    2010-01-01

    or as sensor devices based on e.g., the selective permeation of metalloids. In principle a MIP based membrane sensor/separation device requires the supporting biomimetic matrix to be virtually impermeable to anything but water or the solute in question. In practice, however, a biomimetic support matrix....../separation technology, a unique class of membrane transport proteins is especially interesting the major intrinsic proteins (MIPs). Generally, MIPs conduct water molecules and selected solutes in and out of the cell while preventing the passage of other solutes, a property critical for the conservation of the cells...... internal pH and salt concentration. Also known as water channels or aquaporins they are highly efficient membrane pore proteins some of which are capable of transporting water at very high rates up to 109 molecules per second. Some MIPs transport other small, uncharged solutes, such as glycerol and other...

  12. Intrinsic Ambipolarity and Rotation in Stellarators

    International Nuclear Information System (INIS)

    Helander, P.; Simakov, A. N.

    2008-01-01

    It is shown that collisional plasma transport is intrinsically ambipolar only in quasiaxisymmetric or quasihelically symmetric magnetic configurations. Only in such fields can the plasma rotate freely, and then only in the direction of quasisymmetry. In a non-quasi-symmetric magnetic field, the average radial electric field is determined by parallel viscosity, which in turn is usually governed by collisional processes. Locally, the radial electric field may be affected by turbulent Reynolds stress producing zonal flows, but on a radial average taken over several ion gyroradii, it is determined by parallel viscosity, at least if the turbulence is electrostatic and obeys the conventional gyrokinetic orderings. This differs from the situation in a tokamak, where there is no flow damping by parallel viscosity in the symmetry direction and the turbulent Reynolds stress may affect the global radial electric field

  13. And what if gravity is intrinsically quantic?

    International Nuclear Information System (INIS)

    Ziaeepour, Houri

    2009-01-01

    Since the early days of search for a quantum theory of gravity the attempts have been mostly concentrated on the quantization of an otherwise classical system. The two most contentious candidate theories of gravity, string theory and quantum loop gravity are based on a quantum field theory - the latter is a quantum field theory of connections on a SU(2) group manifold and the former is a quantum field theory in two dimensional spaces. Here we argue that there is a very close relation between quantum mechanics (QM) and gravity. Without gravity, QM becomes ambiguous. We consider this observation as the evidence for an intrinsic relation between these fundamental laws of nature. We suggest a quantum role and definition for gravity in the context of a quantum Universe, and present a preliminary formulation for gravity in a system with a finite number of particles.

  14. Intrinsic Dynamics of Quantum-Dash Lasers

    KAUST Repository

    Chen, Cheng

    2011-10-01

    Temperature-dependent intrinsic modulation response of InAs/InAlGaAs quantum-dash lasers was investigated by using pulse optical injection modulation to minimize the effects of parasitics and self-heating. Compared to typical quantum-well lasers, the quantum-dash lasers were found to have comparable differential gain but approximately twice the gain compression factor, probably due to carrier heating by free-carrier absorption, as opposed to stimulated transition. Therefore, the narrower modulation bandwidth of the quantum-dash lasers than that of quantum-well lasers was attributed to their higher gain compression factor. In addition, as expected, quantum-dash lasers with relatively long and uniform dashes exhibit higher temperature stability than quantum-well lasers. However, the lasers with relatively short and nonuniform dashes exhibit stronger temperature dependence, probably due to their higher surface-to-volume ratio and nonuniform dash sizes. © 2011 IEEE.

  15. Intrinsic shapes of discy and boxy ellipticals

    International Nuclear Information System (INIS)

    Fasano, Giovanni

    1991-01-01

    Statistical tests for intrinsic shapes of elliptical galaxies have given so far inconclusive and sometimes contradictory results. These failures have been often charged to the fact that classical tests consider only the two axisymmetric shapes (oblate versus prolate), while ellipticals are truly triaxial bodies. On the other hand, recent analyses indicate that the class of elliptical galaxies could be a mixture of (at least) two families having different morphology and dynamical behaviour: (i) a family of fast-rotating, disc-like ellipticals (discy); (ii) a family of slow-rotating, box-shaped ellipticals (boxy). In this paper we review the tests for instrinsic shapes of elliptical galaxies using data of better quality (CCD) with respect to previous applications. (author)

  16. Intrinsic Chirality Origination in Carbon Nanotubes.

    Science.gov (United States)

    Pierce, Neal; Chen, Gugang; P Rajukumar, Lakshmy; Chou, Nam Hawn; Koh, Ai Leen; Sinclair, Robert; Maruyama, Shigeo; Terrones, Mauricio; Harutyunyan, Avetik R

    2017-10-24

    Elucidating the origin of carbon nanotube chirality is key for realizing their untapped potential. Currently, prevalent theories suggest that catalyst structure originates chirality via an epitaxial relationship. Here we studied chirality abundances of carbon nanotubes grown on floating liquid Ga droplets, which excludes the influence of catalyst features, and compared them with abundances grown on solid Ru nanoparticles. Results of growth on liquid droplets bolsters the intrinsic preference of carbon nuclei toward certain chiralities. Specifically, the abundance of the (11,1)/χ = 4.31° tube can reach up to 95% relative to (9,4)/χ = 17.48°, although they have exactly the same diameter, (9.156 Å). However, the comparative abundances for the pair, (19,3)/χ = 7.2° and (17,6)/χ = 14.5°, with bigger diameter, (16.405 Å), fluctuate depending on synthesis temperature. The abundances of the same pairs of tubes grown on floating solid polyhedral Ru nanoparticles show completely different trends. Analysis of abundances in relation to nucleation probability, represented by a product of the Zeldovich factor and the deviation interval of a growing nuclei from equilibrium critical size, explain the findings. We suggest that the chirality in the nanotube in general is a result of interplay between intrinsic preference of carbon cluster and induction by catalyst structure. This finding can help to build the comprehensive theory of nanotube growth and offers a prospect for chirality-preferential synthesis of carbon nanotubes by the exploitation of liquid catalyst droplets.

  17. On the development of an intrinsic hybrid composite

    International Nuclear Information System (INIS)

    Kießling, R; Ihlemann, J; Riemer, M; Drossel, W-G; Scharf, I; Lampke, T; Sharafiev, S; Pouya, M; Wagner, M F-X

    2016-01-01

    Hybrid parts, which combine low weight with high strength, are moving into the focus of the automotive industry, due to their high potential for usage in the field of crash-relevant structures. In this contribution, the development of an intrinsic hybrid composite is presented, with a focus on the manufacturing process, complex simulations of the material behaviour and material testing. The hybrid composite is made up of a continuous fibre- reinforced plastic (FRP), in which a metallic insert is integrated. The mechanical behaviour of the individual components is characterised. For material modelling, an approach is pointed out that enables modelling at large strains by directly connected rheological elements. The connection between the FRP and the metallic insert is realised by a combination of form fit and adhesive bonds. On the one hand, adhesive bonds are generated within a sol gel process. On the other hand, local form elements of the metallic insert are pressed into the FRP. We show how these form elements are generated during the macroscopic forming process. In addition, the applied sol gel process is explained. Finally, we consider design concepts for a specimen type for high strain testing of the resulting interfaces. (paper)

  18. DNA Vaccines

    Indian Academy of Sciences (India)

    diseases. Keywords. DNA vaccine, immune response, antibodies, infectious diseases. GENERAL .... tein vaccines require expensive virus/protein purification tech- niques as ... sphere continue to remain major health hazards in developing nations. ... significance since it can be produced at a very low cost and can be stored ...

  19. DNA Investigations.

    Science.gov (United States)

    Mayo, Ellen S.; Bertino, Anthony J.

    1991-01-01

    Presents a simulation activity that allow students to work through the exercise of DNA profiling and to grapple with some analytical and ethical questions involving a couple arranging with a surrogate mother to have a baby. Can be used to teach the principles of restriction enzyme digestion, gel electrophoresis, and probe hybridization. (MDH)

  20. Personality traits associated with intrinsic academic motivation in medical students.

    Science.gov (United States)

    Tanaka, Masaaki; Mizuno, Kei; Fukuda, Sanae; Tajima, Seiki; Watanabe, Yasuyoshi

    2009-04-01

    Motivation is one of the most important psychological concepts in education and is related to academic outcomes in medical students. In this study, the relationships between personality traits and intrinsic academic motivation were examined in medical students. The study group consisted of 119 Year 2 medical students at Osaka City University Graduate School of Medicine. They completed questionnaires dealing with intrinsic academic motivation (the Intrinsic Motivation Scale toward Learning) and personality (the Temperament and Character Inventory [TCI]). On simple regression analyses, the TCI dimensions of persistence, self-directedness, co-operativeness and self-transcendence were positively associated with intrinsic academic motivation. On multiple regression analysis adjusted for age and gender, the TCI dimensions of persistence, self-directedness and self-transcendence were positively associated with intrinsic academic motivation. The temperament dimension of persistence and the character dimensions of self-directedness and self-transcendence are associated with intrinsic academic motivation in medical students.

  1. Increased intrinsic mitochondrial function in humans with mitochondrial haplogroup H

    DEFF Research Database (Denmark)

    Larsen, Steen; Díez-Sánchez, Carmen; Rabøl, Rasmus

    2014-01-01

    and determined their mitochondrial haplogroup, mitochondrial oxidative phosphorylation capacity (OXPHOS), mitochondrial content (citrate synthase (CS)) and VO2max. Intrinsic mitochondrial function is calculated as mitochondrial OXPHOS capacity divided by mitochondrial content (CS). Haplogroup H showed a 30......% higher intrinsic mitochondrial function compared with the other haplo group U. There was no relationship between haplogroups and VO2max. In skeletal muscle from men with mitochondrial haplogroup H, an increased intrinsic mitochondrial function is present....

  2. Do intrinsic and extrinsic motivation relate differently to employee outcomes?

    OpenAIRE

    Kuvaas, Bard; Buch, Robert; Weibel, Antoinette; Dysvik, Anders; Nerstad, Christina

    2017-01-01

    In most theories that address how individual financial incentives affect work performance, researchers have assumed that two types of motivation—intrinsic and extrinsic—mediate the relationship between incentives and performance. Empirically, however, extrinsic motivation is rarely investigated. To explore the predictive validity of these theories of intrinsic and extrinsic motivation in work settings, we tested how both intrinsic and extrinsic motivation affected supervisor-ra...

  3. The effects of extrinsic rewards on children's intrinsic motivation

    OpenAIRE

    大槻, 千秋

    1981-01-01

    An experiment was conducted with preschool children to test whether a person's intrinsic motivation in an activity may be decreased by extrinsic salient rewards in Japan like in America. Children solved some jigsaw puzzles and received assorted candies, then they were observed how long they did other jigsaw puzzles. The results showed that the effects of extrinsic rewards on intrinsic motivation in an activity varied with the subject's social background. In uptown children's intrinsic motivat...

  4. Sources of intrinsic rotation in the low-flow ordering

    International Nuclear Information System (INIS)

    Parra, Felix I.; Barnes, Michael; Catto, Peter J.

    2011-01-01

    A low flow, δf gyrokinetic formulation to obtain the intrinsic rotation profiles is presented. The momentum conservation equation in the low-flow ordering contains new terms, neglected in previous first-principles formulations, that may explain the intrinsic rotation observed in tokamaks in the absence of external sources of momentum. The intrinsic rotation profile depends on the density and temperature profiles and on the up-down asymmetry.

  5. Asymmetric PCR for good quality ssDNA generation towards DNA aptamer production

    Directory of Open Access Journals (Sweden)

    Junji Tominaga4

    2012-04-01

    Full Text Available Aptamers are ssDNA or RNA that binds to wide variety of target molecules with high affinity and specificity producedby systematic evolution of ligands by exponential enrichment (SELEX. Compared to RNA aptamer, DNA aptamer is muchmore stable, favourable to be used in many applications. The most critical step in DNA SELEX experiment is the conversion ofdsDNA to ssDNA. The purpose of this study was to develop an economic and efficient approach of generating ssDNA byusing asymmetric PCR. Our results showed that primer ratio (sense primer:antisense primer of 20:1 and sense primer amountof 10 to 100 pmol, up to 20 PCR cycles using 20 ng of initial template, in combination with polyacrylamide gel electrophoresis,were the optimal conditions for generating good quality and quantity of ssDNA. The generation of ssDNA via this approachcan greatly enhance the success rate of DNA aptamer generation.

  6. Characterization of the intrinsic density profiles for liquid surfaces

    International Nuclear Information System (INIS)

    Chacon, Enrique; Tarazona, Pedro

    2005-01-01

    This paper presents recent advances in the characterization of the intrinsic structures in computer simulations of liquid surfaces. The use of operational definitions for the intrinsic surface, associated with each molecular configuration of a liquid slab, gives direct access to the intrinsic profile and to the wavevector dependent surface tension. However, the characteristics of these functions depend on the definition used for the intrinsic surface. We discuss the pathologies associated with a local Gibbs dividing surface definition, and consider the alternative definition of a minimal area surface, going though a set of surface pivots, self-consistently chosen to represent the first liquid layer

  7. The DNA damage response during mitosis

    International Nuclear Information System (INIS)

    Heijink, Anne Margriet; Krajewska, Małgorzata; Vugt, Marcel A.T.M. van

    2013-01-01

    Cells are equipped with a cell-intrinsic signaling network called the DNA damage response (DDR). This signaling network recognizes DNA lesions and initiates various downstream pathways to coordinate a cell cycle arrest with the repair of the damaged DNA. Alternatively, the DDR can mediate clearance of affected cells that are beyond repair through apoptosis or senescence. The DDR can be activated in response to DNA damage throughout the cell cycle, although the extent of DDR signaling is different in each cell cycle phase. Especially in response to DNA double strand breaks, only a very marginal response was observed during mitosis. Early on it was recognized that cells which are irradiated during mitosis continued division without repairing broken chromosomes. Although these initial observations indicated diminished DNA repair and lack of an acute DNA damage-induced cell cycle arrest, insight into the mechanistic re-wiring of DDR signaling during mitosis was only recently provided. Different mechanisms appear to be at play to inactivate specific signaling axes of the DDR network in mitosis. Importantly, mitotic cells not simply inactivate the entire DDR, but appear to mark their DNA damage for repair after mitotic exit. Since the treatment of cancer frequently involves agents that induce DNA damage as well as agents that block mitotic progression, it is clinically relevant to obtain a better understanding of how cancer cells deal with DNA damage during interphase versus mitosis. In this review, the molecular details concerning DDR signaling during mitosis as well as the consequences of encountering DNA damage during mitosis for cellular fate are discussed

  8. The DNA damage response during mitosis

    Energy Technology Data Exchange (ETDEWEB)

    Heijink, Anne Margriet; Krajewska, Małgorzata; Vugt, Marcel A.T.M. van, E-mail: m.vugt@umcg.nl

    2013-10-15

    Cells are equipped with a cell-intrinsic signaling network called the DNA damage response (DDR). This signaling network recognizes DNA lesions and initiates various downstream pathways to coordinate a cell cycle arrest with the repair of the damaged DNA. Alternatively, the DDR can mediate clearance of affected cells that are beyond repair through apoptosis or senescence. The DDR can be activated in response to DNA damage throughout the cell cycle, although the extent of DDR signaling is different in each cell cycle phase. Especially in response to DNA double strand breaks, only a very marginal response was observed during mitosis. Early on it was recognized that cells which are irradiated during mitosis continued division without repairing broken chromosomes. Although these initial observations indicated diminished DNA repair and lack of an acute DNA damage-induced cell cycle arrest, insight into the mechanistic re-wiring of DDR signaling during mitosis was only recently provided. Different mechanisms appear to be at play to inactivate specific signaling axes of the DDR network in mitosis. Importantly, mitotic cells not simply inactivate the entire DDR, but appear to mark their DNA damage for repair after mitotic exit. Since the treatment of cancer frequently involves agents that induce DNA damage as well as agents that block mitotic progression, it is clinically relevant to obtain a better understanding of how cancer cells deal with DNA damage during interphase versus mitosis. In this review, the molecular details concerning DDR signaling during mitosis as well as the consequences of encountering DNA damage during mitosis for cellular fate are discussed.

  9. The DNA damage response during mitosis.

    Science.gov (United States)

    Heijink, Anne Margriet; Krajewska, Małgorzata; van Vugt, Marcel A T M

    2013-10-01

    Cells are equipped with a cell-intrinsic signaling network called the DNA damage response (DDR). This signaling network recognizes DNA lesions and initiates various downstream pathways to coordinate a cell cycle arrest with the repair of the damaged DNA. Alternatively, the DDR can mediate clearance of affected cells that are beyond repair through apoptosis or senescence. The DDR can be activated in response to DNA damage throughout the cell cycle, although the extent of DDR signaling is different in each cell cycle phase. Especially in response to DNA double strand breaks, only a very marginal response was observed during mitosis. Early on it was recognized that cells which are irradiated during mitosis continued division without repairing broken chromosomes. Although these initial observations indicated diminished DNA repair and lack of an acute DNA damage-induced cell cycle arrest, insight into the mechanistic re-wiring of DDR signaling during mitosis was only recently provided. Different mechanisms appear to be at play to inactivate specific signaling axes of the DDR network in mitosis. Importantly, mitotic cells not simply inactivate the entire DDR, but appear to mark their DNA damage for repair after mitotic exit. Since the treatment of cancer frequently involves agents that induce DNA damage as well as agents that block mitotic progression, it is clinically relevant to obtain a better understanding of how cancer cells deal with DNA damage during interphase versus mitosis. In this review, the molecular details concerning DDR signaling during mitosis as well as the consequences of encountering DNA damage during mitosis for cellular fate are discussed. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Interventions for primary (intrinsic tracheomalacia in children

    Directory of Open Access Journals (Sweden)

    Vikas Goyal

    Full Text Available BACKGROUNDTracheomalacia, a disorder of the large airways where the trachea is deformed or malformed during respiration, is commonly seen in tertiary paediatric practice. It is associated with a wide spectrum of respiratory symptoms from life-threatening recurrent apnoea to common respiratory symptoms such as chronic cough and wheeze. Current practice following diagnosis of tracheomalacia includes medical approaches aimed at reducing associated symptoms of tracheomalacia, ventilation modalities of continuous positive airway pressure (CPAP and bi-level positive airway pressure (BiPAP, and surgical approaches aimed at improving the calibre of the airway (airway stenting, aortopexy, tracheopexy.OBJECTIVESTo evaluate the efficacy of medical and surgical therapies for children with intrinsic (primary tracheomalacia.METHODSSearchThe Cochrane Airways Group searched the Cochrane Central Register of Controlled Trials (CENTRAL, the Cochrane Airways Group's Specialized Register, Medline and Embase databases. The Cochrane Airways Group performed the latest searches in March 2012.Selection criteriaAll randomized controlled trials (RCTs of therapies related to symptoms associated with primary or intrinsic tracheomalacia.Data collection and analysisTwo reviewers extracted data from the included study independently and resolved disagreements by consensus.MAIN RESULTSWe included one RCT that compared nebulized recombinant human deoxyribonuclease (rhDNase with placebo in 40 children with airway malacia and a respiratory tract infection. We assessed it to be a RCT with overall low risk of bias. Data analyzed in this review showed that there was no significant difference between groups for the primary outcome of proportion cough-free at two weeks (odds ratio (OR 1.38; 95% confidence interval (CI 0.37 to 5.14. However, the mean change in night time cough diary scores significantly favoured the placebo group (mean difference (MD 1.00; 95% CI 0.17 to 1.83, P = 0

  11. HSV-1 ICP0: An E3 Ubiquitin Ligase That Counteracts Host Intrinsic and Innate Immunity

    Directory of Open Access Journals (Sweden)

    Mirna Perusina Lanfranca

    2014-05-01

    Full Text Available The herpes simplex virus type 1 (HSV-1 encoded E3 ubiquitin ligase, infected cell protein 0 (ICP0, is required for efficient lytic viral replication and regulates the switch between the lytic and latent states of HSV-1. As an E3 ubiquitin ligase, ICP0 directs the proteasomal degradation of several cellular targets, allowing the virus to counteract different cellular intrinsic and innate immune responses. In this review, we will focus on how ICP0’s E3 ubiquitin ligase activity inactivates the host intrinsic defenses, such as nuclear domain 10 (ND10, SUMO, and the DNA damage response to HSV-1 infection. In addition, we will examine ICP0’s capacity to impair the activation of interferon (innate regulatory mediators that include IFI16 (IFN γ-inducible protein 16, MyD88 (myeloid differentiation factor 88, and Mal (MyD88 adaptor-like protein. We will also consider how ICP0 allows HSV-1 to evade activation of the NF-κB (nuclear factor kappa B inflammatory signaling pathway. Finally, ICP0’s paradoxical relationship with USP7 (ubiquitin specific protease 7 and its roles in intrinsic and innate immune responses to HSV-1 infection will be discussed.

  12. DNA repair

    International Nuclear Information System (INIS)

    Setlow, R.

    1978-01-01

    Some topics discussed are as follows: difficulty in extrapolating data from E. coli to mammalian systems; mutations caused by UV-induced changes in DNA; mutants deficient in excision repair; other postreplication mechanisms; kinds of excision repair systems; detection of repair by biochemical or biophysical means; human mutants deficient in repair; mutagenic effects of UV on XP cells; and detection of UV-repair defects among XP individuals

  13. A polarized view on DNA under tension

    Science.gov (United States)

    van Mameren, Joost; Vermeulen, Karen; Wuite, Gijs J. L.; Peterman, Erwin J. G.

    2018-03-01

    In the past decades, sensitive fluorescence microscopy techniques have contributed significantly to our understanding of the dynamics of DNA. The specific labeling of DNA using intercalating dyes has allowed for quantitative measurement of the thermal fluctuations the polymers undergo. On the other hand, recent advances in single-molecule manipulation techniques have unraveled the mechanical and elastic properties of this intricate polymer. Here, we have combined these two approaches to study the conformational dynamics of DNA under a wide range of tensions. Using polarized fluorescence microscopy in conjunction with optical-tweezers-based manipulation of YOYO-intercalated DNA, we controllably align the YOYO dyes using DNA tension, enabling us to disentangle the rapid dynamics of the dyes from that of the DNA itself. With unprecedented control of the DNA alignment, we resolve an inconsistency in reports about the tilted orientation of intercalated dyes. We find that intercalated dyes are on average oriented perpendicular to the long axis of the DNA, yet undergo fast dynamics on the time scale of absorption and fluorescence emission. In the overstretching transition of double-stranded DNA, we do not observe changes in orientation or orientational dynamics of the dyes. Only beyond the overstretching transition, a considerable depolarization is observed, presumably caused by an average tilting of the DNA base pairs. Our combined approach thus contributes to the elucidation of unique features of the molecular dynamics of DNA.

  14. Isolation of deletion alleles by G4 DNA-induced mutagenesis

    NARCIS (Netherlands)

    Pontier, Daphne B; Kruisselbrink, Evelien; Guryev, Victor; Tijsterman, Marcel

    Metazoan genomes contain thousands of sequence tracts that match the guanine-quadruplex (G4) DNA signature G(3)N(x)G(3)N(x)G(3)N(x)G(3), a motif that is intrinsically mutagenic, probably because it can form secondary structures during DNA replication. Here we show how and to what extent this feature

  15. Use of sperm plasmid DNA lipofection combined with REMI (restriction enzyme-mediated insertion) for production of transgenic chickens expressing eGFP (enhanced green fluorescent protein) or human follicle-stimulating hormone.

    Science.gov (United States)

    Harel-Markowitz, Eliane; Gurevich, Michael; Shore, Laurence S; Katz, Adi; Stram, Yehuda; Shemesh, Mordechai

    2009-05-01

    Linearized p-eGFP (plasmid-enhanced green fluorescent protein) or p-hFSH (plasmid human FSH) sequences with the corresponding restriction enzyme were lipofected into sperm genomic DNA. Sperm transfected with p-eGFP were used for artificial insemination in hens, and in 17 out of 19 of the resultant chicks, the exogenous DNA was detected in their lymphocytes as determined by PCR and expressed in tissues as determined by (a) PCR, (b) specific emission of green fluorescence by the eGFP, and (c) Southern blot analysis. A complete homology was found between the Aequorea Victoria eGFP DNA and a 313-bp PCR product of extracted DNA from chick blood cells. Following insemination with sperm lipofected with p-hFSH, transgenic offspring were obtained for two generations as determined by detection of the transgene for human FSH (PCR) and expression of the gene (RT-PCR and quantitative real-time PCR) and the presence of the protein in blood (radioimmunoassay). Data demonstrate that lipofection of plasmid DNA with restriction enzyme is a highly efficient method for the production of transfected sperm to produce transgenic offspring by direct artificial insemination.

  16. Combined Targeted DNA Sequencing in Non-Small Cell Lung Cancer (NSCLC Using UNCseq and NGScopy, and RNA Sequencing Using UNCqeR for the Detection of Genetic Aberrations in NSCLC.

    Directory of Open Access Journals (Sweden)

    Xiaobei Zhao

    Full Text Available The recent FDA approval of the MiSeqDx platform provides a unique opportunity to develop targeted next generation sequencing (NGS panels for human disease, including cancer. We have developed a scalable, targeted panel-based assay termed UNCseq, which involves a NGS panel of over 200 cancer-associated genes and a standardized downstream bioinformatics pipeline for detection of single nucleotide variations (SNV as well as small insertions and deletions (indel. In addition, we developed a novel algorithm, NGScopy, designed for samples with sparse sequencing coverage to detect large-scale copy number variations (CNV, similar to human SNP Array 6.0 as well as small-scale intragenic CNV. Overall, we applied this assay to 100 snap-frozen lung cancer specimens lacking same-patient germline DNA (07-0120 tissue cohort and validated our results against Sanger sequencing, SNP Array, and our recently published integrated DNA-seq/RNA-seq assay, UNCqeR, where RNA-seq of same-patient tumor specimens confirmed SNV detected by DNA-seq, if RNA-seq coverage depth was adequate. In addition, we applied the UNCseq assay on an independent lung cancer tumor tissue collection with available same-patient germline DNA (11-1115 tissue cohort and confirmed mutations using assays performed in a CLIA-certified laboratory. We conclude that UNCseq can identify SNV, indel, and CNV in tumor specimens lacking germline DNA in a cost-efficient fashion.

  17. Development of biometric DNA ink for authentication security.

    Science.gov (United States)

    Hashiyada, Masaki

    2004-10-01

    Among the various types of biometric personal identification systems, DNA provides the most reliable personal identification. It is intrinsically digital and unchangeable while the person is alive, and even after his/her death. Increasing the number of DNA loci examined can enhance the power of discrimination. This report describes the development of DNA ink, which contains synthetic DNA mixed with printing inks. Single-stranded DNA fragments encoding a personalized set of short tandem repeats (STR) were synthesized. The sequence was defined as follows. First, a decimal DNA personal identification (DNA-ID) was established based on the number of STRs in the locus. Next, this DNA-ID was encrypted using a binary, 160-bit algorithm, using a hashing function to protect privacy. Since this function is irreversible, no one can recover the original information from the encrypted code. Finally, the bit series generated above is transformed into base sequences, and double-stranded DNA fragments are amplified by the polymerase chain reaction (PCR) to protect against physical attacks. Synthesized DNA was detected successfully after samples printed in DNA ink were subjected to several resistance tests used to assess the stability of printing inks. Endurance test results showed that this DNA ink would be suitable for practical use as a printing ink and was resistant to 40 hours of ultraviolet exposure, performance commensurate with that of photogravure ink. Copyright 2004 Tohoku University Medical Press

  18. Functional Anthology of Intrinsic Disorder. III. Ligands, Postranslational Modifications and Diseases Associated with Intrinsically Disordered Proteins

    Science.gov (United States)

    Xie, Hongbo; Vucetic, Slobodan; Iakoucheva, Lilia M.; Oldfield, Christopher J.; Dunker, A. Keith; Obradovic, Zoran; Uversky, Vladimir N.

    2008-01-01

    Currently, the understanding of the relationships between function, amino acid sequence and protein structure continues to represent one of the major challenges of the modern protein science. As much as 50% of eukaryotic proteins are likely to contain functionally important long disordered regions. Many proteins are wholly disordered but still possess numerous biologically important functions. However, the number of experimentally confirmed disordered proteins with known biological functions is substantially smaller than their actual number in nature. Therefore, there is a crucial need for novel bioinformatics approaches that allow projection of the current knowledge from a few experimentally verified examples to much larger groups of known and potential proteins. The elaboration of a bioinformatics tool for the analysis of functional diversity of intrinsically disordered proteins and application of this data mining tool to >200,000 proteins from Swiss-Prot database, each annotated with at least one of the 875 functional keywords was described in the first paper of this series (Xie H., Vucetic S., Iakoucheva L.M., Oldfield C.J., Dunker A.K., Obradovic Z., Uversky V.N. (2006) Functional anthology of intrinsic disorder. I. Biological processes and functions of proteins with long disordered regions. J. Proteome Res.). Using this tool, we have found that out of the 711 Swiss-Prot functional keywords associated with at least 20 proteins, 262 were strongly positively correlated with long intrinsically disordered regions, and 302 were strongly negatively correlated. Illustrative examples of functional disorder or order were found for the vast majority of keywords showing strongest positive or negative correlation with intrinsic disorder, respectively. Some 80 Swiss-Prot keywords associated with disorder- and order-driven biological processes and protein functions were described in the first paper (Xie H., Vucetic S., Iakoucheva L.M., Oldfield C.J., Dunker A.K., Obradovic

  19. Exploiting intrinsic fluctuations to identify model parameters.

    Science.gov (United States)

    Zimmer, Christoph; Sahle, Sven; Pahle, Jürgen

    2015-04-01

    Parameterisation of kinetic models plays a central role in computational systems biology. Besides the lack of experimental data of high enough quality, some of the biggest challenges here are identification issues. Model parameters can be structurally non-identifiable because of functional relationships. Noise in measured data is usually considered to be a nuisance for parameter estimation. However, it turns out that intrinsic fluctuations in particle numbers can make parameters identifiable that were previously non-identifiable. The authors present a method to identify model parameters that are structurally non-identifiable in a deterministic framework. The method takes time course recordings of biochemical systems in steady state or transient state as input. Often a functional relationship between parameters presents itself by a one-dimensional manifold in parameter space containing parameter sets of optimal goodness. Although the system's behaviour cannot be distinguished on this manifold in a deterministic framework it might be distinguishable in a stochastic modelling framework. Their method exploits this by using an objective function that includes a measure for fluctuations in particle numbers. They show on three example models, immigration-death, gene expression and Epo-EpoReceptor interaction, that this resolves the non-identifiability even in the case of measurement noise with known amplitude. The method is applied to partially observed recordings of biochemical systems with measurement noise. It is simple to implement and it is usually very fast to compute. This optimisation can be realised in a classical or Bayesian fashion.

  20. i=0 (Information has no intrinsic meaning

    Directory of Open Access Journals (Sweden)

    F.J. Miller

    2002-01-01

    Full Text Available This paper was written mainly to help identify some contradictions that can be found in the notion of knowledge management though its application is wider-ranging. The author suggests that knowledge - that is to say 'what we know' - can scarcely be understood and managed even by ourselves, much less by means of sophisticated information and communications (ie groupware and shareware technologies. We have progressed from the industrial age through the information age into what is being promoted as the 'golden age' of knowledge and, in the process, we've been led to believe that information contains meaning - rather than just standing for, provoking or evoking meaning in others. The paper argues that unless we take the trouble to face and understand the significance and implications of i=0 (ie that information has no intrinsic meaning and that knowledge is the uniquely human capability of making meaning from information - ideally in face-to-face relationships with other human beings - we may never emerge into any 'golden' age at all! The consequences of i=0 for communications, learning, safety, quality, management (itself, and winning work are also discussed.

  1. Altered intrinsic and extrinsic connectivity in schizophrenia.

    Science.gov (United States)

    Zhou, Yuan; Zeidman, Peter; Wu, Shihao; Razi, Adeel; Chen, Cheng; Yang, Liuqing; Zou, Jilin; Wang, Gaohua; Wang, Huiling; Friston, Karl J

    2018-01-01

    Schizophrenia is a disorder characterized by functional dysconnectivity among distributed brain regions. However, it is unclear how causal influences among large-scale brain networks are disrupted in schizophrenia. In this study, we used dynamic causal modeling (DCM) to assess the hypothesis that there is aberrant directed (effective) connectivity within and between three key large-scale brain networks (the dorsal attention network, the salience network and the default mode network) in schizophrenia during a working memory task. Functional MRI data during an n-back task from 40 patients with schizophrenia and 62 healthy controls were analyzed. Using hierarchical modeling of between-subject effects in DCM with Parametric Empirical Bayes, we found that intrinsic (within-region) and extrinsic (between-region) effective connectivity involving prefrontal regions were abnormal in schizophrenia. Specifically, in patients (i) inhibitory self-connections in prefrontal regions of the dorsal attention network were decreased across task conditions; (ii) extrinsic connectivity between regions of the default mode network was increased; specifically, from posterior cingulate cortex to the medial prefrontal cortex; (iii) between-network extrinsic connections involving the prefrontal cortex were altered; (iv) connections within networks and between networks were correlated with the severity of clinical symptoms and impaired cognition beyond working memory. In short, this study revealed the predominance of reduced synaptic efficacy of prefrontal efferents and afferents in the pathophysiology of schizophrenia.

  2. Intrinsic and extrinsic measurement for Brownian motion

    International Nuclear Information System (INIS)

    Castro-Villarreal, Pavel

    2014-01-01

    Based upon the Smoluchowski equation on curved manifolds, three physical observables are considered for Brownian displacement, namely geodesic displacement s, Euclidean displacement δR, and projected displacement δR ⊥ . The Weingarten–Gauss equations are used to calculate the mean-square Euclidean displacements in the short-time regime. Our findings show that from an extrinsic point of view the geometry of the space affects the Brownian motion in such a way that the particle’s diffusion is decelerated, contrasting with the intrinsic point of view where dynamics is controlled by the sign of the Gaussian curvature (Castro-Villarreal, 2010 J. Stat. Mech. P08006). Furthermore, it is possible to give exact formulas for 〈δR〉 and 〈δR 2 〉 on spheres and minimal surfaces, which are valid for all values of time. In the latter case, surprisingly, Brownian motion corresponds to the usual diffusion in flat geometries, albeit minimal surfaces have non-zero Gaussian curvature. Finally, the two-dimensional case is emphasized due to its close relation to surface self-diffusion in fluid membranes. (paper)

  3. Intrinsic ferromagnetism in hexagonal boron nitride nanosheets

    Energy Technology Data Exchange (ETDEWEB)

    Si, M. S.; Gao, Daqiang, E-mail: gaodq@lzu.edu.cn, E-mail: xueds@lzu.edu.cn; Yang, Dezheng; Peng, Yong; Zhang, Z. Y.; Xue, Desheng, E-mail: gaodq@lzu.edu.cn, E-mail: xueds@lzu.edu.cn [Key Laboratory for Magnetism and Magnetic Materials of the Ministry of Education, Lanzhou University, Lanzhou 730000 (China); Liu, Yushen [Jiangsu Laboratory of Advanced Functional Materials and College of Physics and Engineering, Changshu Institute of Technology, Changshu 215500 (China); Deng, Xiaohui [Department of Physics and Electronic Information Science, Hengyang Normal University, Hengyang 421008 (China); Zhang, G. P. [Department of Physics, Indiana State University, Terre Haute, Indiana 47809 (United States)

    2014-05-28

    Understanding the mechanism of ferromagnetism in hexagonal boron nitride nanosheets, which possess only s and p electrons in comparison with normal ferromagnets based on localized d or f electrons, is a current challenge. In this work, we report an experimental finding that the ferromagnetic coupling is an intrinsic property of hexagonal boron nitride nanosheets, which has never been reported before. Moreover, we further confirm it from ab initio calculations. We show that the measured ferromagnetism should be attributed to the localized π states at edges, where the electron-electron interaction plays the role in this ferromagnetic ordering. More importantly, we demonstrate such edge-induced ferromagnetism causes a high Curie temperature well above room temperature. Our systematical work, including experimental measurements and theoretical confirmation, proves that such unusual room temperature ferromagnetism in hexagonal boron nitride nanosheets is edge-dependent, similar to widely reported graphene-based materials. It is believed that this work will open new perspectives for hexagonal boron nitride spintronic devices.

  4. Does intrinsic motivation enhance motor cortex excitability?

    Science.gov (United States)

    Radel, Rémi; Pjevac, Dusan; Davranche, Karen; d'Arripe-Longueville, Fabienne; Colson, Serge S; Lapole, Thomas; Gruet, Mathieu

    2016-11-01

    Intrinsic motivation (IM) is often viewed as a spontaneous tendency for action. Recent behavioral and neuroimaging evidence indicate that IM, in comparison to extrinsic motivation (EM), solicits the motor system. Accordingly, we tested whether IM leads to greater excitability of the motor cortex than EM. To test this hypothesis, we used two different tasks to induce the motivational orientation using either words representing each motivational orientation or pictures previously linked to each motivational orientation through associative learning. Single-pulse transcranial magnetic stimulation over the motor cortex was applied when viewing the stimuli. Electromyographic activity was recorded on the contracted first dorsal interosseous muscle. Two indexes of corticospinal excitability (the amplitude of motor-evoked potential and the length of cortical silent period) were obtained through unbiased automatic detection and analyzed using a mixed model that provided both statistical power and a high level of control over all important individual, task, and stimuli characteristics. Across the two tasks and the two indices of corticospinal excitability, the exposure to IM-related stimuli did not lead to a greater corticospinal excitability than EM-related stimuli or than stimuli with no motivational valence (ps > .20). While these results tend to dismiss the advantage of IM at activating the motor cortex, we suggest alternative hypotheses to explain this lack of effect, which deserves further research. © 2016 Society for Psychophysiological Research.

  5. Intrinsic bioremediation of an Arctic spill

    International Nuclear Information System (INIS)

    Ziervogel, H.; Selann, J.

    2002-01-01

    An environmental site assessment was conducted in summer 2001 at Repulse Bay, Nunavut where a recent diesel spill flowed from groundwater into a small creek leading to Hudson Bay. The spill produced a microbial mat several mm in thickness and which colonized the creek for about 50 m from the point where the groundwater entered the creek. Further down the gradient, the mat increased in thickness and changed in colour from yellowish brown to green. Sedimentary iron deposition was occurring along the banks of the creek where the mat was found and a free phase diesel product was found a few mm below the sediment-water interface. The microbial mats were found to have gradients of oxygen which peaked at surface and decreased with depth. Hydrogen sulphide concentrations were formed by sulphate reduction. In comparison, an older weathered diesel spill did not appear to have much effect on the stream's geochemistry and did not form a microbial mat. It is noted that the mat may have formed in the new spill because its' volatile component may have had a toxic effect on bacterial predators in the stream. It was concluded that intrinsic bioremediation takes place through dissimilatory sulphate and iron reduction and aerobic degradation. This may be cause for about 13 per cent ppm of hydrocarbon degradation known as BTEX (benzene, toluene, ethylbenzene, and xylene). 12 refs., 1 tab., 5 figs

  6. Diffuse intrinsic pontine glioma: poised for progress

    International Nuclear Information System (INIS)

    Warren, Katherine E.

    2012-01-01

    Diffuse intrinsic pontine gliomas (DIPGs) are amongst the most challenging tumors to treat. Surgery is not an option, the effects of radiation therapy are temporary, and no chemotherapeutic agent has demonstrated significant efficacy. Numerous clinical trials of new agents and novel therapeutic approaches have been performed over the course of several decades in efforts to improve the outcome of children with DIPG, yet without success. The diagnosis of DIPG is based on radiographic findings in the setting of a typical clinical presentation, and tissue is not routinely obtained as the standard of care. The paradigm for treating children with these tumors has been based on that for supratentorial high-grade gliomas in adults as the biology of these lesions were presumed to be similar. However, recent pivotal studies demonstrate that DIPGs appear to be their own entity. Simply identifying this fact releases a number of constraints and opens opportunities for biologic investigation of these lesions, setting the stage to move forward in identifying DIPG-specific treatments. This review will summarize the current state of knowledge of DIPG, discuss obstacles to therapy, and summarize results of recent biologic studies.

  7. Understanding oceanic migrations with intrinsic biogeochemical markers.

    Directory of Open Access Journals (Sweden)

    Raül Ramos

    2009-07-01

    Full Text Available Migratory marine vertebrates move annually across remote oceanic water masses crossing international borders. Many anthropogenic threats such as overfishing, bycatch, pollution or global warming put millions of marine migrants at risk especially during their long-distance movements. Therefore, precise knowledge about these migratory movements to understand where and when these animals are more exposed to human impacts is vital for addressing marine conservation issues. Because electronic tracking devices suffer from several constraints, mainly logistical and financial, there is emerging interest in finding appropriate intrinsic markers, such as the chemical composition of inert tissues, to study long-distance migrations and identify wintering sites. Here, using tracked pelagic seabirds and some of their own feathers which were known to be grown at different places and times within the annual cycle, we proved the value of biogeochemical analyses of inert tissue as tracers of marine movements and habitat use. Analyses of feathers grown in summer showed that both stable isotope signatures and element concentrations can signal the origin of breeding birds feeding in distinct water masses. However, only stable isotopes signalled water masses used during winter because elements mainly accumulated during the long breeding period are incorporated into feathers grown in both summer and winter. Our findings shed new light on the simple and effective assignment of marine organisms to distinct oceanic areas, providing new opportunities to study unknown migration patterns of secretive species, including in relation to human-induced mortality on specific populations in the marine environment.

  8. Intrinsic Turbulence Stabilization in a Stellarator

    Directory of Open Access Journals (Sweden)

    P. Xanthopoulos

    2016-06-01

    Full Text Available The magnetic surfaces of modern stellarators are characterized by complex, carefully optimized shaping and exhibit locally compressed regions of strong turbulence drive. Massively parallel computer simulations of plasma turbulence reveal, however, that stellarators also possess two intrinsic mechanisms to mitigate the effect of this drive. In the regime where the length scale of the turbulence is very small compared to the equilibrium scale set by the variation of the magnetic field, the strongest fluctuations form narrow bandlike structures on the magnetic surfaces. Thanks to this localization, the average transport through the surface is significantly smaller than that predicted at locations of peak turbulence. This feature results in a numerically observed upshift of the onset of turbulence on the surface towards higher ion temperature gradients as compared with the prediction from the most unstable regions. In a second regime lacking scale separation, the localization is lost and the fluctuations spread out on the magnetic surface. Nonetheless, stabilization persists through the suppression of the large eddies (relative to the equilibrium scale, leading to a reduced stiffness for the heat flux dependence on the ion temperature gradient. These fundamental differences with tokamak turbulence are exemplified for the QUASAR stellarator [G. H. Neilson et al., IEEE Trans. Plasma Sci. 42, 489 (2014].

  9. Toward a tripartite model of intrinsic motivation.

    Science.gov (United States)

    Carbonneau, Noémie; Vallerand, Robert J; Lafrenière, Marc-André K

    2012-10-01

    Intrinsic motivation (IM) refers to engaging in an activity for the pleasure inherent in the activity. The present article presents a tripartite model of IM consisting of IM to know (i.e., engaging in an activity to experience pleasure while learning and trying to understand something new), IM toward accomplishment (i.e., engaging in an activity for the pleasure experienced when attempting task mastery), and IM to experience stimulation (i.e., engaging in an activity for feelings of sensory pleasure). The tripartite model of IM posits that each type of IM can result from task, situational, and personality determinants and can lead to specific types of cognitive, affective, and behavioral outcomes. The purpose of this research was to test some predictions derived from this model. Across 4 studies (Study 1: N = 331; Study 2: N = 113; Study 3: N = 58; Study 4: N = 135), the 3 types of IM as well as potential determinants and consequences were assessed. Results revealed that experiencing one type of IM over the others depends in part on people's personality styles. Also, each type of IM was found to predict specific outcomes (i.e., affective states and behavioral choices). The implications of the tripartite model of IM for motivation research are discussed. © 2011 The Authors. Journal of Personality © 2011, Wiley Periodicals, Inc.

  10. Intrinsic gain modulation and adaptive neural coding.

    Directory of Open Access Journals (Sweden)

    Sungho Hong

    2008-07-01

    Full Text Available In many cases, the computation of a neural system can be reduced to a receptive field, or a set of linear filters, and a thresholding function, or gain curve, which determines the firing probability; this is known as a linear/nonlinear model. In some forms of sensory adaptation, these linear filters and gain curve adjust very rapidly to changes in the variance of a randomly varying driving input. An apparently similar but previously unrelated issue is the observation of gain control by background noise in cortical neurons: the slope of the firing rate versus current (f-I curve changes with the variance of background random input. Here, we show a direct correspondence between these two observations by relating variance-dependent changes in the gain of f-I curves to characteristics of the changing empirical linear/nonlinear model obtained by sampling. In the case that the underlying system is fixed, we derive relationships relating the change of the gain with respect to both mean and variance with the receptive fields derived from reverse correlation on a white noise stimulus. Using two conductance-based model neurons that display distinct gain modulation properties through a simple change in parameters, we show that coding properties of both these models quantitatively satisfy the predicted relationships. Our results describe how both variance-dependent gain modulation and adaptive neural computation result from intrinsic nonlinearity.

  11. Hydrodynamic characterization and molecular weight estimation of ultrasonically sheared DNA

    International Nuclear Information System (INIS)

    Casal, J. I.; Garces, F.; Garcia-Sacristan, A.

    1981-01-01

    The sedimentation coefficients and intrinsic viscosities of ultrasonically sheared calf thymus DNA have been determined. The molecular weight estimation according to this parameters have been compared with the ones obtained from the electrophoretic migration rates based on the calibration proposed using the known molecular weight restriction fragments of X-ENA. (Author) 35 refs

  12. Goal-orientation, epistemological beliefs towards intrinsic motivation among engineering students: A review

    Science.gov (United States)

    Benlahcene, Abderrahim; Lashari, Sana Anwar; Lashari, Tahira Anwar

    2017-08-01

    An aspect that has been exhaustively researched in the motivation of the higher education discipline is the engineering students’ process of goal-orientation, epistemological beliefs towards intrinsic motivation. However, the focus of those researchers as commonly the influence of goal orientations and epistemological beliefs on intrinsic motivation; they have not combined the two factors and examined relationships among goal orientation, epistemological beliefs, and intrinsic motivation. Therefore, although there is a plethora of research on the matter in related disciplines, the researchers commonly do not have consensus on a term that could be used to discuss how engineering students are motivation. This paper identifies literature whose characteristics have focused on the concept of motivation. Attempts were made to retrieve related lietarure empirically examined motivation, extrinsic motivation, Goal orientation, Epistemological beliefs, and intrinsic motivation to gain insight information. It is believed that the present study may help educators in organizing content, preparing curriculum, and evaluate student tasks, so that students can begin to develop more mature and effective epistemological beliefs and design their proper goals for their learning process.

  13. Charge transfer through DNA/DNA duplexes and DNA/RNA hybrids: complex theoretical and experimental studies.

    Science.gov (United States)

    Kratochvílová, Irena; Vala, Martin; Weiter, Martin; Špérová, Miroslava; Schneider, Bohdan; Páv, Ondřej; Šebera, Jakub; Rosenberg, Ivan; Sychrovský, Vladimír

    2013-01-01

    Oligonucleotides conduct electric charge via various mechanisms and their characterization and understanding is a very important and complicated task. In this work, experimental (temperature dependent steady state fluorescence spectroscopy, time-resolved fluorescence spectroscopy) and theoretical (Density Functional Theory) approaches were combined to study charge transfer processes in short DNA/DNA and RNA/DNA duplexes with virtually equivalent sequences. The experimental results were consistent with the theoretical model - the delocalized nature of HOMO orbitals and holes, base stacking, electronic coupling and conformational flexibility formed the conditions for more effective short distance charge transfer processes in RNA/DNA hybrids. RNA/DNA and DNA/DNA charge transfer properties were strongly connected with temperature affected structural changes of molecular systems - charge transfer could be used as a probe of even tiny changes of molecular structures and settings. © 2013. Published by Elsevier B.V. All rights reserved.

  14. Intrinsic and Extrinsic Motivation for Stereotypic and Repetitive Behavior

    Science.gov (United States)

    Joosten, Annette V.; Bundy, Anita C.; Einfeld, Stewart L.

    2009-01-01

    This study provides evidence for intrinsic and extrinsic motivators for stereotypical and repetitive behavior in children with autism and intellectual disability and children with intellectual disability alone. We modified the Motivation Assessment Scale (MAS) (1988b); dividing it into intrinsic and extrinsic measures and adding items to assess…

  15. A prototype empirical framework of intrinsic and extrinsic EERQI indicators

    NARCIS (Netherlands)

    Mooij, Ton

    2012-01-01

    The research question is: What do statistical analyses show us about the relationships between intrinsic and extrinsic indicators of quality and what does this mean when constructing a prototype EERQI framework? The pilot study involved the scoring on both intrinsic and extrinsic indica-tors for 177

  16. Intrinsic Motivation and Flow Condition on the Music Teacher's Performance

    Science.gov (United States)

    Torres Delgado, Gabriela

    2017-01-01

    The aim of these research is to identify if music teachers and teachers from other areas are intrinsically or extrinsically motivated, to identify the dimensions of the flow state, and to identify if there is a relationship between intrinsic motivation and flow state in these teachers. The sample was made up of 738 active teachers. The presence of…

  17. Palatalization and Intrinsic Prosodic Vowel Features in Russian

    Science.gov (United States)

    Ordin, Mikhail

    2011-01-01

    The presented study is aimed at investigating the interaction of palatalization and intrinsic prosodic features of the vowel in CVC (consonant+vowel+consonant) syllables in Russian. The universal nature of intrinsic prosodic vowel features was confirmed with the data from the Russian language. It was found that palatalization of the consonants…

  18. Cooperative motion of intrinsic and actuated semiflexible swimmers

    NARCIS (Netherlands)

    Llopis, I.; Pagonabarraga, I.; Lagomarsino, M.C.; Lowe, C.P.

    2013-01-01

    We examine the phenomenon of hydrodynamic-induced cooperativity for pairs of flagellated micro-organism swimmers, of which spermatozoa cells are an example. We consider semiflexible swimmers, where inextensible filaments are driven by an internal intrinsic force and torque-free mechanism (intrinsic

  19. The Relations of Mothers' Controlling Vocalizations to Children's Intrinsic Motivation.

    Science.gov (United States)

    Deci, Edward L.; And Others

    1993-01-01

    Coded maternal vocalizations during videotaped play sessions of mothers and their six- or seven-year-old children. Children's intrinsic motivation was assessed by observing children's play when they were alone in a room. Found a negative relationship between maternal controlling vocalizations and children's intrinsic motivation. (MM)

  20. Importance of Intrinsic and Instrumental Value of Education in Pakistan

    Science.gov (United States)

    Kumar, Mahendar

    2017-01-01

    Normally, effectiveness of any object or thing is judged by two values; intrinsic and instrumental. To compare intrinsic value of education with instrumental value, this study has used the following variables: getting knowledge for its own sake, getting knowledge for social status, getting knowledge for job or business endeavor and getting…

  1. College Student Intrinsic and/or Extrinsic Motivation and Learning.

    Science.gov (United States)

    Lin, Yi-Guang; McKeachie, Wilbert J.

    This paper investigates the joint effects of intrinsic and extrinsic goals on college students' learning in an introductory psychology course, a biology course, and several social science courses. The study questioned whether higher levels of motivation lead to better student performance. College students were surveyed using the Intrinsic Goal…

  2. Self-Determination Theory: Intrinsic Motivation and Behavioral Change.

    Science.gov (United States)

    Flannery, Marie

    2017-03-01

    Motivation is a central concept in behavioral change. This article reviews the self-determination theory with an emphasis on "intrinsic motivation," which is facilitated when three basic psychological needs (autonomy, competence, and relatedness) are met. Intrinsic motivation is associated with improved well-being and sustained behavioral change.

  3. Leadership style and employees' intrinsic job satisfaction in the ...

    African Journals Online (AJOL)

    This study investigates the impact of leadership style on employees' intrinsic job satisfaction in the Cross River State Newspaper Corporation, Calabar, Nigeria. The study examined the problem of dissatisfaction in the work place as far as intrinsic factors of job satisfaction are concerned. Structured questionnaire was used ...

  4. Elderly Taiwanese's Intrinsic Risk Factors for Fall-related Injuries

    Directory of Open Access Journals (Sweden)

    In-Fun Li

    2016-09-01

    Conclusion: Elderly Taiwanese inpatients with existing intrinsic conditions of cancer, vertigo, and lower leg weakness were at high risk of falling, resulting in severe injuries. Additional research including controlled trials is necessary to further identify treatable, causal intrinsic risk factors for this elderly group.

  5. Genetic recombination induced by DNA double-strand break in bacteriophage T4: nature of the left/right bias.

    Science.gov (United States)

    Shcherbakov, Victor P; Shcherbakova, Tamara; Plugina, Lidiya; Sizova, Svetlana; Kudryashova, Elena; Granovsky, Igor

    2008-06-01

    The experimental system combining double-strand breaks (DSBs), produced site-specifically by SegC endonuclease, with the famous advantages of the bacteriophage T4 rII mutant recombination analysis was used here to elucidate the origin of the recombination bias on two sides of the DSB, especially pronounced in gene 39 (topoisomerase II) and gene 59 (41-helicase loader) mutants. Three sources were found to contribute to the bias: (1) the SegC endonuclease may remain bound to the end of the broken DNA and thus protect it from exonuclease degradation; (2) in heteroduplex heterozygotes (HHs), arising as the recombinant products in the left-hand crosses, the transcribed strands are of rII mutant phenotype, so they, in contrast to the right-hand HHs, do not produce plaques on the lawn of the lambda-lysogenic host; and (3) the intrinsic polarity of T4 chromosome, reflected in transcription, may be a cause for discrimination of promoter-proximal and promoter-distal DNA sequences. It is shown that the apparent recombination bias does not imply one-sidedness of the DSB repair but just reflects a different depth of the end processing. It is inferred that the cause, underlying the "intrinsic" bias, might be interference between strand exchange and transcription. Topoisomerase and helicase functions are necessary to turn the process in favor of strand exchange. The idea is substantiated that the double-stranded to single-stranded DNA transition edge (not ss-DNA tip) serves as an actual recombinogenic element.

  6. Intrinsic motivation and sportsmanship: mediating role of interpersonal relationships.

    Science.gov (United States)

    Núñez, Juan L; Martín-Albo, José; Navarro, José G; Sánchez, Juana M; González-Cutre, David

    2009-06-01

    This study analyzed the mediating role of interpersonal relations between intrinsic motivation and sportsmanship. Athletes (98 men, 97 women), ages 11 to 43 years, completed measures of intrinsic motivation toward sports, self-concept of social and family relations, and sportsmanship orientation. A structural equation model indicated that self-concept of interpersonal relations mediated the relation between intrinsic motivation and sportsmanship. Also, intrinsic motivation was directly and positively associated with self-concept of interpersonal relations, which, in turn, was positively and significantly related to sportsmanship. Variances explained by self-concept of interpersonal relations and by sportsmanship were 32 and 56%, respectively. The motivational interaction between the context of interpersonal relations and the sports context proposed in the hierarchical model of intrinsic and extrinsic motivation was discussed.

  7. Ethnic Stigma, Academic Anxiety, and Intrinsic Motivation in Middle Childhood

    Science.gov (United States)

    Gillen-O’Neel, Cari; Ruble, Diane N.; Fuligni, Andrew J.

    2011-01-01

    Previous research addressing the dynamics of stigma and academics has focused on African-American adolescents and adults. The present study examined stigma awareness, academic anxiety, and intrinsic motivation among 451 young (ages 6–11) and diverse (African-American, Chinese, Dominican, Russian, and European-American) students. Results indicated that ethnic-minority children reported higher stigma awareness than European-American children. For all children, stigma awareness was associated with higher academic anxiety and lower intrinsic motivation. Despite these associations, ethnic-minority children reported higher levels of intrinsic motivation than their European-American peers. A significant portion of the higher intrinsic motivation among Dominican students was associated with their higher levels of school belonging, suggesting that supportive school environments may be important sources of intrinsic motivation among some ethnic-minority children. PMID:21883152

  8. Extrinsic and intrinsic regulation of axon regeneration at a crossroads.

    Science.gov (United States)

    Kaplan, Andrew; Ong Tone, Stephan; Fournier, Alyson E

    2015-01-01

    Repair of the injured spinal cord is a major challenge in medicine. The limited intrinsic regenerative response mounted by adult central nervous system (CNS) neurons is further hampered by astrogliosis, myelin debris and scar tissue that characterize the damaged CNS. Improved axon regeneration and recovery can be elicited by targeting extrinsic factors as well as by boosting neuron-intrinsic growth regulators. Our knowledge of the molecular basis of intrinsic and extrinsic regulators of regeneration has expanded rapidly, resulting in promising new targets to promote repair. Intriguingly certain neuron-intrinsic growth regulators are emerging as promising targets to both stimulate growth and relieve extrinsic inhibition of regeneration. This crossroads between the intrinsic and extrinsic aspects of spinal cord injury is a promising target for effective therapies for this unmet need.

  9. Motivating crowding theory - opening the black box of intrinsic motivation

    DEFF Research Database (Denmark)

    Jacobsen, Christian Bøtcher

    2010-01-01

    Public employees work for many other reasons than because they are paid for it. In other words, intrinsic motivation is an important determinant for their performance. Nonetheless, public sector organizations increasingly rely on extrinsic motivation factors such as monetary incentives to motivate...... employees. Motivation crowding theory claims that this may be at the expense of intrinsic motivation, if the extrinsic motivation factor is perceived to be controlling. On the other hand, intrinsic motivation will be enhanced (crowded in), if the extrinsic motivation factor is perceived to be supportive......, monetary incentives are found to cause different crowding effects for these different types of intrinsic motivation. The results call for more theoretical work on the drivers of motivation crowding effects and for practitioners to pay more attention to what type of intrinsic motivation is at stake, when...

  10. Sorting fluorescent nanocrystals with DNA

    Energy Technology Data Exchange (ETDEWEB)

    Gerion, Daniele; Parak, Wolfgang J.; Williams, Shara C.; Zanchet, Daniela; Micheel, Christine M.; Alivisatos, A. Paul

    2001-12-10

    Semiconductor nanocrystals with narrow and tunable fluorescence are covalently linked to oligonucleotides. These biocompounds retain the properties of both nanocrystals and DNA. Therefore, different sequences of DNA can be coded with nanocrystals and still preserve their ability to hybridize to their complements. We report the case where four different sequences of DNA are linked to four nanocrystal samples having different colors of emission in the range of 530-640 nm. When the DNA-nanocrystal conjugates are mixed together, it is possible to sort each type of nanoparticle using hybridization on a defined micrometer -size surface containing the complementary oligonucleotide. Detection of sorting requires only a single excitation source and an epifluorescence microscope. The possibility of directing fluorescent nanocrystals towards specific biological targets and detecting them, combined with their superior photo-stability compared to organic dyes, opens the way to improved biolabeling experiments, such as gene mapping on a nanometer scale or multicolor microarray analysis.

  11. Detection of Non-Amplified Genomic DNA

    CERN Document Server

    Corradini, Roberto

    2012-01-01

    This book offers a state-of-the-art overview on non amplified DNA detection methods and provides chemists, biochemists, biotechnologists and material scientists with an introduction to these methods. In fact all these fields have dedicated resources to the problem of nucleic acid detection, each contributing with their own specific methods and concepts. This book will explain the basic principles of the different non amplified DNA detection methods available, highlighting their respective advantages and limitations. The importance of non-amplified DNA sequencing technologies will be also discussed. Non-amplified DNA detection can be achieved by adopting different techniques. Such techniques have allowed the commercialization of innovative platforms for DNA detection that are expected to break into the DNA diagnostics market. The enhanced sensitivity required for the detection of non amplified genomic DNA has prompted new strategies that can achieve ultrasensitivity by combining specific materials with specifi...

  12. Disorder and defects are not intrinsic to boron carbide

    Science.gov (United States)

    Mondal, Swastik; Bykova, Elena; Dey, Somnath; Ali, Sk Imran; Dubrovinskaia, Natalia; Dubrovinsky, Leonid; Parakhonskiy, Gleb; van Smaalen, Sander

    2016-01-01

    A unique combination of useful properties in boron-carbide, such as extreme hardness, excellent fracture toughness, a low density, a high melting point, thermoelectricity, semi-conducting behavior, catalytic activity and a remarkably good chemical stability, makes it an ideal material for a wide range of technological applications. Explaining these properties in terms of chemical bonding has remained a major challenge in boron chemistry. Here we report the synthesis of fully ordered, stoichiometric boron-carbide B13C2 by high-pressure-high-temperature techniques. Our experimental electron-density study using high-resolution single-crystal synchrotron X-ray diffraction data conclusively demonstrates that disorder and defects are not intrinsic to boron carbide, contrary to what was hitherto supposed. A detailed analysis of the electron density distribution reveals charge transfer between structural units in B13C2 and a new type of electron-deficient bond with formally unpaired electrons on the C-B-C group in B13C2. Unprecedented bonding features contribute to the fundamental chemistry and materials science of boron compounds that is of great interest for understanding structure-property relationships and development of novel functional materials.

  13. State-dependent intrinsic predictability of cortical network dynamics.

    Directory of Open Access Journals (Sweden)

    Leila Fakhraei

    Full Text Available The information encoded in cortical circuit dynamics is fleeting, changing from moment to moment as new input arrives and ongoing intracortical interactions progress. A combination of deterministic and stochastic biophysical mechanisms governs how cortical dynamics at one moment evolve from cortical dynamics in recently preceding moments. Such temporal continuity of cortical dynamics is fundamental to many aspects of cortex function but is not well understood. Here we study temporal continuity by attempting to predict cortical population dynamics (multisite local field potential based on its own recent history in somatosensory cortex of anesthetized rats and in a computational network-level model. We found that the intrinsic predictability of cortical dynamics was dependent on multiple factors including cortical state, synaptic inhibition, and how far into the future the prediction extends. By pharmacologically tuning synaptic inhibition, we obtained a continuum of cortical states with asynchronous population activity at one extreme and stronger, spatially extended synchrony at the other extreme. Intermediate between these extremes we observed evidence for a special regime of population dynamics called criticality. Predictability of the near future (10-100 ms increased as the cortical state was tuned from asynchronous to synchronous. Predictability of the more distant future (>1 s was generally poor, but, surprisingly, was higher for asynchronous states compared to synchronous states. These experimental results were confirmed in a computational network model of spiking excitatory and inhibitory neurons. Our findings demonstrate that determinism and predictability of network dynamics depend on cortical state and the time-scale of the dynamics.

  14. Intrinsic and Antipsychotic Drug-Induced Metabolic Dysfunction in Schizophrenia

    Directory of Open Access Journals (Sweden)

    Zachary Freyberg

    2017-07-01

    Full Text Available For decades, there have been observations demonstrating significant metabolic disturbances in people with schizophrenia including clinically relevant weight gain, hypertension, and disturbances in glucose and lipid homeostasis. Many of these findings pre-date the use of antipsychotic drugs (APDs which on their own are also strongly associated with metabolic side effects. The combination of APD-induced metabolic changes and common adverse environmental factors associated with schizophrenia have made it difficult to determine the specific contributions of each to the overall metabolic picture. Data from drug-naïve patients, both from the pre-APD era and more recently, suggest that there may be an intrinsic metabolic risk associated with schizophrenia. Nevertheless, these findings remain controversial due to significant clinical variability in both psychiatric and metabolic symptoms throughout patients' disease courses. Here, we provide an extensive review of classic and more recent literature describing the metabolic phenotype associated with schizophrenia. We also suggest potential mechanistic links between signaling pathways associated with schizophrenia and metabolic dysfunction. We propose that, beyond its symptomatology in the central nervous system, schizophrenia is also characterized by pathophysiology in other organ systems directly related to metabolic control.

  15. Developing chemotherapy for diffuse pontine intrinsic gliomas (DIPG).

    Science.gov (United States)

    Gwak, Ho-Shin; Park, Hyeon Jin

    2017-12-01

    Prognosis of diffuse intrinsic pontine glioma (DIPG) is poor, with a median survival of 10 months after radiation. At present, chemotherapy has failed to show benefits over radiation. Advances in biotechnology have enabled the use of autopsy specimens for genomic analyses and molecular profiling of DIPG, which are quite different from those of supratentorial high grade glioma. Recently, combined treatments of cytotoxic agents with target inhibitors, based on biopsied tissue, are being examined in on-going trials. Spontaneous DIPG mice models have been recently developed that is useful for preclinical studies. Finally, the convection-enhanced delivery could be used to infuse drugs directly into the brainstem parenchyma, to which conventional systemic administration fails to achieve effective concentration. The WHO glioma classification defines a diffuse midline glioma with a H3-K27M-mutation, and we expect increase of tissue confirmation of DIPG, which will give us the biological information helping the development of a targeted therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Sequential addition of short DNA oligos in DNA-polymerase-based synthesis reactions

    Science.gov (United States)

    Gardner, Shea N; Mariella, Jr., Raymond P; Christian, Allen T; Young, Jennifer A; Clague, David S

    2013-06-25

    A method of preselecting a multiplicity of DNA sequence segments that will comprise the DNA molecule of user-defined sequence, separating the DNA sequence segments temporally, and combining the multiplicity of DNA sequence segments with at least one polymerase enzyme wherein the multiplicity of DNA sequence segments join to produce the DNA molecule of user-defined sequence. Sequence segments may be of length n, where n is an odd integer. In one embodiment the length of desired hybridizing overlap is specified by the user and the sequences and the protocol for combining them are guided by computational (bioinformatics) predictions. In one embodiment sequence segments are combined from multiple reading frames to span the same region of a sequence, so that multiple desired hybridizations may occur with different overlap lengths.

  17. Intrinsic Evaporative Cooling by Hygroscopic Earth Materials

    Directory of Open Access Journals (Sweden)

    Alexandra R. Rempel

    2016-08-01

    Full Text Available The phase change of water from liquid to vapor is one of the most energy-intensive physical processes in nature, giving it immense potential for cooling. Diverse evaporative cooling strategies have resulted worldwide, including roof ponds and sprinklers, courtyard fountains, wind catchers with qanats, irrigated green roofs, and fan-assisted evaporative coolers. These methods all require water in bulk liquid form. The evaporation of moisture that has been sorbed from the atmosphere by hygroscopic materials is equally energy-intensive, however, yet has not been examined for its cooling potential. In arid and semi-arid climates, hygroscopic earth buildings occur widely and are known to maintain comfortable indoor temperatures, but evaporation of moisture from their walls and roofs has been regarded as unimportant since water scarcity limits irrigation and rainfall; instead, their cool interiors are attributed to well-established mass effects in delaying the transmission of sensible gains. Here, we investigate the cooling accomplished by daily cycles of moisture sorption and evaporation which, requiring only ambient humidity, we designate as “intrinsic” evaporative cooling. Connecting recent soil science to heat and moisture transport studies in building materials, we use soils, adobe, cob, unfired earth bricks, rammed earth, and limestone to reveal the effects of numerous parameters (temperature and relative humidity, material orientation, thickness, moisture retention properties, vapor diffusion resistance, and liquid transport properties on the magnitude of intrinsic evaporative cooling and the stabilization of indoor relative humidity. We further synthesize these effects into concrete design guidance. Together, these results show that earth buildings in diverse climates have significant potential to cool themselves evaporatively through sorption of moisture from humid night air and evaporation during the following day’s heat. This finding

  18. DNA repair

    International Nuclear Information System (INIS)

    Van Zeeland, A.A.

    1984-01-01

    In this chapter a series of DNA repair pathways are discussed which are available to the cell to cope with the problem of DNA damaged by chemical or physical agents. In the case of microorganisms our knowledge about the precise mechanism of each DNA repair pathway and the regulation of it has been improved considerably when mutants deficient in these repair mechanisms became available. In the case of mammalian cells in culture, until recently there were very little repair deficient mutants available, because in almost all mammalian cells in culture at least the diploid number of chromosomes is present. Therefore the frequency of repair deficient mutants in such populations is very low. Nevertheless because replica plating techniques are improving some mutants from Chinese hamsters ovary cells and L5178Y mouse lymphoma cells are now available. In the case of human cells, cultures obtained from patients with certain genetic diseases are available. A number of cells appear to be sensitive to some chemical or physical mutagens. These include cells from patients suffering from xeroderma pigmentosum, Ataxia telangiectasia, Fanconi's anemia, Cockayne's syndrome. However, only in the case of xeroderma pigmentosum cells, has the sensitivity to ultraviolet light been clearly correlated with a deficiency in excision repair of pyrimidine dimers. Furthermore the work with strains obtained from biopsies from man is difficult because these cells generally have low cloning efficiencies and also have a limited lifespan in vitro. It is therefore very important that more repair deficient mutants will become available from established cell lines from human or animal origin

  19. Disruption of Aneuploidy and Senescence Induced by Aurora Inhibition Promotes Intrinsic Apoptosis in Double Hit or Double Expressor Diffuse Large B-cell Lymphomas.

    Science.gov (United States)

    Islam, Shariful; Qi, Wenqing; Morales, Carla; Cooke, Laurence; Spier, Catherine; Weterings, Eric; Mahadevan, Daruka

    2017-10-01

    Double hit (DH) or double expressor (DE) diffuse large B-cell lymphomas (DLBCL) are aggressive non-Hodgkin's lymphomas (NHL) with translocations and/or overexpressions of MYC and BCL-2 , which are difficult to treat. Aurora kinase (AK) inhibition with alisertib in DH/DE-DLBCL induces cell death in ∼30%, while ∼70% are aneuploid and senescent cells (AASC), a mitotic escape mechanism contributing to drug resistance. These AASCs elaborated a high metabolic rate by increased AKT/mTOR and ERK/MAPK activity via BTK signaling through the chronic active B-cell receptor (BCR) pathway. Combinations of alisertib + ibrutinib or alisertib + ibrutinib + rituximab significantly reduced AASCs with enhanced intrinsic cell death. Inhibition of AK + BTK reduced phosphorylation of AKT/mTOR and ERK-1/2, upregulated phospho-H2A-X and Chk-2 (DNA damage), reduced Bcl-6, and decreased Bcl-2 and Bcl-xL and induced apoptosis by PARP cleavage. In a DE-DLBCL SCID mouse xenograft model, ibrutinib alone was inactive, while alisertib + ibrutinib was additive with a tumor growth inhibition (TGI) rate of ∼25%. However, TGI for ibrutinib + rituximab was ∼50% to 60%. In contrast, triple therapy showed a TGI rate of >90%. Kaplan-Meier survival analysis showed that 67% of mice were alive at day 89 with triple therapy versus 20% with ibrutinib + rituximab. All treatments were well tolerated with no changes in body weights. A novel triple therapy consisting of alisertib + ibrutinib + rituximab inhibits AASCs induced by AK inhibition in DH/DE-DLBCL leading to a significant antiproliferative signal, enhanced intrinsic apoptosis and may be of therapeutic potential in these lymphomas. Mol Cancer Ther; 16(10); 2083-93. ©2017 AACR . ©2017 American Association for Cancer Research.

  20. Combined theoretical and computational study of interstrand DNA guanine-guanine cross-linking by trans-[Pt(pyridine)2] derived from the photoactivated prodrug trans,trans,trans-[Pt(N3)2(OH)2(pyridine)2

    Czech Academy of Sciences Publication Activity Database

    Tai, H.-Ch.; Brodbeck, R.; Kašpárková, Jana; Farrer, N.J.; Brabec, Viktor; Sadler, P.J.; Deeth, R.J.

    2012-01-01

    Roč. 51, č. 12 (2012), s. 6830-6841 ISSN 0020-1669 R&D Projects: GA ČR(CZ) GAP301/10/0598 Institutional research plan: CEZ:AV0Z50040702 Keywords : platinum * photoactivation * DNA Subject RIV: BO - Biophysics Impact factor: 4.593, year: 2012

  1. Combination of intratumoral injections of vaccinia virus MVA expressing GM-CSF and immunization with DNA vaccine prolongs the survival of mice bearing HPV16 induced tumors with downregulated expression of MHC class I molecules

    Czech Academy of Sciences Publication Activity Database

    Němečková, Š.; Šmahel, M.; Hainz, P.; Macková, J.; Zurková, K.; Gabriel, P.; Indrová, Marie; Kutinová, L.

    2007-01-01

    Roč. 54, č. 4 (2007), s. 326-333 ISSN 0028-2685 R&D Projects: GA MZd NR8004 Institutional research plan: CEZ:AV0Z50520514 Keywords : vaccinia virus MVA expressing GM- CSF * DNA vaccine * HPV16 induced tumors Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.208, year: 2007

  2. UVA photoactivation of DNA containing halogenated thiopyrimidines induces cytotoxic DNA lesions

    Science.gov (United States)

    Brem, Reto; Zhang, Xiaohui; Xu, Yao-Zhong; Karran, Peter

    2015-01-01

    Photochemotherapy, the combination of a photosensitiser and ultraviolet (UV) or visible light, is an effective treatment for skin conditions including cancer. The high mutagenicity and non-selectivity of photochemotherapy regimes warrants the development of alternative approaches. We demonstrate that the thiopyrimidine nucleosides 5-bromo-4-thiodeoxyuridine (SBrdU) and 5-iodo-4-thiodeoxyuridine (SIdU) are incorporated into the DNA of cultured human and mouse cells where they synergistically sensitise killing by low doses of UVA radiation. The DNA halothiopyrimidine/UVA combinations induce DNA interstrand crosslinks, DNA-protein crosslinks, DNA strand breaks, nucleobase damage and lesions that resemble UV-induced pyrimidine(6-4)pyrimidone photoproducts. These are potentially lethal DNA lesions and cells defective in their repair are hypersensitive to killing by SBrdU/UVA and SIdU/UVA. DNA SIdU and SBrdU generate lethal DNA photodamage by partially distinct mechanisms that reflect the different photolabilities of their C–I and C–Br bonds. Although singlet oxygen is involved in photolesion formation, DNA SBrdU and SIdU photoactivation does not detectably increase DNA 8-oxoguanine levels. The absence of significant collateral damage to normal guanine suggests that UVA activation of DNA SIdU or SBrdU might offer a strategy to target hyperproliferative skin conditions that avoids the extensive formation of a known mutagenic DNA lesion. PMID:25747491

  3. Comparative assessment of intrinsic mechanical stimuli on knee cartilage and compressed agarose constructs.

    Science.gov (United States)

    Completo, A; Bandeiras, C; Fonseca, F

    2017-06-01

    A well-established cue for improving the properties of tissue-engineered cartilage is mechanical stimulation. However, the explicit ranges of mechanical stimuli that correspond to favorable metabolic outcomes are elusive. Usually, these outcomes have only been associated with the applied strain and frequency, an oversimplification that can hide the fundamental relationship between the intrinsic mechanical stimuli and the metabolic outcomes. This highlights two important key issues: the firstly is related to the evaluation of the intrinsic mechanical stimuli of native cartilage; the second, assuming that the intrinsic mechanical stimuli will be important, deals with the ability to replicate them on the tissue-engineered constructs. This study quantifies and compares the volume of cartilage and agarose subjected to a given magnitude range of each intrinsic mechanical stimulus, through a numerical simulation of a patient-specific knee model coupled with experimental data of contact during the stance phase of gait, and agarose constructs under direct-dynamic compression. The results suggest that direct compression loading needs to be parameterized with time-dependence during the initial culture period in order to better reproduce each one of the intrinsic mechanical stimuli developed in the patient-specific cartilage. A loading regime which combines time periods of low compressive strain (5%) and frequency (0.5Hz), in order to approach the maximal principal strain and fluid velocity stimulus of the patient-specific cartilage, with time periods of high compressive strain (20%) and frequency (3Hz), in order to approach the pore pressure values, may be advantageous relatively to a single loading regime throughout the full culture period. Copyright © 2017 IPEM. Published by Elsevier Ltd. All rights reserved.

  4. The Frequency of Intrinsic X-Ray Weakness among Broad Absorption Line Quasars

    Science.gov (United States)

    Liu, Hezhen; Luo, B.; Brandt, W. N.; Gallagher, S. C.; Garmire, G. P.

    2018-06-01

    We present combined ≈14–37 ks Chandra observations of seven z = 1.6–2.7 broad absorption line (BAL) quasars selected from the Large Bright Quasar Survey (LBQS). These seven objects are high-ionization BAL (HiBAL) quasars, and they were undetected in the Chandra hard band (2–8 keV) in previous observations. The stacking analyses of previous Chandra observations suggested that these seven objects likely contain some candidates for intrinsically X-ray weak BAL quasars. With the new Chandra observations, six targets are detected. We calculate their effective power-law photon indices and hard-band flux weakness, and find that two objects, LBQS 1203+1530 and LBQS 1442–0011, show soft/steep spectral shapes ({{{Γ }}}eff}={2.2}-0.9+0.9 and {1.9}-0.8+0.9) and significant X-ray weakness in the hard band (by factors of ≈15 and 12). We conclude that the two HiBAL quasars are good candidates for intrinsically X-ray weak BAL quasars. The mid-infrared-to-ultraviolet spectral energy distributions of the two candidates are consistent with those of typical quasars. We constrain the fraction of intrinsically X-ray weak active galactic nuclei (AGNs) among HiBAL quasars to be ≈7%–10% (2/29–3/29), and we estimate it is ≈6%–23% (2/35–8/35) among the general BAL quasar population. Such a fraction is considerably larger than that among non-BAL quasars, and we suggest that intrinsically X-ray weak quasars are preferentially observed as BAL quasars. Intrinsically X-ray weak AGNs likely comprise a small minority of the luminous type 1 AGN population, and they should not affect significantly the completeness of these AGNs found in deep X-ray surveys.

  5. Connecting localized DNA strand displacement reactions

    Science.gov (United States)

    Mullor Ruiz, Ismael; Arbona, Jean-Michel; Lad, Amitkumar; Mendoza, Oscar; Aimé, Jean-Pierre; Elezgaray, Juan

    2015-07-01

    Logic circuits based on DNA strand displacement reactions have been shown to be versatile enough to compute the square root of four-bit numbers. The implementation of these circuits as a set of bulk reactions faces difficulties which include leaky reactions and intrinsically slow, diffusion-limited reaction rates. In this paper, we consider simple examples of these circuits when they are attached to platforms (DNA origamis). As expected, constraining distances between DNA strands leads to faster reaction rates. However, it also induces side-effects that are not detectable in the solution-phase version of this circuitry. Appropriate design of the system, including protection and asymmetry between input and fuel strands, leads to a reproducible behaviour, at least one order of magnitude faster than the one observed under bulk conditions.Logic circuits based on DNA strand displacement reactions have been shown to be versatile enough to compute the square root of four-bit numbers. The implementation of these circuits as a set of bulk reactions faces difficulties which include leaky reactions and intrinsically slow, diffusion-limited reaction rates. In this paper, we consider simple examples of these circuits when they are attached to platforms (DNA origamis). As expected, constraining distances between DNA strands leads to faster reaction rates. However, it also induces side-effects that are not detectable in the solution-phase version of this circuitry. Appropriate design of the system, including protection and asymmetry between input and fuel strands, leads to a reproducible behaviour, at least one order of magnitude faster than the one observed under bulk conditions. Electronic supplementary information (ESI) available. See DOI: 10.1039/C5NR02434J

  6. Firing rate dynamics in recurrent spiking neural networks with intrinsic and network heterogeneity.

    Science.gov (United States)

    Ly, Cheng

    2015-12-01

    Heterogeneity of neural attributes has recently gained a lot of attention and is increasing recognized as a crucial feature in neural processing. Despite its importance, this physiological feature has traditionally been neglected in theoretical studies of cortical neural networks. Thus, there is still a lot unknown about the consequences of cellular and circuit heterogeneity in spiking neural networks. In particular, combining network or synaptic heterogeneity and intrinsic heterogeneity has yet to be considered systematically despite the fact that both are known to exist and likely have significant roles in neural network dynamics. In a canonical recurrent spiking neural network model, we study how these two forms of heterogeneity lead to different distributions of excitatory firing rates. To analytically characterize how these types of heterogeneities affect the network, we employ a dimension reduction method that relies on a combination of Monte Carlo simulations and probability density function equations. We find that the relationship between intrinsic and network heterogeneity has a strong effect on the overall level of heterogeneity of the firing rates. Specifically, this relationship can lead to amplification or attenuation of firing rate heterogeneity, and these effects depend on whether the recurrent network is firing asynchronously or rhythmically firing. These observations are captured with the aforementioned reduction method, and furthermore simpler analytic descriptions based on this dimension reduction method are developed. The final analytic descriptions provide compact and descriptive formulas for how the relationship between intrinsic and network heterogeneity determines the firing rate heterogeneity dynamics in various settings.

  7. Intrinsic Radiation Source Generation with the ISC Package: Data Comparisons and Benchmarking

    International Nuclear Information System (INIS)

    Solomon, Clell J. Jr.

    2012-01-01

    The characterization of radioactive emissions from unstable isotopes (intrinsic radiation) is necessary for shielding and radiological-dose calculations from radioactive materials. While most radiation transport codes, e.g., MCNP [X-5 Monte Carlo Team, 2003], provide the capability to input user prescribed source definitions, such as radioactive emissions, they do not provide the capability to calculate the correct radioactive-source definition given the material compositions. Special modifications to MCNP have been developed in the past to allow the user to specify an intrinsic source, but these modification have not been implemented into the primary source base [Estes et al., 1988]. To facilitate the description of the intrinsic radiation source from a material with a specific composition, the Intrinsic Source Constructor library (LIBISC) and MCNP Intrinsic Source Constructor (MISC) utility have been written. The combination of LIBISC and MISC will be herein referred to as the ISC package. LIBISC is a statically linkable C++ library that provides the necessary functionality to construct the intrinsic-radiation source generated by a material. Furthermore, LIBISC provides the ability use different particle-emission databases, radioactive-decay databases, and natural-abundance databases allowing the user flexibility in the specification of the source, if one database is preferred over others. LIBISC also provides functionality for aging materials and producing a thick-target bremsstrahlung photon source approximation from the electron emissions. The MISC utility links to LIBISC and facilitates the description of intrinsic-radiation sources into a format directly usable with the MCNP transport code. Through a series of input keywords and arguments the MISC user can specify the material, age the material if desired, and produce a source description of the radioactive emissions from the material in an MCNP readable format. Further details of using the MISC utility can

  8. Beyond the evoked/intrinsic neural process dichotomy

    Directory of Open Access Journals (Sweden)

    Taylor Bolt

    2018-03-01

    Full Text Available Contemporary functional neuroimaging research has increasingly focused on characterization of intrinsic or “spontaneous” brain activity. Analysis of intrinsic activity is often contrasted with analysis of task-evoked activity that has traditionally been the focus of cognitive neuroscience. But does this evoked/intrinsic dichotomy adequately characterize human brain function? Based on empirical data demonstrating a close functional interdependence between intrinsic and task-evoked activity, we argue that the dichotomy between intrinsic and task-evoked activity as unobserved contributions to brain activity is artificial. We present an alternative picture of brain function in which the brain’s spatiotemporal dynamics do not consist of separable intrinsic and task-evoked components, but reflect the enaction of a system of mutual constraints to move the brain into and out of task-appropriate functional configurations. According to this alternative picture, cognitive neuroscientists are tasked with describing both the temporal trajectory of brain activity patterns across time, and the modulation of this trajectory by task states, without separating this process into intrinsic and task-evoked components. We argue that this alternative picture of brain function is best captured in a novel explanatory framework called enabling constraint. Overall, these insights call for a reconceptualization of functional brain activity, and should drive future methodological and empirical efforts.

  9. SELECTING QUASARS BY THEIR INTRINSIC VARIABILITY

    International Nuclear Information System (INIS)

    Schmidt, Kasper B.; Rix, Hans-Walter; Jester, Sebastian; Hennawi, Joseph F.; Marshall, Philip J.; Dobler, Gregory

    2010-01-01

    We present a new and simple technique for selecting extensive, complete, and pure quasar samples, based on their intrinsic variability. We parameterize the single-band variability by a power-law model for the light-curve structure function, with amplitude A and power-law index γ. We show that quasars can be efficiently separated from other non-variable and variable sources by the location of the individual sources in the A-γ plane. We use ∼60 epochs of imaging data, taken over ∼5 years, from the SDSS stripe 82 (S82) survey, where extensive spectroscopy provides a reference sample of quasars, to demonstrate the power of variability as a quasar classifier in multi-epoch surveys. For UV-excess selected objects, variability performs just as well as the standard SDSS color selection, identifying quasars with a completeness of 90% and a purity of 95%. In the redshift range 2.5 < z < 3, where color selection is known to be problematic, variability can select quasars with a completeness of 90% and a purity of 96%. This is a factor of 5-10 times more pure than existing color selection of quasars in this redshift range. Selecting objects from a broad griz color box without u-band information, variability selection in S82 can afford completeness and purity of 92%, despite a factor of 30 more contaminants than quasars in the color-selected feeder sample. This confirms that the fraction of quasars hidden in the 'stellar locus' of color space is small. To test variability selection in the context of Pan-STARRS 1 (PS1) we created mock PS1 data by down-sampling the S82 data to just six epochs over 3 years. Even with this much sparser time sampling, variability is an encouragingly efficient classifier. For instance, a 92% pure and 44% complete quasar candidate sample is attainable from the above griz-selected catalog. Finally, we show that the presented A-γ technique, besides selecting clean and pure samples of quasars (which are stochastically varying objects), is also

  10. Footprinting of Chlorella virus DNA ligase bound at a nick in duplex DNA.

    Science.gov (United States)

    Odell, M; Shuman, S

    1999-05-14

    The 298-amino acid ATP-dependent DNA ligase of Chlorella virus PBCV-1 is the smallest eukaryotic DNA ligase known. The enzyme has intrinsic specificity for binding to nicked duplex DNA. To delineate the ligase-DNA interface, we have footprinted the enzyme binding site on DNA and the DNA binding site on ligase. The size of the exonuclease III footprint of ligase bound a single nick in duplex DNA is 19-21 nucleotides. The footprint is asymmetric, extending 8-9 nucleotides on the 3'-OH side of the nick and 11-12 nucleotides on the 5'-phosphate side. The 5'-phosphate moiety is essential for the binding of Chlorella virus ligase to nicked DNA. Here we show that the 3'-OH moiety is not required for nick recognition. The Chlorella virus ligase binds to a nicked ligand containing 2',3'-dideoxy and 5'-phosphate termini, but cannot catalyze adenylation of the 5'-end. Hence, the 3'-OH is important for step 2 chemistry even though it is not itself chemically transformed during DNA-adenylate formation. A 2'-OH cannot substitute for the essential 3'-OH in adenylation at a nick or even in strand closure at a preadenylated nick. The protein side of the ligase-DNA interface was probed by limited proteolysis of ligase with trypsin and chymotrypsin in the presence and absence of nicked DNA. Protease accessible sites are clustered within a short segment from amino acids 210-225 located distal to conserved motif V. The ligase is protected from proteolysis by nicked DNA. Protease cleavage of the native enzyme prior to DNA addition results in loss of DNA binding. These results suggest a bipartite domain structure in which the interdomain segment either comprises part of the DNA binding site or undergoes a conformational change upon DNA binding. The domain structure of Chlorella virus ligase inferred from the solution experiments is consistent with the structure of T7 DNA ligase determined by x-ray crystallography.

  11. The structure of DNA by direct imaging

    KAUST Repository

    Marini, Monica; Falqui, Andrea; Moretti, Manola; Limongi, Tania; Allione, Marco; Genovese, Alessandro; Lopatin, Sergei; Tirinato, Luca; Das, Gobind; Torre, Bruno; Giugni, Andrea; Gentile, Francesco; Candeloro, Patrizio; Di Fabrizio, Enzo M.

    2015-01-01

    The structure of DNA was determined in 1953 by x-ray fiber diffraction. Several attempts have been made to obtain a direct image of DNA with alternative techniques. The direct image is intended to allow a quantitative evaluation of all relevant characteristic lengths present in a molecule. A direct image of DNA, which is different from diffraction in the reciprocal space, is difficult to obtain for two main reasons: the intrinsic very low contrast of the elements that form the molecule and the difficulty of preparing the sample while preserving its pristine shape and size. We show that through a preparation procedure compatible with the DNA physiological conditions, a direct image of a single suspended DNA molecule can be obtained. In the image, all relevant lengths of A-form DNA are measurable. A high-resolution transmission electron microscope that operates at 80 keV with an ultimate resolution of 1.5 Å was used for this experiment. Direct imaging of a single molecule can be used as a method to address biological problems that require knowledge at the single-molecule level, given that the average information obtained by x-ray diffraction of crystals or fibers is not sufficient for detailed structure determination, or when crystals cannot be obtained from biological molecules or are not sufficient in understanding multiple protein configurations.

  12. The structure of DNA by direct imaging

    KAUST Repository

    Marini, Monica

    2015-08-28

    The structure of DNA was determined in 1953 by x-ray fiber diffraction. Several attempts have been made to obtain a direct image of DNA with alternative techniques. The direct image is intended to allow a quantitative evaluation of all relevant characteristic lengths present in a molecule. A direct image of DNA, which is different from diffraction in the reciprocal space, is difficult to obtain for two main reasons: the intrinsic very low contrast of the elements that form the molecule and the difficulty of preparing the sample while preserving its pristine shape and size. We show that through a preparation procedure compatible with the DNA physiological conditions, a direct image of a single suspended DNA molecule can be obtained. In the image, all relevant lengths of A-form DNA are measurable. A high-resolution transmission electron microscope that operates at 80 keV with an ultimate resolution of 1.5 Å was used for this experiment. Direct imaging of a single molecule can be used as a method to address biological problems that require knowledge at the single-molecule level, given that the average information obtained by x-ray diffraction of crystals or fibers is not sufficient for detailed structure determination, or when crystals cannot be obtained from biological molecules or are not sufficient in understanding multiple protein configurations.

  13. Recent Progress in Functional Micellar Carriers with Intrinsic Therapeutic Activities for Anticancer Drug Delivery.

    Science.gov (United States)

    Qu, Ying; Chu, BingYang; Shi, Kun; Peng, JinRong; Qian, ZhiYong

    2017-12-01

    Polymeric micelles have presented superior delivery properties for poorly water-soluble chemotherapeutic agents. However, it remains discouraging that there may be some additional short or long-term toxicities caused by the metabolites of high quantities of carriers. If carriers had simultaneous therapeutic effects with the drug, these issues would not be a concern. For this, carriers not only simply act as drug carriers, but also exert an intrinsic therapeutic effect as a therapeutic agent. The functional micellar carriers would be beneficial to maximize the anticancer effect, overcome the drug resistance and reduce the systemic toxicity. In this review, we aim to summarize the recent progress on the development of functional micellar carriers with intrinsic anticancer activities for the delivery of anticancer drugs. This review focuses on the design strategies, properties of carriers and the drug loading behavior. In addition, the combinational therapeutic effects between carriers and chemotherapeutic agents are also discussed.

  14. PECVD deposition of device-quality intrinsic amorphous silicon at high growth rate

    Energy Technology Data Exchange (ETDEWEB)

    Carabe, J [Inst. de Energias Renovables, CIEMAT, Madrid (Spain); Gandia, J J [Inst. de Energias Renovables, CIEMAT, Madrid (Spain); Gutierrez, M T [Inst. de Energias Renovables, CIEMAT, Madrid (Spain)

    1993-11-01

    The combined influence of RF-power density (RFP) and silane flow-rate ([Phi]) on the deposition rate of plasma-enhanced chemical vapour deposition (PECVD) intrinsic amorphous silicon has been investigated. The correlation of the results obtained from the characterisation of the material with the silane deposition efficiency, as deduced from mass spectrometry, has led to an interpretation allowing to deposit intrinsic amorphous-silicon films having an optical gap of 1.87 eV and a photoconductive ratio (ratio of ambient-temperature conductivities under 1 sun AM1 and in dark) of 6 orders of magnitude at growth rates up to 10 A/s, without any structural modification of the PECVD system used. Such results are considered of high relevance regarding industrial competitiveness. (orig.)

  15. Anthraquinones quinizarin and danthron unwind negatively supercoiled DNA and lengthen linear DNA

    International Nuclear Information System (INIS)

    Verebová, Valéria; Adamcik, Jozef; Danko, Patrik; Podhradský, Dušan; Miškovský, Pavol; Staničová, Jana

    2014-01-01

    Highlights: • Anthraquinones quinizarin and danthron unwind negatively supercoiled DNA. • Anthraquinones quinizarin and danthron lengthen linear DNA. • Anthraquinones quinizarin and danthron possess middle binding affinity to DNA. • Anthraquinones quinizarin and danthron interact with DNA by intercalating mode. - Abstract: The intercalating drugs possess a planar aromatic chromophore unit by which they insert between DNA bases causing the distortion of classical B-DNA form. The planar tricyclic structure of anthraquinones belongs to the group of chromophore units and enables anthraquinones to bind to DNA by intercalating mode. The interactions of simple derivatives of anthraquinone, quinizarin (1,4-dihydroxyanthraquinone) and danthron (1,8-dihydroxyanthraquinone), with negatively supercoiled and linear DNA were investigated using a combination of the electrophoretic methods, fluorescence spectrophotometry and single molecule technique an atomic force microscopy. The detection of the topological change of negatively supercoiled plasmid DNA, unwinding of negatively supercoiled DNA, corresponding to appearance of DNA topoisomers with the low superhelicity and an increase of the contour length of linear DNA in the presence of quinizarin and danthron indicate the binding of both anthraquinones to DNA by intercalating mode

  16. Anthraquinones quinizarin and danthron unwind negatively supercoiled DNA and lengthen linear DNA

    Energy Technology Data Exchange (ETDEWEB)

    Verebová, Valéria [Institute of Biophysics, University of Veterinary Medicine and Pharmacy, Komenského 73, 041 81 Košice (Slovakia); Adamcik, Jozef [Food and Soft Materials Science, Institute of Food, Nutrition and Health, ETH Zurich, Schmelzbergstrasse 9, CH-8092 Zürich (Switzerland); Danko, Patrik; Podhradský, Dušan [Department of Biochemistry, Institute of Chemistry, Faculty of Sciences, P.J. Šafárik University, Moyzesova 11, 041 54 Košice (Slovakia); Miškovský, Pavol [Department of Biophysics, Faculty of Sciences, P.J. Šafárik University, Jesenná 5, 041 54 Košice (Slovakia); Center for Interdisciplinary Biosciences, Faculty of Sciences, P.J. Šafárik University, Jesenná 5, 041 54 Košice (Slovakia); Staničová, Jana, E-mail: jana.stanicova@uvlf.sk [Institute of Biophysics, University of Veterinary Medicine and Pharmacy, Komenského 73, 041 81 Košice (Slovakia)

    2014-01-31

    Highlights: • Anthraquinones quinizarin and danthron unwind negatively supercoiled DNA. • Anthraquinones quinizarin and danthron lengthen linear DNA. • Anthraquinones quinizarin and danthron possess middle binding affinity to DNA. • Anthraquinones quinizarin and danthron interact with DNA by intercalating mode. - Abstract: The intercalating drugs possess a planar aromatic chromophore unit by which they insert between DNA bases causing the distortion of classical B-DNA form. The planar tricyclic structure of anthraquinones belongs to the group of chromophore units and enables anthraquinones to bind to DNA by intercalating mode. The interactions of simple derivatives of anthraquinone, quinizarin (1,4-dihydroxyanthraquinone) and danthron (1,8-dihydroxyanthraquinone), with negatively supercoiled and linear DNA were investigated using a combination of the electrophoretic methods, fluorescence spectrophotometry and single molecule technique an atomic force microscopy. The detection of the topological change of negatively supercoiled plasmid DNA, unwinding of negatively supercoiled DNA, corresponding to appearance of DNA topoisomers with the low superhelicity and an increase of the contour length of linear DNA in the presence of quinizarin and danthron indicate the binding of both anthraquinones to DNA by intercalating mode.

  17. Intrinsic and Extrinsic Motivations: Classic Definitions and New Directions.

    Science.gov (United States)

    Ryan; Deci

    2000-01-01

    Intrinsic and extrinsic types of motivation have been widely studied, and the distinction between them has shed important light on both developmental and educational practices. In this review we revisit the classic definitions of intrinsic and extrinsic motivation in light of contemporary research and theory. Intrinsic motivation remains an important construct, reflecting the natural human propensity to learn and assimilate. However, extrinsic motivation is argued to vary considerably in its relative autonomy and thus can either reflect external control or true self-regulation. The relations of both classes of motives to basic human needs for autonomy, competence and relatedness are discussed. Copyright 2000 Academic Press.

  18. Congenital hypertrophy of multiple intrinsic muscles of the foot.

    Science.gov (United States)

    Shiraishi, Tomohiro; Park, Susam; Niu, Atushi; Hasegawa, Hiromi

    2014-12-01

    Congenital hypertrophy of a single intrinsic muscle of the foot is rare, and as far as we know, only six cases have been reported. We describe a case of congenital anomaly that showed hypertrophy of multiple intrinsic muscles of the foot; the affected muscles were all the intrinsic muscles of the foot except the extensor digitorum brevis or extensor hallucis. Other tissues such as adipose tissue, nervous tissue, or osseous tissue showed no abnormalities. To reduce the volume of the foot we removed parts of the enlarged muscles.

  19. Some chaotic features of intrinsically coupled Josephson junctions

    International Nuclear Information System (INIS)

    Kolahchi, M.R.; Shukrinov, Yu.M.; Hamdipour, M.; Botha, A.E.; Suzuki, M.

    2013-01-01

    Highlights: ► Intrinsically coupled Josephson junctions model a high-T c superconductor. ► Intrinsically coupled Josephson junctions can act as a chaotic nonlinear system. ► Chaos could be due to resonance overlap. ► Avoiding parameters that lead to chaos is important for the design of resonators. -- Abstract: We look for chaos in an intrinsically coupled system of Josephson junctions. This study has direct applications for the high-T c resonators which require coherence amongst the junctions

  20. Intrinsic Density Matrices of the Nuclear Shell Model

    International Nuclear Information System (INIS)

    Deveikis, A.; Kamuntavichius, G.

    1996-01-01

    A new method for calculation of shell model intrinsic density matrices, defined as two-particle density matrices integrated over the centre-of-mass position vector of two last particles and complemented with isospin variables, has been developed. The intrinsic density matrices obtained are completely antisymmetric, translation-invariant, and do not employ a group-theoretical classification of antisymmetric states. They are used for exact realistic density matrix expansion within the framework of the reduced Hamiltonian method. The procedures based on precise arithmetic for calculation of the intrinsic density matrices that involve no numerical diagonalization or orthogonalization have been developed and implemented in the computer code. (author). 11 refs., 2 tabs

  1. The intrinsic stochasticity of near-integrable Hamiltonian systems

    Energy Technology Data Exchange (ETDEWEB)

    Krlin, L [Ceskoslovenska Akademie Ved, Prague (Czechoslovakia). Ustav Fyziky Plazmatu

    1989-09-01

    Under certain conditions, the dynamics of near-integrable Hamiltonian systems appears to be stochastic. This stochasticity (intrinsic stochasticity, or deterministic chaos) is closely related to the Kolmogorov-Arnold-Moser (KAM) theorem of the stability of near-integrable multiperiodic Hamiltonian systems. The effect of the intrinsic stochasticity attracts still growing attention both in theory and in various applications in contemporary physics. The paper discusses the relation of the intrinsic stochasticity to the modern ergodic theory and to the KAM theorem, and describes some numerical experiments on related astrophysical and high-temperature plasma problems. Some open questions are mentioned in conclusion. (author).

  2. "In Situ Vascular Nerve Graft" for Restoration of Intrinsic Hand Function: An Anatomical Study.

    Science.gov (United States)

    Mozaffarian, Kamran; Zemoodeh, Hamid Reza; Zarenezhad, Mohammad; Owji, Mohammad

    2018-06-01

    In combined high median and ulnar nerve injury, transfer of the posterior interosseous nerve branches to the motor branch of the ulnar nerve (MUN) is previously described in order to restore intrinsic hand function. In this operation a segment of sural nerve graft is required to close the gap between the donor and recipient nerves. However the thenar muscles are not innervated by this nerve transfer. The aim of the present study was to evaluate whether the superficial radial nerve (SRN) can be used as an "in situ vascular nerve graft" to connect the donor nerves to the MUN and the motor branch of median nerve (MMN) at the same time in order to address all denervated intrinsic and thenar muscles. Twenty fresh male cadavers were dissected in order to evaluate the feasibility of this modification of technique. The size of nerve branches, the number of axons and the tension at repair site were evaluated. This nerve transfer was technically feasible in all specimens. There was no significant size mismatch between the donor and recipient nerves Conclusions: The possible advantages of this modification include innervation of both median and ulnar nerve innervated intrinsic muscles, preservation of vascularity of the nerve graft which might accelerate the nerve regeneration, avoidance of leg incision and therefore the possibility of performing surgery under regional instead of general anesthesia. Briefly, this novel technique is a viable option which can be used instead of conventional nerve graft in some brachial plexus or combined high median and ulnar nerve injuries when restoration of intrinsic hand function by transfer of posterior interosseous nerve branches is attempted.

  3. Risk assessment of DNA-reactive carcinogens in food

    International Nuclear Information System (INIS)

    Jeffrey, A.M.; Williams, G.M.

    2005-01-01

    Risk assessment of DNA-reactive carcinogens in food requires knowledge of the extent of DNA damage in the target organ which results from the competition between DNA adduct formation and repair. Estimates of DNA adduct levels can be made by direct measurement or indirectly as a consequence of their presence, for example, by tumor formation in animal models or exposed populations epidemiologically. Food-borne DNA-reactive carcinogens are present from a variety of sources. They are generally not intrinsically DNA-reactive but require bioactivation to DNA-reactive metabolites a process which may be modulated by the compound itself or the presence of other xenobiotics. A single DNA reactant may form several distinct DNA adducts each undergoing different rates of repair. Some DNA reactants may be photochemically activated or produce reactive oxygen species and thus indirect oxidative DNA damage. The levels of DNA adducts arising from exposures influenced by variations in the doses, the frequency with which an individual is exposed, and rates of DNA repair for specific adducts. Each adduct has a characteristic efficiency with which it induces mutations. Based on experience with the well-studied DNA-reactive food carcinogen aflatoxin B 1 (AFB 1 ), a limit of 20 ppb or ∼30 μg/day has been set and is considered a tolerable daily intake (TDI). Since AFB 1 is considered a potent carcinogen, doses of 32 P-postlabeling or the use of surrogates such as hemoglobin adducts, together with approaches to evaluate the results. A discussion of approaches to estimating possible threshold effects for DNA-reactive carcinogens is made

  4. Computational applications of DNA physical scales

    DEFF Research Database (Denmark)

    Baldi, Pierre; Chauvin, Yves; Brunak, Søren

    1998-01-01

    that these scales provide an alternative or complementary compact representation of DNA sequences. As an example we construct a strand invariant representation of DNA sequences. The scales can also be used to analyze and discover new DNA structural patterns, especially in combinations with hidden Markov models......The authors study from a computational standpoint several different physical scales associated with structural features of DNA sequences, including dinucleotide scales such as base stacking energy and propellor twist, and trinucleotide scales such as bendability and nucleosome positioning. We show...

  5. Computational applications of DNA structural scales

    DEFF Research Database (Denmark)

    Baldi, P.; Chauvin, Y.; Brunak, Søren

    1998-01-01

    that these scales provide an alternative or complementary compact representation of DNA sequences. As an example, we construct a strand-invariant representation of DNA sequences. The scales can also be used to analyze and discover new DNA structural patterns, especially in combination with hidden Markov models......Studies several different physical scales associated with the structural features of DNA sequences from a computational standpoint, including dinucleotide scales, such as base stacking energy and propeller twist, and trinucleotide scales, such as bendability and nucleosome positioning. We show...

  6. DNA damage and repair in plants

    International Nuclear Information System (INIS)

    Britt, A.B.

    1996-01-01

    The biological impact of any DNA damaging agent is a combined function of the chemical nature of the induced lesions and the efficiency and accuracy of their repair. Although much has been learned frommicrobes and mammals about both the repair of DNA damage and the biological effects of the persistence of these lesions, much remains to be learned about the mechanism and tissue-specificity of repair in plants. This review focuses on recent work on the induction and repair of DNA damage in higher plants, with special emphasis on UV-induced DNA damage products. (author)

  7. Conjugation of Benzylvanillin and Benzimidazole Structure Improves DNA Binding with Enhanced Antileukemic Properties

    Science.gov (United States)

    Al-Mudarris, Ban A.; Chen, Shih-Hsun; Liang, Po-Huang; Osman, Hasnah; Jamal Din, Shah Kamal Khan; Abdul Majid, Amin M. S.

    2013-01-01

    Benzyl-o-vanillin and benzimidazole nucleus serve as important pharmacophore in drug discovery. The benzyl vanillin (2-(benzyloxy)-3-methoxybenzaldehyde) compound shows anti-proliferative activity in HL60 leukemia cancer cells and can effect cell cycle progression at G2/M phase. Its apoptosis activity was due to disruption of mitochondrial functioning. In this study, we have studied a series of compounds consisting of benzyl vanillin and benzimidazole structures. We hypothesize that by fusing these two structures we can produce compounds that have better anticancer activity with improved specificity particularly towards the leukemia cell line. Here we explored the anticancer activity of three compounds namely 2-(2-benzyloxy-3-methoxyphenyl)-1H-benzimidazole, 2MP, N-1-(2-benzyloxy-3-methoxybenzyl)-2-(2-benzyloxy-3-methoxyphenyl)-1H-benzimidazole, 2XP, and (R) and (S)-1-(2-benzyloxy-3-methoxyphenyl)-2, 2, 2-trichloroethyl benzenesulfonate, 3BS and compared their activity to 2-benzyloxy-3-methoxybenzaldehyde, (Bn1), the parent compound. 2XP and 3BS induces cell death of U937 leukemic cell line through DNA fragmentation that lead to the intrinsic caspase 9 activation. DNA binding study primarily by the equilibrium binding titration assay followed by the Viscosity study reveal the DNA binding through groove region with intrinsic binding constant 7.39 µM/bp and 6.86 µM/bp for 3BS and 2XP respectively. 2XP and 3BS showed strong DNA binding activity by the UV titration method with the computational drug modeling showed that both 2XP and 3BS failed to form any electrostatic linkages except via hydrophobic interaction through the minor groove region of the nucleic acid. The benzylvanillin alone (Bn1) has weak anticancer activity even after it was combined with the benzimidazole (2MP), but after addition of another benzylvanillin structure (2XP), stronger activity was observed. Also, the combination of benzylvanillin with benzenesulfonate (3BS) significantly improved the

  8. Forecast Combinations

    OpenAIRE

    Timmermann, Allan G

    2005-01-01

    Forecast combinations have frequently been found in empirical studies to produce better forecasts on average than methods based on the ex-ante best individual forecasting model. Moreover, simple combinations that ignore correlations between forecast errors often dominate more refined combination schemes aimed at estimating the theoretically optimal combination weights. In this paper we analyse theoretically the factors that determine the advantages from combining forecasts (for example, the d...

  9. Small molecule probes finely differentiate between various ds- and ss-DNA and RNA by fluorescence, CD and NMR response

    Energy Technology Data Exchange (ETDEWEB)

    Crnolatac, Ivo; Rogan, Iva; Majić, Boris; Tomić, Sanja [Division of Organic Chemistry and Biochemistry, Division of Physical Chemistry, Ruđer Bošković Institute, P.O. Box 180, 10002 Zagreb (Croatia); Deligeorgiev, Todor [Faculty of Chemistry and Pharmacy, University of Sofia (Bulgaria); Horvat, Gordan [Department of Physical Chemistry, Faculty of Science/Chemistry, Horvatovac 102A, HR-10000 Zagreb (Croatia); Makuc, Damjan; Plavec, Janez [Slovenian NMR Centre, National Institute of Chemistry, Hajdrihova 19, Ljubljana (Slovenia); EN-FIST Centre of Excellence, Trg Osvobodilne Fronte 13, Ljubljana (Slovenia); Pescitelli, Gennaro [Department of Chemistry, University of Pisa, Via Moruzzi 13, Pisa (Italy); Piantanida, Ivo, E-mail: pianta@irb.hr [Division of Organic Chemistry and Biochemistry, Division of Physical Chemistry, Ruđer Bošković Institute, P.O. Box 180, 10002 Zagreb (Croatia)

    2016-10-12

    Two small molecules showed intriguing properties of analytical multipurpose probes, whereby one chromophore gives different signal for many different DNA/RNA by application of several highly sensitive spectroscopic methods. Dyes revealed pronounced fluorescence ratiomeric differentiation between ds-AU-RNA, AT-DNA and GC-DNA in approximate order 10:8:1. Particularly interesting, dyes showed specific fluorimetric response for poly rA even at 10-fold excess of any other ss-RNA, and moreover such emission selectivity is preserved in multicomponent ss-RNA mixtures. The dyes also showed specific chiral recognition of poly rU in respect to the other ss-RNA by induced CD (ICD) pattern in visible range (400–500 nm), which was attributed to the dye-side-chain contribution to binding (confirmed by absence of any ICD band for reference compound lacking side-chain). Most intriguingly, minor difference in the side-chain attached to dye chromophore resulted in opposite sign of dye-ICD pattern, whereby differences in NMR NOESY contacts and proton chemical shifts between two dye/oligo rU complexes combined with MD simulations and CD calculations attributed observed bisignate ICD to the dimeric dye aggregate within oligo rU. - Highlights: • Novel dyes emit fluorescence only for poly rA even at high excess of all other ss-RNA. • Fluorescence response for AT-DNA is 8 times stronger than for GC-DNA. • Florescence induced by ds-RNA is 20% stronger that emission induced by ds-DNA. • Intrinsically non-chiral, dyes show strong and characteristic ICD response for poly rU.

  10. DNA-scaffolded nanoparticle structures

    Energy Technology Data Exchange (ETDEWEB)

    Hoegberg, Bjoern; Olin, Haakan [Department of Engineering Physics and Mathematics, Mid Sweden University, SE-851 70 Sundsvall, Sweden (Sweden)

    2007-03-15

    DNA self-assembly is a powerful route to the production of very small, complex structures. When used in combination with nanoparticles it is likely to become a key technology in the production of nanoelectronics in the future. Previously, demonstrated nanoparticle assemblies have mainly been periodic and highly symmetric arrays, unsuited as building blocks for any complex circuits. With the invention of DNA-scaffolded origami reported earlier this year (Rothemund P W K 2006 Nature 440 (7082) 297-302), a new route to complex nanostructures using DNA has been opened. Here, we give a short review of the field and present the current status of our experiments were DNA origami is used in conjunction with nanoparticles. Gold nanoparticles are functionalized with thiolated single stranded DNA. Strands that are complementary to the gold particle strands can be positioned on the self-assembled DNA-structure in arbitrary patterns. This property should allow an accurate positioning of the particles by letting them hybridize on the lattice. We report on our recent experiments on this system and discuss open problems and future applications.

  11. DNA-scaffolded nanoparticle structures

    International Nuclear Information System (INIS)

    Hoegberg, Bjoern; Olin, Haakan

    2007-01-01

    DNA self-assembly is a powerful route to the production of very small, complex structures. When used in combination with nanoparticles it is likely to become a key technology in the production of nanoelectronics in the future. Previously, demonstrated nanoparticle assemblies have mainly been periodic and highly symmetric arrays, unsuited as building blocks for any complex circuits. With the invention of DNA-scaffolded origami reported earlier this year (Rothemund P W K 2006 Nature 440 (7082) 297-302), a new route to complex nanostructures using DNA has been opened. Here, we give a short review of the field and present the current status of our experiments were DNA origami is used in conjunction with nanoparticles. Gold nanoparticles are functionalized with thiolated single stranded DNA. Strands that are complementary to the gold particle strands can be positioned on the self-assembled DNA-structure in arbitrary patterns. This property should allow an accurate positioning of the particles by letting them hybridize on the lattice. We report on our recent experiments on this system and discuss open problems and future applications

  12. The Development of Intrinsic Motivation for Physical Activity

    National Research Council Canada - National Science Library

    Beaty, James D

    2005-01-01

    .... Having found this to be so, it is worthy of researchers' efforts to determine the constructs that will move individuals to become more intrinsically motivated to engage in regular exercise and/or physical activity...

  13. Stochastic synchronization of neuronal populations with intrinsic and extrinsic noise.

    KAUST Repository

    Bressloff, Paul C; Lai, Yi Ming

    2011-01-01

    We extend the theory of noise-induced phase synchronization to the case of a neural master equation describing the stochastic dynamics of an ensemble of uncoupled neuronal population oscillators with intrinsic and extrinsic noise. The master

  14. Detergent-induced aggregation of an amyloidogenic intrinsically ...

    Indian Academy of Sciences (India)

    Shruti Arya

    2017-11-02

    Nov 2, 2017 ... the effect of a well-known anionic lipid mimetic, sodium dodecyl sulfate (SDS), on the aggregation ... for the fabrication of nano-structures for a wide variety ...... M 2014 Classification of intrinsically disordered regions.

  15. Intrinsic and extrinsic motivation for stereotypic and repetitive behavior.

    Science.gov (United States)

    Joosten, Annette V; Bundy, Anita C; Einfeld, Stewart L

    2009-03-01

    This study provides evidence for intrinsic and extrinsic motivators for stereotypical and repetitive behavior in children with autism and intellectual disability and children with intellectual disability alone. We modified the Motivation Assessment Scale (MAS) (1988b); dividing it into intrinsic and extrinsic measures and adding items to assess anxiety as an intrinsic motivator. Rasch analysis of data from 279 MASs (74 children) revealed that the items formed two unidimensional scales. Anxiety was a more likely intrinsic motivator than sensory seeking for children with dual diagnoses; the reverse was true for children with intellectual disability only. Escape and gaining a tangible object were the most common extrinsic motivators for those with dual diagnoses and attention and escape for children with intellectual disability.

  16. Possible mechanism for d0 ferromagnetism mediated by intrinsic defects

    KAUST Repository

    Zhang, Zhenkui; Schwingenschlö gl, Udo; Roqan, Iman S.

    2014-01-01

    We examine the effects of several intrinsic defects on the magnetic behavior of ZnS nanostructures using hybrid density functional theory to gain insights into d0 ferromagnetism. Previous studies have predicted that the magnetism is due to a

  17. Values, Norms, and Intrinsic Motivation to Act Proenvironmentally

    NARCIS (Netherlands)

    Steg, Linda

    2016-01-01

    Environmental problems can be reduced if people more consistently engage in proenvironmental actions. In this article, I discuss factors that motivate or inhibit individuals to act proenvironmentally. Many people are intrinsically motivated to engage in proenvironmental actions, because protecting

  18. Exploring the link between intrinsic motivation and quality

    Science.gov (United States)

    Christy, Steven M.

    1992-12-01

    This thesis proposes that it is workers' intrinsic motivation that leads them to produce quality work. It reviews two different types of evidence- expert opinion and empirical studies--to attempt to evaluate a link between intrinsic motivation and work quality. The thesis reviews the works of Total Quality writers and behavioral scientists for any connection they might have made between intrinsic motivation and quality. The thesis then looks at the works of Deming and his followers in an attempt to establish a match between Deming's motivational assumptions and the four task rewards in the Thomas/Tymon model of intrinsic motivation: choice, competence, meaningfulness, and progress. Based upon this analysis, it is proposed that the four Thomas/Tymon task rewards are a promising theoretical foundation for explaining the motivational basis of quality for workers in Total Quality organizations.

  19. The Role of Intrinsic Motivations in Attention Allocation and Shifting

    Directory of Open Access Journals (Sweden)

    Dario edi Nocera

    2014-04-01

    Full Text Available The concepts of attention and intrinsic motivations are of great interest within adaptive robotic systems, and can be exploited in order to guide, activate, and coordinate multiple concurrent behaviors. Attention allocation strategies represent key capabilities of human beings, which are strictly connected with action selection and execution mechanisms, while intrinsic motivations directly affect the allocation of attentional resources. In this paper we propose a model of Reinforcement Learning (RL, where both these capabilities are involved. RL is deployed to learn how to allocate attentional resources in a behavior-based robotic system, while action selection is obtained as a side effect of the resulting motivated attentional behaviors. Moreover, the influence of intrinsic motivations in attention orientation is obtained by introducing rewards associated with curiosity drives. In this way, the learning process is affected not only by goal-specific rewards, but also by intrinsic motivations.

  20. The dynamic multisite interactions between two intrinsically disordered proteins

    KAUST Repository

    Wu, Shaowen; Wang, Dongdong; Liu, Jin; Feng, Yitao; Weng, Jingwei; Li, Yu; Gao, Xin; Liu, Jianwei; Wang, Wenning

    2017-01-01

    Protein interactions involving intrinsically disordered proteins (IDPs) comprise a variety of binding modes, from the well characterized folding upon binding to dynamic fuzzy complex. To date, most studies concern the binding of an IDP to a