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Sample records for bounds reveals early

  1. The Early Careers of Non-College-Bound Men.

    Science.gov (United States)

    Grogger, Jeff

    Data drawn from the Sophomore Cohort of the High School and Beyond study, also known as the Class of 1982 data, were studied to provide baseline data on the early careers of noncollege-bound (NCB) men. The analysis used data primarily from two post-high school interviews in 1984 and 1986. This report also focuses on restaurant employment, an…

  2. Complementarity reveals bound entanglement of two twisted photons

    Science.gov (United States)

    Hiesmayr, Beatrix C.; Löffler, Wolfgang

    2013-08-01

    We demonstrate the detection of bipartite bound entanglement as predicted by the Horodecki's in 1998. Bound entangled states, being heavily mixed entangled quantum states, can be produced by incoherent addition of pure entangled states. Until 1998 it was thought that such mixing could always be reversed by entanglement distillation; however, this turned out to be impossible for bound entangled states. The purest form of bound entanglement is that of only two particles, which requires higher-dimensional (d > 2) quantum systems. We realize this using photon qutrit (d = 3) pairs produced by spontaneous parametric downconversion, that are entangled in the orbital angular momentum degrees of freedom, which is scalable to high dimensions. Entanglement of the photons is confirmed via a ‘maximum complementarity protocol’. This conceptually simple protocol requires only maximized complementary of measurement bases; we show that it can also detect bound entanglement. We explore the bipartite qutrit space and find that, also experimentally, a significant portion of the entangled states are actually bound entangled.

  3. Minimal Z' models present bounds and early LHC reach

    CERN Document Server

    Salvioni, Ennio; Zwirner, Fabio

    2009-01-01

    We consider `minimal' Z' models, whose phenomenology is controlled by only three parameters beyond the Standard Model ones: the Z' mass and two effective coupling constants. They encompass many popular models motivated by grand unification, as well as many arising in other theoretical contexts. This parameterization takes also into account both mass and kinetic mixing effects, which we show to be sizable in some cases. After discussing the interplay between the bounds from electroweak precision tests and recent direct searches at the Tevatron, we extend our analysis to estimate the early LHC discovery potential. We consider a center-of-mass energy from 7 towards 10 TeV and an integrated luminosity from 50 to several hundred pb^-1, taking all existing bounds into account. We find that the LHC will start exploring virgin land in parameter space for M_Z' around 700 GeV, with lower masses still excluded by the Tevatron and higher masses still excluded by electroweak precision tests. Increasing the energy up to 10...

  4. Di- or polysulphide-bound biomarkers in sulphur-rich geomacromolecules as revealed by selective chemolysis

    Science.gov (United States)

    Kohnen, Math E. l.; Sinninghe Damsté, Jaap S.; Kock-van Dalen, A. c.; Jan, W. De Leeuw

    1991-05-01

    Three types of sulphur-rich high-molecular-weight material in the alkylsulphide, the polar, and the asphaltene fractions isolated from the bitumen of an immature bituminous shale from the Vena del Gesso basin (Italy) were desulphurised using Raney Ni and were treated with MeLi/MeI, a chemical degradation method which cleaves selectively and quantitatively di- or polysulphide linkages. The products formed were characterised by gas chromatography-mass spectrometry. Raney Ni desulphurisation revealed that these S-rich macromolecules are in substantial part composed of sulphur-linked biomarkers with linear, branched, isoprenoid, steroid, hopanoid, and carotenoid carbon skeletons. MeLi/Mel treatment provided evidence that a major part of the total amount of macromolecularly bound biomarkers are linked via di- or polysulphide moieties to the macromolecular network. Since the di- or polysulphide linkages are attached at specific positions of the bound biomarkers it is proposed that they are formed by intermolecular incorporation reactions of HS x- into low-molecular-weight functionalised biological lipids during early diagenesis. The different properties (solubility and molecular weight) of the sulphur-rich macromolecules in the alkylsulphide, the resin, and the asphaltene fractions can be explained simply by differences in degree of sulphur cross-linking.

  5. New bound on low reheating temperature for dark matter in models with early matter domination

    Science.gov (United States)

    Choi, Ki-Young; Takahashi, Tomo

    2017-08-01

    We investigate a new bound on the low reheating temperature in a scenario where the Universe experiences early matter domination before reheating after which the standard big bang cosmology begins. In many models of dark matter (DM), the small scale fluctuations of DM grow during the early matter-domination era and seed the formation of the ultracompact minihalos (UCMHs). Using the constraints on the number of UCMHs from gamma-ray observations, we find a lower bound on the reheating temperature between O (10 )-O (100 ) MeV for WIMP dark matter depending on the nature of DM. A similar bound could be obtained for non-WIMP dark matter by observing UCMHs gravitationally such as pulsar timing, microlensing and so on, in some future observations.

  6. Early LHC bound on the W{sup Prime} boson mass in the nonuniversal gauge interaction model

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yeong Gyun [Department of Science Education, Gwangju National University of Education, Gwangju 500-703 (Korea, Republic of); Lee, Kang Young, E-mail: kylee14214@gmail.com [Division of Quantum Phases and Devices, School of Physics, Konkuk University, Seoul 143-701 (Korea, Republic of)

    2012-01-05

    We study the phenomenology of the heavy charged gauge boson and obtain the lower bounds on its mass with the early LHC data at 7 TeV center-of-mass energy in the nonuniversal gauge interaction model, in which the electroweak SU(2) gauge group depends upon the fermion family. We found that the direct bound with the early data of the LHC is already better than the indirect bound on the mass of the W{sup Prime} boson.

  7. Crystal structure of the adenosine A2Areceptor bound to an antagonist reveals a potential allosteric pocket.

    Science.gov (United States)

    Sun, Bingfa; Bachhawat, Priti; Chu, Matthew Ling-Hon; Wood, Martyn; Ceska, Tom; Sands, Zara A; Mercier, Joel; Lebon, Florence; Kobilka, Tong Sun; Kobilka, Brian K

    2017-02-21

    The adenosine A 2A receptor (A 2A R) has long been implicated in cardiovascular disorders. As more selective A 2A R ligands are being identified, its roles in other disorders, such as Parkinson's disease, are starting to emerge, and A 2A R antagonists are important drug candidates for nondopaminergic anti-Parkinson treatment. Here we report the crystal structure of A 2A receptor bound to compound 1 (Cmpd-1), a novel A 2A R/ N -methyl d-aspartate receptor subtype 2B (NR2B) dual antagonist and potential anti-Parkinson candidate compound, at 3.5 Å resolution. The A 2A receptor with a cytochrome b562-RIL (BRIL) fusion (A 2A R-BRIL) in the intracellular loop 3 (ICL3) was crystallized in detergent micelles using vapor-phase diffusion. Whereas A 2A R-BRIL bound to the antagonist ZM241385 has previously been crystallized in lipidic cubic phase (LCP), structural differences in the Cmpd-1-bound A 2A R-BRIL prevented formation of the lattice observed with the ZM241385-bound receptor. The crystals grew with a type II crystal lattice in contrast to the typical type I packing seen from membrane protein structures crystallized in LCP. Cmpd-1 binds in a position that overlaps with the native ligand adenosine, but its methoxyphenyl group extends to an exosite not previously observed in other A 2A R structures. Structural analysis revealed that Cmpd-1 binding results in the unique conformations of two tyrosine residues, Tyr9 1.35 and Tyr271 7.36 , which are critical for the formation of the exosite. The structure reveals insights into antagonist binding that are not observed in other A 2A R structures, highlighting flexibility in the binding pocket that may facilitate the development of A 2A R-selective compounds for the treatment of Parkinson's disease.

  8. Substrate-bound structures of benzylsuccinate synthase reveal how toluene is activated in anaerobic hydrocarbon degradation.

    Science.gov (United States)

    Funk, Michael A; Marsh, E Neil G; Drennan, Catherine L

    2015-09-11

    Various bacteria perform anaerobic degradation of small hydrocarbons as a source of energy and cellular carbon. To activate non-reactive hydrocarbons such as toluene, enzymes conjugate these molecules to fumarate in a radical-catalyzed, C-C bond-forming reaction. We have determined x-ray crystal structures of the glycyl radical enzyme that catalyzes the addition of toluene to fumarate, benzylsuccinate synthase (BSS), in two oligomeric states with fumarate alone or with both substrates. We find that fumarate is secured at the bottom of a long active site cavity with toluene bound directly above it. The two substrates adopt orientations that appear ideal for radical-mediated C-C bond formation; the methyl group of toluene is positioned between fumarate and a cysteine that forms a thiyl radical during catalysis, which is in turn adjacent to the glycine that serves as a radical storage residue. Toluene is held in place by fumarate on one face and tight packing by hydrophobic residues on the other face and sides. These hydrophobic residues appear to become ordered, thus encapsulating toluene, only in the presence of BSSβ, a small protein subunit that forms a tight complex with BSSα, the catalytic subunit. Enzymes related to BSS are able to metabolize a wide range of hydrocarbons through attachment to fumarate. Using our structures as a guide, we have constructed homology models of several of these "X-succinate synthases" and determined conservation patterns that will be useful in understanding the basis for catalysis and specificity in this family of enzymes. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. Substrate-bound Structures of Benzylsuccinate Synthase Reveal How Toluene Is Activated in Anaerobic Hydrocarbon Degradation*

    Science.gov (United States)

    Funk, Michael A.; Marsh, E. Neil G.; Drennan, Catherine L.

    2015-01-01

    Various bacteria perform anaerobic degradation of small hydrocarbons as a source of energy and cellular carbon. To activate non-reactive hydrocarbons such as toluene, enzymes conjugate these molecules to fumarate in a radical-catalyzed, C—C bond-forming reaction. We have determined x-ray crystal structures of the glycyl radical enzyme that catalyzes the addition of toluene to fumarate, benzylsuccinate synthase (BSS), in two oligomeric states with fumarate alone or with both substrates. We find that fumarate is secured at the bottom of a long active site cavity with toluene bound directly above it. The two substrates adopt orientations that appear ideal for radical-mediated C—C bond formation; the methyl group of toluene is positioned between fumarate and a cysteine that forms a thiyl radical during catalysis, which is in turn adjacent to the glycine that serves as a radical storage residue. Toluene is held in place by fumarate on one face and tight packing by hydrophobic residues on the other face and sides. These hydrophobic residues appear to become ordered, thus encapsulating toluene, only in the presence of BSSβ, a small protein subunit that forms a tight complex with BSSα, the catalytic subunit. Enzymes related to BSS are able to metabolize a wide range of hydrocarbons through attachment to fumarate. Using our structures as a guide, we have constructed homology models of several of these “X-succinate synthases” and determined conservation patterns that will be useful in understanding the basis for catalysis and specificity in this family of enzymes. PMID:26224635

  10. Targeting Membrane-Bound Viral RNA Synthesis Reveals Potent Inhibition of Diverse Coronaviruses Including the Middle East Respiratory Syndrome Virus

    Science.gov (United States)

    Bergström, Tomas; Kann, Nina; Adamiak, Beata; Hannoun, Charles; Kindler, Eveline; Jónsdóttir, Hulda R.; Muth, Doreen; Kint, Joeri; Forlenza, Maria; Müller, Marcel A.; Drosten, Christian; Thiel, Volker; Trybala, Edward

    2014-01-01

    Coronaviruses raise serious concerns as emerging zoonotic viruses without specific antiviral drugs available. Here we screened a collection of 16671 diverse compounds for anti-human coronavirus 229E activity and identified an inhibitor, designated K22, that specifically targets membrane-bound coronaviral RNA synthesis. K22 exerts most potent antiviral activity after virus entry during an early step of the viral life cycle. Specifically, the formation of double membrane vesicles (DMVs), a hallmark of coronavirus replication, was greatly impaired upon K22 treatment accompanied by near-complete inhibition of viral RNA synthesis. K22-resistant viruses contained substitutions in non-structural protein 6 (nsp6), a membrane-spanning integral component of the viral replication complex implicated in DMV formation, corroborating that K22 targets membrane bound viral RNA synthesis. Besides K22 resistance, the nsp6 mutants induced a reduced number of DMVs, displayed decreased specific infectivity, while RNA synthesis was not affected. Importantly, K22 inhibits a broad range of coronaviruses, including Middle East respiratory syndrome coronavirus (MERS–CoV), and efficient inhibition was achieved in primary human epithelia cultures representing the entry port of human coronavirus infection. Collectively, this study proposes an evolutionary conserved step in the life cycle of positive-stranded RNA viruses, the recruitment of cellular membranes for viral replication, as vulnerable and, most importantly, druggable target for antiviral intervention. We expect this mode of action to serve as a paradigm for the development of potent antiviral drugs to combat many animal and human virus infections. PMID:24874215

  11. Crystal Structure of Inhibitor-Bound P450BM-3 Reveals Open Conformation of Substrate Access Channel

    Energy Technology Data Exchange (ETDEWEB)

    Haines, Donovan C.; Chen, Baozhi; Tomchick, Diana R.; Bondlela, Muralidhar; Hegde, Amita; Machius, Mischa; Peterson, Julian A. (Texas); (UTSMC)

    2008-08-19

    P450BM-3 is an extensively studied P450 cytochrome that is naturally fused to a cytochrome P450 reductase domain. Crystal structures of the heme domain of this enzyme have previously generated many insights into features of P450 structure, substrate binding specificity, and conformational changes that occur on substrate binding. Although many P450s are inhibited by imidazole, this compound does not effectively inhibit P450BM-3. {omega}-Imidazolyl fatty acids have previously been found to be weak inhibitors of the enzyme and show some unusual cooperativity with the substrate lauric acid. We set out to improve the properties of these inhibitors by attaching the {omega}-imidazolyl fatty acid to the nitrogen of an amino acid group, a tactic that we used previously to increase the potency of substrates. The resulting inhibitors were significantly more potent than their parent compounds lacking the amino acid group. A crystal structure of one of the new inhibitors bound to the heme domain of P450BM-3 reveals that the mode of interaction of the amino acid group with the enzyme is different from that previously observed for acyl amino acid substrates. Further, required movements of residues in the active site to accommodate the imidazole group provide an explanation for the low affinity of imidazole itself. Finally, the previously observed cooperativity with lauric acid is explained by a surprisingly open substrate-access channel lined with hydrophobic residues that could potentially accommodate lauric acid in addition to the inhibitor itself.

  12. Early Neolithic water wells reveal the world's oldest wood architecture.

    Science.gov (United States)

    Tegel, Willy; Elburg, Rengert; Hakelberg, Dietrich; Stäuble, Harald; Büntgen, Ulf

    2012-01-01

    The European Neolithization ~6000-4000 BC represents a pivotal change in human history when farming spread and the mobile style of life of the hunter-foragers was superseded by the agrarian culture. Permanent settlement structures and agricultural production systems required fundamental innovations in technology, subsistence, and resource utilization. Motivation, course, and timing of this transformation, however, remain debatable. Here we present annually resolved and absolutely dated dendroarchaeological information from four wooden water wells of the early Neolithic period that were excavated in Eastern Germany. A total of 151 oak timbers preserved in a waterlogged environment were dated between 5469 and 5098 BC and reveal unexpectedly refined carpentry skills. The recently discovered water wells enable for the first time a detailed insight into the earliest wood architecture and display the technological capabilities of humans ~7000 years ago. The timbered well constructions made of old oak trees feature an unopened tree-ring archive from which annually resolved and absolutely dated environmental data can be culled. Our results question the principle of continuous evolutionary development in prehistoric technology, and contradict the common belief that metal was necessary for complex timber constructions. Early Neolithic craftsmanship now suggests that the first farmers were also the first carpenters.

  13. Crystal Structures of Staphylococcus epidermidis Mevalonate Diphosphate Decarboxylase Bound to Inhibitory Analogs Reveal New Insight into Substrate Binding and Catalysis

    Energy Technology Data Exchange (ETDEWEB)

    Barta, Michael L.; Skaff, D. Andrew; McWhorter, William J.; Herdendorf, Timothy J.; Miziorko, Henry M.; Geisbrecht, Brian V. (UMKC)

    2011-10-28

    The polyisoprenoid compound undecaprenyl phosphate is required for biosynthesis of cell wall peptidoglycans in Gram-positive bacteria, including pathogenic Enterococcus, Streptococcus, and Staphylococcus spp. In these organisms, the mevalonate pathway is used to produce the precursor isoprenoid, isopentenyl 5-diphosphate. Mevalonate diphosphate decarboxylase (MDD) catalyzes formation of isopentenyl 5-diphosphate in an ATP-dependent irreversible reaction and is therefore an attractive target for inhibitor development that could lead to new antimicrobial agents. To facilitate exploration of this possibility, we report the crystal structure of Staphylococcus epidermidis MDD (1.85 {angstrom} resolution) and, to the best of our knowledge, the first structures of liganded MDD. These structures include MDD bound to the mevalonate 5-diphosphate analogs diphosphoglycolyl proline (2.05 {angstrom} resolution) and 6-fluoromevalonate diphosphate (FMVAPP; 2.2 {angstrom} resolution). Comparison of these structures provides a physical basis for the significant differences in K{sub i} values observed for these inhibitors. Inspection of enzyme/inhibitor structures identified the side chain of invariant Ser{sup 192} as making potential contributions to catalysis. Significantly, Ser {yields} Ala substitution of this side chain decreases k{sub cat} by {approx}10{sup 3}-fold, even though binding interactions between FMVAPP and this mutant are similar to those observed with wild type MDD, as judged by the 2.1 {angstrom} cocrystal structure of S192A with FMVAPP. Comparison of microbial MDD structures with those of mammalian counterparts reveals potential targets at the active site periphery that may be exploited to selectively target the microbial enzymes. These studies provide a structural basis for previous observations regarding the MDD mechanism and inform future work toward rational inhibitor design.

  14. Crystal structure of the adenosine A2A receptor bound to an antagonist reveals a potential allosteric pocket

    OpenAIRE

    Sun, Bingfa; Bachhawat, Priti; Chu, Matthew Ling-Hon; Wood, Martyn; Ceska, Tom; Sands, Zara A.; Mercier, Joel; Lebon, Florence; Kobilka, Tong Sun; Kobilka, Brian K.

    2017-01-01

    The A2AR is a G protein-coupled receptor (GPCR) that plays important roles in cardiovascular physiology and immune function. The A2AR is also a target for the treatment of Parkinson?s disease, where A2AR antagonists have been shown to enhance signaling through the D2 dopamine receptor. Here we present the crystal structure of the A2AR bound to a novel bitopic antagonist. As a result of structural changes needed to accommodate the bound antagonist, crystals could not be grown in lipidic cubic ...

  15. Phasor fluorescence lifetime microscopy of free and protein-bound NADH reveals neural stem cell differentiation potential.

    Directory of Open Access Journals (Sweden)

    Chiara Stringari

    Full Text Available In the stem cell field there is a lack of non invasive and fast methods to identify stem cell's metabolic state, differentiation state and cell-lineage commitment. Here we describe a label-free method that uses NADH as an intrinsic biomarker and the Phasor approach to Fluorescence Lifetime microscopy to measure the metabolic fingerprint of cells. We show that different metabolic states are related to different cell differentiation stages and to stem cell bias to neuronal and glial fate, prior the expression of lineage markers. Our data demonstrate that the NADH FLIM signature distinguishes non-invasively neurons from undifferentiated neural progenitor and stem cells (NPSCs at two different developmental stages (E12 and E16. NPSCs follow a metabolic trajectory from a glycolytic phenotype to an oxidative phosphorylation phenotype through different stages of differentiation. NSPCs are characterized by high free/bound NADH ratio, while differentiated neurons are characterized by low free/bound NADH ratio. We demonstrate that the metabolic signature of NPSCs correlates with their differentiation potential, showing that neuronal progenitors and glial progenitors have a different free/bound NADH ratio. Reducing conditions in NPSCs correlates with their neurogenic potential, while oxidative conditions correlate with glial potential. For the first time we show that FLIM NADH metabolic fingerprint provides a novel, and quantitative measure of stem cell potential and a label-free and non-invasive means to identify neuron- or glial- biased progenitors.

  16. Conformation of membrane-bound proteins revealed by vacuum-ultraviolet circular-dichroism and linear-dichroism spectroscopy.

    Science.gov (United States)

    Matsuo, Koichi; Maki, Yasuyuki; Namatame, Hirofumi; Taniguchi, Masaki; Gekko, Kunihiko

    2016-03-01

    Knowledge of the conformations of a water-soluble protein bound to a membrane is important for understanding the membrane-interaction mechanisms and the membrane-mediated functions of the protein. In this study we applied vacuum-ultraviolet circular-dichroism (VUVCD) and linear-dichroism (LD) spectroscopy to analyze the conformations of α-lactalbumin (LA), thioredoxin (Trx), and β-lactoglobulin (LG) bound to phosphatidylglycerol liposomes. The VUVCD analysis coupled with a neural-network analysis showed that these three proteins have characteristic helix-rich conformations involving several helical segments, of which two amphiphilic or hydrophobic segments take part in interactions with the liposome. The LD analysis predicted the average orientations of these helix segments on the liposome: two amphiphilic helices parallel to the liposome surface for LA, two hydrophobic helices perpendicular to the liposome surface for Trx, and a hydrophobic helix perpendicular to and an amphiphilic helix parallel to the liposome surface for LG. This sequence-level information about the secondary structures and orientations was used to formulate interaction models of the three proteins at the membrane surface. This study demonstrates the validity of a combination of VUVCD and LD spectroscopy in conformational analyses of membrane-binding proteins, which are difficult targets for X-ray crystallography and nuclear magnetic resonance spectroscopy. © 2016 Wiley Periodicals, Inc.

  17. Crystal structure of the adenosine A 2A receptor bound to an antagonist reveals a potential allosteric pocket

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Bingfa; Bachhawat, Priti; Chu, Matthew Ling-Hon; Wood, Martyn; Ceska, Tom; Sands, Zara A.; Mercier, Joel; Lebon, Florence; Kobilka, Tong Sun; Kobilka, Brian K. (Stanford-MED); (ConfometRx); (UCB Pharma)

    2017-02-06

    The adenosine A2A receptor (A2AR) has long been implicated in cardiovascular disorders. As more selective A2AR ligands are being identified, its roles in other disorders, such as Parkinson’s disease, are starting to emerge, and A2AR antagonists are important drug candidates for nondopaminergic anti-Parkinson treatment. Here we report the crystal structure of A2A receptor bound to compound 1 (Cmpd-1), a novel A2AR/N-methyl D-aspartate receptor subtype 2B (NR2B) dual antagonist and potential anti-Parkinson candidate compound, at 3.5 Å resolution. The A2A receptor with a cytochrome b562-RIL (BRIL) fusion (A2AR–BRIL) in the intracellular loop 3 (ICL3) was crystallized in detergent micelles using vapor-phase diffusion. Whereas A2AR–BRIL bound to the antagonist ZM241385 has previously been crystallized in lipidic cubic phase (LCP), structural differences in the Cmpd-1–bound A2AR–BRIL prevented formation of the lattice observed with the ZM241385–bound receptor. The crystals grew with a type II crystal lattice in contrast to the typical type I packing seen from membrane protein structures crystallized in LCP. Cmpd-1 binds in a position that overlaps with the native ligand adenosine, but its methoxyphenyl group extends to an exosite not previously observed in other A2AR structures. Structural analysis revealed that Cmpd-1 binding results in the unique conformations of two tyrosine residues, Tyr91.35 and Tyr2717.36, which are critical for the formation of the exosite. The structure reveals insights into antagonist binding that are not observed in other A2AR structures, highlighting flexibility in the binding pocket that may facilitate the development of A2AR-selective compounds for the treatment of Parkinson’s disease.

  18. Ancient European dog genomes reveal continuity since the Early Neolithic

    Science.gov (United States)

    Botigué, Laura R.; Song, Shiya; Scheu, Amelie; Gopalan, Shyamalika; Pendleton, Amanda L.; Oetjens, Matthew; Taravella, Angela M.; Seregély, Timo; Zeeb-Lanz, Andrea; Arbogast, Rose-Marie; Bobo, Dean; Daly, Kevin; Unterländer, Martina; Burger, Joachim; Kidd, Jeffrey M.; Veeramah, Krishna R.

    2017-01-01

    Europe has played a major role in dog evolution, harbouring the oldest uncontested Palaeolithic remains and having been the centre of modern dog breed creation. Here we sequence the genomes of an Early and End Neolithic dog from Germany, including a sample associated with an early European farming community. Both dogs demonstrate continuity with each other and predominantly share ancestry with modern European dogs, contradicting a previously suggested Late Neolithic population replacement. We find no genetic evidence to support the recent hypothesis proposing dual origins of dog domestication. By calibrating the mutation rate using our oldest dog, we narrow the timing of dog domestication to 20,000–40,000 years ago. Interestingly, we do not observe the extreme copy number expansion of the AMY2B gene characteristic of modern dogs that has previously been proposed as an adaptation to a starch-rich diet driven by the widespread adoption of agriculture in the Neolithic. PMID:28719574

  19. Ancient European dog genomes reveal continuity since the Early Neolithic.

    Science.gov (United States)

    Botigué, Laura R; Song, Shiya; Scheu, Amelie; Gopalan, Shyamalika; Pendleton, Amanda L; Oetjens, Matthew; Taravella, Angela M; Seregély, Timo; Zeeb-Lanz, Andrea; Arbogast, Rose-Marie; Bobo, Dean; Daly, Kevin; Unterländer, Martina; Burger, Joachim; Kidd, Jeffrey M; Veeramah, Krishna R

    2017-07-18

    Europe has played a major role in dog evolution, harbouring the oldest uncontested Palaeolithic remains and having been the centre of modern dog breed creation. Here we sequence the genomes of an Early and End Neolithic dog from Germany, including a sample associated with an early European farming community. Both dogs demonstrate continuity with each other and predominantly share ancestry with modern European dogs, contradicting a previously suggested Late Neolithic population replacement. We find no genetic evidence to support the recent hypothesis proposing dual origins of dog domestication. By calibrating the mutation rate using our oldest dog, we narrow the timing of dog domestication to 20,000-40,000 years ago. Interestingly, we do not observe the extreme copy number expansion of the AMY2B gene characteristic of modern dogs that has previously been proposed as an adaptation to a starch-rich diet driven by the widespread adoption of agriculture in the Neolithic.

  20. Different functions of the insect soluble and membrane-bound trehalase genes in chitin biosynthesis revealed by RNA interference.

    Directory of Open Access Journals (Sweden)

    Jie Chen

    Full Text Available BACKGROUND: Trehalase, an enzyme that hydrolyzes trehalose to yield two glucose molecules, plays a pivotal role in various physiological processes. In recent years, trehalase proteins have been purified from several insect species and are divided into soluble (Tre-1 and membrane-bound (Tre-2 trehalases. However, no functions of the two trehalases in chitin biosynthesis in insects have yet been reported. PRINCIPAL FINDINGS: The membrane-bound trehalase of Spodoptera exigua (SeTre-2 was characterized in our laboratory previously. In this study, we cloned the soluble trehalase gene (SeTre-1 and investigated the tissue distribution and developmental expression pattern of the two trehalase genes. SeTre-1 was expressed highly in cuticle and Malpighian tubules, while SeTre-2 was expressed in tracheae and fat body. In the midgut, the two trehalase genes were expressed in different locations. Additionally, the expression profiles of both trehalase mRNAs and their enzyme activities suggest that they may play different roles in chitin biosynthesis. The RNA interference (RNAi of either SeTre-1 or SeTre-2 was gene-specific and effective, with efficiency rates up to 83% at 72 h post injection. After RNAi of SeTre-1 and SeTre-2, significant higher mortality rates were observed during the larva-pupa stage and pupa-adult stage, and the lethal phenotypes were classified and analyzed. Additionally, the change trends of concentration of trehalose and glucose appeared reciprocally in RNAi-mutants. Moreover, knockdown of SeTre-1 gene largely inhibited the expression of chitin synthase gene A (CHSA and reduced the chitin content in the cuticle to two-thirds relative to the control insects. The chitin synthase gene B (CHSB expression, however, was inhibited more by the injection of dsRNA for SeTre-2, and the chitin content in the midgut decreased by about 25%. CONCLUSIONS: SeTre-1 plays a major role in CHSA expression and chitin synthesis in the cuticle, and SeTre-2

  1. Crystal structure of the PEG-bound SH3 domain of myosin IB from Entamoeba histolytica reveals its mode of ligand recognition.

    Science.gov (United States)

    Gautam, Gunjan; Rehman, Syed Arif Abdul; Pandey, Preeti; Gourinath, Samudrala

    2017-08-01

    The versatility in the recognition of various interacting proteins by the SH3 domain drives a variety of cellular functions. Here, the crystal structure of the C-terminal SH3 domain of myosin IB from Entamoeba histolytica (EhMySH3) is reported at a resolution of 1.7 Å in native and PEG-bound states. Comparisons with other structures indicated that the PEG molecules occupy protein-protein interaction pockets similar to those occupied by the peptides in other peptide-bound SH3-domain structures. Also, analysis of the PEG-bound EhMySH3 structure led to the recognition of two additional pockets, apart from the conventional polyproline and specificity pockets, that are important for ligand interaction. Molecular-docking studies combined with various comparisons revealed structural similarity between EhMySH3 and the SH3 domain of β-Pix, and this similarity led to the prediction that EhMySH3 preferentially binds targets containing type II-like PXXP motifs. These studies expand the understanding of the EhMySH3 domain and provide extensive structural knowledge, which is expected to help in predicting the interacting partners which function together with myosin IB during phagocytosis in E. histolytica infections.

  2. Comparative proteomics, network analysis and post-translational modification identification reveal differential profiles of plasma Con A-bound glycoprotein biomarkers in gastric cancer.

    Science.gov (United States)

    Uen, Yih-Huei; Lin, Kai-Yuan; Sun, Ding-Ping; Liao, Chen-Chung; Hsieh, Ming-Song; Huang, Yung-Kai; Chen, Yen-Wei; Huang, Pei-Hsuan; Chen, Wei-Jung; Tai, Chih-Chun; Lee, Kuan-Wei; Chen, You-Chia; Lin, Ching-Yu

    2013-05-27

    In the study, we used Con A affinity chromatography, 1-D gel electrophoresis, and nano-LC-MS/MS to screen biomarker candidates in plasma samples obtained from 30 patients with gastric cancer and 30 healthy volunteers. First, we pooled plasma samples matched by age and sex. We identified 17 differentially expressed Con A-bound glycoproteins, including 10 upregulated proteins and 7 downregulated proteins; these differences were significant (Student's t-test, p-valueresponse signaling, the complement system, LXR/RXR activation, hematopoiesis from pluripotent stem cells, and primary immunodeficiency signaling. Our results suggest that Con A-bound LRG1 and ITIH3 may not be practically applicable as a robust biomarker for the early detection of gastric cancer. Additionally, three novel PTMs in ITIH3 were identified and include hexose-N-acetyl-hexosamine at asparagine-(41), trimethylation at aspartic acid-(290), and flavin adenine dinucleotide at histidine-(335). Our study was to describe a combinatorial approach of Con A affinity chromatography, 1-D SDS-PAGE, and nano-LC/MS/MS that provides a label-free, comparative glycoproteomic quantification strategy for the investigation of glycoprotein profiles in plasma from gastric cancer patients versus healthy volunteers and to identify glycoprotein biomarkers for the early clinical detection of gastric cancer. Three novel PTMs, HexHexNAc, trimethylation and FAD, in Con A-bound ITIH3 were identified and built in molecular modeling. The aspartic acid-(290) trimethylation site was located in a metal ion-dependent adhesion site (MIDAS motif; (290)-DXSXS…T…D-(313)) that may influence important function for binding protein ligands. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Single-molecule studies reveal a hidden key step in the activation mechanism of membrane-bound protein kinase C-α.

    Science.gov (United States)

    Ziemba, Brian P; Li, Jianing; Landgraf, Kyle E; Knight, Jefferson D; Voth, Gregory A; Falke, Joseph J

    2014-03-18

    Protein kinase C-α (PKCα) is a member of the conventional family of protein kinase C isoforms (cPKCs) that regulate diverse cellular signaling pathways, share a common activation mechanism, and are linked to multiple pathologies. The cPKC domain structure is modular, consisting of an N-terminal pseudosubstrate peptide, two inhibitory domains (C1A and C1B), a targeting domain (C2), and a kinase domain. Mature, cytoplasmic cPKCs are inactive until they are switched on by a multistep activation reaction that occurs largely on the plasma membrane surface. Often, this activation begins with a cytoplasmic Ca(2+) signal that triggers C2 domain targeting to the plasma membrane where it binds phosphatidylserine (PS) and phosphatidylinositol 4,5-bisphosphate (PIP2). Subsequently, the appearance of the signaling lipid diacylglycerol (DAG) activates the membrane-bound enzyme by recruiting the inhibitory pseudosubstrate and one or both C1 domains away from the kinase domain. To further investigate this mechanism, this study has utilized single-molecule total internal reflection fluorescence microscopy (TIRFM) to quantitate the binding and lateral diffusion of full-length PKCα and fragments missing specific domain(s) on supported lipid bilayers. Lipid binding events, and events during which additional protein is inserted into the bilayer, were detected by their effects on the equilibrium bound particle density and the two-dimensional diffusion rate. In addition to the previously proposed activation steps, the findings reveal a major, undescribed, kinase-inactive intermediate. On bilayers containing PS or PS and PIP2, full-length PKCα first docks to the membrane via its C2 domain, and then its C1A domain embeds itself in the bilayer even before DAG appears. The resulting pre-DAG intermediate with membrane-bound C1A and C2 domains is the predominant state of PKCα while it awaits the DAG signal. The newly detected, membrane-embedded C1A domain of this pre-DAG intermediate

  4. Ultrastructural Characterization of Turnip Mosaic Virus-Induced Cellular Rearrangements Reveals Membrane-Bound Viral Particles Accumulating in Vacuoles.

    Science.gov (United States)

    Wan, Juan; Basu, Kaustuv; Mui, Jeannie; Vali, Hojatollah; Zheng, Huanquan; Laliberté, Jean-François

    2015-12-01

    Positive-strand RNA [(+) RNA] viruses remodel cellular membranes to facilitate virus replication and assembly. In the case of turnip mosaic virus (TuMV), the viral membrane protein 6K2 plays an essential role in endomembrane alterations. Although 6K2-induced membrane dynamics have been widely studied by confocal microscopy, the ultrastructure of this remodeling has not been extensively examined. In this study, we investigated the formation of TuMV-induced membrane changes by chemical fixation and high-pressure freezing/freeze substitution (HPF/FS) for transmission electron microscopy at different times of infection. We observed the formation of convoluted membranes connected to rough endoplasmic reticulum (rER) early in the infection process, followed by the production of single-membrane vesicle-like (SMVL) structures at the midstage of infection. Both SMVL and double-membrane vesicle-like structures with electron-dense cores, as well as electron-dense bodies, were found late in the infection process. Immunogold labeling results showed that the vesicle-like structures were 6K2 tagged and suggested that only the SMVL structures were viral RNA replication sites. Electron tomography (ET) was used to regenerate a three-dimensional model of these vesicle-like structures, which showed that they were, in fact, tubules. Late in infection, we observed filamentous particle bundles associated with electron-dense bodies, which suggests that these are sites for viral particle assembly. In addition, TuMV particles were observed to accumulate in the central vacuole as membrane-associated linear arrays. Our work thus unravels the sequential appearance of distinct TuMV-induced membrane structures for viral RNA replication, viral particle assembly, and accumulation. Positive-strand RNA viruses remodel cellular membranes for different stages of the infection process, such as protein translation and processing, viral RNA synthesis, particle assembly, and virus transmission. The

  5. Roles of Dynein and Dynactin in Early Endosome Dynamics Revealed Using Automated Tracking and Global Analysis

    Science.gov (United States)

    Flores-Rodriguez, Neftali; Rogers, Salman S.; Kenwright, David A.; Waigh, Thomas A.

    2011-01-01

    Microtubule-dependent movement is crucial for the spatial organization of endosomes in most eukaryotes, but as yet there has been no systematic analysis of how a particular microtubule motor contributes to early endosome dynamics. Here we tracked early endosomes labeled with GFP-Rab5 on the nanometer scale, and combined this with global, first passage probability (FPP) analysis to provide an unbiased description of how the minus-end microtubule motor, cytoplasmic dynein, supports endosome motility. Dynein contributes to short-range endosome movement, but in particular drives 85–98% of long, inward translocations. For these, it requires an intact dynactin complex to allow membrane-bound p150Glued to activate dynein, since p50 over-expression, which disrupts the dynactin complex, inhibits inward movement even though dynein and p150Glued remain membrane-bound. Long dynein-dependent movements occur via bursts at up to ∼8 µms−1 that are linked by changes in rate or pauses. These peak speeds during rapid inward endosome movement are still seen when cellular dynein levels are 50-fold reduced by RNAi knock-down of dynein heavy chain, while the number of movements is reduced 5-fold. Altogether, these findings identify how dynein helps define the dynamics of early endosomes. PMID:21915335

  6. Comparative LC-MS/MS profiling of free and protein-bound early and advanced glycation-induced lysine modifications in dairy products

    Energy Technology Data Exchange (ETDEWEB)

    Hegele, Joerg [Nestle Research Centre, Nestec Ltd., Vers-chez-les-Blanc, CH-1000 Lausanne 26 (Switzerland)], E-mail: joerg.hegele@rdls.nestle.com; Buetler, Timo; Delatour, Thierry [Nestle Research Centre, Nestec Ltd., Vers-chez-les-Blanc, CH-1000 Lausanne 26 (Switzerland)

    2008-06-09

    Free and protein-bound forms of early and advanced glycation-induced lysine (Lys) modifications were quantified in dairy products by LC-MS/MS using a stable isotope dilution assay. The glycation profiles for N{sup {epsilon}}-fructoselysine (FL), N{sup {epsilon}}-carboxymethyllysine (CML) and pyrraline (Pyr) were monitored in raw and processed cow milk to investigate whether free glycation products could serve as fast and simple markers to assess the extent of protein glycation in dairy products. In all milk samples, the fraction of free glycation adducts was predominantly composed of advanced modifications, e.g. 8.34 {+-} 3.81 nmol CML per {mu}mol of free Lys (Lys{sub free}) and 81.5 {+-} 87.8 nmol Pyr {mu}mol{sup -1} Lys{sub free}{sup -1} vs. 3.72 {+-} 1.29 nmol FL {mu}mol{sup -1} Lys{sub free}{sup -1}. In contrast, the protein-bound early glycation product FL considerably outweighed the content of CML and Pyr in milk proteins of raw and processed cow milk, whereas severely heat treated milk products, e.g. condensed milk, contained a higher amount of protein-bound advanced glycation adducts. Typical values recorded for milk samples processed under mild conditions were 0.47 {+-} 0.08 nmol FL {mu}mol{sup -1} of protein-bound Lys (Lys{sub p-b}), 0.04 {+-} 0.03 nmol CML {mu}mol{sup -1} Lys{sub p-b}{sup -1} and 0.06 {+-} 0.02 nmol Pyr {mu}mol{sup -1} Lys{sub p-b}{sup -1}. It was particularly noticeable, however, that mild heat treatment of raw milk, i.e. pasteurization and UHT treatment, did not significantly increase the amount of both free and protein-bound Lys modifications. In conclusion, the profiles of free and protein-bound glycation-induced Lys modifications were found to be different and a screening of free glycation adducts does, therefore, not allow for a conclusion about the protein glycation status of dairy products.

  7. Altered anatomical network in early blindness revealed by diffusion tensor tractography.

    Directory of Open Access Journals (Sweden)

    Ni Shu

    Full Text Available The topological architecture of the cerebral anatomical network reflects the structural organization of the human brain. Recently, topological measures based on graph theory have provided new approaches for quantifying large-scale anatomical networks. Diffusion MRI studies have revealed the efficient small-world properties and modular structure of the anatomical network in normal subjects. However, no previous study has used diffusion MRI to reveal changes in the brain anatomical network in early blindness. Here, we utilized diffusion tensor imaging to construct binary anatomical networks for 17 early blind subjects and 17 age- and gender-matched sighted controls. We established the existence of structural connections between any pair of the 90 cortical and sub-cortical regions using deterministic tractography. Compared with controls, early blind subjects showed a decreased degree of connectivity, a reduced global efficiency, and an increased characteristic path length in their brain anatomical network, especially in the visual cortex. Moreover, we revealed some regions with motor or somatosensory function have increased connections with other brain regions in the early blind, which suggested experience-dependent compensatory plasticity. This study is the first to show alterations in the topological properties of the anatomical network in early blindness. From the results, we suggest that analyzing the brain's anatomical network obtained using diffusion MRI data provides new insights into the understanding of the brain's re-organization in the specific population with early visual deprivation.

  8. Altered anatomical network in early blindness revealed by diffusion tensor tractography.

    Science.gov (United States)

    Shu, Ni; Liu, Yong; Li, Jun; Li, Yonghui; Yu, Chunshui; Jiang, Tianzi

    2009-09-28

    The topological architecture of the cerebral anatomical network reflects the structural organization of the human brain. Recently, topological measures based on graph theory have provided new approaches for quantifying large-scale anatomical networks. Diffusion MRI studies have revealed the efficient small-world properties and modular structure of the anatomical network in normal subjects. However, no previous study has used diffusion MRI to reveal changes in the brain anatomical network in early blindness. Here, we utilized diffusion tensor imaging to construct binary anatomical networks for 17 early blind subjects and 17 age- and gender-matched sighted controls. We established the existence of structural connections between any pair of the 90 cortical and sub-cortical regions using deterministic tractography. Compared with controls, early blind subjects showed a decreased degree of connectivity, a reduced global efficiency, and an increased characteristic path length in their brain anatomical network, especially in the visual cortex. Moreover, we revealed some regions with motor or somatosensory function have increased connections with other brain regions in the early blind, which suggested experience-dependent compensatory plasticity. This study is the first to show alterations in the topological properties of the anatomical network in early blindness. From the results, we suggest that analyzing the brain's anatomical network obtained using diffusion MRI data provides new insights into the understanding of the brain's re-organization in the specific population with early visual deprivation.

  9. Integration of Bayesian molecular clock methods and fossil-based soft bounds reveals early Cenozoic origin of African lacertid lizards

    Directory of Open Access Journals (Sweden)

    Metzler Dirk

    2009-07-01

    Full Text Available Abstract Background Although current molecular clock methods offer greater flexibility in modelling evolutionary events, calibration of the clock with dates from the fossil record is still problematic for many groups. Here we implement several new approaches in molecular dating to estimate the evolutionary ages of Lacertidae, an Old World family of lizards with a poor fossil record and uncertain phylogeny. Four different models of rate variation are tested in a new program for Bayesian phylogenetic analysis called TreeTime, based on a combination of mitochondrial and nuclear gene sequences. We incorporate paleontological uncertainty into divergence estimates by expressing multiple calibration dates as a range of probabilistic distributions. We also test the reliability of our proposed calibrations by exploring effects of individual priors on posterior estimates. Results According to the most reliable model, as indicated by Bayes factor comparison, modern lacertids arose shortly after the K/T transition and entered Africa about 45 million years ago, with the majority of their African radiation occurring in the Eocene and Oligocene. Our findings indicate much earlier origins for these clades than previously reported, and we discuss our results in light of paleogeographic trends during the Cenozoic. Conclusion This study represents the first attempt to estimate evolutionary ages of a specific group of reptiles exhibiting uncertain phylogenetic relationships, molecular rate variation and a poor fossil record. Our results emphasize the sensitivity of molecular divergence dates to fossil calibrations, and support the use of combined molecular data sets and multiple, well-spaced dates from the fossil record as minimum node constraints. The bioinformatics program used here, TreeTime, is publicly available, and we recommend its use for molecular dating of taxa faced with similar challenges.

  10. Molecular dynamics simulations of apo, holo, and inactivator bound GABA-at reveal the role of active site residues in PLP dependent enzymes.

    Science.gov (United States)

    Gökcan, Hatice; Monard, Gerald; Sungur Konuklar, F Aylin

    2016-07-01

    The pyridoxal 5-phosphate (PLP) cofactor is a significant organic molecule in medicinal chemistry. It is often found covalently bound to lysine residues in proteins to form PLP dependent enzymes. An example of this family of PLP dependent enzymes is γ-aminobutyric acid aminotransferase (GABA-AT) which is responsible for the degradation of the neurotransmitter GABA. Its inhibition or inactivation can be used to prevent the reduction of GABA concentration in brain which is the source of several neurological disorders. As a test case for PLP dependent enzymes, we have performed molecular dynamics simulations of GABA-AT to reveal the roles of the protein residues and its cofactor. Three different states have been considered: the apoenzyme, the holoenzyme, and the inactive state obtained after the suicide inhibition by vigabatrin. Different protonation states have also been considered for PLP and two key active site residues: Asp298 and His190. Together, 24 independent molecular dynamics trajectories have been simulated for a cumulative total of 2.88 µs. Our results indicate that, unlike in aqueous solution, the PLP pyridine moiety is protonated in GABA-AT. This is a consequence of a pKa shift triggered by a strong charge-charge interaction with an ionic "diad" formed by Asp298 and His190 that would help the activation of the first half-reaction of the catalytic mechanism in GABA-AT: the conversion of PLP to free pyridoxamine phosphate (PMP). In addition, our MD simulations exhibit additional strong hydrogen bond networks between the protein and PLP: the phosphate group is held in place by the donation of at least three hydrogen bonds while the carbonyl oxygen of the pyridine ring interacts with Gln301; Phe181 forms a π-π stacking interaction with the pyridine ring and works as a gate keeper with the assistance of Val300. All these interactions are hypothesized to help maintain free PMP in place inside the protein active site to facilitate the second half

  11. Bounded Rationality

    National Research Council Canada - National Science Library

    Ballester Pla, Coralio; Hernández, Penélope

    2012-01-01

    The observation of the actual behavior by economic decision makers in the lab and in the field justifies that bounded rationality has been a generally accepted assumption in many socio-economic models...

  12. Bounding the $\

    CERN Document Server

    Gutiérrez-Rodríguez, A

    2003-01-01

    A bound on the nu /sup tau / magnetic moment is calculated through the reaction e/sup +/e/sup -/ to nu nu gamma at the Z/sub 1/-pole, and in the framework of a left-right symmetric model at LEP energies. We find that the bound is almost independent of the mixing angle phi of the model in the allowed experimental range for this parameter. (31 refs).

  13. X-ray structures of the proprotein convertase furin bound with substrate analog inhibitors reveal substrate specificity determinants beyond the S4 pocket.

    Science.gov (United States)

    Dahms, Sven O; Hardes, Kornelia; Steinmetzer, Torsten; Than, Manuel E

    2018-01-09

    The proprotein convertase (PC) furin is a highly specific serine protease modifying and thereby activating proteins in the secretory pathway by proteolytic cleavage. Its substrates are involved in many diseases including cancer and infections caused by bacteria and viruses. Understanding furin's substrate specificity is of crucial importance for the development of pharmacologically applicable inhibitors. Using protein X-ray crystallography we investigated the extended substrate binding site of furin in complex with three peptide derived inhibitors at up to 1.9 Å resolution. The structure of the protease bound with a hexapeptide inhibitor revealed molecular details of its S6 pocket, which remained completely unknown so far. The arginine residue at P6 induced an unexpected turn-like conformation of the inhibitor backbone, which is stabilized by intra- and intermolecular H-bonds. In addition, we confirmed the binding of arginine to the previously proposed S5 pocket (S51). An alternative S5 site (S52) could be utilized by shorter sidechains as demonstrated for a 4-aminomethyl-phenylacetyl residue, which shows steric properties similar to a lysine side chain. Interestingly, we also observed binding of a peptide with citrulline at P4 substituting the highly conserved arginine. The structural data might indicate an unusual protonation state of Asp264 maintaining the interaction with uncharged citrulline. The herein identified molecular interaction sites at P5 and P6 can be utilized to improve next generation furin inhibitors. Our data will also help to predict furin substrates more precisely based on the additional specificity determinants observed for P5 and P6.

  14. A branch-and-bound algorithm for single-machine earliness-tardiness scheduling with idle time

    NARCIS (Netherlands)

    Hoogeveen, J.A.; van de Velde, S.L.; van de Velde, S.L.

    1996-01-01

    We address the NP-hard single-machine problem of scheduling n independent jobs so as to minimize the sum of α times total completion time and β times total earliness with β > α, which can be rewritten as an earliness–tardiness problem. Postponing jobs by leaving the machine idle may then be

  15. Early revealing of neurogenic disorders of urination in patients with anorectal anomalies

    Directory of Open Access Journals (Sweden)

    Makedonsky I.O.

    2013-03-01

    Full Text Available 148 patients with anorectal malformations (ARM were examined. Using clinical, X-ray, ultrasound and urodynamical methods of detections, factors which can cause bladder dysfunction in anorectal malformations are revealed. It was noted that patients with high and low forms of this defect have significant percentage of neurogenec disorders of urination. Absence of anomalies of spinal column development does not exclude these children from the group of scheduled profound urologic investigation. We propose ultrasound measurement of bladder wall thickness and 4-hour monitoring of voiding, urodynamic examination as early diagnostic methods of neurogenic bladder dysfunctions. For timely revealing and treatment of neurogenic disorders of urination we recommend urologic inves¬tigation to all ARM patients. Improvement of diagnostic methods and development of algorithm of revealing mentioned pathologies against ARM with the aim to prevent com¬plications in the urinary system, being perspective in decreasing lethality and disability.

  16. Analysis of meteorology and emission in haze episode prevalence over mountain-bounded region for early warning.

    Science.gov (United States)

    Kim Oanh, Nguyen Thi; Leelasakultum, Ketsiri

    2011-05-01

    This study investigated the main causes of haze episodes in the northwestern Thailand to provide early warning and prediction. In an absence of emission input data required for chemical transport modeling to predict the haze, the climatological approach in combination with statistical analysis was used. An automatic meteorological classification scheme was developed using regional meteorological station data of 8years (2001-2008) which classified the prevailing synoptic patterns over Northern Thailand into 4 patterns. Pattern 2, occurring with high frequency in March, was found to associate with the highest levels of 24h PM(10) in Chiangmai, the largest city in Northern Thailand. Typical features of this pattern were the dominance of thermal lows over India, Western China and Northern Thailand with hot, dry and stagnant air in Northern Thailand. March 2007, the month with the most severe haze episode in Chiangmai, was found to have a high frequency of occurrence of pattern 2 coupled with the highest emission intensities from biomass open burning. Backward trajectories showed that, on haze episode days, air masses passed over the region of dense biomass fire hotspots before arriving at Chiangmai. A stepwise regression model was developed to predict 24h PM(10) for days of meteorology pattern 2 using February-April data of 2007-2009 and tested with 2004-2010 data. The model performed satisfactorily for the model development dataset (R(2)=87%) and test dataset (R(2)=81%), which appeared to be superior over a simple persistence regression of 24h PM(10) (R(2)=76%). Our developed model had an accuracy over 90% for the categorical forecast of PM(10)>120μg/m(3). The episode warning procedure would identify synoptic pattern 2 and predict 24h PM(10) in Chiangmai 24h in advance. This approach would be applicable for air pollution episode management in other areas with complex terrain where similar conditions exist. Copyright © 2011 Elsevier B.V. All rights reserved.

  17. Characteristics of depositional sequences, systems tracts and bounding surfaces in Early Ordovician greenhouse passive margin carbonates to Late Ordovician glacio-eustatic influenced foreland basin facies

    Energy Technology Data Exchange (ETDEWEB)

    Pope, M.C.; Read, J.F. (Virginia Polytechnic Inst. and State Univ., Blacksburg, VA (United States). Dept. of Geology)

    1994-03-01

    Passive margin, cyclic carbonates of the Early Ordovician Knox Group, Appalachians are dominated by meter scale dolomitized carbonate cycles. These are stacked into 1 to 5 m.y. depositional sequences that appear to be relatively conformable. The sequences are defined by stacking patterns on Fischer plots that graph long term changes in accommodation with thick less dolomitized cycles in the TST, and thin, highly dolomitized cycles in the HST, becoming quartzose in the late HST and LST. Sequence and systems tract boundaries are subtle and typically marked by zones of cycles rather than single discrete surfaces. In contrast, sequences in the later Ordovician foreland basin fill locally show: (1) sequence bounding unconformities on the Knox, the Camp Nelson and on top of the Ordovician, (2) well defined low stand deposits as in the subaerial breccias and detrital dolomite muds veneering the Knox unconformity; redbeds and associated quartz sands and conglomerates with intercalated peritidal carbonate layers and their distal equivalent peritidal laminites; (3) TST's in the lower part of the Middle Ordovician limestones include regionally traceable cyclic peritidal carbonates or in the lower Lexington Limestone, transgressive high energy grainstones; (4) HST's consist of poorly cyclic deeper water up into shallow water grainstone bank and northward prograding peritidal carbonate facies; The ongoing study of detailed logs of outcrop and core should help refine the understanding of the fine scale makeup of sequences developed in these contrasting tectonic and global climatic settings.

  18. The X-ray structure of Plasmodium falciparum dihydroorotate dehydrogenase bound to a potent and selective N-phenylbenzamide inhibitor reveals novel binding-site interactions.

    Science.gov (United States)

    Deng, Xiaoyi; Matthews, David; Rathod, Pradipsinh K; Phillips, Margaret A

    2015-05-01

    Plasmodium species are protozoan parasites that are the causative agent of malaria. Malaria is a devastating disease, and its treatment and control have been hampered by the propensity of the parasite to become drug-resistant. Dihydroorotate dehydrogenase (DHODH) has been identified as a promising new target for the development of antimalarial agents. Here, the X-ray structure of P. falciparum DHODH bound to a potent and selective N-phenylbenzamide-based inhibitor (DSM59) is described at 2.3 Å resolution. The structure elucidates novel binding-site interactions and shows how conformational flexibility of the enzyme leads to the ability to bind diverse chemical structures with high affinity. This information provides new insight into the design of high-affinity DHODH inhibitors for the treatment of malaria.

  19. Bounded Rationality

    Directory of Open Access Journals (Sweden)

    Ballester Pla, Coralio

    2012-03-01

    Full Text Available The observation of the actual behavior by economic decision makers in the lab and in the field justifies that bounded rationality has been a generally accepted assumption in many socio-economic models. The goal of this paper is to illustrate the difficulties involved in providing a correct definition of what a rational (or irrational agent is. In this paper we describe two frameworks that employ different approaches for analyzing bounded rationality. The first is a spatial segregation set-up that encompasses two optimization methodologies: backward induction and forward induction. The main result is that, even under the same state of knowledge, rational and non-rational agents may match their actions. The second framework elaborates on the relationship between irrationality and informational restrictions. We use the beauty contest (Nagel, 1995 as a device to explain this relationship.

    La observación del comportamiento de los agentes económicos tanto en el laboratorio como en la vida real justifica que la racionalidad acotada sea un supuesto aceptado en numerosos modelos socio-económicos. El objetivo de este artículo es ilustrar las dificultades que conlleva una correcta definición de qué es un agente racional (irracional. En este artículo se describen dos marcos que emplean diferentes metodologías para analizar la racionalidad acotada. El primero es un modelo de segregación espacial donde se contrastan dos metodologías de optimización: inducción hacia atrás y hacia adelante. El resultado principal es que, incluso con el mismo nivel de conocimiento, tanto agentes racionales como irracionales podrían coincidir en sus acciones. El segundo marco trabaja sobre la relación entre irracionalidad y restricción de información. Se utiliza el juego llamado “beauty contest” (Nagel 1995 como mecanismo para explicar dicha relación.

  20. EEG reveals an early influence of social conformity on visual processing in group pressure situations.

    Science.gov (United States)

    Trautmann-Lengsfeld, Sina Alexa; Herrmann, Christoph Siegfried

    2013-01-01

    Humans are social beings and often have to perceive and perform within groups. In conflict situations, this puts them under pressure to either adhere to the group opinion or to risk controversy with the group. Psychological experiments have demonstrated that study participants adapt to erroneous group opinions in visual perception tasks, which they can easily solve correctly when performing on their own. Until this point, however, it is unclear whether this phenomenon of social conformity influences early stages of perception that might not even reach awareness or later stages of conscious decision-making. Using electroencephalography, this study has revealed that social conformity to the wrong group opinion resulted in a decrease of the posterior-lateral P1 in line with a decrease of the later centro-parietal P3. These results suggest that group pressure situations impact early unconscious visual perceptual processing, which results in a later diminished stimulus discrimination and an adaptation even to the wrong group opinion. These findings might have important implications for understanding social behavior in group settings and are discussed within the framework of social influence on eyewitness testimony.

  1. Dynamic landscape of pancreatic carcinogenesis reveals early molecular networks of malignancy.

    Science.gov (United States)

    Kong, Bo; Bruns, Philipp; Behler, Nora A; Chang, Ligong; Schlitter, Anna Melissa; Cao, Jing; Gewies, Andreas; Ruland, Jürgen; Fritzsche, Sina; Valkovskaya, Nataliya; Jian, Ziying; Regel, Ivonne; Raulefs, Susanne; Irmler, Martin; Beckers, Johannes; Friess, Helmut; Erkan, Mert; Mueller, Nikola S; Roth, Susanne; Hackert, Thilo; Esposito, Irene; Theis, Fabian J; Kleeff, Jörg; Michalski, Christoph W

    2016-09-19

    The initial steps of pancreatic regeneration versus carcinogenesis are insufficiently understood. Although a combination of oncogenic Kras and inflammation has been shown to induce malignancy, molecular networks of early carcinogenesis remain poorly defined. We compared early events during inflammation, regeneration and carcinogenesis on histological and transcriptional levels with a high temporal resolution using a well-established mouse model of pancreatitis and of inflammation-accelerated KrasG12D-driven pancreatic ductal adenocarcinoma. Quantitative expression data were analysed and extensively modelled in silico. We defined three distinctive phases-termed inflammation, regeneration and refinement-following induction of moderate acute pancreatitis in wild-type mice. These corresponded to different waves of proliferation of mesenchymal, progenitor-like and acinar cells. Pancreas regeneration required a coordinated transition of proliferation between progenitor-like and acinar cells. In mice harbouring an oncogenic Kras mutation and challenged with pancreatitis, there was an extended inflammatory phase and a parallel, continuous proliferation of mesenchymal, progenitor-like and acinar cells. Analysis of high-resolution transcriptional data from wild-type animals revealed that organ regeneration relied on a complex interaction of a gene network that normally governs acinar cell homeostasis, exocrine specification and intercellular signalling. In mice with oncogenic Kras, a specific carcinogenic signature was found, which was preserved in full-blown mouse pancreas cancer. These data define a transcriptional signature of early pancreatic carcinogenesis and a molecular network driving formation of preneoplastic lesions, which allows for more targeted biomarker development in order to detect cancer earlier in patients with pancreatitis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  2. Geologically Controlled Isotope-Time Patterns Reveal Early Differentiation and Crust Formation Processes

    Science.gov (United States)

    Bennett, V. C.; Nutman, A. P.

    2014-12-01

    The mechanisms of continental crust production and evolution in the early Earth remain controversial, as are questions of the relative roles of early differentiation versus subsequent tectonic procssing in creating Earth's chemical signatures. Here we present geologic observations integrated with whole rock major, trace element and Sm-Nd isotopic signatures and combined with U-Pb and Lu-Hf isotopic compositions of zircon populations from the same rocks, from the most extensive early rock record comprising the 3.9 Ga to 3.6 Ga terranes of southwest Greenland. These data reveal repeated patterns of formation of juvenile TTG crust and associated mafic and ultramafic rocks in convergent margin settings followed by formation of more evolved granites [1]. Our new zircon Lu-Hf data from rare 3.6-3.7 Ga tonalites within the Itsaq Gneiss Complex, obtained from single component, non-migmatitic gneisses with simple zircon populations, limited within sample Hf isotopic variability and accurate U-Pb ages, now document extraction of juvenile tonalites from a near chondritic mantle source between 3.9 Ga and 3.6 Ga. The more evolved, granitic rocks in each area show slightly negative initial ɛHf in accord with crustal reworking of the older (3.8-3.9 Ga) gniesses. There is no evidence for Hadean material in the sources of the granitoids. The Hf isotope-time patterns are consistent with juvenile crust production from a mantle source that experienced only modest amounts of prior crustal extraction. They are distinct from those predicted by reprocessing of an enriched Hadean mafic crust, as has been proposed for this region [2] and for the source of the Hadean Jack Hills zircons [3]. The well-documented, time decreasing, positive 142Nd anomalies [e.g., 4] from these rocks are further evidence of crustal derivation from a convecting mantle source, rather than reworking of an enriched mafic lithosphere. The 143Nd isotopic -time patterns are more complex, reflecting the interplay

  3. The crystal structure of the interleukin 21 receptor bound to interleukin 21 reveals that a sugar chain interacting with the WSXWS motif is an integral part of the interleukin 21 receptor

    DEFF Research Database (Denmark)

    Hamming, Ole Jensen; Kang, Lishan; Svensson, Anders

    2012-01-01

    Interleukin (IL) 21 is a class I cytokine, which exerts pleiotropic effects on both innate and adaptive immune responses. It signals through a heterodimeric receptor complex consisting of the IL-21 receptor (IL-21R) and the common gamma chain (gC). A hallmark of the class I cytokine receptors...... to be a consensus sequence for C-mannosylation. Here we present the crystal structure of IL-21 bound to IL-21R and reveal that the WSXWS motif of IL-21R is C-mannosylated on the first tryptophan. We furthermore demonstrate that a sugar chain bridge the two fibronectin domains which constitute the extracellular...

  4. A short-time scale colloidal system reveals early bacterial adhesion dynamics.

    Directory of Open Access Journals (Sweden)

    Christophe Beloin

    2008-07-01

    Full Text Available The development of bacteria on abiotic surfaces has important public health and sanitary consequences. However, despite several decades of study of bacterial adhesion to inert surfaces, the biophysical mechanisms governing this process remain poorly understood, due, in particular, to the lack of methodologies covering the appropriate time scale. Using micrometric colloidal surface particles and flow cytometry analysis, we developed a rapid multiparametric approach to studying early events in adhesion of the bacterium Escherichia coli. This approach simultaneously describes the kinetics and amplitude of early steps in adhesion, changes in physicochemical surface properties within the first few seconds of adhesion, and the self-association state of attached and free-floating cells. Examination of the role of three well-characterized E. coli surface adhesion factors upon attachment to colloidal surfaces--curli fimbriae, F-conjugative pilus, and Ag43 adhesin--showed clear-cut differences in the very initial phases of surface colonization for cell-bearing surface structures, all known to promote biofilm development. Our multiparametric analysis revealed a correlation in the adhesion phase with cell-to-cell aggregation properties and demonstrated that this phenomenon amplified surface colonization once initial cell-surface attachment was achieved. Monitoring of real-time physico-chemical particle surface properties showed that surface-active molecules of bacterial origin quickly modified surface properties, providing new insight into the intricate relations connecting abiotic surface physicochemical properties and bacterial adhesion. Hence, the biophysical analytical method described here provides a new and relevant approach to quantitatively and kinetically investigating bacterial adhesion and biofilm development.

  5. Structure of the Human Angiotensin II Type 1 (AT1) Receptor Bound to Angiotensin II from Multiple Chemoselective Photoprobe Contacts Reveals a Unique Peptide Binding Mode*

    Science.gov (United States)

    Fillion, Dany; Cabana, Jérôme; Guillemette, Gaétan; Leduc, Richard; Lavigne, Pierre; Escher, Emanuel

    2013-01-01

    Breakthroughs in G protein-coupled receptor structure determination based on crystallography have been mainly obtained from receptors occupied in their transmembrane domain core by low molecular weight ligands, and we have only recently begun to elucidate how the extracellular surface of G protein-coupled receptors (GPCRs) allows for the binding of larger peptide molecules. In the present study, we used a unique chemoselective photoaffinity labeling strategy, the methionine proximity assay, to directly identify at physiological conditions a total of 38 discrete ligand/receptor contact residues that form the extracellular peptide-binding site of an activated GPCR, the angiotensin II type 1 receptor. This experimental data set was used in homology modeling to guide the positioning of the angiotensin II (AngII) peptide within several GPCR crystal structure templates. We found that the CXC chemokine receptor type 4 accommodated the results better than the other templates evaluated; ligand/receptor contact residues were spatially grouped into defined interaction clusters with AngII. In the resulting receptor structure, a β-hairpin fold in extracellular loop 2 in conjunction with two extracellular disulfide bridges appeared to open and shape the entrance of the ligand-binding site. The bound AngII adopted a somewhat vertical binding mode, allowing concomitant contacts across the extracellular surface and deep within the transmembrane domain core of the receptor. We propose that such a dualistic nature of GPCR interaction could be well suited for diffusible linear peptide ligands and a common feature of other peptidergic class A GPCRs. PMID:23386604

  6. Integrative analyses reveal novel strategies in HPV11,-16 and-45 early infection

    DEFF Research Database (Denmark)

    Kaczkowski, Bogumil; Rossing, Maria; Andersen, Ditte

    2012-01-01

    The interaction between human papillomavirus (HPV) and host cells is not well understood. We investigate the early stage of HPV infections by global expression profiling in a cell model, in which HaCaT cells were transfected with HPV11, HPV16 or HPV45 genomes. We report the differential expression...... of genes not previously implicated in HPV biology, such as the PSG family and ANKRD1, and of genes implicated in the biology of other viruses, e. g. MX1, IFI44 and DDX60. Carcinogenesis-related genes, e. g. ABL2, MGLL and CYR61, were upregulated by high-risk HPV16 and -45. The integrative analysis revealed...... the suppression of DNA repair by HPV11 and -16, and downregulation of cytoskeleton genes by all HPV types. Various signalling pathways were affected by the HPVs: IL-2 by HPV11; JAK-STAT by HPV16; and TGF-beta, NOTCH and tyrosine kinase signalling by HPV45. This study uncovered novel strategies employed by HPV...

  7. MMP-13 In-Vivo Molecular Imaging Reveals Early Expression in Lung Adenocarcinoma

    Science.gov (United States)

    Salaün, Mathieu; Peng, Jing; Hensley, Harvey H.; Roder, Navid; Flieder, Douglas B.; Houlle-Crépin, Solène; Abramovici-Roels, Olivia; Sabourin, Jean-Christophe; Thiberville, Luc; Clapper, Margie L.

    2015-01-01

    Introduction Several matrix metalloproteinases (MMPs) are overexpressed in lung cancer and may serve as potential targets for the development of bioactivable probes for molecular imaging. Objective To characterize and monitor the activity of MMPs during the progression of lung adenocarcinoma. Methods K-rasLSL-G12D mice were imaged serially during the development of adenocarcinomas using fluorescence molecular tomography (FMT) and a probe specific for MMP-2, -3, -9 and -13. Lung tumors were identified using FMT and MRI co-registration, and the probe concentration in each tumor was assessed at each time-point. The expression of Mmp2, -3, -9, -13 was quantified by qRT-PCR using RNA isolated from microdissected tumor cells. Immunohistochemical staining of overexpressed MMPs in animals was assessed on human lung tumors. Results In mice, 7 adenomas and 5 adenocarcinomas showed an increase in fluorescent signal on successive FMT scans, starting between weeks 4 and 8. qRT-PCR assays revealed significant overexpression of only Mmp-13 in mice lung tumors. In human tumors, a high MMP-13 immunostaining index was found in tumor cells from invasive lesions (24/27), but in none of the non-invasive (0/4) (p=0.001). Conclusion MMP-13 is detected in early pulmonary invasive adenocarcinomas and may be a potential target for molecular imaging of lung cancer. PMID:26193700

  8. Ancient DNA from European Early Neolithic Farmers Reveals Their Near Eastern Affinities

    Science.gov (United States)

    Haak, Wolfgang; Balanovsky, Oleg; Sanchez, Juan J.; Koshel, Sergey; Zaporozhchenko, Valery; Adler, Christina J.; Der Sarkissian, Clio S. I.; Brandt, Guido; Schwarz, Carolin; Nicklisch, Nicole; Dresely, Veit; Fritsch, Barbara; Balanovska, Elena; Villems, Richard; Meller, Harald; Alt, Kurt W.; Cooper, Alan

    2010-01-01

    In Europe, the Neolithic transition (8,000–4,000 b.c.) from hunting and gathering to agricultural communities was one of the most important demographic events since the initial peopling of Europe by anatomically modern humans in the Upper Paleolithic (40,000 b.c.). However, the nature and speed of this transition is a matter of continuing scientific debate in archaeology, anthropology, and human population genetics. To date, inferences about the genetic make up of past populations have mostly been drawn from studies of modern-day Eurasian populations, but increasingly ancient DNA studies offer a direct view of the genetic past. We genetically characterized a population of the earliest farming culture in Central Europe, the Linear Pottery Culture (LBK; 5,500–4,900 calibrated b.c.) and used comprehensive phylogeographic and population genetic analyses to locate its origins within the broader Eurasian region, and to trace potential dispersal routes into Europe. We cloned and sequenced the mitochondrial hypervariable segment I and designed two powerful SNP multiplex PCR systems to generate new mitochondrial and Y-chromosomal data from 21 individuals from a complete LBK graveyard at Derenburg Meerenstieg II in Germany. These results considerably extend the available genetic dataset for the LBK (n = 42) and permit the first detailed genetic analysis of the earliest Neolithic culture in Central Europe (5,500–4,900 calibrated b.c.). We characterized the Neolithic mitochondrial DNA sequence diversity and geographical affinities of the early farmers using a large database of extant Western Eurasian populations (n = 23,394) and a wide range of population genetic analyses including shared haplotype analyses, principal component analyses, multidimensional scaling, geographic mapping of genetic distances, and Bayesian Serial Simcoal analyses. The results reveal that the LBK population shared an affinity with the modern-day Near East and Anatolia, supporting a major

  9. Ancient DNA from European early neolithic farmers reveals their near eastern affinities.

    Directory of Open Access Journals (Sweden)

    Wolfgang Haak

    Full Text Available In Europe, the Neolithic transition (8,000-4,000 B.C. from hunting and gathering to agricultural communities was one of the most important demographic events since the initial peopling of Europe by anatomically modern humans in the Upper Paleolithic (40,000 B.C.. However, the nature and speed of this transition is a matter of continuing scientific debate in archaeology, anthropology, and human population genetics. To date, inferences about the genetic make up of past populations have mostly been drawn from studies of modern-day Eurasian populations, but increasingly ancient DNA studies offer a direct view of the genetic past. We genetically characterized a population of the earliest farming culture in Central Europe, the Linear Pottery Culture (LBK; 5,500-4,900 calibrated B.C. and used comprehensive phylogeographic and population genetic analyses to locate its origins within the broader Eurasian region, and to trace potential dispersal routes into Europe. We cloned and sequenced the mitochondrial hypervariable segment I and designed two powerful SNP multiplex PCR systems to generate new mitochondrial and Y-chromosomal data from 21 individuals from a complete LBK graveyard at Derenburg Meerenstieg II in Germany. These results considerably extend the available genetic dataset for the LBK (n = 42 and permit the first detailed genetic analysis of the earliest Neolithic culture in Central Europe (5,500-4,900 calibrated B.C.. We characterized the Neolithic mitochondrial DNA sequence diversity and geographical affinities of the early farmers using a large database of extant Western Eurasian populations (n = 23,394 and a wide range of population genetic analyses including shared haplotype analyses, principal component analyses, multidimensional scaling, geographic mapping of genetic distances, and Bayesian Serial Simcoal analyses. The results reveal that the LBK population shared an affinity with the modern-day Near East and Anatolia, supporting

  10. Ancient DNA from European early neolithic farmers reveals their near eastern affinities.

    Science.gov (United States)

    Haak, Wolfgang; Balanovsky, Oleg; Sanchez, Juan J; Koshel, Sergey; Zaporozhchenko, Valery; Adler, Christina J; Der Sarkissian, Clio S I; Brandt, Guido; Schwarz, Carolin; Nicklisch, Nicole; Dresely, Veit; Fritsch, Barbara; Balanovska, Elena; Villems, Richard; Meller, Harald; Alt, Kurt W; Cooper, Alan

    2010-11-09

    In Europe, the Neolithic transition (8,000-4,000 B.C.) from hunting and gathering to agricultural communities was one of the most important demographic events since the initial peopling of Europe by anatomically modern humans in the Upper Paleolithic (40,000 B.C.). However, the nature and speed of this transition is a matter of continuing scientific debate in archaeology, anthropology, and human population genetics. To date, inferences about the genetic make up of past populations have mostly been drawn from studies of modern-day Eurasian populations, but increasingly ancient DNA studies offer a direct view of the genetic past. We genetically characterized a population of the earliest farming culture in Central Europe, the Linear Pottery Culture (LBK; 5,500-4,900 calibrated B.C.) and used comprehensive phylogeographic and population genetic analyses to locate its origins within the broader Eurasian region, and to trace potential dispersal routes into Europe. We cloned and sequenced the mitochondrial hypervariable segment I and designed two powerful SNP multiplex PCR systems to generate new mitochondrial and Y-chromosomal data from 21 individuals from a complete LBK graveyard at Derenburg Meerenstieg II in Germany. These results considerably extend the available genetic dataset for the LBK (n = 42) and permit the first detailed genetic analysis of the earliest Neolithic culture in Central Europe (5,500-4,900 calibrated B.C.). We characterized the Neolithic mitochondrial DNA sequence diversity and geographical affinities of the early farmers using a large database of extant Western Eurasian populations (n = 23,394) and a wide range of population genetic analyses including shared haplotype analyses, principal component analyses, multidimensional scaling, geographic mapping of genetic distances, and Bayesian Serial Simcoal analyses. The results reveal that the LBK population shared an affinity with the modern-day Near East and Anatolia, supporting a major

  11. Quasi-bounded sets

    Directory of Open Access Journals (Sweden)

    Jan Kucera

    1990-01-01

    Full Text Available It is proved in [1] & [2] that a set bounded in an inductive limit E=indlim En of Fréchet spaces is also bounded in some En iff E is fast complete. In the case of arbitrary locally convex spaces En every bounded set in a fast complete indlim En is quasi-bounded in some En, though it may not be bounded or even contained in any En. Every bounded set is quasi-bounded. In a Fréchet space every quasi-bounded set is also bounded.

  12. Transcriptomic analysis reveals key early events of narciclasine signaling in Arabidopsis root apex.

    Science.gov (United States)

    Cao, Xiaoning; Ma, Fei; Xu, Tingting; Wang, Junjie; Liu, Sichen; Li, Gaihong; Su, Qian; Qiao, Zhijun; Na, XiaoFan

    2016-11-01

    Histochemical staining and RNA-seq data demonstrated that the ROS- and plant hormone-regulated stress responses are the key early events of narciclasine signaling in Arabidopsis root cells. Narciclasine, an amaryllidaceae alkaloid isolated from Narcissus tazetta bulbs, employs a broad range of functions on plant development and growth. However, its molecular interactions that modulate these roles in plants are not fully understood. To elucidate the global responses of Arabidopsis roots to short-term narciclasine exposure, we first measured the accumulation of H2O2 and O2- with histochemical staining, and then profiled the gene expression pattern in Arabidopsis root tips treated with 0.5 µM narciclasine across different exposure times by RNA-seq. Physiological measurements showed a significant increase in H2O2 began at 30-60 min of narciclasine treatment and O2- accumulated by 120 min. Compared with controls, 236 genes were upregulated and 54 genes were downregulated with 2 h of narciclasine treatment, while 968 genes were upregulated and 835 genes were downregulated with 12 h of treatment. The Gene Ontology analysis revealed that the differentially expressed genes were highly enriched during oxidative stress, including those involved in the "regulation of transcription", "response to oxidative stress", "plant-pathogen interaction", "ribonucleotide binding", "plant cell wall organization", and "ribosome biogenesis". Moreover, Kyoto Encyclopedia of Genes and Genomes pathway enrichment statistics suggested that carbohydrate metabolism, amino acid metabolism, amino sugar and nucleotide sugar metabolism, and biosynthesis of phenylpropanoid and secondary metabolites were significantly inhibited by 12 h of narciclasine exposure. Hence, our results demonstrate that hormones and H2O2 are important regulators of narciclasine signaling and help to uncover the factors involved in the molecular interplay between narciclasine and phytohormones in Arabidopsis root cells.

  13. Journal Club: MRI reveals acute inflammation in cortical lesions during early MS.

    Science.gov (United States)

    Bateman, Emily M; Schleicher, Wolfgang E; Smith, Elana J; Sweet, David R; Gaudet, Andrew D

    2018-02-20

    Early multiple sclerosis is characterized by immune-associated demyelination of CNS axons. In a recent Neurology® article, Maranzano et al. evaluated MRI scans of patients with early multiple sclerosis to study the evolution of leukocortical lesions. Their novel data suggest that acute inflammation after blood-brain barrier leakage may contribute to gray matter cortical lesions in early multiple sclerosis. © 2018 American Academy of Neurology.

  14. Differences in bitumen and kerogen-bound fatty acid fractions during diagenesis and early catagenesis in a maturity series of New Zealand coals

    DEFF Research Database (Denmark)

    Glombitza, Clemens; Mangelsdorf, Kai; Horsfield, Brian

    2016-01-01

    Oxygen-bearing functional groups, in particular the carboxylic groups of acids and esters, are mainly responsible for the chemical reactivity of sedimentary organic matter. We have studied kerogen and bitumen fractions from a coalification series from the New Zealand Coal Band covering the rank...... range from 0.28% to 0.80% vitrinite reflectance. We investigated the composition of fatty acids separated from the bitumen, and compared this to the distribution of kerogen-bound fatty acids (esters) obtained after selective chemical degradation of the macromolecular organic matter. We found remarkable...... differences in the fatty acid composition between bitumen and kerogen-bound acids, both in the short (bitumen...

  15. Early herding practices revealed through organic residue analysis of pottery from the early Neolithic rock shelter of Mala Triglavca, Slovenia

    Directory of Open Access Journals (Sweden)

    Lucija Šoberl

    2008-12-01

    Full Text Available A collection of pottery from the early Neolithic site of Mala Triglavca was analysed with the aim of obtaining insights into vessel use and early animal domestication and husbandry practices in the Adriatic region. Total lipid extracts were submitted to gas chromatography (GC, GC-mass spectrometry (GC-MS and GC-combustion-isotope ratio MS (GC-C-IRMS in order to obtain molecular and stable carbon isotope signatures as the basis for determining the nature and origins of the residues. The extracts were dominated by degraded animal fats. The majority (70% of the total lipid extracts displayed intact triacylglycerol distributions attributable to ruminant adipose and dairy fats, which were subsequently confirmed through C16:0 and C18:0 fatty acid δ13C values.

  16. Oxygen restriction as challenge test reveals early high-fat-diet-induced changes in glucose and lipid metabolism

    NARCIS (Netherlands)

    Duivenvoorde, L.P.M.; Schothorst, van E.M.; Derous, D.; Stelt, van der I.; Masania, J.; Rabbani, N.; Thornalley, P.J.; Keijer, J.

    2015-01-01

    Challenge tests stress homeostasis and may reveal deviations in health that remain masked under unchallenged conditions. Ideally, challenge tests are non-invasive and applicable in an early phase of an animal experiment. Oxygen restriction (OxR; based on ambient, mild normobaric hypoxia) is a

  17. Altered Evoked Gamma-Band Responses Reveal Impaired Early Visual Processing in ADHD Children

    Science.gov (United States)

    Lenz, Daniel; Krauel, Kerstin; Flechtner, Hans-Henning; Schadow, Jeanette; Hinrichs, Hermann; Herrmann, Christoph S.

    2010-01-01

    Neurophysiological studies yield contrary results whether attentional problems of patients with attention-deficit/hyperactivity disorder (ADHD) are related to early visual processing deficits or not. Evoked gamma-band responses (GBRs), being among the first cortical responses occurring as early as 90 ms after visual stimulation in human EEG, have…

  18. Development of tight junctions between odontoblasts in early dentinogenesis as revealed by freeze-fracture

    OpenAIRE

    Arana-Chavez, V.E.; Katchburian, Eduardo

    1997-01-01

    Background: Mature odontoblasts possess junctional structures constituted by adherens, gap, and tight junctions. Although adherens and gap junctions appear early between odontoblasts, there is no information on the appearance and development of tight junctions between odontoblasts. in this study, we have examined freeze-fracture replicas of early dentinogenesis to study the development of tight junctions between odontoblasts and to determine whether these junctions are of zonular or macular t...

  19. Starch grains on human teeth reveal early broad crop diet in northern Peru

    OpenAIRE

    Piperno, Dolores R.; Dillehay, Tom D.

    2008-01-01

    Previous research indicates that the Ñanchoc Valley in northern Peru was an important locus of early and middle Holocene human settlement, and that between 9200 and 5500 14C yr B.P. the valley inhabitants adopted major crop plants such as squash (Cucurbita moschata), peanuts (Arachis sp.), and cotton (Gossypium barbadense). We report here an examination of starch grains preserved in the calculus of human teeth from these sites that provides direct evidence for the early consumption of cultiva...

  20. Early metal-silicate differentiation during planetesimal formation revealed by acapulcoite and lodranite meteorites

    Science.gov (United States)

    Dhaliwal, Jasmeet K.; Day, James M. D.; Corder, Christopher A.; Tait, Kim T.; Marti, Kurt; Assayag, Nelly; Cartigny, Pierre; Rumble, Doug; Taylor, Lawrence A.

    2017-11-01

    In order to establish the role and expression of silicate-metal fractionation in early planetesimal bodies, we have conducted a highly siderophile element (HSE: Os, Ir, Ru, Pt, Pd, Re) abundance and 187Re-187Os study of acapulcoite-lodranite meteorites. These data are reported with new petrography, mineral chemistry, bulk-rock major and trace element geochemistry, and oxygen isotopes for Acapulco, Allan Hills (ALHA) 81187, Meteorite Hills (MET) 01195, Northwest Africa (NWA) 2871, NWA 4833, NWA 4875, NWA 7474 and two examples of transitional acapulcoite-lodranites, Elephant Moraine (EET) 84302 and Graves Nunataks (GRA) 95209. These data support previous studies that indicate that these meteorites are linked to the same parent body and exhibit limited degrees (2 × CI chondrite) HSE abundances in transitional acapulcoite-lodranite meteorites (EET 84302, GRA 95209). All of the meteorites have chondritic Re/Os with measured 187Os/188Os ratios of 0.1271 ± 0.0040 (2 St. Dev.). These geochemical characteristics imply that the precursor material of the acapulcoites and lodranites was broadly chondritic in composition, and were then heated and subject to melting of metal and sulfide in the Fe-Ni-S system. This resulted in metallic melt removal and accumulation to form lodranites and transitional acapulcoite-lodranites. There is considerable variation in the absolute abundances of the HSE, both among samples and between aliquots of the same sample, consistent with both inhomogeneous distribution of HSE-rich metal, and of heterogeneous melting and incomplete mixing of silicate material within the acapulcoite-lodranite parent body. Oxygen isotope data for acapulcoite-lodranites are also consistent with inhomogeneous melting and mixing of accreted components from different nebular sources, and do not form a well-defined mass-dependent fractionation line. Modeling of HSE inter-element fractionation suggests a continuum of melting in the Fe-Ni-S system and partitioning between

  1. Development of tight junctions between odontoblasts in early dentinogenesis as revealed by freeze-fracture.

    Science.gov (United States)

    Arana-Chavez, V E; Katchburian, E

    1997-07-01

    Mature odontoblasts possess junctional structures constituted by adherens, gap, and tight junctions. Although adherens and gap junctions appear early between odontoblasts, there is no information on the appearance and development of tight junctions between odontoblasts. In this study, we have examined freeze-fracture replicas of early dentinogenesis to study the development of tight junctions between odontoblasts and to determine whether these junctions are of zonular or macular type. Upper first molar tooth germs of Wistar rats between 1 and 3 days old were fixed in buffered 4% glutaraldehyde/4% formaldehyde and subsequently cryoprotected with cacodylate-buffered glycerol. Freeze-fracture replicas were obtained in a Balzers 301 apparatus, and early stages of dentinogenesis were examined in a Jeol 100 CX II electron microscope. In the stage of early dentine matrix prior to mineralization, odontoblasts exhibit only gap junctions. With the progression of development, the distal plasma membranes of odontoblasts show numerous short tight junctions formed by fused particles and grooves. In the stage of advanced mineralization, branched and continuous rows of fused particles or grooves constitute tight junctions of the focal or macular type. The present study shows that tight junctions of focal or macular type appear on distal plasma membrane of early odontoblasts during differentiation. Formation of tight junctions indicates the establishment of a distal membrane domain and maturation of odontoblasts. These events occur as mantle dentine formation ceases and circumpulpar dentine formation begins.

  2. Barium distributions in teeth reveal early-life dietary transitions in primates.

    Science.gov (United States)

    Austin, Christine; Smith, Tanya M; Bradman, Asa; Hinde, Katie; Joannes-Boyau, Renaud; Bishop, David; Hare, Dominic J; Doble, Philip; Eskenazi, Brenda; Arora, Manish

    2013-06-13

    Early-life dietary transitions reflect fundamental aspects of primate evolution and are important determinants of health in contemporary human populations. Weaning is critical to developmental and reproductive rates; early weaning can have detrimental health effects but enables shorter inter-birth intervals, which influences population growth. Uncovering early-life dietary history in fossils is hampered by the absence of prospectively validated biomarkers that are not modified during fossilization. Here we show that large dietary shifts in early life manifest as compositional variations in dental tissues. Teeth from human children and captive macaques, with prospectively recorded diet histories, demonstrate that barium (Ba) distributions accurately reflect dietary transitions from the introduction of mother's milk through the weaning process. We also document dietary transitions in a Middle Palaeolithic juvenile Neanderthal, which shows a pattern of exclusive breastfeeding for seven months, followed by seven months of supplementation. After this point, Ba levels in enamel returned to baseline prenatal levels, indicating an abrupt cessation of breastfeeding at 1.2 years of age. Integration of Ba spatial distributions and histological mapping of tooth formation enables novel studies of the evolution of human life history, dietary ontogeny in wild primates, and human health investigations through accurate reconstructions of breastfeeding history.

  3. Barium distributions in teeth reveal early life dietary transitions in primates

    Science.gov (United States)

    Austin, Christine; Smith, Tanya M.; Bradman, Asa; Hinde, Katie; Joannes-Boyau, Renaud; Bishop, David; Hare, Dominic J.; Doble, Philip; Eskenazi, Brenda; Arora, Manish

    2013-01-01

    Early life dietary transitions reflect fundamental aspects of primate evolution and are important determinants of health in contemporary human populations1,2. Weaning is critical to developmental and reproductive rates; early weaning can have detrimental health effects but enables shorter inter-birth intervals, which influences population growth3. Uncovering early life dietary history in fossils is hampered by the absence of prospectively-validated biomarkers that are not modified during fossilisation4. Here we show that major dietary shifts in early life manifest as compositional variations in dental tissues. Teeth from human children and captive macaques, with prospectively-recorded diet histories, demonstrate that barium (Ba) distributions accurately reflect dietary transitions from the introduction of mother’s milk and through the weaning process. We also document transitions in a Middle Palaeolithic juvenile Neanderthal, which shows a pattern of exclusive breastfeeding for seven months, followed by seven months of supplementation. After this point, Ba levels in enamel returned to baseline prenatal levels, suggesting an abrupt cessation of breastfeeding at 1.2 years of age. Integration of Ba spatial distributions and histological mapping of tooth formation enables novel studies of the evolution of human life history, dietary ontogeny in wild primates, and human health investigations through accurate reconstructions of breastfeeding history. PMID:23698370

  4. Starch grains on human teeth reveal early broad crop diet in northern Peru.

    Science.gov (United States)

    Piperno, Dolores R; Dillehay, Tom D

    2008-12-16

    Previous research indicates that the Nanchoc Valley in northern Peru was an important locus of early and middle Holocene human settlement, and that between 9200 and 5500 (14)C yr B.P. the valley inhabitants adopted major crop plants such as squash (Cucurbita moschata), peanuts (Arachis sp.), and cotton (Gossypium barbadense). We report here an examination of starch grains preserved in the calculus of human teeth from these sites that provides direct evidence for the early consumption of cultivated squash and peanuts along with two other major food plants not previously detected. Starch from the seeds of Phaseolus and Inga feuillei, the flesh of Cucurbita moschata fruits, and the nuts of Arachis was routinely present on numerous teeth that date to between 8210 and 6970 (14)C yr B.P. Early plant diets appear to have been diverse and stable through time and were rich in cultivated foods typical of later Andean agriculture. Our data provide early archaeological evidence for Phaseolus beans and I. feuillei, an important tree crop, and indicate that effective food production systems that contributed significant dietary inputs were present in the Nanchoc region by 8000 (14)C yr B.P. Starch grain studies of dental remains document plants and edible parts of them not normally preserved in archaeological records and can assume primary roles as direct indicators of ancient human diets and agriculture.

  5. Dynamic locomotor capabilities revealed by early dinosaur trackmakers from southern Africa.

    Directory of Open Access Journals (Sweden)

    Jeffrey A Wilson

    Full Text Available BACKGROUND: A new investigation of the sedimentology and ichnology of the Early Jurassic Moyeni tracksite in Lesotho, southern Africa has yielded new insights into the behavior and locomotor dynamics of early dinosaurs. METHODOLOGY/PRINCIPAL FINDINGS: The tracksite is an ancient point bar preserving a heterogeneous substrate of varied consistency and inclination that includes a ripple-marked riverbed, a bar slope, and a stable algal-matted bar top surface. Several basal ornithischian dinosaurs and a single theropod dinosaur crossed its surface within days or perhaps weeks of one another, but responded to substrate heterogeneity differently. Whereas the theropod trackmaker accommodated sloping and slippery surfaces by gripping the substrate with its pedal claws, the basal ornithischian trackmakers adjusted to the terrain by changing between quadrupedal and bipedal stance, wide and narrow gauge limb support (abduction range = 31 degrees , and plantigrade and digitigrade foot posture. CONCLUSIONS/SIGNIFICANCE: The locomotor adjustments coincide with changes in substrate consistency along the trackway and appear to reflect 'real time' responses to a complex terrain. It is proposed that these responses foreshadow important locomotor transformations characterizing the later evolution of the two main dinosaur lineages. Ornithischians, which shifted from bipedal to quadrupedal posture at least three times in their evolutionary history, are shown to have been capable of adopting both postures early in their evolutionary history. The substrate-gripping behavior demonstrated by the early theropod, in turn, is consistent with the hypothesized function of pedal claws in bird ancestors.

  6. Metabolomic markers reveal novel pathways of ageing and early development in human populations

    OpenAIRE

    Menni, C.; Kastenmuller, G.; Petersen, A.K.; Bell, J.T.; Psatha, M.; Tsai, P.-C.; Gieger, C.; Schulz, H.; I. Erte; John, S.; Brosnan, M J; Wilson, S. G.; Tsaprouni, L.; Lim, E. M.; Stuckey, B.

    2013-01-01

    Background Human ageing is a complex, multifactorial process and early developmental factors affect health outcomes in old age. Methods Metabolomic profiling on fasting blood was carried out in 6055 individuals from the UK. Stepwise regression was performed to identify a panel of independent metabolites which could be used as a surrogate for age. We also investigated the association with birthweight overall and within identical discordant twins and with genome-wide methylation levels. Results...

  7. Transcriptional dynamics reveal critical roles for non-coding RNAs in the immediate-early response.

    Directory of Open Access Journals (Sweden)

    Stuart Aitken

    2015-04-01

    Full Text Available The immediate-early response mediates cell fate in response to a variety of extracellular stimuli and is dysregulated in many cancers. However, the specificity of the response across stimuli and cell types, and the roles of non-coding RNAs are not well understood. Using a large collection of densely-sampled time series expression data we have examined the induction of the immediate-early response in unparalleled detail, across cell types and stimuli. We exploit cap analysis of gene expression (CAGE time series datasets to directly measure promoter activities over time. Using a novel analysis method for time series data we identify transcripts with expression patterns that closely resemble the dynamics of known immediate-early genes (IEGs and this enables a comprehensive comparative study of these genes and their chromatin state. Surprisingly, these data suggest that the earliest transcriptional responses often involve promoters generating non-coding RNAs, many of which are produced in advance of canonical protein-coding IEGs. IEGs are known to be capable of induction without de novo protein synthesis. Consistent with this, we find that the response of both protein-coding and non-coding RNA IEGs can be explained by their transcriptionally poised, permissive chromatin state prior to stimulation. We also explore the function of non-coding RNAs in the attenuation of the immediate early response in a small RNA sequencing dataset matched to the CAGE data: We identify a novel set of microRNAs responsible for the attenuation of the IEG response in an estrogen receptor positive cancer cell line. Our computational statistical method is well suited to meta-analyses as there is no requirement for transcripts to pass thresholds for significant differential expression between time points, and it is agnostic to the number of time points per dataset.

  8. Bird-Like Anatomy, Posture, and Behavior Revealed by an Early Jurassic Theropod Dinosaur Resting Trace

    OpenAIRE

    Milner, Andrew R. C.; Harris, Jerald D.; LOCKLEY,Martin G.; Kirkland, James I.; Neffra A Matthews

    2009-01-01

    BACKGROUND: Fossil tracks made by non-avian theropod dinosaurs commonly reflect the habitual bipedal stance retained in living birds. Only rarely-captured behaviors, such as crouching, might create impressions made by the hands. Such tracks provide valuable information concerning the often poorly understood functional morphology of the early theropod forelimb. METHODOLOGY/PRINCIPAL FINDINGS: Here we describe a well-preserved theropod trackway in a Lower Jurassic ( approximately 198 million-ye...

  9. The TESIS Project: Revealing Massive Early-Type Galaxies at z > 1

    Science.gov (United States)

    Saracco, P.; Longhetti, M.; Severgnini, P.; Della Ceca, R.; Braito, V.; Bender, R.; Drory, N.; Feulner, G.; Hopp, U.; Mannucci, F.; Maraston, C.

    How and when present-day massive early-type galaxies built up and what type of evolution has characterized their growth (star formation and/or merging) still remain open issues. The different competing scenarios of galaxy formation predict much different properties of early-type galaxies at z > 1. The "monolithic" collapse predicts that massive spheroids formed at high redshift (z > 2.5-3) and that their comoving density is constant at z 1, their comoving density decreases from z = 0 to z ~ 1.5 and they should experience their last burst of star formation at z 1 can be probed observationally once a well defined sample of massive early-types at z > 1 is available. We are constructing such a sample through a dedicated near-IR very low resolution (λ/Δλ≃50) spectroscopic survey (TNG EROs Spectroscopic Identification Survey, TESIS, [6]) of a complete sample of 30 bright (K < 18.5) Extremely Red Objects (EROs).

  10. Novel gene expression domains reveal early patterning of the Xenopus endoderm.

    Science.gov (United States)

    Costa, Ricardo M B; Mason, Julia; Lee, Monica; Amaya, Enrique; Zorn, Aaron M

    2003-08-01

    The endoderm gives rise the respiratory and digestive tract epithelia as well as associated organs such as the liver, lungs and pancreas. Investigations examining the molecular basis of embryonic endodermal patterning and organogenesis have been hampered by the lack of regionally expressed molecular markers in the early endoderm. By differentially screening an arrayed cDNA library, combined with an in situ hybridization screen we identified 13 new genes regionally expressed in the early tailbud endoderm of the Xenopus embryo. The putative proteins encoded by these cDNAs include a cell surface transporter, secreted proteins, a protease, a protease inhibitor, an RNA-binding protein, a phosphatase inhibitor and several enzymes. We find that the expression of these genes falls into one of three re-occurring domains in the tailbud embryo; (1). a ventral midgut, (2). posterior to the midgut and (3). in the dorsal endoderm beneath the notochord. Several of these genes are also regionally expressed at gastrula and neurula stages and appear to mark territories that were previously only predicted by the endoderm fate map. This indicates that there is significant positional identity in the early endoderm long before stages 28-32 when regional specification of the endoderm is thought to occur. These new genes provide valuable tools for studying endodermal patterning and organogenesis in Xenopus.

  11. Bird-like anatomy, posture, and behavior revealed by an early jurassic theropod dinosaur resting trace

    Science.gov (United States)

    Milner, A.R.C.; Harris, J.D.; Lockley, M.G.; Kirkland, J.I.; Matthews, N.A.

    2009-01-01

    Background: Fossil tracks made by non-avian theropod dinosaurs commonly reflect the habitual bipedal stance retained in living birds. Only rarely-captured behaviors, such as crouching, might create impressions made by the hands. Such tracks provide valuable information concerning the often poorly understood functional morphology of the early theropod forelimb. Methodology/Principal Findings: Here we describe a well-preserved theropod trackway in a Lower Jurassic (???198 millionyear- old) lacustrine beach sandstone in the Whitmore Point Member of the Moenave Formation in southwestern Utah. The trackway consists of prints of typical morphology, intermittent tail drags and, unusually, traces made by the animal resting on the substrate in a posture very similar to modern birds. The resting trace includes symmetrical pes impressions and well-defined impressions made by both hands, the tail, and the ischial callosity. Conclusions/Significance: The manus impressions corroborate that early theropods, like later birds, held their palms facing medially, in contrast to manus prints previously attributed to theropods that have forward-pointing digits. Both the symmetrical resting posture and the medially-facing palms therefore evolved by the Early Jurassic, much earlier in the theropod lineage than previously recognized, and may characterize all theropods.

  12. Bird-like anatomy, posture, and behavior revealed by an early jurassic theropod dinosaur resting trace.

    Directory of Open Access Journals (Sweden)

    Andrew R C Milner

    Full Text Available BACKGROUND: Fossil tracks made by non-avian theropod dinosaurs commonly reflect the habitual bipedal stance retained in living birds. Only rarely-captured behaviors, such as crouching, might create impressions made by the hands. Such tracks provide valuable information concerning the often poorly understood functional morphology of the early theropod forelimb. METHODOLOGY/PRINCIPAL FINDINGS: Here we describe a well-preserved theropod trackway in a Lower Jurassic ( approximately 198 million-year-old lacustrine beach sandstone in the Whitmore Point Member of the Moenave Formation in southwestern Utah. The trackway consists of prints of typical morphology, intermittent tail drags and, unusually, traces made by the animal resting on the substrate in a posture very similar to modern birds. The resting trace includes symmetrical pes impressions and well-defined impressions made by both hands, the tail, and the ischial callosity. CONCLUSIONS/SIGNIFICANCE: The manus impressions corroborate that early theropods, like later birds, held their palms facing medially, in contrast to manus prints previously attributed to theropods that have forward-pointing digits. Both the symmetrical resting posture and the medially-facing palms therefore evolved by the Early Jurassic, much earlier in the theropod lineage than previously recognized, and may characterize all theropods.

  13. Bird-like anatomy, posture, and behavior revealed by an early jurassic theropod dinosaur resting trace.

    Science.gov (United States)

    Milner, Andrew R C; Harris, Jerald D; Lockley, Martin G; Kirkland, James I; Matthews, Neffra A

    2009-01-01

    Fossil tracks made by non-avian theropod dinosaurs commonly reflect the habitual bipedal stance retained in living birds. Only rarely-captured behaviors, such as crouching, might create impressions made by the hands. Such tracks provide valuable information concerning the often poorly understood functional morphology of the early theropod forelimb. Here we describe a well-preserved theropod trackway in a Lower Jurassic ( approximately 198 million-year-old) lacustrine beach sandstone in the Whitmore Point Member of the Moenave Formation in southwestern Utah. The trackway consists of prints of typical morphology, intermittent tail drags and, unusually, traces made by the animal resting on the substrate in a posture very similar to modern birds. The resting trace includes symmetrical pes impressions and well-defined impressions made by both hands, the tail, and the ischial callosity. The manus impressions corroborate that early theropods, like later birds, held their palms facing medially, in contrast to manus prints previously attributed to theropods that have forward-pointing digits. Both the symmetrical resting posture and the medially-facing palms therefore evolved by the Early Jurassic, much earlier in the theropod lineage than previously recognized, and may characterize all theropods.

  14. Aerodynamic modelling of a Cretaceous bird reveals thermal soaring capabilities during early avian evolution.

    Science.gov (United States)

    Serrano, Francisco José; Chiappe, Luis María

    2017-07-01

    Several flight modes are thought to have evolved during the early evolution of birds. Here, we use a combination of computational modelling and morphofunctional analyses to infer the flight properties of the raven-sized, Early Cretaceous bird Sapeornis chaoyangensis-a likely candidate to have evolved soaring capabilities. Specifically, drawing information from (i) mechanical inferences of the deltopectoral crest of the humerus, (ii) wing shape (i.e. aspect ratio), (iii) estimations of power margin (i.e. difference between power required for flight and available power from muscles), (iv) gliding behaviour (i.e. forward speed and sinking speed), and (v) palaeobiological evidence, we conclude that S. chaoyangensis was a thermal soarer with an ecology similar to that of living South American screamers. Our results indicate that as early as 125 Ma, some birds evolved the morphological and aerodynamic requirements for soaring on continental thermals, a conclusion that highlights the degree of ecological, functional and behavioural diversity that resulted from the first major evolutionary radiation of birds. © 2017 The Author(s).

  15. Lipidomics reveals early metabolic changes in subjects with schizophrenia: effects of atypical antipsychotics.

    Directory of Open Access Journals (Sweden)

    Joseph McEvoy

    Full Text Available There is a critical need for mapping early metabolic changes in schizophrenia to capture failures in regulation of biochemical pathways and networks. This information could provide valuable insights about disease mechanisms, trajectory of disease progression, and diagnostic biomarkers. We used a lipidomics platform to measure individual lipid species in 20 drug-naïve patients with a first episode of schizophrenia (FE group, 20 patients with chronic schizophrenia that had not adhered to prescribed medications (RE group, and 29 race-matched control subjects without schizophrenia. Lipid metabolic profiles were evaluated and compared between study groups and within groups before and after treatment with atypical antipsychotics, risperidone and aripiprazole. Finally, we mapped lipid profiles to n3 and n6 fatty acid synthesis pathways to elucidate which enzymes might be affected by disease and treatment. Compared to controls, the FE group showed significant down-regulation of several n3 polyunsaturated fatty acids (PUFAs, including 20:5n3, 22:5n3, and 22:6n3 within the phosphatidylcholine and phosphatidylethanolamine lipid classes. Differences between FE and controls were only observed in the n3 class PUFAs; no differences where noted in n6 class PUFAs. The RE group was not significantly different from controls, although some compositional differences within PUFAs were noted. Drug treatment was able to correct the aberrant PUFA levels noted in FE patients, but changes in re patients were not corrective. Treatment caused increases in both n3 and n6 class lipids. These results supported the hypothesis that phospholipid n3 fatty acid deficits are present early in the course of schizophrenia and tend not to persist throughout its course. These changes in lipid metabolism could indicate a metabolic vulnerability in patients with schizophrenia that occurs early in development of the disease.

  16. Bound states and the Bekenstein bound

    Energy Technology Data Exchange (ETDEWEB)

    Bousso, Raphael

    2003-10-16

    We explore the validity of the generalized Bekenstein bound, S<= pi M a. We define the entropy S as the logarithm of the number of states which have energy eigenvalue below M and are localized to a flat space region of width alpha. If boundary conditions that localize field modes are imposed by fiat, then the bound encounters well-known difficulties with negative Casimir energy and large species number, as well as novel problems arising only in the generalized form. In realistic systems, however, finite-size effects contribute additional energy. We study two different models for estimating such contributions. Our analysis suggests that the bound is both valid and nontrivial if interactions are properly included, so that the entropy S counts the bound states of interacting fields.

  17. Synchrotron Reveals Early Triassic Odd Couple: Injured Amphibian and Aestivating Therapsid Share Burrow.

    Science.gov (United States)

    Fernandez, Vincent; Abdala, Fernando; Carlson, Kristian J; Cook, Della Collins; Rubidge, Bruce S; Yates, Adam; Tafforeau, Paul

    2013-01-01

    Fossorialism is a beneficial adaptation for brooding, predator avoidance and protection from extreme climate. The abundance of fossilised burrow casts from the Early Triassic of southern Africa is viewed as a behavioural response by many tetrapods to the harsh conditions following the Permo-Triassic mass-extinction event. However, scarcity of vertebrate remains associated with these burrows leaves many ecological questions unanswered. Synchrotron scanning of a lithified burrow cast from the Early Triassic of the Karoo unveiled a unique mixed-species association: an injured temnospondyl amphibian (Broomistega) that sheltered in a burrow occupied by an aestivating therapsid (Thrinaxodon). The discovery of this rare rhinesuchid represents the first occurrence in the fossil record of a temnospondyl in a burrow. The amphibian skeleton shows signs of a crushing trauma with partially healed fractures on several consecutive ribs. The presence of a relatively large intruder in what is interpreted to be a Thrinaxodon burrow implies that the therapsid tolerated the amphibian's presence. Among possible explanations for such unlikely cohabitation, Thrinaxodon aestivation is most plausible, an interpretation supported by the numerous Thrinaxodon specimens fossilised in curled-up postures. Recent advances in synchrotron imaging have enabled visualization of the contents of burrow casts, thus providing a novel tool to elucidate not only anatomy but also ecology and biology of ancient tetrapods.

  18. Turning visual shapes into sounds: early stages of reading acquisition revealed in the ventral occipitotemporal cortex.

    Science.gov (United States)

    Perrone-Bertolotti, M; Vidal, J R; de Palma, L; Hamamé, C M; Ossandon, T; Kahane, P; Minotti, L; Bertrand, O; Lachaux, J-P

    2014-04-15

    The exact role of the left ventral occipitotemporal cortex (VOTC) during the initial stages of reading acquisition is a hotly debated issue, especially regarding the comparative effect of learning on early stimulus-dependent vs. later task-dependent processes. We show that this controversy can be solved with high-temporal resolution intracerebral EEG recordings of the VOTC. We measured High-Frequency Activity (50-150 Hz) as a proxy of population-level spiking activity while participants learned Japanese Katakana symbols, and found that learning primarily affects top-down/task-dependent neural processing, after a few minutes only. In contrast, adaptation of early bottom-up/stimulus-dependent processing takes several days to adapt and provides the basis for fluent reading. Such evidence that two consecutive stages of neural processing, stimulus- and task-dependent are differentially affected by learning, can reconcile seemingly opposite hypotheses on the role of the VOTC during reading acquisition. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Starch grains reveal early root crop horticulture in the Panamanian tropical forest.

    Science.gov (United States)

    Piperno, D R; Ranere, A J; Holst, I; Hansell, P

    2000-10-19

    Native American populations are known to have cultivated a large number of plants and domesticated them for their starch-rich underground organs. Suggestions that the likely source of many of these crops, the tropical forest, was an early and influential centre of plant husbandry have long been controversial because the organic remains of roots and tubers are poorly preserved in archaeological sediments from the humid tropics. Here we report the occurrence of starch grains identifiable as manioc (Manihot esculenta Crantz), yams (Dioscorea sp.) and arrowroot (Maranta arundinacea L.) on assemblages of plant milling stones from preceramic horizons at the Aguadulce Shelter, Panama, dated between 7,000 and 5,000 years before present (BP). The artefacts also contain maize starch (Zea mays L.), indicating that early horticultural systems in this region were mixtures of root and seed crops. The data provide the earliest direct evidence for root crop cultivation in the Americas, and support an ancient and independent emergence of plant domestication in the lowland Neotropical forest.

  20. Immediate relativity: EEG reveals early engagement of comparison in social information processing.

    Science.gov (United States)

    Ohmann, Katharina; Stahl, Jutta; Mussweiler, Thomas; Kedia, Gayannée

    2016-11-01

    A wide array of social decisions relies on social comparisons. As such, these decisions require fast access to relative information. Therefore, we expect that signatures of the comparative process should be observable in electrophysiological components at an early stage of information processing. However, to date, little is known about the neural time course of social target comparisons. Therefore, we tested this hypothesis in 2 electroencephalography (EEG) studies using a social distance effect paradigm. The distance effect capitalizes on the fact that stimuli close on a certain dimension take longer to compare than stimuli clearly differing on this dimension. Here, we manipulated the distance of face characteristics regarding their levels of attractiveness (Study 1) and trustworthiness (Study 2), 2 essential social dimensions. In both studies, size comparisons served as a nonsocial control condition. In Study 1, distance related effects were apparent 170 ms (vertex positive potential, VPP) and 200 ms (N2) after stimulus onset for attractiveness comparisons. In Study 2, trustworthiness comparisons took effect already after 100 ms (N1) and likewise carried over to an event-related N2. Remarkably, we observed a similar temporal pattern for social (attractiveness, trustworthiness) and nonsocial (size) dimensions. These results speak in favor of an early encoding of comparative information and emphasize the primary role of comparison in social information processing. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  1. Space-bounded communication complexity

    DEFF Research Database (Denmark)

    Brody, Joshua Eric; Chen, Shiteng; Papakonstantinou, Periklis A.

    2013-01-01

    -obliviousness shows up. For this model we also introduce new techniques through which certain limitations of space-bounded computation are revealed. One of the main motivations of this work is in understanding the difference in the use of space when computing the following functions: Equality (EQ), Inner Product (IP......In the past thirty years, Communication Complexity has emerged as a foundational tool to proving lower bounds in many areas of computer science. Its power comes from its generality, but this generality comes at a price---no superlinear communication lower bound is possible, since a player may...... communicate his entire input. However, what if the players are limited in their ability to recall parts of their interaction? We introduce memory models for 2-party communication complexity. Our general model is as follows: two computationally unrestricted players, Alice and Bob, each have s(n) bits of memory...

  2. Integration of Metabolomics and Transcriptomics Reveals a Complex Diet of Mycobacterium tuberculosis during Early Macrophage Infection.

    Science.gov (United States)

    Zimmermann, Michael; Kogadeeva, Maria; Gengenbacher, Martin; McEwen, Gayle; Mollenkopf, Hans-Joachim; Zamboni, Nicola; Kaufmann, Stefan Hugo Ernst; Sauer, Uwe

    2017-01-01

    Nutrient acquisition from the host environment is crucial for the survival of intracellular pathogens, but conceptual and technical challenges limit our knowledge of pathogen diets. To overcome some of these technical roadblocks, we exploited an experimentally accessible model for early infection of human macrophages by Mycobacterium tuberculosis, the etiological agent of tuberculosis, to study host-pathogen interactions with a multi-omics approach. We collected metabolomics and complete transcriptome RNA sequencing (dual RNA-seq) data of the infected macrophages, integrated them in a genome-wide reaction pair network, and identified metabolic subnetworks in host cells and M. tuberculosis that are modularly regulated during infection. Up- and downregulation of these metabolic subnetworks suggested that the pathogen utilizes a wide range of host-derived compounds, concomitant with the measured metabolic and transcriptional changes in both bacteria and host. To quantify metabolic interactions between the host and intracellular pathogen, we used a combined genome-scale model of macrophage and M. tuberculosis metabolism constrained by the dual RNA-seq data. Metabolic flux balance analysis predicted coutilization of a total of 33 different carbon sources and enabled us to distinguish between the pathogen's substrates directly used as biomass precursors and the ones further metabolized to gain energy or to synthesize building blocks. This multiple-substrate fueling confers high robustness to interventions with the pathogen's metabolism. The presented approach combining multi-omics data as a starting point to simulate system-wide host-pathogen metabolic interactions is a useful tool to better understand the intracellular lifestyle of pathogens and their metabolic robustness and resistance to metabolic interventions. IMPORTANCE The nutrients consumed by intracellular pathogens are mostly unknown. This is mainly due to the challenge of disentangling host and pathogen

  3. The behavior of larval zebrafish reveals stressor-mediated anorexia during early vertebrate development

    Science.gov (United States)

    De Marco, Rodrigo J.; Groneberg, Antonia H.; Yeh, Chen-Min; Treviño, Mario; Ryu, Soojin

    2014-01-01

    The relationship between stress and food consumption has been well documented in adults but less so in developing vertebrates. Here we demonstrate that an encounter with a stressor can suppress food consumption in larval zebrafish. Furthermore, we provide indication that food intake suppression cannot be accounted for by changes in locomotion, oxygen consumption and visual responses, as they remain unaffected after exposure to a potent stressor. We also show that feeding reoccurs when basal levels of cortisol (stress hormone in humans and teleosts) are re-established. The results present evidence that the onset of stress can switch off the drive for feeding very early in vertebrate development, and add a novel endpoint for analyses of metabolic and behavioral disorders in an organism suitable for high-throughput genetics and non-invasive brain imaging. PMID:25368561

  4. The behaviour of larval zebrafish reveals stress-mediated anorexia during early development

    Directory of Open Access Journals (Sweden)

    Rodrigo eDe Marco

    2014-10-01

    Full Text Available The relationship between stress and food consumption has been well documented in adults but less so in developing vertebrates. Here we demonstrate that an encounter with a stressor can suppress food consumption in larval zebrafish. Furthermore, we provide indication that food intake suppression cannot be accounted for by changes in locomotion, oxygen consumption and visual responses, as they remain unaffected after exposure to a potent stressor. We also show that feeding reoccurs when basal levels of cortisol (stress hormone in humans and teleosts are re-established. The results present evidence that the onset of stress can switch off the drive for feeding very early in vertebrate development, and add a novel endpoint for analyses of metabolic and behavioral disorders in an organism suitable for high-throughput genetics and non-invasive brain imaging.

  5. Early Gene Expression in Wounded Human Keratinocytes Revealed by DNA Microarray Analysis

    Directory of Open Access Journals (Sweden)

    Pascal Barbry

    2006-04-01

    Full Text Available Wound healing involves several steps: spreading of the cells, migration and proliferation. We have profiled gene expression during the early events of wound healing in normal human keratinocytes with a home-made DNA microarray containing about 1000 relevant human probes. An original wounding machine was used, that allows the wounding of up to 40% of the surface of a confluent monolayer of cultured cells grown on a Petri dish (compared with 5% with a classical ‘scratch’ method. The two aims of the present study were: (a to validate a limited number of genes by comparing the expression levels obtained with this technique with those found in the literature; (b to combine the use of the wounding machine with DNA microarray analysis for large-scale detection of the molecular events triggered during the early stages of the wound-healing process. The time-courses of RNA expression observed at 0.5, 1.5, 3, 6 and 15 h after wounding for genes such as c-Fos, c-Jun, Egr1, the plasminogen activator PLAU (uPA and the signal transducer and transcription activator STAT3, were consistent with previously published data. This suggests that our methodologies are able to perform quantitative measurement of gene expression. Transcripts encoding two zinc finger proteins, ZFP36 and ZNF161, and the tumour necrosis factor α-induced protein TNFAIP3, were also overexpressed after wounding. The role of the p38 mitogen-activated protein kinase (p38MAPK in wound healing was shown after the inhibition of p38 by SB203580, but our results also suggest the existence of surrogate activating pathways.

  6. Functional characterization of chitinase-3 reveals involvement of chitinases in early embryo immunity in zebrafish.

    Science.gov (United States)

    Teng, Zinan; Sun, Chen; Liu, Shousheng; Wang, Hongmiao; Zhang, Shicui

    2014-10-01

    The function and mechanism of chitinases in early embryonic development remain largely unknown. We show here that recombinant chitinase-3 (rChi3) is able to hydrolyze the artificial chitin substrate, 4-methylumbelliferyl-β-D-N,N',N″-triacetylchitotrioside, and to bind to and inhibit the growth of the fungus Candida albicans, implicating that Chi3 plays a dual function in innate immunity and chitin-bearing food digestion in zebrafish. This is further corroborated by the expression profile of Chi3 in the liver and gut, which are both immune- and digestion-relevant organs. Compared with rChi3, rChi3-CD lacking CBD still retains partial capacity to bind to C. albicans, but its enzymatic and antifungal activities are significantly reduced. By contrast, rChi3-E140N with the putative catalytic residue E140 mutated shows little affinity to chitin, and its enzymatic and antifungal activities are nearly completely lost. These suggest that both enzymatic and antifungal activities of Chi3 are dependent on the presence of CBD and E140. We also clearly demonstrate that in zebrafish, both the embryo extract and the developing embryo display antifungal activity against C. albicans, and all the findings point to chitinase-3 (Chi3) being a newly-identified factor involved in the antifungal activity. Taken together, a dual function in both innate immunity and food digestion in embryo is proposed for zebrafish Chi3. It also provides a new angle to understand the immune role of chitinases in early embryonic development of animals. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Exploring white matter microstructure and olfaction dysfunction in early parkinson disease: diffusion MRI reveals new insight.

    Science.gov (United States)

    Sobhani, Soheila; Rahmani, Farzaneh; Aarabi, Mohammad Hadi; Sadr, Alireza Vafaei

    2017-11-13

    Olfaction dysfunction is considered as a robust marker of prodromal Parkinson disease (PD). Measurement of olfaction function as a screening test is unsatisfactory due to long lead time interval and low specificity for detection of PD. Use of imaging markers might yield more accurate predictive values and provide bases for combined use of imaging and clinical markers for early PD. Diffusion MRI connectometry was conducted on 85 de novo PD patients in and 36 healthy controls to find: first, white matter tracts with significant difference in quantitative anisotropy between PD groups with various degrees of olfaction dysfunction and second, second fibers with correlation with University of Pennsylvania Smell Identification Test (UPSIT) score in each group using a multiple regression analysis considering age, sex, GDS and MoCA score. Local connectomes were determined in seven of all the possible comparisons, correcting for false discovery rate (FDR). PD patients with anosmia and normal olfaction had the highest number of fibers with decreased connectivity in left inferior longitudinal fasciculus, bilateral fornix, bilateral middle cerebellar peduncle (MCP), bilateral cingulum, bilateral corticospinal tract (CST) and body, genu and splenium of corpus callosum (CC) (FDR = 0.0013). In multiple regression analysis, connectivity in the body, genu and splenium of CC and bilateral fornix had significant negative correlation (FDR between 0.019 and 0.083), and bilateral cingulum and MCP had significant positive correlation (FDR between 0.022 and 0.092) with UPSIT score. White matter connectivity in healthy controls could not be predicted by UPSIT score using the same model. The results of this study provide compelling evidence that microstructural degenerative changes in these areas underlie the clinical phenotype of prodromal olfaction dysfunction in PD and that diffusion parameters of these areas might be able to serve as signature markers for early detection of PD. This

  8. Early Eurasian migration traces in the Tarim Basin revealed by mtDNA polymorphisms.

    Science.gov (United States)

    Cui, Yinqiu; Li, Chunxiang; Gao, Shizhu; Xie, Chengzhi; Zhou, Hui

    2010-08-01

    The mitochondrial DNA (mtDNA) polymorphisms of 58 samples from the Daheyan village located in the central Taklamakan Desert of the Tarim Basin were determined in this study. Among the 58 samples, 29 haplotypes belonging to 18 different haplogroups were analyzed. Almost all the mtDNAs belong to a subset of either the defined Western or Eastern Eurasian pool. Extensive Eastern Eurasian lineages exist in the Daheyan population in which Northern-prevalent haplogroups present higher frequencies. In the limited existing Western Eurasian lineages, two sub-haplogroups, U3 and X2, that are rare in Central Asia were found in this study, which may be indicative of the remnants of an early immigrant population from the Near East and Caucasus regions preserved only in the Tarim Basin. The presence of U3 in modern and archeological samples in the Tarim Basin suggests that the immigration took place earlier than 2,000 years ago and points to human continuity in this area, with at least one Western lineage originating from the Near East and Caucasus regions. Copyright 2010 Wiley-Liss, Inc.

  9. Towards a molecular phylogeny of Mollusks: bivalves' early evolution as revealed by mitochondrial genes.

    Science.gov (United States)

    Plazzi, Federico; Passamonti, Marco

    2010-11-01

    Despite huge fossil, morphological and molecular data, bivalves' early evolutionary history is still a matter of debate: recently, established phylogeny has been mostly challenged by DNA studies, and little agreement has been reached in literature, because of a substantial lack of widely-accepted methodological approaches to retrieve and analyze bivalves' molecular data. Here we present a molecular phylogeny of the class based on four mitochondrial genes (12s, 16s, cox1, cytb) and a methodological pipeline that proved to be useful to obtain robust results. Actually, best-performing taxon sampling and alignment strategies were tested, and several data partitioning and molecular evolution models were analyzed, thus demonstrating the utility of Bayesian inference and the importance of molding and implementing non-trivial evolutionary models. Therefore, our analysis allowed to target many taxonomic questions of Bivalvia, and to obtain a complete time calibration of the tree depicting bivalves' earlier natural history main events, which mostly dated in the late Cambrian. Copyright © 2010. Published by Elsevier Inc.

  10. Multiplex lexical networks reveal patterns in early word acquisition in children

    Science.gov (United States)

    Stella, Massimo; Beckage, Nicole M.; Brede, Markus

    2017-04-01

    Network models of language have provided a way of linking cognitive processes to language structure. However, current approaches focus only on one linguistic relationship at a time, missing the complex multi-relational nature of language. In this work, we overcome this limitation by modelling the mental lexicon of English-speaking toddlers as a multiplex lexical network, i.e. a multi-layered network where N = 529 words/nodes are connected according to four relationship: (i) free association, (ii) feature sharing, (iii) co-occurrence, and (iv) phonological similarity. We investigate the topology of the resulting multiplex and then proceed to evaluate single layers and the full multiplex structure on their ability to predict empirically observed age of acquisition data of English speaking toddlers. We find that the multiplex topology is an important proxy of the cognitive processes of acquisition, capable of capturing emergent lexicon structure. In fact, we show that the multiplex structure is fundamentally more powerful than individual layers in predicting the ordering with which words are acquired. Furthermore, multiplex analysis allows for a quantification of distinct phases of lexical acquisition in early learners: while initially all the multiplex layers contribute to word learning, after about month 23 free associations take the lead in driving word acquisition.

  11. Timing of early activity in the visual cortex as revealed by simultaneous MEG and ERG recordings.

    Science.gov (United States)

    Inui, Koji; Sannan, Hiromi; Miki, Kensaku; Kaneoke, Yoshiki; Kakigi, Ryusuke

    2006-03-01

    To clarify the latency of the earliest cortical activity in visual processing, electroretinograms (ERGs) and visual evoked magnetic fields (VEFs) following flash stimulation were recorded simultaneously in six human subjects. Flash stimuli were applied to the right eye and ERGs were recorded from a skin electrode placed on the lower lid. ERGs showed two major deflections in all subjects: an eyelid-negativity around 20 ms and a positivity around 60 ms corresponding to an a- and b-waves, respectively. The mean onset and peak latency of the earliest component of VEFs (37 M) was 30.2 and 36.9 ms, respectively. There was a linear correlation between the peak latency of the a-wave and the onset latency of the 37 M (r=0.90, P=0.011). When a single equivalent current dipole analysis was applied to the 37 M, four out of six subjects showed highly reliable results. The generator of the 37 M was estimated to be located in the striate cortex in all four subjects. Since post-receptoral activities in the retina are expected to start around the peak of the a-wave (20 ms), the early cortical activity, which appears 10 ms later than the a-wave peak, is considered to be the earliest cortical activity following flash stimulation.

  12. PET and MRI reveal early evidence of neurodegeneration in spinocerebellar ataxia type 17.

    Science.gov (United States)

    Brockmann, Kathrin; Reimold, Matthias; Globas, Christoph; Hauser, Till Karsten; Walter, Uwe; Machulla, Hans-Jürgen; Rolfs, Arndt; Schöls, Ludger

    2012-07-01

    Spinocerebellar ataxia type 17 (SCA17) is a rare autosomal dominantly inherited neurodegenerative disorder presenting with a variable phenotype including ataxia, dystonia, chorea, and parkinsonism, as well as cognitive impairment. We evaluated morphologic and functional imaging characteristics to elucidate evidence of neurodegeneration in SCA17, even in the presymptomatic stage of the disease. Nine individuals of 3 large SCA17 pedigrees, including 4 presymptomatic mutation carriers, underwent cranial 3-dimensional MRI volumetry, as well as multitracer PET with (18)F-FDG, (11)C-d-threo-methylphenidate, and (11)C-raclopride. Healthy subjects showing no signs of a neurologic or psychiatric disease served as controls. MRI volumetry revealed atrophy of the cerebellum and caudate nucleus in manifesting patients (P = 0.04 and 0.05, respectively) and in presymptomatic mutation carriers (P = 0.04 and 0.01, respectively). PET demonstrated decreased glucose metabolism in the striatum, as well as in the cuneus, cingulum, and parietal lobe, in all SCA17 patients and presymptomatic mutation carriers. In addition, PET was closely correlated with motor performance as assessed by the Scale for the Assessment and Rating of Ataxia (P = 0.037) and Unified Parkinson Disease Rating Scale (P = 0.05) and with cognitive function as assessed by the Mini-Mental Status Examination (P = 0.037). Furthermore, (11)C-raclopride PET showed impairment of the postsynaptic dopaminergic compartment of the putamen and caudate nucleus not only in manifest SCA17 patients (P = 0.04 and 0.008, respectively) but also in yet-unaffected mutation carriers (P = 0.05 and 0.05, respectively). The degree of postsynaptic dopaminergic dysfunction was associated with impairment of motor performance. In contrast, significant presynaptic dopaminergic deficits assessed with (11)C-d-threo-methylphenidate PET were not detected. MRI volumetry, as well as (11)C-raclopride and (18)F-FDG PET, reveal neuronal dysfunction and

  13. Comparative Genomics of Early-Diverging Brucella Strains Reveals a Novel Lipopolysaccharide Biosynthesis Pathway

    Science.gov (United States)

    Wattam, Alice R.; Inzana, Thomas J.; Williams, Kelly P.; Mane, Shrinivasrao P.; Shukla, Maulik; Almeida, Nalvo F.; Dickerman, Allan W.; Mason, Steven; Moriyón, Ignacio; O’Callaghan, David; Whatmore, Adrian M.; Sobral, Bruno W.; Tiller, Rebekah V.; Hoffmaster, Alex R.; Frace, Michael A.; De Castro, Cristina; Molinaro, Antonio; Boyle, Stephen M.; De, Barun K.; Setubal, João C.

    2012-01-01

    ABSTRACT Brucella species are Gram-negative bacteria that infect mammals. Recently, two unusual strains (Brucella inopinata BO1T and B. inopinata-like BO2) have been isolated from human patients, and their similarity to some atypical brucellae isolated from Australian native rodent species was noted. Here we present a phylogenomic analysis of the draft genome sequences of BO1T and BO2 and of the Australian rodent strains 83-13 and NF2653 that shows that they form two groups well separated from the other sequenced Brucella spp. Several important differences were noted. Both BO1T and BO2 did not agglutinate significantly when live or inactivated cells were exposed to monospecific A and M antisera against O-side chain sugars composed of N-formyl-perosamine. While BO1T maintained the genes required to synthesize a typical Brucella O-antigen, BO2 lacked many of these genes but still produced a smooth LPS (lipopolysaccharide). Most missing genes were found in the wbk region involved in O-antigen synthesis in classic smooth Brucella spp. In their place, BO2 carries four genes that other bacteria use for making a rhamnose-based O-antigen. Electrophoretic, immunoblot, and chemical analyses showed that BO2 carries an antigenically different O-antigen made of repeating hexose-rich oligosaccharide units that made the LPS water-soluble, which contrasts with the homopolymeric O-antigen of other smooth brucellae that have a phenol-soluble LPS. The results demonstrate the existence of a group of early-diverging brucellae with traits that depart significantly from those of the Brucella species described thus far. PMID:22930339

  14. Charcoal reflectance reveals early holocene boreal deciduous forests burned at high intensities.

    Science.gov (United States)

    Hudspith, Victoria A; Belcher, Claire M; Kelly, Ryan; Hu, Feng Sheng

    2015-01-01

    Wildfire size, frequency, and severity are increasing in the Alaskan boreal forest in response to climate warming. One of the potential impacts of this changing fire regime is the alteration of successional trajectories, from black spruce to mixed stands dominated by aspen, a vegetation composition not experienced since the early Holocene. Such changes in vegetation composition may consequently alter the intensity of fires, influencing fire feedbacks to the ecosystem. Paleorecords document past wildfire-vegetation dynamics and as such, are imperative for our understanding of how these ecosystems will respond to future climate warming. For the first time, we have used reflectance measurements of macroscopic charcoal particles (>180μm) from an Alaskan lake-sediment record to estimate ancient charring temperatures (termed pyrolysis intensity). We demonstrate that pyrolysis intensity increased markedly from an interval of birch tundra 11 ky ago (mean 1.52%Ro; 485°C), to the expansion of trees on the landscape ~10.5 ky ago, remaining high to the present (mean 3.54%Ro; 640°C) irrespective of stand composition. Despite differing flammabilities and adaptations to fire, the highest pyrolysis intensities derive from two intervals with distinct vegetation compositions. 1) the expansion of mixed aspen and spruce woodland at 10 cal. kyr BP, and 2) the establishment of black spruce, and the modern boreal forest at 4 cal. kyr BP. Based on our analysis, we infer that predicted expansion of deciduous trees into the boreal forest in the future could lead to high intensity, but low severity fires, potentially moderating future climate-fire feedbacks.

  15. Charcoal reflectance reveals early holocene boreal deciduous forests burned at high intensities.

    Directory of Open Access Journals (Sweden)

    Victoria A Hudspith

    Full Text Available Wildfire size, frequency, and severity are increasing in the Alaskan boreal forest in response to climate warming. One of the potential impacts of this changing fire regime is the alteration of successional trajectories, from black spruce to mixed stands dominated by aspen, a vegetation composition not experienced since the early Holocene. Such changes in vegetation composition may consequently alter the intensity of fires, influencing fire feedbacks to the ecosystem. Paleorecords document past wildfire-vegetation dynamics and as such, are imperative for our understanding of how these ecosystems will respond to future climate warming. For the first time, we have used reflectance measurements of macroscopic charcoal particles (>180μm from an Alaskan lake-sediment record to estimate ancient charring temperatures (termed pyrolysis intensity. We demonstrate that pyrolysis intensity increased markedly from an interval of birch tundra 11 ky ago (mean 1.52%Ro; 485°C, to the expansion of trees on the landscape ~10.5 ky ago, remaining high to the present (mean 3.54%Ro; 640°C irrespective of stand composition. Despite differing flammabilities and adaptations to fire, the highest pyrolysis intensities derive from two intervals with distinct vegetation compositions. 1 the expansion of mixed aspen and spruce woodland at 10 cal. kyr BP, and 2 the establishment of black spruce, and the modern boreal forest at 4 cal. kyr BP. Based on our analysis, we infer that predicted expansion of deciduous trees into the boreal forest in the future could lead to high intensity, but low severity fires, potentially moderating future climate-fire feedbacks.

  16. Ultrastructure of stomatal development in early-divergent angiosperms reveals contrasting patterning and pre-patterning

    Science.gov (United States)

    Rudall, Paula J.; Knowles, Emma V. W.

    2013-01-01

    Background and Aims Angiosperm stomata consistently possess a pair of guard cells, but differ between taxa in the patterning and developmental origin of neighbour cells. Developmental studies of phylogenetically pivotal taxa are essential as comparative yardsticks for understanding the evolution of stomatal development. Methods We present a novel ultrastructural study of developing stomata in leaves of Amborella (Amborellales), Nymphaea and Cabomba (Nymphaeales), and Austrobaileya and Schisandra (Austrobaileyales), representing the three earliest-divergent lineages of extant angiosperms (the ANITA-grade). Key Results Alternative developmental pathways occur in early-divergent angiosperms, resulting partly from differences in pre-patterning and partly from the presence or absence of highly polarized (asymmetric) mitoses in the stomatal cell lineage. Amplifying divisions are absent from ANITA-grade taxa, indicating that ostensible similarities with the stomatal patterning of Arabidopsis are superficial. In Amborella, ‘squared’ pre-patterning occurs in intercostal regions, with groups of four protodermal cells typically arranged in a rectangle; most guard-mother cells are formed by asymmetric division of a precursor cell (the mesoperigenous condition) and are typically triangular or trapezoidal. In contrast, water-lily stomata are always perigenous (lacking asymmetric divisions). Austrobaileya has occasional ‘giant’ stomata. Conclusions Similar mature stomatal phenotypes can result from contrasting morphogenetic factors, although the results suggest that paracytic stomata are invariably the product of at least one asymmetric division. Loss of asymmetric divisions in stomatal development could be a significant factor in land plant evolution, with implications for the diversity of key structural and physiological pathways. PMID:23969762

  17. Phase noise reveals early category-specific modulation of the event-related potentials

    Directory of Open Access Journals (Sweden)

    Kornél eNémeth

    2014-04-01

    Full Text Available Previous studies have found that the amplitude of the early event-related potential (ERP components evoked by faces, such as N170 and P2, changes systematically as a function of noise added to the stimuli. This change has been linked to an increased perceptual processing demand and to enhanced difficulty in perceptual decision making about faces. However, to date it has not yet been tested whether noise manipulation affects the neural correlates of decisions about face and non-face stimuli similarly. To this end, we measured the event-related potentials for faces and cars at three different phase noise levels. Subjects performed the same two-alternative age-discrimination task on stimuli chosen from young-old morphing continua that were created from faces as well as cars and were calibrated to lead to similar performances at each noise-level. Adding phase noise to the stimuli reduced performance and enhanced response latency for the two categories to the same extent. Parallel to that, phase noise reduced the amplitude and prolonged the latency of the face-specific N170 component. The amplitude of the P1 showed category-specific noise dependence: it was enhanced over the right hemisphere for cars and over the left hemisphere for faces as a result of adding phase noise to the stimuli, but remained stable across noise levels for cars over the left and for faces over the right hemisphere. Moreover, noise modulation altered the category-selectivity of the N170, while the P2 ERP component, typically associated with task decision difficulty, was larger for the more noisy stimuli regardless of stimulus category. Our results suggest that the category-specificity of noise-induced modulations of ERP responses starts at around 100 ms post-stimulus.

  18. Lethality in PARP-1/Ku80 double mutant mice reveals physiologicalsynergy during early embryogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Henrie, Melinda S.; Kurimasa, Akihiro; Burma, Sandeep; Menissier-de Murcia, Josiane; de Murcia, Gilbert; Li, Gloria C.; Chen,David J.

    2002-09-24

    Ku is an abundant heterodimeric nuclear protein, consisting of 70-kDa and 86-kDa tightly associated subunits that comprise the DNA binding component of DNA-dependent protein kinase. Poly(ADP)ribose polymerase-1 (PARP-1) is a 113-kDa protein that catalyzes the synthesis of poly(ADP-ribose) on target proteins. Both Ku and PARP-1 recognize and bind to DNA ends. Ku functions in the non-homologous end joining (NHEJ) repair pathway whereas PARP-1 functions in the single strand break repair and base excision repair (BER) pathways. Recent studies have revealed that PARP-1 and Ku80 interact in vitro. To determine whether the association of PARP-1 and Ku80 has any physiological significance or synergistic function in vivo, mice lacking both PARP-1 and Ku80 were generated. The resulting offspring died during embryonic development displaying abnormalities around the gastrulation stage. In addition, PARP-1-/-Ku80-/- cultured blastocysts had an increased level of apoptosis. These data suggest that the functions of both Ku80 and PARP-1 are essential for normal embryogenesis and that a loss of genomic integrity leading to cell death through apoptosis is likely the cause of the embryonic lethality observed in these mice.

  19. Correlation of transcriptomic responses and metal bioaccumulation in Mytilus edulis L. reveals early indicators of stress

    Energy Technology Data Exchange (ETDEWEB)

    Poynton, Helen C., E-mail: helen.poynton@umb.edu; Robinson, William E.; Blalock, Bonnie J.; Hannigan, Robyn E.

    2014-10-15

    , three transcripts directly involved in the unfolded protein response (UPR) were induced in the metal treatments at 2 weeks and were further up-regulated at 4 weeks. Overall, correlation of tissue concentrations and gene expression responses indicates that as mussels accumulate higher concentrations of metals, initial stress responses are mobilized to protect tissues. However, given the role of UPR in apoptosis, it serves as an early indicator of stress, which once overwhelmed will result in adverse physiological effects.

  20. Methods of early revealing, prognosis of further course and complications of pollinosis

    Directory of Open Access Journals (Sweden)

    Chukhrienko N.D.

    2013-10-01

    Full Text Available Under our observation there were 59 patients with pollinosis – 39 females and 20 males at the age from 18 to 68 years. All patients were in the phase of disease exacerbation. General clinical symptoms were: rhinitis, conjunctivitis and bronchial spasm. The results showed that first clinical manifestations appear in persons of young age. Half of the patients had aggravated allergologic anamnesis. Taking into account that pollinosis is a typical representative of diseases having mechanism of immunoglobulin E (IgE-dependent allergic reactions of the first type, the authors have studied in detail level of IgE and its link with other factors. Practically in all patients with pollinosis level of total IgE exceeded the norm. As a result of studies performed, it was established that high IgE level, presence of phagocytosis defect and prolong duration of illness are the criteria which affect disease progress, aggravation of patients’ state, less efficacy of treatment. Due to the fact that development of bronchial obstruction and transformation of pollinosis into bronchial asthma is the most topical issue nowadays, the authors studied its link with other factors and findings. It was established that risk of pollinosis transformation into pollen bronchial asthma increases in the presence of high level of total IgE, aggravation of allergologic anamnesis, decrease of forced expiration volume (FEV, significant duration of disease course. In the course of investigation it was revealed that the highest efficacy of treatment is noted in patients receiving allergen-specific therapy; this confirms data of world scientific literature. The best treatment results are observed in pollinosis patients, with aggravated family history not in parents but in grandparents.

  1. Early post-metamorphic, Carboniferous blastoid reveals the evolution and development of the digestive system in echinoderms.

    Science.gov (United States)

    Rahman, Imran A; Waters, Johnny A; Sumrall, Colin D; Astolfo, Alberto

    2015-10-01

    Inferring the development of the earliest echinoderms is critical to uncovering the evolutionary assembly of the phylum-level body plan but has long proven problematic because early ontogenetic stages are rarely preserved as fossils. Here, we use synchrotron tomography to describe a new early post-metamorphic blastoid echinoderm from the Carboniferous (approx. 323 Ma) of China. The resulting three-dimensional reconstruction reveals a U-shaped tubular structure in the fossil interior, which is interpreted as the digestive tract. Comparisons with the developing gut of modern crinoids demonstrate that crinoids are an imperfect analogue for many extinct groups. Furthermore, consideration of our findings in a phylogenetic context allows us to reconstruct the evolution and development of the digestive system in echinoderms more broadly; there was a transition from a straight to a simple curved gut early in the phylum's evolution, but additional loops and coils of the digestive tract (as seen in crinoids) were not acquired until much later. © 2015 The Author(s).

  2. Physical Uncertainty Bounds (PUB)

    Energy Technology Data Exchange (ETDEWEB)

    Vaughan, Diane Elizabeth [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Preston, Dean L. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-03-19

    This paper introduces and motivates the need for a new methodology for determining upper bounds on the uncertainties in simulations of engineered systems due to limited fidelity in the composite continuum-level physics models needed to simulate the systems. We show that traditional uncertainty quantification methods provide, at best, a lower bound on this uncertainty. We propose to obtain bounds on the simulation uncertainties by first determining bounds on the physical quantities or processes relevant to system performance. By bounding these physics processes, as opposed to carrying out statistical analyses of the parameter sets of specific physics models or simply switching out the available physics models, one can obtain upper bounds on the uncertainties in simulated quantities of interest.

  3. Clinical whole-genome sequencing in severe early-onset epilepsy reveals new genes and improves molecular diagnosis.

    Science.gov (United States)

    Martin, Hilary C; Kim, Grace E; Pagnamenta, Alistair T; Murakami, Yoshiko; Carvill, Gemma L; Meyer, Esther; Copley, Richard R; Rimmer, Andrew; Barcia, Giulia; Fleming, Matthew R; Kronengold, Jack; Brown, Maile R; Hudspith, Karl A; Broxholme, John; Kanapin, Alexander; Cazier, Jean-Baptiste; Kinoshita, Taroh; Nabbout, Rima; Bentley, David; McVean, Gil; Heavin, Sinéad; Zaiwalla, Zenobia; McShane, Tony; Mefford, Heather C; Shears, Deborah; Stewart, Helen; Kurian, Manju A; Scheffer, Ingrid E; Blair, Edward; Donnelly, Peter; Kaczmarek, Leonard K; Taylor, Jenny C

    2014-06-15

    In severe early-onset epilepsy, precise clinical and molecular genetic diagnosis is complex, as many metabolic and electro-physiological processes have been implicated in disease causation. The clinical phenotypes share many features such as complex seizure types and developmental delay. Molecular diagnosis has historically been confined to sequential testing of candidate genes known to be associated with specific sub-phenotypes, but the diagnostic yield of this approach can be low. We conducted whole-genome sequencing (WGS) on six patients with severe early-onset epilepsy who had previously been refractory to molecular diagnosis, and their parents. Four of these patients had a clinical diagnosis of Ohtahara Syndrome (OS) and two patients had severe non-syndromic early-onset epilepsy (NSEOE). In two OS cases, we found de novo non-synonymous mutations in the genes KCNQ2 and SCN2A. In a third OS case, WGS revealed paternal isodisomy for chromosome 9, leading to identification of the causal homozygous missense variant in KCNT1, which produced a substantial increase in potassium channel current. The fourth OS patient had a recessive mutation in PIGQ that led to exon skipping and defective glycophosphatidyl inositol biosynthesis. The two patients with NSEOE had likely pathogenic de novo mutations in CBL and CSNK1G1, respectively. Mutations in these genes were not found among 500 additional individuals with epilepsy. This work reveals two novel genes for OS, KCNT1 and PIGQ. It also uncovers unexpected genetic mechanisms and emphasizes the power of WGS as a clinical tool for making molecular diagnoses, particularly for highly heterogeneous disorders. © The Author 2014. Published by Oxford University Press.

  4. The DMM Bound

    DEFF Research Database (Denmark)

    Emiris, Ioannis Z.; Mourrain, Bernard; Tsigaridas, Elias

    2010-01-01

    In this paper we derive aggregate separation bounds, named after Davenport-Mahler-Mignotte (DMM), on the isolated roots of polynomial systems, specifically on the minimum distance between any two such roots. The bounds exploit the structure of the system and the height of the sparse (or toric) re...... bound on the number of steps that subdivision-based algorithms perform in order to isolate all real roots of a polynomial system. This leads to the first complexity bound of Milne's algorithm [22] in 2D....

  5. Early doors (Edo) mutant mouse reveals the importance of period 2 (PER2) PAS domain structure for circadian pacemaking.

    Science.gov (United States)

    Militi, Stefania; Maywood, Elizabeth S; Sandate, Colby R; Chesham, Johanna E; Barnard, Alun R; Parsons, Michael J; Vibert, Jennifer L; Joynson, Greg M; Partch, Carrie L; Hastings, Michael H; Nolan, Patrick M

    2016-03-08

    The suprachiasmatic nucleus (SCN) defines 24 h of time via a transcriptional/posttranslational feedback loop in which transactivation of Per (period) and Cry (cryptochrome) genes by BMAL1-CLOCK complexes is suppressed by PER-CRY complexes. The molecular/structural basis of how circadian protein complexes function is poorly understood. We describe a novel N-ethyl-N-nitrosourea (ENU)-induced mutation, early doors (Edo), in the PER-ARNT-SIM (PAS) domain dimerization region of period 2 (PER2) (I324N) that accelerates the circadian clock of Per2(Edo/Edo) mice by 1.5 h. Structural and biophysical analyses revealed that Edo alters the packing of the highly conserved interdomain linker of the PER2 PAS core such that, although PER2(Edo) complexes with clock proteins, its vulnerability to degradation mediated by casein kinase 1ε (CSNK1E) is increased. The functional relevance of this mutation is revealed by the ultrashort (Edo/Edo); Csnk1e(Tau/Tau) mice and the SCN. These periods are unprecedented in mice. Thus, Per2(Edo) reveals a direct causal link between the molecular structure of the PER2 PAS core and the pace of SCN circadian timekeeping.

  6. Bounded Parikh Automata

    Directory of Open Access Journals (Sweden)

    Michaël Cadilhac

    2011-08-01

    Full Text Available The Parikh finite word automaton model (PA was introduced and studied by Klaedtke and Ruess in 2003. Here, by means of related models, it is shown that the bounded languages recognized by PA are the same as those recognized by deterministic PA. Moreover, this class of languages is the class of bounded languages whose set of iterations is semilinear.

  7. Bounded Gaussian process regression

    DEFF Research Database (Denmark)

    Jensen, Bjørn Sand; Nielsen, Jens Brehm; Larsen, Jan

    2013-01-01

    We extend the Gaussian process (GP) framework for bounded regression by introducing two bounded likelihood functions that model the noise on the dependent variable explicitly. This is fundamentally different from the implicit noise assumption in the previously suggested warped GP framework. We...

  8. Bounding Species Distribution Models

    Science.gov (United States)

    Stohlgren, Thomas J.; Jarnevich, Cahterine S.; Morisette, Jeffrey T.; Esaias, Wayne E.

    2011-01-01

    Species distribution models are increasing in popularity for mapping suitable habitat for species of management concern. Many investigators now recognize that extrapolations of these models with geographic information systems (GIS) might be sensitive to the environmental bounds of the data used in their development, yet there is no recommended best practice for "clamping" model extrapolations. We relied on two commonly used modeling approaches: classification and regression tree (CART) and maximum entropy (Maxent) models, and we tested a simple alteration of the model extrapolations, bounding extrapolations to the maximum and minimum values of primary environmental predictors, to provide a more realistic map of suitable habitat of hybridized Africanized honey bees in the southwestern United States. Findings suggest that multiple models of bounding, and the most conservative bounding of species distribution models, like those presented here, should probably replace the unbounded or loosely bounded techniques currently used [Current Zoology 57 (5): 642-647, 2011].

  9. Single-virus tracking approach to reveal the interaction of Dengue virus with autophagy during the early stage of infection

    Science.gov (United States)

    Chu, Li-Wei; Huang, Yi-Lung; Lee, Jin-Hui; Huang, Long-Ying; Chen, Wei-Jun; Lin, Ya-Hsuan; Chen, Jyun-Yu; Xiang, Rui; Lee, Chau-Hwang; Ping, Yueh-Hsin

    2014-01-01

    Dengue virus (DENV) is one of the major infectious pathogens worldwide. DENV infection is a highly dynamic process. Currently, no antiviral drug is available for treating DENV-induced diseases since little is known regarding how the virus interacts with host cells during infection. Advanced molecular imaging technologies are powerful tools to understand the dynamics of intracellular interactions and molecular trafficking. This study exploited a single-virus particle tracking technology to address whether DENV interacts with autophagy machinery during the early stage of infection. Using confocal microscopy and three-dimensional image analysis, we showed that DENV triggered the formation of green fluorescence protein-fused microtubule-associated protein 1A/1B-light chain 3 (GFP-LC3) puncta, and DENV-induced autophagosomes engulfed DENV particles within 15-min postinfection. Moreover, single-virus particle tracking revealed that both DENV particles and autophagosomes traveled together during the viral infection. Finally, in the presence of autophagy suppressor 3-methyladenine, the replication of DENV was inhibited and the location of DENV particles spread in cytoplasma. In contrast, the numbers of newly synthesized DENV were elevated and the co-localization of DENV particles and autophagosomes was detected while the cells were treated with autophagy inducer rapamycin. Taken together, we propose that DENV particles interact with autophagosomes at the early stage of viral infection, which promotes the replication of DENV.

  10. A comparative proteomic analysis reveals important proteins for the fertilization and early embryonic development of the oyster Crassostrea gigas.

    Science.gov (United States)

    Huang, Xiaohong; Huan, Pin; Liu, Baozhong

    2017-01-01

    Molluscan development involves important features that are important to understanding not only molluscan ontogeny but also animal evolution. To gain insight into the gamete proteome and protein function in fertilization and early development, we analyzed the proteomes of unfertilized oocytes and early embryos (2/4-cell stage) of the Pacific oyster, Crassostrea gigas. An oocyte reference map containing 116 protein spots, of which 69 were identified, revealed a high abundance of vitellogenin-derived protein spots. The differentially regulated protein spots during fertilization were screened using comparative proteomic approaches. In total, 18 differentially regulated protein spots were screened, and 15 of these were identified and divided into three groups. The proteins belonging to the first group function in energy supply and antioxidation and are proposed to ensure successful fertilization by regulating the levels of adenosine triphosphate, resisting oxidative stress, and preventing polyspermy. The proteins of the second group are associated with protein synthesis and modification, reflecting active protein synthesis after fertilization. The three proteins belonging to the final group are hypothesized to function in the regulation of embryonic development through the establishment of cell polarity and modulation of methylation reactions in nuclei. These results will enhance our knowledge of molluscan fertilization and development. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Absolute pitch: evidence for early cognitive facilitation during passive listening as revealed by reduced P3a amplitudes.

    Science.gov (United States)

    Rogenmoser, Lars; Elmer, Stefan; Jäncke, Lutz

    2015-03-01

    Absolute pitch (AP) is the rare ability to identify or produce different pitches without using reference tones. At least two sequential processing stages are assumed to contribute to this phenomenon. The first recruits a pitch memory mechanism at an early stage of auditory processing, whereas the second is driven by a later cognitive mechanism (pitch labeling). Several investigations have used active tasks, but it is unclear how these two mechanisms contribute to AP during passive listening. The present work investigated the temporal dynamics of tone processing in AP and non-AP (NAP) participants by using EEG. We applied a passive oddball paradigm with between- and within-tone category manipulations and analyzed the MMN reflecting the early stage of auditory processing and the P3a response reflecting the later cognitive mechanism during the second processing stage. Results did not reveal between-group differences in MMN waveforms. By contrast, the P3a response was specifically associated with AP and sensitive to the processing of different pitch types. Specifically, AP participants exhibited smaller P3a amplitudes, especially in between-tone category conditions, and P3a responses correlated significantly with the age of commencement of musical training, suggesting an influence of early musical exposure on AP. Our results reinforce the current opinion that the representation of pitches at the processing level of the auditory-related cortex is comparable among AP and NAP participants, whereas the later processing stage is critical for AP. Results are interpreted as reflecting cognitive facilitation in AP participants, possibly driven by the availability of multiple codes for tones.

  12. Origin and diagenetic transformations of C 25 and C 30 highly branched isoprenoid sulphur compounds: Further evidence for the formation of organically bound sulphur during early diagenesis

    Science.gov (United States)

    Kohnen, M. E. L.; Damsté, J. S. Slnninghe; Kock-van Dalen, A. C.; Haven, H. L. Ten; Rullkötter, J.; De Leeuw, J. W.

    1990-11-01

    A number of C 25 and C 30 highly branched isoprenoid (HBI) sulphur compounds (E.G., thiolanes, 1-oxo-thiolanes, thiophenes, and benzo[ b]thiophenes) with 2,6,10,14-tetramethyl-7-(3-methylpentyl)pentadecane and 2,6,10,14,18-pentamethyl-7-(3-methylpentyl)nonadecane carbon skeletons were identified in sediments, ranging from Holocene to Upper Cretaceous. These identifications are based on mass spectral characterisation, desulphurisation, and, in some cases, by comparison of mass spectral and relative retention time data with those of authentic standards. The presence of unsaturated C 25 and C 30 HBI thiolanes in a Recent sediment from the Black Sea (age 3-6 × 10 3 a) strongly supports their formation during early diagenesis. The co-occurrence of HBI polyenes (C 25 and C 30) and unsaturated HBI thiolanes (C 25 and C 30) possessing two double bonds less than the corresponding HBI polyenes, in this Recent sediment, testifies to the formation of unsaturated HBI thiolanes by a reaction of inorganic sulphur species with double bonds of the HBI polyenes. Furthermore, a diagenetic scheme for HBI sulphur compounds is proposed based on the identification of HBI sulphur compounds in sediment samples with different maturity levels.

  13. Virial Expansion Bounds

    Science.gov (United States)

    Tate, Stephen James

    2013-10-01

    In the 1960s, the technique of using cluster expansion bounds in order to achieve bounds on the virial expansion was developed by Lebowitz and Penrose (J. Math. Phys. 5:841, 1964) and Ruelle (Statistical Mechanics: Rigorous Results. Benjamin, Elmsford, 1969). This technique is generalised to more recent cluster expansion bounds by Poghosyan and Ueltschi (J. Math. Phys. 50:053509, 2009), which are related to the work of Procacci (J. Stat. Phys. 129:171, 2007) and the tree-graph identity, detailed by Brydges (Phénomènes Critiques, Systèmes Aléatoires, Théories de Jauge. Les Houches 1984, pp. 129-183, 1986). The bounds achieved by Lebowitz and Penrose can also be sharpened by doing the actual optimisation and achieving expressions in terms of the Lambert W-function. The different bound from the cluster expansion shows some improvements for bounds on the convergence of the virial expansion in the case of positive potentials, which are allowed to have a hard core.

  14. Visible induced luminescence reveals invisible rays shining from Christ in the early Christian wall painting of the Transfiguration in Shivta

    Science.gov (United States)

    Tepper, Yotam; Bar-Oz, Guy

    2017-01-01

    The Transfiguration scene depicted in a Byzantine church at Shivta, Israel, is one of two figurative examples of the scene from the early Christian period. The use of Egyptian blue pigment in the wall painting was investigated with various analytical methods. Visible Induced Luminescence (VIL) imaging was used in-situ in order to map the distribution of the Egyptian blue pigment in the painting. The VIL imaging revealed surprising insights into the understanding of the iconography and the technology of this rare painting. Previously undetected elements of the painting include rays of light that were discovered emerging from the body of Christ and illuminating the other figures in the painting. Although this motif is an important part of the Transfiguration narrative and appears in most of its scenes depicted elsewhere, it had not been previously identified in this painting as it was undetectable by any other inspection technique. Another important result is the identification of Egyptian blue as a common blue pigment used at Shivta during the Byzantine period, when it is considered to be very rare. PMID:28949982

  15. Hierarchical development of the primate visual cortex, as revealed by neurofilament immunoreactivity: early maturation of the middle temporal area (MT).

    Science.gov (United States)

    Bourne, James A; Rosa, Marcello G P

    2006-03-01

    It has been suggested that the development of the cerebral cortex reflects its hierarchical organization, with the primary sensory areas being the first to reach structural and functional maturity, and higher-order association areas being the last. In the present study, we labelled the cortex of New World marmoset monkeys of late fetal and early postnatal ages with an antibody to non-phosphorylated neurofilament, a marker of structural maturation of a subset of pyramidal cells. Supporting the concept of hierarchical maturation, we found that at birth labelled cells were found in the primary visual, auditory and somatosensory areas, but not in most other cortical fields. The exception was visual area MT, which revealed an infragranular pattern of labelling comparable to the one observed in the primary areas, as well as some supragranular staining. In MT, an adult-like pattern of labelled cells, including both supragranular and infragranular layer neurons, emerged within the first postnatal month. In comparison, the development of other extrastriate areas was delayed, with the first signs of neurofilament staining not present until the third week. The present results support the concept of MT as another primary visual area, an idea previously advanced on the basis of functional and anatomical evidence.

  16. Validation of EMP bounds

    Energy Technology Data Exchange (ETDEWEB)

    Warne, L.K.; Merewether, K.O.; Chen, K.C.; Jorgenson, R.E.; Morris, M.E.; Solberg, J.E.; Lewis, J.G. [Sandia National Labs., Albuquerque, NM (United States); Derr, W. [Derr Enterprises, Albuquerque, NM (United States)

    1996-07-01

    Test data on canonical weapon-like fixtures are used to validate previously developed analytical bounding results. The test fixtures were constructed to simulate (but be slightly worse than) weapon ports of entry but have known geometries (and electrical points of contact). The exterior of the test fixtures exhibited exterior resonant enhancement of the incident fields at the ports of entry with magnitudes equal to those of weapon geometries. The interior consisted of loaded transmission lines adjusted to maximize received energy or voltage but incorporating practical weapon geometrical constraints. New analytical results are also presented for bounding the energies associated with multiple bolt joints and for bounding the exterior resonant enhancement of the exciting fields.

  17. Bounded Tamper Resilience

    DEFF Research Database (Denmark)

    Damgård, Ivan Bjerre; Faust, Sebastian; Mukherjee, Pratyay

    2013-01-01

    a bounded tamper and leakage resilient CCA secure public key cryptosystem based on the DDH assumption. We first define a weaker CPA-like security notion that we can instantiate based on DDH, and then we give a general compiler that yields CCA-security with tamper and leakage resilience. This requires...... a public tamper-proof common reference string. Finally, we explain how to boost bounded tampering and leakage resilience (as in 1. and 2. above) to continuous tampering and leakage resilience, in the so-called floppy model where each user has a personal hardware token (containing leak- and tamper...

  18. Time-resolved dual transcriptomics reveal early induced Nicotiana benthamiana root genes and conserved infection-promoting Phytophthora palmivora effectors.

    Science.gov (United States)

    Evangelisti, Edouard; Gogleva, Anna; Hainaux, Thomas; Doumane, Mehdi; Tulin, Frej; Quan, Clément; Yunusov, Temur; Floch, Kévin; Schornack, Sebastian

    2017-05-11

    Plant-pathogenic oomycetes are responsible for economically important losses in crops worldwide. Phytophthora palmivora, a tropical relative of the potato late blight pathogen, causes rotting diseases in many tropical crops including papaya, cocoa, oil palm, black pepper, rubber, coconut, durian, mango, cassava and citrus. Transcriptomics have helped to identify repertoires of host-translocated microbial effector proteins which counteract defenses and reprogram the host in support of infection. As such, these studies have helped in understanding how pathogens cause diseases. Despite the importance of P. palmivora diseases, genetic resources to allow for disease resistance breeding and identification of microbial effectors are scarce. We employed the model plant Nicotiana benthamiana to study the P. palmivora root infections at the cellular and molecular levels. Time-resolved dual transcriptomics revealed different pathogen and host transcriptome dynamics. De novo assembly of P. palmivora transcriptome and semi-automated prediction and annotation of the secretome enabled robust identification of conserved infection-promoting effectors. We show that one of them, REX3, suppresses plant secretion processes. In a survey for early transcriptionally activated plant genes we identified a N. benthamiana gene specifically induced at infected root tips that encodes a peptide with danger-associated molecular features. These results constitute a major advance in our understanding of P. palmivora diseases and establish extensive resources for P. palmivora pathogenomics, effector-aided resistance breeding and the generation of induced resistance to Phytophthora root infections. Furthermore, our approach to find infection-relevant secreted genes is transferable to other pathogen-host interactions and not restricted to plants.

  19. The complete mitochondrial genome of Pauropus longiramus (Myriapoda: Pauropoda): implications on early diversification of the myriapods revealed from comparative analysis.

    Science.gov (United States)

    Dong, Yan; Sun, Hongying; Guo, Hua; Pan, Da; Qian, Changyuan; Hao, Sijing; Zhou, Kaiya

    2012-08-15

    Myriapods are among the earliest arthropods and may have evolved to become part of the terrestrial biota more than 400 million years ago. A noticeable lack of mitochondrial genome data from Pauropoda hampers phylogenetic and evolutionary studies within the subphylum Myriapoda. We sequenced the first complete mitochondrial genome of a microscopic pauropod, Pauropus longiramus (Arthropoda: Myriapoda), and conducted comprehensive mitogenomic analyses across the Myriapoda. The pauropod mitochondrial genome is a circular molecule of 14,487 bp long and contains the entire set of thirty-seven genes. Frequent intergenic overlaps occurred between adjacent tRNAs, and between tRNA and protein-coding genes. This is the first example of a mitochondrial genome with multiple intergenic overlaps and reveals a strategy for arthropods to effectively compact the mitochondrial genome by overlapping and truncating tRNA genes with neighbor genes, instead of only truncating tRNAs. Phylogenetic analyses based on protein-coding genes provide strong evidence that the sister group of Pauropoda is Symphyla. Additionally, approximately unbiased (AU) tests strongly support the Progoneata and confirm the basal position of Chilopoda in Myriapoda. This study provides an estimation of myriapod origins around 555 Ma (95% CI: 444-704 Ma) and this date is comparable with that of the Cambrian explosion and candidate myriapod-like fossils. A new time-scale suggests that deep radiations during early myriapod diversification occurred at least three times, not once as previously proposed. A Carboniferous origin of pauropods is congruent with the idea that these taxa are derived, rather than basal, progoneatans. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. Novel genes involved in severe early-onset obesity revealed by rare copy number and sequence variants.

    Directory of Open Access Journals (Sweden)

    Clara Serra-Juhé

    2017-05-01

    Full Text Available Obesity is a multifactorial disorder with high heritability (50-75%, which is probably higher in early-onset and severe cases. Although rare monogenic forms and several genes and regions of susceptibility, including copy number variants (CNVs, have been described, the genetic causes underlying the disease still remain largely unknown. We searched for rare CNVs (>100kb in size, altering genes and present in 3 standard deviations above the mean at <3 years of age using SNP array molecular karyotypes. We then performed case control studies (480 EOO cases/480 non-obese controls with the validated CNVs and rare sequence variants (RSVs detected by targeted resequencing of selected CNV genes (n = 14, and also studied the inheritance patterns in available first-degree relatives. A higher burden of gain-type CNVs was detected in EOO cases versus controls (OR = 1.71, p-value = 0.0358. In addition to a gain of the NPY gene in a familial case with EOO and attention deficit hyperactivity disorder, likely pathogenic CNVs included gains of glutamate receptors (GRIK1, GRM7 and the X-linked gastrin-peptide receptor (GRPR, all inherited from obese parents. Putatively functional RSVs absent in controls were also identified in EOO cases at NPY, GRIK1 and GRPR. A patient with a heterozygous deletion disrupting two contiguous and related genes, SLCO4C1 and SLCO6A1, also had a missense RSV at SLCO4C1 on the other allele, suggestive of a recessive model. The genes identified showed a clear enrichment of shared co-expression partners with known genes strongly related to obesity, reinforcing their role in the pathophysiology of the disease. Our data reveal a higher burden of rare CNVs and RSVs in several related genes in patients with EOO compared to controls, and implicate NPY, GRPR, two glutamate receptors and SLCO4C1 in highly penetrant forms of familial obesity.

  1. Exome Sequencing Analysis Reveals Variants in Primary Immunodeficiency Genes in Patients With Very Early Onset Inflammatory Bowel Disease

    Science.gov (United States)

    Kelsen, Judith R.; Dawany, Noor; Moran, Christopher J.; Petersen, Britt-Sabina; Sarmady, Mahdi; Sasson, Ariella; Pauly-Hubbard, Helen; Martinez, Alejandro; Maurer, Kelly; Soong, Joanne; Rappaport, Eric; Franke, Andre; Keller, Andreas; Winter, Harland S.; Mamula, Petar; Piccoli, David; Artis, David; Sonnenberg, Gregory F.; Daly, Mark; Sullivan, Kathleen E.; Baldassano, Robert N.; Devoto, Marcella

    2016-01-01

    Background & Aims Very early onset inflammatory bowel disease (VEO-IBD), IBD diagnosed ≤5 y of age, frequently presents with a different and more severe phenotype than older-onset IBD. We investigated whether patients with VEO-IBD carry rare or novel variants in genes associated with immunodeficiencies that might contribute to disease development. Methods Patients with VEO-IBD and parents (when available) were recruited from the Children's Hospital of Philadelphia from March 2013 through July 2014. We analyzed DNA from 125 patients with VEO-IBD (ages 3 weeks to 4 y) and 19 parents, 4 of whom also had IBD. Exome capture was performed by Agilent SureSelect V4, and sequencing was performed using the Illumina HiSeq platform. Alignment to human genome GRCh37 was achieved followed by post-processing and variant calling. Following functional annotation, candidate variants were analyzed for change in protein function, minor allele frequency 1 Mbp of coding sequence, were selected from the whole exome data. Our analysis revealed novel and rare variants within these genes that could contribute to the development of VEO-IBD, including rare heterozygous missense variants in IL10RA and previously unidentified variants in MSH5 and CD19. Conclusions In an exome sequence analysis of patients with VEO-IBD and their parents, we identified variants in genes that regulate B- and T-cell functions and could contribute to pathogenesis. Our analysis could lead to the identification of previously unidentified IBD-associated variants. PMID:26193622

  2. Novel genes involved in severe early-onset obesity revealed by rare copy number and sequence variants.

    Science.gov (United States)

    Serra-Juhé, Clara; Martos-Moreno, Gabriel Á; Bou de Pieri, Francesc; Flores, Raquel; González, Juan R; Rodríguez-Santiago, Benjamín; Argente, Jesús; Pérez-Jurado, Luis A

    2017-05-01

    Obesity is a multifactorial disorder with high heritability (50-75%), which is probably higher in early-onset and severe cases. Although rare monogenic forms and several genes and regions of susceptibility, including copy number variants (CNVs), have been described, the genetic causes underlying the disease still remain largely unknown. We searched for rare CNVs (>100kb in size, altering genes and present in obesity (EOO: body mass index >3 standard deviations above the mean at obese controls) with the validated CNVs and rare sequence variants (RSVs) detected by targeted resequencing of selected CNV genes (n = 14), and also studied the inheritance patterns in available first-degree relatives. A higher burden of gain-type CNVs was detected in EOO cases versus controls (OR = 1.71, p-value = 0.0358). In addition to a gain of the NPY gene in a familial case with EOO and attention deficit hyperactivity disorder, likely pathogenic CNVs included gains of glutamate receptors (GRIK1, GRM7) and the X-linked gastrin-peptide receptor (GRPR), all inherited from obese parents. Putatively functional RSVs absent in controls were also identified in EOO cases at NPY, GRIK1 and GRPR. A patient with a heterozygous deletion disrupting two contiguous and related genes, SLCO4C1 and SLCO6A1, also had a missense RSV at SLCO4C1 on the other allele, suggestive of a recessive model. The genes identified showed a clear enrichment of shared co-expression partners with known genes strongly related to obesity, reinforcing their role in the pathophysiology of the disease. Our data reveal a higher burden of rare CNVs and RSVs in several related genes in patients with EOO compared to controls, and implicate NPY, GRPR, two glutamate receptors and SLCO4C1 in highly penetrant forms of familial obesity.

  3. The early asthmatic response is associated with glycolysis, calcium binding and mitochondria activity as revealed by proteomic analysis in rats

    Directory of Open Access Journals (Sweden)

    Xu Yu-Dong

    2010-08-01

    Full Text Available Abstract Background The inhalation of allergens by allergic asthmatics results in the early asthmatic response (EAR, which is characterized by acute airway obstruction beginning within a few minutes. The EAR is the earliest indicator of the pathological progression of allergic asthma. Because the molecular mechanism underlying the EAR is not fully defined, this study will contribute to a better understanding of asthma. Methods In order to gain insight into the molecular basis of the EAR, we examined changes in protein expression patterns in the lung tissue of asthmatic rats during the EAR using 2-DE/MS-based proteomic techniques. Bioinformatic analysis of the proteomic data was then performed using PPI Spider and KEGG Spider to investigate the underlying molecular mechanism. Results In total, 44 differentially expressed protein spots were detected in the 2-DE gels. Of these 44 protein spots, 42 corresponded to 36 unique proteins successfully identified using mass spectrometry. During subsequent bioinformatic analysis, the gene ontology classification, the protein-protein interaction networking and the biological pathway exploration demonstrated that the identified proteins were mainly involved in glycolysis, calcium binding and mitochondrial activity. Using western blot and semi-quantitative RT-PCR, we confirmed the changes in expression of five selected proteins, which further supports our proteomic and bioinformatic analyses. Conclusions Our results reveal that the allergen-induced EAR in asthmatic rats is associated with glycolysis, calcium binding and mitochondrial activity, which could establish a functional network in which calcium binding may play a central role in promoting the progression of asthma.

  4. Bounded variation and around

    CERN Document Server

    Appell, Jürgen; Merentes Díaz, Nelson José

    2013-01-01

    This monographis a self-contained exposition of the definition and properties of functionsof bounded variation and their various generalizations; the analytical properties of nonlinear composition operators in spaces of such functions; applications to Fourier analysis, nonlinear integral equations, and boundary value problems. The book is written for non-specialists. Every chapter closes with a list of exercises and open problems.

  5. Born Level Bound States

    Science.gov (United States)

    Hoyer, Paul

    2017-05-01

    Bound state poles in the S-matrix of perturbative QED are generated by the divergence of the expansion in α . The perturbative corrections are necessarily singular when expanding around free, {O}( α ^0 ) in and out states that have no overlap with finite-sized atomic wave functions. Nevertheless, measurables such as binding energies do have well-behaved expansions in powers of α (and log α ). It is desirable to formulate the concept of "lowest order" for gauge theory bound states such that higher order corrections vanish in the α → 0 limit. This may allow to determine a lowest order term for QCD hadrons which incorporates essential features such as confinement and chiral symmetry breaking, and thus can serve as the starting point of a useful perturbative expansion. I discuss a "Born" (no loop, lowest order in \\hbar ) approximation. Born level states are bound by gauge fields which satisfy the classical field equations. Gauss' law determines a distinct field A^0({\\varvec{x}}) for each instantaneous position of the charges. A Poincaré covariant boundary condition for the gluon field leads to a confining potential for q\\bar{q} and qqq states. In frames where the bound state is in motion the classical gauge field is obtained by a Lorentz boost of the rest frame field.

  6. Convergence of topological domain boundaries, insulators, and polytene interbands revealed by high-resolution mapping of chromatin contacts in the early Drosophila melanogaster embryo

    Science.gov (United States)

    Stadler, Michael R; Haines, Jenna E

    2017-01-01

    High-throughput assays of three-dimensional interactions of chromosomes have shed considerable light on the structure of animal chromatin. Despite this progress, the precise physical nature of observed structures and the forces that govern their establishment remain poorly understood. Here we present high resolution Hi-C data from early Drosophila embryos. We demonstrate that boundaries between topological domains of various sizes map to DNA elements that resemble classical insulator elements: short genomic regions sensitive to DNase digestion that are strongly bound by known insulator proteins and are frequently located between divergent promoters. Further, we show a striking correspondence between these elements and the locations of mapped polytene interband regions. We believe it is likely this relationship between insulators, topological boundaries, and polytene interbands extends across the genome, and we therefore propose a model in which decompaction of boundary-insulator-interband regions drives the organization of interphase chromosomes by creating stable physical separation between adjacent domains. PMID:29148971

  7. Bound Exciton Complexes

    Science.gov (United States)

    Meyer, B. K.

    In the preceding chapter, we concentrated on the properties of free excitons. These free excitons may move through the sample and hit a trap, a nonradiative or a radiative recombination center. At low temperatures, the latter case gives rise to either deep center luminescence, mentioned in Sect. 7.1 and discussed in detail in Chap. 9, or to the luminescence of bound exciton complexes (BE or BEC). The chapter continues with the most prominent of these BECs, namely A-excitons bound to neutral donors. The next aspects are the more weakly BEs at ionized donors. The Sect. 7.4 treats the binding or localization energies of BEC from a theoretical point of view, while Sect. 7.5 is dedicated to excited states of BECs, which contain either holes from deeper valence bands or an envelope function with higher quantum numbers. The last section is devoted to donor-acceptor pair transitions. There is no section devoted specifically to excitons bound to neutral acceptors, because this topic is still partly controversially discussed. Instead, information on these A0X complexes is scattered over the whole chapter, however, with some special emphasis seen in Sects. 7.1, 7.4, and 7.5.

  8. Verifying bound entanglement of dephased Werner states

    Science.gov (United States)

    Thomas, P.; Bohmann, M.; Vogel, W.

    2017-10-01

    The verification of quantum entanglement under the influence of realistic noise and decoherence is crucial for the development of quantum technologies. Unfortunately, a full entanglement characterization is generally not possible with most entanglement criteria such as entanglement witnesses or the partial transposition criterion. In particular, so-called bound entanglement cannot be certified via the partial transposition criterion. Here we present the full entanglement verification of dephased qubit and qutrit Werner states via entanglement quasiprobabilities. Remarkably, we are able to reveal bound entanglement for noisy mixed states in the qutrit case. This example demonstrates the strength of the entanglement quasiprobabilities for verifying the full entanglement of quantum states suffering from noise.

  9. Dromions bound states

    Energy Technology Data Exchange (ETDEWEB)

    Maccari, Attilio

    2003-03-01

    The asymptotic perturbation (AP) method is applied to the study of the nonlinear Klein-Gordon equation in 3+1 dimensions with harmonic potential and external periodic excitation supposed to be in primary resonance with the frequency of a generic mode. The AP method uses two different procedures for the solutions: introducing an asymptotic temporal rescaling and balancing of the harmonic terms with a simple iteration. Standard quantum mechanics can be used to derive the lowest order approximate solution and amplitude and phase modulation equations are obtained. External force-response and frequency-response curves are found and the existence of dromions trapped in bound states is demonstrated.

  10. Crystal structure of thioflavin T bound to the peripheral site of Torpedo californica acetylcholinesterase reveals how thioflavin T acts as a sensitive fluorescent reporter of ligand binding to the acylation site.

    Science.gov (United States)

    Harel, Michal; Sonoda, Leilani K; Silman, Israel; Sussman, Joel L; Rosenberry, Terrone L

    2008-06-25

    Acetylcholinesterase plays a key role in cholinergic synaptic transmission by hydrolyzing the neurotransmitter acetylcholine with one of the highest known catalytic rate constants. Hydrolysis occurs in a narrow and deep gorge that contains two sites of ligand binding: A peripheral site, or P-site, near the gorge entrance that contributes to catalytic efficiency both by transiently trapping substrate molecules as they enter the gorge and by allosterically accelerating the transfer of the substrate acyl group to a serine hydroxyl in an acylation site or A-site at the base of the gorge. Thioflavin T is a useful reporter of ligand interactions with the A-site. It binds specifically to the P-site with fluorescence that is enhanced approximately 1000-fold over that of unbound thioflavin T, and the enhanced fluorescence is quenched 1.5- to 4-fold when another ligand binds to the A-site in a ternary complex. To clarify the structural basis of this advantageous signal change, we here report the X-ray structure of the complex of thioflavin T with Torpedo californica acetylcholinesterase. The two aromatic rings in thioflavin T are coplanar and are packed snugly parallel to the aromatic side chains of Trp279, Tyr334, and Phe330. Overlays of this structure with the crystal structures of Torpedo californica acetylcholinesterase complexes with either edrophonium or m-( N, N, N-trimethylammonio)-2,2,2-trifluoroacetophenone, two small aromatic ligands that bind specifically to the A-site, indicate that the phenyl side chain of Phe330 must rotate to sterically accommodate both thioflavin T and the A-site ligand in the ternary complex. This rotation may allow some relaxation of the strict coplanarity of the aromatic rings in the bound thioflavin T and result in partial quenching of its fluorescence.

  11. Early corticospinal tract damage in prodromal SCA2 revealed by EEG-EMG and EMG-EMG coherence.

    Science.gov (United States)

    Velázquez-Pérez, Luis; Tünnerhoff, Johannes; Rodríguez-Labrada, Roberto; Torres-Vega, Reidenis; Ruiz-Gonzalez, Yusely; Belardinelli, Paolo; Medrano-Montero, Jacqueline; Canales-Ochoa, Nalia; González-Zaldivar, Yanetza; Vazquez-Mojena, Yaimeé; Auburger, Georg; Ziemann, Ulf

    2017-12-01

    Clinical data suggest early involvement of the corticospinal tract (CST) in spinocerebellar ataxia type 2 (SCA2). Here we tested if early CST degeneration can be detected in prodromal SCA2 mutation carriers by electrophysiological markers of CST integrity. CST integrity was tested in 15 prodromal SCA2 mutation carriers, 19 SCA2 patients and 25 age-matched healthy controls, using corticomuscular (EEG-EMG) and intermuscular (EMG-EMG) coherence measures in upper and lower limb muscles. Significant reductions of EEG-EMG and EMG-EMG coherences were observed in the SCA2 patients, and to a similar extent in the prodromal SCA2 mutation carriers. In prodromal SCA2, EEG-EMG and EMG-EMG coherences correlated with the predicted time to ataxia onset. Findings indicate early CST neurodegeneration in SCA2. EEG-EMG and EMG-EMG coherence may serve as biomarkers of early CST neurodegeneration in prodromal SCA2 mutation carriers. Findings are important for developing preclinical disease markers in the context of currently emerging disease-modifying therapies of neurodegenerative disorders. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

  12. Characteristics of juvenile survivors reveal spatio-temporal differences in early life stage survival of Baltic cod

    DEFF Research Database (Denmark)

    Huwer, Bastian; Hinrichsen, H.H.; Böttcher, U.

    2014-01-01

    simulations of early life stages of Baltic cod up to the pelagic juvenile stage was validated by comparing model simulations with the catch distribution from a survey targeting pelagic juveniles, and mortality rates and hatch date distributions of pelagic and demersal juveniles were estimated. Hatch dates...

  13. High Resolution MRI Reveals Detailed Layer Structures in Early Human Fetal Stages: In Vitro Study with Histologic Correlation.

    Science.gov (United States)

    Wang, Rongpin; Dai, Guangping; Takahashi, Emi

    2015-01-01

    An understanding of normal fetal brain development is essential in detecting the early onset of brain disorders. It is challenging to obtain high-quality images that show detailed local anatomy in the early fetal stages because the fetal brain is very small with rapidly-changing complex structures related to brain development, including neurogenesis, neuronal migration, and axonal elongation. Previous magnetic resonance imaging (MRI) studies detected three layers throughout the fetal cerebral wall that showed differences in MR contrasts at 10 gestational weeks (GW), which is one of the earliest ages studied using MRI. Contrary to the MRI studies, histological studies found more layers at this fetal age. The purpose of this work is to study the development of brain structures from an early fetal period to an early second trimester stage using ex vivo MRI and compare it to histology. Special attention was paid to laminar structures in the cerebral wall. T2-weighted imaging was performed on fetal brain specimens ranging from 10 GW to 18 GW on a 4.7 tesla MR scanner. We obtained standard grayscale as well as color-coded images using weighted red-green-blue scales, and compared them with the histological images. Our study confirmed laminar structure in the cerebral wall in all the fetal specimens studied. We found that MRI detected four layers within the cerebral wall as early as 10 GW during the early fetal period (10-13 GW). Early second trimester (15-18 GW) was characterized by the emergence of subplate structures and five layers within the cerebral wall. The color-coded images were more useful than the standard grayscale images in detecting the laminar structures. Scans with appropriate parameters from a high tesla MR scanner showed detailed laminar structures even through a very small and thin cerebral wall at 10 GW ex vivo. A combination of high-resolution structural imaging and color-coding processing with histological analysis may be a potential tool for

  14. High resolution MRI reveals detailed layer structures in early human fetal stages: In vitro study with histologic correlation

    Directory of Open Access Journals (Sweden)

    Rongpin eWang

    2015-11-01

    Full Text Available An understanding of normal fetal brain development is essential in detecting the early onset of brain disorders. It is challenging to obtain high-quality images that show detailed local anatomy in the early fetal stages because the fetal brain is very small with rapidly-changing complex structures related to brain development, including neurogenesis, neuronal migration, and axonal elongation. Previous magnetic resonance imaging (MRI studies detected three layers throughout the fetal cerebral wall that showed differences in MR contrasts at 10 gestational weeks (GW, which is one of the earliest ages studied using MRI. Contrary to the MRI studies, histological studies found more layers at this fetal age. The purpose of this work is to study the development of brain structures from an early fetal period to an early second trimester stage using ex vivo MRI and compare it to histology. Special attention was paid to laminar structures in the cerebral wall. T2-weighted imaging was performed on fetal brain specimens ranging from 10 GW to 18 GW on a 4.7 tesla MR scanner. We obtained standard grayscale as well as color-coded images using weighted red-green-blue scales, and compared them with the histological images. Our study confirmed laminar structure in the cerebral wall in all the fetal specimens studied. We found that MRI detected four layers within the cerebral wall as early as 10 GW during the early fetal period (10-13 GW. Early second trimester (15-18 GW was characterized by the emergence of subplate structures and five layers within the cerebral wall. The color-coded images were more useful than the standard grayscale images in detecting the laminar structures. Scans with appropriate parameters from a high tesla MR scanner showed detailed laminar structures even through a very small and thin cerebral wall at 10 GW ex vivo. A combination of high-resolution structural imaging and color-coding processing with histological analysis may be a potential

  15. Refining Multivariate Value Set Bounds

    Science.gov (United States)

    Smith, Luke Alexander

    Over finite fields, if the image of a polynomial map is not the entire field, then its cardinality can be bounded above by a significantly smaller value. Earlier results bound the cardinality of the value set using the degree of the polynomial, but more recent results make use of the powers of all monomials. In this paper, we explore the geometric properties of the Newton polytope and show how they allow for tighter upper bounds on the cardinality of the multivariate value set. We then explore a method which allows for even stronger upper bounds, regardless of whether one uses the multivariate degree or the Newton polytope to bound the value set. Effectively, this provides an alternate proof of Kosters' degree bound, an improved Newton polytope-based bound, and an improvement of a degree matrix-based result given by Zan and Cao.

  16. Event-related brain potentials reveal the time-course of language change detection in early bilinguals.

    Science.gov (United States)

    Kuipers, Jan-Rouke; Thierry, Guillaume

    2010-05-01

    Using event-related brain potentials, we investigated the temporal course of language change detection in proficient bilinguals as compared to matched controls. Welsh-English bilingual participants and English controls were presented with a variant of the oddball paradigm involving picture-word pairs. The language of the spoken word was manipulated such that English was the frequent stimulus (75%) and Welsh the infrequent stimulus (25%). We also manipulated semantic relatedness between pictures and words, such that only half of the pictures were followed by a word that corresponded with the identity of the picture. The P2 wave was significantly modulated by language in the bilingual group only, suggesting that this group detected a language change as early as 200 ms after word onset. Monolinguals also reliably detected the language change, but at a later stage of semantic integration (N400 range), since Welsh words were perceived as meaningless. The early detection of a language change in bilinguals triggered stimulus re-evaluation mechanisms reflected by a significant P600 modulation by Welsh words. Furthermore, compared to English unrelated words, English words matching the picture identity elicited significantly greater P2 amplitudes in the bilingual group only, suggesting that proficient bilinguals validate an incoming word against their expectation based on the context. Overall, highly proficient bilinguals appear to detect language changes very early on during speech perception and to consciously monitor language changes when they occur. 2010 Elsevier Inc. All rights reserved.

  17. Genome-Wide Detection of SNP and SV Variations to Reveal Early Ripening-Related Genes in Grape.

    Directory of Open Access Journals (Sweden)

    Yanshuai Xu

    Full Text Available Early ripening in grape (Vitis vinifera L. is a crucial agronomic trait. The fruits of the grape line 'Summer Black' (SBBM, which contains a bud mutation, can be harvested approximately one week earlier than the 'Summer Black' (SBCcontrol. To investigate the molecular mechanism of the bud mutation related to early ripening, we detected genome-wide genetic variations based on re-sequencing. In total, 3,692,777 single nucleotide polymorphisms (SNPs and 81,223 structure variations (SVs in the SBC genome and 3,823,464 SNPs and 85,801 SVs in the SBBM genome were detected compared with the reference grape sequence. Of these, 635 SBC-specific genes and 665 SBBM-specific genes were screened. Ripening and colour-associated unigenes with non-synonymous mutations (NS, SVs or frame-shift mutations (F were analysed. The results showed that 90 unigenes in SBC, 76 unigenes in SBBM and 13 genes that mapped to large fragment indels were filtered. The expression patterns of eight genes were confirmed using quantitative reverse transcription-polymerase chain reaction (qRT-PCR.The re-sequencing data showed that 635 SBC-specific genes and 665 SBBM-specific genes associated with early ripening were screened. Among these, NCED6 expression appears to be related to NCED1 and is involved in ABA biosynthesis in grape, which might play a role in the onset of anthocyanin accumulation. The SEP and ERF genes probably play roles in ethylene response.

  18. Small RNA Sequencing Reveals Differential miRNA Expression in the Early Development of Broccoli (Brassica oleracea var. italica) Pollen.

    Science.gov (United States)

    Li, Hui; Wang, Yu; Wu, Mei; Li, Lihong; Jin, Chuan; Zhang, Qingli; Chen, Chengbin; Song, Wenqin; Wang, Chunguo

    2017-01-01

    Pollen development is an important and complex biological process in the sexual reproduction of flowering plants. Although the cytological characteristics of pollen development are well defined, the regulation of its early stages remains largely unknown. In the present study, miRNAs were explored in the early development of broccoli (Brassica oleracea var. italica) pollen. A total of 333 known miRNAs that originated from 235 miRNA families were detected. Fifty-five novel miRNA candidates were identified. Sixty of the 333 known miRNAs and 49 of the 55 predicted novel miRNAs exhibited significantly differential expression profiling in the three distinct developmental stages of broccoli pollen. Among these differentially expressed miRNAs, miRNAs that would be involved in the developmental phase transition from uninucleate microspores to binucleate pollen grains or from binucleate to trinucleate pollen grains were identified. miRNAs that showed significantly enriched expression in a specific early stage of broccoli pollen development were also observed. In addition, 552 targets for 127 known miRNAs and 69 targets for 40 predicted novel miRNAs were bioinformatically identified. Functional annotation and GO (Gene Ontology) analysis indicated that the putative miRNA targets showed significant enrichment in GO terms that were related to plant organ formation and morphogenesis. Some of enriched GO terms were detected for the targets directly involved in plant male reproduction development. These findings provided new insights into the functions of miRNA-mediated regulatory networks in broccoli pollen development.

  19. New early Eocene vertebrate assemblage from western India reveals a mixed fauna of European and Gondwana affinities

    Directory of Open Access Journals (Sweden)

    Thierry Smith

    2016-11-01

    Full Text Available The Ypresian Cambay Shale Formation at Vastan and Mangrol lignite mines in Gujarat, western India, has yielded a rich vertebrate fauna with numerous taxa of European affinities. Here we report a new, approximately contemporary vertebrate assemblage from two fossiliferous layers in the nearby mine of Tadkeshwar. These layers have yielded a similar mammal fauna with the co-occurrence of the perissodactyl-like cambaytheriid Cambaytherium thewissi, the adapoid primates Marcgodinotius indicus and cf. Asiadapis cambayensis, and the hyaenodontid Indohyaenodon raoi. The presence of these species in both Vastan and Tadkeshwar mines and at different levels suggests that the deposits between the two major lignite seams represent a single land mammal age. Apart from the aforementioned species there is a new, smaller species of Cambaytherium, and a new genus and species of esthonychid tillodont. This fauna also contains the first large early Eocene vertebrates from India, including an unidentified Coryphodon-like pantodont, a dyrosaurid crocodyliform and a new giant madtsoiid snake. Among the Tadkeshwar vertebrates several taxa are of Gondwana affinities, such as Pelomedusoides turtles, dyrosaurids, and large madtsoiids, attesting that the early Eocene was a crucial period in India during which Laurasian taxa of European affinities co-existed with relict taxa from Gondwana before the India-Asia collision. Our results suggest that terrestrial faunas could have dispersed to or from Europe during episodes of contact between the Indian subcontinent and different island blocks along the northern margin of the Neotethys, such as the Kohistan–Ladakh island-arc system. Gondwana taxa might represent remnants of ghost lineages shared with Madagascar, which reached the Indian subcontinent during the late Cretaceous; alternatively they might have come from North Africa and passed along the southern margin of the Neotethys to reach the Indian subcontinent. These

  20. Ancient DNA from South-East Europe Reveals Different Events during Early and Middle Neolithic Influencing the European Genetic Heritage

    Science.gov (United States)

    Hervella, Montserrat; Rotea, Mihai; Izagirre, Neskuts; Constantinescu, Mihai; Alonso, Santos; Ioana, Mihai; Lazăr, Cătălin; Ridiche, Florin; Soficaru, Andrei Dorian; Netea, Mihai G.; de-la-Rua, Concepcion

    2015-01-01

    The importance of the process of Neolithization for the genetic make-up of European populations has been hotly debated, with shifting hypotheses from a demic diffusion (DD) to a cultural diffusion (CD) model. In this regard, ancient DNA data from the Balkan Peninsula, which is an important source of information to assess the process of Neolithization in Europe, is however missing. In the present study we show genetic information on ancient populations of the South-East of Europe. We assessed mtDNA from ten sites from the current territory of Romania, spanning a time-period from the Early Neolithic to the Late Bronze Age. mtDNA data from Early Neolithic farmers of the Starčevo Criş culture in Romania (Cârcea, Gura Baciului and Negrileşti sites), confirm their genetic relationship with those of the LBK culture (Linienbandkeramik Kultur) in Central Europe, and they show little genetic continuity with modern European populations. On the other hand, populations of the Middle-Late Neolithic (Boian, Zau and Gumelniţa cultures), supposedly a second wave of Neolithic migration from Anatolia, had a much stronger effect on the genetic heritage of the European populations. In contrast, we find a smaller contribution of Late Bronze Age migrations to the genetic composition of Europeans. Based on these findings, we propose that permeation of mtDNA lineages from a second wave of Middle-Late Neolithic migration from North-West Anatolia into the Balkan Peninsula and Central Europe represent an important contribution to the genetic shift between Early and Late Neolithic populations in Europe, and consequently to the genetic make-up of modern European populations. PMID:26053041

  1. Simultaneous EEG-fMRI reveals attention-dependent coupling of early face processing with a distributed cortical network.

    Science.gov (United States)

    Bayer, Mareike; Rubens, Michael T; Johnstone, Tom

    2017-12-12

    The speed of visual processing is central to our understanding of face perception. Yet the extent to which early visual processing influences later processing in distributed face processing networks, and the top-down modulation of such bottom-up effects, remains unclear. We used simultaneous EEG-fMRI to investigate cortical activity that showed unique covariation with ERP components of face processing (C1, P1, N170, P3), while manipulating sustained attention and transient cognitive conflict employing an emotional face-word Stroop task. ERP markers of visual processing within 100 ms after stimulus onset showed covariation with brain activation in precuneous, posterior cingulate gyrus, left middle temporal gyrus, left inferior frontal gyrus and frontal operculum, and a left lateral parietal-occipital cluster, illustrating the impact of early stage processing on higher-order mechanisms. Crucially, this covariation depended on sustained attentional focus and was absent for incongruent trials, suggesting flexible top-down gating of bottom-up processing. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  2. New Genetic Insights into Pearl Millet Diversity As Revealed by Characterization of Early- and Late-Flowering Landraces from Senegal

    Directory of Open Access Journals (Sweden)

    Oumar Diack

    2017-05-01

    Full Text Available Pearl millet (Pennisetum glaucum (L. R. Br. is a staple food and a drought-tolerant cereal well adapted to Sub-Saharan Africa agro-ecosystems. An important diversity of pearl millet landraces has been widely conserved by farmers and therefore could help copping with climate changes and contribute to future food security. Hence, characterizing its genetic diversity and population structure can contribute to better assist breeding programs for a sustainable agricultural productivity enhancement. Toward this goal, a comprehensive panel of 404 accessions were used that correspond to 12 improved varieties, 306 early flowering and 86 late-flowering cultivated landraces from Senegal. Twelve highly polymorphic SSR markers were used to study diversity and population structure. Two genes, PgMADS11 and PgPHYC, were genotyped to assess their association to flowering phenotypic difference in landraces. Results indicate a large diversity and untapped potential of Senegalese pearl millet germplasm as well as a genetic differentiation between early- and late-flowering landraces. Further, a fine-scale genetic difference of PgPHYC and PgMADS11 (SNP and indel, respectively and co-variation of their alleles with flowering time were found among landraces. These findings highlight new genetic insights of pearl millet useful to define heterotic populations for breeding, genomic association panel, or crosses for trait-specific mapping.

  3. Transcriptome analysis of the hormone-sensing cells in mammary epithelial reveals dynamic changes in early pregnancy.

    Science.gov (United States)

    De Silva, Duvini; Kunasegaran, Kamini; Ghosh, Sujoy; Pietersen, Alexandra M

    2015-01-27

    Alveoli, the milk-producing units of the mammary gland, are generated during pregnancy by collaboration of different epithelial cell types. We present the first analysis of transcriptional changes within the hormone sensing population during pregnancy. Hormone-receptor positive (HR+) cells play a key role in the initiation of alveologenesis as they sense systemic hormonal changes and translate these into local instructions for neighboring HR- cells. We recently showed that IGF2 is produced specifically by HR+ cells in early pregnancy, but is undetectable in the virgin state. Here, we define the transcriptome of HR+ cells in early pregnancy with the aim to elucidate additional changes that are unique for this dynamic developmental time window. We harvested mammary glands from virgin, 3-day and 7-day pregnant mice and isolated a few hundred hormone-sensing cells per animal by FACS for microarray analysis. There was a high concordance between animals with a clear induction of cell cycle progression genes at day 3 of pregnancy and molecules involved in paracrine signalling at day 7. These findings underscore the proliferative capacity of HR+ cells upon specific stimuli and elucidate developmentally-restricted changes in cellular communication. Since the majority of breast cancers are HR+, with a variable proportion of HR+ cells per tumor, we anticipate that this data set will aid further studies into the regulation of HR+ cell proliferation and the role of heterotypic signalling within tumors.

  4. Historical DNA reveals the demographic history of Atlantic cod (Gadus morhua) in medieval and early modern Iceland.

    Science.gov (United States)

    Ólafsdóttir, Guðbjörg Ásta; Westfall, Kristen M; Edvardsson, Ragnar; Pálsson, Snæbjörn

    2014-02-22

    Atlantic cod (Gadus morhua) vertebrae from archaeological sites were used to study the history of the Icelandic Atlantic cod population in the time period of 1500-1990. Specifically, we used coalescence modelling to estimate population size and fluctuations from the sequence diversity at the cytochrome b (cytb) and Pantophysin I (PanI) loci. The models are consistent with an expanding population during the warm medieval period, large historical effective population size (NE), a marked bottleneck event at 1400-1500 and a decrease in NE in early modern times. The model results are corroborated by the reduction of haplotype and nucleotide variation over time and pairwise population distance as a significant portion of nucleotide variation partitioned across the 1550 time mark. The mean age of the historical fished stock is high in medieval times with a truncation in age in early modern times. The population size crash coincides with a period of known cooling in the North Atlantic, and we conclude that the collapse may be related to climate or climate-induced ecosystem change.

  5. Problem Analysis in Community Violence Assessment: Revealing Early Childhood Trauma as a Driver of Youth and Gang Violence.

    Science.gov (United States)

    Ross, Laurie; Arsenault, Samantha

    2017-11-01

    Problem analysis conducted by a university-based research partner can provide communities with data-driven options to address the local drivers of serious youth and gang violence. Situated in Worcester, Massachusetts, this article describes how subsequent to early childhood trauma being identified as a potential driver of adolescent and young adult violence; problem analysis using local data confirmed that being the victim or witness of a traumatic incident before the age of 12 years was significantly correlated with involvement in violence in adolescence or young adulthood. Although there is a robust literature on the relationship between early childhood trauma and later delinquency, local decision makers did not consider this knowledge actionable until the research partner used the city's own police records to demonstrate the extent of the problem in the city. Rigorous problem analysis, conducted collaboratively between practitioners and an academic research partner, helped to compel local change and ensured that strategies addressed the right risk factors and directed service to the appropriate target population.

  6. High-throughput RNA structure probing reveals critical folding events during early 60S ribosome assembly in yeast.

    Science.gov (United States)

    Burlacu, Elena; Lackmann, Fredrik; Aguilar, Lisbeth-Carolina; Belikov, Sergey; Nues, Rob van; Trahan, Christian; Hector, Ralph D; Dominelli-Whiteley, Nicholas; Cockroft, Scott L; Wieslander, Lars; Oeffinger, Marlene; Granneman, Sander

    2017-09-28

    While the protein composition of various yeast 60S ribosomal subunit assembly intermediates has been studied in detail, little is known about ribosomal RNA (rRNA) structural rearrangements that take place during early 60S assembly steps. Using a high-throughput RNA structure probing method, we provide nucleotide resolution insights into rRNA structural rearrangements during nucleolar 60S assembly. Our results suggest that many rRNA-folding steps, such as folding of 5.8S rRNA, occur at a very specific stage of assembly, and propose that downstream nuclear assembly events can only continue once 5.8S folding has been completed. Our maps of nucleotide flexibility enable making predictions about the establishment of protein-rRNA interactions, providing intriguing insights into the temporal order of protein-rRNA as well as long-range inter-domain rRNA interactions. These data argue that many distant domains in the rRNA can assemble simultaneously during early 60S assembly and underscore the enormous complexity of 60S synthesis.Ribosome biogenesis is a dynamic process that involves the ordered assembly of ribosomal proteins and numerous RNA structural rearrangements. Here the authors apply ChemModSeq, a high-throughput RNA structure probing method, to quantitatively measure changes in RNA flexibility during the nucleolar stages of 60S assembly in yeast.

  7. Combined chromatin and expression analysis reveals specific regulatory mechanisms within cytokine genes in the macrophage early immune response.

    Directory of Open Access Journals (Sweden)

    Maria Jesus Iglesias

    Full Text Available Macrophages play a critical role in innate immunity, and the expression of early response genes orchestrate much of the initial response of the immune system. Macrophages undergo extensive transcriptional reprogramming in response to inflammatory stimuli such as Lipopolysaccharide (LPS.To identify gene transcription regulation patterns involved in early innate immune responses, we used two genome-wide approaches--gene expression profiling and chromatin immunoprecipitation-sequencing (ChIP-seq analysis. We examined the effect of 2 hrs LPS stimulation on early gene expression and its relation to chromatin remodeling (H3 acetylation; H3Ac and promoter binding of Sp1 and RNA polymerase II phosphorylated at serine 5 (S5P RNAPII, which is a marker for transcriptional initiation. Our results indicate novel and alternative gene regulatory mechanisms for certain proinflammatory genes. We identified two groups of up-regulated inflammatory genes with respect to chromatin modification and promoter features. One group, including highly up-regulated genes such as tumor necrosis factor (TNF, was characterized by H3Ac, high CpG content and lack of TATA boxes. The second group, containing inflammatory mediators (interleukins and CCL chemokines, was up-regulated upon LPS stimulation despite lacking H3Ac in their annotated promoters, which were low in CpG content but did contain TATA boxes. Genome-wide analysis showed that few H3Ac peaks were unique to either +/-LPS condition. However, within these, an unpacking/expansion of already existing H3Ac peaks was observed upon LPS stimulation. In contrast, a significant proportion of S5P RNAPII peaks (approx 40% was unique to either condition. Furthermore, data indicated a large portion of previously unannotated TSSs, particularly in LPS-stimulated macrophages, where only 28% of unique S5P RNAPII peaks overlap annotated promoters. The regulation of the inflammatory response appears to occur in a very specific manner at

  8. Studies of Physcomitrella patens reveal that ethylene-mediated submergence responses arose relatively early in land-plant evolution

    KAUST Repository

    Yasumura, Yuki

    2012-10-18

    Colonization of the land by multicellular green plants was a fundamental step in the evolution of life on earth. Land plants evolved from fresh-water aquatic algae, and the transition to a terrestrial environment required the acquisition of developmental plasticity appropriate to the conditions of water availability, ranging from drought to flood. Here we show that extant bryophytes exhibit submergence-induced developmental plasticity, suggesting that submergence responses evolved relatively early in the evolution of land plants. We also show that a major component of the bryophyte submergence response is controlled by the phytohormone ethylene, using a perception mechanism that has subsequently been conserved throughout the evolution of land plants. Thus a plant environmental response mechanism with major ecological and agricultural importance probably had its origins in the very earliest stages of the colonization of the land. © 2012 Blackwell Publishing Ltd.

  9. Indicators of early and late processing reveal the importance of within-trial-time for theories of associative learning.

    Science.gov (United States)

    Lachnit, Harald; Thorwart, Anna; Schultheis, Holger; Lotz, Anja; Koenig, Stephan; Uengoer, Metin

    2013-01-01

    In four human learning experiments (Pavlovian skin conductance, causal learning, speeded classification task), we evaluated several associative learning theories that assume either an elemental (modified unique cue model and Harris' model) or a configural (Pearce's configural theory and an extension of it) form of stimulus processing. The experiments used two modified patterning problems (A/B/C+, AB/BC/AC+ vs. ABC-; A+, BC+ vs. ABC-). Pearce's configural theory successfully predicted all of our data reflecting early stimulus processing, while the predictions of the elemental theories were in accord with all of our data reflecting later stages of stimulus processing. Our results suggest that the form of stimulus representation depends on the amount of time available for stimulus processing. Our findings highlight the necessity to investigate stimulus processing during conditioning on a finer time scale than usually done in contemporary research.

  10. Bioinformatics approach reveals evidence for impaired endometrial maturation before and during early pregnancy in women who developed preeclampsia.

    Science.gov (United States)

    Rabaglino, Maria B; Post Uiterweer, Emiel D; Jeyabalan, Arun; Hogge, William A; Conrad, Kirk P

    2015-02-01

    Impaired uterine invasion by extravillous trophoblast in early gestation is implicated in the genesis of preeclampsia, a potentially lethal malady of human pregnancy. However, reasons for extravillous trophoblast dysfunction remain unclear because of virtual inaccessibility of early placental and uterine tissues from women who develop preeclampsia, and the absence of animal models in which the disease spontaneously occurs. Consequently, the possibility that deficient or defective maturation of the endometrium (decidualization) may compromise extravillous trophoblast invasion in preeclampsia remains unexplored. Using a bioinformatics approach, we tested this hypothesis identifying 396 differentially expressed genes (DEG) in chorionic villous samples from women at ≈11.5 gestational weeks who developed severe preeclampsia symptoms 6 months later compared with chorionic villous samples from normal pregnancies. A large number, 154 or 40%, overlapped with DEG associated with various stages of normal endometrial maturation before and after implantation as identified by other microarray data sets (P=4.7×10(-14)). One-hundred and sixteen of the 154 DEG or 75% overlapped with DEG associated with normal decidualization in the absence of extravillous trophoblast, ie, late-secretory endometrium (LSE) and endometrium from tubal ectopic pregnancy (EP; P=4.2×10(-9)). Finally, 112 of these 154 DEG or 73% changed in the opposite direction in microarray data sets related to normal endometrial maturation (P=0.01), including 16 DEG upregulated in decidual (relative to peripheral blood) natural killer cells that were downregulated in chorionic villous samples from women who developed preeclampsia (Ppreeclampsia. © 2014 American Heart Association, Inc.

  11. Gene expression profiling of early hepatic stellate cell activation reveals a role for Igfbp3 in cell migration.

    Directory of Open Access Journals (Sweden)

    Inge Mannaerts

    Full Text Available BACKGROUND: Scarring of the liver is the result of prolonged exposure to exogenous or endogenous stimuli. At the onset of fibrosis, quiescent hepatic stellate cells (HSCs activate and transdifferentiate into matrix producing, myofibroblast-like cells. AIM AND METHODS: To identify key players during early HSC activation, gene expression profiling was performed on primary mouse HSCs cultured for 4, 16 and 64 hours. Since valproic acid (VPA can partly inhibit HSC activation, we included VPA-treated cells in the profiling experiments to facilitate this search. RESULTS: Gene expression profiling confirmed early changes for known genes related to HSC activation such as alpha smooth muscle actin (Acta2, lysyl oxidase (Lox and collagen, type I, alpha 1 (Col1a1. In addition we noticed that, although genes which are related to fibrosis change between 4 and 16 hours in culture, most gene expression changes occur between 16 and 64 hours. Insulin-like growth factor binding protein 3 (Igfbp3 was identified as a gene strongly affected by VPA treatment. During normal HSC activation Igfbp3 is up regulated and this can thus be prevented by VPA treatment in vitro and in vivo. siRNA-mediated silencing of Igfbp3 in primary mouse HSCs induced matrix metalloproteinase (Mmp 9 mRNA expression and strongly reduced cell migration. The reduced cell migration after Igfbp3 knock-down could be overcome by tissue inhibitor of metalloproteinase (TIMP 1 treatment. CONCLUSION: Igfbp3 is a marker for culture-activated HSCs and plays a role in HSC migration. VPA treatment prevents Igfbp3 transcription during activation of HSCs in vitro and in vivo.

  12. Noncanonical compensation of zygotic X transcription in early Drosophila melanogaster development revealed through single-embryo RNA-seq.

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    Susan E Lott

    2011-02-01

    Full Text Available When Drosophila melanogaster embryos initiate zygotic transcription around mitotic cycle 10, the dose-sensitive expression of specialized genes on the X chromosome triggers a sex-determination cascade that, among other things, compensates for differences in sex chromosome dose by hypertranscribing the single X chromosome in males. However, there is an approximately 1 hour delay between the onset of zygotic transcription and the establishment of canonical dosage compensation near the end of mitotic cycle 14. During this time, zygotic transcription drives segmentation, cellularization, and other important developmental events. Since many of the genes involved in these processes are on the X chromosome, we wondered whether they are transcribed at higher levels in females and whether this might lead to sex-specific early embryonic patterning. To investigate this possibility, we developed methods to precisely stage, sex, and characterize the transcriptomes of individual embryos. We measured genome-wide mRNA abundance in male and female embryos at eight timepoints, spanning mitotic cycle 10 through late cycle 14, using polymorphisms between parental lines to distinguish maternal and zygotic transcription. We found limited sex-specific zygotic transcription, with a weak tendency for genes on the X to be expressed at higher levels in females. However, transcripts derived from the single X chromosome in males were more abundant that those derived from either X chromosome in females, demonstrating that there is widespread dosage compensation prior to the activation of the canonical MSL-mediated dosage compensation system. Crucially, this new system of early zygotic dosage compensation results in nearly identical transcript levels for key X-linked developmental regulators, including giant (gt, brinker (brk, buttonhead (btd, and short gastrulation (sog, in male and female embryos.

  13. Muscle spindle composition and distribution in human young masseter and biceps brachii muscles reveal early growth and maturation.

    Science.gov (United States)

    Osterlund, Catharina; Liu, Jing-Xia; Thornell, Lars-Eric; Eriksson, Per-Olof

    2011-04-01

    Significant changes in extrafusal fiber type composition take place in the human masseter muscle from young age, 3-7 years, to adulthood, in parallel with jaw-face skeleton growth, changes of dentitions and improvement of jaw functions. As motor and sensory control systems of muscles are interlinked, also the intrafusal fiber population, that is, muscle spindles, should undergo age-related changes in fiber type appearance. To test this hypothesis, we examined muscle spindles in the young masseter muscle and compared the result with previous data on adult masseter spindles. Also muscle spindles in the young biceps brachii muscle were examined. The result showed that muscle spindle composition and distribution were alike in young and adult masseter. As for the adult masseter, young masseter contained exceptionally large muscle spindles, and with the highest spindle density and most complex spindles found in the deep masseter portion. Hence, contrary to our hypothesis, masseter spindles do not undergo major morphological changes between young age and adulthood. Also in the biceps, young spindles were alike adult spindles. Taken together, the results showed that human masseter and biceps muscle spindles are morphologically mature already at young age. We conclude that muscle spindles in the human young masseter and biceps precede the extrafusal fiber population in growth and maturation. This in turn suggests early reflex control and proprioceptive demands in learning and maturation of jaw motor skills. Similarly, well-developed muscle spindles in young biceps reflect early need of reflex control in learning and performing arm motor behavior. Copyright © 2011 Wiley-Liss, Inc.

  14. Bounding approaches to system identification

    CERN Document Server

    Norton, John; Piet-Lahanier, Hélène; Walter, Éric

    1996-01-01

    In response to the growing interest in bounding error approaches, the editors of this volume offer the first collection of papers to describe advances in techniques and applications of bounding of the parameters, or state variables, of uncertain dynamical systems. Contributors explore the application of the bounding approach as an alternative to the probabilistic analysis of such systems, relating its importance to robust control-system design.

  15. with Bounded Failure Intensity

    Directory of Open Access Journals (Sweden)

    Preeti Wanti Srivastava

    2011-01-01

    Full Text Available This paper deals with the Bayes prediction of the future failures of a deteriorating repairable mechanical system subject to minimal repairs and periodic overhauls. To model the effect of overhauls on the reliability of the system a proportional age reduction model is assumed and the 2-parameter Engelhardt-Bain process (2-EBP is used to model the failure process between two successive overhauls. 2-EBP has an advantage over Power Law Process (PLP models. It is found that the failure intensity of deteriorating repairable systems attains a finite bound when repeated minimal repair actions are combined with some overhauls. If such a data is analyzed through models with unbounded increasing failure intensity, such as the PLP, then pessimistic estimates of the system reliability will arise and incorrect preventive maintenance policy may be defined. On the basis of the observed data and of a number of suitable prior densities reflecting varied degrees of belief on the failure/repair process and effectiveness of overhauls, the prediction of the future failure times and the number of failures in a future time interval is found. Finally, a numerical application is used to illustrate the advantages from overhauls and sensitivity analysis of the improvement parameter carried out.

  16. The crystal structures of apo and cAMP-bound GlxR from Corynebacterium glutamicum reveal structural and dynamic changes upon cAMP binding in CRP/FNR family transcription factors.

    Science.gov (United States)

    Townsend, Philip D; Jungwirth, Britta; Pojer, Florence; Bußmann, Michael; Money, Victoria A; Cole, Stewart T; Pühler, Alfred; Tauch, Andreas; Bott, Michael; Cann, Martin J; Pohl, Ehmke

    2014-01-01

    The cyclic AMP-dependent transcriptional regulator GlxR from Corynebacterium glutamicum is a member of the super-family of CRP/FNR (cyclic AMP receptor protein/fumarate and nitrate reduction regulator) transcriptional regulators that play central roles in bacterial metabolic regulatory networks. In C. glutamicum, which is widely used for the industrial production of amino acids and serves as a non-pathogenic model organism for members of the Corynebacteriales including Mycobacterium tuberculosis, the GlxR homodimer controls the transcription of a large number of genes involved in carbon metabolism. GlxR therefore represents a key target for understanding the regulation and coordination of C. glutamicum metabolism. Here we investigate cylic AMP and DNA binding of GlxR from C. glutamicum and describe the crystal structures of apo GlxR determined at a resolution of 2.5 Å, and two crystal forms of holo GlxR at resolutions of 2.38 and 1.82 Å, respectively. The detailed structural analysis and comparison of GlxR with CRP reveals that the protein undergoes a distinctive conformational change upon cyclic AMP binding leading to a dimer structure more compatible to DNA-binding. As the two binding sites in the GlxR homodimer are structurally identical dynamic changes upon binding of the first ligand are responsible for the allosteric behavior. The results presented here show how dynamic and structural changes in GlxR lead to optimization of orientation and distance of its two DNA-binding helices for optimal DNA recognition.

  17. The crystal structures of apo and cAMP-bound GlxR from Corynebacterium glutamicum reveal structural and dynamic changes upon cAMP binding in CRP/FNR family transcription factors.

    Directory of Open Access Journals (Sweden)

    Philip D Townsend

    Full Text Available The cyclic AMP-dependent transcriptional regulator GlxR from Corynebacterium glutamicum is a member of the super-family of CRP/FNR (cyclic AMP receptor protein/fumarate and nitrate reduction regulator transcriptional regulators that play central roles in bacterial metabolic regulatory networks. In C. glutamicum, which is widely used for the industrial production of amino acids and serves as a non-pathogenic model organism for members of the Corynebacteriales including Mycobacterium tuberculosis, the GlxR homodimer controls the transcription of a large number of genes involved in carbon metabolism. GlxR therefore represents a key target for understanding the regulation and coordination of C. glutamicum metabolism. Here we investigate cylic AMP and DNA binding of GlxR from C. glutamicum and describe the crystal structures of apo GlxR determined at a resolution of 2.5 Å, and two crystal forms of holo GlxR at resolutions of 2.38 and 1.82 Å, respectively. The detailed structural analysis and comparison of GlxR with CRP reveals that the protein undergoes a distinctive conformational change upon cyclic AMP binding leading to a dimer structure more compatible to DNA-binding. As the two binding sites in the GlxR homodimer are structurally identical dynamic changes upon binding of the first ligand are responsible for the allosteric behavior. The results presented here show how dynamic and structural changes in GlxR lead to optimization of orientation and distance of its two DNA-binding helices for optimal DNA recognition.

  18. Behavioral characterization of A53T mice reveals early and late stage deficits related to Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Katrina L Paumier

    Full Text Available Parkinson's disease (PD pathology is characterized by the formation of intra-neuronal inclusions called Lewy bodies, which are comprised of alpha-synuclein (α-syn. Duplication, triplication or genetic mutations in α-syn (A53T, A30P and E46K are linked to autosomal dominant PD; thus implicating its role in the pathogenesis of PD. In both PD patients and mouse models, there is increasing evidence that neuronal dysfunction occurs before the accumulation of protein aggregates (i.e., α-syn and neurodegeneration. Characterization of the timing and nature of symptomatic dysfunction is important for understanding the impact of α-syn on disease progression. Furthermore, this knowledge is essential for identifying pathways and molecular targets for therapeutic intervention. To this end, we examined various functional and morphological endpoints in the transgenic mouse model expressing the human A53T α-syn variant directed by the mouse prion promoter at specific ages relating to disease progression (2, 6 and 12 months of age. Our findings indicate A53T mice develop fine, sensorimotor, and synaptic deficits before the onset of age-related gross motor and cognitive dysfunction. Results from open field and rotarod tests show A53T mice develop age-dependent changes in locomotor activity and reduced anxiety-like behavior. Additionally, digigait analysis shows these mice develop an abnormal gait by 12 months of age. A53T mice also exhibit spatial memory deficits at 6 and 12 months, as demonstrated by Y-maze performance. In contrast to gross motor and cognitive changes, A53T mice display significant impairments in fine- and sensorimotor tasks such as grooming, nest building and acoustic startle as early as 1-2 months of age. These mice also show significant abnormalities in basal synaptic transmission, paired-pulse facilitation and long-term depression (LTD. Combined, these data indicate the A53T model exhibits early- and late-onset behavioral and synaptic

  19. Behavioral characterization of A53T mice reveals early and late stage deficits related to Parkinson's disease.

    Science.gov (United States)

    Paumier, Katrina L; Sukoff Rizzo, Stacey J; Berger, Zdenek; Chen, Yi; Gonzales, Cathleen; Kaftan, Edward; Li, Li; Lotarski, Susan; Monaghan, Michael; Shen, Wei; Stolyar, Polina; Vasilyev, Dmytro; Zaleska, Margaret; D Hirst, Warren; Dunlop, John

    2013-01-01

    Parkinson's disease (PD) pathology is characterized by the formation of intra-neuronal inclusions called Lewy bodies, which are comprised of alpha-synuclein (α-syn). Duplication, triplication or genetic mutations in α-syn (A53T, A30P and E46K) are linked to autosomal dominant PD; thus implicating its role in the pathogenesis of PD. In both PD patients and mouse models, there is increasing evidence that neuronal dysfunction occurs before the accumulation of protein aggregates (i.e., α-syn) and neurodegeneration. Characterization of the timing and nature of symptomatic dysfunction is important for understanding the impact of α-syn on disease progression. Furthermore, this knowledge is essential for identifying pathways and molecular targets for therapeutic intervention. To this end, we examined various functional and morphological endpoints in the transgenic mouse model expressing the human A53T α-syn variant directed by the mouse prion promoter at specific ages relating to disease progression (2, 6 and 12 months of age). Our findings indicate A53T mice develop fine, sensorimotor, and synaptic deficits before the onset of age-related gross motor and cognitive dysfunction. Results from open field and rotarod tests show A53T mice develop age-dependent changes in locomotor activity and reduced anxiety-like behavior. Additionally, digigait analysis shows these mice develop an abnormal gait by 12 months of age. A53T mice also exhibit spatial memory deficits at 6 and 12 months, as demonstrated by Y-maze performance. In contrast to gross motor and cognitive changes, A53T mice display significant impairments in fine- and sensorimotor tasks such as grooming, nest building and acoustic startle as early as 1-2 months of age. These mice also show significant abnormalities in basal synaptic transmission, paired-pulse facilitation and long-term depression (LTD). Combined, these data indicate the A53T model exhibits early- and late-onset behavioral and synaptic impairments

  20. Behavioral Characterization of A53T Mice Reveals Early and Late Stage Deficits Related to Parkinson’s Disease

    Science.gov (United States)

    Paumier, Katrina L.; Sukoff Rizzo, Stacey J.; Berger, Zdenek; Chen, Yi; Gonzales, Cathleen; Kaftan, Edward; Li, Li; Lotarski, Susan; Monaghan, Michael; Shen, Wei; Stolyar, Polina; Vasilyev, Dmytro; Zaleska, Margaret; D. Hirst, Warren; Dunlop, John

    2013-01-01

    Parkinson's disease (PD) pathology is characterized by the formation of intra-neuronal inclusions called Lewy bodies, which are comprised of alpha-synuclein (α-syn). Duplication, triplication or genetic mutations in α-syn (A53T, A30P and E46K) are linked to autosomal dominant PD; thus implicating its role in the pathogenesis of PD. In both PD patients and mouse models, there is increasing evidence that neuronal dysfunction occurs before the accumulation of protein aggregates (i.e., α-syn) and neurodegeneration. Characterization of the timing and nature of symptomatic dysfunction is important for understanding the impact of α-syn on disease progression. Furthermore, this knowledge is essential for identifying pathways and molecular targets for therapeutic intervention. To this end, we examined various functional and morphological endpoints in the transgenic mouse model expressing the human A53T α-syn variant directed by the mouse prion promoter at specific ages relating to disease progression (2, 6 and 12 months of age). Our findings indicate A53T mice develop fine, sensorimotor, and synaptic deficits before the onset of age-related gross motor and cognitive dysfunction. Results from open field and rotarod tests show A53T mice develop age-dependent changes in locomotor activity and reduced anxiety-like behavior. Additionally, digigait analysis shows these mice develop an abnormal gait by 12 months of age. A53T mice also exhibit spatial memory deficits at 6 and 12 months, as demonstrated by Y-maze performance. In contrast to gross motor and cognitive changes, A53T mice display significant impairments in fine- and sensorimotor tasks such as grooming, nest building and acoustic startle as early as 1–2 months of age. These mice also show significant abnormalities in basal synaptic transmission, paired-pulse facilitation and long-term depression (LTD). Combined, these data indicate the A53T model exhibits early- and late-onset behavioral and synaptic impairments

  1. ExtremeBounds: Extreme Bounds Analysis in R

    Directory of Open Access Journals (Sweden)

    Marek Hlavac

    2016-08-01

    Full Text Available This article introduces the R package ExtremeBounds to perform extreme bounds analysis (EBA, a sensitivity test that examines how robustly the dependent variable of a regression model is related to a variety of possible determinants. ExtremeBounds supports Leamer's EBA that focuses on the upper and lower extreme bounds of regression coefficients, as well as Sala-i-Martin's EBA which considers their entire distribution. In contrast to existing alternatives, it can estimate models of a variety of user-defined sizes, use regression models other than ordinary least squares, incorporate non-linearities in the model specification, and apply custom weights and standard errors. To alleviate concerns about the multicollinearity and conceptual overlap of examined variables, ExtremeBounds allows users to specify sets of mutually exclusive variables, and can restrict the analysis to coefficients from regression models that yield a variance inflation factor within a prespecified limit.

  2. Early activation of Broca's area in grammar processing as revealed by the syntactic mismatch negativity and distributed source analysis.

    Science.gov (United States)

    Hanna, Jeff; Mejias, Sandrine; Schelstraete, Marie-Anne; Pulvermüller, Friedemann; Shtyrov, Yury; Van der Lely, Heather K J

    2014-01-01

    Though activation of Broca's region in the combinatorial processing of symbols (language, music) has been revealed by neurometabolic studies, most previous neurophysiological research found the earliest grammar indices in the temporal cortex, with inferior-frontal generators becoming active at relatively late stages. We use the attention- and task-free syntactic mismatch negativity (sMMN) event-related potential (ERP) to measure rapid and automatic sensitivity of the human brain to grammatical information in participants' native language (French). Further, sources underlying the MMN were estimated by applying the Parametrical Empirical Bayesian (PEB) approach, with the Multiple Sparse Priors (MSP) technique. Results showed reliable grammar-related activation focused on Broca's region already in the 150-190 ms time window, providing robust documentation of its involvement in the first stages of syntactic processing.

  3. Targeted Metabolomics Reveals Early Dominant Optic Atrophy Signature in Optic Nerves of Opa1delTTAG/+ Mice.

    Science.gov (United States)

    Chao de la Barca, Juan Manuel; Simard, Gilles; Sarzi, Emmanuelle; Chaumette, Tanguy; Rousseau, Guillaume; Chupin, Stéphanie; Gadras, Cédric; Tessier, Lydie; Ferré, Marc; Chevrollier, Arnaud; Desquiret-Dumas, Valérie; Gueguen, Naïg; Leruez, Stéphanie; Verny, Christophe; Miléa, Dan; Bonneau, Dominique; Amati-Bonneau, Patrizia; Procaccio, Vincent; Hamel, Christian; Lenaers, Guy; Reynier, Pascal; Prunier-Mirebeau, Delphine

    2017-02-01

    Dominant optic atrophy (MIM No. 165500) is a blinding condition related to mutations in OPA1, a gene encoding a large GTPase involved in mitochondrial inner membrane dynamics. Although several mouse models mimicking the disease have been developed, the pathophysiological mechanisms responsible for retinal ganglion cell degeneration remain poorly understood. Using a targeted metabolomic approach, we measured the concentrations of 188 metabolites in nine tissues, that is, brain, three types of skeletal muscle, heart, liver, retina, optic nerve, and plasma in symptomatic 11-month-old Opa1delTTAG/+ mice. Significant metabolic signatures were found only in the optic nerve and plasma of female mice. The optic nerve signature was characterized by altered concentrations of phospholipids, amino acids, acylcarnitines, and carnosine, whereas the plasma signature showed decreased concentrations of amino acids and sarcosine associated with increased concentrations of several phospholipids. In contrast, the investigation of 3-month-old presymptomatic Opa1delTTAG/+ mice showed no specific plasma signature but revealed a significant optic nerve signature in both sexes, although with a sex effect. The Opa1delTTAG/+ versus wild-type optic nerve signature was characterized by the decreased concentrations of 10 sphingomyelins and 10 lysophosphatidylcholines, suggestive of myelin sheath alteration, and by alteration in the concentrations of metabolites involved in neuroprotection, such as dimethylarginine, carnitine, spermine, spermidine, carnosine, and glutamate, suggesting a concomitant axonal metabolic dysfunction. Our comprehensive metabolomic investigations revealed in symptomatic as well as in presymptomatic Opa1delTTAG/+ mice, a specific sensitiveness of the optic nerve to Opa1 insufficiency, opening new routes for protective therapeutic strategies.

  4. Connectivity Reveals Sources of Predictive Coding Signals in Early Visual Cortex During Processing of Visual Optic Flow.

    Science.gov (United States)

    Schindler, Andreas; Bartels, Andreas

    2017-05-01

    Superimposed on the visual feed-forward pathway, feedback connections convey higher level information to cortical areas lower in the hierarchy. A prominent framework for these connections is the theory of predictive coding where high-level areas send stimulus interpretations to lower level areas that compare them with sensory input. Along these lines, a growing body of neuroimaging studies shows that predictable stimuli lead to reduced blood oxygen level-dependent (BOLD) responses compared with matched nonpredictable counterparts, especially in early visual cortex (EVC) including areas V1-V3. The sources of these modulatory feedback signals are largely unknown. Here, we re-examined the robust finding of relative BOLD suppression in EVC evident during processing of coherent compared with random motion. Using functional connectivity analysis, we show an optic flow-dependent increase of functional connectivity between BOLD suppressed EVC and a network of visual motion areas including MST, V3A, V6, the cingulate sulcus visual area (CSv), and precuneus (Pc). Connectivity decreased between EVC and 2 areas known to encode heading direction: entorhinal cortex (EC) and retrosplenial cortex (RSC). Our results provide first evidence that BOLD suppression in EVC for predictable stimuli is indeed mediated by specific high-level areas, in accord with the theory of predictive coding. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  5. A multi-gene dataset reveals a tropical New World origin and Early Miocene diversification of croakers (Perciformes: Sciaenidae).

    Science.gov (United States)

    Lo, Pei-Chun; Liu, Shu-Hui; Chao, Ning Labbish; Nunoo, Francis K E; Mok, Hin-Kiu; Chen, Wei-Jen

    2015-07-01

    Widely distributed groups of living animals, such as the predominantly marine fish family Sciaenidae, have always attracted the attention of biogeographers to document the origins and patterns of diversification in time and space. In this study, the historical biogeography of the global Sciaenidae is reconstructed within a molecular phylogenetic framework to investigate their origin and to test the hypotheses explaining the present-day biogeographic patterns. Our data matrix comprises six mitochondrial and nuclear genes in 93 globally sampled sciaenid species from 52 genera. Within the inferred phylogenetic tree of the Sciaenidae, we identify 15 main and well-supported lineages; some of which have not been recognized previously. Reconstruction of habitat preferences shows repeated habitat transitions between marine and euryhaline environments. This implies that sciaenids can easily adapt to some variations in salinity, possibly as the consequence of their nearshore habitats and migratory life history. Conversely, complete marine/euryhaline to freshwater transitions occurred only three times, in South America, North America and South Asia. Ancestral range reconstruction analysis concomitant with fossil evidence indicates that sciaenids first originated and diversified in the tropical America during the Oligocene to Early Miocene before undergoing two range expansions, to Eastern Atlantic and to the Indo-West Pacific where a maximum species richness is observed. The uncommon biogeographic pattern identified is discussed in relation to current knowledge on origin of gradients of marine biodiversity toward the center of origin hypothesis in the Indo-West Pacific. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. iPSC-derived neuronal models of PANK2-associated neurodegeneration reveal mitochondrial dysfunction contributing to early disease.

    Directory of Open Access Journals (Sweden)

    Charles Arber

    Full Text Available Mutations in PANK2 lead to neurodegeneration with brain iron accumulation. PANK2 has a role in the biosynthesis of coenzyme A (CoA from dietary vitamin B5, but the neuropathological mechanism and reasons for iron accumulation remain unknown. In this study, atypical patient-derived fibroblasts were reprogrammed into induced pluripotent stem cells (iPSCs and subsequently differentiated into cortical neuronal cells for studying disease mechanisms in human neurons. We observed no changes in PANK2 expression between control and patient cells, but a reduction in protein levels was apparent in patient cells. CoA homeostasis and cellular iron handling were normal, mitochondrial function was affected; displaying activated NADH-related and inhibited FADH-related respiration, resulting in increased mitochondrial membrane potential. This led to increased reactive oxygen species generation and lipid peroxidation in patient-derived neurons. These data suggest that mitochondrial deficiency is an early feature of the disease process and can be explained by altered NADH/FADH substrate supply to oxidative phosphorylation. Intriguingly, iron chelation appeared to exacerbate the mitochondrial phenotype in both control and patient neuronal cells. This raises caution for the use iron chelation therapy in general when iron accumulation is absent.

  7. Early Cenomanian "hot greenhouse" revealed by oxygen isotope record of exceptionally well-preserved foraminifera from Tanzania

    Science.gov (United States)

    Ando, Atsushi; Huber, Brian T.; MacLeod, Kenneth G.; Watkins, David K.

    2015-11-01

    The search into Earth's mid-Cretaceous greenhouse conditions has recently been stimulated by the Tanzania Drilling Project (TDP) which has recovered exceptionally well-preserved biogenic carbonates from subsurface pre-Neogene marine sediments in the eastern margin of central Africa. Published Tanzanian oxygen isotope records measured on exquisitely preserved foraminiferal tests, dating to as old as ~93 Ma, provided evidence for a Turonian "hot greenhouse" with very high and stable water-column temperatures. We have generated a comparable data set of exceptionally well-preserved foraminifera from a lower Cenomanian interval of TDP Site 24 spanning 99.9-95.9 Ma (planktonic foraminiferal Thalmanninella globotruncanoides Zone; nannofossil Corollithion kennedyi to Lithraphidites eccentricus Zones), thereby extending the age coverage of the Tanzanian foraminiferal δ18O record back by ~7 million years. Throughout the interval analyzed, the new foraminiferal δ18O data are consistently around -4.3‰ for surface-dwelling planktonic taxa and -1.9‰ for benthic Lenticulina spp., which translate to conservative paleotemperature estimates of >31°C at the surface and >17°C at the sea floor (upper bathyal depths). Considering the ~40°S Cenomanian paleolatitude of TDP Site 24, these estimates are higher than computer simulation results for accepted "normal" greenhouse conditions (those with up to 4X preindustrial pCO2 level) and suggest that the climate mode of the early Cenomanian was very similar to the Turonian hot greenhouse. Taking account of other comparable data sources from different regions, the hot greenhouse mode within the normal mid-Cretaceous greenhouse may have begun by the latest Albian, but the precise timing of the critical transition remains uncertain.

  8. A zebrafish model of congenital disorders of glycosylation with phosphomannose isomerase deficiency reveals an early opportunity for corrective mannose supplementation

    Directory of Open Access Journals (Sweden)

    Jaime Chu

    2013-01-01

    Individuals with congenital disorders of glycosylation (CDG have recessive mutations in genes required for protein N-glycosylation, resulting in multi-systemic disease. Despite the well-characterized biochemical consequences in these individuals, the underlying cellular defects that contribute to CDG are not well understood. Synthesis of the lipid-linked oligosaccharide (LLO, which serves as the sugar donor for the N-glycosylation of secretory proteins, requires conversion of fructose-6-phosphate to mannose-6-phosphate via the phosphomannose isomerase (MPI enzyme. Individuals who are deficient in MPI present with bleeding, diarrhea, edema, gastrointestinal bleeding and liver fibrosis. MPI-CDG patients can be treated with oral mannose supplements, which is converted to mannose-6-phosphate through a minor complementary metabolic pathway, restoring protein glycosylation and ameliorating most symptoms, although liver disease continues to progress. Because Mpi deletion in mice causes early embryonic lethality and thus is difficult to study, we used zebrafish to establish a model of MPI-CDG. We used a morpholino to block mpi mRNA translation and established a concentration that consistently yielded 13% residual Mpi enzyme activity at 4 days post-fertilization (dpf, which is within the range of MPI activity detected in fibroblasts from MPI-CDG patients. Fluorophore-assisted carbohydrate electrophoresis detected decreased LLO and N-glycans in mpi morphants. These deficiencies resulted in 50% embryonic lethality by 4 dpf. Multi-systemic abnormalities, including small eyes, dysmorphic jaws, pericardial edema, a small liver and curled tails, occurred in 82% of the surviving larvae. Importantly, these phenotypes could be rescued with mannose supplementation. Thus, parallel processes in fish and humans contribute to the phenotypes caused by Mpi depletion. Interestingly, mannose was only effective if provided prior to 24 hpf. These data provide insight into treatment efficacy

  9. Differentially expressed androgen-regulated genes in androgen-sensitive tissues reveal potential biomarkers of early prostate cancer.

    Science.gov (United States)

    Altintas, Dogus Murat; Allioli, Nathalie; Decaussin, Myriam; de Bernard, Simon; Ruffion, Alain; Samarut, Jacques; Vlaeminck-Guillem, Virginie

    2013-01-01

    Several data favor androgen receptor implication in prostate cancer initiation through the induction of several gene activation programs. The aim of the study is to identify potential biomarkers for early diagnosis of prostate cancer (PCa) among androgen-regulated genes (ARG) and to evaluate comparative expression of these genes in normal prostate and normal prostate-related androgen-sensitive tissues that do not (or rarely) give rise to cancer. ARG were selected in non-neoplastic adult human prostatic epithelial RWPE-1 cells stably expressing an exogenous human androgen receptor, using RNA-microarrays and validation by qRT-PCR. Expression of 48 preselected genes was quantified in tissue samples (seminal vesicles, prostate transitional zones and prostate cancers, benign prostatic hypertrophy obtained from surgical specimens) using TaqMan® low-density arrays. The diagnostic performances of these potential biomarkers were compared to that of genes known to be associated with PCa (i.e. PCA3 and DLX1). By crossing expression studies in 26 matched PCa and normal prostate transitional zone samples, and 35 matched seminal vesicle and PCa samples, 14 genes were identified. Similarly, 9 genes were overexpressed in 15 benign prostatic hypertrophy samples, as compared to PCa samples. Overall, we selected 8 genes of interest to evaluate their diagnostic performances in comparison with that of PCA3 and DLX1. Among them, 3 genes: CRYAB, KCNMA1 and SDPR, were overexpressed in all 3 reference non-cancerous tissues. The areas under ROC curves of these genes reached those of PCA3 (0.91) and DLX1 (0.94). We identified ARG with reduced expression in PCa and with significant diagnostic values for discriminating between cancerous and non-cancerous prostatic tissues, similar that of PCA3. Given their expression pattern, they could be considered as potentially protective against prostate cancer. Moreover, they could be complementary to known genes overexpressed in PCa and included along

  10. Kinetic analyses reveal potent and early blockade of hepatitis C virus assembly by NS5A inhibitors.

    Science.gov (United States)

    McGivern, David R; Masaki, Takahiro; Williford, Sara; Ingravallo, Paul; Feng, Zongdi; Lahser, Frederick; Asante-Appiah, Ernest; Neddermann, Petra; De Francesco, Raffaele; Howe, Anita Y; Lemon, Stanley M

    2014-08-01

    All-oral regimens combining different classes of direct-acting antivirals (DAA) are highly effective for treatment of patients with chronic hepatitis C. NS5A inhibitors will likely form a component of future interferon-sparing treatment regimens. However, despite their potential, the detailed mechanism of action of NS5A inhibitors is unclear. To study their mechanisms, we compared their kinetics of antiviral suppression with those of other classes of DAA, using the hepatitis C virus genotype 1a cell culture-infectious virus H77S.3. We performed detailed kinetic analyses of specific steps in the hepatitis C virus life cycle using cell cultures incubated with protease inhibitors, polymerase inhibitors, or NS5A inhibitors. Assays were designed to measure active viral RNA synthesis and steady-state RNA abundance, polyprotein synthesis, virion assembly, and infectious virus production. Despite their high potency, NS5A inhibitors were slow to inhibit viral RNA synthesis compared with protease or polymerase inhibitors. By 24 hours after addition of an NS5A inhibitor, polyprotein synthesis was reduced <50%, even at micromolar concentrations. In contrast, inhibition of virus release by NS5A inhibitors was potent and rapid, with onset of inhibition as early as 2 hours. Cells incubated with NS5A inhibitors were rapidly depleted of intracellular infectious virus and RNA-containing hepatitis C virus particles, indicating a block in virus assembly. DAAs that target NS5A rapidly inhibit intracellular assembly of genotype 1a virions. They also inhibit formation of functional replicase complexes, but have no activity against preformed replicase, thereby resulting in slow shut-off of viral RNA synthesis. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

  11. Whole transcriptome profiling of maize during early somatic embryogenesis reveals altered expression of stress factors and embryogenesis-related genes.

    Directory of Open Access Journals (Sweden)

    Stella A G D Salvo

    Full Text Available Embryogenic tissue culture systems are utilized in propagation and genetic engineering of crop plants, but applications are limited by genotype-dependent culture response. To date, few genes necessary for embryogenic callus formation have been identified or characterized. The goal of this research was to enhance our understanding of gene expression during maize embryogenic tissue culture initiation. In this study, we highlight the expression of candidate genes that have been previously regarded in the literature as having important roles in somatic embryogenesis. We utilized RNA based sequencing (RNA-seq to characterize the transcriptome of immature embryo explants of the highly embryogenic and regenerable maize genotype A188 at 0, 24, 36, 48, and 72 hours after placement of explants on tissue culture initiation medium. Genes annotated as functioning in stress response, such as glutathione-S-transferases and germin-like proteins, and genes involved with hormone transport, such as PINFORMED, increased in expression over 8-fold in the study. Maize genes with high sequence similarity to genes previously described in the initiation of embryogenic cultures, such as transcription factors BABY BOOM, LEAFY COTYLEDON, and AGAMOUS, and important receptor-like kinases such as SOMATIC EMBRYOGENESIS RECEPTOR LIKE KINASES and CLAVATA, were also expressed in this time course study. By combining results from whole genome transcriptome analysis with an in depth review of key genes that play a role in the onset of embryogenesis, we propose a model of coordinated expression of somatic embryogenesis-related genes, providing an improved understanding of genomic factors involved in the early steps of embryogenic culture initiation in maize and other plant species.

  12. The Effect of Early Trauma Exposure on Serotonin Type 1B Receptor Expression Revealed by Reduced Selective Radioligand Binding

    Science.gov (United States)

    Murrough, James W.; Czermak, Christoph; Henry, Shannan; Nabulsi, Nabeel; Gallezot, Jean-Dominique; Gueorguieva, Ralitza; Planeta-Wilson, Beata; Krystal, John H.; Neumaier, John F.; Huang, Yiyun; Ding, Yu-Shin; Carson, Richard E.; Neumeister, Alexander

    2011-01-01

    Context Serotonergic dysfunction is implicated in the pathogenesis of posttraumatic stress disorder (PTSD), and recent animal models suggest that disturbances in serotonin type 1B receptor function, in particular, may contribute to chronic anxiety. However, the specific role of the serotonin type 1B receptor has not been studied in patients with PTSD. Objective To investigate in vivo serotonin type 1B receptor expression in individuals with PTSD, trauma-exposed control participants without PTSD (TC), and healthy (non–trauma-exposed) control participants (HC) using positron emission tomography and the recently developed serotonin type 1B receptor selective radiotracer [11C]P943. Design Cross-sectional positron emission tomography study under resting conditions. Setting Academic and Veterans Affairs medical centers. Participants Ninety-six individuals in 3 study groups: PTSD (n=49), TC (n=20), and HC (n=27). Main Outcome Measure Regional [11C]P943 binding potential (BPND) values in an a priori–defined limbic corticostriatal circuit investigated using multivariate analysis of variance and multiple regression analysis. Results A history of severe trauma exposure in the PTSD and TC groups was associated with marked reductions in [11C]P943 BPND in the caudate, the amygdala, and the anterior cingulate cortex. Participant age at first trauma exposure was strongly associated with low [11C]P943 BPND. Developmentally earlier trauma exposure also was associated with greater PTSD symptom severity and major depression comorbidity. Conclusions These data suggest an enduring effect of trauma history on brain function and the phenotype of PTSD. The association of early age at first trauma and more pronounced neurobiological and behavioral alterations in PTSD suggests a developmental component in the cause of PTSD. PMID:21893657

  13. Bounds for Asian basket options

    Science.gov (United States)

    Deelstra, Griselda; Diallo, Ibrahima; Vanmaele, Michèle

    2008-09-01

    In this paper we propose pricing bounds for European-style discrete arithmetic Asian basket options in a Black and Scholes framework. We start from methods used for basket options and Asian options. First, we use the general approach for deriving upper and lower bounds for stop-loss premia of sums of non-independent random variables as in Kaas et al. [Upper and lower bounds for sums of random variables, Insurance Math. Econom. 27 (2000) 151-168] or Dhaene et al. [The concept of comonotonicity in actuarial science and finance: theory, Insurance Math. Econom. 31(1) (2002) 3-33]. We generalize the methods in Deelstra et al. [Pricing of arithmetic basket options by conditioning, Insurance Math. Econom. 34 (2004) 55-57] and Vanmaele et al. [Bounds for the price of discrete sampled arithmetic Asian options, J. Comput. Appl. Math. 185(1) (2006) 51-90]. Afterwards we show how to derive an analytical closed-form expression for a lower bound in the non-comonotonic case. Finally, we derive upper bounds for Asian basket options by applying techniques as in Thompson [Fast narrow bounds on the value of Asian options, Working Paper, University of Cambridge, 1999] and Lord [Partially exact and bounded approximations for arithmetic Asian options, J. Comput. Finance 10 (2) (2006) 1-52]. Numerical results are included and on the basis of our numerical tests, we explain which method we recommend depending on moneyness and time-to-maturity.

  14. Environmental proteomics reveals early microbial community responses to biostimulation at a uranium- and nitrate-contaminated site

    Energy Technology Data Exchange (ETDEWEB)

    Chourey, Karuna [ORNL; Nissen, Silke [ORNL; Vishnivetskaya, T. [University of Tennessee, Knoxville (UTK); Shah, Manesh B [ORNL; Pffifner, Susan [University of Tennessee, Knoxville (UTK); Hettich, Robert {Bob} L [ORNL; Loeffler, Frank E [ORNL

    2013-01-01

    High performance mass spectrometry instrumentation coupled with improved protein extraction techniques enable metaproteomics to identify active members of soil and groundwater microbial communities. Metaproteomics workflows were applied to study the initial responses (i.e., 4 days post treatment) of the indigenous aquifer microbiota to biostimulation with emulsified vegetable oil (EVO) at a uranium-contaminated site. Members of the Betaproteobacteria (i.e., Dechloromonas, Ralstonia, Rhodoferax, Polaromonas, Delftia, Chromobacterium) and Firmicutes dominated the biostimulated aquifer community. Proteome characterization revealed distinct differences in protein expression between the microbial biomass collected from groundwater influenced by biostimulation and groundwater collected up-gradient of the EVO injection points. In particular, proteins involved in ammonium assimilation, EVO degradation, and polyhydroxybutyrate (PHB) granule formation were prominent following biostimulation. Interestingly, the atypical NosZ of a Dechloromonas sp. was highly expressed suggesting active nitrous oxide (N2O) respiration. c-type cytochromes were barely detected, as was citrate synthase, a biomarker for hexavalent uranium reduction activity, suggesting that metal reduction has not commenced 4 days post EVO delivery. Environmental metaproteomics identified microbial community responses to biostimulation and elucidated active pathways demonstrating the value of this technique for complementing nucleic acid-based approaches.

  15. Hadron-nucleus bound states

    CERN Document Server

    Yamazaki, T

    2000-01-01

    A new type of nuclear spectroscopy to study hadron-nucleus bound states is described. The first successful experiment was to search for deeply bound pi sup - states in heavy nuclei using the sup 2 sup 0 sup 8 Pb(d, sup 3 He) reaction at GSI, in which a narrow peak arising from the 2p pi sup - orbital coupled with the neutron-hole states was observed at 135 MeV excitation energy. An improved experiment has just been carried out to separately identify the 1s and 2p pi sup - states. These experiments provide important information on the local potential strength, from which the effective mass of pi sup - is deduced to be 20 MeV. This method will be extended to search for eta and omega bound states as well as for K sup - bound states. The advantage of the bound-state spectroscopy versus invariant mass spectroscopy is emphasized.

  16. Market Access through Bound Tariffs

    DEFF Research Database (Denmark)

    Sala, Davide; Schröder, Philipp J.H.; Yalcin, Erdal

    on the risk that exporters face in destination markets. The present paper formalizes the underlying interaction of risk, fixed export costs and firms' market entry decisions based on techniques known from the real options literature; doing so we highlight the important role of bound tariffs at the extensive......WTO negotiations deal predominantly with bound - besides applied - tariff rates. But, how can reductions in tariffs ceilings, i.e. tariff rates that no exporter may ever actually be confronted with, generate market access? The answer to this question relates to the effects of tariff bindings...... margin of trade. We find that bound tariffs are more effective with higher risk destination markets, that a large binding overhang may still command substantial market access, and that reductions in bound tariffs generate effective market access even when bound rates are above current and long...

  17. Market access through bound tariffs

    DEFF Research Database (Denmark)

    Sala, Davide; Schröder, Philipp J.H.; Yalcin, Erdal

    2010-01-01

    on the risk that exporters face in destination markets. The present paper formalizes the underlying interaction of risk, fixed export costs and firms' market entry decisions based on techniques known from the real options literature; doing so we highlight the important role of bound tariffs at the extensive......WTO negotiations deal predominantly with bound - besides applied - tariff rates. But, how can reductions in tariffs ceilings, i.e. tariff rates that no exporter may ever actually be confronted with, generate market access? The answer to this question relates to the effects of tariff bindings...... margin of trade. We find that bound tariffs are more effective with higher risk destination markets, that a large binding overhang may still command substantial market access, and that reductions in bound tariffs generate effective market access even when bound rates are above current and longterm...

  18. Cosmological bounds on neutrino degeneracy and the Dirac neutrino magnetic moment

    Science.gov (United States)

    Semikoz, V. B.

    2017-11-01

    The amplification of a seed cosmological magnetic field (CMF) in a hot electroweak plasma of early Universe driven by neutrino degeneracy (asymmetry) is provided by a lower bound on such asymmetries that is in agreement with the known upper (BBN) bound on the electron neutrino asymmetry. Independently of a mechanism for CMF generation one predicts a stringent upper bound on the Dirac neutrino magnetic moment using the lower bound on CMF amplitude found from the Fermi satellite experiment.

  19. Differentially expressed androgen-regulated genes in androgen-sensitive tissues reveal potential biomarkers of early prostate cancer.

    Directory of Open Access Journals (Sweden)

    Dogus Murat Altintas

    Full Text Available BACKGROUND: Several data favor androgen receptor implication in prostate cancer initiation through the induction of several gene activation programs. The aim of the study is to identify potential biomarkers for early diagnosis of prostate cancer (PCa among androgen-regulated genes (ARG and to evaluate comparative expression of these genes in normal prostate and normal prostate-related androgen-sensitive tissues that do not (or rarely give rise to cancer. METHODS: ARG were selected in non-neoplastic adult human prostatic epithelial RWPE-1 cells stably expressing an exogenous human androgen receptor, using RNA-microarrays and validation by qRT-PCR. Expression of 48 preselected genes was quantified in tissue samples (seminal vesicles, prostate transitional zones and prostate cancers, benign prostatic hypertrophy obtained from surgical specimens using TaqMan® low-density arrays. The diagnostic performances of these potential biomarkers were compared to that of genes known to be associated with PCa (i.e. PCA3 and DLX1. RESULTS AND DISCUSSION: By crossing expression studies in 26 matched PCa and normal prostate transitional zone samples, and 35 matched seminal vesicle and PCa samples, 14 genes were identified. Similarly, 9 genes were overexpressed in 15 benign prostatic hypertrophy samples, as compared to PCa samples. Overall, we selected 8 genes of interest to evaluate their diagnostic performances in comparison with that of PCA3 and DLX1. Among them, 3 genes: CRYAB, KCNMA1 and SDPR, were overexpressed in all 3 reference non-cancerous tissues. The areas under ROC curves of these genes reached those of PCA3 (0.91 and DLX1 (0.94. CONCLUSIONS: We identified ARG with reduced expression in PCa and with significant diagnostic values for discriminating between cancerous and non-cancerous prostatic tissues, similar that of PCA3. Given their expression pattern, they could be considered as potentially protective against prostate cancer. Moreover, they could

  20. HR-MAS MRS of the pancreas reveals reduced lipid and elevated lactate and taurine associated with early pancreatic cancer.

    Science.gov (United States)

    Wang, Alan S; Lodi, Alessia; Rivera, Lee B; Izquierdo-Garcia, Jose L; Firpo, Matthew A; Mulvihill, Sean J; Tempero, Margaret A; Bergers, Gabriele; Ronen, Sabrina M

    2014-11-01

    The prognosis for patients with pancreatic cancer is extremely poor, as evidenced by the disease's five-year survival rate of ~5%. New approaches are therefore urgently needed to improve detection, treatment, and monitoring of pancreatic cancer. MRS-detectable metabolic changes provide useful biomarkers for tumor detection and response-monitoring in other cancers. The goal of this study was to identify MRS-detectable biomarkers of pancreatic cancer that could enhance currently available imaging approaches. We used (1) H high-resolution magic angle spinning MRS to probe metabolite levels in pancreatic tissue samples from mouse models and patients. In mice, the levels of lipids dropped significantly in pancreata with lipopolysaccharide-induced inflammation, in pancreata with pre-cancerous metaplasia (4 week old p48-Cre;LSL-Kras(G12D) mice), and in pancreata with pancreatic intraepithelial neoplasia, which precedes invasive pancreatic cancer (8 week old p48-Cre LSL-Kras(G12D) mice), to 26 ± 19% (p = 0.03), 19 ± 16% (p = 0.04), and 26 ± 10% (p = 0.05) of controls, respectively. Lactate and taurine remained unchanged in inflammation and in pre-cancerous metaplasia but increased significantly in pancreatic intraepithelial neoplasia to 266 ± 61% (p = 0.0001) and 999 ± 174% (p pancreatitis and in invasive cancer biopsies to 29 ± 15% (p = 0.01) and 26 ± 38% (p = 0.02) of normal tissue. In addition, lactate and taurine levels remained unchanged in inflammation but rose in tumor samples to 244 ± 155% (p = 0.02) and 188 ± 67% (p = 0.02), respectively, compared with normal tissue. Based on these findings, we propose that a drop in lipid levels could serve to inform on pancreatitis and cancer-associated inflammation, whereas elevated lactate and taurine could serve to identify the presence of pancreatic intraepithelial neoplasia and invasive tumor. Our findings may help enhance current imaging methods to improve early pancreatic cancer detection and monitoring

  1. Exome sequencing analysis reveals variants in primary immunodeficiency genes in patients with very early onset inflammatory bowel disease.

    Science.gov (United States)

    Kelsen, Judith R; Dawany, Noor; Moran, Christopher J; Petersen, Britt-Sabina; Sarmady, Mahdi; Sasson, Ariella; Pauly-Hubbard, Helen; Martinez, Alejandro; Maurer, Kelly; Soong, Joanne; Rappaport, Eric; Franke, Andre; Keller, Andreas; Winter, Harland S; Mamula, Petar; Piccoli, David; Artis, David; Sonnenberg, Gregory F; Daly, Mark; Sullivan, Kathleen E; Baldassano, Robert N; Devoto, Marcella

    2015-11-01

    Very early onset inflammatory bowel disease (VEO-IBD), IBD diagnosed at 5 years of age or younger, frequently presents with a different and more severe phenotype than older-onset IBD. We investigated whether patients with VEO-IBD carry rare or novel variants in genes associated with immunodeficiencies that might contribute to disease development. Patients with VEO-IBD and parents (when available) were recruited from the Children's Hospital of Philadelphia from March 2013 through July 2014. We analyzed DNA from 125 patients with VEO-IBD (age, 3 wk to 4 y) and 19 parents, 4 of whom also had IBD. Exome capture was performed by Agilent SureSelect V4, and sequencing was performed using the Illumina HiSeq platform. Alignment to human genome GRCh37 was achieved followed by postprocessing and variant calling. After functional annotation, candidate variants were analyzed for change in protein function, minor allele frequency less than 0.1%, and scaled combined annotation-dependent depletion scores of 10 or less. We focused on genes associated with primary immunodeficiencies and related pathways. An additional 210 exome samples from patients with pediatric IBD (n = 45) or adult-onset Crohn's disease (n = 20) and healthy individuals (controls, n = 145) were obtained from the University of Kiel, Germany, and used as control groups. Four hundred genes and regions associated with primary immunodeficiency, covering approximately 6500 coding exons totaling more than 1 Mbp of coding sequence, were selected from the whole-exome data. Our analysis showed novel and rare variants within these genes that could contribute to the development of VEO-IBD, including rare heterozygous missense variants in IL10RA and previously unidentified variants in MSH5 and CD19. In an exome sequence analysis of patients with VEO-IBD and their parents, we identified variants in genes that regulate B- and T-cell functions and could contribute to pathogenesis. Our analysis could lead to the

  2. Screening of the Open Source Malaria Box Reveals an Early Lead Compound for the Treatment of Alveolar Echinococcosis.

    Directory of Open Access Journals (Sweden)

    Britta Stadelmann

    2016-03-01

    Full Text Available The metacestode (larval stage of the tapeworm Echinococcus multilocularis causes alveolar echinococcosis (AE, a very severe and in many cases incurable disease. To date, benzimidazoles such as albendazole and mebendazole are the only approved chemotherapeutical treatment options. Benzimidazoles inhibit metacestode proliferation, but do not act parasiticidal. Thus, benzimidazoles have to be taken a lifelong, can cause adverse side effects such as hepatotoxicity, and are ineffective in some patients. We here describe a newly developed screening cascade for the evaluation of the in vitro efficacy of new compounds that includes assessment of parasiticidal activity. The Malaria Box from Medicines for Malaria Venture (MMV, comprised of 400 commercially available chemicals that show in vitro activity against Plasmodium falciparum, was repurposed. Primary screening was carried out at 10 μM by employing the previously described PGI assay, and resulted in the identification of 24 compounds that caused physical damage in metacestodes. Seven out of these 24 drugs were also active at 1 μM. Dose-response assays revealed that only 2 compounds, namely MMV665807 and MMV665794, exhibited an EC50 value below 5 μM. Assessments using human foreskin fibroblasts and Reuber rat hepatoma cells showed that the salicylanilide MMV665807 was less toxic for these two mammalian cell lines than for metacestodes. The parasiticidal activity of MMV665807 was then confirmed using isolated germinal layer cell cultures as well as metacestode vesicles by employing viability assays, and its effect on metacestodes was morphologically evaluated by electron microscopy. However, both oral and intraperitoneal application of MMV665807 to mice experimentally infected with E. multilocularis metacestodes did not result in any reduction of the parasite load.

  3. Screening of the Open Source Malaria Box Reveals an Early Lead Compound for the Treatment of Alveolar Echinococcosis.

    Science.gov (United States)

    Stadelmann, Britta; Rufener, Reto; Aeschbacher, Denise; Spiliotis, Markus; Gottstein, Bruno; Hemphill, Andrew

    2016-03-01

    The metacestode (larval) stage of the tapeworm Echinococcus multilocularis causes alveolar echinococcosis (AE), a very severe and in many cases incurable disease. To date, benzimidazoles such as albendazole and mebendazole are the only approved chemotherapeutical treatment options. Benzimidazoles inhibit metacestode proliferation, but do not act parasiticidal. Thus, benzimidazoles have to be taken a lifelong, can cause adverse side effects such as hepatotoxicity, and are ineffective in some patients. We here describe a newly developed screening cascade for the evaluation of the in vitro efficacy of new compounds that includes assessment of parasiticidal activity. The Malaria Box from Medicines for Malaria Venture (MMV), comprised of 400 commercially available chemicals that show in vitro activity against Plasmodium falciparum, was repurposed. Primary screening was carried out at 10 μM by employing the previously described PGI assay, and resulted in the identification of 24 compounds that caused physical damage in metacestodes. Seven out of these 24 drugs were also active at 1 μM. Dose-response assays revealed that only 2 compounds, namely MMV665807 and MMV665794, exhibited an EC50 value below 5 μM. Assessments using human foreskin fibroblasts and Reuber rat hepatoma cells showed that the salicylanilide MMV665807 was less toxic for these two mammalian cell lines than for metacestodes. The parasiticidal activity of MMV665807 was then confirmed using isolated germinal layer cell cultures as well as metacestode vesicles by employing viability assays, and its effect on metacestodes was morphologically evaluated by electron microscopy. However, both oral and intraperitoneal application of MMV665807 to mice experimentally infected with E. multilocularis metacestodes did not result in any reduction of the parasite load.

  4. RNA-Seq reveals the dynamic and diverse features of digestive enzymes during early development of Pacific white shrimp Litopenaeus vannamei.

    Science.gov (United States)

    Wei, Jiankai; Zhang, Xiaojun; Yu, Yang; Li, Fuhua; Xiang, Jianhai

    2014-09-01

    The Pacific white shrimp (Litopenaeus vannamei), with high commercial value, has a typical metamorphosis pattern by going through embryo, nauplius, zoea, mysis and postlarvae during early development. Its diets change continually in this period, and a high mortality of larvae also occurs in this period. Since there is a close relationship between diets and digestive enzymes, a comprehensive investigation about the types and expression patterns of all digestive enzyme genes during early development of L. vannamei is of considerable significance for shrimp diets and larvae culture. Using RNA-Seq data, the types and expression characteristics of the digestive enzyme genes were analyzed during five different development stages (embryo, nauplius, zoea, mysis and postlarvae) in L. vannamei. Among the obtained 66,815 unigenes, 296 were annotated as 16 different digestive enzymes including five types of carbohydrase, seven types of peptidase and four types of lipase. Such a diverse suite of enzymes illustrated the capacity of L. vannamei to exploit varied diets to fit their nutritional requirements. The analysis of their dynamic expression patterns during development also indicated the importance of transcriptional regulation to adapt to the diet transition. Our study revealed the diverse and dynamic features of digestive enzymes during early development of L. vannamei. These results would provide support to better understand the physiological changes during diet transition. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Synergism between soluble and dietary fiber bound antioxidants.

    Science.gov (United States)

    Çelik, Ecem Evrim; Gökmen, Vural; Skibsted, Leif H

    2015-03-04

    This study investigates the synergism between antioxidants bound to dietary fibers (DF) of grains and soluble antioxidants of highly consumed beverages or their pure antioxidants. The interaction between insoluble fractions of grains containing bound antioxidants and soluble antioxidants was investigated using (i) a liposome-based system by measuring the lag phase before the onset of oxidation and (ii) an ESR-based system by measuring the reduction percentage of Fremy's salt radical. In both procedures, antioxidant capacities of DF-bound and soluble antioxidants were measured as well as their combinations, which were prepared at different ratios. The simple addition effects of DF-bound and soluble antioxidants were compared with measured values. The results revealed a clear synergism for almost all combinations in both liposome- and ESR-based systems. The synergism observed in DF-bound-soluble antioxidant system paints a promising picture considering the role of fiber in human gastrointestinal (GI) tract health.

  6. Quantum engine efficiency bound beyond the second law of thermodynamics.

    Science.gov (United States)

    Niedenzu, Wolfgang; Mukherjee, Victor; Ghosh, Arnab; Kofman, Abraham G; Kurizki, Gershon

    2018-01-11

    According to the second law, the efficiency of cyclic heat engines is limited by the Carnot bound that is attained by engines that operate between two thermal baths under the reversibility condition whereby the total entropy does not increase. Quantum engines operating between a thermal and a squeezed-thermal bath have been shown to surpass this bound. Yet, their maximum efficiency cannot be determined by the reversibility condition, which may yield an unachievable efficiency bound above unity. Here we identify the fraction of the exchanged energy between a quantum system and a bath that necessarily causes an entropy change and derive an inequality for this change. This inequality reveals an efficiency bound for quantum engines energised by a non-thermal bath. This bound does not imply reversibility, unless the two baths are thermal. It cannot be solely deduced from the laws of thermodynamics.

  7. Reassessment of an Arabidopsis cell wall invertase inhibitor AtCIF1 reveals its role in seed germination and early seedling growth.

    Science.gov (United States)

    Su, Tao; Wolf, Sebastian; Han, Mei; Zhao, Hongbo; Wei, Hongbin; Greiner, Steffen; Rausch, Thomas

    2016-01-01

    In higher plants, cell wall invertase (CWI) and vacuolar invertase (VI) are recognized as essential players in sugar metabolism and sugar signaling, thereby affecting source-sink interactions, plant development and responses to environmental cues. CWI and VI expression levels are transcriptionally controlled; however, both enzymes are also subject to posttranslational control by invertase inhibitor proteins. The physiological significances of inhibitor proteins during seed germination and early seedling development are not yet fully understood. Here, we demonstrate that the inhibitor isoform AtCIF1 impacted on seed germination and early seedling growth in Arabidopsis. The primary target of AtCIF1 was shown to be localized to the apoplast after expressing an AtCIF1 YFP-fusion construct in tobacco epidermis and transgenic Arabidopsis root. The analysis of expression patterns showed that AtCWI1 was co-expressed spatiotemporally with AtCIF1 within the early germinating seeds. Seed germination was observed to be accelerated independently of exogenous abscisic acid (ABA) in the AtCIF1 loss-of-function mutant cif1-1. This effect coincided with a drastic increase of CWI activity in cif1-1 mutant seeds by 24 h after the onset of germination, both in vitro and in planta. Accordingly, quantification of sugar content showed that hexose levels were significantly boosted in germinating seeds of the cif1-1 mutant. Further investigation of AtCIF1 overexpressors in Arabidopsis revealed a markedly suppressed CWI activity as well as delayed seed germination. Thus, we conclude that the posttranslational modulation of CWI activity by AtCIF1 helps to orchestrate seed germination and early seedling growth via fine-tuning sucrose hydrolysis and, possibly, sugar signaling.

  8. Combining Alphas via Bounded Regression

    Directory of Open Access Journals (Sweden)

    Zura Kakushadze

    2015-11-01

    Full Text Available We give an explicit algorithm and source code for combining alpha streams via bounded regression. In practical applications, typically, there is insufficient history to compute a sample covariance matrix (SCM for a large number of alphas. To compute alpha allocation weights, one then resorts to (weighted regression over SCM principal components. Regression often produces alpha weights with insufficient diversification and/or skewed distribution against, e.g., turnover. This can be rectified by imposing bounds on alpha weights within the regression procedure. Bounded regression can also be applied to stock and other asset portfolio construction. We discuss illustrative examples.

  9. Computational Lower Bounds Using Diagonalization

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 14; Issue 7. Computational Lower Bounds Using Diagonalization - Languages, Turing Machines and Complexity Classes. M V Panduranga Rao. General Article Volume 14 Issue 7 July 2009 pp 682-690 ...

  10. Comparative Genomics Including the Early-Diverging Smut Fungus Ceraceosorus bombacis Reveals Signatures of Parallel Evolution within Plant and Animal Pathogens of Fungi and Oomycetes.

    Science.gov (United States)

    Sharma, Rahul; Xia, Xiaojuan; Riess, Kai; Bauer, Robert; Thines, Marco

    2015-08-27

    Ceraceosorus bombacis is an early-diverging lineage of smut fungi and a pathogen of cotton trees (Bombax ceiba). To study the evolutionary genomics of smut fungi in comparison with other fungal and oomycete pathogens, the genome of C. bombacis was sequenced and comparative genomic analyses were performed. The genome of 26.09 Mb encodes for 8,024 proteins, of which 576 are putative-secreted effector proteins (PSEPs). Orthology analysis revealed 30 ortholog PSEPs among six Ustilaginomycotina genomes, the largest groups of which are lytic enzymes, such as aspartic peptidase and glycoside hydrolase. Positive selection analyses revealed the highest percentage of positively selected PSEPs in C. bombacis compared with other Ustilaginomycotina genomes. Metabolic pathway analyses revealed the absence of genes encoding for nitrite and nitrate reductase in the genome of the human skin pathogen Malassezia globosa, but these enzymes are present in the sequenced plant pathogens in smut fungi. Interestingly, these genes are also absent in cultivable oomycete animal pathogens, while nitrate reductase has been lost in cultivable oomycete plant pathogens. Similar patterns were also observed for obligate biotrophic and hemi-biotrophic fungal and oomycete pathogens. Furthermore, it was found that both fungal and oomycete animal pathogen genomes are lacking cutinases and pectinesterases. Overall, these findings highlight the parallel evolution of certain genomic traits, revealing potential common evolutionary trajectories among fungal and oomycete pathogens, shaping the pathogen genomes according to their lifestyle. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  11. Universal Bound on the Fano Factor in Enzyme Kinetics

    CERN Document Server

    Barato, Andre C

    2015-01-01

    The Fano factor, an observable quantifying fluctuations of product generation by a single enzyme, can reveal information about the underlying reaction scheme. A lower bound on this Fano factor that depends on the thermodynamic affinity driving the transformation from substrate to product constrains the number of intermediate states of an enzymatic cycle. So far, this bound has been proven only for a unicyclic network of states. We show that the bound can be extended to arbitrary multicyclic networks, with the Fano factor constraining the largest value of the effective length, which is the ratio between the number of states and the number of products, among all cycles.

  12. Bounded Rationality in Transposition Processes

    DEFF Research Database (Denmark)

    Vollaard, Hans; Martinsen, Dorte Sindbjerg

    2014-01-01

    perspective may affect the commonly employed explanatory factors of administrative capacities, misfit and the heterogeneity of preferences among veto players. To prevent retrospective rationalisation of the transposition process, this paper traces this process as it unfolded in Denmark and the Netherlands....... As bounded rationality is apparent in the transposition processes in these relatively well-organised countries, future transposition studies should devote greater consideration to the bounded rationality perspective....

  13. Transmission of clonal hepatitis C virus genomes reveals the dominant but transitory role of CD8¿ T cells in early viral evolution

    DEFF Research Database (Denmark)

    Callendret, Benoît; Bukh, Jens; Eccleston, Heather B

    2011-01-01

    occurred slowly over several years of chronic infection. Together these observations indicate that during acute hepatitis C, virus evolution was driven primarily by positive selection pressure exerted by CD8(+) T cells. This influence of immune pressure on viral evolution appears to subside as chronic......The RNA genome of the hepatitis C virus (HCV) diversifies rapidly during the acute phase of infection, but the selective forces that drive this process remain poorly defined. Here we examined whether Darwinian selection pressure imposed by CD8(+) T cells is a dominant force driving early amino acid...... virus at frequent intervals revealed that most acute-phase nonsynonymous mutations were clustered in class I epitopes and appeared much earlier than those in the remainder of the HCV genome. Moreover, the ratio of nonsynonymous to synonymous mutations, a measure of positive selection pressure...

  14. Gene expression analysis reveals early changes in several molecular pathways in cerebral malaria-susceptible mice versus cerebral malaria-resistant mice

    Directory of Open Access Journals (Sweden)

    Grau Georges E

    2007-12-01

    Full Text Available Abstract Background Microarray analyses allow the identification and assessment of molecular signatures in whole tissues undergoing pathological processes. To better understand cerebral malaria pathogenesis, we investigated intra-cerebral gene-expression profiles in well-defined genetically cerebral malaria-resistant (CM-R and CM-susceptible (CM-S mice, upon infection by Plasmodium berghei ANKA (PbA. We investigated mouse transcriptional responses at early and late stages of infection by use of cDNA microarrays. Results Through a rigorous statistical approach with multiple testing corrections, we showed that PbA significantly altered brain gene expression in CM-R (BALB/c, and in CM-S (CBA/J and C57BL/6 mice, and that 327 genes discriminated between early and late infection stages, between mouse strains, and between CM-R and CM-S mice. We further identified 104, 56, 84 genes with significant differential expression between CM-R and CM-S mice on days 2, 5, and 7 respectively. The analysis of their functional annotation indicates that genes involved in metabolic energy pathways, the inflammatory response, and the neuroprotection/neurotoxicity balance play a major role in cerebral malaria pathogenesis. In addition, our data suggest that cerebral malaria and Alzheimer's disease may share some common mechanisms of pathogenesis, as illustrated by the accumulation of β-amyloid proteins in brains of CM-S mice, but not of CM-R mice. Conclusion Our microarray analysis highlighted marked changes in several molecular pathways in CM-S compared to CM-R mice, particularly at early stages of infection. This study revealed some promising areas for exploration that may both provide new insight into the knowledge of CM pathogenesis and the development of novel therapeutic strategies.

  15. Switch of sensitivity dynamics revealed with DyGloSA toolbox for dynamical global sensitivity analysis as an early warning for system's critical transition.

    Science.gov (United States)

    Baumuratova, Tatiana; Dobre, Simona; Bastogne, Thierry; Sauter, Thomas

    2013-01-01

    Systems with bifurcations may experience abrupt irreversible and often unwanted shifts in their performance, called critical transitions. For many systems like climate, economy, ecosystems it is highly desirable to identify indicators serving as early warnings of such regime shifts. Several statistical measures were recently proposed as early warnings of critical transitions including increased variance, autocorrelation and skewness of experimental or model-generated data. The lack of automatized tool for model-based prediction of critical transitions led to designing DyGloSA - a MATLAB toolbox for dynamical global parameter sensitivity analysis (GPSA) of ordinary differential equations models. We suggest that the switch in dynamics of parameter sensitivities revealed by our toolbox is an early warning that a system is approaching a critical transition. We illustrate the efficiency of our toolbox by analyzing several models with bifurcations and predicting the time periods when systems can still avoid going to a critical transition by manipulating certain parameter values, which is not detectable with the existing SA techniques. DyGloSA is based on the SBToolbox2 and contains functions, which compute dynamically the global sensitivity indices of the system by applying four main GPSA methods: eFAST, Sobol's ANOVA, PRCC and WALS. It includes parallelized versions of the functions enabling significant reduction of the computational time (up to 12 times). DyGloSA is freely available as a set of MATLAB scripts at http://bio.uni.lu/systems_biology/software/dyglosa. It requires installation of MATLAB (versions R2008b or later) and the Systems Biology Toolbox2 available at www.sbtoolbox2.org. DyGloSA can be run on Windows and Linux systems, -32 and -64 bits.

  16. Switch of sensitivity dynamics revealed with DyGloSA toolbox for dynamical global sensitivity analysis as an early warning for system's critical transition.

    Directory of Open Access Journals (Sweden)

    Tatiana Baumuratova

    Full Text Available Systems with bifurcations may experience abrupt irreversible and often unwanted shifts in their performance, called critical transitions. For many systems like climate, economy, ecosystems it is highly desirable to identify indicators serving as early warnings of such regime shifts. Several statistical measures were recently proposed as early warnings of critical transitions including increased variance, autocorrelation and skewness of experimental or model-generated data. The lack of automatized tool for model-based prediction of critical transitions led to designing DyGloSA - a MATLAB toolbox for dynamical global parameter sensitivity analysis (GPSA of ordinary differential equations models. We suggest that the switch in dynamics of parameter sensitivities revealed by our toolbox is an early warning that a system is approaching a critical transition. We illustrate the efficiency of our toolbox by analyzing several models with bifurcations and predicting the time periods when systems can still avoid going to a critical transition by manipulating certain parameter values, which is not detectable with the existing SA techniques. DyGloSA is based on the SBToolbox2 and contains functions, which compute dynamically the global sensitivity indices of the system by applying four main GPSA methods: eFAST, Sobol's ANOVA, PRCC and WALS. It includes parallelized versions of the functions enabling significant reduction of the computational time (up to 12 times. DyGloSA is freely available as a set of MATLAB scripts at http://bio.uni.lu/systems_biology/software/dyglosa. It requires installation of MATLAB (versions R2008b or later and the Systems Biology Toolbox2 available at www.sbtoolbox2.org. DyGloSA can be run on Windows and Linux systems, -32 and -64 bits.

  17. Successful in vitro expansion and differentiation of cord blood derived CD34+ cells into early endothelial progenitor cells reveals highly differential gene expression.

    Directory of Open Access Journals (Sweden)

    Ingo Ahrens

    Full Text Available Endothelial progenitor cells (EPCs can be purified from peripheral blood, bone marrow or cord blood and are typically defined by a limited number of cell surface markers and a few functional tests. A detailed in vitro characterization is often restricted by the low cell numbers of circulating EPCs. Therefore in vitro culturing and expansion methods are applied, which allow at least distinguishing two different types of EPCs, early and late EPCs. Herein, we describe an in vitro culture technique with the aim to generate high numbers of phenotypically, functionally and genetically defined early EPCs from human cord blood. Characterization of EPCs was done by flow cytometry, immunofluorescence microscopy, colony forming unit (CFU assay and endothelial tube formation assay. There was an average 48-fold increase in EPC numbers. EPCs expressed VEGFR-2, CD144, CD18, and CD61, and were positive for acetylated LDL uptake and ulex lectin binding. The cells stimulated endothelial tube formation only in co-cultures with mature endothelial cells and formed CFUs. Microarray analysis revealed highly up-regulated genes, including LL-37 (CAMP, PDK4, and alpha-2-macroglobulin. In addition, genes known to be associated with cardioprotective (GDF15 or pro-angiogenic (galectin-3 properties were also significantly up-regulated after a 72 h differentiation period on fibronectin. We present a novel method that allows to generate high numbers of phenotypically, functionally and genetically characterized early EPCs. Furthermore, we identified several genes newly linked to EPC differentiation, among them LL-37 (CAMP was the most up-regulated gene.

  18. Successful In Vitro Expansion and Differentiation of Cord Blood Derived CD34+ Cells into Early Endothelial Progenitor Cells Reveals Highly Differential Gene Expression

    Science.gov (United States)

    Topcic, Denijal; Haviv, Izhak; Merivirta, Ruusu-Maaria; Agrotis, Alexander; Leitner, Ephraem; Jowett, Jeremy B.; Bode, Christoph; Lappas, Martha; Peter, Karlheinz

    2011-01-01

    Endothelial progenitor cells (EPCs) can be purified from peripheral blood, bone marrow or cord blood and are typically defined by a limited number of cell surface markers and a few functional tests. A detailed in vitro characterization is often restricted by the low cell numbers of circulating EPCs. Therefore in vitro culturing and expansion methods are applied, which allow at least distinguishing two different types of EPCs, early and late EPCs. Herein, we describe an in vitro culture technique with the aim to generate high numbers of phenotypically, functionally and genetically defined early EPCs from human cord blood. Characterization of EPCs was done by flow cytometry, immunofluorescence microscopy, colony forming unit (CFU) assay and endothelial tube formation assay. There was an average 48-fold increase in EPC numbers. EPCs expressed VEGFR-2, CD144, CD18, and CD61, and were positive for acetylated LDL uptake and ulex lectin binding. The cells stimulated endothelial tube formation only in co-cultures with mature endothelial cells and formed CFUs. Microarray analysis revealed highly up-regulated genes, including LL-37 (CAMP), PDK4, and alpha-2-macroglobulin. In addition, genes known to be associated with cardioprotective (GDF15) or pro-angiogenic (galectin-3) properties were also significantly up-regulated after a 72 h differentiation period on fibronectin. We present a novel method that allows to generate high numbers of phenotypically, functionally and genetically characterized early EPCs. Furthermore, we identified several genes newly linked to EPC differentiation, among them LL-37 (CAMP) was the most up-regulated gene. PMID:21858032

  19. Structure of the protein core of translation initiation factor 2 in apo, GTP-bound and GDP-bound forms

    Energy Technology Data Exchange (ETDEWEB)

    Simonetti, Angelita [IGBMC (Institute of Genetics and of Molecular and Cellular Biology), Centre National de la Recherche Scientifique (CNRS) UMR 7104/Institut National de la Santé de la Recherche Médicale - INSERM U964/Université de Strasbourg, 1 Rue Laurent Fries, 67404 Illkirch (France); Marzi, Stefano [Architecture et Réactivité de l’ARN, UPR 9002 CNRS, IBMC (Institute of Molecular and Cellular Biology), 15 Rue R. Descartes, 67084 Strasbourg, France, Université de Strasbourg, 67000 Strasbourg (France); Fabbretti, Attilio [University of Camerino, 62032 Camerino (Monaco) (Italy); Hazemann, Isabelle; Jenner, Lasse [IGBMC (Institute of Genetics and of Molecular and Cellular Biology), Centre National de la Recherche Scientifique (CNRS) UMR 7104/Institut National de la Santé de la Recherche Médicale -INSERM U964/Université de Strasbourg, 1 Rue Laurent Fries, 67404 Illkirch (France); Urzhumtsev, Alexandre [IGBMC (Institute of Genetics and of Molecular and Cellular Biology), Centre National de la Recherche Scientifique (CNRS) UMR 7104/Institut National de la Santé de la Recherche Médicale - INSERM U964/Université de Strasbourg, 1 Rue Laurent Fries, 67404 Illkirch (France); Université de Lorraine, 54506 Vandoeuvre-lès-Nancy (France); Gualerzi, Claudio O. [University of Camerino, 62032 Camerino (Monaco) (Italy); Klaholz, Bruno P., E-mail: klaholz@igbmc.fr [IGBMC (Institute of Genetics and of Molecular and Cellular Biology), Centre National de la Recherche Scientifique (CNRS) UMR 7104/Institut National de la Santé de la Recherche Médicale - INSERM U964/Université de Strasbourg, 1 Rue Laurent Fries, 67404 Illkirch (France)

    2013-06-01

    The crystal structures of the eubacterial translation initiation factor 2 in apo form and with bound GDP and GTP reveal conformational changes upon nucleotide binding and hydrolysis, notably of the catalytically important histidine in the switch II region. Translation initiation factor 2 (IF2) is involved in the early steps of bacterial protein synthesis. It promotes the stabilization of the initiator tRNA on the 30S initiation complex (IC) and triggers GTP hydrolysis upon ribosomal subunit joining. While the structure of an archaeal homologue (a/eIF5B) is known, there are significant sequence and functional differences in eubacterial IF2, while the trimeric eukaryotic IF2 is completely unrelated. Here, the crystal structure of the apo IF2 protein core from Thermus thermophilus has been determined by MAD phasing and the structures of GTP and GDP complexes were also obtained. The IF2–GTP complex was trapped by soaking with GTP in the cryoprotectant. The structures revealed conformational changes of the protein upon nucleotide binding, in particular in the P-loop region, which extend to the functionally relevant switch II region. The latter carries a catalytically important and conserved histidine residue which is observed in different conformations in the GTP and GDP complexes. Overall, this work provides the first crystal structure of a eubacterial IF2 and suggests that activation of GTP hydrolysis may occur by a conformational repositioning of the histidine residue.

  20. Genomic Reconstruction of the History of Native Sheep Reveals the Peopling Patterns of Nomads and the Expansion of Early Pastoralism in East Asia.

    Science.gov (United States)

    Zhao, Yong-Xin; Yang, Ji; Lv, Feng-Hua; Hu, Xiao-Ju; Xie, Xing-Long; Zhang, Min; Li, Wen-Rong; Liu, Ming-Jun; Wang, Yu-Tao; Li, Jin-Quan; Liu, Yong-Gang; Ren, Yan-Ling; Wang, Feng; Hehua, EEr; Kantanen, Juha; Arjen Lenstra, Johannes; Han, Jian-Lin; Li, Meng-Hua

    2017-09-01

    China has a rich resource of native sheep (Ovis aries) breeds associated with historical movements of several nomadic societies. However, the history of sheep and the associated nomadic societies in ancient China remains poorly understood. Here, we studied the genomic diversity of Chinese sheep using genome-wide SNPs, mitochondrial and Y-chromosomal variations in > 1,000 modern samples. Population genomic analyses combined with archeological records and historical ethnic demographics data revealed genetic signatures of the origins, secondary expansions and admixtures, of Chinese sheep thereby revealing the peopling patterns of nomads and the expansion of early pastoralism in East Asia. Originating from the Mongolian Plateau ∼5,000‒5,700 years ago, Chinese sheep were inferred to spread in the upper and middle reaches of the Yellow River ∼3,000‒5,000 years ago following the expansions of the Di-Qiang people. Afterwards, sheep were then inferred to reach the Qinghai-Tibetan and Yunnan-Kweichow plateaus ∼2,000‒2,600 years ago by following the north-to-southwest routes of the Di-Qiang migration. We also unveiled two subsequent waves of migrations of fat-tailed sheep into northern China, which were largely commensurate with the migrations of ancestors of Hui Muslims eastward and Mongols southward during the 12th‒13th centuries. Furthermore, we revealed signs of argali introgression into domestic sheep, extensive historical mixtures among domestic populations and strong artificial selection for tail type and other traits, reflecting various breeding strategies by nomadic societies in ancient China. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  1. The origin of snakes: revealing the ecology, behavior, and evolutionary history of early snakes using genomics, phenomics, and the fossil record.

    Science.gov (United States)

    Hsiang, Allison Y; Field, Daniel J; Webster, Timothy H; Behlke, Adam D B; Davis, Matthew B; Racicot, Rachel A; Gauthier, Jacques A

    2015-05-20

    The highly derived morphology and astounding diversity of snakes has long inspired debate regarding the ecological and evolutionary origin of both the snake total-group (Pan-Serpentes) and crown snakes (Serpentes). Although speculation abounds on the ecology, behavior, and provenance of the earliest snakes, a rigorous, clade-wide analysis of snake origins has yet to be attempted, in part due to a dearth of adequate paleontological data on early stem snakes. Here, we present the first comprehensive analytical reconstruction of the ancestor of crown snakes and the ancestor of the snake total-group, as inferred using multiple methods of ancestral state reconstruction. We use a combined-data approach that includes new information from the fossil record on extinct crown snakes, new data on the anatomy of the stem snakes Najash rionegrina, Dinilysia patagonica, and Coniophis precedens, and a deeper understanding of the distribution of phenotypic apomorphies among the major clades of fossil and Recent snakes. Additionally, we infer time-calibrated phylogenies using both new 'tip-dating' and traditional node-based approaches, providing new insights on temporal patterns in the early evolutionary history of snakes. Comprehensive ancestral state reconstructions reveal that both the ancestor of crown snakes and the ancestor of total-group snakes were nocturnal, widely foraging, non-constricting stealth hunters. They likely consumed soft-bodied vertebrate and invertebrate prey that was subequal to head size, and occupied terrestrial settings in warm, well-watered, and well-vegetated environments. The snake total-group - approximated by the Coniophis node - is inferred to have originated on land during the middle Early Cretaceous (~128.5 Ma), with the crown-group following about 20 million years later, during the Albian stage. Our inferred divergence dates provide strong evidence for a major radiation of henophidian snake diversity in the wake of the Cretaceous-Paleogene (K

  2. Genome-resolved metaproteomic characterization of preterm infant gut microbiota development reveals species-specific metabolic shifts and variabilities during early life.

    Science.gov (United States)

    Xiong, Weili; Brown, Christopher T; Morowitz, Michael J; Banfield, Jillian F; Hettich, Robert L

    2017-07-10

    ) utilization and short-chain fatty acid production. Overall, this study reports species-specific proteome profiles and metabolic functions of human gut microbiota during early colonization. In particular, our work contributes to reveal microbiota-associated shifts and variations in the metabolism of three major nutrient sources and short-chain fatty acid during colonization of preterm infant gut.

  3. Bounded Densities and Their Derivatives

    DEFF Research Database (Denmark)

    Kozine, Igor; Krymsky, V.

    2009-01-01

    This paper describes how one can compute interval-valued statistical measures given limited information about the underlying distribution. The particular focus is on a bounded derivative of a probability density function and its combination with other available statistical evidence for computing ...

  4. Physics with loosely bound nuclei

    Indian Academy of Sciences (India)

    nuclear physics changed drastically as the new generation of accelerators started providing more and more rare isotopes, which are away from the line of stability. These weakly bound nuclei are found to exhibit new forms of nuclear matter and unprecedented exotic behaviour. The low breakup thresholds of these rare ...

  5. Distance bounds on quantum dynamics

    Science.gov (United States)

    Lidar, Daniel A.; Zanardi, Paolo; Khodjasteh, Kaveh

    2008-07-01

    We derive rigorous upper bounds on the distance between quantum states in an open-system setting in terms of the operator norm between Hamiltonians describing their evolution. We illustrate our results with an example taken from protection against decoherence using dynamical decoupling.

  6. Moderate deviations for bounded subsequences

    Directory of Open Access Journals (Sweden)

    George Stoica

    2006-01-01

    Full Text Available We study Davis' series of moderate deviations probabilities for Lp-bounded sequences of random variables (p>2. A certain subseries therein is convergent for the same range of parameters as in the case of martingale difference or i.i.d. sequences.

  7. Interactions between macromolecule-bound antioxidants and Trolox during liposome autoxidation

    DEFF Research Database (Denmark)

    Celik, Ecem Evrim; Amigo Rubio, Jose Manuel; Andersen, Mogens Larsen

    2017-01-01

    The interactions between free and macromolecule-bound antioxidants were investigated in order to evaluate their combined effects on the antioxidant environment. Dietary fiber (DF), protein and lipid-bound antioxidants, obtained from whole wheat, soybean and olive oil products, respectively...... of the simple addition effects of Trolox and bound antioxidants with measured values on lipid oxidation revealed synergetic interactions for DF and refined olive oil-bound antioxidants, and antagonistic interactions for protein and extra virgin olive oil-bound antioxidants with Trolox. A generalized version...

  8. Global analysis of human duplicated genes reveals the relative importance of whole-genome duplicates originated in the early vertebrate evolution.

    Science.gov (United States)

    Acharya, Debarun; Ghosh, Tapash C

    2016-01-22

    Gene duplication is a genetic mutation that creates functionally redundant gene copies that are initially relieved from selective pressures and may adapt themselves to new functions with time. The levels of gene duplication may vary from small-scale duplication (SSD) to whole genome duplication (WGD). Studies with yeast revealed ample differences between these duplicates: Yeast WGD pairs were functionally more similar, less divergent in subcellular localization and contained a lesser proportion of essential genes. In this study, we explored the differences in evolutionary genomic properties of human SSD and WGD genes, with the identifiable human duplicates coming from the two rounds of whole genome duplication occurred early in vertebrate evolution. We observed that these two groups of duplicates were also dissimilar in terms of their evolutionary and genomic properties. But interestingly, this is not like the same observed in yeast. The human WGDs were found to be functionally less similar, diverge more in subcellular level and contain a higher proportion of essential genes than the SSDs, all of which are opposite from yeast. Additionally, we explored that human WGDs were more divergent in their gene expression profile, have higher multifunctionality and are more often associated with disease, and are evolutionarily more conserved than human SSDs. Our study suggests that human WGD duplicates are more divergent and entails the adaptation of WGDs to novel and important functions that consequently lead to their evolutionary conservation in the course of evolution.

  9. Tracking the Emergence of Host-Specific Simian Immunodeficiency Virus env and nef Populations Reveals nef Early Adaptation and Convergent Evolution in Brain of Naturally Progressing Rhesus Macaques.

    Science.gov (United States)

    Lamers, Susanna L; Nolan, David J; Rife, Brittany D; Fogel, Gary B; McGrath, Michael S; Burdo, Tricia H; Autissier, Patrick; Williams, Kenneth C; Goodenow, Maureen M; Salemi, Marco

    2015-08-01

    evolutionary patterns in the gp120 and nef genes leading to the emergence of host-specific viral populations and potentially linked to disease progression. Although each macaque exhibited unique immune profiles, macaque-specific nef sequences evolving under selection were consistently detected in plasma samples at 3 months postinfection, significantly earlier than in gp120 macaque-specific sequences. On the other hand, nef sequences in brain tissues, collected at necropsy of two animals with detectable infection in the central nervous system (CNS), revealed convergent evolution. The results not only indicate that early adaptation of nef in the new host may be essential for successful infection, but also suggest that specific nef variants may be required for SIV to efficiently invade CNS macrophages and/or enhance macrophage migration, resulting in HIV neuropathology. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  10. Ionically Bound Peroxidase from Peach Fruit

    Directory of Open Access Journals (Sweden)

    Neves Valdir Augusto

    2002-01-01

    Full Text Available Soluble, ionically bound peroxidase (POD and polyphenoloxidase (PPO were extracted from the pulp of peach fruit during ripening at 20°C. Ionically bound form was purified 6.1-fold by DEAE-cellulose and Sephadex G-100 chromatography. The purified enzyme showed only one peak of activity on Sephadex G-100 and PAGE revealed that the enzyme was purified by the procedures adopted. The purified enzyme showed a molecular weight of 29000 Da, maximum activity at pH 5.0 and at 40ºC. The calculated apparent activation energy (Ea for the reaction was10.04 kcal/mol. The enzyme was heat-labile in the temperature range of 60 to 75ºC with a fast inactivation at 75ºC. Measurement of residual activity showed a stabilizing effect of sucrose at various temperature/sugar concentrations (0, 10, 20 %, w/w, with an activation energy (Ea for inactivation increasing with sucrose concentration from 0 to 20% (w/w. The Km and Vmax values were 9.35 and 15.38 mM for 0-dianisidine and H2O2, respectively. The bound enzyme was inhibited competitively by ferulic, caffeic and protocatechuic acids with different values of Ki,. L-cysteine, p-coumaric and indolacetic acid and Fe++ also inhibited the enzyme but at a lower grade. N-ethylmaleimide and p-CMB were not effective to inhibit the enzyme demonstrating the non-essentiality of SH groups.

  11. Coherent structures in wall-bounded turbulence.

    Science.gov (United States)

    Dennis, David J C

    2015-01-01

    The inherent difficulty of understanding turbulence has led to researchers attacking the topic in many different ways over the years of turbulence research. Some approaches have been more successful than others, but most only deal with part of the problem. One approach that has seen reasonable success (or at least popularity) is that of attempting to deconstruct the complex and disorganised turbulent flow field into to a set of motions that are in some way organised. These motions are generally called "coherent structures". There are several strands to this approach, from identifying the coherent structures within the flow, defining their characteristics, explaining how they are created, sustained and destroyed, to utilising their features to model the turbulent flow. This review considers research on coherent structures in wall-bounded turbulent flows: a class of flow which is extremely interesting to many scientists (mainly, but not exclusively, physicists and engineers) due to their prevalence in nature, industry and everyday life. This area has seen a lot of activity, particularly in recent years, much of which has been driven by advances in experimental and computational techniques. However, several ideas, developed many years ago based on flow visualisation and intuition, are still both informative and relevant. Indeed, much of the more recent research is firmly indebted to some of the early pioneers of the coherent structures approach. Therefore, in this review, selected historical research is discussed along with the more contemporary advances in an attempt to provide the reader with a good overview of how the field has developed and to highlight the perspicacity of some of the early researchers, as well as providing an overview of our current understanding of the role of coherent structures in wall-bounded turbulent flows.

  12. Coherent structures in wall-bounded turbulence

    Directory of Open Access Journals (Sweden)

    David J.C. Dennis

    2015-06-01

    Full Text Available The inherent difficulty of understanding turbulence has led to researchers attacking the topic in many different ways over the years of turbulence research. Some approaches have been more successful than others, but most only deal with part of the problem. One approach that has seen reasonable success (or at least popularity is that of attempting to deconstruct the complex and disorganised turbulent flow field into to a set of motions that are in some way organised. These motions are generally called "coherent structures". There are several strands to this approach, from identifying the coherent structures within the flow, defining their characteristics, explaining how they are created, sustained and destroyed, to utilising their features to model the turbulent flow. This review considers research on coherent structures in wall-bounded turbulent flows: a class of flow which is extremely interesting to many scientists (mainly, but not exclusively, physicists and engineers due to their prevalence in nature, industry and everyday life. This area has seen a lot of activity, particularly in recent years, much of which has been driven by advances in experimental and computational techniques. However, several ideas, developed many years ago based on flow visualisation and intuition, are still both informative and relevant. Indeed, much of the more recent research is firmly indebted to some of the early pioneers of the coherent structures approach. Therefore, in this review, selected historical research is discussed along with the more contemporary advances in an attempt to provide the reader with a good overview of how the field has developed and to highlight the perspicacity of some of the early researchers, as well as providing an overview of our current understanding of the role of coherent structures in wall-bounded turbulent flows.

  13. Lower bounds in differential privacy

    OpenAIRE

    De, Anindya

    2011-01-01

    This is a paper about private data analysis, in which a trusted curator holding a confidential database responds to real vector-valued queries. A common approach to ensuring privacy for the database elements is to add appropriately generated random noise to the answers, releasing only these {\\em noisy} responses. In this paper, we investigate various lower bounds on the noise required to maintain different kind of privacy guarantees.

  14. Geometry of Homogeneous Bounded Domains

    CERN Document Server

    Vesentini, E

    2011-01-01

    This title includes: S.G. Gindikin, I.I. Pjateckii-Sapiro, E.B. Vinberg: Homogeneous Kahler manifolds; S.G. Greenfield: Extendibility properties of real submanifolds of Cn; W. Kaup: Holomorphische Abbildungen in Hyperbolische Raume; A. Koranyi: Holomorphic and harmonic functions on bounded symmetric domains; J.L. Koszul: Formes harmoniques vectorielles sur les espaces localement symetriques; S. Murakami: Plongements holomorphes de domaines symetriques; and E.M. Stein: The analogues of Fatous' theorem and estimates for maximal functions.

  15. Wronskian method for bound states

    Energy Technology Data Exchange (ETDEWEB)

    Fernandez, Francisco M, E-mail: fernande@quimica.unlp.edu.ar [INIFTA (UNLP, CONICET), Division Quimica Teorica, Boulevard 113 S/N, Sucursal 4, Casilla de Correo 16, 1900 La Plata (Argentina)

    2011-05-15

    We propose a simple and straightforward method based on Wronskians for the calculation of bound-state energies and wavefunctions of one-dimensional quantum-mechanical problems. We explicitly discuss the asymptotic behaviour of the wavefunction and show that the allowed energies make the divergent part vanish. As illustrative examples we consider an exactly solvable model, the Gaussian potential well, and a two-well potential proposed earlier for the interpretation of the infrared spectrum of ammonia.

  16. Cyclotron transitions of bound ions

    Science.gov (United States)

    Bezchastnov, Victor G.; Pavlov, George G.

    2017-06-01

    A charged particle in a magnetic field possesses discrete energy levels associated with particle rotation around the field lines. The radiative transitions between these levels are the well-known cyclotron transitions. We show that a bound complex of particles with a nonzero net charge displays analogous transitions between the states of confined motion of the entire complex in the field. The latter bound-ion cyclotron transitions are affected by a coupling between the collective and internal motions of the complex and, as a result, differ from the transitions of a "reference" bare ion with the same mass and charge. We analyze the cyclotron transitions for complex ions by including the coupling within a rigorous quantum approach. Particular attention is paid to comparison of the transition energies and oscillator strengths to those of the bare ion. Selection rules based on integrals of collective motion are derived for the bound-ion cyclotron transitions analytically, and the perturbation and coupled-channel approaches are developed to study the transitions quantitatively. Representative examples are considered and discussed for positive and negative atomic and cluster ions.

  17. In-medium K̄ interactions and bound states

    Directory of Open Access Journals (Sweden)

    Gal Avraham

    2014-01-01

    Full Text Available Correct treatment of subthreshold K̄ N dynamics is mandatory in K− -atom and K̄ -nuclear bound-state calculations, as demonstrated by using in-medium chirally-based models of K̄ N interactions. Recent studies of kaonic atom data reveal appreciable multi-nucleon contributions. K̄ -nuclear widths larger than 50 MeV are anticipated.

  18. Chiral Symmetry, Heavy Quark Symmetry and Bound States

    OpenAIRE

    Yoshida, Yuhsuke

    1995-01-01

    I investigate the bound state problems of lowest-lying mesons and heavy mesons. Chiral symmetry is essential when one consider lowest-lying mesons. Heavy quark symmetry plays an central role in considering the semi-leptonic form factors of heavy mesons. Various properties based on the symmetries are revealed using Bethe-Salpeter equations.

  19. Complete sequencing of an IncX3 plasmid carrying blaNDM-5 allele reveals an early stage in the dissemination of the blaNDM gene

    Directory of Open Access Journals (Sweden)

    M Krishnaraju

    2015-01-01

    Full Text Available Purpose: The aim of the present study was to perform molecular characterisation of the blaNDM plasmids and to understand the mechanism of its spread among pathogenic bacteria. Materials and Methods: Seventy-six non-repetitive carbapenem-resistant isolates which were collected during Nov 2011 to April 2013 from four hospitals in Chennai were analyzed for the presence of the blaNDM gene by PCR. Further, the genetic context of the blaNDM gene was analyzed by PCR specific to ISAba125 and bleMBL gene. One of the blaNDM plasmid was completely sequenced in the Illumina HiSeq platform. Results: Twenty-three isolates consisting of 8 Escherichia coli, 8 Klebsiella pneumoniae, 3 Klebsiella oxytoca, 3 Acinetobacter baumanii and 1 Pseudomonas aeruginosa were found to carry the blaNDM gene. In 18 isolates the blaNDM gene was associated with a bleMBL gene and the ISAba125 element. The complete sequencing of pNDM-MGR194 revealed an IncX3 replication type plasmid, with a length of 46,253 bp, an average GC content of 47% and 59 putative ORFs. The iteron region contained the blaNDM5 gene and the bleMBL , trpF and dsbC genes downstream and an IS5 inserted within the ISAba125 element upstream. Conclusion: This is the first report where the blaNDM gene insertion in a plasmid is not accompanied by other resistance gene determinants. These observations suggest that the IncX3 plasmid pNDM-MGR194 is an early stage in the dissemination of the blaNDM .

  20. Host-Mycobacterium avium subsp. paratuberculosis interactome reveals a novel iron assimilation mechanism linked to nitric oxide stress during early infection.

    Science.gov (United States)

    Lamont, Elise A; Xu, Wayne W; Sreevatsan, Srinand

    2013-10-10

    The initial interaction between host cell and pathogen sets the stage for the ensuing infection and ultimately determine the course of disease. However, there is limited knowledge of the transcripts utilized by host and pathogen and how they may impact one another during this critical step. The purpose of this study was to create a host-Mycobacterium avium subsp. paratuberculosis (MAP) interactome for early infection in an epithelium-macrophage co-culture system using RNA-seq. Establishment of the host-MAP interactome revealed a novel iron assimilation system for carboxymycobactin. Iron assimilation is linked to nitric oxide synthase-2 production by the host and subsequent nitric oxide buildup. Iron limitation as well as nitric oxide is a prompt for MAP to enter into an iron sequestration program. This new iron sequestration program provides an explanation for mycobactin independence in some MAP strains grown in vitro as well as during infection within the host cell. Utilization of such a pathway is likely to aid MAP establishment and long-term survival within the host. The host-MAP interactome identified a number of metabolic, DNA repair and virulence genes worthy for consideration as novel drug targets as well as future pathogenesis studies. Reported interactome data may also be utilized to conduct focused, hypothesis-driven research. Co-culture of uninfected bovine epithelial cells (MAC-T) and primary bovine macrophages creates a tolerant genotype as demonstrated by downregulation of inflammatory pathways. This co-culture system may serve as a model to investigate other bovine enteric pathogens.

  1. Early events in plastid protein degradation in stay-green Arabidopsis reveal differential regulation beyond the retention of LHCII and chlorophyll.

    Science.gov (United States)

    Grassl, Julia; Pružinská, Adriana; Hörtensteiner, Stefan; Taylor, Nicolas L; Millar, A Harvey

    2012-11-02

    An individually darkened leaf model was used to study protein changes in the Arabidopsis mutant stay-green1 (sgr1) to partially mimic the process of leaf covering senescence that occurs naturally in the shaded rosettes of Arabidopsis plants. Utilizing this controlled and predictable induced senescence model has allowed the direct comparison of sgr1 with Col-0 during the developmental period preceding the retention of chlorophyll and light harvesting complex II (LHCII) in sgr1 and the induction of senescence in Col-0. Quantitative proteomic analysis of soluble leaf proteins from sgr1 and Col-0 before the initiation of senescence has revealed a range of differences in plastid soluble protein abundance in sgr1 when compared to Col-0. Changes were also observed in membrane located machinery for photosystem II (PSII), in Calvin cycle components, proteins involved in redox control of the stromal compartment and ammonia assimilation that differentiated sgr1 during the early stages of the senescence process. The changes in PSII abundance were accompanied with a lower capacity of photosynthetic CO(2) assimilation in sgr1 than Col-0 after return of plants to lighted conditions following 3 and 5 days of darkness. A light-harvesting chlorophyll-a/b binding protein (LHCB2) was retained during the later stages of senescence in sgr1 but this was accompanied by an enhanced loss of oxygen evolving complex (OEC) subunits from PSII, which was confirmed by Western blotting, and an enhanced stability of PSII repair proteins in sgr1, compared to Col-0. Together these data provide insights into the significant differences in the steady-state proteome in sgr1 and its response to senescence, showing this cosmetic stay-green mutant is in fact significantly different to wild-type plants both before and during leaf senescence.

  2. Ancient DNA analyses of early archaeological sites in New Zealand reveal extreme exploitation of moa (Aves: Dinornithiformes) at all life stages

    Science.gov (United States)

    Oskam, Charlotte L.; Allentoft, Morten E.; Walter, Richard; Scofield, R. Paul; Haile, James; Holdaway, Richard N.; Bunce, Michael; Jacomb, Chris

    2012-10-01

    The human colonisation of New Zealand in the late thirteenth century AD led to catastrophic impacts on the local biota and is among the most compelling examples of human over-exploitation of native fauna, including megafauna. Nearly half of the species in New Zealand' s pre-human avifauna are now extinct, including all nine species of large, flightless moa (Aves: Dinornithiformes). The abundance of moa in early archaeological sites demonstrates the significance of these megaherbivores in the diet of the first New Zealanders. Combining moa assemblage data, based on DNA identification of eggshell and bone, with morphological identification of bone (literature and museum catalogued specimens), we present the most comprehensive audit of moa to date from several significant 13th-15th century AD archaeological deposits across the east coast of the South Island. Mitochondrial DNA (mtDNA) was amplified from 251 of 323 (78%) eggshell fragments and 22 of 27 (88%) bone samples, and the analyses revealed the presence of four moa species: Anomalopteryx didiformis; Dinornis robustus; Emeus crassus and Euryapteryx curtus. The mtDNA, along with polymorphic microsatellite markers, enabled an estimate of the minimum number of individual eggs consumed at each site. Remarkably, in one deposit over 50 individual eggs were identified - a number that likely represents a considerable proportion of the total reproductive output of moa in the area and emphasises that human predation of all life stages of moa was intense. Molecular sexing was conducted on bones (n = 11). Contrary to previous ancient DNA studies from natural sites that consistently report an excess of female moa, we observed an excess of males (2.7:1), suggestive that males were preferential targets. This could be related to different behaviour between the two highly size-dimorphic sexes in moa. Lastly, we investigated the moa species from recovered skeletal and eggshell remains from seven Wairau Bar burials, and identified

  3. Predicting survival in pulmonary arterial hypertension: insights from the Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL).

    Science.gov (United States)

    Benza, Raymond L; Miller, Dave P; Gomberg-Maitland, Mardi; Frantz, Robert P; Foreman, Aimee J; Coffey, Christopher S; Frost, Adaani; Barst, Robyn J; Badesch, David B; Elliott, C Gregory; Liou, Theodore G; McGoon, Michael D

    2010-07-13

    Factors that determine survival in pulmonary arterial hypertension (PAH) drive clinical management. A quantitative survival prediction tool has not been established for research or clinical use. Data from 2716 patients with PAH enrolled consecutively in the US Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) were analyzed to assess predictors of 1-year survival. We identified independent prognosticators of survival and derived a multivariable, weighted risk formula for clinical use. One-year survival from the date of enrollment was 91.0% (95% confidence interval [CI], 89.9 to 92.1). In a multivariable analysis with Cox proportional hazards, variables independently associated with increased mortality included pulmonary vascular resistance >32 Wood units (hazard ratio [HR], 4.1; 95% CI, 2.0 to 8.3), PAH associated with portal hypertension (HR, 3.6; 95% CI, 2.4 to 5.4), modified New York Heart Association/World Health Organization functional class IV (HR, 3.1; 95% CI, 2.2 to 4.4), men >60 years of age (HR, 2.2; 95% CI, 1.6 to 3.0), and family history of PAH (HR, 2.2; 95% CI, 1.2 to 4.0). Renal insufficiency, PAH associated with connective tissue disease, functional class III, mean right atrial pressure, resting systolic blood pressure and heart rate, 6-minute walk distance, brain natriuretic peptide, percent predicted carbon monoxide diffusing capacity, and pericardial effusion on echocardiogram all predicted mortality. Based on these multivariable analyses, a prognostic equation was derived and validated by bootstrapping technique. We identified key predictors of survival based on the patient's most recent evaluation and formulated a contemporary prognostic equation. Use of this tool may allow the individualization and optimization of therapeutic strategies. Serial follow-up and reassessment are warranted. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00370214.

  4. Temporary, but Essential Requirement of CD8+ T Cells Early in the Pathogenesis of Diabetes in BB Rats as Revealed by Thymectomy and CD8 Depletion

    Directory of Open Access Journals (Sweden)

    Herman Groen

    2003-01-01

    Full Text Available Autoimmunity-prone BB rats demonstrate a T lymphocytopenia and abnormal T cell subset distribution. To test whether the life span of all T cells or only of certain subsets is reduced in BB rats, we thymectomised 8-week-old BB and PVG rats and subsequently assessed size and composition of the T cell population over a 6-week-period. In both strains, thymectomy (Tx was followed by a decrease in peripheral T cell numbers, which was proportionally larger in BB rats. The decline of the Thy-1+ recent thymic migrant (RTM T cell phenotype was similar in both strains. BB rats showed a rapid preferential loss of CD8+ and CD45RC+ T cells, whereas the relative loss of RT6+ T cells was proportional to that of all T cells and not significantly different from that in PVG rats. Tx at 8-week did not prevent diabetes. Tx of 4-week-old BB rats revealed essentially the same changes in peripheral T cell subset distribution as in 8-week-old animals. However, Tx at week 4 did prevent diabetes. Since this raised the possibility of a temporary requirement of CD8+ T cells for the development of diabetes, we performed CD8 depletions during different pre-diabetic intervals. We found that CD8 depletion from 4 to 8 and 4 to 14 weeks, but not from 8 to 14 weeks of age prevented diabetes. We conclude that the protective effect of early adult Tx is, at least in part, due to the rapid loss of CD8+ T cells, and that these cells are only required between 4 and 8 weeks of age for diabetes to develop in BB rats.

  5. Anisotropy-induced photonic bound states in the continuum

    Science.gov (United States)

    Gomis-Bresco, Jordi; Artigas, David; Torner, Lluis

    2017-03-01

    Bound states in the continuum (BICs) are radiationless localized states embedded in the part of the parameter space that otherwise corresponds to radiative modes. Many decades after their original prediction and early observations in acoustic systems, such states have been demonstrated recently in photonic structures with engineered geometries. Here, we put forward a mechanism, based on waveguiding structures that contain anisotropic birefringent materials, that affords the existence of BICs with fundamentally new properties. In particular, anisotropy-induced BICs may exist in symmetric as well as in asymmetric geometries; they may form in tunable angular propagation directions; their polarization may be pure transverse electric, pure transverse magnetic or full vector with tunable polarization hybridity; and they may be the only possible bound states of properly designed structures, and thus appear as a discrete, isolated bound state embedded in a whole sea of radiative states.

  6. Lower bounds for randomized Exclusive Write PRAMs

    Energy Technology Data Exchange (ETDEWEB)

    MacKenzie, P.D.

    1995-05-02

    In this paper we study the question: How useful is randomization in speeding up Exclusive Write PRAM computations? Our results give further evidence that randomization is of limited use in these types of computations. First we examine a compaction problem on both the CREW and EREW PRAM models, and we present randomized lower bounds which match the best deterministic lower bounds known. (For the CREW PRAM model, the lower bound is asymptotically optimal.) These are the first non-trivial randomized lower bounds known for the compaction problem on these models. We show that our lower bounds also apply to the problem of approximate compaction. Next we examine the problem of computing boolean functions on the CREW PRAM model, and we present a randomized lower bound, which improves on the previous best randomized lower bound for many boolean functions, including the OR function. (The previous lower bounds for these functions were asymptotically optimal, but we improve the constant multiplicative factor.) We also give an alternate proof for the randomized lower bound on PARITY, which was already optimal to within a constant additive factor. Lastly, we give a randomized lower bound for integer merging on an EREW PRAM which matches the best deterministic lower bound known. In all our proofs, we use the Random Adversary method, which has previously only been used for proving lower bounds on models with Concurrent Write capabilities. Thus this paper also serves to illustrate the power and generality of this method for proving parallel randomized lower bounds.

  7. Early Triassic change in the erosional level in the eastern part of the Bohemian Massif revealed by detrital garnet assemblages from the Buntsandstein siliciclastics of southern Poland

    Science.gov (United States)

    Kowal-Linka, Monika; Walczak, Klaudia

    2017-04-01

    Garnets, as constituents of various magmatic and metamorphic rocks, show different chemical compositions depending on the type of magma or primary rock, the temperature, and the pressure. This diversity of chemical compositions makes detrital garnets a very useful tool for provenance analysis and deciphering changes in erosional levels of source areas. Preliminary works reveal that the Lower and Middle Buntsandstein terrigenous and marine sandstones cropping out in southern Poland (50˚ 28'20"N, 18˚ 04'33"E and 50˚ 27'35"N, 18˚ 07'23"E) are characterized by very different heavy mineral assemblages (HMA) and types of detrital garnets. The aim of the research is to recognize the source areas and causes of these distinct variations using petrographic analysis, heavy mineral analysis, and electron probe microanalysis. During the Early Triassic, the area under study was located between two landmasses: the eastern margin of the Bohemian Massif (BM) to the west and Pre-Carpathian Land (PCL) to the east. Presently, the sampled area is situated ˜50 km from the NE margin of the BM, which consists of many garnet-bearing rocks and is a presumable source area for the examined grains. The PCL was hidden under the Carpathians during the Alpine orogeny and knowledge of its composition is very limited. Petrographic analysis shows that the older sandstones are red to rusty quartz arenites with a hematite-rich matrix and well-rounded grains (aeolian deposits). The younger sandstones are bicolored quartz wackes (dirty pink with grey patches) with a calcite matrix and angular to rounded grains (shallow marine deposits). The arenites contain zircon, tourmaline, and rutile grains accompanied by garnet, staurolite, apatite, and topaz. The opaque heavy minerals include ilmenite, ilmenite-rutile aggregates, magnetite and rarely chromian spinel. In contrast, the HMA from the wackes consist mostly of garnets, while the minerals listed above occur in subordinate amounts. The garnets from

  8. The complete chloroplast DNA sequence of the green alga Oltmannsiellopsis viridis reveals a distinctive quadripartite architecture in the chloroplast genome of early diverging ulvophytes

    Directory of Open Access Journals (Sweden)

    Lemieux Claude

    2006-02-01

    Full Text Available Abstract Background The phylum Chlorophyta contains the majority of the green algae and is divided into four classes. The basal position of the Prasinophyceae has been well documented, but the divergence order of the Ulvophyceae, Trebouxiophyceae and Chlorophyceae is currently debated. The four complete chloroplast DNA (cpDNA sequences presently available for representatives of these classes have revealed extensive variability in overall structure, gene content, intron composition and gene order. The chloroplast genome of Pseudendoclonium (Ulvophyceae, in particular, is characterized by an atypical quadripartite architecture that deviates from the ancestral type by a large inverted repeat (IR featuring an inverted rRNA operon and a small single-copy (SSC region containing 14 genes normally found in the large single-copy (LSC region. To gain insights into the nature of the events that led to the reorganization of the chloroplast genome in the Ulvophyceae, we have determined the complete cpDNA sequence of Oltmannsiellopsis viridis, a representative of a distinct, early diverging lineage. Results The 151,933 bp IR-containing genome of Oltmannsiellopsis differs considerably from Pseudendoclonium and other chlorophyte cpDNAs in intron content and gene order, but shares close similarities with its ulvophyte homologue at the levels of quadripartite architecture, gene content and gene density. Oltmannsiellopsis cpDNA encodes 105 genes, contains five group I introns, and features many short dispersed repeats. As in Pseudendoclonium cpDNA, the rRNA genes in the IR are transcribed toward the single copy region featuring the genes typically found in the ancestral LSC region, and the opposite single copy region harbours genes characteristic of both the ancestral SSC and LSC regions. The 52 genes that were transferred from the ancestral LSC to SSC region include 12 of those observed in Pseudendoclonium cpDNA. Surprisingly, the overall gene organization of

  9. Transcriptome profiling of early developing cotton fiber by deep-sequencing reveals significantly differential expression of genes in a fuzzless/lintless mutant.

    Science.gov (United States)

    Wang, Qin Qin; Liu, Fei; Chen, Xu Sheng; Ma, Xiao Jie; Zeng, Hou Qing; Yang, Zhi Min

    2010-12-01

    Cotton fiber as a single-celled trichome is a biological model system for studying cell differentiation and elongation. However, the complexity of its gene expression and regulatory mechanism allows only marginal progress. Here, we report the high-throughput tag-sequencing (Tag-seq) analysis using Solexa Genome Analyzer platform on transcriptome of -2 to 1 (fiber initiation, stage I) and 2-8 (fiber elongation, stage II) days post anthesis (DPA) cotton (Gossypium hirsutum) ovules (wild type: WT; Xuzhou 142 and its mutant: fuzzless/lintless or flM, in the same background). To this end, we sequenced 3.5-3.8 million tags representing 0.7-1.0 million unique transcripts for each library (WT1, WT2, M1, and M2). After removal of low quality tags, we obtained a total of 2,973,104, 3,139,306, 2,943,654, and 3,392,103 clean sequences that corresponded to 357,852, 280,787, 372,952, and 382,503 distinct tags for WT1, WT2, M1, and M2, respectively. All clean tags were aligned to the publicly available cotton transcript database (TIGR, http://www.tigr.org). About 15% of the distinct tags were uniquely mapped to the reference genes, and 31.4% of existing genes were matched by tags. The tag mapping to the database sequences generated 23,854, 24,442, 23,497, and 19,957 annotated genes for WT1, WT2, M1, and M2 libraries, respectively. Analyses of differentially expressed genes revealed the substantial changes in gene type and abundance between the wild type and mutant libraries. Among the 20 most differentially expressed genes in WT1/M1 and WT2/M2 libraries were cellulose synthase, phosphatase, and dehydrogenase, all of which are involved in the fiber cell development. Overall, the deep-sequencing analyses demonstrate the high degree of transcriptional complexity in early developing fibers and represent a major improvement over the microarrays for analyzing transcriptional changes on a large scale. Copyright © 2010 Elsevier Inc. All rights reserved.

  10. Towards Automatic Resource Bound Analysis for OCaml

    OpenAIRE

    Hoffmann, Jan; Das, Ankush; Weng, Shu-Chun

    2016-01-01

    This article presents a resource analysis system for OCaml programs. This system automatically derives worst-case resource bounds for higher-order polymorphic programs with user-defined inductive types. The technique is parametric in the resource and can derive bounds for time, memory allocations and energy usage. The derived bounds are multivariate resource polynomials which are functions of different size parameters that depend on the standard OCaml types. Bound inference is fully automatic...

  11. Distance hijacking attacks on distance bounding protocols

    OpenAIRE

    Cremers, Cas; Rasmussen, Kasper Bonne; Čapkun, Srdjan

    2011-01-01

    Distance bounding protocols are typically analyzed with respect to three types of attacks: Distance Fraud, Mafia Fraud, and Terrorist Fraud. We define and analyze a fourth main type of attack on distance bounding protocols, called Distance Hijacking. We show that many proposed distance bounding protocols are vulnerable to this type of attack, and we propose solutions to make these protocols resilient to Distance Hijacking. We further show that verifying distance bounding protocols using exist...

  12. Purity- and Gaussianity-bounded uncertainty relations

    Science.gov (United States)

    Mandilara, A.; Karpov, E.; Cerf, N. J.

    2014-01-01

    Bounded uncertainty relations provide the minimum value of the uncertainty assuming some additional information on the state. We derive analytically an uncertainty relation bounded by a pair of constraints, those of purity and Gaussianity. In a limiting case this uncertainty relation reproduces the purity-bounded derived by Man’ko and Dodonov and the Gaussianity-bounded one (Mandilara and Cerf 2012 Phys. Rev. A 86 030102R).

  13. Bounded rationality and heterogeneous expectations in macroeconomics

    NARCIS (Netherlands)

    Massaro, D.

    2012-01-01

    This thesis studies the effect of individual bounded rationality on aggregate macroeconomic dynamics. Boundedly rational agents are specified as using simple heuristics in their decision making. An important aspect of the type of bounded rationality described in this thesis is that the population of

  14. Labeling schemes for bounded degree graphs

    DEFF Research Database (Denmark)

    Adjiashvili, David; Rotbart, Noy Galil

    2014-01-01

    graphs. Our results complement a similar bound recently obtained for bounded depth trees [Fraigniaud and Korman, SODA 2010], and may provide new insights for closing the long standing gap for adjacency in trees [Alstrup and Rauhe, FOCS 2002]. We also provide improved labeling schemes for bounded degree...

  15. Upper bound on quantum stabilizer codes

    Science.gov (United States)

    Li, Zhuo; Xing, Li-Juan

    2009-03-01

    By studying sets of operators having constant weight, we present an analytical upper bound on the pure quantum stabilizer codes whose underlying quantum system can be of arbitrary dimension, which outperforms the well-known quantum Hamming bound, the optimal analytical upper bound so far for small code length.

  16. Capacity Bounds for Parallel Optical Wireless Channels

    KAUST Repository

    Chaaban, Anas

    2016-01-01

    A system consisting of parallel optical wireless channels with a total average intensity constraint is studied. Capacity upper and lower bounds for this system are derived. Under perfect channel-state information at the transmitter (CSIT), the bounds have to be optimized with respect to the power allocation over the parallel channels. The optimization of the lower bound is non-convex, however, the KKT conditions can be used to find a list of possible solutions one of which is optimal. The optimal solution can then be found by an exhaustive search algorithm, which is computationally expensive. To overcome this, we propose low-complexity power allocation algorithms which are nearly optimal. The optimized capacity lower bound nearly coincides with the capacity at high SNR. Without CSIT, our capacity bounds lead to upper and lower bounds on the outage probability. The outage probability bounds meet at high SNR. The system with average and peak intensity constraints is also discussed.

  17. Performance Bounds of Quaternion Estimators.

    Science.gov (United States)

    Xia, Yili; Jahanchahi, Cyrus; Nitta, Tohru; Mandic, Danilo P

    2015-12-01

    The quaternion widely linear (WL) estimator has been recently introduced for optimal second-order modeling of the generality of quaternion data, both second-order circular (proper) and second-order noncircular (improper). Experimental evidence exists of its performance advantage over the conventional strictly linear (SL) as well as the semi-WL (SWL) estimators for improper data. However, rigorous theoretical and practical performance bounds are still missing in the literature, yet this is crucial for the development of quaternion valued learning systems for 3-D and 4-D data. To this end, based on the orthogonality principle, we introduce a rigorous closed-form solution to quantify the degree of performance benefits, in terms of the mean square error, obtained when using the WL models. The cases when the optimal WL estimation can simplify into the SWL or the SL estimation are also discussed.

  18. Spectral computations for bounded operators

    CERN Document Server

    Ahues, Mario; Limaye, Balmohan

    2001-01-01

    Exact eigenvalues, eigenvectors, and principal vectors of operators with infinite dimensional ranges can rarely be found. Therefore, one must approximate such operators by finite rank operators, then solve the original eigenvalue problem approximately. Serving as both an outstanding text for graduate students and as a source of current results for research scientists, Spectral Computations for Bounded Operators addresses the issue of solving eigenvalue problems for operators on infinite dimensional spaces. From a review of classical spectral theory through concrete approximation techniques to finite dimensional situations that can be implemented on a computer, this volume illustrates the marriage of pure and applied mathematics. It contains a variety of recent developments, including a new type of approximation that encompasses a variety of approximation methods but is simple to verify in practice. It also suggests a new stopping criterion for the QR Method and outlines advances in both the iterative refineme...

  19. On order bounded subsets of locally solid Riesz spaces | Hong ...

    African Journals Online (AJOL)

    In a topological Riesz space there are two types of bounded subsets: order bounded subsets and topologically bounded subsets. It is natural to ask (1) whether an order bounded subset is topologically bounded and (2) whether a topologically bounded subset is order bounded. A classical result gives a partial answer to (1) ...

  20. Dynamic gene expression patterns in animal models of early and late heart failure reveal biphasic-bidirectional transcriptional activation of signaling pathways.

    Science.gov (United States)

    Rowell, Janelle; Koitabashi, Norimichi; Kass, David A; Barth, Andreas S

    2014-10-15

    Altered cardiac gene expression in heart failure (HF) has mostly been identified by single-point analysis of end-stage disease. This may miss earlier changes in gene expression that are transient and/or directionally opposite to those observed later. Myocardial datasets from the largest microarray data repository (Gene Expression Omnibus) yielded six HF studies with time-course data. Differentially expressed transcripts between nonfailing controls, early HF (2 wk) were determined, and analysis of KEGG pathways and predicted regulatory control elements performed. We found that gene expression followed varying patterns: Downregulation of metabolic pathways occurred early and was sustained into late-stage HF. In contrast, most signaling pathways undergo a complex biphasic pattern: Calcium signaling, p53, apoptosis, and MAPK pathways displayed a bidirectional response, declining early but rising late. These profiles were compatible with specific microRNA (miRNA) and transcription regulators: Estrogen-related receptor-α and myocyte-enhancer factor-2 binding sites were overrepresented in the promoter regions of downregulated transcripts. Concurrently, there were overrepresented binding sites for E2f and ETS family members (E-Twenty Six, including Gabp, Elf1, and Ets2), serum response and interferon regulated factor in biphasic-bidirectional and late-upregulated transcripts. Binding sites for miRNAs downregulated by HF were more common in upregulated transcripts (e.g., miRNA-22,-133a/b, and -150 in early HF and miRNA-1,-9,-499 in late HF). During the development of HF, gene expression is characterized by dynamic overlapping sets of transcripts controlled by specific interrelated regulatory mechanisms. While metabolic gene classes show early and sustained downregulation in HF, signaling pathways undergo a complex biphasic pattern with early down- and more pronounced late upregulation. Copyright © 2014 the American Physiological Society.

  1. Transferrin-bound proteins as potential biomarkers for advanced breast cancer patients

    Directory of Open Access Journals (Sweden)

    Paul Dowling

    2014-12-01

    General significance: Mass spectrometry profiling of Transferrin-bound proteins has revealed serum proteins that can distinguish between serum from advanced breast cancer patients and healthy control subjects with high confidence.

  2. Using tolerance bounds in scientific investigations

    Energy Technology Data Exchange (ETDEWEB)

    Wendelberger, J.R.

    1996-07-01

    Assessment of the variability in population values plays an important role in the analysis of scientific data. Analysis of scientific data often involves developing a bound on a proportion of a population. Sometimes simple probability bounds are obtained using formulas involving known mean and variance parameters and replacing the parameters by sample estimates. The resulting bounds are only approximate and fail to account for the variability in the estimated parameters. Tolerance bounds provide bounds on population proportions which account for the variation resulting from the estimated mean and variance parameters. A beta content, gamma confidence tolerance interval is constructed so that a proportion beta of the population lies within the region bounded by the interval with confidence gamma. An application involving corrosion measurements is used to illustrate the use of tolerance bounds for different situations. Extensions of standard tolerance intervals are applied to generate regression tolerance bounds, tolerance bounds for more general models of measurements collected over time, and tolerance intervals for varying precision data. Tolerance bounds also provide useful information for designing the collection of future data.

  3. Interactions between macromolecule-bound antioxidants and Trolox during liposome autoxidation: A multivariate approach.

    Science.gov (United States)

    Çelik, Ecem Evrim; Rubio, Jose Manuel Amigo; Andersen, Mogens L; Gökmen, Vural

    2017-12-15

    The interactions between free and macromolecule-bound antioxidants were investigated in order to evaluate their combined effects on the antioxidant environment. Dietary fiber (DF), protein and lipid-bound antioxidants, obtained from whole wheat, soybean and olive oil products, respectively and Trolox were used for this purpose. Experimental studies were carried out in autoxidizing liposome medium by monitoring the development of fluorescent products formed by lipid oxidation. Chemometric methods were used both at experimental design and multivariate data analysis stages. Comparison of the simple addition effects of Trolox and bound antioxidants with measured values on lipid oxidation revealed synergetic interactions for DF and refined olive oil-bound antioxidants, and antagonistic interactions for protein and extra virgin olive oil-bound antioxidants with Trolox. A generalized version of logistic function was successfully used for modelling the oxidation curve of liposomes. Principal component analysis revealed two separate phases of liposome autoxidation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Functional Genomic and Proteomic Analysis Reveals Disruption of Myelin-Related Genes and Translation in a Mouse Model of Early Life Neglect

    Science.gov (United States)

    Bordner, Kelly A.; George, Elizabeth D.; Carlyle, Becky C.; Duque, Alvaro; Kitchen, Robert R.; Lam, TuKiet T.; Colangelo, Christopher M.; Stone, Kathryn L.; Abbott, Thomas B.; Mane, Shrikant M.; Nairn, Angus C.; Simen, Arthur A.

    2011-01-01

    Early life neglect is an important public health problem which can lead to lasting psychological dysfunction. Good animal models are necessary to understand the mechanisms responsible for the behavioral and anatomical pathology that results. We recently described a novel model of early life neglect, maternal separation with early weaning (MSEW), that produces behavioral changes in the mouse that persist into adulthood. To begin to understand the mechanism by which MSEW leads to these changes we applied cDNA microarray, next-generation RNA-sequencing (RNA-seq), label-free proteomics, multiple reaction monitoring (MRM) proteomics, and methylation analysis to tissue samples obtained from medial prefrontal cortex to determine the molecular changes induced by MSEW that persist into adulthood. The results show that MSEW leads to dysregulation of markers of mature oligodendrocytes and genes involved in protein translation and other categories, an apparent downward biasing of translation, and methylation changes in the promoter regions of selected dysregulated genes. These findings are likely to prove useful in understanding the mechanism by which early life neglect affects brain structure, cognition, and behavior. PMID:21629843

  5. Hippocampal Proteomic Analysis Reveals Distinct Pathway Deregulation Profiles at Early and Late Stages in a Rat Model of Alzheimer's-Like Amyloid Pathology.

    Science.gov (United States)

    Do Carmo, Sonia; Crynen, Gogce; Paradis, Tiffany; Reed, Jon; Iulita, M Florencia; Ducatenzeiler, Adriana; Crawford, Fiona; Cuello, A Claudio

    2017-05-13

    The cerebral accumulation and cytotoxicity of amyloid beta (Aβ) is central to Alzheimer's pathogenesis. However, little is known about how the amyloid pathology affects the global expression of brain proteins at different disease stages. In order to identify genotype and time-dependent significant changes in protein expression, we employed quantitative proteomics analysis of hippocampal tissue from the McGill-R-Thy1-APP rat model of Alzheimer-like amyloid pathology. McGill transgenic rats were compared to wild-type rats at early and late pathology stages, i.e., when intraneuronal Aβ amyloid burden is conspicuous and when extracellular amyloid plaques are abundant with more pronounced cognitive deficits. After correction for multiple testing, the expression levels of 64 proteins were found to be considerably different in transgenic versus wild-type rats at the pre-plaque stage (3 months), and 86 proteins in the post-plaque group (12 months), with only 9 differentially regulated proteins common to the 2 time-points. This minimal overlap supports the hypothesis that different molecular pathways are affected in the hippocampus at early and late stages of the amyloid pathology throughout its continuum. At early stages, disturbances in pathways related to cellular responses to stress, protein homeostasis, and neuronal structure are predominant, while disturbances in metabolic energy generation dominate at later stages. These results shed new light on the molecular pathways affected by the early accumulation of Aβ and how the evolving amyloid pathology impacts other complex metabolic pathways.

  6. Bound anionic states of adenine

    Energy Technology Data Exchange (ETDEWEB)

    Haranczyk, Maciej; Gutowski, Maciej S; Li, Xiang; Bowen, Kit H

    2007-03-20

    Anionic states of nucleic acid bases are involved in DNA damage by low-energy electrons and in charge transfer through DNA. Previous gas phase studies of free, unsolvated nucleic acid base parent anions probed only dipole-bound states, which are not present in condensed phase environments, but did not observe valence anionic states, which for purine bases, are thought to be adiabatically unbound. Contrary to this expectation, we have demonstrated that some thus far ignored tautomers of adenine, which result from enamine-imine transformations, support valence anionic states with electron vertical detachment energies as large as 2.2 eV, and at least one of these anionic tautomers is adiabatically bound. Moreover, we predict that the new anionic tautomers should also dominate in solutions and should be characterized by larger values of electron vertical detachment energy than the canonical valence anion. All of the new-found anionic tautomers might be formed in the course of dissociative electron attachment followed by a hydrogen atom attachment to a carbon atom, and they might affect the structure and properties of DNA and RNA exposed to low-energy electrons. The discovery of these valence anionic states of adenine was facilitated by the development of: (i) a new experimental method for preparing parent anions of nucleic acid bases for photoelectron experiments, and (ii) a new combinatorial/ quantum chemical approach for identification of the most stable tautomers of organic molecules. The computational portion of this work was supported by the: (i) Polish State Committee for Scientific Research (KBN) Grants: DS/8000-4-0140-7 (M.G.) and N204 127 31/2963 (M.H.), (ii) European Social Funds (EFS) ZPORR/2.22/II/2.6/ARP/U/2/05 (M.H.), and (iii) US DOE Office of Biological and Environmental Research, Low Dose Radiation Research Program (M.G.). M.H. holds the Foundation for Polish Science (FNP) award for young scientists. The calculations were performed at the Academic

  7. Quality Is Culture-Bound.

    Science.gov (United States)

    Ebbeck, Fred

    Presenting a case study of the African nation of Burundi to illustrate the great variation in the environment in which children are raised in developing and developed nations, this paper focuses on the importance of considering the context of a particular culture and society when educators talk about the quality of early childhood services.…

  8. Bubble-seq analysis of the human genome reveals distinct chromatin-mediated mechanisms for regulating early- and late-firing origins

    Science.gov (United States)

    Mesner, Larry D.; Valsakumar, Veena; Cieślik, Marcin; Pickin, Rebecca; Hamlin, Joyce L.; Bekiranov, Stefan

    2013-01-01

    We have devised a method for isolating virtually pure and comprehensive libraries of restriction fragments that contained replication initiation sites (bubbles) in vivo. We have now sequenced and mapped the bubble-containing fragments from GM06990, a near-normal EBV-transformed lymphoblastoid cell line, and have compared origin distributions with a comprehensive replication timing study recently published for this cell line. We find that early-firing origins, which represent ∼32% of all origins, overwhelmingly represent zones, associate only marginally with active transcription units, are localized within large domains of open chromatin, and are significantly associated with DNase I hypersensitivity. Origin “density” falls from early- to mid-S-phase, but rises again in late S-phase to levels only 17% lower than in early S-phase. Unexpectedly, late origin density calculated on the 1-Mb scale increases as a function of increasing chromatin compaction. Furthermore, the median efficiency of origins in late-replicating, heterochromatic domains is only 25% lower than in early-replicating euchromatic loci. Thus, the activation of early- and late-firing origins must be regulated by quintessentially different mechanisms. The aggregate data can be unified into a model in which initiation site selection is driven almost entirely by epigenetic factors that fashion both the long-range and local chromatin environments, with underlying DNA sequence and local transcriptional activity playing only minor roles. Importantly, the comprehensive origin map we have prepared for GM06990 overlaps moderately well with origin maps recently reported for the genomes of four different human cell lines based on the distributions of small nascent strands. PMID:23861383

  9. Instanton bound states in ABJM theory

    Energy Technology Data Exchange (ETDEWEB)

    Hatsuda, Yasuyuki [DESY Hamburg (Germany). Theory Group; Tokyo Institute of Technology (Japan). Dept. of Physics; Moriyama, Sanefumi [Nagoya Univ. (Japan). Kobayashi Maskawa Inst. and Graduate School of Mathematics; Okuyama, Kazumi [Shinshu Univ., Matsumoto, Nagano (Japan). Dept. of Physics

    2013-06-15

    The partition function of the ABJM theory receives non-perturbative corrections due to instanton effects. We study these non-perturbative corrections, including bound states of worldsheet instantons and membrane instantons, in the Fermi-gas approach. We require that the total non-perturbative correction should be always finite for arbitrary Chern-Simons level. This finiteness is realized quite non-trivially because each bound state contribution naively diverges at some levels. The poles of each contribution should be canceled out in total. We use this pole cancellation mechanism to find unknown bound state corrections from known ones. We conjecture a general expression of the bound state contribution. Summing up all the bound state contributions, we find that the effect of bound states is simply incorporated into the worldsheet instanton correction by a redefinition of the chemical potential in the Fermi-gas system. Analytic expressions of the 3- and 4-membrane instanton corrections are also proposed.

  10. Decision theory with resource-bounded agents.

    Science.gov (United States)

    Halpern, Joseph Y; Pass, Rafael; Seeman, Lior

    2014-04-01

    There have been two major lines of research aimed at capturing resource-bounded players in game theory. The first, initiated by Rubinstein (), charges an agent for doing costly computation; the second, initiated by Neyman (), does not charge for computation, but limits the computation that agents can do, typically by modeling agents as finite automata. We review recent work on applying both approaches in the context of decision theory. For the first approach, we take the objects of choice in a decision problem to be Turing machines, and charge players for the "complexity" of the Turing machine chosen (e.g., its running time). This approach can be used to explain well-known phenomena like first-impression-matters biases (i.e., people tend to put more weight on evidence they hear early on) and belief polarization (two people with different prior beliefs, hearing the same evidence, can end up with diametrically opposed conclusions) as the outcomes of quite rational decisions. For the second approach, we model people as finite automata, and provide a simple algorithm that, on a problem that captures a number of settings of interest, provably performs optimally as the number of states in the automaton increases. Copyright © 2014 Cognitive Science Society, Inc.

  11. Distance hijacking attacks on distance bounding protocols

    OpenAIRE

    Cremers, Cas; Rasmussen, Kasper Bonne; Čapkun, Srdjan

    2011-01-01

    Distance bounding protocols are typically analyzed with respect to three types of attacks: Distance Fraud, Mafia Fraud, and Terrorist Fraud. We define a fourth main type of attacks on distance bounding protocols, called Distance Hijacking attacks. We show that many proposed distance bounding protocols are vulnerable to these attacks, and we propose solutions to make these protocols resilient to Distance Hijacking. Additionally, we generalize Distance Hijacking to Location Hijacking, to which ...

  12. Boundedly UC spaces: characterisations and preservation | Jain ...

    African Journals Online (AJOL)

    A metric space (X, d) is called a boundedly UC space if every closed and bounded subset of X is a UC space. A metric space (X, d) is called a UC space if each real-valued continuous function on (X, d) is uniformly continuous. In this paper, we study twenty-two equivalent conditions for a metric space to be a boundedly UC ...

  13. Bounded cohomology of discrete groups

    CERN Document Server

    Frigerio, Roberto

    2017-01-01

    The author manages a near perfect equilibrium between necessary technicalities (always well motivated) and geometric intuition, leading the readers from the first simple definition to the most striking applications of the theory in 13 very pleasant chapters. This book can serve as an ideal textbook for a graduate topics course on the subject and become the much-needed standard reference on Gromov's beautiful theory. -Michelle Bucher The theory of bounded cohomology, introduced by Gromov in the late 1980s, has had powerful applications in geometric group theory and the geometry and topology of manifolds, and has been the topic of active research continuing to this day. This monograph provides a unified, self-contained introduction to the theory and its applications, making it accessible to a student who has completed a first course in algebraic topology and manifold theory. The book can be used as a source for research projects for master's students, as a thorough introduction to the field for graduate student...

  14. Bounded sets in fast complete inductive limits

    Directory of Open Access Journals (Sweden)

    Jan Kucera

    1984-01-01

    Full Text Available Let E1⊂E2⊂… be a sequence of locally convex spaces with all identity maps: En→En+1 continuous and E=indlim En fast complete. Then each set bounded in E is also bounded in some En iff for any Banach disk B bounded in E and n∈N, the closure of B⋂En in B is bounded in some Em. This holds, in particular, if all spaces En are webbed.

  15. Valuation models and Simon's bounded rationality

    National Research Council Canada - National Science Library

    Alexandra Strommer de Farias Godoi

    2009-01-01

    This paper aims at reconciling the evidence that sophisticated valuation models are increasingly used by companies in their investment appraisal with the literature of bounded rationality, according...

  16. Some Improved Nonperturbative Bounds for Fermionic Expansions

    Energy Technology Data Exchange (ETDEWEB)

    Lohmann, Martin, E-mail: marlohmann@gmail.com [Universita di Roma Tre, Dipartimento di Matematica (Italy)

    2016-06-15

    We reconsider the Gram-Hadamard bound as it is used in constructive quantum field theory and many body physics to prove convergence of Fermionic perturbative expansions. Our approach uses a recursion for the amplitudes of the expansion, discovered in a model problem by Djokic (2013). It explains the standard way to bound the expansion from a new point of view, and for some of the amplitudes provides new bounds, which avoid the use of Fourier transform, and are therefore superior to the standard bounds for models like the cold interacting Fermi gas.

  17. A strongly quasiconvex PAC-Bayesian bound

    DEFF Research Database (Denmark)

    Thiemann, Niklas; Igel, Christian; Wintenberger, Olivier

    We propose a new PAC-Bayesian bound and a way of constructing a hypothesis space, so that the bound is convex in the posterior distribution and also convex in a trade-off parameter between empirical performance of the posterior distribution and its complexity. The complexity is measured by the Ku......We propose a new PAC-Bayesian bound and a way of constructing a hypothesis space, so that the bound is convex in the posterior distribution and also convex in a trade-off parameter between empirical performance of the posterior distribution and its complexity. The complexity is measured...

  18. New lower bound for the Capacitated Arc Routing Problem

    DEFF Research Database (Denmark)

    Wøhlk, Sanne

    2006-01-01

    We present a new lower bound, the Multiple Cuts Node Duplication Lower Bound, for the undirected Capacitated Arc Routing Problem.We prove that this new bound dominates the existing bounds for the problem. Computational results are also provided.......We present a new lower bound, the Multiple Cuts Node Duplication Lower Bound, for the undirected Capacitated Arc Routing Problem.We prove that this new bound dominates the existing bounds for the problem. Computational results are also provided....

  19. Viewing Majorana Bound States by Rabi Oscillations.

    Science.gov (United States)

    Wang, Zhi; Liang, Qi-Feng; Yao, Dao-Xin; Hu, Xiao

    2015-07-08

    We propose to use Rabi oscillation as a probe to view the fractional Josepshon relation (FJR) associated with Majorana bound states (MBSs) expected in one-dimensional topological superconductors. The system consists of a quantum dot (QD) and an rf-SQUID with MBSs at the Josephson junction. Rabi oscillations between energy levels formed by MBSs are induced by ac gate voltage controlling the coupling between QD and MBS when the photon energy proportional to the ac frequency matches gap between quantum levels formed by MBSs and QD. As a manifestation of the Rabi oscillation in the whole system involving MBSs, the electron occupation on QD oscillates with time, which can be measured by charge sensing techniques. With Floquet theorem and numerical analysis we reveal that from the resonant driving frequency for coherent Rabi oscillation one can directly map out the FJR cos(πΦ/Φ0) as a signature of MBSs, with Φ the magnetic flux through SQUID and Φ0 = hc/2e the flux quantum. The present scheme is expected to provide a clear evidence for MBSs under intensive searching.

  20. Effect of Telecollaboration on Translation of Culture-Bound Texts

    Directory of Open Access Journals (Sweden)

    Vahid Rafieyan

    2016-07-01

    Full Text Available One of the most problematic perspectives of translation phenomenon is the cultural gap between the source language and the target language (Yang, 2010. This gap can be ideally filled through telecollaboration which provides internationally dispersed language learners in parallel language classes with cost-effective access to, and engagement with, peers who are expert speakers of the language under study (Belz, 2005. To investigate the effect of telecollaboration on the quality of translation of culture-bound texts, the current study was conducted on 64 Iranian undergraduate students of English translation at a university in Iran. Instruments used in the study consisted of three texts containing news excerpts from Voice of America (VOA. The study consisted of three phases: 1 assessing quality of translation of culture-bound texts, 2 random assignment of participants to two groups: one merely receiving cultural instruction while the other being linked to native English speakers through LinkedIn alongside receiving cultural instruction, and 3 assessing quality of translation of culture-bound texts immediately and two months following treatment. The results of mixed between-within subjects analysis of variance revealed the significant positive effect of telecollaboration on developing quality of translation of culture-bound texts and sustaining the attained knowledge. The pedagogical implications of the findings suggested incorporation of cultural components of source language society into translation courses and providing opportunities for translation students to be exposed to authentic and intensive source language culture through telecollaboration.

  1. DNA methylation profiling of sorted cells from myelofibrosis patients reveals aberrant epigenetic regulation of immune pathways and identifies early MPN driver genes

    DEFF Research Database (Denmark)

    Nielsen, Helene Myrtue; Andersen, Christen Lykkegaard; Kristensen, Lasse Sommer

    2015-01-01

    , PV) toadvancedMF. Multiple studies report frequent mutations in epigenetic regulators. However, the association to epigenetic changes and the role of epigenetic aberrations in different cell populations is still unknown. Aims: We therefore performed DNA methylation profiling of sorted cells from MF...... patients to unravel pathways contributing to disease phenotype and gain insight into MF pathogenesis. As an aberrant DNA methylation pattern may be an early event in tumorigenesis and may be crucial for progression of the malignant clone towards the more aggressive forms of MPN, we further aimed...

  2. Zif268 mRNA Expression Patterns Reveal a Distinct Impact of Early Pattern Vision Deprivation on the Development of Primary Visual Cortical Areas in the Cat

    OpenAIRE

    Laskowska-Macios, Karolina; Zapasnik, Monika; Hu, Tjing; Kossut, Malgorzata; Arckens, Lut; Burnat, Kalina

    2014-01-01

    Pattern vision deprivation (BD) can induce permanent deficits in global motion perception. The impact of timing and duration of BD on the maturation of the central and peripheral visual field representations in cat primary visual areas 17 and 18 remains unknown. We compared early BD, from eye opening for 2, 4, or 6 months, with late onset BD, after 2 months of normal vision, using the expression pattern of the visually driven activity reporter gene zif268 as readout. Decreasing zif268 mRNA le...

  3. Bounded rationality and learning in complex markets

    NARCIS (Netherlands)

    Hommes, C.H.; Barkely Rosser Jr, J.

    2009-01-01

    This chapter reviews some work on bounded rationality, expectation formation and learning in complex markets, using the familiar demand-supply cobweb model. We emphasize two stories of bounded rationality, one story of adaptive learning and another story of evolutionary selection. According to the

  4. Bounded rationality and learning in complex markets

    NARCIS (Netherlands)

    Hommes, C.H.

    2007-01-01

    This chapter reviews some work on bounded rationality, expectation formation and learning in complex markets, using the familiar demand-supply cobweb model. We emphasize two stories of bounded rationality, one story of adaptive learning and another story of evolutionary selection. According to the

  5. Spatial coagulation with bounded coagulation rate

    OpenAIRE

    Bailleul, Ismael

    2010-01-01

    We prove that the spatial coagulation equation with bounded coagulation rate is well-posed for all times in a given class of kernels if the convection term of the underlying particle dynamics has divergence bounded below by a positive constant. Multiple coagulations, fragmentation and scattering are also considered.

  6. Schroedinger upper bounds to semirelativistic eigenvalues

    Energy Technology Data Exchange (ETDEWEB)

    Hall, Richard L [Department of Mathematics and Statistics, Concordia University, 1455 de Maisonneuve Boulevard West, Montreal, Quebec, H3G 1M8 (Canada); Lucha, Wolfgang [Institut fuer Hochenergiephysik, Oesterreichische Akademie der Wissenschaften, Nikolsdorfergasse 18, A-1050 Vienna (Austria)

    2005-09-16

    Problems posed by semirelativistic Hamiltonians of the form H = {radical}(m{sup 2} + p{sup 2}) + V(r) are studied. It is shown that energy upper bounds can be constructed in terms of certain related Schroedinger operators; these bounds include free parameters which can be chosen optimally.

  7. No-arbitrage bounds for financial scenarios

    DEFF Research Database (Denmark)

    Geyer, Alois; Hanke, Michael; Weissensteiner, Alex

    2014-01-01

    We derive no-arbitrage bounds for expected excess returns to generate scenarios used in financial applications. The bounds allow to distinguish three regions: one where arbitrage opportunities will never exist, a second where arbitrage may be present, and a third, where arbitrage opportunities...

  8. Nonatomic dual bakery algorithm with bounded tokens

    NARCIS (Netherlands)

    Aravind, Alex A.; Hesselink, Wim H.

    A simple mutual exclusion algorithm is presented that only uses nonatomic shared variables of bounded size, and that satisfies bounded overtaking. When the shared variables behave atomically, it has the first-come-first-served property (FCFS). Nonatomic access makes information vulnerable. The

  9. Polynomially Bounded Sequences and Polynomial Sequences

    Directory of Open Access Journals (Sweden)

    Okazaki Hiroyuki

    2015-09-01

    Full Text Available In this article, we formalize polynomially bounded sequences that plays an important role in computational complexity theory. Class P is a fundamental computational complexity class that contains all polynomial-time decision problems [11], [12]. It takes polynomially bounded amount of computation time to solve polynomial-time decision problems by the deterministic Turing machine. Moreover we formalize polynomial sequences [5].

  10. Upper Bounds on Numerical Approximation Errors

    DEFF Research Database (Denmark)

    Raahauge, Peter

    2004-01-01

    This paper suggests a method for determining rigorous upper bounds on approximationerrors of numerical solutions to infinite horizon dynamic programming models.Bounds are provided for approximations of the value function and the policyfunction as well as the derivatives of the value function...

  11. On the range of completely bounded maps

    Directory of Open Access Journals (Sweden)

    Richard I. Loebl

    1978-01-01

    Full Text Available It is shown that if every bounded linear map from a C*-algebra α to a von Neumann algebra β is completely bounded, then either α is finite-dimensional or β⫅⊗Mn, where is a commutative von Neumann algebra and Mn is the algebra of n×n complex matrices.

  12. A polynomial lower bound for testing monotonicity

    NARCIS (Netherlands)

    A. Belovs (Aleksandr); Blais, E. (Eric)

    2016-01-01

    textabstractWe show that every algorithm for testing n-variate Boolean functions for monotonicity has query complexity Ω(n1/4). All previous lower bounds for this problem were designed for nonadaptive algorithms and, as a result, the best previous lower bound for general (possibly adaptive)

  13. Analysis of the early heterocyst Cys-proteome in the multicellular cyanobacterium Nostoc punctiforme reveals novel insights into the division of labor within diazotrophic filaments.

    Science.gov (United States)

    Sandh, Gustaf; Ramström, Margareta; Stensjö, Karin

    2014-12-04

    In the filamentous cyanobacterium Nostoc punctiforme ATCC 29133, removal of combined nitrogen induces the differentiation of heterocysts, a cell-type specialized in N2 fixation. The differentiation involves genomic, structural and metabolic adaptations. In cyanobacteria, changes in the availability of carbon and nitrogen have also been linked to redox regulated posttranslational modifications of protein bound thiol groups. We have here employed a thiol targeting strategy to relatively quantify the putative redox proteome in heterocysts as compared to N2-fixing filaments, 24 hours after combined nitrogen depletion. The aim of the study was to expand the coverage of the cell-type specific proteome and metabolic landscape of heterocysts. Here we report the first cell-type specific proteome of newly formed heterocysts, compared to N2-fixing filaments, using the cysteine-specific selective ICAT methodology. The data set defined a good quantitative accuracy of the ICAT reagent in complex protein samples. The relative abundance levels of 511 proteins were determined and 74% showed a cell-type specific differential abundance. The majority of the identified proteins have not previously been quantified at the cell-type specific level. We have in addition analyzed the cell-type specific differential abundance of a large section of proteins quantified in both newly formed and steady-state diazotrophic cultures in N. punctiforme. The results describe a wide distribution of members of the putative redox regulated Cys-proteome in the central metabolism of both vegetative cells and heterocysts of N. punctiforme. The data set broadens our understanding of heterocysts and describes novel proteins involved in heterocyst physiology, including signaling and regulatory proteins as well as a large number of proteins with unknown function. Significant differences in cell-type specific abundance levels were present in the cell-type specific proteomes of newly formed diazotrophic filaments

  14. The massacre mass grave of Schöneck-Kilianstädten reveals new insights into collective violence in Early Neolithic Central Europe.

    Science.gov (United States)

    Meyer, Christian; Lohr, Christian; Gronenborn, Detlef; Alt, Kurt W

    2015-09-08

    Conflict and warfare are central but also disputed themes in discussions about the European Neolithic. Although a few recent population studies provide broad overviews, only a very limited number of currently known key sites provide precise insights into moments of extreme and mass violence and their impact on Neolithic societies. The massacre sites of Talheim, Germany, and Asparn/Schletz, Austria, have long been the focal points around which hypotheses concerning a final lethal crisis of the first Central European farmers of the Early Neolithic Linearbandkeramik Culture (LBK) have concentrated. With the recently examined LBK mass grave site of Schöneck-Kilianstädten, Germany, we present new conclusive and indisputable evidence for another massacre, adding new data to the discussion of LBK violence patterns. At least 26 individuals were violently killed by blunt force and arrow injuries before being deposited in a commingled mass grave. Although the absence and possible abduction of younger females has been suggested for other sites previously, a new violence-related pattern was identified here: the intentional and systematic breaking of lower limbs. The abundance of the identified perimortem fractures clearly indicates torture and/or mutilation of the victims. The new evidence presented here for unequivocal lethal violence on a large scale is put into perspective for the Early Neolithic of Central Europe and, in conjunction with previous results, indicates that massacres of entire communities were not isolated occurrences but rather were frequent features of the last phases of the LBK.

  15. Early expression of aromatase and the membrane estrogen receptor GPER in neuromasts reveals a role for estrogens in the development of the frog lateral line system.

    Science.gov (United States)

    Hamilton, Christine K; Navarro-Martin, Laia; Neufeld, Miriam; Basak, Ajoy; Trudeau, Vance L

    2014-09-01

    Estrogens and their receptors are present at very early stages of vertebrate embryogenesis before gonadal tissues are formed. However, the cellular source and the function of estrogens in embryogenesis remain major questions in developmental endocrinology. We demonstrate the presence of estrogen-synthesizing enzyme aromatase and G protein-coupled estrogen receptor (GPER) proteins throughout early embryogenesis in the model organism, Silurana tropicalis. We provide the first evidence of aromatase in the vertebrate lateral line. High levels of aromatase were detected in the mantle cells of neuromasts, the mechanosensory units of the lateral line, which persisted throughout the course of development (Nieuwkoop and Faber stages 34-47). We show that GPER is expressed in both the accessory and hair cells. Pharmacological activation of GPER with the agonist G-1 disrupted neuromast development and migration. Future study of this novel estrogen system in the amphibian lateral line may shed light on similar systems such as the mammalian inner ear. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. The estrous cycle surpasses sex differences in regulating the transcriptome in the rat medial prefrontal cortex and reveals an underlying role of early growth response 1.

    Science.gov (United States)

    Duclot, Florian; Kabbaj, Mohamed

    2015-12-02

    Males and females differ in cognitive functions and emotional processing, which in part have been associated with baseline sex differences in gene expression in the medial prefrontal cortex. Nevertheless, a growing body of evidence suggests that sex differences in medial prefrontal cortex-dependent cognitive functions are attenuated by hormonal fluctuations within the menstrual cycle. Despite known genomic effects of ovarian hormones, the interaction of the estrous cycle with sex differences in gene expression in the medial prefrontal cortex remains unclear and warrants further investigations. We undertake a large-scale characterization of sex differences and their interaction with the estrous cycle in the adult medial prefrontal cortex transcriptome and report that females with high and low ovarian hormone levels exhibited a partly opposed sexually biased transcriptome. The extent of regulation within females vastly exceeds sex differences, and supports a multi-level reorganization of synaptic function across the estrous cycle. Genome-wide analysis of the transcription factor early growth response 1 binding highlights its role in controlling the synapse-related genes varying within females. We uncover a critical influence of the estrous cycle on the adult rat medial prefrontal cortex transcriptome resulting in partly opposite sex differences in proestrus when compared to diestrus females, and we discovered a direct role for Early Growth Response 1 in this opposite regulation. In addition to illustrating the importance of accounting for the estrous cycle in females, our data set the ground for a better understanding of the female specificities in cognition and emotional processing.

  17. Diffusion tractography and graph theory analysis reveal the disrupted rich-club organization of white matter structural networks in early Tourette Syndrome children

    Science.gov (United States)

    Wen, Hongwei; Liu, Yue; Wang, Shengpei; Zhang, Jishui; Peng, Yun; He, Huiguang

    2017-03-01

    Tourette syndrome (TS) is a childhood-onset neurobehavioral disorder. At present, the topological disruptions of the whole brain white matter (WM) structural networks remain poorly understood in TS children. Considering the unique position of the topologically central role of densely interconnected brain hubs, namely the rich club regions, therefore, we aimed to investigate whether the rich club regions and their related connections would be particularly vulnerable in early TS children. In our study, we used diffusion tractography and graph theoretical analyses to explore the rich club structures in 44 TS children and 48 healthy children. The structural networks of TS children exhibited significantly increased normalized rich club coefficient, suggesting that TS is characterized by increased structural integrity of this centrally embedded rich club backbone, potentially resulting in increased global communication capacity. In addition, TS children showed a reorganization of rich club regions, as well as significantly increased density and decreased number in feeder connections. Furthermore, the increased rich club coefficients and feeder connections density of TS children were significantly positively correlated to tic severity, indicating that TS may be characterized by a selective alteration of the structural connectivity of the rich club regions, tending to have higher bridging with non-rich club regions, which may increase the integration among tic-related brain circuits with more excitability but less inhibition for information exchanges between highly centered brain regions and peripheral areas. In all, our results suggest the disrupted rich club organization in early TS children and provide structural insights into the brain networks.

  18. Zif268 mRNA Expression Patterns Reveal a Distinct Impact of Early Pattern Vision Deprivation on the Development of Primary Visual Cortical Areas in the Cat.

    Science.gov (United States)

    Laskowska-Macios, Karolina; Zapasnik, Monika; Hu, Tjing-Tjing; Kossut, Malgorzata; Arckens, Lutgarde; Burnat, Kalina

    2015-10-01

    Pattern vision deprivation (BD) can induce permanent deficits in global motion perception. The impact of timing and duration of BD on the maturation of the central and peripheral visual field representations in cat primary visual areas 17 and 18 remains unknown. We compared early BD, from eye opening for 2, 4, or 6 months, with late onset BD, after 2 months of normal vision, using the expression pattern of the visually driven activity reporter gene zif268 as readout. Decreasing zif268 mRNA levels between months 2 and 4 characterized the normal maturation of the (supra)granular layers of the central and peripheral visual field representations in areas 17 and 18. In general, all BD conditions had higher than normal zif268 levels. In area 17, early BD induced a delayed decrease, beginning later in peripheral than in central area 17. In contrast, the decrease occurred between months 2 and 4 throughout area 18. Lack of pattern vision stimulation during the first 4 months of life therefore has a different impact on the development of areas 17 and 18. A high zif268 expression level at a time when normal vision is restored seems to predict the capacity of a visual area to compensate for BD. © The Author 2014. Published by Oxford University Press.

  19. Adjuvanted influenza-H1N1 vaccination reveals lymphoid signatures of age-dependent early responses and of clinical adverse events.

    Science.gov (United States)

    Sobolev, Olga; Binda, Elisa; O'Farrell, Sean; Lorenc, Anna; Pradines, Joel; Huang, Yongqing; Duffner, Jay; Schulz, Reiner; Cason, John; Zambon, Maria; Malim, Michael H; Peakman, Mark; Cope, Andrew; Capila, Ishan; Kaundinya, Ganesh V; Hayday, Adrian C

    2016-02-01

    Adjuvanted vaccines afford invaluable protection against disease, and the molecular and cellular changes they induce offer direct insight into human immunobiology. Here we show that within 24 h of receiving adjuvanted swine flu vaccine, healthy individuals made expansive, complex molecular and cellular responses that included overt lymphoid as well as myeloid contributions. Unexpectedly, this early response was subtly but significantly different in people older than ∼35 years. Wide-ranging adverse clinical events can seriously confound vaccine adoption, but whether there are immunological correlates of these is unknown. Here we identify a molecular signature of adverse events that was commonly associated with an existing B cell phenotype. Thus immunophenotypic variation among healthy humans may be manifest in complex pathophysiological responses.

  20. Early breakdown of isolation revealed by marriage behaviour in a Ladin-speaking community (Gardena Valley, South Tyrol, Italy, 1825-1924).

    Science.gov (United States)

    Gueresi, Paola

    2012-05-01

    The aim of this study was to investigate marriage behaviour from 1825 to 1924 in an Alpine valley inhabited by Ladin speakers (Gardena Valley, South Tyrol, Italy), where the particular geographic, linguistic and economic characteristics may have influenced the level of reproductive isolation. A total of 2183 marriage acts from the two main parishes of Santa Cristina and Ortisei were examined. Birth and residence endogamy, inbreeding coefficients from dispensations and from isonymy, birth place distribution of the spouses and isonymic relationships were analysed in four 25-year sub-periods. All the indicators considered point to a lower level of reproductive isolation at Ortisei, a main centre for the woodcarving industry, which appeared to be experiencing an early and effective breakdown of isolation. Marriage behaviour in the Gardena Valley between 1825 and 1924 seems to have been mostly influenced by socioeconomic factors rather than linguistic and cultural ones.

  1. Eye-tracking Reveals Abnormal Visual Preference for Geometric Images as an Early Biomarker of an ASD Subtype Associated with Increased Symptom Severity

    Science.gov (United States)

    Pierce, Karen; Marinero, Steven; Hazin, Roxana; McKenna, Benjamin; Barnes, Cynthia Carter; Malige, Ajith

    2015-01-01

    Background Clinically and biologically, ASD is heterogeneous. Unusual patterns of visual preference as indexed by eye-tracking are hallmarks, yet whether they can be used to define an early biomarker of ASD as a whole, or leveraged to define a subtype is unclear. To begin to examine this issue, large cohorts are required. Methods A sample of 334 toddlers from 6 distinct groups (115 ASD, 20 ASD-Features, 57 DD, 53 Other, 64 TD, and 25 Typ SIB) participated. Toddlers watched a movie containing both geometric and social images. Fixation duration and number of saccades within each AOI and validation statistics for this independent sample computed. Next, to maximize power, data from our previous study (N=110) was added totaling 444 subjects. A subset of toddlers repeated the eye-tracking procedure. Results As in the original study, a subset of toddlers with ASD fixated on geometric images greater than 69%. Using this cutoff, sensitivity for ASD was 21%, specificity 98%, and PPV 86%. Toddlers with ASD who strongly preferred geometric images had (a) worse cognitive, language, and social skills relative to toddlers with ASD who strongly preferred social images and (b) fewer saccades when viewing geometric images. Unaffected siblings of ASD probands did not show evidence of heightened preference for geometric images. Test-retest reliability was good. Examination of age effects suggest that this test may not be appropriate with children > 4 years. Conclusions Enhanced visual preference for geometric repetition may be an early developmental biomarker of an ASD subtype with more severe symptoms. PMID:25981170

  2. Eye Tracking Reveals Abnormal Visual Preference for Geometric Images as an Early Biomarker of an Autism Spectrum Disorder Subtype Associated With Increased Symptom Severity.

    Science.gov (United States)

    Pierce, Karen; Marinero, Steven; Hazin, Roxana; McKenna, Benjamin; Barnes, Cynthia Carter; Malige, Ajith

    2016-04-15

    Clinically and biologically, autism spectrum disorder (ASD) is heterogeneous. Unusual patterns of visual preference as indexed by eye tracking are hallmarks; however, whether they can be used to define an early biomarker of ASD as a whole or leveraged to define a subtype is unclear. To begin to examine this issue, large cohorts are required. A sample of 334 toddlers from six distinct groups (115 toddlers with ASD, 20 toddlers with ASD features, 57 toddlers with developmental delay, 53 toddlers with other conditions [e.g., premature birth, prenatal drug exposure], 64 toddlers with typical development, and 25 unaffected toddlers with siblings with ASD) was studied. Toddlers watched a movie containing geometric and social images. Fixation duration and number of saccades within each area of interest and validation statistics for this independent sample were computed. Next, to maximize power, data from our previous study (n = 110) were added for a total of 444 subjects. A subset of toddlers repeated the eye-tracking procedure. As in the original study, a subset of toddlers with ASD fixated on geometric images >69% of the time. Using this cutoff, sensitivity for ASD was 21%, specificity was 98%, and positive predictive value was 86%. Toddlers with ASD who strongly preferred geometric images had 1) worse cognitive, language, and social skills relative to toddlers with ASD who strongly preferred social images and 2) fewer saccades when viewing geometric images. Unaffected siblings of ASD probands did not show evidence of heightened preference for geometric images. Test-retest reliability was good. Examination of age effects suggested that this test may not be appropriate with children >4 years old. Enhanced visual preference for geometric repetition may be an early developmental biomarker of an ASD subtype with more severe symptoms. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  3. Event related potentials reveal early phonological and orthographic processing of single letters in letter-detection and letter-rhyme paradigms

    Directory of Open Access Journals (Sweden)

    Sewon Adrian Bann

    2016-04-01

    Full Text Available Introduction: When and where phonological processing occurs in the brain is still under some debate. Most paired-rhyme and phonological priming studies used word stimuli, which involve complex neural networks for word recognition and semantics. This study investigates early (300ms orthographic and phonological processing of letters.Methods: Eighteen participants aged 20-35 engaged in three two-forced choice experiments, one letter-detection (LetterID and two letter-rhyme (Paired-Rhyme and Letter-Rhyme tasks. From the EEG recordings, ERP differences within and across task stimuli were found. We also calculated the global field power (GFP for each participant. Accuracies and reaction times were also measured from their button presses for each task. Results: Behavioural: Reaction times were 18ms faster to letter than pseudoletter stimuli, and 27ms faster to rhyme than nonrhyme stimuli. ERP/GFP: In the LetterID task, grand-mean EPs showed typical P1, N1, P2, and P3 waveform morphologies to letter and pseudoletter stimuli, with GFPs to pseudoletters being greater than letters from 160-600ms. Across both rhyme tasks, there were greater negativities for nonrhyme than for rhyme stimuli at 145ms and 426ms. The P2 effect for rhyme stimuli was smaller than letter stimuli when compared across tasks.Conclusion: Differences in early processing of letters versus pseudoletters between 130-190ms suggest that letters are processed earlier and perhaps faster in the brain than pseudoletters. The P2 effect between letter and rhyme stimuli likely reflect sublexical phonological processing. Together, findings from our study fill in evidence for the temporal dynamics of orthographic and phonological processing of single letters.

  4. How 'love' and 'hate' differ from 'sleep': using combined electro/magnetoencephalographic data to reveal the sources of early cortical responses to emotional words.

    Science.gov (United States)

    Keuper, Kati; Zwanzger, Peter; Nordt, Marisa; Eden, Annuschka; Laeger, Inga; Zwitserlood, Pienie; Kissler, Johanna; Junghöfer, Markus; Dobel, Christian

    2014-03-01

    Emotional words--as symbols for biologically relevant concepts--are preferentially processed in brain regions including the visual cortex, frontal and parietal regions, and a corticolimbic circuit including the amygdala. Some of the brain structures found in functional magnetic resonance imaging are not readily apparent in electro- and magnetoencephalographic (EEG; MEG) measures. By means of a combined EEG/MEG source localization procedure to fully exploit the available information, we sought to reduce these discrepancies and gain a better understanding of spatiotemporal brain dynamics underlying emotional-word processing. Eighteen participants read high-arousing positive and negative, and low-arousing neutral nouns, while EEG and MEG were recorded simultaneously. Combined current-density reconstructions (L2-minimum norm least squares) for two early emotion-sensitive time intervals, the P1 (80-120 ms) and the early posterior negativity (EPN, 200-300 ms), were computed using realistic individual head models with a cortical constraint. The P1 time window uncovered an emotion effect peaking in the left middle temporal gyrus. In the EPN time window, processing of emotional words was associated with enhanced activity encompassing parietal and occipital areas, and posterior limbic structures. We suggest that lexical access, being underway within 100 ms, is speeded and/or favored for emotional words, possibly on the basis of an "emotional tagging" of the word form during acquisition. This gives rise to their differential processing in the EPN time window. The EPN, as an index of natural selective attention, appears to reflect an elaborate interplay of distributed structures, related to cognitive functions, such as memory, attention, and evaluation of emotional stimuli. Copyright © 2012 Wiley Periodicals, Inc.

  5. On Parameterized Gallager's First Bounds for Binary Linear Codes over AWGN Channels

    CERN Document Server

    Ma, Xiao; Bai, Baoming

    2012-01-01

    In this paper, nested Gallager regions with a single parameter is introduced to exploit Gallager's first bounding technique (GFBT). We present a necessary and sufficient condition on the optimal parameter. We also present a sufficient condition (with a simple geometrical explanation) under which the optimal parameter does not depend on the signal-to-noise ratio (SNR). With this general framework, three existing upper bounds are revisited, including the tangential bound (TB) of Berlekamp, the sphere bound (SB) of Herzberg and Poltyrev, and the tangential-sphere bound (TSB) of Poltyrev. This paper also reveals that the SB of Herzberg and Poltyrev is equivalent to the SB of Kasami et al., which was rarely cited in literature.

  6. Match-bounded String Rewriting Systems

    Science.gov (United States)

    Geser, Alfons; Hofbauer, Dieter; Waldmann, Johannes

    2003-01-01

    We introduce a new class of automated proof methods for the termination of rewriting systems on strings. The basis of all these methods is to show that rewriting preserves regular languages. To this end, letters are annotated with natural numbers, called match heights. If the minimal height of all positions in a redex is h+1 then every position in the reduct will get height h+1. In a match-bounded system, match heights are globally bounded. Using recent results on deleting systems, we prove that rewriting by a match-bounded system preserves regular languages. Hence it is decidable whether a given rewriting system has a given match bound. We also provide a sufficient criterion for the abence of a match-bound. The problem of existence of a match-bound is still open. Match-boundedness for all strings can be used as an automated criterion for termination, for match-bounded systems are terminating. This criterion can be strengthened by requiring match-boundedness only for a restricted set of strings, for instance the set of right hand sides of forward closures.

  7. Lower and Upper Bounds for Deniable Public-Key Encryption

    DEFF Research Database (Denmark)

    Bendlin, Rikke; Nielsen, Jesper Buus; Nordholt, Peter Sebastian

    2011-01-01

    A deniable cryptosystem allows a sender and a receiver to communicate over an insecure channel in such a way that the communication is still secure even if the adversary can threaten the parties into revealing their internal states after the execution of the protocol. This is done by allowing...... the parties to change their internal state to make it look like a given ciphertext decrypts to a message different from what it really decrypts to. Deniable encryption was in this way introduced to allow to deny a message exchange and hence combat coercion. Depending on which parties can be coerced...... that it is impossible to construct a non-interactive bi-deniable public-key encryption scheme with better than polynomial security. Specifically, we give an explicit bound relating the security of the scheme to how efficient the scheme is in terms of key size. Our impossibility result establishes a lower bound...

  8. Spin relaxation via exchange with donor impurity-bound electrons

    Science.gov (United States)

    Appelbaum, Ian

    In the Bir-Aronov-Pikus depolarization process affecting conduction electrons in p-type cubic semiconductors, spin relaxation is driven by exchange with short-lived valence band hole states. We have identified an analogous spin relaxation mechanism in nominally undoped silicon at low temperatures, when many electrons are bound to dilute dopant ion potentials. Inelastic scattering with externally injected conduction electrons accelerated by electric fields can excite transitions into highly spin-orbit-mixed bound excited states, driving strong spin relaxation of the conduction electrons via exchange interaction. We reveal the consequences of this spin depolarization mechanism both below and above the impact ionization threshold, where conventional charge and spin transport are restored. Based upon: Lan Qing, Jing Li, Ian Appelbaum, and Hanan Dery, Phys Rev. B 91, 241405(R) (2015). We acknowledge support from NSF, DTRA, and ONR.

  9. Sound velocity bound and neutron stars.

    Science.gov (United States)

    Bedaque, Paulo; Steiner, Andrew W

    2015-01-23

    It has been conjectured that the velocity of sound in any medium is smaller than the velocity of light in vacuum divided by sqrt[3]. Simple arguments support this bound in nonrelativistic and/or weakly coupled theories. The bound has been demonstrated in several classes of strongly coupled theories with gravity duals and is saturated only in conformal theories. We point out that the existence of neutron stars with masses around two solar masses combined with the knowledge of the equation of state of hadronic matter at "low" densities is in strong tension with this bound.

  10. Lability of copper bound to humic acid

    OpenAIRE

    Mao, Lingchen; Young, Scott D.; Bailey, Liz

    2015-01-01

    Geochemical speciation models generally include the assumption that all metal bound to humic acid and fulvic acid (HA, FA) is labile. However, in the current study, we determined the presence of a soluble ‘non-labile’ Cu fraction bound to HA extracted from grassland and peat soils. This was quantified by determining isotopically-exchangeable Cu (E-value) and EDTA-extraction of HA-bound Cu, separated by size-exclusion chromatography (SEC) and assayed by coupled ICP-MS. Evidence of time-depend...

  11. Positivity bounds on double parton distributions

    Energy Technology Data Exchange (ETDEWEB)

    Diehl, Markus; Kasemets, Tomas

    2013-03-15

    Double hard scattering in proton-proton collisions is described in terms of double parton distributions. We derive bounds on these distributions that follow from their interpretation as probability densities, taking into account all possible spin correlations between two partons in an unpolarized proton. These bounds constrain the size of the polarized distributions and can for instance be used to set upper limits on the effects of spin correlations in double hard scattering. We show that the bounds are stable under leading-order DGLAP evolution to higher scales.

  12. Lower bound for the nuclear kinetic energy

    Energy Technology Data Exchange (ETDEWEB)

    Dehesa, J.S. (Granada Univ. (Spain). Dept. de Fisica Nuclear); Galvez, F.J. (Granada Univ. (Spain). Dept. de Fisica Teorica)

    1985-06-27

    We argue that the kinetic energy of a many-fermion system is bounded from below by Kqsup(-2/3)A sup(5/3) / , with K = 0.565 where q is the number of spin states available to each particle and sup(1/2) is the root mean square radius of the single-particle density. A simple lower bound for the nuclear kinetic energy is found. Numerical values of the bound for several nuclei are shown, and a comparison with some self-consistent calculations and some pseudo-empirical values is made.

  13. Continuous bounded cohomology of locally compact groups

    CERN Document Server

    2001-01-01

    Recent research has repeatedly led to connections between important rigidity questions and bounded cohomology. However, the latter has remained by and large intractable. This monograph introduces the functorial study of the continuous bounded cohomology for topological groups, with coefficients in Banach modules. The powerful techniques of this more general theory have successfully solved a number of the original problems in bounded cohomology. As applications, one obtains, in particular, rigidity results for actions on the circle, for representations on complex hyperbolic spaces and on Teichmüller spaces. A special effort has been made to provide detailed proofs or references in quite some generality.

  14. Unbiased cell quantification reveals a continued increase in the number of neocortical neurones during early post-natal development in mice

    DEFF Research Database (Denmark)

    Lyck, Lise; Krøigård, Thomas; Finsen, Bente

    2007-01-01

    the number of neurones and glia in the neocortex during post-natal development in two separate strains of mice. Cell counting by the optical fractionator revealed that the number of neurones increased 80-100% from the time of birth to post-natal day (P)16, followed by a reduction by approximately 25...... was delayed until P16. The number of glia reached its maximum at P16, whereas the number of oligodendroglia, identified using a transgenic marker, increased until P55, the latest time of observation. Neurones continued to accumulate in the developing neocortex during the first 2 weeks of post......-natal development, underscoring fundamental differences in brain development in the mouse compared with human and non-human primates. Further, delayed acquisition of NeuN by neurones in the deepest neocortical layers and continued addition of oligodendroglia to the neocortex suggested that neocortical maturation...

  15. Early brain changes associated with psychotherapy in major depressive disorder revealed by resting-state fMRI: evidence for the top-down regulation theory.

    Science.gov (United States)

    Huang, Xiaolan; Huang, Peiyu; Li, Dan; Zhang, Yong; Wang, Tao; Mu, Jun; Li, Qi; Xie, Peng

    2014-12-01

    Major depressive disorder (MDD) is associated with dysfunction of the emotional circuitry in the brain. Psychotherapy and antidepressant treatment both aid in modulating this dysfunction, albeit probably through different mechanisms. A plausible "top-down" emotional regulation mechanism for psychotherapy has been described in previous studies, but the underlying findings are still contradictory. A total of 23 MDD patients and 20 healthy controls were enrolled. The early neural effects within 5 weeks of guided imagery-a psychotherapeutic method for treating depression-were assessed through resting-state functional magnetic resonance imaging using the regional homogeneity analytical method. At baseline, regional homogeneity was reduced in cortical regions and increased in limbic areas in the pre-treatment scans of MDD patients as compared to controls. After 5 weeks of guided imagery therapy, regional homogeneity in the ventromedial prefrontal cortex and the anterior cingulate gyrus both increased. Higher pre-treatment regional homogeneity in the dorsal anterior cingulate gyrus was positively correlated with an improved response to guided imagery therapy. The changes in regional homogeneity induced by guided imagery therapy demonstrate that this method of psychotherapy takes effect through a "top-down" mechanism. Future studies comparing various psychotherapeutic methodologies across multiple time points in the treatment course should yield more valuable insights on this topic. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. RNA-Seq reveals early distinctions and late convergence of gene expression between diapause and quiescence in the Asian tiger mosquito, Aedes albopictus

    Science.gov (United States)

    Poelchau, Monica F.; Reynolds, Julie A.; Elsik, Christine G.; Denlinger, David L.; Armbruster, Peter A.

    2013-01-01

    SUMMARY Dormancy is a crucial adaptation allowing insects to withstand harsh environmental conditions. The pre-programmed developmental arrest of diapause is a form of dormancy that is distinct from quiescence, in which development arrests in immediate response to hardship. Much progress has been made in understanding the environmental and hormonal controls of diapause. However, studies identifying transcriptional changes unique to diapause, rather than quiescence, are lacking, making it difficult to disentangle the transcriptional profiles of diapause from dormancy in general. The Asian tiger mosquito, Aedes albopictus, presents an ideal model for such a study, as diapausing and quiescent eggs can be staged and collected for global gene expression profiling using a newly developed transcriptome. Here, we use RNA-Seq to contrast gene expression during diapause with quiescence to identify transcriptional changes specific to the diapause response. We identify global trends in gene expression that show gradual convergence of diapause gene expression upon gene expression during quiescence. Functionally, early diapause A. albopictus show strong expression differences of genes involved in metabolism, which diminish over time. Of these, only expression of lipid metabolism genes remained distinct in late diapause. We identify several genes putatively related to hormonal control of development that are persistently differentially expressed throughout diapause, suggesting these might be involved in the maintenance of diapause. Our results identify key biological differences between diapausing and quiescent pharate larvae, and suggest candidate pathways for studying metabolism and the hormonal control of development during diapause in other species. PMID:23913949

  17. The ENU-induced cetus mutation reveals an essential role of the DNA helicase DDX11 for mesoderm development during early mouse embryogenesis.

    Science.gov (United States)

    Cota, Christina D; García-García, María J

    2012-08-01

    DDX11 is a DNA helicase of the conserved FANCJ/RAD3/XPD family involved in maintaining genome stability. Studies in yeast and humans have shown requirements for DDX11 in sister chromatid cohesion and DNA repair. In mouse, loss of Ddx11 results in embryonic lethality. However, the developmental defects of Ddx11 mutants are poorly understood. We describe the characterization and positional cloning of cetus, a mouse ENU-induced mutation in Ddx11. We demonstrate that cetus causes a nonconservative amino acid change in DDX11 motif V and that this mutation is a null allele of Ddx11. cetus mutant embryos failed to thrive beyond embryonic day 8.5 and displayed placental defects similar to those described in Ddx11 null embryos. Additionally, our characterization of Ddx11(cetus) mutants identified embryonic phenotypes that had not been previously reported in Ddx11(KO) embryos, including loss of somitic mesoderm, an open kinked neural tube and abnormal heart looping. We show that loss of Ddx11 causes widespread apoptosis from early embryonic stages and that loss of Ddx11 disrupts somitic mesoderm more dramatically than other embryonic cells. Our results identify novel roles of Ddx11 during embryo morphogenesis and demonstrate that the activity of its motif V is essential for DDX11 function. Copyright © 2012 Wiley Periodicals, Inc.

  18. Fetal and Early Post-Natal Mineralization of the Tympanic Bulla in Fin Whales May Reveal a Hitherto Undiscovered Evolutionary Trait

    Science.gov (United States)

    Cozzi, Bruno; Podestà, Michela; Mazzariol, Sandro; Zotti, Alessandro

    2012-01-01

    The evolution of the cetacean skeleton followed a path that differentiated this group from other terrestrial mammals about 50 million years ago [1], and debate is still going on about the relationships between Cetacea and Artiodactyla [2], [3], [4]. Some skeletal traits of the basilosaurids (the more advanced forms of Archaeocetes), such as the expansion of the peribullary air sinuses, dental modification and vertebral size uniformity [5] are maintained and further emphasized also in contemporary odontocetes and mysticetes. Using Dual-Energy X-Ray Absorptiometry here we report that the deposition of bone mineral in fetal and newborn specimens of the fin whale Balaenoptera physalus is remarkably higher in the bulla tympanica than in the adjacent basal skull or in the rest of the skeleton. Ossification of the tympanic bulla in fetal Artiodactyla (bovine, hippopotamus) is minimal, becomes sensible after birth and then progresses during growth, contrarily to the precocious mineralization that we observed in fin whales. Given the importance of the ear bones for the precise identification of phylogenetic relationship in therian evolution [6], this feature may indicate a specific evolutionary trait of fin whales and possibly other cetacean species or families. Early mineralization of the tympanic bulla allows immediate sound conduction in the aquatic medium and consequently holds potential importance for mother-calf relationship and postnatal survival. PMID:22615912

  19. Fetal and early post-natal mineralization of the tympanic bulla in fin whales may reveal a Hitherto undiscovered evolutionary trait.

    Science.gov (United States)

    Cozzi, Bruno; Podestà, Michela; Mazzariol, Sandro; Zotti, Alessandro

    2012-01-01

    The evolution of the cetacean skeleton followed a path that differentiated this group from other terrestrial mammals about 50 million years ago [1], and debate is still going on about the relationships between Cetacea and Artiodactyla [2], [3], [4]. Some skeletal traits of the basilosaurids (the more advanced forms of Archaeocetes), such as the expansion of the peribullary air sinuses, dental modification and vertebral size uniformity [5] are maintained and further emphasized also in contemporary odontocetes and mysticetes. Using Dual-Energy X-Ray Absorptiometry here we report that the deposition of bone mineral in fetal and newborn specimens of the fin whale Balaenoptera physalus is remarkably higher in the bulla tympanica than in the adjacent basal skull or in the rest of the skeleton. Ossification of the tympanic bulla in fetal Artiodactyla (bovine, hippopotamus) is minimal, becomes sensible after birth and then progresses during growth, contrarily to the precocious mineralization that we observed in fin whales. Given the importance of the ear bones for the precise identification of phylogenetic relationship in therian evolution [6], this feature may indicate a specific evolutionary trait of fin whales and possibly other cetacean species or families. Early mineralization of the tympanic bulla allows immediate sound conduction in the aquatic medium and consequently holds potential importance for mother-calf relationship and postnatal survival.

  20. Global distribution of Y-chromosome haplogroup C reveals the prehistoric migration routes of African exodus and early settlement in East Asia.

    Science.gov (United States)

    Zhong, Hua; Shi, Hong; Qi, Xue-Bin; Xiao, Chun-Jie; Jin, Li; Ma, Runlin Z; Su, Bing

    2010-07-01

    The regional distribution of an ancient Y-chromosome haplogroup C-M130 (Hg C) in Asia provides an ideal tool of dissecting prehistoric migration events. We identified 465 Hg C individuals out of 4284 males from 140 East and Southeast Asian populations. We genotyped these Hg C individuals using 12 Y-chromosome biallelic markers and 8 commonly used Y-short tandem repeats (Y-STRs), and performed phylogeographic analysis in combination with the published data. The results show that most of the Hg C subhaplogroups have distinct geographical distribution and have undergone long-time isolation, although Hg C individuals are distributed widely across Eurasia. Furthermore, a general south-to-north and east-to-west cline of Y-STR diversity is observed with the highest diversity in Southeast Asia. The phylogeographic distribution pattern of Hg C supports a single coastal 'Out-of-Africa' route by way of the Indian subcontinent, which eventually led to the early settlement of modern humans in mainland Southeast Asia. The northward expansion of Hg C in East Asia started approximately 40 thousand of years ago (KYA) along the coastline of mainland China and reached Siberia approximately 15 KYA and finally made its way to the Americas.

  1. Molecular analysis of the early interaction between the grapevine flower and Botrytis cinerea reveals that prompt activation of specific host pathways leads to fungus quiescence.

    Science.gov (United States)

    Haile, Zeraye Mehari; Pilati, Stefania; Sonego, Paolo; Malacarne, Giulia; Vrhovsek, Urska; Engelen, Kristof; Tudzynski, Paul; Zottini, Michela; Baraldi, Elena; Moser, Claudio

    2017-08-01

    Grape quality and yield can be impaired by bunch rot, caused by the necrotrophic fungus Botrytis cinerea. Infection often occurs at flowering, and the pathogen stays quiescent until fruit maturity. Here, we report a molecular analysis of the early interaction between B. cinerea and Vitis vinifera flowers, using a controlled infection system, confocal microscopy and integrated transcriptomic and metabolic analysis of the host and the pathogen. Flowers from fruiting cuttings of the cultivar Pinot Noir were infected with green fluorescent protein (GFP)-labelled B. cinerea and studied at 24 and 96 hours post-inoculation (h.p.i.). We observed that penetration of the epidermis by B. cinerea coincided with increased expression of genes encoding cell-wall-degrading enzymes, phytotoxins and proteases. Grapevine responded with a rapid defence reaction involving 1193 genes associated with the accumulation of antimicrobial proteins, polyphenols, reactive oxygen species and cell wall reinforcement. At 96 h.p.i., the reaction appears largely diminished both in the host and in the pathogen. Our data indicate that the defence responses of the grapevine flower collectively are able to restrict invasive fungal growth into the underlying tissues, thereby forcing the fungus to enter quiescence until the conditions become more favourable to resume pathogenic development. © 2017 John Wiley & Sons Ltd.

  2. Pollen donor composition during the early phases of reproduction revealed by DNA genotyping of pollen grains and seeds of Castanea crenata.

    Science.gov (United States)

    Hasegawa, Yoichi; Suyama, Yoshihisa; Seiwa, Kenji

    2009-06-01

    In plants, pollen donor composition can differ during the early phases of reproduction through various selection mechanisms favouring self, related or nonrelated pollen donors, but such differences have not been examined under natural conditions because paternity is difficult to analyse in a natural setting. Here, we performed paternity analyses based on microsatellite genotyping of individual pollen grains deposited on female flowers (n = 773) and seeds (n = 304) to evaluate pollen donor composition from three individuals of the insect-pollinated monoecious tree Castanea crenata in a natural forest. Spatial genetic structure was also investigated. A mean self-pollen rate of 90.2% was observed at the pollination stage, but a low selfing rate of 0.3% was observed at the seed stage. In outcross events, however, pairwise distance and relatedness between maternal and paternal parents were not different between pollination and seed stages. We also observed significant positive relatedness, based on clear fine-scale genetic structure of individual trees within 80 m of one another, and 71% of seeds were derived using pollen grains of related trees within 80 m. The results suggest that the mechanism of self-incompatibility strongly avoids self-pollen before seed production. However, the avoidance of biparental inbreeding was not obvious between pollination and seed stages.

  3. Detection of histone acetylation levels in the dorsal hippocampus reveals early tagging on specific residues of H2B and H4 histones in response to learning.

    Directory of Open Access Journals (Sweden)

    Olivier Bousiges

    Full Text Available The recent literature provides evidence that epigenetic mechanisms such as DNA methylation and histone modification are crucial to gene transcription linked to synaptic plasticity in the mammalian brain--notably in the hippocampus--and memory formation. We measured global histone acetylation levels in the rat hippocampus at an early stage of spatial or fear memory formation. We found that H3, H4 and H2B underwent differential acetylation at specific sites depending on whether rats had been exposed to the context of a task without having to learn or had to learn about a place or fear therein: H3K9K14 acetylation was mostly responsive to any experimental conditions compared to naive animals, whereas H2B N-terminus and H4K12 acetylations were mostly associated with memory for either spatial or fear learning. Altogether, these data suggest that behavior/experience-dependent changes differently regulate specific acetylation modifications of histones in the hippocampus, depending on whether a memory trace is established or not: tagging of H3K9K14 could be associated with perception/processing of testing-related manipulations and context, thereby enhancing chromatin accessibility, while tagging of H2B N-terminus tail and H4K12 could be more closely associated with the formation of memories requiring an engagement of the hippocampus.

  4. Fetal and early post-natal mineralization of the tympanic bulla in fin whales may reveal a Hitherto undiscovered evolutionary trait.

    Directory of Open Access Journals (Sweden)

    Bruno Cozzi

    Full Text Available The evolution of the cetacean skeleton followed a path that differentiated this group from other terrestrial mammals about 50 million years ago [1], and debate is still going on about the relationships between Cetacea and Artiodactyla [2], [3], [4]. Some skeletal traits of the basilosaurids (the more advanced forms of Archaeocetes, such as the expansion of the peribullary air sinuses, dental modification and vertebral size uniformity [5] are maintained and further emphasized also in contemporary odontocetes and mysticetes. Using Dual-Energy X-Ray Absorptiometry here we report that the deposition of bone mineral in fetal and newborn specimens of the fin whale Balaenoptera physalus is remarkably higher in the bulla tympanica than in the adjacent basal skull or in the rest of the skeleton. Ossification of the tympanic bulla in fetal Artiodactyla (bovine, hippopotamus is minimal, becomes sensible after birth and then progresses during growth, contrarily to the precocious mineralization that we observed in fin whales. Given the importance of the ear bones for the precise identification of phylogenetic relationship in therian evolution [6], this feature may indicate a specific evolutionary trait of fin whales and possibly other cetacean species or families. Early mineralization of the tympanic bulla allows immediate sound conduction in the aquatic medium and consequently holds potential importance for mother-calf relationship and postnatal survival.

  5. Integrative testis transcriptome analysis reveals differentially expressed miRNAs and their mRNA targets during early puberty in Atlantic salmon.

    Science.gov (United States)

    Skaftnesmo, K O; Edvardsen, R B; Furmanek, T; Crespo, D; Andersson, E; Kleppe, L; Taranger, G L; Bogerd, J; Schulz, R W; Wargelius, A

    2017-10-18

    Our understanding of the molecular mechanisms implementing pubertal maturation of the testis in vertebrates is incomplete. This topic is relevant in Atlantic salmon aquaculture, since precocious male puberty negatively impacts animal welfare and growth. We hypothesize that certain miRNAs modulate mRNAs relevant for the initiation of puberty. To explore which miRNAs regulate mRNAs during initiation of puberty in salmon, we performed an integrated transcriptome analysis (miRNA and mRNA-seq) of salmon testis at three stages of development: an immature, long-term quiescent stage, a prepubertal stage just before, and a pubertal stage just after the onset of single cell proliferation activity in the testis. Differentially expressed miRNAs clustered into 5 distinct expression profiles related to the immature, prepubertal and pubertal salmon testis. Potential mRNA targets of these miRNAs were predicted with miRmap and filtered for mRNAs displaying negatively correlated expression patterns. In summary, this analysis revealed miRNAs previously known to be regulated in immature vertebrate testis (miR-101, miR-137, miR-92b, miR-18a, miR-20a), but also miRNAs first reported here as regulated in the testis (miR-new289, miR-30c, miR-724, miR-26b, miR-new271, miR-217, miR-216a, miR-135a, miR-new194 and the novel predicted n268). By KEGG enrichment analysis, progesterone signaling and cell cycle pathway genes were found regulated by these differentially expressed miRNAs. During the transition into puberty we found differential expression of miRNAs previously associated (let7a/b/c), or newly associated (miR-15c, miR-2184, miR-145 and the novel predicted n7a and b) with this stage. KEGG enrichment analysis revealed that mRNAs of the Wnt, Hedgehog and Apelin signaling pathways were potential regulated targets during the transition into puberty. Likewise, several regulated miRNAs in the pubertal stage had earlier been associated (miR-20a, miR-25, miR-181a, miR-202, let7c/d/a, miR-125b

  6. Gene expression profiling in a mouse model of infantile neuronal ceroid lipofuscinosis reveals upregulation of immediate early genes and mediators of the inflammatory response

    Directory of Open Access Journals (Sweden)

    Hofmann Sandra L

    2007-11-01

    Full Text Available Abstract Background The infantile form of neuronal ceroid lipofuscinosis (also known as infantile Batten disease is caused by hereditary deficiency of a lysosomal enzyme, palmitoyl-protein thioesterase-1 (PPT1, and is characterized by severe cortical degeneration with blindness and cognitive and motor dysfunction. The PPT1-deficient knockout mouse recapitulates the key features of the disorder, including seizures and death by 7–9 months of age. In the current study, we compared gene expression profiles of whole brain from PPT1 knockout and normal mice at 3, 5 and 8 months of age to identify temporal changes in molecular pathways implicated in disease pathogenesis. Results A total of 267 genes were significantly (approximately 2-fold up- or downregulated over the course of the disease. Immediate early genes (Arc, Cyr61, c-fos, jun-b, btg2, NR4A1 were among the first genes upregulated during the presymptomatic period whereas immune response genes dominated at later time points. Chemokine ligands and protease inhibitors were among the most transcriptionally responsive genes. Neuronal survival factors (IGF-1 and CNTF and a negative regulator of neuronal apoptosis (DAP kinase-1 were upregulated late in the course of the disease. Few genes were downregulated; these included the α2 subunit of the GABA-A receptor, a component of cortical and hippocampal neurons, and Hes5, a transcription factor important in neuronal differentiation. Conclusion A molecular description of gene expression changes occurring in the brain throughout the course of neuronal ceroid lipofuscinosis suggests distinct phases of disease progression, provides clues to potential markers of disease activity, and points to new targets for therapy.

  7. Challenge of Pigs with Classical Swine Fever Viruses after C-Strain Vaccination Reveals Remarkably Rapid Protection and Insights into Early Immunity

    Science.gov (United States)

    Haines, Felicity J.; Johns, Helen L.; Sosan, Olubukola A.; Salguero, Francisco J.; Clifford, Derek J.; Steinbach, Falko; Drew, Trevor W.; Crooke, Helen R.

    2012-01-01

    Pre-emptive culling is becoming increasingly questioned as a means of controlling animal diseases, including classical swine fever (CSF). This has prompted discussions on the use of emergency vaccination to control future CSF outbreaks in domestic pigs. Despite a long history of safe use in endemic areas, there is a paucity of data on aspects important to emergency strategies, such as how rapidly CSFV vaccines would protect against transmission, and if this protection is equivalent for all viral genotypes, including highly divergent genotype 3 strains. To evaluate these questions, pigs were vaccinated with the Riemser® C-strain vaccine at 1, 3 and 5 days prior to challenge with genotype 2.1 and 3.3 challenge strains. The vaccine provided equivalent protection against clinical disease caused by for the two challenge strains and, as expected, protection was complete at 5 days post-vaccination. Substantial protection was achieved after 3 days, which was sufficient to prevent transmission of the 3.3 strain to animals in direct contact. Even by one day post-vaccination approximately half the animals were partially protected, and were able to control the infection, indicating that a reduction of the infectious potential is achieved very rapidly after vaccination. There was a close temporal correlation between T cell IFN-γ responses and protection. Interestingly, compared to responses of animals challenged 5 days after vaccination, challenge of animals 3 or 1 days post-vaccination resulted in impaired vaccine-induced T cell responses. This, together with the failure to detect a T cell IFN-γ response in unprotected and unvaccinated animals, indicates that virulent CSFV can inhibit the potent antiviral host defences primed by C-strain in the early period post vaccination. PMID:22235283

  8. MRI and biomechanics multidimensional data analysis reveals R2 -R1ρ as an early predictor of cartilage lesion progression in knee osteoarthritis.

    Science.gov (United States)

    Pedoia, Valentina; Haefeli, Jenny; Morioka, Kazuhito; Teng, Hsiang-Ling; Nardo, Lorenzo; Souza, Richard B; Ferguson, Adam R; Majumdar, Sharmila

    2017-05-04

    To couple quantitative compositional MRI, gait analysis, and machine learning multidimensional data analysis to study osteoarthritis (OA). OA is a multifactorial disorder accompanied by biochemical and morphological changes in the articular cartilage, modulated by skeletal biomechanics and gait. While we can now acquire detailed information about the knee joint structure and function, we are not yet able to leverage the multifactorial factors for diagnosis and disease management of knee OA. We mapped 178 subjects in a multidimensional space integrating: demographic, clinical information, gait kinematics and kinetics, cartilage compositional T1ρ and T2 and R2 -R1ρ (1/T2 -1/T1ρ ) acquired at 3T and whole-organ magnetic resonance imaging score morphological grading. Topological data analysis (TDA) and Kolmogorov-Smirnov test were adopted for data integration, analysis, and hypothesis generation. Regression models were used for hypothesis testing. The results of the TDA showed a network composed of three main patient subpopulations, thus potentially identifying new phenotypes. T2 and T1ρ values (T2 lateral femur P = 1.45*10-8 , T1ρ medial tibia P = 1.05*10-5 ), the presence of femoral cartilage defects (P = 0.0013), lesions in the meniscus body (P = 0.0035), and race (P = 2.44*10-4 ) were key markers in the subpopulation classification. Within one of the subpopulations we observed an association between the composite metric R2 -R1ρ and the longitudinal progression of cartilage lesions. The analysis presented demonstrates some of the complex multitissue biochemical and biomechanical interactions that define joint degeneration and OA using a multidimensional approach, and potentially indicates that R2 -R1ρ may be an imaging biomarker for early OA. 3 J. Magn. Reson. Imaging 2017. © 2017 International Society for Magnetic Resonance in Medicine.

  9. Tracking post-hibernation behavior and early migration does not reveal the expected sex-differences in a "female-migrating" bat.

    Directory of Open Access Journals (Sweden)

    Dina K N Dechmann

    Full Text Available Long-distance migration is a rare phenomenon in European bats. Genetic analyses and banding studies show that females can cover distances of up to 1,600 km, whereas males are sedentary or migrate only short distances. The onset of this sex-biased migration is supposed to occur shortly after rousing from hibernation and when the females are already pregnant. We therefore predicted that the sexes are exposed to different energetic pressures in early spring, and this should be reflected in their behavior and physiology. We investigated this in one of the three Central European long-distance migrants, the common noctule (Nyctalus noctula in Southern Germany recording the first individual partial migration tracks of this species. In contrast to our predictions, we found no difference between male and female home range size, activity, habitat use or diet. Males and females emerged from hibernation in similar body condition and mass increase rate was the same in males and females. We followed the first migration steps, up to 475 km, of radio-tagged individuals from an airplane. All females, as well as some of the males, migrated away from the wintering area in the same northeasterly direction. Sex differences in long-distance migratory behavior were confirmed through stable isotope analysis of hair, which showed greater variation in females than in males. We hypothesize that both sexes faced similarly good conditions after hibernation and fattened at maximum rates, thus showing no differences in their local behavior. Interesting results that warrant further investigation are the better initial condition of the females and the highly consistent direction of the first migratory step in this population as summering habitats of the common noctule occur at a broad range in Northern Europe. Only research focused on individual strategies will allow us to fully understand the migratory behavior of European bats.

  10. Comparative genomics of oral isolates of Streptococcus mutans by in silico genome subtraction does not reveal accessory DNA associated with severe early childhood caries.

    Science.gov (United States)

    Argimón, Silvia; Konganti, Kranti; Chen, Hao; Alekseyenko, Alexander V; Brown, Stuart; Caufield, Page W

    2014-01-01

    Comparative genomics is a popular method for the identification of microbial virulence determinants, especially since the sequencing of a large number of whole bacterial genomes from pathogenic and non-pathogenic strains has become relatively inexpensive. The bioinformatics pipelines for comparative genomics usually include gene prediction and annotation and can require significant computer power. To circumvent this, we developed a rapid method for genome-scale in silico subtractive hybridization, based on blastn and independent of feature identification and annotation. Whole genome comparisons by in silico genome subtraction were performed to identify genetic loci specific to Streptococcus mutans strains associated with severe early childhood caries (S-ECC), compared to strains isolated from caries-free (CF) children. The genome similarity of the 20 S. mutans strains included in this study, calculated by Simrank k-mer sharing, ranged from 79.5% to 90.9%, confirming this is a genetically heterogeneous group of strains. We identified strain-specific genetic elements in 19 strains, with sizes ranging from 200 to 39 kb. These elements contained protein-coding regions with functions mostly associated with mobile DNA. We did not, however, identify any genetic loci consistently associated with dental caries, i.e., shared by all the S-ECC strains and absent in the CF strains. Conversely, we did not identify any genetic loci specific with the healthy group. Comparison of previously published genomes from pathogenic and carriage strains of Neisseria meningitidis with our in silico genome subtraction yielded the same set of genes specific to the pathogenic strains, thus validating our method. Our results suggest that S. mutans strains derived from caries active or caries free dentitions cannot be differentiated based on the presence or absence of specific genetic elements. Our in silico genome subtraction method is available as the Microbial Genome Comparison (MGC) tool

  11. Redshift-space limits of bound structures

    NARCIS (Netherlands)

    Duenner, Rolando; Reisenegger, Andreas; Meza, Andres; Araya, Pablo A.; Quintana, Hernan

    2007-01-01

    An exponentially expanding Universe, possibly governed by a cosmological constant, forces gravitationally bound structures to become more and more isolated, eventually becoming causally disconnected from each other and forming so-called 'island universes'. This new scenario reformulates the question

  12. A comparison of error bounds for a nonlinear tracking system with detection probability Pd < 1.

    Science.gov (United States)

    Tong, Huisi; Zhang, Hao; Meng, Huadong; Wang, Xiqin

    2012-12-14

    Error bounds for nonlinear filtering are very important for performance evaluation and sensor management. This paper presents a comparative study of three error bounds for tracking filtering, when the detection probability is less than unity. One of these bounds is the random finite set (RFS) bound, which is deduced within the framework of finite set statistics. The others, which are the information reduction factor (IRF) posterior Cramer-Rao lower bound (PCRLB) and enumeration method (ENUM) PCRLB are introduced within the framework of finite vector statistics. In this paper, we deduce two propositions and prove that the RFS bound is equal to the ENUM PCRLB, while it is tighter than the IRF PCRLB, when the target exists from the beginning to the end. Considering the disappearance of existing targets and the appearance of new targets, the RFS bound is tighter than both IRF PCRLB and ENUM PCRLB with time, by introducing the uncertainty of target existence. The theory is illustrated by two nonlinear tracking applications: ballistic object tracking and bearings-only tracking. The simulation studies confirm the theory and reveal the relationship among the three bounds.

  13. A Comparison of Error Bounds for a Nonlinear Tracking System with Detection Probability Pd < 1

    Directory of Open Access Journals (Sweden)

    Xiqin Wang

    2012-12-01

    Full Text Available Error bounds for nonlinear filtering are very important for performance evaluation and sensor management. This paper presents a comparative study of three error bounds for tracking filtering, when the detection probability is less than unity. One of these bounds is the random finite set (RFS bound, which is deduced within the framework of finite set statistics. The others, which are the information reduction factor (IRF posterior Cramer-Rao lower bound (PCRLB and enumeration method (ENUM PCRLB are introduced within the framework of finite vector statistics. In this paper, we deduce two propositions and prove that the RFS bound is equal to the ENUM PCRLB, while it is tighter than the IRF PCRLB, when the target exists from the beginning to the end. Considering the disappearance of existing targets and the appearance of new targets, the RFS bound is tighter than both IRF PCRLB and ENUM PCRLB with time, by introducing the uncertainty of target existence. The theory is illustrated by two nonlinear tracking applications: ballistic object tracking and bearings-only tracking. The simulation studies confirm the theory and reveal the relationship among the three bounds.

  14. A Comparison of Error Bounds for a Nonlinear Tracking System with Detection Probability Pd < 1

    Science.gov (United States)

    Tong, Huisi; Zhang, Hao; Meng, Huadong; Wang, Xiqin

    2012-01-01

    Error bounds for nonlinear filtering are very important for performance evaluation and sensor management. This paper presents a comparative study of three error bounds for tracking filtering, when the detection probability is less than unity. One of these bounds is the random finite set (RFS) bound, which is deduced within the framework of finite set statistics. The others, which are the information reduction factor (IRF) posterior Cramer-Rao lower bound (PCRLB) and enumeration method (ENUM) PCRLB are introduced within the framework of finite vector statistics. In this paper, we deduce two propositions and prove that the RFS bound is equal to the ENUM PCRLB, while it is tighter than the IRF PCRLB, when the target exists from the beginning to the end. Considering the disappearance of existing targets and the appearance of new targets, the RFS bound is tighter than both IRF PCRLB and ENUM PCRLB with time, by introducing the uncertainty of target existence. The theory is illustrated by two nonlinear tracking applications: ballistic object tracking and bearings-only tracking. The simulation studies confirm the theory and reveal the relationship among the three bounds. PMID:23242274

  15. Fossil worm burrows reveal very early terrestrial animal activity and shed light on trophic resources after the end-cretaceous mass extinction.

    Science.gov (United States)

    Chin, Karen; Pearson, Dean; Ekdale, A A

    2013-01-01

    The widespread mass extinctions at the end of the Cretaceous caused world-wide disruption of ecosystems, and faunal responses to the one-two punch of severe environmental perturbation and ecosystem collapse are still unclear. Here we report the discovery of in situ terrestrial fossil burrows from just above the impact-defined Cretaceous-Paleogene (K/Pg) boundary in southwestern North Dakota. The crisscrossing networks of horizontal burrows occur at the interface of a lignitic coal and silty sandstone, and reveal intense faunal activity within centimeters of the boundary clay. Estimated rates of sedimentation and coal formation suggest that the burrows were made less than ten thousand years after the end-Cretaceous impact. The burrow characteristics are most consistent with burrows of extant earthworms. Moreover, the burrowing and detritivorous habits of these annelids fit models that predict the trophic and sheltering lifestyles of terrestrial animals that survived the K/Pg extinction event. In turn, such detritus-eaters would have played a critical role in supporting secondary consumers. Thus, some of the carnivorous vertebrates that radiated after the K/Pg extinction may owe their evolutionary success to thriving populations of earthworms.

  16. 'Get in Early'; Biofilm and Wax Moth (Galleria mellonella) Models Reveal New Insights into the Therapeutic Potential of Clostridium difficile Bacteriophages.

    Science.gov (United States)

    Nale, Janet Y; Chutia, Mahananda; Carr, Philippa; Hickenbotham, Peter T; Clokie, Martha R J

    2016-01-01

    Clostridium difficile infection (CDI) is a global health threat associated with high rates of morbidity and mortality. Conventional antibiotic CDI therapy can result in treatment failure and recurrent infection. C. difficile produces biofilms which contribute to its virulence and impair antimicrobial activity. Some bacteriophages (phages) can penetrate biofilms and thus could be developed to either replace or supplement antibiotics. Here, we determined the impact of a previously optimized 4-phage cocktail on C. difficile ribotype 014/020 biofilms, and additionally as adjunct to vancomycin treatment in Galleria mellonella larva CDI model. The phages were applied before or after biofilm establishment in vitro, and the impact was analyzed according to turbidity, viability counts and topography as observed using scanning electron and confocal microscopy. The infectivity profiles and efficacies of orally administered phages and/or vancomycin were ascertained by monitoring colonization levels and larval survival rates. Phages prevented biofilm formation, and penetrated established biofilms. A single phage application reduced colonization causing extended longevity in the remedial treatment and prevented disease in the prophylaxis group. Multiple phage doses significantly improved the larval remedial regimen, and this treatment is comparable to vancomycin and the combined treatments. Taken together, our data suggest that the phages significantly reduce C. difficile biofilms, and prevent colonization in the G. mellonella model when used alone or in combination with vancomycin. The phages appear to be highly promising therapeutics in the targeted eradication of CDI and the use of these models has revealed that prophylactic use could be a propitious therapeutic option.

  17. Fossil worm burrows reveal very early terrestrial animal activity and shed light on trophic resources after the end-cretaceous mass extinction.

    Directory of Open Access Journals (Sweden)

    Karen Chin

    Full Text Available The widespread mass extinctions at the end of the Cretaceous caused world-wide disruption of ecosystems, and faunal responses to the one-two punch of severe environmental perturbation and ecosystem collapse are still unclear. Here we report the discovery of in situ terrestrial fossil burrows from just above the impact-defined Cretaceous-Paleogene (K/Pg boundary in southwestern North Dakota. The crisscrossing networks of horizontal burrows occur at the interface of a lignitic coal and silty sandstone, and reveal intense faunal activity within centimeters of the boundary clay. Estimated rates of sedimentation and coal formation suggest that the burrows were made less than ten thousand years after the end-Cretaceous impact. The burrow characteristics are most consistent with burrows of extant earthworms. Moreover, the burrowing and detritivorous habits of these annelids fit models that predict the trophic and sheltering lifestyles of terrestrial animals that survived the K/Pg extinction event. In turn, such detritus-eaters would have played a critical role in supporting secondary consumers. Thus, some of the carnivorous vertebrates that radiated after the K/Pg extinction may owe their evolutionary success to thriving populations of earthworms.

  18. Transcriptome analysis of the couch potato (CPO) protein reveals an expression pattern associated with early development in the salmon louse Caligus rogercresseyi.

    Science.gov (United States)

    Gallardo-Escárate, Cristian; Valenzuela-Muñoz, Valentina; Nuñez-Acuña, Gustavo; Chávez-Mardones, Jacqueline; Maldonado-Aguayo, Waleska

    2014-02-15

    The couch potato (CPO) protein is a key biomolecule involved in regulating diapause through the RNA-binding process of the peripheral and central nervous systems in insects and also recently discovered in a few crustacean species. As such, ectoparasitic copepods are interesting model species that have no evidence of developmental arrest. The present study is the first to report on the cloning of a putative CPO gene from the salmon louse Caligus rogercresseyi (CrCPO), as identified by high-throughput transcriptome sequencing. In addition, the transcription expression in larvae and adults was evaluated using quantitative real-time PCR. The CrCPO cDNA sequence showed 3261 base pairs (bp), consisting of 713bp of 5' UTR, 1741bp of 3' UTR, and an open reading frame of 807bp encoding for 268 amino acids. The highly conserved RNA binding regions RNP2 (LFVSGL) and RNP1 (SPVGFVTF), as well the dimerization site (LEF), were also found. Furthermore, eight single nucleotide polymorphisms located in the untranslated regions and one located in the coding region were detected. Gene transcription analysis revealed that CrCPO has ubiquitous expression across larval stages and in adult individuals, with the highest expression from nauplius to copepodid stages. The present study suggests a putative biological function of CrCPO associated with the development of the nervous system in salmon lice and contributes molecular evidence for candidate genes related to host-parasite interactions. Copyright © 2013 Elsevier B.V. All rights reserved.

  19. New Spectral Features from Bound Dark Matter

    DEFF Research Database (Denmark)

    Catena, Riccardo; Kouvaris, Chris

    2016-01-01

    We demonstrate that dark matter particles gravitationally bound to the Earth can induce a characteristic nuclear recoil signal at low energies in direct detection experiments. The new spectral feature we predict can provide the ultimate smoking gun for dark matter discovery for experiments...... with positive signal but unclear background. The new feature is universal, in that the ratio of bound over halo dark matter event rates at detectors is independent of the dark matter-nucleon cross section....

  20. On bounds for symmetric divergence measures

    Science.gov (United States)

    Furuichi, S.; Yanagi, K.; Kuriyama, K.

    2017-06-01

    In the paper [1], tight bounds for symmetric divergence measures applying the results established by G.L.Gilardoni. In this article, we report on two kinds of extensions for the Sason's results, namely a classical q-extension and a non-commutative(quantum) extension. Especially, we improve Sason's bound of the summation of the absolute value for the difference between two probability distributions, applying the parameter q of Tsallis entropy, under a certain assumption.

  1. Stable Bound States of Asymmetric Dark Matter

    OpenAIRE

    Wise, Mark B.; Zhang, Yue

    2014-01-01

    The simplest renormalizable effective field theories with asymmetric dark matter bound states contain two additional gauge singlet fields one being the dark matter and the other a mediator particle that the dark matter annihilates into. We examine the physics of one such model with a Dirac fermion as the dark matter and a real scalar mediator. For a range of parameters the Yukawa coupling of the dark matter to the mediator gives rise to stable asymmetric dark matter bound states. We derive pr...

  2. Malabsorption of protein bound vitamin B12.

    OpenAIRE

    Dawson, D W; Sawers, A H; Sharma, R K

    1984-01-01

    Patients with subnormal serum vitamin B12 concentrations were tested for absorption of protein bound vitamin B12 and compared with controls. Absorption of the protein bound vitamin appeared to decrease with increasing age in healthy subjects. Differences between the result of this test and the result of the Schilling test in patients who had undergone gastric surgery were confirmed; such differences were also seen in some patients who had iron deficiency anaemia, an excessive alcohol intake, ...

  3. Dynamic optimization problems with bounded terminal conditions

    Science.gov (United States)

    Lee, A. Y.

    1987-01-01

    Bounded terminal conditions of nonlinear optimization problems are converted to equality terminal conditions via Valentine's device. In so doing, additional unknown parameters are introduced into the problem. The transformed problems can still be easily solved using the sequential gradient-restoration algorithm (SGRA) via a simple augmentation of the unknown parameter vector pi. Three example problems with bounded terminal conditions are solved to verify this technique.

  4. Next Generation Sequencing Reveals High Prevalence of BRCA1 and BRCA2 Variants of Unknown Significance in Early-Onset Breast Cancer in African American Women.

    Science.gov (United States)

    Ricks-Santi, Luisel; McDonald, J Tyson; Gold, Bert; Dean, Michael; Thompson, Nicole; Abbas, Muneer; Wilson, Bradford; Kanaan, Yasmine; Naab, Tammey J; Dunston, Georgia

    2017-01-01

    Variants of unknown significance (VUSs) have been identified in BRCA1 and BRCA2 and account for the majority of all identified sequence alterations. Notably, VUSs occur disproportionately in people of African descent hampering breast cancer (BCa) management and prevention efforts in the population. Our study sought to identify and characterize mutations associated with increased risk of BCa at young age. In our study, the spectrum of mutations in BRCA1 and BRCA2 was enumerated in a cohort of 31 African American women of early age at onset breast cancer, with a family history of breast or cancer in general and/or with triple negative breast cancer. To improve the characterization of the BRCA1 and BRCA2 variants, bioinformatics tools were utilized to predict the potential function of each of the variants. Using next generation sequencing methods and in silico analysis of variants, a total of 197 BRCA1 and 266 BRCA2 variants comprising 77 unique variants were identified in 31 patients. Of the 77 unique variants, one (1.3%) was a pathogenic frameshift mutation (rs80359304; BRCA2 Met591Ile), 13 (16.9%) were possibly pathogenic, 34 (44.2%) were benign, and 29 (37.7%) were VUSs. Genetic epidemiological approaches were used to determine the association with variant, haplotype, and phenotypes, such as age at diagnosis, family history of cancer and family history of breast cancer. There were 5 BRCA1 SNPs associated with age at diagnosis; rs1799966 (P=.045; Log Additive model), rs16942 (P=.033; Log Additive model), rs1799949 (P=.058; Log Additive model), rs373413425 (P=.040 and .023; Dominant and Log Additive models, respectively) and rs3765640 (P=.033 Log Additive model). Additionally, a haplotype composed of all 5 SNPs was found to be significantly associated with younger age at diagnosis using linear regression modeling (P=.023). Specifically, the haplotype containing all the variant alleles was associated with older age at diagnosis (OR= 5.03 95% CI=.91-9.14). Knowing a

  5. Serum lipidomics reveals early differential effects of gastric bypass compared with banding on phospholipids and sphingolipids independent of differences in weight loss.

    Science.gov (United States)

    Kayser, B D; Lhomme, M; Dao, M C; Ichou, F; Bouillot, J-L; Prifti, E; Kontush, A; Chevallier, J-M; Aron-Wisnewsky, J; Dugail, I; Clément, K

    2017-06-01

    Circulating phospholipids and sphingolipids are implicated in obesity-related comorbidities such as insulin resistance and cardiovascular disease. How bariatric surgery affects these important lipid markers is poorly understood. We sought to determine whether Roux-en-Y gastric bypass (RYGB), which is associated with greater metabolic improvement, differentially affects the phosphosphingolipidome compared with adjustable gastric banding (AGB). Fasting sera were available from 59 obese women (body mass index range 37-51 kg m-2; n=37 RYGB and 22 AGB) before surgery, then at 1 (21 RYGB, 12 AGB) and 3 months follow-up (19 RYGB, 12 AGB). HPLC-MS/MS was used to quantify 131 lipids from nine structural classes. DXA measurements and laboratory parameters were also obtained. The associations between lipids and clinical measurements were studied with P-values adjusted for the false discovery rate (FDR). Both surgical procedures rapidly induced weight loss and improved clinical profiles, with RYGB producing better improvements in fat mass, and serum total cholesterol, low-density lipoprotein-cholesterol (LDL-C) and orosomucoid (FDR <10%). Ninety-three (of 131) lipids were altered by surgery-the majority decreasing-with 29 lipids differentially affected by RYGB during the study period. The differential effect of the surgeries remained statistically significant for 20 of these lipids after adjusting for differences in weight loss between surgery types. The RYGB signature consisted of phosphatidylcholine species not exceeding 36 carbons, and ceramides and sphingomyelins containing C22 to C25 fatty acids. RYGB also led to a sustained increase in unsaturated ceramide and sphingomyelin species. The RYGB-specific lipid changes were associated with decreases in body weight, total and LDL-C, orosomucoid and increased HOMA-S (FDR <10%). Concomitant with greater metabolic improvement, RYGB induced early and sustained changes in phosphatidylcholines, sphingomyelins and ceramides

  6. Molecular phenotyping of immune cells from young NOD mice reveals abnormal metabolic pathways in the early induction phase of autoimmune diabetes.

    Science.gov (United States)

    Wu, Jian; Kakoola, Dorothy N; Lenchik, Nataliya I; Desiderio, Dominic M; Marshall, Dana R; Gerling, Ivan C

    2012-01-01

    Islet leukocytic infiltration (insulitis) is first obvious at around 4 weeks of age in the NOD mouse--a model for human type 1 diabetes (T1D). The molecular events that lead to insulitis and initiate autoimmune diabetes are poorly understood. Since TID is caused by numerous genes, we hypothesized that multiple molecular pathways are altered and interact to initiate this disease. We evaluated the molecular phenotype (mRNA and protein expression) and molecular networks of ex vivo unfractionated spleen leukocytes from 2 and 4 week-old NOD mice in comparison to two control strains. Analysis of the global gene expression profiles and hierarchical clustering revealed that the majority (~90%) of the differentially expressed genes in NOD mice were repressed. Furthermore, analysis using a modern suite of multiple bioinformatics approaches identified abnormal molecular pathways that can be divided broadly into 2 categories: metabolic pathways, which were predominant at 2 weeks, and immune response pathways, which were predominant at 4 weeks. Network analysis by Ingenuity pathway analysis identified key genes/molecules that may play a role in regulating these pathways. These included five that were common to both ages (TNF, HNF4A, IL15, Progesterone, and YWHAZ), and others that were unique to 2 weeks (e.g. MYC/MYCN, TGFB1, and IL2) and to 4 weeks (e.g. IFNG, beta-estradiol, p53, NFKB, AKT, PRKCA, IL12, and HLA-C). Based on the literature, genes that may play a role in regulating metabolic pathways at 2 weeks include Myc and HNF4A, and at 4 weeks, beta-estradiol, p53, Akt, HNF4A and AR. Our data suggest that abnormalities in regulation of metabolic pathways in the immune cells of young NOD mice lead to abnormalities in the immune response pathways and as such may play a role in the initiation of autoimmune diabetes. Thus, targeting metabolism may provide novel approaches to preventing and/or treating autoimmune diabetes.

  7. A Systems Level Analysis Reveals Transcriptomic and Proteomic Complexity in Ixodes Ricinus Midgut and Salivary Glands During Early Attachment and Feeding*

    Science.gov (United States)

    Schwarz, Alexandra; Tenzer, Stefan; Hackenberg, Michael; Erhart, Jan; Gerhold-Ay, Aslihan; Mazur, Johanna; Kuharev, Jörg; Ribeiro, José M. C.; Kotsyfakis, Michail

    2014-01-01

    Although pathogens are usually transmitted within the first 24–48 h of attachment of the castor bean tick Ixodes ricinus, little is known about the tick's biological responses at these earliest phases of attachment. Tick midgut and salivary glands are the main tissues involved in tick blood feeding and pathogen transmission but the limited genomic information for I. ricinus delays the application of high-throughput methods to study their physiology. We took advantage of the latest advances in the fields of Next Generation RNA-Sequencing and Label-free Quantitative Proteomics to deliver an unprecedented, quantitative description of the gene expression dynamics in the midgut and salivary glands of this disease vector upon attachment to the vertebrate host. A total of 373 of 1510 identified proteins had higher expression in the salivary glands, but only 110 had correspondingly high transcript levels in the same tissue. Furthermore, there was midgut-specific expression of 217 genes at both the transcriptome and proteome level. Tissue-dependent transcript, but not protein, accumulation was revealed for 552 of 885 genes. Moreover, we discovered the enrichment of tick salivary glands in proteins involved in gene transcription and translation, which agrees with the secretory role of this tissue; this finding also agrees with our finding of lower tick t-RNA representation in the salivary glands when compared with the midgut. The midgut, in turn, is enriched in metabolic components and proteins that support its mechanical integrity in order to accommodate and metabolize the ingested blood. Beyond understanding the physiological events that support hematophagy by arthropod ectoparasites, we discovered more than 1500 proteins located at the interface between ticks, the vertebrate host, and the tick-borne pathogens. Thus, our work significantly improves the knowledge of the genetics underlying the transmission lifecycle of this tick species, which is an essential step for

  8. Tight bounds on computing error-correcting codes by bounded-depth circuits with arbitrary gates

    DEFF Research Database (Denmark)

    Gal, A.; Hansen, Kristoffer Arnsfelt; Koucky, Michal

    2013-01-01

    We bound the minimum number w of wires needed to compute any (asymptotically good) error-correcting code C:{0,1}Ω(n)→{0,1}n with minimum distance Ω(n), using unbounded fan-in circuits of depth d with arbitrary gates. Our main results are: 1) if d=2, then w=Θ(n (lgn/lglgn)2); 2) if d=3, then w...... bound gives the largest known lower bound for computing any linear map. The upper bounds imply that a (necessarily dense) generator matrix for our code can be written as the product of two sparse matrices. Using known techniques, we also obtain similar (but not tight) bounds for computing pairwise......-independent hash functions. Our lower bounds are based on a superconcentrator-like condition that the graphs of circuits computing good codes must satisfy. This condition is provably intermediate between superconcentrators and their weakenings considered before...

  9. Dynamics of quadratic polynomials: Complex bounds for real maps

    OpenAIRE

    Lyubich, Mikhail; Yampolsky, Michael

    1995-01-01

    We extend Sullivan's complex a priori bounds to real quadratic polynomials with essentially bounded combinatorics. Combined with the previous results of the first author, this yields complex bounds for all real quadratics. Local connectivity of the corresponding Julia sets follows.

  10. Bounds Estimation Via Regression with Asymmetric Cost Functions

    Science.gov (United States)

    DeCoste, D.

    1997-01-01

    This paper addresses a significant but mostly-neglected class of problems that we call bounds estimation. This includes learning empirical best-case and worst-case algorithmic complexity bounds and red-line bounds on sensor data.

  11. From 'I' to 'L' and back again: the odyssey of membrane-bound M13 protein.

    Science.gov (United States)

    Vos, Werner L; Nazarov, Petr V; Koehorst, Rob B M; Spruijt, Ruud B; Hemminga, Marcus A

    2009-05-01

    The major coat protein of the filamentous bacteriophage M13 is a surprising protein because it exists both as a membrane protein and as part of the M13 phage coat during its life cycle. Early studies showed that the phage-bound structure of the coat protein was a continuous I-shaped alpha-helix. However, throughout the years various structural models, both I-shaped and L-shaped, have been proposed for the membrane-bound state of the coat protein. Recently, site-directed labelling approaches have enabled the study of the coat protein under conditions that more closely mimic the in vivo membrane-bound state. Interestingly, the structure that has emerged from this work is I-shaped and similar to the structure in the phage-bound state.

  12. Universal bounds in even-spin CFTs

    Energy Technology Data Exchange (ETDEWEB)

    Qualls, Joshua D. [Department of Physics, National Taiwan University,Taipei, Taiwan (China)

    2015-12-01

    We prove using invariance under the modular S− and ST−transformations that every unitary two-dimensional conformal field theory (CFT) having only even-spin primary operators (with no extended chiral algebra and with right- and left-central charges c,c̃>1) contains a primary operator with dimension Δ{sub 1} satisfying 0<Δ{sub 1}<((c+c̃)/24)+0.09280…. After deriving both analytical and numerical bounds, we discuss how to extend our methods to bound higher conformal dimensions before deriving lower and upper bounds on the number of primary operators in a given energy range. Using the AdS{sub 3}/CFT{sub 2} dictionary, the bound on Δ{sub 1} proves the lightest massive excitation in appropriate theories of 3D matter and gravity with cosmological constant Λ<0 can be no heavier than 1/8G{sub N}+O(√(−Λ)); the bounds on the number of operators are related via AdS/CFT to the entropy of states in the dual gravitational theory. In the flat-space approximation, the limiting mass is exactly that of the lightest BTZ black hole.

  13. Multipole-bound molecular negative ions

    CERN Document Server

    Abdul-Karim, H; Desfrançois, C

    2002-01-01

    Within the framework of a simple electrostatic model, as compared to recent experimental results, we here discuss the stability of very weakly bound molecular negative ions. In contrast with the case of conventional valence anions, the excess electron is then located in a very diffuse orbital and is mainly bound by electrostatic dipolar, quadrupolar, and polarization forces, at large distances from the neutral molecular core. By fitting a single repulsion parameter of the model to the available experimental data, it is possible to make quantitative predictions of the excess-electron binding energies in these species. Critical values of the dipole moment, quadrupole moment or polarizability required for the observation of stable multipole-bound negative ions are predicted and compared to available experimental data and ab initio calculations. Refs. 26 (author)

  14. Resistivity bound for hydrodynamic bad metals

    Science.gov (United States)

    Lucas, Andrew; Hartnoll, Sean A.

    2017-10-01

    We obtain a rigorous upper bound on the resistivity ρ of an electron fluid whose electronic mean free path is short compared with the scale of spatial inhomogeneities. When such a hydrodynamic electron fluid supports a nonthermal diffusion process—such as an imbalance mode between different bands—we show that the resistivity bound becomes ρ≲AΓ. The coefficient A is independent of temperature and inhomogeneity lengthscale, and Γ is a microscopic momentum-preserving scattering rate. In this way, we obtain a unified mechanism—without umklapp—for ρ˜T2 in a Fermi liquid and the crossover to ρ˜T in quantum critical regimes. This behavior is widely observed in transition metal oxides, organic metals, pnictides, and heavy fermion compounds and has presented a long-standing challenge to transport theory. Our hydrodynamic bound allows phonon contributions to diffusion constants, including thermal diffusion, to directly affect the electrical resistivity.

  15. Properties of Water Bound in Hydrogels

    Directory of Open Access Journals (Sweden)

    Vladimir M. Gun’ko

    2017-10-01

    Full Text Available In this review, the importance of water in hydrogel (HG properties and structure is analyzed. A variety of methods such as 1H NMR (nuclear magnetic resonance, DSC (differential scanning calorimetry, XRD (X-ray powder diffraction, dielectric relaxation spectroscopy, thermally stimulated depolarization current, quasi-elastic neutron scattering, rheometry, diffusion, adsorption, infrared spectroscopy are used to study water in HG. The state of HG water is rather non-uniform. According to thermodynamic features of water in HG, some of it is non-freezing and strongly bound, another fraction is freezing and weakly bound, and the third fraction is non-bound, free water freezing at 0 °C. According to structural features of water in HG, it can be divided into two fractions with strongly associated and weakly associated waters. The properties of the water in HG depend also on the amounts and types of solutes, pH, salinity, structural features of HG functionalities.

  16. Correlation Distance and Bounds for Mutual Information

    Directory of Open Access Journals (Sweden)

    Michael J. W. Hall

    2013-09-01

    Full Text Available The correlation distance quantifies the statistical independence of two classical or quantum systems, via the distance from their joint state to the product of the marginal states. Tight lower bounds are given for the mutual information between pairs of two-valued classical variables and quantum qubits, in terms of the corresponding classical and quantum correlation distances. These bounds are stronger than the Pinsker inequality (and refinements thereof for relative entropy. The classical lower bound may be used to quantify properties of statistical models that violate Bell inequalities. Partially entangled qubits can have lower mutual information than can any two-valued classical variables having the same correlation distance. The qubit correlation distance also provides a direct entanglement criterion, related to the spin covariance matrix. Connections of results with classically-correlated quantum states are briefly discussed.

  17. Equivalence principle and bound kinetic energy.

    Science.gov (United States)

    Hohensee, Michael A; Müller, Holger; Wiringa, R B

    2013-10-11

    We consider the role of the internal kinetic energy of bound systems of matter in tests of the Einstein equivalence principle. Using the gravitational sector of the standard model extension, we show that stringent limits on equivalence principle violations in antimatter can be indirectly obtained from tests using bound systems of normal matter. We estimate the bound kinetic energy of nucleons in a range of light atomic species using Green's function Monte Carlo calculations, and for heavier species using a Woods-Saxon model. We survey the sensitivities of existing and planned experimental tests of the equivalence principle, and report new constraints at the level of between a few parts in 10(6) and parts in 10(8) on violations of the equivalence principle for matter and antimatter.

  18. Yukawa Bound States and Their LHC Phenomenology

    Directory of Open Access Journals (Sweden)

    Enkhbat Tsedenbaljir

    2013-01-01

    Full Text Available We present the current status on the possible bound states of extra generation quarks. These include phenomenology and search strategy at the LHC. If chiral fourth-generation quarks do exist their strong Yukawa couplings, implied by current experimental lower bound on their masses, may lead to formation of bound states. Due to nearly degenerate 4G masses suggested by Precision Electroweak Test one can employ “heavy isospin” symmetry to classify possible spectrum. Among these states, the color-octet isosinglet vector ω 8 is the easiest to be produced at the LHC. The discovery potential and corresponding decay channels are covered in this paper. With possible light Higgs at ~125 GeV two-Higgs doublet version is briefly discussed.

  19. Braneworld black holes and entropy bounds

    Directory of Open Access Journals (Sweden)

    Y. Heydarzade

    2018-01-01

    Full Text Available The Bousso's D-bound entropy for the various possible black hole solutions on a 4-dimensional brane is checked. It is found that the D-bound entropy here is apparently different from that of obtained for the 4-dimensional black hole solutions. This difference is interpreted as the extra loss of information, associated to the extra dimension, when an extra-dimensional black hole is moved outward the observer's cosmological horizon. Also, it is discussed that N-bound entropy is hold for the possible solutions here. Finally, by adopting the recent Bohr-like approach to black hole quantum physics for the excited black holes, the obtained results are written also in terms of the black hole excited states.

  20. Braneworld black holes and entropy bounds

    Science.gov (United States)

    Heydarzade, Y.; Hadi, H.; Corda, C.; Darabi, F.

    2018-01-01

    The Bousso's D-bound entropy for the various possible black hole solutions on a 4-dimensional brane is checked. It is found that the D-bound entropy here is apparently different from that of obtained for the 4-dimensional black hole solutions. This difference is interpreted as the extra loss of information, associated to the extra dimension, when an extra-dimensional black hole is moved outward the observer's cosmological horizon. Also, it is discussed that N-bound entropy is hold for the possible solutions here. Finally, by adopting the recent Bohr-like approach to black hole quantum physics for the excited black holes, the obtained results are written also in terms of the black hole excited states.

  1. Entropy Bounds, Holographic Principle and Uncertainty Relation

    Directory of Open Access Journals (Sweden)

    I. V. Volovich

    2001-06-01

    Full Text Available Abstract: A simple derivation of the bound on entropy is given and the holographic principle is discussed. We estimate the number of quantum states inside space region on the base of uncertainty relation. The result is compared with the Bekenstein formula for entropy bound, which was initially derived from the generalized second law of thermodynamics for black holes. The holographic principle states that the entropy inside a region is bounded by the area of the boundary of that region. This principle can be called the kinematical holographic principle. We argue that it can be derived from the dynamical holographic principle which states that the dynamics of a system in a region should be described by a system which lives on the boundary of the region. This last principle can be valid in general relativity because the ADM hamiltonian reduces to the surface term.

  2. Career Development and Personal Functioning Differences between Work-Bound and Non-Work Bound Students

    Science.gov (United States)

    Creed, Peter A.; Patton, Wendy; Hood, Michelle

    2010-01-01

    We surveyed 506 Australian high school students on career development (exploration, planning, job-knowledge, decision-making, indecision), personal functioning (well-being, self-esteem, life satisfaction, school satisfaction) and control variables (parent education, school achievement), and tested differences among work-bound, college-bound and…

  3. 78 FR 18326 - Agency Information Collection Activities; Comment Request; Upward Bound and Upward Bound Math...

    Science.gov (United States)

    2013-03-26

    ... Agency Information Collection Activities; Comment Request; Upward Bound and Upward Bound Math Science... hand delivery. Please note that comments submitted by fax or email and those submitted after the... 1995 (PRA) (44 U.S.C. 3506(c)(2)(A)), provides the general public and Federal agencies with an...

  4. Tight bounds on computing error-correcting codes by bounded-depth circuits with arbitrary gates

    DEFF Research Database (Denmark)

    Gál, Anna; Hansen, Kristoffer Arnsfelt; Koucký, Michal

    2011-01-01

    We bound the minimum number w of wires needed to compute any (asymptotically good) error-correcting code C:01(n)01n with minimum distance (n), using unbounded fan-in circuits of depth d with arbitrary gates. Our main results are: (1) If d=2 then w=(n(lognloglogn)2) . (2) If d=3 then w=(nlglgn). (3......, our (n(lognloglogn)2) lower bound gives the largest known lower bound for computing any linear map, improving on the (nlg32n) bound of Pudlak and Rodl (Discrete Mathematics '94). We find the upper bounds surprising. They imply that a (necessarily dense) generator matrix for the code can be written...... as the product of two sparse matrices. The upper bounds are non-explicit: we show the existence of circuits (consisting of only XOR gates) computing good codes within the stated bounds. Using a result by Ishai, Kushilevitz, Ostrovsky, and Sahai (STOC '08), we also obtain similar bounds for computing pairwise...

  5. Controlling the bound states in a quantum-dot hybrid nanowire

    Science.gov (United States)

    Ptok, Andrzej; Kobiałka, Aksel; Domański, Tadeusz

    2017-11-01

    Recent experiments using the quantum dot coupled to the topological superconducting nanowire [Deng et al., Science 354, 1557 (2016), 10.1126/science.aaf3961] revealed that the zero-energy bound state coalesces from the Andreev bound states. Such quasiparticle states, present in the quantum dot, can be controlled by magnetic and electrostatic means. We use a microscopic model of the quantum-dot-nanowire structure to reproduce the experimental results, applying the Bogoliubov-de Gennes technique. This is done by studying the gate voltage dependence of the various types of bound states and mutual influence between them. We show that the zero-energy bound states can emerge from the Andreev bound states in the topologically trivial phase and can be controlled using various means. In the nontrivial topological phase we show the possible resonance between these zero-energy levels with Majorana bound states. We discuss and explain this phenomenon as a result of dominant spin character of discussed bound states. Presented results can be applied in experimental studies by using the proposed nanodevice.

  6. Culture-Bound Words of the Danube Basin Countries: Translation into English

    Directory of Open Access Journals (Sweden)

    Chetverikova Olena

    2015-08-01

    Full Text Available Any course in linguistic country study or popular text translation is impossible without adequate understanding and presentation of culture-bound elements, which present one of the most difficult topics to deal with, especially in multicultural countries. Our investigation aims to show the problems, which appear when we deal with equivalent-lacking words related to culture. Sometimes equivalent-lacking words are associated with culture-bound words, the Ukrainian equivalent for them is “реалії” (derived from Latin realis, pl. realia. However, the term “culture-bound word” is of narrower meaning than the term “equivalent-lacking word”. A culture-bound word names an object peculiar to this or that ethnic culture. Equivalent-lacking words include, along with culture-bound words, neologisms, i.e. newly coined forms, dialect words, slang, taboo-words, foreign (third language terms, proper names, misspellings, archaisms. Comparison of languages and cultures reveals the various types of culture-bound words. Reasons for using them can be extralinguistic, lexical or stylistic. When translating culture-bound words a translator should be aware of the receptor’s potential problems, take into account his background knowledge and choose the best means of translation.

  7. Violation of Energy Bounds in Designer Gravity

    CERN Document Server

    Hertog, T

    2007-01-01

    We continue our study of the stability of designer gravity theories, where one considers anti-de Sitter gravity coupled to certain tachyonic scalars with boundary conditions defined by a smooth function W. It has recently been argued there is a lower bound on the conserved energy in terms of the global minimum of W, if the scalar potential arises from a superpotential P and the scalar reaches an extremum of P at infinity. We show, however, there are superpotentials for which these bounds do not hold.

  8. G-frames with bounded linear operators

    OpenAIRE

    Xiao, Xiang-chun; Zhu, Yu-can; Shu, Zhi-biao; Ding, Ming-ling

    2015-01-01

    In this paper, we introduce the more general g-frame which is called a $K$-g-frame by combining a g-frame with a bounded linear operator $K$ in a Hilbert space. We give several equivalent characterizations for $K$-g-frames and discuss the stability of perturbation for $K$-g-frames. We also investigate the relationship between a $K$-g-frame and the range of the bounded linear operator $K$. In the end, we give two sufficient conditions for the remainder of a $K$-g-frame after an erasure to stil...

  9. Bounds on fake weighted projective space

    OpenAIRE

    Kasprzyk, Alexander M.

    2009-01-01

    A fake weighted projective space X is a Q-factorial toric variety with Picard number one. As with weighted projective space, X comes equipped with a set of weights (λ0, ..., λn). We see how the singularities of P (λ0, ..., λn) influence the singularities of X, and how the weights bound the number of possible fake weighted projective spaces for a fixed dimension. Finally, we present an upper bound on the ratios λj/Σλi if we wish X to have only terminal (or canonical) singularities.

  10. Fibered Transverse Knots and the Bennequin Bound

    OpenAIRE

    Etnyre, John B.; Van Horn-Morris, Jeremy

    2008-01-01

    We prove that a nicely fibered link (by which we mean the binding of an open book) in a tight contact manifold $(M,\\xi)$ with zero Giroux torsion has a transverse representative realizing the Bennequin bound if and only if the contact structure it supports (since it is also the binding of an open book) is $\\xi.$ This gives a geometric reason for the non-sharpness of the Bennequin bound for fibered links. We also note that this allows the classification, up to contactomorphism, of maximal self...

  11. A note on BPS vortex bound states

    Directory of Open Access Journals (Sweden)

    A. Alonso-Izquierdo

    2016-02-01

    Full Text Available In this note we investigate bound states, where scalar and vector bosons are trapped by BPS vortices in the Abelian Higgs model with a critical ratio of the couplings. A class of internal modes of fluctuation around cylindrically symmetric BPS vortices is characterized mathematically, analyzing the spectrum of the second-order fluctuation operator when the Higgs and vector boson masses are equal. A few of these bound states with low values of quantized magnetic flux are described fully, and their main properties are discussed.

  12. A note on BPS vortex bound states

    Energy Technology Data Exchange (ETDEWEB)

    Alonso-Izquierdo, A., E-mail: alonsoiz@usal.es [Departamento de Matematica Aplicada, Universidad de Salamanca (Spain); Garcia Fuertes, W., E-mail: wifredo@uniovi.es [Departamento de Fisica, Universidad de Oviedo (Spain); Mateos Guilarte, J., E-mail: guilarte@usal.es [Departamento de Fisica Fundamental, Universidad de Salamanca (Spain)

    2016-02-10

    In this note we investigate bound states, where scalar and vector bosons are trapped by BPS vortices in the Abelian Higgs model with a critical ratio of the couplings. A class of internal modes of fluctuation around cylindrically symmetric BPS vortices is characterized mathematically, analyzing the spectrum of the second-order fluctuation operator when the Higgs and vector boson masses are equal. A few of these bound states with low values of quantized magnetic flux are described fully, and their main properties are discussed.

  13. Characterization of plasma membrane bound inorganic ...

    African Journals Online (AJOL)

    Background: Currently, a major problem in the management of visceral leishmaniasis or kala-azar, especially in the Indian subcontinent, is the growing unresponsiveness to conventional antimonial therapy. Membrane bound pyrophophatase (PPases) do not exist in plasma membrane from mammals. Thus, H+-PPases ...

  14. Stacked spheres and lower bound theorem

    Indian Academy of Sciences (India)

    BASUDEB DATTA

    2011-11-20

    Nov 20, 2011 ... Using Kalai's result, Tay (1995) proved LBT for a bigger class of simplicial complexes (namely, normal pseudomanifolds). In 2008, we (Bagchi & Datta) have presented a self-contained combinatorial proof of LBT for normal pseudomanifolds. Stacked spheres and lower bound theorem. Basudeb Datta.

  15. Computational Lower Bounds Using Diagonalization-II

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 15; Issue 4. Computational Lower Bounds Using Diagonalization - II. M V Panduranga Rao. General Article Volume 15 Issue 4 April 2010 pp 337-346 ... Keywords. Diagonalization; time–hierarchy theorem; relativization; Baker–Gill–Solovay theorem.

  16. Vulnerable Derivatives and Good Deal Bounds

    DEFF Research Database (Denmark)

    Murgoci, Agatha

    2013-01-01

    We price vulnerable derivatives – i.e. derivatives where the counterparty may default. These are basically the derivatives traded on the over-the-counter (OTC) markets. Default is modelled in a structural framework. The technique employed for pricing is good deal bounds (GDBs). The method imposes...

  17. ASSESSMENT OF REAP-UPWARD BOUND.

    Science.gov (United States)

    LANG, MELVIN; HOPP, LAURENCE

    THE IMPACT OF AN UPWARD BOUND (UB) PROGRAM ON THE ATTITUDES, MOTIVATION, AND ACADEMIC ACHIEVEMENT OF DISADVANTAGED STUDENTS WITH COLLEGE POTENTIAL IS EVALUATED. THE PROGRAM IS ONE OF THE 21 UB PROGRAMS RANDOMLY SELECTED FOR INTENSIVE STUDY. AT RUTGERS UB STUDENTS' ATTITUDES AND MOTIVATION TOWARD COLLEGE GOALS, SELF-EVALUATION AND SELF-ESTEEM,…

  18. Lower Bounds for External Memory Dictionaries

    DEFF Research Database (Denmark)

    Brodal, Gerth Stølting; Fagerberg, Rolf

    2003-01-01

    We study trade-offs between the update time and the query time for comparison based external memory dictionaries. The main contributions of this paper are two lower bound trade offs between the I/O complexity of member queries and insertions: If N

  19. Book Selection, Collection Development, and Bounded Rationality.

    Science.gov (United States)

    Schwartz, Charles A.

    1989-01-01

    Reviews previously proposed schemes of classical rationality in book selection, describes new approaches to rational choice behavior, and presents a model of book selection based on bounded rationality in a garbage can decision process. The role of tacit knowledge and symbolic content in the selection process are also discussed. (102 references)…

  20. The metamorphosis of 'culture-bound' syndromes.

    Science.gov (United States)

    Jilek, W G; Jilek-Aall, L

    1985-01-01

    Starting from a critical review of the concept of 'culture-bound' disorders and its development in comparative psychiatry, the authors present the changing aspects of two so-called culture-bound syndromes as paradigms of transcultural metamorphosis (koro) and intra-cultural metamorphosis (Salish Indian spirit sickness), respectively. The authors present recent data on epidemics of koro, which is supposedly bound to Chinese culture, in Thailand and India among non-Chinese populations. Neither the model of Oedipal castration anxiety nor the model of culture-specific pathogenicity, commonly adduced in psychiatric and ethnological literature, explain these phenomena. The authors' data on Salish Indian spirit sickness describes the contemporary condition as anomic depression, which is significantly different from its traditional namesake. The traditional concept was redefined by Salish ritual specialists in response to current needs imposed by social changes. The stresses involved in creating the contemporary phenomena of koro and spirit sickness are neither culture-specific nor culture-inherent, as postulated for 'culture-bound' syndromes, rather they are generated by a feeling of powerlessness caused by perceived threats to ethnic survival.

  1. Bounded relative motion under zonal harmonics perturbations

    Science.gov (United States)

    Baresi, Nicola; Scheeres, Daniel J.

    2017-04-01

    The problem of finding natural bounded relative trajectories between the different units of a distributed space system is of great interest to the astrodynamics community. This is because most popular initialization methods still fail to establish long-term bounded relative motion when gravitational perturbations are involved. Recent numerical searches based on dynamical systems theory and ergodic maps have demonstrated that bounded relative trajectories not only exist but may extend up to hundreds of kilometers, i.e., well beyond the reach of currently available techniques. To remedy this, we introduce a novel approach that relies on neither linearized equations nor mean-to-osculating orbit element mappings. The proposed algorithm applies to rotationally symmetric bodies and is based on a numerical method for computing quasi-periodic invariant tori via stroboscopic maps, including extra constraints to fix the average of the nodal period and RAAN drift between two consecutive equatorial plane crossings of the quasi-periodic solutions. In this way, bounded relative trajectories of arbitrary size can be found with great accuracy as long as these are allowed by the natural dynamics and the physical constraints of the system (e.g., the surface of the gravitational attractor). This holds under any number of zonal harmonics perturbations and for arbitrary time intervals as demonstrated by numerical simulations about an Earth-like planet and the highly oblate primary of the binary asteroid (66391) 1999 KW4.

  2. Upper Bounds for Mutations of Potentials

    Directory of Open Access Journals (Sweden)

    John Alexander Cruz Morales

    2013-01-01

    Full Text Available In this note we provide a new, algebraic proof of the excessive Laurent phenomenon for mutations of potentials (in the sense of [Galkin S., Usnich A., Preprint IPMU 10-0100, 2010] by introducing to this theory the analogue of the upper bounds from [Berenstein A., Fomin S., Zelevinsky A., Duke Math. J. 126 (2005, 1-52].

  3. Analysis of the asymmetrically expressed Ablim1 locus reveals existence of a lateral plate Nodal-independent left sided signal and an early, left-right independent role for nodal flow

    Directory of Open Access Journals (Sweden)

    Hilton Helen

    2010-05-01

    Full Text Available Abstract Background Vertebrates show clear asymmetry in left-right (L-R patterning of their organs and associated vasculature. During mammalian development a cilia driven leftwards flow of liquid leads to the left-sided expression of Nodal, which in turn activates asymmetric expression of the transcription factor Pitx2. While Pitx2 asymmetry drives many aspects of asymmetric morphogenesis, it is clear from published data that additional asymmetrically expressed loci must exist. Results A L-R expression screen identified the cytoskeletally-associated gene, actin binding lim protein 1 (Ablim1, as asymmetrically expressed in both the node and left lateral plate mesoderm (LPM. LPM expression closely mirrors that of Nodal. Significantly, Ablim1 LPM asymmetry was detected in the absence of detectable Nodal. In the node, Ablim1 was initially expressed symmetrically across the entire structure, resolving to give a peri-nodal ring at the headfold stage in a flow and Pkd2-dependent manner. The peri-nodal ring of Ablim1 expression became asymmetric by the mid-headfold stage, showing stronger right than left-sided expression. Node asymmetry became more apparent as development proceeded; expression retreated in an anticlockwise direction, disappearing first from the left anterior node. Indeed, at early somite stages Ablim1 shows a unique asymmetric expression pattern, in the left lateral plate and to the right side of the node. Conclusion Left LPM Ablim1 is expressed in the absence of detectable LPM Nodal, clearly revealing existence of a Pitx2 and Nodal-independent left-sided signal in mammals. At the node, a previously unrecognised action of early nodal flow and Pkd2 activity, within the pit of the node, influences gene expression in a symmetric manner. Subsequent Ablim1 expression in the peri-nodal ring reveals a very early indication of L-R asymmetry. Ablim1 expression analysis at the node acts as an indicator of nodal flow. Together these results make

  4. Analysis of the asymmetrically expressed Ablim1 locus reveals existence of a lateral plate Nodal-independent left sided signal and an early, left-right independent role for nodal flow

    Science.gov (United States)

    2010-01-01

    Background Vertebrates show clear asymmetry in left-right (L-R) patterning of their organs and associated vasculature. During mammalian development a cilia driven leftwards flow of liquid leads to the left-sided expression of Nodal, which in turn activates asymmetric expression of the transcription factor Pitx2. While Pitx2 asymmetry drives many aspects of asymmetric morphogenesis, it is clear from published data that additional asymmetrically expressed loci must exist. Results A L-R expression screen identified the cytoskeletally-associated gene, actin binding lim protein 1 (Ablim1), as asymmetrically expressed in both the node and left lateral plate mesoderm (LPM). LPM expression closely mirrors that of Nodal. Significantly, Ablim1 LPM asymmetry was detected in the absence of detectable Nodal. In the node, Ablim1 was initially expressed symmetrically across the entire structure, resolving to give a peri-nodal ring at the headfold stage in a flow and Pkd2-dependent manner. The peri-nodal ring of Ablim1 expression became asymmetric by the mid-headfold stage, showing stronger right than left-sided expression. Node asymmetry became more apparent as development proceeded; expression retreated in an anticlockwise direction, disappearing first from the left anterior node. Indeed, at early somite stages Ablim1 shows a unique asymmetric expression pattern, in the left lateral plate and to the right side of the node. Conclusion Left LPM Ablim1 is expressed in the absence of detectable LPM Nodal, clearly revealing existence of a Pitx2 and Nodal-independent left-sided signal in mammals. At the node, a previously unrecognised action of early nodal flow and Pkd2 activity, within the pit of the node, influences gene expression in a symmetric manner. Subsequent Ablim1 expression in the peri-nodal ring reveals a very early indication of L-R asymmetry. Ablim1 expression analysis at the node acts as an indicator of nodal flow. Together these results make Ablim1 a candidate for

  5. Insoluble-Bound Phenolics in Food.

    Science.gov (United States)

    Shahidi, Fereidoon; Yeo, Ju-Dong

    2016-09-11

    This contribution provides a review of the topic of insoluble-bound phenolics, especially their localization, synthesis, transfer and formation in plant cells, as well as their metabolism in the human digestive system and corresponding bioactivities. In addition, their release from the food matrix during food processing and extraction methods are discussed. The synthesis of phenolics takes place mainly at the endoplasmic reticulum and they are then transferred to each organ through transport proteins such as the ATP-binding cassette (ABC) and multidrug and toxic compound extrusion (MATE) transporter at the organ's compartment membrane or via transport vesicles such as cytoplasmic and Golgi vesicles, leading to the formation of soluble and insoluble-bound phenolics at the vacuole and cell wall matrix, respectively. This part has not been adequately discussed in the food science literature, especially regarding the synthesis site and their transfer at the cellular level, thus this contribution provides valuable information to the involved scientists. The bound phenolics cannot be absorbed at the small intestine as the soluble phenolics do (5%-10%), thus passing into the large intestine and undergoing fermentation by a number of microorganisms, partially released from cell wall matrix of foods. Bound phenolics such as phenolic acids and flavonoids display strong bioactivities such as anticancer, anti-inflammation and cardiovascular disease ameliorating effects. They can be extracted by several methods such as acid, alkali and enzymatic hydrolysis to quantify their contents in foods. In addition, they can also be released from the cell wall matrix during food processing procedures such as fermentation, germination, roasting, extrusion cooking and boiling. This review provides critical information for better understanding the insoluble-bound phenolics in food and fills an existing gap in the literature.

  6. Bounded scalar perturbations in bouncing brane world cosmologies

    Science.gov (United States)

    Maier, Rodrigo; Pace, Francesco; Soares, Ivano Damião

    2013-11-01

    We examine the dynamics of scalar perturbations in closed Friedmann-Lemaître-Robertson-Walker universes in the framework of brane world theory with a timelike extra dimension. In this scenario, the unperturbed Friedmann equations contain additional terms arising from the bulk-brane interaction that implement nonsingular bounces in the models with a cosmological constant and noninteracting perfect fluids. The structure of the phase space of the models allows for two basic configurations, namely, one bounce solutions and eternal universes. Assuming that the matter content of the model is given by dust and radiation, we derive the dynamical field equations for scalar hydrodynamical perturbations considering either a conformally flat (de Sitter) bulk or a perturbed bulk. The dynamical system built with these equations is extremely involved. Nevertheless, in this paper we perform a numerical analysis which can shed some light on the study of cosmological scalar perturbations in bouncing brane world models. From a mathematical point of view we show that although the bounce enhances the amplitudes of scalar perturbations for one bounce models in the case of a de Sitter bulk, the amplitudes of the perturbations remain sufficiently small and bounded relative to the background values up to a certain scale. For one bounce models in the case of a perturbed bulk the amplitudes of all perturbations (apart from the Weyl fluid energy density) remain sufficiently small and bounded relative to the background values for any scale of the perturbations. We also discuss and compare the stability and bounded behavior of the perturbations in the late accelerated phase of one bounce solutions. For eternal universes we argue that some of these features are maintained only for early times (typically of the order of the first bounce). In this sense we show that eternal solutions are highly unstable configurations considering the background model of this paper.

  7. Sulfur Atom in its Bound State Is a Unique Element Involved in Physiological Functions in Mammals

    Directory of Open Access Journals (Sweden)

    Shin Koike

    2016-12-01

    Full Text Available It was in the 1950s that the term polysulfide or persulfide was introduced in biological studies. The unfamiliar term “sulfane sulfur” sometimes appeared in papers published in the 1970s, and was defined in the review article by Westley in 1983. In the article, sulfane sulfur is described as sulfur atoms that are covalently bound only with sulfur atoms, and as this explanation was somewhat difficult to comprehend, it was not generally accepted. Thus, in the early 1990s, we redefined these sulfur species as “bound sulfur”, which easily converts to hydrogen sulfide on reduction with a thiol reducing agent. In other words, bound sulfur refers to a sulfur atom that exists in a zero to divalent form (0 to −2. The first part of this review focuses on the fluorescent derivatization HPLC method—which we developed for measurement of bound sulfur—and explains the distribution of bound sulfur and the hydrogen sulfide-producing ability of various tissues, as clarified by this method. Next, we discuss diverse physiological functions and involvement of polysulfide, a typical type of bound sulfur, in the redox regulation system. Additionally, we also address its possible physiological role in the central nervous system, based on its action of scavenging reactive carbonyl compounds.

  8. Increased non-protein bound iron in Down syndrome: contribution to lipid peroxidation and cognitive decline.

    Science.gov (United States)

    Manna, Caterina; Officioso, Arbace; Trojsi, Francesca; Tedeschi, Gioacchino; Leoncini, Silvia; Signorini, Cinzia; Ciccoli, Lucia; De Felice, Claudio

    2016-12-01

    Down syndrome (DS, trisomy 21) is the leading cause of chromosomal-related intellectual disability. At an early age, adults with DS develop with the neuropathological hallmarks of Alzheimer's disease, associated with a chronic oxidative stress. To investigate if non-protein bound iron (NPBI) can contribute to building up a pro-oxidative microenvironment, we evaluated NPBI in both plasma and erythrocytes from DS and age-matched controls, together with in vivo markers of lipid peroxidation (F2-isoprostanes, F2-dihomo-isoprostanes, F4-neuroprostanes) and in vitro reactive oxygen species (ROS) formation in erythrocytes. The serum iron panel and uric acid were also measured. Second, we explored possible correlation between NPBI, lipid peroxidation and cognitive performance. Here, we report NPBI increase in DS, which correlates with increased serum ferritin and uric acid. High levels of lipid peroxidation markers and intraerythrocyte ROS formations were also reported. Furthermore, the scores of Raven's Colored Progressive Matrices (RCPM) test, performed as a measure of current cognitive function, are inversely related to NPBI, serum uric acid, and ferritin. Likewise, ROS production, F2-isoprostanes, and F4-neuroprostanes were also inversely related to cognitive performance, whereas serum transferrin positively correlated to RCPM scores. Our data reveal that increased availability of free redox-active iron, associated with enhanced lipid peroxidation, may be involved in neurodegeneration and cognitive decline in DS. In this respect, we propose chelation therapy as a potential preventive/therapeutic tool in DS.

  9. Bounds on the gluon mass from nucleon decay

    Energy Technology Data Exchange (ETDEWEB)

    Avila, M.A. [Universidad Autonoma del Estado de Morelos, Morelos (Mexico)

    2001-04-01

    Permanent confinement of quarks is assumed to hold in QCD. However, if the gluon has a small mass it is possible to produce-quarks in hadron decays, high-energy reactions or in the early-universe. This situation is modelled by a quark-diquark potential composed of a linear (or harmonic) plus a Yukawa term. We compare our prediction for the proton decay with the experimental lower bound on its life-time, and obtain an upper bound on the gluon mass. [Spanish] Se supone se cumple el confinamiento permanente de quarks en cromodinamica cuantica. Si el gluon tiene masa pequena es posible producir quarks libres en decaimiento hadronicos, reacciones de altas energias o en el universo temprano. Esta situacion es modelada por un potencial quark-diquark, compuesto de un termino lineal (o armonico) mas un termino Yukawa. Comparamos nuestra prediccion para el decaimiento del proton con la cota inferior experimental de su vida media y obtenemos una cota superior sobre la masa del gluon.

  10. Aerodynamics of intermittent bounds in flying birds

    Science.gov (United States)

    Tobalske, Bret W.; Hearn, Jason W. D.; Warrick, Douglas R.

    Flap-bounding is a common flight style in small birds in which flapping phases alternate with flexed-wing bounds. Body lift is predicted to be essential to making this flight style an aerodynamically attractive flight strategy. To elucidate the contributions of the body and tail to lift and drag during the flexed-wing bound phase, we used particle image velocimetry (PIV) and measured properties of the wake of zebra finch (Taeniopygia guttata, N = 5), flying at 6-10 m s- 1 in a variable speed wind tunnel as well as flow around taxidermically prepared specimens (N = 4) mounted on a sting instrumented with force transducers. For the specimens, we varied air velocity from 2 to 12 m s- 1 and body angle from -15∘ to 50∘. The wake of bounding birds and mounted specimens consisted of a pair of counterrotating vortices shed into the wake from the tail, with induced downwash in the sagittal plane and upwash in parasagittal planes lateral to the bird. This wake structure was present even when the tail was entirely removed. We observed good agreement between force measures derived from PIV and force transducers over the range of body angles typically used by zebra finch during forward flight. Body lift:drag (L:D) ratios averaged 1.4 in live birds and varied between 1 and 1.5 in specimens at body angles from 10∘ to 30∘. Peak (L:D) ratio was the same in live birds and specimens (1.5) and was exhibited in specimens at body angles of 15∘ or 20∘, consistent with the lower end of body angles utilized during bounds. Increasing flight velocity in live birds caused a decrease in CL and CD from maximum values of 1.19 and 0.95 during flight at 6 m s- 1 to minimum values of 0.70 and 0.54 during flight at 10 m s- 1. Consistent with delta-wing theory as applied to birds with a graduated-tail shape, trimming the tail to 0 and 50% of normal length reduced L:D ratios and extending tail length to 150% of normal increased L:D ratio. As downward induced velocity is present in the

  11. Stability of bound species during alkene reactions on solid acids

    Science.gov (United States)

    Sarazen, Michele L.; Iglesia, Enrique

    2017-05-01

    This study reports the thermodynamics of bound species derived from ethene, propene, n-butene, and isobutene on solid acids with diverse strength and confining voids. Density functional theory (DFT) and kinetic data indicate that covalently bound alkoxides form C-C bonds in the kinetically relevant step for dimerization turnovers on protons within TON (0.57 nm) and MOR (0.67 nm) zeolitic channels and on stronger acids HPW (polyoxometalate clusters on silica). Turnover rates for mixed alkenes give relative alkoxide stabilities; the respective adsorption constants are obtained from in situ infrared spectra. Tertiary alkoxides (from isobutene) within larger voids (MOR, HPW) are more stable than less substituted isomers but are destabilized within smaller concave environments (TON) because framework distortions are required to avoid steric repulsion. Adsorption constants are similar on MOR and HPW for each alkoxide, indicating that binding is insensitive to acid strength for covalently bound species. DFT-derived formation free energies for alkoxides with different framework attachments and backbone length/structure agree with measurements when dispersion forces, which mediate stabilization by confinement in host-guest systems, are considered. Theory reveals previously unrecognized framework distortions that balance the C-O bond lengths required for covalency with host-guest distances that maximize van der Waals contacts. These distortions, reported here as changes in O-atom locations and dihedral angles, become stronger for larger, more substituted alkoxides. The thermodynamic properties reported here for alkoxides and acid hosts differing in size and conjugate-anion stability are benchmarked against DFT-derived free energies; their details are essential to design host-guest pairs that direct alkoxide species toward specific products.

  12. Optimal Bounds in Parametric LTL Games

    Directory of Open Access Journals (Sweden)

    Martin Zimmermann

    2011-06-01

    Full Text Available We consider graph games of infinite duration with winning conditions in parameterized linear temporal logic, where the temporal operators are equipped with variables for time bounds. In model checking such specifications were introduced as "PLTL" by Alur et al. and (in a different version called "PROMPT-LTL" by Kupferman et al.. We present an algorithm to determine optimal variable valuations that allow a player to win a game. Furthermore, we show how to determine whether a player wins a game with respect to some, infinitely many, or all valuations. All our algorithms run in doubly-exponential time; so, adding bounded temporal operators does not increase the complexity compared to solving plain LTL games.

  13. Bounded rational choice behaviour: applications in transport

    DEFF Research Database (Denmark)

    Jensen, Anders Fjendbo

    2016-01-01

    Even though the theory of rational behaviour has been challenged for almost 100 years, the dominant approach within the field of transport has been based upon the assumptions of neoclassical economics that we live in a world of rational decision makers who always have perfect knowledge and aim to...... and limited processing may occur due to time constraints, low involvement in the decision at hand, relying on habits or the task requiring too high a mental effort....... to maximise some subjective measure. Where other fields, for example within the social sciences and psychology, have made serious efforts to explore alternative models derived from principles of bounded rationality, this direction has begun to take speed within transport applications only recently. Bounded...

  14. Tight Bounds for Distributed Functional Monitoring

    DEFF Research Database (Denmark)

    Woodruff, David P.; Zhang, Qin

    2011-01-01

    output to a function $f$ computed over the union of the inputs. The goal is to minimize the communication. We show the randomized communication complexity of estimating the number of distinct elements up to a $1+\\eps$ factor is $\\Omega(k/\\eps^2)$, improving the previous $\\Omega(k + 1/\\eps^2)$ bound......} t))$ to $\\tilde{\\Omega}(n^{1-2/p}/(\\eps^{4/p} t))$, giving the first bound for estimating $F_0$ in $t$ passes of $\\Omega(1/(\\eps^2 t))$ bits of space that does not use the gap-hamming problem, and showing a distribution for the gap-hamming problem with high external information cost or super...

  15. A holographic bound for D3-brane

    Energy Technology Data Exchange (ETDEWEB)

    Momeni, Davood; Myrzakul, Aizhan; Myrzakulov, Ratbay [Eurasian National University, Eurasian International Center for Theoretical Physics, Astana (Kazakhstan); Eurasian National University, Department of General Theoretical Physics, Astana (Kazakhstan); Faizal, Mir [University of British Columbia-Okanagan, Irving K. Barber School of Arts and Sciences, Kelowna, BC (Canada); University of Lethbridge, Department of Physics and Astronomy, Lethbridge, AB (Canada); Bahamonde, Sebastian [University College London, Department of Mathematics, London (United Kingdom)

    2017-06-15

    In this paper, we will regularize the holographic entanglement entropy, holographic complexity and fidelity susceptibility for a configuration of D3-branes. We will also study the regularization of the holographic complexity from the action for a configuration of D3-branes. It will be demonstrated that for a spherical shell of D3-branes the regularized holographic complexity is always greater than or equal to the regularized fidelity susceptibility. Furthermore, we will also demonstrate that the regularized holographic complexity is related to the regularized holographic entanglement entropy for this system. Thus, we will obtain a holographic bound involving regularized holographic complexity, regularized holographic entanglement entropy and regularized fidelity susceptibility of a configuration of D3-brane. We will also discuss a bound for regularized holographic complexity from action, for a D3-brane configuration. (orig.)

  16. Novel black hole bound states and entropy

    CERN Document Server

    Govindarajan, T R

    2011-01-01

    We solve for the spectrum of the Laplacian as Hamiltonian on $\\mathbb{R}^{2}-\\mathbb{D}$ and in $\\mathbb{R}^{3}-\\mathbb{B}$. A self-adjointness analysis with $\\partial\\mathbb{D}$ and $\\partial\\mathbb{B}$ as the boundary for the two cases shows that a general class of boundary conditions for which the Hamiltonian operator is essentially self-adjoint are of the mixed (Robin) type. With this class of boundary conditions we obtain 'bound state' solutions for the Schroedinger equation. Interestingly, these solutions are all localized near the boundary. We further show that the number of bound states is finite and is infact proportional to the perimeter or area of the removed \\emph{disc} or \\emph{ball}. We then argue that similar considerations should hold for static black hole backgrounds with the horizon treated as the boundary.

  17. Spectral singularities and zero energy bound states

    Energy Technology Data Exchange (ETDEWEB)

    Heiss, W.D. [National Institute for Theoretical Physics, Stellenbosch Institute for Advanced Study, and Institute of Theoretical Physics, University of Stellenbosch, 7602 Matieland (South Africa); Nazmitdinov, R.G. [Department de Fisica, Universitat de les Illes Balears, E-07122 Palma de Mallorca (Spain); Bogoliubov Laboratory of Theoretical Physics, Joint Institute for Nuclear Research, 141980 Dubna (Russian Federation)

    2011-08-15

    Single particle scattering around zero energy is re-analysed in view of recent experiments with ultra-cold atoms, nano-structures and nuclei far from the stability valley. For non-zero orbital angular momentum the low energy scattering cross section exhibits dramatic changes depending on the occurrence of either a near resonance or a bound state or the situation in between, that is a bound state at zero energy. Such state is singular in that it has an infinite scattering length, behaves for the eigenvalues but not for the eigenfunctions as an exceptional point and has no pole in the scattering function. These results should be observable whenever the interaction or scattering length can be controlled. (authors)

  18. Volume Stability of Bitumen Bound Building Blocks

    OpenAIRE

    Thanaya I.N.A.

    2010-01-01

    This paper covers results of laboratory investigations on the volume stability of masonry units incorporating waste materials bound with bitumen (Bitublocks), due to moisture adsorption, thermal exposure and vacuum saturation. The materials used were steel slag, crushed glass, coal fly ash, and 50 pen bitumen. The samples were produced in hot mix method, compacted, then exposed to moist and temperature. It was found that moisture adsorption from the environment caused the Bitublock to expand....

  19. Closed form bound-state perturbation theory

    Directory of Open Access Journals (Sweden)

    Ollie J. Rose

    1980-01-01

    Full Text Available The perturbed Schrödinger eigenvalue problem for bound states is cast into integral form using Green's Functions. A systematic algorithm is developed and applied to the resulting equation giving rise to approximate solutions expressed as functions of the given perturbation parameter. As a by-product, convergence radii for the traditional Rayleigh-Schrödinger and Brillouin-Wigner perturbation theories emerge in a natural way.

  20. EXPLICIT LOWER BOUNDS FOR LINEAR FORMS

    DEFF Research Database (Denmark)

    Leppälä, Kalle

    2016-01-01

    Let I be the field of rational numbers or an imaginary quadratic field and Z(I) its ring of integers. We study some general lemmas that produce lower bounds vertical bar B-0 + B-1 theta(1) +... + B-r theta(r)vertical bar >= 1/max{vertical bar B-1 vertical bar,...,vertical bar B-r vertical bar}(mu...

  1. Exact BPS bound for noncommutative baby Skyrmions

    Energy Technology Data Exchange (ETDEWEB)

    Domrin, Andrei, E-mail: domrin@mi.ras.ru [Department of Mathematics and Mechanics, Moscow State University, Leninskie gory, 119992, GSP-2, Moscow (Russian Federation); Lechtenfeld, Olaf, E-mail: lechtenf@itp.uni-hannover.de [Institut für Theoretische Physik and Riemann Center for Geometry and Physics, Leibniz Universität Hannover, Appelstraße 2, 30167 Hannover (Germany); Linares, Román, E-mail: lirr@xanum.uam.mx [Departamento de Física, Universidad Autónoma Metropolitana Iztapalapa, San Rafael Atlixco 186, C.P. 09340, México D.F. (Mexico); Maceda, Marco, E-mail: mmac@xanum.uam.mx [Departamento de Física, Universidad Autónoma Metropolitana Iztapalapa, San Rafael Atlixco 186, C.P. 09340, México D.F. (Mexico)

    2013-11-25

    The noncommutative baby Skyrme model is a Moyal deformation of the two-dimensional sigma model plus a Skyrme term, with a group-valued or Grassmannian target. Exact abelian solitonic solutions have been identified analytically in this model, with a singular commutative limit. Inside any given Grassmannian, we establish a BPS bound for the energy functional, which is saturated by these baby Skyrmions. This asserts their stability for unit charge, as we also test in second-order perturbation theory.

  2. Bounding symbolic powers via asymptotic multiplier ideals

    Directory of Open Access Journals (Sweden)

    Zach Teitler

    2009-04-01

    Full Text Available We revisit a bound on symbolic powers found by Ein-Lazarsfeld-Smith and subsequently improved by Takagi-Yoshida. We show that the original argument of [6] actually gives the same improvement. On the other hand, we show by examples that any further improvement based on the same technique appears unlikely. This is primarily an exposition; only some examples and remarks might be new.

  3. Herbert Simon: bounded rationality and organizations theory

    OpenAIRE

    Estrada, Fernando

    2012-01-01

    This article evaluates Herbert A. Simon’s contribution to organization theory, placing special emphasis on the criterion of bounded rationality. Simon’s criticism of the orthodox version of organizational bureaucracy is interpreted and his analysis is extended to institutional economics. One of Simon’s main achievements in organizational theory consisted of analytically evaluating the psychology of individual and collective behaviour, thereby opening up the way for future investigation by D. ...

  4. Safe, Multiphase Bounds Check Elimination in Java

    Science.gov (United States)

    2010-01-28

    National Science Foundation under grants CCF-0846010, EIA-0117255, CCF-0702527, and CNS-0855247. References [1] Elvira Albert, Germán Puebla, and Manuel ...David Grove, Michael Hind, Vivek Sarkar, Mauricio J. Serrano , V. C. Sreedhar, Harini Srinivasan, and John Whaley. The jalapeño dynamic optimizing...Computer Science, pages 137–153, August 2009. 40 Gampe, et al. Multiphase Bounds Check Elimination CS-TR-2010-001 [44] Martin Odersky and Philip Wadler

  5. On Lower Bounds for Statistical Learning Theory

    Directory of Open Access Journals (Sweden)

    Po-Ling Loh

    2017-11-01

    Full Text Available In recent years, tools from information theory have played an increasingly prevalent role in statistical machine learning. In addition to developing efficient, computationally feasible algorithms for analyzing complex datasets, it is of theoretical importance to determine whether such algorithms are “optimal” in the sense that no other algorithm can lead to smaller statistical error. This paper provides a survey of various techniques used to derive information-theoretic lower bounds for estimation and learning. We focus on the settings of parameter and function estimation, community recovery, and online learning for multi-armed bandits. A common theme is that lower bounds are established by relating the statistical learning problem to a channel decoding problem, for which lower bounds may be derived involving information-theoretic quantities such as the mutual information, total variation distance, and Kullback–Leibler divergence. We close by discussing the use of information-theoretic quantities to measure independence in machine learning applications ranging from causality to medical imaging, and mention techniques for estimating these quantities efficiently in a data-driven manner.

  6. Heterotrophic free-living and particle-bound bacterial cell size in the ...

    Indian Academy of Sciences (India)

    Regression analysis revealed that 18% of the variation in mean heterotrophic free-living bacterial cell size was due to biological oxygen demand (BOD) in the river Arkavathy, 11% due to surface water velocity (SWV) in the river Cauvery and 11% due to temperature in the river Kapila. Heterotrophic particle-bound bacterial ...

  7. Capillary electrophoretic studies on displacement and proteolytic cleavage of surface bound oligohistidine peptide on quantum dots

    Energy Technology Data Exchange (ETDEWEB)

    Wang Jianhao, E-mail: minuswan@gmail.com [Department of Chemistry, Chinese University of Hong Kong, Shatin (Hong Kong); Xia Jiang, E-mail: jiangxia@cuhk.edu.hk [Department of Chemistry, Chinese University of Hong Kong, Shatin (Hong Kong)

    2012-01-04

    Highlights: Black-Right-Pointing-Pointer Capillary electrophoresis reveals details in QD-oligohistidine peptide binding. Black-Right-Pointing-Pointer An ordered assembly of peptides on QDs was revealed. Black-Right-Pointing-Pointer Intermediates of QD-peptide binding were found. Black-Right-Pointing-Pointer Detailed displacement kinetics was revealed. Black-Right-Pointing-Pointer Proteolysis of surface ligands causes mobility shift and peak broadening in CE. - Abstract: Subtle changes in the chemical structure or the composition of surface bound ligands on quantum dots (QDs) remain difficult to detect. Here we describe a facile setup for fluorescence detection coupled capillary electrophoresis (CE-FL) and its application in monitoring ligand displacement on QDs through metal-affinity driven assembly. We also describe the use of CE-FL to monitor amide bond cleavage by a specific protease, based on Foerster resonance energy transfer (FRET) between Cy5 and QDs spaced by a hexahistidine peptide (H6-Cy5). CE-FL allowed separation of unbound QDs and ligand bound QDs and also revealed an ordered assembly of H6-Cy5 on QDs. In a ligand displacement experiment, unlabeled hexahistidine peptide gradually displaced surface bound H6-Cy5 until finally reaching equilibrium. The displacement intermediates were clearly separated on CE-FL. Proteolytic cleavage of surface bound H6-Cy5 by thrombin was monitored by CE-FL through mobility shift, peak broadening, and FRET changes. Enzymatic parameters thus obtained were comparable with those measured by fluorescence spectroscopy.

  8. Prognostic implications of serial risk score assessments in patients with pulmonary arterial hypertension: a Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL) analysis.

    Science.gov (United States)

    Benza, Raymond L; Miller, Dave P; Foreman, Aimee J; Frost, Adaani E; Badesch, David B; Benton, Wade W; McGoon, Michael D

    2015-03-01

    Data from the Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL) were used previously to develop a risk score calculator to predict 1-year survival. We evaluated prognostic implications of changes in the risk score and individual risk-score parameters over 12 months. Patients were grouped by decreased, unchanged, or increased risk score from enrollment to 12 months. Kaplan-Meier estimates of subsequent 1-year survival were made based on change in the risk score during the initial 12 months of follow-up. Cox regression was used for multivariable analysis. Of 2,529 patients in the analysis cohort, the risk score was decreased in 800, unchanged in 959, and increased in 770 at 12 months post-enrollment. Six parameters (functional class, systolic blood pressure, heart rate, 6-minute walk distance, brain natriuretic peptide levels, and pericardial effusion) each changed sufficiently over time to improve or worsen risk scores in ≥5% of patients. One-year survival estimates in the subsequent year were 93.7%, 90.3%, and 84.6% in patients with a decreased, unchanged, and increased risk score at 12 months, respectively. Change in risk score significantly predicted future survival, adjusting for risk at enrollment. Considering follow-up risk concurrently with risk at enrollment, follow-up risk was a much stronger predictor, although risk at enrollment maintained a significant effect on future survival. Changes in REVEAL risk scores occur in most patients with pulmonary arterial hypertension over a 12-month period and are predictive of survival. Thus, serial risk score assessments can identify changes in disease trajectory that may warrant treatment modifications. Copyright © 2015 International Society for Heart and Lung Transplantation. All rights reserved.

  9. Heterogeneous nuclear ribonucleoprotein (HnRNP) K genome-wide binding survey reveals its role in regulating 3'-end RNA processing and transcription termination at the early growth response 1 (EGR1) gene through XRN2 exonuclease.

    Science.gov (United States)

    Mikula, Michal; Bomsztyk, Karol; Goryca, Krzysztof; Chojnowski, Krzysztof; Ostrowski, Jerzy

    2013-08-23

    The heterogeneous nuclear ribonucleoprotein K (hnRNPK) is a nucleic acid-binding protein that acts as a docking platform integrating signal transduction pathways to nucleic acid-related processes. Given that hnRNPK could be involved in other steps that compose gene expression the definition of its genome-wide occupancy is important to better understand its role in transcription and co-transcriptional processes. Here, we used chromatin immunoprecipitation followed by deep sequencing (ChIP-Seq) to analyze the genome-wide hnRNPK-DNA interaction in colon cancer cell line HCT116. 9.1/3.6 and 7.0/3.4 million tags were sequenced/mapped, then 1809 and 642 hnRNPK binding sites were detected in quiescent and 30-min serum-stimulated cells, respectively. The inspection of sequencing tracks revealed inducible hnRNPK recruitment along a number of immediate early gene loci, including EGR1 and ZFP36, with the highest densities present at the transcription termination sites. Strikingly, hnRNPK knockdown with siRNA resulted in increased pre-RNA levels transcribed downstream of the EGR1 polyadenylation (A) site suggesting altered 3'-end pre-RNA degradation. Further ChIP survey of hnRNPK knockdown uncovered decreased recruitment of the 5'-3' exonuclease XRN2 along EGR1 and downstream of the poly(A) signal without altering RNA polymerase II density at these sites. Immunoprecipitation of hnRNPK and XRN2 from intact and RNase A-treated nuclear extracts followed by shotgun mass spectrometry revealed the presence of hnRNPK and XRN2 in the same complexes along with other spliceosome-related proteins. Our data suggest that hnRNPK may play a role in recruitment of XRN2 to gene loci thus regulating coupling 3'-end pre-mRNA processing to transcription termination.

  10. Global bounds on nitrogen gas emissions from humid tropical forests

    Science.gov (United States)

    Brookshire, E. N. J.; Gerber, S.; Greene, W.; Jones, R. T.; Thomas, S. A.

    2017-03-01

    Denitrification and hydrologic leaching are the two major pathways by which nitrogen (N) is lost from the terrestrial biosphere. Humid tropical forests are thought to dominate denitrification losses from unmanaged lands globally, but there is large uncertainty about the range and key drivers of total N gas emissions across the biome. We combined pantropical measures of small watershed stream chemistry with ecosystem modeling to determine total N gas losses and associated uncertainty across humid tropical forests. Our calculations reveal that denitrification in soils and along hydrologic flow paths contributes on average >45% of total watershed N losses. However, when denitrification occurs exclusively in shallow soils, simulations indicate that gas emissions would exceed N inputs and render plants severely N limited, which contradicts observations of widespread N sufficiency in tropical forests. Our analyses suggest an upper bound on soil denitrification of 80% of total external N losses beyond which tropical plant growth would be compromised.

  11. Study of vison-spinon bound states on the kagome lattice

    Science.gov (United States)

    Shao, Junping; Ghosh, Shivam; Cho, Gil-Young; Lawler, Michael

    2014-03-01

    We search for low-energy vison-spinon bound states on the kagome lattice. We do this by applying an optimization algorithm to a bosonic spin liquid state with a well separated pair of visons inserted. The resulting wavefunction reveals that the low energy eigen-modes correspond to bound spinon states localized around the visons. We study these modes and their symmetry properties. Our results provide evidence supporting the low energy effective theories of Z2 spin liquids whose bosonic spinons, fermonic spinons and visions are characterized by projective symmetry groups consistent with the expected fusion rules and duality relations.

  12. Maturation related changes in the distribution of ester bound fatty acids and alcohols in a coal series from the New Zealand Coal Band covering diagenetic to catagenetic coalification levels

    Energy Technology Data Exchange (ETDEWEB)

    Glombitza, C.; Mangelsdorf, K.; Horsfield, B. [German Research Cemter of Geoscience GFZ, Potsdam (Germany)

    2009-10-15

    Several lignites and coals of low to moderate maturation levels from the New Zealand Coal Band were investigated using alkaline ester cleavage experiments to reveal compositional changes of ester bound components during increasing maturation. Ester bound alcohols are found to be present in highest amounts in the very immature lignite samples but show a rapid decrease during early diagenesis. Ester bound fatty acids also show an initial exponential decrease during diagenesis but reveal an intermittent increase during early catagenesis before decreasing again during main catagenesis. This was related to the short chain fatty acids. To obtain a maturity related signal and to eliminate facies related scattering in the amounts of fatty acids in the coal samples, the carbon preference index of fatty acids (CPIFA) parameter is introduced. For the long chain fatty acids the CPIFA decreases with increasing maturity. During diagenesis, the same trend can be observed for the short chain fatty acids but the intermittent increase in the amounts of short chain fatty acids is also accompanied by high CPIFA values. This indicates less altered organic biomass at this maturation level and is in contrast to the mature CPIFA signal of the long chain fatty acids of the same samples. Thus could be due to extremely different amounts of short and long chain fatty acids in the original source organic matter or it could due to the incorporation of immature bacterial biomass from deep microbial communities containing C{sub 16} and C{sub 18} fatty acids as main cell membrane components. Deep microbial life might be stimulated at this interval by the increasing release of thermally generated potential substrates from the organic matrix during early catagenesis. The high amounts of alcohols in the immature lignite samples are also visible in the alkene distribution from the open system pyrolysis experiments of the organic matrix before and after saponification.

  13. Structures of potent anticancer compounds bound to tubulin.

    Science.gov (United States)

    McNamara, Dan E; Senese, Silvia; Yeates, Todd O; Torres, Jorge Z

    2015-07-01

    Small molecules that bind to tubulin exert powerful effects on cell division and apoptosis (programmed cell death). Cell-based high-throughput screening combined with chemo/bioinformatic and biochemical analyses recently revealed a novel compound MI-181 as a potent mitotic inhibitor with heightened activity towards melanomas. MI-181 causes tubulin depolymerization, activates the spindle assembly checkpoint arresting cells in mitosis, and induces apoptotic cell death. C2 is an unrelated compound previously shown to have lethal effects on microtubules in tumorigenic cell lines. We report 2.60 Å and 3.75 Å resolution structures of MI-181 and C2, respectively, bound to a ternary complex of αβ-tubulin, the tubulin-binding protein stathmin, and tubulin tyrosine ligase. In the first of these structures, our crystallographic results reveal a unique binding mode for MI-181 extending unusually deep into the well-studied colchicine-binding site on β-tubulin. In the second structure the C2 compound occupies the colchicine-binding site on β-tubulin with two chemical moieties recapitulating contacts made by colchicine, in combination with another system of atomic contacts. These insights reveal the source of the observed effects of MI-181 and C2 on microtubules, mitosis, and cultured cancer cell lines. The structural details of the interaction between tubulin and the described compounds may guide the development of improved derivative compounds as therapeutic candidates or molecular probes to study cancer cell division. © 2015 The Protein Society.

  14. Bound values for Hall conductivity of heterogeneous medium under ...

    Indian Academy of Sciences (India)

    - ditions in inhomogeneous medium has been studied. It is shown that bound values for. Hall conductivity differ from bound values for metallic conductivity. This is due to the unusual character of current percolation under quantum Hall effect ...

  15. The S-matrix for systems with bound states

    NARCIS (Netherlands)

    Ruijgrok, Th.W.

    A unitary S-matrix is defined for a system of three particles, two of which can form a bound state. It is shown how for elastic scattering the polarization of the bound state must be taken into account.

  16. Linear Plotkin bound for entanglement-assisted quantum codes

    Science.gov (United States)

    Guo, Luobin; Li, Ruihu

    2013-03-01

    The entanglement-assisted (EA) formalism is a generalization of the standard stabilizer formalism, and it can transform arbitrary quaternary classical linear codes into entanglement-assisted quantum error correcting codes (EAQECCs) by using of shared entanglement between the sender and the receiver. Using the special structure of linear EAQECCs, we derive an EA-Plotkin bound for linear EAQECCs, which strengthens the previous known EA-Plotkin bound. This linear EA-Plotkin bound is tighter then the EA-Singleton bound, and matches the EA-Hamming bound and the EA-linear programming bound in some cases. We also construct three families of EAQECCs with good parameters. Some of these EAQECCs saturate this linear EA-Plotkin bound and the others are near optimal according to this bound; almost all of these linear EAQECCs are degenerate codes.

  17. Bound states in the strong coupling limit

    CERN Document Server

    Martin, A

    1972-01-01

    The author shows that the number of bound states of a particle in a short-range potential in n dimensions is given asymptotically by N=g /sup n/2/S/sub n//(2 pi )/sup n/ integral mod 2MV/sup -//h(cross)/sup 2/ mod /sup n/2/d/sup n/x+0(g/sup n/2-g/) for g to infinity , where gV /sup -/ is the attractive part of the potential, and S/sub /n is the volume of the n dimensional sphere with unit radius. (10 refs).

  18. Topological edge states of bound photon pairs

    Science.gov (United States)

    Gorlach, Maxim A.; Poddubny, Alexander N.

    2017-05-01

    We predict the existence of interaction-driven edge states of bound two-photon quasiparticles in a dimer periodic array of nonlinear optical cavities. The energy spectrum of photon pairs is dramatically richer than in the noninteracting case or in a simple lattice, featuring collapse and revival of multiple edge and bulk modes as well as edge states in continuum. We link the edge-state existence to the two-photon quantum walk graph connectivity. Our results offer a route to control quantum entanglement and provide insights into the physics of many-body topological states.

  19. Properties of Excitons Bound to Ionized Donors

    DEFF Research Database (Denmark)

    Skettrup, Torben; Suffczynski, M.; Gorzkowski, W.

    1971-01-01

    Binding energies, interparticle distances, oscillator strengths, and exchange corrections are calculated for the three-particle complex corresponding to an exciton bound to an ionized donor. The results are given as functions of the mass ratio of the electron and hole. Binding of the complex...... is obtained for mass ratios up to 0.426. The interparticle distances are up to 50 times larger than the corresponding exciton radius. The oscillator strengths are about 104 times greater than those of free excitons, while the exchange corrections for the complex are comparable to those of free excitions...

  20. Landauer Bound for Analog Computing Systems

    CERN Document Server

    Diamantini, M. Cristina; Trugenberger, Carlo A.

    2016-01-01

    By establishing a relation between information erasure and continuous phase transitions we generalise the Landauer bound to analog computing systems. The entropy production per degree of freedom during erasure of an analog variable (reset to standard value) is given by the logarithm of the configurational volume measured in units of its minimal quantum. As a consequence every computation has to be carried on with a finite number of bits and infinite precision is forbidden by the fundamental laws of physics, since it would require an infinite amount of energy.

  1. Model Independent Bounds on Kinetic Mixing

    Energy Technology Data Exchange (ETDEWEB)

    Hook, Anson; Izaguirre, Eder; Wacker, Jay G.; /SLAC

    2011-08-22

    New Abelian vector bosons can kinetically mix with the hypercharge gauge boson of the Standard Model. This letter computes the model independent limits on vector bosons with masses from 1 GeV to 1 TeV. The limits arise from the numerous e{sup +}e{sup -} experiments that have been performed in this energy range and bound the kinetic mixing by {epsilon} {approx}< 0.03 for most of the mass range studied, regardless of any additional interactions that the new vector boson may have.

  2. Engineering the coupling between Majorana bound states

    Science.gov (United States)

    Shi, Z. C.; Shao, X. Q.; Xia, Y.; Yi, X. X.

    2017-09-01

    We study the coupling between Majorana bound states (CMBS), which is mediated by a topologically trivial chain in the presence of pairing coupling and long-range coupling. The results show that CMBS can be enhanced by the pairing coupling and long-range coupling of the trivial chain. When driving the trivial chain by periodic driving field, we deduce the analytical expressions of CMBS in the high-frequency limit, and demonstrate that CMBS can be modulated by the frequency and amplitude of driving field. Finally we exhibit the application of tunable CMBS in realizing quantum logic gates.

  3. Valuation models and Simon's bounded rationality

    Directory of Open Access Journals (Sweden)

    Alexandra Strommer de Farias Godoi

    2009-09-01

    Full Text Available This paper aims at reconciling the evidence that sophisticated valuation models are increasingly used by companies in their investment appraisal with the literature of bounded rationality, according to which objective optimization is impracticable in the real world because it would demand an immense level of sophistication of the analytical and computational processes of human beings. We show how normative valuation models should rather be viewed as forms of reality representation, frameworks according to which the real world is perceived, fragmented for a better understanding, and recomposed, providing an orderly method for undertaking a task as complex as the investment decision.

  4. Andreev bound states. Some quasiclassical reflections

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Y., E-mail: yiriolin@illinois.edu; Leggett, A. J. [University of Illinois at Urhana-Champaign, Dept. of Physics (United States)

    2014-12-15

    We discuss a very simple and essentially exactly solvable model problem which illustrates some nice features of Andreev bound states, namely, the trapping of a single Bogoliubov quasiparticle in a neutral s-wave BCS superfluid by a wide and shallow Zeeman trap. In the quasiclassical limit, the ground state is a doublet with a splitting which is proportional to the exponentially small amplitude for “normal” reflection by the edges of the trap. We comment briefly on a prima facie paradox concerning the continuity equation and conjecture a resolution to it.

  5. Score Bounded Monte-Carlo Tree Search

    Science.gov (United States)

    Cazenave, Tristan; Saffidine, Abdallah

    Monte-Carlo Tree Search (MCTS) is a successful algorithm used in many state of the art game engines. We propose to improve a MCTS solver when a game has more than two outcomes. It is for example the case in games that can end in draw positions. In this case it improves significantly a MCTS solver to take into account bounds on the possible scores of a node in order to select the nodes to explore. We apply our algorithm to solving Seki in the game of Go and to Connect Four.

  6. Infrared spectroscopy of weakly bound molecular ions

    Energy Technology Data Exchange (ETDEWEB)

    Yeh, Lisa I-Ching

    1988-11-01

    The infrared spectra of a series of hydrated hydronium cluster ions and of protonated ethane ion are presented. A tandem mass spectrometer is ideally suited to obtaining the spectra of such weakly bound molecular ions. Traditional absorption spectroscopy is not feasible in these situations, so the techniques described in this thesis make use of some consequence of photon absorption with higher sensitivity than simply attenuation of laser power. That consequence is dissociation. By first mass selecting the parent ion under study and then mass selecting the fragment ion formed from dissociation, the near unit detection efficiency of ion counting methods has been used to full advantage.

  7. BOUND PERIODICAL HOLDINGS BATTELLE - NORTHWEST LIBRARY

    Energy Technology Data Exchange (ETDEWEB)

    None

    1967-05-01

    This report lists the bound periodicals in the Technical Library at the Pacific Northwest Laboratory, operated by Battelle Memorial Institute. It was prepared from a computer program and is arranged in two parts. Part one is an alphabetical list of journals by title; part two is an arrangement of the journals by subject. The list headings are self-explanatory, with the exception of the title code, which is necessary in the machine processing. The listing is complete through June, 1966 and updates an earlier publication issued in March, 1965.

  8. A lower bound of concurrence for multipartite quantum systems

    Science.gov (United States)

    Zhu, Xue-Na; Li, Ming; Fei, Shao-Ming

    2018-02-01

    We present a lower bound of concurrence for four-partite systems in terms of the concurrence for M (2≤ M≤ 3) part quantum systems and give an analytical lower bound for 2⊗ 2⊗ 2⊗ 2 mixed quantum sates. It is shown that these lower bounds are able to improve the existing bounds and detect entanglement better. Furthermore, our approach can be generalized to multipartite quantum systems.

  9. Semirelativistic N-boson systems bound by attractive pair potentials

    Energy Technology Data Exchange (ETDEWEB)

    Hall, Richard L [Department of Mathematics and Statistics, Concordia University, 1455 de Maisonneuve Boulevard West, Montreal, Quebec, H3G 1M8 (Canada); Lucha, Wolfgang [Institute for High Energy Physics, Austrian Academy of Sciences, Nikolsdorfergasse 18, A-1050 Vienna (Austria)], E-mail: rhall@mathstat.concordia.ca, E-mail: wolfgang.lucha@oeaw.ac.at

    2009-10-02

    We establish bounds on the energy of a system of N identical bosons bound by attractive pair potentials and obeying the semirelativistic Salpeter equation. The lower bound is provided by a 'reduction', with the aid of Jacobi relative coordinates, to a suitably scaled one-body Klein-Gordon problem. Complementary upper energy bounds are provided by means of a Gaussian trial function. Detailed results are presented for the exponential pair potential V(r) = -vexp(-r/a)

  10. Bounding the number of remarkable values via Jouanolou's theorem

    OpenAIRE

    Chèze, Guillaume

    2015-01-01

    In this article we bound the number of remarkable values of a polynomial vector field. The proof is short and based on Jouanolou's theorem about rational first integrals of planar polynomial derivations. Our bound is given in term of the size of a Newton polygon associated to the vector field. We prove that this bound is almost reached.

  11. Bounding the number of remarkable values via Jouanolou's theorem

    Science.gov (United States)

    Chèze, Guillaume

    2015-05-01

    In this article we bound the number of remarkable values of a polynomial vector field. The proof is short and based on Jouanolou's theorem about rational first integrals of planar polynomial derivations. Our bound is given in term of the size of a Newton polygon associated to the vector field. We prove that this bound is almost reached.

  12. Bound values for Hall conductivity of heterogeneous medium under ...

    Indian Academy of Sciences (India)

    Bound values for Hall conductivity under quantum Hall effect (QHE) conditions in inhomogeneous medium has been studied. It is shown that bound values for Hall conductivity differ from bound values for metallic conductivity. This is due to the unusual character of current percolation under quantum Hall effect conditions.

  13. Bounds in the generalized Weber problem under locational uncertainty

    DEFF Research Database (Denmark)

    Juel, Henrik

    1981-01-01

    An existing analysis of the bounds on the Weber problem solution under uncertainty is incorrect. For the generalized problem with arbitrary measures of distance, we give easily computable ranges on the bounds and state the conditions under which the exact values of the bounds can be found...

  14. Generalized bounds for convex multistage stochastic programs

    CERN Document Server

    Künzi, H; Fandel, G; Trockel, W; Basile, A; Drexl, A; Dawid, H; Inderfurth, K; Kürsten, W; Schittko, U

    2005-01-01

    This work was completed during my tenure as a scientific assistant and d- toral student at the Institute for Operations Research at the University of St. Gallen. During that time, I was involved in several industry projects in the field of power management, on the occasion of which I was repeatedly c- fronted with complex decision problems under uncertainty. Although usually hard to solve, I quickly learned to appreciate the benefit of stochastic progr- ming models and developed a strong interest in their theoretical properties. Motivated both by practical questions and theoretical concerns, I became p- ticularly interested in the art of finding tight bounds on the optimal value of a given model. The present work attempts to make a contribution to this important branch of stochastic optimization theory. In particular, it aims at extending some classical bounding methods to broader problem classes of practical relevance. This book was accepted as a doctoral thesis by the University of St. Gallen in June 2004.1...

  15. Bounds of parameter estimation for interference signals.

    Science.gov (United States)

    Li, Chengshuai; Zhu, Yizheng

    2017-08-20

    Parameter estimation, especially frequency estimation, from noisy observations of interference is essential in optical interferometric sensing and metrology. The Cramer-Rao bound (CRB) of such estimation determines measurement sensitivity limit. Unlike the well-studied complex sinusoids in communication theory, an optical interference signal is distinctly different in its model parameters and noise statistics. The connection between these parameters and their estimation bounds has not been well understood. Here we propose a complete, realistic multiparameter interference model corrupted by a combination of shot noise, dark noise, and readout noise. We derive the Fisher information matrix and the CRBs for all model parameters, including intensity, visibility, optical path length (frequency), and initial phase. We show that the CRBs of frequency and phase are coupled but not affected by the knowledge of intensity and visibility. Knowing the initial phase offers significant sensitivity advantage, which is verified by both theoretical derivations and numerical simulations. In addition to the complete model, a shot noise-limited case is studied, permitting the calculation of the CRBs directly from measured data.

  16. More loosely bound hadron molecules at CDF?

    CERN Document Server

    Bignamini, C; Piccinini, F; Polosa, A D; Riquer, V; Sabelli, C

    2010-01-01

    In a recent paper we have proposed a method to estimate the prompt production cross section of X(3872) at the Tevatron assuming that this particle is a loosely bound molecule of a D and a D*bar meson. Under this hypothesis we find that it is impossible to explain the high prompt production cross section found by CDF at sigma(X(3872)) \\sim 30-70 nb as our theoretical prediction is about 300 times smaller than the measured one. Following our work, Artoisenet and Braaten, have suggested that final state interactions in the DD*bar system might be so strong to push the result we obtained for the cross section up to the experimental value. Relying on their conclusions we show that the production of another very narrow loosely bound molecule, the X_s=D_s D_s*bar, could be similarly enhanced. X_s should then be detectable at CDF with a mass of 4080 MeV and a prompt production cross section of sigma(X_s) \\sim 1-3 nb.

  17. Search for a bound K− pp system

    Directory of Open Access Journals (Sweden)

    Camerini P.

    2010-04-01

    Full Text Available Data from the K− absorption reaction on 6,7Li, 9Be, 13C and 16O have recently been collected by FINUDA at the DAΦNE φ-factory (Laboratori Nazionali di Frascati-INFN, following an earlier lower statitics run on 12C and some other targets. FINUDA is a high acceptance magnetic spectrometer which performed a wide range of studies by detecting the charged particles and neutrons exiting the targets after the absorption event. In this paper it is discussed about the study of the A(K− , Λp reaction in the context of the search for deeply bound $ar{K}$ - nuclear states. The observation of a bump in the Λp invariant mass distribution is discussed in terms of a possible signature of a deeply bound K− pp kaonic cluster as well as of more conventional physics. An overview of the experimental situation in this field will be given.

  18. A Conjectured Bound on Accidental Symmetries

    CERN Document Server

    Buican, Matthew

    2012-01-01

    In this note, we study a large class of four-dimensional R-symmetric theories, and we describe a new quantity, \\tau_U, which is well-defined in these theories. Furthermore, we conjecture that this quantity is larger in the ultraviolet (UV) than in the infrared (IR), i.e. that \\tau_U^{UV}>\\tau_U^{IR}. While we do not prove this inequality in full generality, it is straightforward to show that our conjecture holds in the subset of theories that do not have accidental symmetries. In addition, we subject our inequality to an array of non-trivial tests in theories with accidental symmetries and dramatically different dynamics both in N=1 and N=2 supersymmetry and find that our inequality is obeyed. One interesting consequence of this conjecture is that the mixing of accidental symmetries with the IR superconformal R current is bounded by the UV quantity, \\tau_U^{UV}. To demonstrate the potential utility of this bound, we apply it to the somewhat mysterious SU(2) gauge theory of Intriligator, Seiberg, and Shenker a...

  19. Bounds for phylogenetic network space metrics.

    Science.gov (United States)

    Francis, Andrew; Huber, Katharina T; Moulton, Vincent; Wu, Taoyang

    2018-04-01

    Phylogenetic networks are a generalization of phylogenetic trees that allow for representation of reticulate evolution. Recently, a space of unrooted phylogenetic networks was introduced, where such a network is a connected graph in which every vertex has degree 1 or 3 and whose leaf-set is a fixed set X of taxa. This space, denoted [Formula: see text], is defined in terms of two operations on networks-the nearest neighbor interchange and triangle operations-which can be used to transform any network with leaf set X into any other network with that leaf set. In particular, it gives rise to a metric d on [Formula: see text] which is given by the smallest number of operations required to transform one network in [Formula: see text] into another in [Formula: see text]. The metric generalizes the well-known NNI-metric on phylogenetic trees which has been intensively studied in the literature. In this paper, we derive a bound for the metric d as well as a related metric [Formula: see text] which arises when restricting d to the subset of [Formula: see text] consisting of all networks with [Formula: see text] vertices, [Formula: see text]. We also introduce two new metrics on networks-the SPR and TBR metrics-which generalize the metrics on phylogenetic trees with the same name and give bounds for these new metrics. We expect our results to eventually have applications to the development and understanding of network search algorithms.

  20. Counting Majorana bound states using complex momenta

    Directory of Open Access Journals (Sweden)

    I. Mandal

    2016-09-01

    Full Text Available Recently, the connection between Majorana fermions bound to the defects in arbitrary dimensions, and complex momentum roots of the vanishing determinant of the corresponding bulk Bogoliubov–de Gennes (BdG Hamiltonian, has been established (EPL, 2015, 110, 67005. Based on this understanding, a formula has been proposed to count the number (n of the zero energy Majorana bound states, which is related to the topological phase of the system. In this paper, we provide a proof of the counting formula and we apply this formula to a variety of 1d and 2d models belonging to the classes BDI, DIII and D. We show that we can successfully chart out the topological phase diagrams. Studying these examples also enables us to explicitly observe the correspondence between these complex momentum solutions in the Fourier space, and the localized Majorana fermion wavefunctions in the position space. Finally, we corroborate the fact that for systems with a chiral symmetry, these solutions are the so-called "exceptional points", where two or more eigenvalues of the complexified Hamiltonian coalesce.

  1. Dilation volumes of sets of bounded perimeter

    DEFF Research Database (Denmark)

    Kiderlen, Markus; Rataj, Jan

    This paper analyzes the first order behavior (that is, the right sided derivative) of the volume of the dilation A ⊕ tQ as t converges to zero. Here A and Q are subsets of n-dimensional Euclidean space, A has bounded perimeter and Q is compact. If Q consists of two points only, x and x+u, say......, this derivative coincides up to sign with the directional derivative of the covariogram of A in direction u. By known results for the covariogram, this derivative can therefore be expressed by the cosine transform of the surface area measure of A. We extend this result to sets Q that are at most countable and use...... it to determine the derivative of the contact distribution function of a stationary random closed set at zero. A variant for uncountable Q is given, too. The proofs are based on approximation of the characteristic function of A by smooth functions of bounded variation and showing corresponding formulas for them....

  2. Magnetic resonance elastography: Inversions in bounded media.

    Science.gov (United States)

    Kolipaka, Arunark; McGee, Kiaran P; Manduca, Armando; Romano, Anthony J; Glaser, Kevin J; Araoz, Philip A; Ehman, Richard L

    2009-12-01

    Magnetic resonance elastography is a noninvasive imaging technique capable of quantifying and spatially resolving the shear stiffness of soft tissues by visualization of synchronized mechanical wave displacement fields. However, magnetic resonance elastography inversions generally assume that the measured tissue motion consists primarily of shear waves propagating in a uniform, infinite medium. This assumption is not valid in organs such as the heart, eye, bladder, skin, fascia, bone and spinal cord, in which the shear wavelength approaches the geometric dimensions of the object. The aim of this study was to develop and test mathematical inversion algorithms capable of resolving shear stiffness from displacement maps of flexural waves propagating in bounded media such as beams, plates, and spherical shells, using geometry-specific equations of motion. Magnetic resonance elastography and finite element modeling of beam, plate, and spherical shell phantoms of various geometries were performed. Mechanical testing of the phantoms agreed with the stiffness values obtained from finite element modeling and magnetic resonance elastography data, and a linear correlation of r(2) >or= 0.99 was observed between the stiffness values obtained using magnetic resonance elastography and finite element modeling data. In conclusion, we have demonstrated new inversion methods for calculating shear stiffness that may be more appropriate for waves propagating in bounded media. (c) 2009 Wiley-Liss, Inc.

  3. A balance for dark matter bound states

    Science.gov (United States)

    Nozzoli, F.

    2017-05-01

    Massive particles with self interactions of the order of 0.2 barn/GeV are intriguing Dark Matter candidates from an astrophysical point of view. Current and past experiments for direct detection of massive Dark Matter particles are focusing to relatively low cross sections with ordinary matter, however they cannot rule out very large cross sections, σ/M > 0.01 barn/GeV, due to atmosphere and material shielding. Cosmology places a strong indirect limit for the presence of large interactions among Dark Matter and baryons in the Universe, however such a limit cannot rule out the existence of a small sub-dominant component of Dark Matter with non negligible interactions with ordinary matter in our galactic halo. Here, the possibility of the existence of bound states with ordinary matter, for a similar Dark Matter candidate with not negligible interactions, is considered. The existence of bound states, with binding energy larger than ∼ 1 meV, would offer the possibility to test in laboratory capture cross sections of the order of a barn (or larger). The signature of the detection for a mass increasing of cryogenic samples, due to the possible particle accumulation, would allow the investigation of these Dark Matter candidates with mass up to the GUT scale. A proof of concept for a possible detection set-up and the evaluation of some noise sources are described.

  4. Performance Bounds on Two Concatenated, Interleaved Codes

    Science.gov (United States)

    Moision, Bruce; Dolinar, Samuel

    2010-01-01

    A method has been developed of computing bounds on the performance of a code comprised of two linear binary codes generated by two encoders serially concatenated through an interleaver. Originally intended for use in evaluating the performances of some codes proposed for deep-space communication links, the method can also be used in evaluating the performances of short-block-length codes in other applications. The method applies, more specifically, to a communication system in which following processes take place: At the transmitter, the original binary information that one seeks to transmit is first processed by an encoder into an outer code (Co) characterized by, among other things, a pair of numbers (n,k), where n (n > k)is the total number of code bits associated with k information bits and n k bits are used for correcting or at least detecting errors. Next, the outer code is processed through either a block or a convolutional interleaver. In the block interleaver, the words of the outer code are processed in blocks of I words. In the convolutional interleaver, the interleaving operation is performed bit-wise in N rows with delays that are multiples of B bits. The output of the interleaver is processed through a second encoder to obtain an inner code (Ci) characterized by (ni,ki). The output of the inner code is transmitted over an additive-white-Gaussian- noise channel characterized by a symbol signal-to-noise ratio (SNR) Es/No and a bit SNR Eb/No. At the receiver, an inner decoder generates estimates of bits. Depending on whether a block or a convolutional interleaver is used at the transmitter, the sequence of estimated bits is processed through a block or a convolutional de-interleaver, respectively, to obtain estimates of code words. Then the estimates of the code words are processed through an outer decoder, which generates estimates of the original information along with flags indicating which estimates are presumed to be correct and which are found to

  5. Isotopic fractionation of hydrate-bound hydrocarbons in the sub-bottom sediments of Lake Baikal

    Science.gov (United States)

    Hachikubo, A.; Khlystov, O.; Sakagami, H.; Minami, H.; Yamashita, S.; Takahashi, N.; Shoji, H.; Kalmychkov, G.; Poort, J.

    2010-12-01

    We investigated the molecular and stable isotope composition of hydrate-bound and dissolved hydrocarbons in pore water in subsurface sediments of Lake Baikal. Hydrate-bearing sediment cores were retrieved at southern and central Baikal basins in 2002-2009. Gas hydrates exist at the mud volcanoes at Malenky, Bolshoy, Malyutka and Peschanka in the southern Baikal basin and Kukuy in the central Baikal basin. The Goloustnoye seepage site in the southern Baikal basin seems active and gas plumes are ascending from the lake bottom. Delta 13C of hydrate-bound methane is several permil lower than that of dissolved methane in pore water at most places, however, delta 13C values of hydrate-bound and dissolved methane are almost the same each other and delta D values of hydrate-bound methane was about 5 permil lower than that of dissolved methane at Goloustnoye. Hachikubo et al. [2007] revealed in their laboratory experiments that delta D of hydrate-bound methane and ethane becomes several permil lower than that of the original gases at a formation of gas hydrate, whereas delta 13C of hydrate-bound and original gases remains almost constant. Based on their results, the current gas dissolved in pore water is not the source of the gas hydrates at most hydrate-bearing sites in Lake Baikal. On the contrary, the gas hydrate at Goloustnoye seems to be rather new crystal. Although isotopic fractionation of ethane also occurs at the formation of gas hydrate in the laboratory experiments, isotopic differences between hydrate-bound and dissolved ethane differ from each other according to the sediment cores. Hachikubo, A., T. Kosaka, M. Kida, A. Krylov, H. Sakagami, H. Minami, N. Takahashi, and H. Shoji (2007), Isotopic fractionation of methane and ethane hydrates between gas and hydrate phases, Geophys. Res. Lett., 34, L21502, doi:10.1029/2007GL030557.

  6. On the Applicability of Lower Bounds for Solving Rectilinear

    DEFF Research Database (Denmark)

    Clausen, Jens; Karisch, Stefan E.; Perregaard, M.

    1998-01-01

    The quadratic assignment problem (QAP) belongs to the hard core of NP-hard optimization problems. After almost forty years of research only relatively small instances can be solved to optimality. The reason is that the quality of the lower bounds available for exact methods is not sufficient....... Recently, lower bounds based on decomposition were proposed for the so called rectilinear QAP that proved to be the strongest for a large class of problem instances. We investigate the strength of these bounds when applied not only at the root node of a search tree but as the bound function used...... in a Branch-and-Bound code solving large scale QAPs....

  7. Degenerate quantum codes and the quantum Hamming bound

    Science.gov (United States)

    Sarvepalli, Pradeep; Klappenecker, Andreas

    2010-03-01

    The parameters of a nondegenerate quantum code must obey the Hamming bound. An important open problem in quantum coding theory is whether the parameters of a degenerate quantum code can violate this bound for nondegenerate quantum codes. In this article we show that Calderbank-Shor-Steane (CSS) codes, over a prime power alphabet q⩾5, cannot beat the quantum Hamming bound. We prove a quantum version of the Griesmer bound for the CSS codes, which allows us to strengthen the Rains’ bound that an [[n,k,d

  8. A sharp upper bound for departure from normality

    Energy Technology Data Exchange (ETDEWEB)

    Lee, S.L.

    1993-08-01

    The departure from normality of a matrix is a real scalar that is impractical to compute if a matrix is large and its eigenvalues are unknown. A simple formula is presented for computing an upper bound for departure from normality in the Frobenius norm. This new upper bound is cheaper to compute than the upper bound derived by Henrici. Moreover, the new bound is sharp for Hermitian matrices, skew-Hermitian matrices and, in general, any matrix with eigenvalues that are horizontally or vertically aligned in the complex plane. In terms of applications, the new bound can be used in computing bounds for the spectral norm of matrix functions or bounds for the sensitivity of eigenvalues to matrix perturbations.

  9. Butterfly velocity bound and reverse isoperimetric inequality

    Science.gov (United States)

    Feng, Xing-Hui; Lü, H.

    2017-03-01

    We study the butterfly effect of the AdS planar black holes in the framework of Einstein's general relativity. We find that the butterfly velocities can be expressed by a universal formula vB2=T S /(2 VthP ). In doing so, we come upon a near-horizon geometrical formula for the thermodynamical volume Vth . We verify the volume formula by examining a variety of AdS black holes. We also show that the volume formula implies that the conjectured reverse isoperimetric inequality follows straightforwardly from the null-energy condition, for static AdS black holes. The inequality is thus related to an upper bound of the butterfly velocities.

  10. Congeniality bounds on quark masses from nucleosynthesis

    Science.gov (United States)

    Ali, M. Hossain; Hossain, M. Jakir; Tariq, Abdullah Shams Bin

    2013-08-01

    The work of Jaffe, Jenkins and Kimchi [Phys. Rev. D 79, 065014 (2009)] is revisited to see if indeed the region of congeniality found in their analysis survives further restrictions from nucleosynthesis. It is observed that much of their congenial region disappears when imposing conditions required to produce the correct and required abundances of the primordial elements as well as ensure that stars can continue to burn hydrogen nuclei to form helium as the first step in forming heavier elements in stellar nucleosynthesis. The remaining region is a very narrow slit reduced in width from around 29 MeV found by Jaffe et al. to only about 2.2 MeV in the difference of the nucleon/quark masses. Further bounds on δmq/mq seem to reduce even this narrow slit to the physical point itself.

  11. CBC bound proteins and RNA fate

    DEFF Research Database (Denmark)

    Giacometti, Simone

    The cap-binding complex (CBC) plays a pivotal role in post-transcriptional processing events and orchestrates a variety of metabolic pathways, through association with different interaction partners. Two CBC sub-complexes, the CBC-ARS2-PHAX (CBCAP) and the CBC-nuclear exosome targeting (NEXT......) binding varies with the RNA maturation stage, with the CBC being highly enriched on mature mRNA, ARS2/PHAX/ZC3H18/MTR4 less so, and RMB7 preferentially bound to pre-mRNAs; (iv) MTR4 and RBM7 show different specificities, with RBM7 being highly enriched on introns and promoter upstream transcripts (PROMPTs......) complex (CBCN), were recently shown to target capped RNA either toward export or degradation, but the mechanisms by which they can discriminate between different RNA families and route them toward different metabolic pathways still remain unclear. A major question to be answered is how and when...

  12. Frenetic Bounds on the Entropy Production

    Science.gov (United States)

    Maes, Christian

    2017-10-01

    We give a systematic derivation of positive lower bounds for the expected entropy production (EP) rate in classical statistical mechanical systems obeying a dynamical large deviation principle. The logic is the same for the return to thermodynamic equilibrium as it is for steady nonequilibria working under the condition of local detailed balance. We recover there recently studied "uncertainty" relations for the EP, appearing in studies about the effectiveness of mesoscopic machines. In general our refinement of the positivity of the expected EP rate is obtained in terms of a positive and even function of the expected current(s) which measures the dynamical activity in the system, a time-symmetric estimate of the changes in the system's configuration. Also underdamped diffusions can be included in the analysis.

  13. Helioscope bounds on hidden sector photons

    Energy Technology Data Exchange (ETDEWEB)

    Redondo, J.

    2007-12-15

    The flux of hypothetical ''hidden photons'' from the Sun is computed under the assumption that they interact with normal matter only through kinetic mixing with the ordinary standard model photon. Requiring that the exotic luminosity is smaller than the standard photon luminosity provides limits for the mixing parameter down to {chi}

  14. Surface-bound states in nanodiamonds

    Science.gov (United States)

    Han, Peng; Antonov, Denis; Wrachtrup, Jörg; Bester, Gabriel

    2017-05-01

    We show via ab initio calculations and an electrostatic model that the notoriously low, but positive, electron affinity of bulk diamond becomes negative for hydrogen passivated nanodiamonds and argue that this peculiar situation (type-II offset with a vacuum level at nearly midgap) and the three further conditions: (i) a surface dipole with positive charge on the outside layer, (ii) a spherical symmetry, and (iii) a dielectric mismatch at the surface, results in the emergence of a peculiar type of surface state localized just outside the nanodiamond. These states are referred to as "surface-bound states" and have consequently a strong environmental sensitivity. These type of states should exist in any nanostructure with negative electron affinity. We further quantify the band offsets of different type of nanostructures as well as the exciton binding energy and contrast the results with results for "conventional" silicon quantum dots.

  15. Volume Stability of Bitumen Bound Building Blocks

    Directory of Open Access Journals (Sweden)

    Thanaya I.N.A.

    2010-01-01

    Full Text Available This paper covers results of laboratory investigations on the volume stability of masonry units incorporating waste materials bound with bitumen (Bitublocks, due to moisture adsorption, thermal exposure and vacuum saturation. The materials used were steel slag, crushed glass, coal fly ash, and 50 pen bitumen. The samples were produced in hot mix method, compacted, then exposed to moist and temperature. It was found that moisture adsorption from the environment caused the Bitublock to expand. The samples with less intense curing regime experienced lower expansion and became stable faster, and vice versa. Under thermal condition (at 70°C, the samples with less intense curing regime underwent higher expansion, and vice versa. They were also highly reversible. Their volume stability was found unique under water exposure. The expansion on first vacuum saturation cycle was irreversible, then largely reversible on the following cycles.

  16. Di- or polysulphide-bound biomarkers in sulphur-rich geomacromolecules as revealed by selective chemolysis

    NARCIS (Netherlands)

    Sinninghe Damsté, J.S.; Kohnen, M.E.L.; Kock-van Dalen, A.C.; Leeuw, J.W. de

    1991-01-01

    Three types of sulphur-rich, high-molecular-weight material in the alkylsulphide, the polar and the asphaltene fracions isolated from the bitumen of an immature bituminous shale from the Vena del Gesso basin (Italy) were desulphurised.

  17. General bounds in Hybrid Natural Inflation

    Science.gov (United States)

    Germán, Gabriel; Herrera-Aguilar, Alfredo; Hidalgo, Juan Carlos; Sussman, Roberto A.; Tapia, José

    2017-12-01

    Recently we have studied in great detail a model of Hybrid Natural Inflation (HNI) by constructing two simple effective field theories. These two versions of the model allow inflationary energy scales as small as the electroweak scale in one of them or as large as the Grand Unification scale in the other, therefore covering the whole range of possible energy scales. In any case the inflationary sector of the model is of the form V(phi)=V0 (1+a cos(phi/f)) where 0<= a<1 and the end of inflation is triggered by an independent waterfall field. One interesting characteristic of this model is that the slow-roll parameter epsilon(phi) is a non-monotonic function of phi presenting a maximum close to the inflection point of the potential. Because the scalar spectrum Script Ps(k) of density fluctuations when written in terms of the potential is inversely proportional to epsilon(phi) we find that Script Ps(k) presents a minimum at phimin. The origin of the HNI potential can be traced to a symmetry breaking phenomenon occurring at some energy scale f which gives rise to a (massless) Goldstone boson. Non-perturbative physics at some temperature Tbounded by the symmetry breaking scale, Δ≡ VH1/4 bounds for the inflationary energy scale Δ and for the tensor-to-scalar ratio r.

  18. Resignation Syndrome: Catatonia? Culture-Bound?

    Science.gov (United States)

    Sallin, Karl; Lagercrantz, Hugo; Evers, Kathinka; Engström, Ingemar; Hjern, Anders; Petrovic, Predrag

    2016-01-01

    Resignation syndrome (RS) designates a long-standing disorder predominately affecting psychologically traumatized children and adolescents in the midst of a strenuous and lengthy migration process. Typically a depressive onset is followed by gradual withdrawal progressing via stupor into a state that prompts tube feeding and is characterized by failure to respond even to painful stimuli. The patient is seemingly unconscious. Recovery ensues within months to years and is claimed to be dependent on the restoration of hope to the family. Descriptions of disorders resembling RS can be found in the literature and the condition is unlikely novel. Nevertheless, the magnitude and geographical distribution stand out. Several hundred cases have been reported exclusively in Sweden in the past decade prompting the Swedish National Board of Health and Welfare to recognize RS as a separate diagnostic entity. The currently prevailing stress hypothesis fails to account for the regional distribution and contributes little to treatment. Consequently, a re-evaluation of diagnostics and treatment is required. Psychogenic catatonia is proposed to supply the best fit with the clinical presentation. Treatment response, altered brain metabolism or preserved awareness would support this hypothesis. Epidemiological data suggests culture-bound beliefs and expectations to generate and direct symptom expression and we argue that culture-bound psychogenesis can accommodate the endemic distribution. Last, we review recent models of predictive coding indicating how expectation processes are crucially involved in the placebo and nocebo effect, delusions and conversion disorders. Building on this theoretical framework we propose a neurobiological model of RS in which the impact of overwhelming negative expectations are directly causative of the down-regulation of higher order and lower order behavioral systems in particularly vulnerable individuals. PMID:26858615

  19. Resignation syndrome: Catatonia? Culture-bound?

    Directory of Open Access Journals (Sweden)

    Karl eSallin

    2016-01-01

    Full Text Available Resignation syndrome (RS designates a long-standing disorder predominately affecting psychologically traumatised children and adolescents in the midst of a strenuous and lengthy migration process. Typically a depressive onset is followed by gradual withdrawal progressing via stupor into a state that prompts tube feeding and is characterised by failure to respond even to painful stimuli. The patient is seemingly unconscious. Recovery ensues within months to years and is claimed to be dependent on the restoration of hope to the family.Descriptions of disorders resembling RS can be found in the literature and the condition is unlikely novel. Nevertheless, the magnitude and geographical distribution stand out. Several hundred cases have been reported exclusively in Sweden in the past decade prompting the Swedish National Board of Health and Welfare to recognise RS as a separate diagnostic entity. The currently prevailing stress hypothesis fails to account for the regional distribution and contributes little to treatment. Consequently, a re-evaluation of diagnostics and treatment is required. Psychogenic catatonia is proposed to supply the best fit with the clinical presentation. Treatment response, altered brain metabolism or preserved awareness would support this hypothesis.Epidemiological data suggests culture-bound beliefs and expectations to generate and direct symptom expression and we argue that culture-bound psychogenesis can accommodate the endemic distribution.Last, we review recent models of predictive coding indicating how expectation processes are crucially involved in the placebo and nocebo effect, delusions and conversion disorders. Building on this theoretical framework we propose a neurobiological model of RS in which the impact of overwhelming negative expectations are directly causative of the down-regulation of higher order and lower order behavioural systems in particularly vulnerable individuals.

  20. Resignation Syndrome: Catatonia? Culture-Bound?

    Science.gov (United States)

    Sallin, Karl; Lagercrantz, Hugo; Evers, Kathinka; Engström, Ingemar; Hjern, Anders; Petrovic, Predrag

    2016-01-01

    Resignation syndrome (RS) designates a long-standing disorder predominately affecting psychologically traumatized children and adolescents in the midst of a strenuous and lengthy migration process. Typically a depressive onset is followed by gradual withdrawal progressing via stupor into a state that prompts tube feeding and is characterized by failure to respond even to painful stimuli. The patient is seemingly unconscious. Recovery ensues within months to years and is claimed to be dependent on the restoration of hope to the family. Descriptions of disorders resembling RS can be found in the literature and the condition is unlikely novel. Nevertheless, the magnitude and geographical distribution stand out. Several hundred cases have been reported exclusively in Sweden in the past decade prompting the Swedish National Board of Health and Welfare to recognize RS as a separate diagnostic entity. The currently prevailing stress hypothesis fails to account for the regional distribution and contributes little to treatment. Consequently, a re-evaluation of diagnostics and treatment is required. Psychogenic catatonia is proposed to supply the best fit with the clinical presentation. Treatment response, altered brain metabolism or preserved awareness would support this hypothesis. Epidemiological data suggests culture-bound beliefs and expectations to generate and direct symptom expression and we argue that culture-bound psychogenesis can accommodate the endemic distribution. Last, we review recent models of predictive coding indicating how expectation processes are crucially involved in the placebo and nocebo effect, delusions and conversion disorders. Building on this theoretical framework we propose a neurobiological model of RS in which the impact of overwhelming negative expectations are directly causative of the down-regulation of higher order and lower order behavioral systems in particularly vulnerable individuals.

  1. Structure of the δ-opioid receptor bound to naltrindole.

    Science.gov (United States)

    Granier, Sébastien; Manglik, Aashish; Kruse, Andrew C; Kobilka, Tong Sun; Thian, Foon Sun; Weis, William I; Kobilka, Brian K

    2012-05-16

    The opioid receptor family comprises three members, the µ-, δ- and κ-opioid receptors, which respond to classical opioid alkaloids such as morphine and heroin as well as to endogenous peptide ligands like endorphins. They belong to the G-protein-coupled receptor (GPCR) superfamily, and are excellent therapeutic targets for pain control. The δ-opioid receptor (δ-OR) has a role in analgesia, as well as in other neurological functions that remain poorly understood. The structures of the µ-OR and κ-OR have recently been solved. Here we report the crystal structure of the mouse δ-OR, bound to the subtype-selective antagonist naltrindole. Together with the structures of the µ-OR and κ-OR, the δ-OR structure provides insights into conserved elements of opioid ligand recognition while also revealing structural features associated with ligand-subtype selectivity. The binding pocket of opioid receptors can be divided into two distinct regions. Whereas the lower part of this pocket is highly conserved among opioid receptors, the upper part contains divergent residues that confer subtype selectivity. This provides a structural explanation and validation for the 'message-address' model of opioid receptor pharmacology, in which distinct 'message' (efficacy) and 'address' (selectivity) determinants are contained within a single ligand. Comparison of the address region of the δ-OR with other GPCRs reveals that this structural organization may be a more general phenomenon, extending to other GPCR families as well.

  2. Accounting for Epistemic and Aleatory Uncertainty in Early System Design Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The proposed work extends Probability Bounds Analysis to model epistemic and aleatory uncertainty during early design of engineered systems in an Integrated...

  3. Accounting for Epistemic and Aleatory Uncertainty in Early System Design Project

    Data.gov (United States)

    National Aeronautics and Space Administration — This project extends Probability Bounds Analysis to model epistemic and aleatory uncertainty during early design of engineered systems in an Integrated Concurrent...

  4. Bounded Semantics of CTL and SAT-Based Verification

    Science.gov (United States)

    Zhang, Wenhui

    Bounded model checking has been proposed as a complementary approach to BDD based symbolic model checking for combating the state explosion problem, esp. for efficient error detection. This has led to a lot of successful work with respect to error detection in the checking of LTL, ACTL (the universal fragment of CTL) and ACTL* properties by satisfiability testing. The use of bounded model checking for verification (in contrast to error detection) of LTL and ACTL properties has later also been studied. This paper studies the potentials and limitations of bounded model checking for the verification of CTL and CTL* formulas. On the theoretical side, we first provide a framework for discussion of bounded semantics, which serves as the basis for bounded model checking, then extend the bounded semantics of ACTL to a bounded semantics of CTL, and discuss the limitation of developing such a bounded semantics for CTL*. On the practical side, a deduction of a SAT-based bounded model checking approach for ACTL properties from the bounded semantics of CTL is demonstrated, and a comparison of such an approach with BDD-based model checking is presented based on experimental results.

  5. Stimulation of Tetrabromobisphenol A Binding to Soil Humic Substances by Birnessite and the Chemical Structure of the Bound Residues.

    Science.gov (United States)

    Tong, Fei; Gu, Xueyuan; Gu, Cheng; Xie, Jinyu; Xie, Xianchuan; Jiang, Bingqi; Wang, Yongfeng; Ertunc, Tanya; Schäffer, Andreas; Ji, Rong

    2016-06-21

    Studies have shown the main fate of the flame retardant tetrabromobisphenol A (TBBPA) in soils is the formation of bound residues, and mechanisms on it are less-understood. This study investigated the effect of birnessite (δ-MnO2), a naturally occurring oxidant in soils, on the formation of bound residues. (14)C-labeled TBBPA was used to investigate the pH dependency of TBBPA bound-residue formation to two soil humic acids (HAs), Elliott soil HA and Steinkreuz soil HA, in the presence of δ-MnO2. The binding of TBBPA and its transformation products to both HAs was markedly increased (3- to 17-fold) at all pH values in the presence of δ-MnO2. More bound residues were formed with the more aromatic Elliott soil HA than with Steinkreuz soil HA. Gel-permeation chromatography revealed a uniform distribution of the bound residues within Steinkreuz soil HA and a nonuniform distribution within Elliott soil HA. (13)C NMR spectroscopy of (13)C-TBBPA residues bound to (13)C-depleted HA suggested that in the presence of δ-MnO2, binding occurred via ester and ether and other types of covalent bonds besides HA sequestration. The insights gained in this study contribute to an understanding of the formation of TBBPA bound residues facilitated by δ-MnO2.

  6. Behaviour of Trolox with macromolecule-bound antioxidants in aqueous medium: Inhibition of auto-regeneration mechanism.

    Science.gov (United States)

    Çelik, Ecem Evrim; Rubio, Jose Manuel Amigo; Gökmen, Vural

    2018-03-15

    This work aimed at investigating the behaviour of Trolox, vitamin E analogue, in presence of macromolecule-bound antioxidants in aqueous radical medium. Three main groups of macromolecule-bound antioxidants were assayed: dietary fiber (DF), protein and lipid-bound antioxidants, represented by whole wheat, soybean and olive oil products, respectively. Experimental studies were carried out in aqueous ABTS (2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid)) radical medium. Trolox and macromolecule-bound antioxidants were added to radical separately and together in different concentrations. Antioxidant capacities were determined using QUENCHER procedure. pH of radical media was altered for DF and protein-bound antioxidant studies to examine its effect. Chemometric tools were used for experimental design and multivariate data analysis. Results revealed antagonistic interactions for Trolox with all macromolecule-bound antioxidants. The reason behind this antagonism was investigated through oxidation reactions of Trolox via mass spectrometry analysis. Consequently, a proof was obtained for inhibitory effect of bound-antioxidants on auto-regeneration reactions of Trolox. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. The neural basis of bounded rational behavior

    Directory of Open Access Journals (Sweden)

    Coricelli, Giorgio

    2012-03-01

    Full Text Available Bounded rational behaviour is commonly observed in experimental games and in real life situations. Neuroeconomics can help to understand the mental processing underlying bounded rationality and out-of-equilibrium behaviour. Here we report results from recent studies on the neural basis of limited steps of reasoning in a competitive setting —the beauty contest game. We use functional magnetic resonance imaging (fMRI to study the neural correlates of human mental processes in strategic games. We apply a cognitive hierarchy model to classify subject’s choices in the experimental game according to the degree of strategic reasoning so that we can identify the neural substrates of different levels of strategizing. We found a correlation between levels of strategic reasoning and activity in a neural network related to mentalizing, i.e. the ability to think about other’s thoughts and mental states. Moreover, brain data showed how complex cognitive processes subserve the higher level of reasoning about others. We describe how a cognitive hierarchy model fits both behavioural and brain data.

    La racionalidad limitada es un fenómeno observado de manera frecuente tanto en juegos experimentales como en situaciones cotidianas. La Neuroeconomía puede mejorar la comprensión de los procesos mentales que caracterizan la racionalidad limitada; en paralelo nos puede ayudar a comprender comportamientos que violan el equilibrio. Nuestro trabajo presenta resultados recientes sobre la bases neuronales del razonamiento estratégico (y sus límite en juegos competitivos —como el juego del “beauty contest”. Estudiamos las bases neuronales del comportamiento estratégico en juegos con interacción entre sujetos usando resonancia magnética funcional (fMRI. Las decisiones de los participantes se clasifican acorde al grado de razonamiento estratégico: el llamado modelo de Jerarquías Cognitivas. Los resultados muestran una correlación entre niveles de

  8. Nutrition Risk in Home-Bound Older Adults: Using Dietician-Trained and Supervised Nutrition Volunteers for Screening and Intervention

    Science.gov (United States)

    Laforest, Sophie; Goldin, Benita; Nour, Kareen; Roy, Marie-Andree; Payette, Helene

    2007-01-01

    Nutrition screening and early intervention in home-bound older adults are key to preventing unfavourable health outcomes and functional decline. This pilot study's objectives were (a) to test the reliability of the Elderly Nutrition Screening Tool (ENS [C]) when administered by dietician-trained and supervised nutrition volunteers, and (b) to…

  9. Bounds on Threshold of Regular Random $k$-SAT

    CERN Document Server

    Rathi, Vishwambhar; Rasmussen, Lars; Skoglund, Mikael

    2010-01-01

    We consider the regular model of formula generation in conjunctive normal form (CNF) introduced by Boufkhad et. al. We derive an upper bound on the satisfiability threshold and NAE-satisfiability threshold for regular random $k$-SAT for any $k \\geq 3$. We show that these bounds matches with the corresponding bound for the uniform model of formula generation. We derive lower bound on the threshold by applying the second moment method to the number of satisfying assignments. For large $k$, we note that the obtained lower bounds on the threshold of a regular random formula converges to the lower bound obtained for the uniform model. Thus, we answer the question posed in \\cite{AcM06} regarding the performance of the second moment method for regular random formulas.

  10. Nonequilibrium quantum bounds to Landauer's principle: Tightness and effectiveness

    Science.gov (United States)

    Campbell, Steve; Guarnieri, Giacomo; Paternostro, Mauro; Vacchini, Bassano

    2017-10-01

    We assess two different nonequilibrium quantum Landauer bounds: the traditional approach based on the change in entropy, referred to as the "entropic bound," and one based on the details of the dynamical map, referred to as the "thermodynamic bound." By first restricting to a simple exactly solvable model of a single two-level system coupled to a finite-dimensional thermal environment and by exploiting an excitation-preserving interaction, we establish the dominant role played by the population terms in dictating the tightness of these bounds with respect to the dissipated heat and clearly establish that coherences only affect the entropic bound. Furthermore, we show that sharp boundaries between the relative performance of the two quantities emerge and find that there are clear instances where both approaches return a bound weaker than Clausius' statement of the second law, rendering them ineffective. Finally, we show that our results extend to generic interaction terms.

  11. Persistence-Based Branch Misprediction Bounds for WCET Analysis

    DEFF Research Database (Denmark)

    Puffitsch, Wolfgang

    2015-01-01

    Branch prediction is an important feature of pipelined processors to achieve high performance. However, it can lead to overly pessimistic worst-case execution time (WCET) bounds when being modeled too conservatively. This paper presents bounds on the number of branch mispredictions for local...... linear programming formulations of the WCET problem. An evaluation on a number of benchmarks shows that with these bounds, dynamic branch prediction does not necessarily lead to higher WCET bounds than static prediction schemes....... dynamic branch predictors. To handle interferences between branch instructions we use the notion of persistence, a concept that is also found in cache analyses. The bounds apply to branches in general, not only to branches that close a loop. Furthermore, the bounds can be easily integrated into integer...

  12. Nuclear structure of bound states of asymmetric dark matter

    Science.gov (United States)

    Gresham, Moira I.; Lou, Hou Keong; Zurek, Kathryn M.

    2017-11-01

    Models of asymmetric dark matter (ADM) with a sufficiently attractive and long-range force give rise to stable bound objects, analogous to nuclei in the Standard Model, called nuggets. We study the properties of these nuggets and compute their profiles and binding energies. Our approach, applicable to both elementary and composite fermionic ADM, utilizes relativistic mean field theory, and allows a more systematic computation of nugget properties, over a wider range of sizes and force mediator masses, compared to previous literature. We identify three separate regimes of nugget property behavior corresponding to (1) nonrelativistic and (2) relativistic constituents in a Coulomb-like limit, and (3) saturation in an anti-Coulomb limit when the nuggets are large compared to the force range. We provide analytical descriptions for nuggets in each regime. Through numerical calculations, we are able to confirm our analytic descriptions and also obtain smooth transitions for the nugget profiles between all three regimes. We also find that over a wide range of parameter space, the binding energy in the saturation limit is an O (1 ) fraction of the constituent's mass, significantly larger than expectations in the nonrelativistic case. In a companion paper, we apply our results to the synthesis of ADM nuggets in the early Universe.

  13. CMB bounds on disk-accreting massive primordial black holes

    Science.gov (United States)

    Poulin, Vivian; Serpico, Pasquale D.; Calore, Francesca; Clesse, Sébastien; Kohri, Kazunori

    2017-10-01

    Stellar-mass primordial black holes (PBH) have been recently reconsidered as a dark matter (DM) candidate after the aLIGO discovery of several binary black hole (BH) mergers with masses of tens of M⊙ . Matter accretion on such massive objects leads to the emission of high-energy photons, capable of altering the ionization and thermal history of the universe. This, in turn, affects the statistical properties of the cosmic microwave background (CMB) anisotropies. Previous analyses have assumed spherical accretion. We argue that this approximation likely breaks down and that an accretion disk should form in the dark ages. Using the most up-to-date tools to compute the energy deposition in the medium, we derive constraints on the fraction of DM in PBH. Provided that disks form early on, even under conservative assumptions for accretion, these constraints exclude a monochromatic distribution of PBH with masses above ˜2 M⊙ as the dominant form of DM. The bound on the median PBH mass gets more stringent if a broad, log-normal mass function is considered. A deepened understanding of nonlinear clustering properties and BH accretion disk physics would permit an improved treatment and possibly lead to more stringent constraints.

  14. Cardiorenal syndrome: role of protein-bound uremic toxins.

    Science.gov (United States)

    Lekawanvijit, Suree; Krum, Henry

    2015-03-01

    Renal impairment is a strong independent risk factor associated with poor prognosis in cardiovascular disease patients. Renal dysfunction is likely contributed by progressive renal structural damage. Accurate detection of kidney injury in a timely manner as well as increased knowledge of the pathophysiology and mechanisms underlying this injury is of great importance in developing therapeutic interventions for combating renal complications at an early stage. Regarding the role of uremic solutes in the pathophysiology of cardiorenal syndrome, a number of further studies are warranted. There may be uremic solutes discovered from proteomics not yet chemically identified or tested for biological activity. Beyond Protein-bound uremic toxins, uremic solutes in other classes (according to the European Uraemic Toxin Work Group classification) may have adverse cardiorenal effects. Although most small water-soluble solutes and middle molecules can be satisfactorily removed by either conventional or newly developed dialysis strategies, targeting uremic toxins with cardiorenal toxicity at predialysis stage of chronic kidney disease may retard or prevent incident dialysis as well as the initiation/progression of cardiorenal syndrome. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  15. Interaction of solitons and the formation of bound states in the generalized Lugiato-Lefever equation

    Science.gov (United States)

    Parra-Rivas, Pedro; Gomila, Damia; Colet, Pere; Gelens, Lendert

    2017-07-01

    Bound states, also called soliton molecules, can form as a result of the interaction between individual solitons. This interaction is mediated through the tails of each soliton that overlap with one another. When such soliton tails have spatial oscillations, locking or pinning between two solitons can occur at fixed distances related with the wavelength of these oscillations, thus forming a bound state. In this work, we study the formation and stability of various types of bound states in the Lugiato-Lefever equation by computing their interaction potential and by analyzing the properties of the oscillatory tails. Moreover, we study the effect of higher order dispersion and noise in the pump intensity on the dynamics of bound states. In doing so, we reveal that perturbations to the Lugiato-Lefever equation that maintain reversibility, such as fourth order dispersion, lead to bound states that tend to separate from one another in time when noise is added. This separation force is determined by the shape of the envelope of the interaction potential, as well as an additional Brownian ratchet effect. In systems with broken reversibility, such as third order dispersion, this ratchet effect continues to push solitons within a bound state apart. However, the force generated by the envelope of the potential is now such that it pushes the solitons towards each other, leading to a null net drift of the solitons. Contribution to the Topical Issue "Theory and Applications of the Lugiato-Lefever Equation", edited by Yanne K. Chembo, Damia Gomila, Mustapha Tlidi, Curtis R. Menyuk.

  16. Heart-bound adiponectin, not serum adiponectin, inversely correlates with cardiac hypertrophy in stroke-prone spontaneously hypertensive rats.

    Science.gov (United States)

    Inoue, Takao; Takemori, Kumiko; Mizuguchi, Nobuyuki; Kimura, Masatomo; Chikugo, Takaaki; Hagiyama, Man; Yoneshige, Azusa; Mori, Tatsufumi; Maenishi, Osamu; Kometani, Takashi; Itoh, Tatsuki; Satou, Takao; Ito, Akihiko

    2017-11-01

    . No significant difference in heart-bound adiponectin among WKYs and SHRs (C and B2) was detected, indicating that heart-bound adiponectin is not related to hypertension. In addition, differences in heart-bound adiponectin did not affect AMP-activated protein kinase in the traditional adiponectin activation cascade. Histopathological analysis revealed that heart-bound adiponectin was inversely correlated with cardiomyocyte hypertrophy and left ventricular wall thickness and, in part, with cardiac fibrosis. These results suggest that the decreased level of heart-bound adiponectin in SHRSPs is more related to their cardiac hypertrophy than circulating adiponectin. © 2017 The Authors. Experimental Physiology © 2017 The Physiological Society.

  17. Upper bounds on minimum cardinality of exact and approximate reducts

    KAUST Repository

    Chikalov, Igor

    2010-01-01

    In the paper, we consider the notions of exact and approximate decision reducts for binary decision tables. We present upper bounds on minimum cardinality of exact and approximate reducts depending on the number of rows (objects) in the decision table. We show that the bound for exact reducts is unimprovable in the general case, and the bound for approximate reducts is almost unimprovable in the general case. © 2010 Springer-Verlag Berlin Heidelberg.

  18. AGGREGATE IMPORT DEMAND BEHAVIOR FOR INDONESIA: EVIDENCE FROM THE BOUNDS TESTING APPROACH

    OpenAIRE

    Tuck Cheong Tang

    2002-01-01

    This paper empirically re-estimates the long-run relationship between Indonesian aggregate import demand and its determinants; namely, real income and relative import prices. In contrast to previous studies (Reinhart, 1995; and Senhadji, 1998), the result of the bounds test (Pesaran et al., 2001) reveals that import volume, real income and relative import prices are cointegrated. This is an important finding from the viewpoint of the Indonesian economic policy. The estimated long-run elastici...

  19. A simple but usually fast branch-and-bound algorithm for the capacitated facility location problem

    DEFF Research Database (Denmark)

    Görtz, Simon; Klose, Andreas

    2012-01-01

    This paper presents a simple branch-and-bound method based on Lagrangean relaxation and subgradient optimization for solving large instances of the capacitated facility location problem (CFLP) to optimality. To guess a primal solution to the Lagrangean dual, we average solutions to the Lagrangean...... subproblem. Branching decisions are then based on this estimated (fractional) primal solution. Extensive numerical results reveal that the method is much faster and more robust than other state-of-the-art methods for solving the CFLP exactly....

  20. NITRO MUSK BOUND TO CARP HEMOGLOBIN ...

    Science.gov (United States)

    Nitroaromatic compounds including synthetic nitro musks are important raw materials and intermediates in the synthesis of explosives, dyes, and pesticides, pharmaceutical and personal care-products (PPCPs). The nitro musks such as musk xylene (MX) and musk ketone (MK) are extensively used as fragrance ingredients in PPCPs and other commercial toiletries. Identification and quantification of a bound 4-amino-MX (4-AMX) metabolite as well as a 2- amino-MK (2-AMK) metabolite were carried out by gas chromatography-mass spectrometry' (GC/MS), with selected ion monitoring (SIM) in both the electron ionization (ElMS) and electron capture (EC) negative ion chemical ionization (NICIMS) modes. Detection of 4-AMX and 2-AMK occurred after the cysteine adducts in carp hemoglobin, derived from the nitroso metabolites, were released by alkaline hydrolysis. The released metabolites were extracted into n-hexane. The extract was preconcentrated by evaporation, and analyzed by GC-SIM-MS. A comparison between the El and EC approaches was made. EC NICIMS detected both metabolites whereas only 4-AMX was detected by ElMS. The EC NICIMS approach exhibited fewer matrix responses and provided a lower detection limit. Quantitation in both approaches was based on internal standard and a calibration plot. The research focused on in the subtasks is the development and application of state-of the-art technologies to meet the needs of the public, Office of Water, and ORD in the area of Water Q

  1. Organically bound tritium analysis in environmental samples

    Energy Technology Data Exchange (ETDEWEB)

    Baglan, N. [CEA/DAM/DIF, Arpajon (France); Kim, S.B. [AECL, Chalk River Laboratories, Chalk River, ON (Canada); Cossonnet, C. [IRSN/PRP-ENV/STEME/LMRE, Orsay (France); Croudace, I.W.; Warwick, P.E. [GAU-Radioanalytical, University of Southampton, Southampton (United Kingdom); Fournier, M. [IRSN/DG/DMQ, Fontenay-aux-Roses (France); Galeriu, D. [IFIN-HH, Horia-Hulubei, Inst. Phys. and Nucl. Eng., Bucharest (Romania); Momoshima, N. [Kyushu University, Radioisotope Ctr., Fukuoka (Japan); Ansoborlo, E. [CEA/DEN/DRCP/CETAMA, Bagnols-sur-Ceze (France)

    2015-03-15

    Organically bound tritium (OBT) has become of increased interest within the last decade, with a focus on its behaviour and also its analysis, which are important to assess tritium distribution in the environment. In contrast, there are no certified reference materials and no standard analytical method through the international organization related to OBT. In order to resolve this issue, an OBT international working group was created in May 2012. Over 20 labs from around the world participated and submitted their results for the first intercomparison exercise results on potato (Sep 2013). The samples, specially-prepared potatoes, were provided in March 2013 to each participant. Technical information and results from this first exercise are discussed here for all the labs which have realised the five replicates necessary to allow a reliable statistical treatment. The results are encouraging as the increased number of participating labs did not degrade the observed dispersion of the results for a similar activity level. Therefore, the results do not seem to depend on the analytical procedure used. From this work an optimised procedure can start to be developed to deal with OBT analysis and will guide subsequent planned OBT trials by the international group.

  2. Dynamics of water bound to crystalline cellulose

    Energy Technology Data Exchange (ETDEWEB)

    O’Neill, Hugh; Pingali, Sai Venkatesh; Petridis, Loukas; He, Junhong; Mamontov, Eugene; Hong, Liang; Urban, Volker; Evans, Barbara; Langan, Paul; Smith, Jeremy C.; Davison, Brian H.

    2017-09-19

    Interactions of water with cellulose are of both fundamental and technological importance. Here, we characterize the properties of water associated with cellulose using deuterium labeling, neutron scattering and molecular dynamics simulation. Quasi-elastic neutron scattering provided quantitative details about the dynamical relaxation processes that occur and was supported by structural characterization using small-angle neutron scattering and X-ray diffraction. We can unambiguously detect two populations of water associated with cellulose. The first is “non-freezing bound” water that gradually becomes mobile with increasing temperature and can be related to surface water. The second population is consistent with confined water that abruptly becomes mobile at ~260 K, and can be attributed to water that accumulates in the narrow spaces between the microfibrils. Quantitative analysis of the QENS data showed that, at 250 K, the water diffusion coefficient was 0.85 ± 0.04 × 10-10 m2sec-1 and increased to 1.77 ± 0.09 × 10-10 m2sec-1 at 265 K. MD simulations are in excellent agreement with the experiments and support the interpretation that water associated with cellulose exists in two dynamical populations. Our results provide clarity to previous work investigating the states of bound water and provide a new approach for probing water interactions with lignocellulose materials.

  3. Neutron bound beta-decay: BOB

    Science.gov (United States)

    McAndrew, Josephine; Paul, Stephan; Emmerich, Ralf; Engels, Ralf; Fierlinger, Peter; Gabriel, Mirko; Gutsmiedl, Erwin; Mellenthin, Johannes; Schön, Johannes; Schott, Wolfgang; Ulrich, Andreas; Grüenauer, Florian; Röhrmoser, Anton

    2012-05-01

    An experiment to observe the bound beta-decay (BOB) of the free neutron into a hydrogen atom and an electron anti-neutrino is described. The hyperfine spin state population of the monoenergetic hydrogen atom yields the neutrino left-handedness or possible right-handed admixture as well as possible small scalar and tensor contributions to the weak force. The BOB H(2s) hyperfine states can be separated with a Lamb-Shift Spin Filter. These monoenergetic H(2s) atoms are ionised into H- by charge exchanging within an argon cell. These ions are then separated using an adaptation of a MAC-E Filter. A first experiment is proposed at the FRMII high thermal-neutron flux beam reactor SR6 through-going beam tube, where we will seek to observe this rare neutron decay-mode for the first time and determine the branching ratio. After successful completion, the hyperfine spin state population will be determined, possibly at the ILL high-flux beam reactor through-going beam tube H6-H7, where the thermal neutron flux is a factor of four larger.

  4. Bound state in positron scattering by allene

    Science.gov (United States)

    Barbosa, Alessandra Souza; Sanchez, Sergio d'Almeida; Bettega, Márcio H. F.

    2017-12-01

    We report integral and differential cross sections for positron collisions with allene, calculated with the Schwinger multichannel method. The cross sections were computed in the static-polarization approximation for energies up to 7 eV. We have tested a series of single-particle basis sets and different polarization schemes to improve the description of low-energy positron scattering by the allene molecule. We have found that the use of extra centers with no net charge with additional single-particle s - and p -type functions centered at them are essential in order to accurately reproduce the polarization potential and, hence, obtain proper scattering cross sections. The choice of the allene molecule was due to the fact that it is a highly symmetric molecule with no permanent dipole moment and would allow several different calculations. Our cross sections are compared to the available experimental data for the total cross section with a reasonable agreement after correcting their results due to the low angular discrimination of their apparatus. Also, a virtual state was observed in the integral cross section that became a bound state when the description of the polarization potential is improved. We also observed a Ramsauer-Townsend minimum in the cross section whose location varies from 2.7 to 3.4 eV, depending on the polarization scheme used in the calculations.

  5. Classical Physics and the Bounds of Quantum Correlations.

    Science.gov (United States)

    Frustaglia, Diego; Baltanás, José P; Velázquez-Ahumada, María C; Fernández-Prieto, Armando; Lujambio, Aintzane; Losada, Vicente; Freire, Manuel J; Cabello, Adán

    2016-06-24

    A unifying principle explaining the numerical bounds of quantum correlations remains elusive, despite the efforts devoted to identifying it. Here, we show that these bounds are indeed not exclusive to quantum theory: for any abstract correlation scenario with compatible measurements, models based on classical waves produce probability distributions indistinguishable from those of quantum theory and, therefore, share the same bounds. We demonstrate this finding by implementing classical microwaves that propagate along meter-size transmission-line circuits and reproduce the probabilities of three emblematic quantum experiments. Our results show that the "quantum" bounds would also occur in a classical universe without quanta. The implications of this observation are discussed.

  6. Tight lower bound for percolation threshold on an infinite graph.

    Science.gov (United States)

    Hamilton, Kathleen E; Pryadko, Leonid P

    2014-11-14

    We construct a tight lower bound for the site percolation threshold on an infinite graph, which becomes exact for an infinite tree. The bound is given by the inverse of the maximal eigenvalue of the Hashimoto matrix used to count nonbacktracking walks on the original graph. Our bound always exceeds the inverse spectral radius of the graph's adjacency matrix, and it is also generally tighter than the existing bound in terms of the maximum degree. We give a constructive proof for existence of such an eigenvalue in the case of a connected infinite quasitransitive graph, a graph-theoretic analog of a translationally invariant system.

  7. What Information Theory Says about Bounded Rational Best Response

    Science.gov (United States)

    Wolpert, David H.

    2005-01-01

    Probability Collectives (PC) provides the information-theoretic extension of conventional full-rationality game theory to bounded rational games. Here an explicit solution to the equations giving the bounded rationality equilibrium of a game is presented. Then PC is used to investigate games in which the players use bounded rational best-response strategies. Next it is shown that in the continuum-time limit, bounded rational best response games result in a variant of the replicator dynamics of evolutionary game theory. It is then shown that for team (shared-payoff) games, this variant of replicator dynamics is identical to Newton-Raphson iterative optimization of the shared utility function.

  8. Upper bounds on quantum uncertainty products and complexity measures

    Energy Technology Data Exchange (ETDEWEB)

    Guerrero, Angel; Sanchez-Moreno, Pablo; Dehesa, Jesus S. [Department of Atomic, Molecular and Nuclear Physics, University of Granada, Granada (Spain); Department of Applied Mathematics, University of Granada, Granada (Spain) and Institute Carlos I for Computational and Theoretical Physics, University of Granada, Granada (Spain); Department of Atomic, Molecular and Nuclear Physics, University of Granada, Granada (Spain); Institute Carlos I for Computational and Theoretical Physics, University of Granada, Granada (Spain)

    2011-10-15

    The position-momentum Shannon and Renyi uncertainty products of general quantum systems are shown to be bounded not only from below (through the known uncertainty relations), but also from above in terms of the Heisenberg-Kennard product . Moreover, the Cramer-Rao, Fisher-Shannon, and Lopez-Ruiz, Mancini, and Calbet shape measures of complexity (whose lower bounds have been recently found) are also bounded from above. The improvement of these bounds for systems subject to spherically symmetric potentials is also explicitly given. Finally, applications to hydrogenic and oscillator-like systems are done.

  9. Is regional species diversity bounded or unbounded?

    Science.gov (United States)

    Cornell, Howard V

    2013-02-01

    Two conflicting hypotheses have been proposed to explain large-scale species diversity patterns and dynamics. The unbounded hypothesis proposes that regional diversity depends only on time and diversification rate and increases without limit. The bounded hypothesis proposes that ecological constraints place upper limits on regional diversity and that diversity is usually close to its limit. Recent evidence from the fossil record, phylogenetic analysis, biogeography, and phenotypic disparity during lineage diversification suggests that diversity is constrained by ecological processes but that it is rarely asymptotic. Niche space is often unfilled or can be more finely subdivided and still permit coexistence, and new niche space is often created before ecological limits are reached. Damped increases in diversity over time are the prevalent pattern, suggesting the need for a new 'damped increase hypothesis'. The damped increase hypothesis predicts that diversity generally increases through time but that its rate of increase is often slowed by ecological constraints. However, slowing due to niche limitation must be distinguished from other possible mechanisms creating similar patterns. These include sampling artifacts, the inability to detect extinctions or declines in clade diversity with some methods, the distorting effects of correlated speciation-extinction dynamics, the likelihood that opportunities for allopatric speciation will vary in space and time, and the role of undetected natural enemies in reducing host ranges and thus slowing speciation rates. The taxonomic scope of regional diversity studies must be broadened to include all ecologically similar species so that ecological constraints may be accurately inferred. The damped increase hypothesis suggests that information on evolutionary processes such as time-for-speciation and intrinsic diversification rates as well as ecological factors will be required to explain why regional diversity varies among times

  10. Structure Biology of Membrane Bound Enzymes

    Energy Technology Data Exchange (ETDEWEB)

    Fu, Dax [Johns Hopkins Univ., Baltimore, MD (United States). School of Medicine. Dept. of Physiology

    2016-11-30

    The overall goal of the proposed research is to understand the membrane-associated active processes catalyzed by an alkane $\\square$-hydroxylase (AlkB) from eubacterium Pseudomonase oleovorans. AlkB performs oxygenation of unactivated hydrocarbons found in crude oils. The enzymatic reaction involves energy-demanding steps in the membrane with the uses of structurally unknown metal active sites featuring a diiron [FeFe] center. At present, a critical barrier to understanding the membrane-associated reaction mechanism is the lack of structural information. The structural biology efforts have been challenged by technical difficulties commonly encountered in crystallization and structural determination of membrane proteins. The specific aims of the current budget cycle are to crystalize AlkB and initiate X-ray analysis to set the stage for structural determination. The long-term goals of our structural biology efforts are to provide an atomic description of AlkB structure, and to uncover the mechanisms of selective modification of hydrocarbons. The structural information will help elucidating how the unactivated C-H bonds of saturated hydrocarbons are oxidized to initiate biodegradation and biotransformation processes. The knowledge gained will be fundamental to biotechnological applications to biofuel transformation of non-edible oil feedstock. Renewable biodiesel is a promising energy carry that can be used to reduce fossil fuel dependency. The proposed research capitalizes on prior BES-supported efforts on over-expression and purification of AlkB to explore the inner workings of a bioenergy-relevant membrane-bound enzyme.

  11. Coarrays, MUSIC, and the Cramér-Rao Bound

    Science.gov (United States)

    Wang, Mianzhi; Nehorai, Arye

    2017-02-01

    Sparse linear arrays, such as co-prime arrays and nested arrays, have the attractive capability of providing enhanced degrees of freedom. By exploiting the coarray structure, an augmented sample covariance matrix can be constructed and MUSIC (MUtiple SIgnal Classification) can be applied to identify more sources than the number of sensors. While such a MUSIC algorithm works quite well, its performance has not been theoretically analyzed. In this paper, we derive a simplified asymptotic mean square error (MSE) expression for the MUSIC algorithm applied to the coarray model, which is applicable even if the source number exceeds the sensor number. We show that the directly augmented sample covariance matrix and the spatial smoothed sample covariance matrix yield the same asymptotic MSE for MUSIC. We also show that when there are more sources than the number of sensors, the MSE converges to a positive value instead of zero when the signal-to-noise ratio (SNR) goes to infinity. This finding explains the "saturation" behavior of the coarray-based MUSIC algorithms in the high SNR region observed in previous studies. Finally, we derive the Cram\\'er-Rao bound (CRB) for sparse linear arrays, and conduct a numerical study of the statistical efficiency of the coarray-based estimator. Experimental results verify theoretical derivations and reveal the complex efficiency pattern of coarray-based MUSIC algorithms.

  12. Structure of Plasmodium falciparum dihydroorotate dehydrogenase with a bound inhibitor.

    Science.gov (United States)

    Hurt, Darrell E; Widom, Joanne; Clardy, Jon

    2006-03-01

    Membrane-associated dihydroorotate dehydrogenase (DHODH) is an antimalarial therapeutic target without an effective inhibitor. Studies on human DHODH (HsDHODH) led to a structural mechanistic model in which respiratory quinones bind in a tunnel formed by the highly variable N-terminus that leads to the flavin mononucleotide-binding site. The therapeutic agents leflunomide (Arava) and brequinar sodium inhibit HsDHODH by binding in this tunnel. Plasmodium falciparum DHODH (PfDHODH) and HsDHODH have markedly different sensitivities to the two drugs. To understand the structural basis of this differential sensitivity and begin a structure-based drug-design cycle for PfDHODH inhibitors, the three-dimensional structure (2.4 Angstroms, R = 20.1%) of PfDHODH bound to the active metabolite of leflunomide was determined by X-ray crystallography. Comparison of the structures of HsDHODH and PfDHODH reveals a completely different binding mode for the same inhibitor in these two catalytically identical enzymes and explains the previously observed species-specific preferential binding. Because no effective inhibitors have been described for PfDHODH, this structure provides critical insight for the design of potential antimalarials.

  13. Dynamic nuclear polarization of nucleic acid with endogenously bound manganese

    Energy Technology Data Exchange (ETDEWEB)

    Wenk, Patricia [University of Tübingen, Werner Siemens Imaging Center and Department of Preclinical Imaging and Radiopharmacy (Germany); Kaushik, Monu; Richter, Diane [Goethe University, Institute of Physical und Theoretical Chemistry, Institute of Biophysical Chemistry und Center for Biomolecular Magnetic Resonance (BMRZ) (Germany); Vogel, Marc; Suess, Beatrix [Technical University Darmstadt, Department of Biology (Germany); Corzilius, Björn, E-mail: corzilius@em.uni-frankfurt.de [Goethe University, Institute of Physical und Theoretical Chemistry, Institute of Biophysical Chemistry und Center for Biomolecular Magnetic Resonance (BMRZ) (Germany)

    2015-09-15

    We report the direct dynamic nuclear polarization (DNP) of {sup 13}C nuclei of a uniformly [{sup 13}C,{sup 15}N]-labeled, paramagnetic full-length hammerhead ribozyme (HHRz) complex with Mn{sup 2+} where the enhanced polarization is fully provided by the endogenously bound metal ion and no exogenous polarizing agent is added. A {sup 13}C enhancement factor of ε = 8 was observed by intra-complex DNP at 9.4 T. In contrast, “conventional” indirect and direct DNP experiments were performed using AMUPol as polarizing agent where we obtained a {sup 1}H enhancement factor of ε ≈ 250. Comparison with the diamagnetic (Mg{sup 2+}) HHRz complex shows that the presence of Mn{sup 2+} only marginally influences the (DNP-enhanced) NMR properties of the RNA. Furthermore two-dimensional correlation spectra ({sup 15}N–{sup 13}C and {sup 13}C–{sup 13}C) reveal structural inhomogeneity in the frozen, amorphous state indicating the coexistence of several conformational states. These demonstrations of intra-complex DNP using an endogenous metal ion as well as DNP-enhanced MAS NMR of RNA in general yield important information for the development of new methods in structural biology.

  14. Structure and orientation of dynorphin bound to lipid bilayers by 13C solid-state NMR

    Science.gov (United States)

    Uezono, Takiko; Toraya, Shuichi; Obata, Maki; Nishimura, Katsuyuki; Tuzi, Satoru; Saitô, Hazime; Naito, Akira

    2005-07-01

    Secondary structure and orientation of dynorphin bound to dimyristoylphosphatidylcholine (DMPC) bilayer were investigated by solid-state 13C NMR spectroscopy. For this purpose, 13C NMR spectra of the site-specifically 13C-labeled dynorphin were measured in the membrane-bound state under static, magic angle spinning (MAS), and slow MAS conditions. In the static experiment, magnetically oriented vesicle system (MOVS) induced by dynorphin was successfully used to investigate the orientation of dynorphin bound to the lipid bilayers. It was found that dynorphin adopts an α-helical structure in the N-terminus from Gly 2 to Leu 5 by analyses of the isotropic chemical shifts obtained from the MAS experiments. In contrast, it adopts disordered conformations from the center to the C-terminus and is located on the membrane surface. The static 13C NMR spectra indicated that MOVS-bound dynorphin was oriented to the magnetic field and rotated rapidly about the bilayer normal. Subsequently, we analyzed the 13C chemical shift tensors of carbonyl carbons in the peptide backbone by considering the rotational motion of the N-terminal α-helix. It was revealed that the N-terminal α-helix is inserted into the membrane with the tilt angle of 21° to the bilayer normal. This structure suggests a possibility that dynorphin interacts with the extracellular loop II of the κ-receptor through a helix-helix interaction.

  15. The Combined Influence of Hydrogel Stiffness and Matrix-Bound Hyaluronic Acid Content on Glioblastoma Invasion.

    Science.gov (United States)

    Chen, Jee-Wei Emily; Pedron, Sara; Harley, Brendan A C

    2017-08-01

    Glioblastoma (GBM) is the most common and lethal form of brain cancer. Its high mortality is associated with its aggressive invasion throughout the brain. The heterogeneity of stiffness and hyaluronic acid (HA) content within the brain makes it difficult to study invasion in vivo. A dextran-bead assay is employed to quantify GBM invasion within HA-functionalized gelatin hydrogels. Using a library of stiffness-matched hydrogels with variable levels of matrix-bound HA, it is reported that U251 GBM invasion is enhanced in softer hydrogels but reduced in the presence of matrix-bound HA. Inhibiting HA-CD44 interactions reduces invasion, even in hydrogels lacking matrix-bound HA. Analysis of HA biosynthesis suggests that GBM cells compensate for a lack of matrix-bound HA by producing soluble HA to stimulate invasion. Together, a robust method is showed to quantify GBM invasion over long culture times to reveal the coordinated effect of matrix stiffness, immobilized HA, and compensatory HA production on GBM invasion. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Structure of the [delta]-opioid receptor bound to naltrindole

    Energy Technology Data Exchange (ETDEWEB)

    Granier, Sébastien; Manglik, Aashish; Kruse, Andrew C.; Kobilka, Tong Sun; Thian, Foon Sun; Weis, William I.; Kobilka, Brian K. (Stanford-MED)

    2012-07-11

    The opioid receptor family comprises three members, the {mu}-, {delta}- and {kappa}-opioid receptors, which respond to classical opioid alkaloids such as morphine and heroin as well as to endogenous peptide ligands like endorphins. They belong to the G-protein-coupled receptor (GPCR) superfamily, and are excellent therapeutic targets for pain control. The {delta}-opioid receptor ({delta}-OR) has a role in analgesia, as well as in other neurological functions that remain poorly understood. The structures of the {mu}-OR and {kappa}-OR have recently been solved. Here we report the crystal structure of the mouse {delta}-OR, bound to the subtype-selective antagonist naltrindole. Together with the structures of the {mu}-OR and {kappa}-OR, the {delta}-OR structure provides insights into conserved elements of opioid ligand recognition while also revealing structural features associated with ligand-subtype selectivity. The binding pocket of opioid receptors can be divided into two distinct regions. Whereas the lower part of this pocket is highly conserved among opioid receptors, the upper part contains divergent residues that confer subtype selectivity. This provides a structural explanation and validation for the 'message-address' model of opioid receptor pharmacology, in which distinct 'message' (efficacy) and 'address' (selectivity) determinants are contained within a single ligand. Comparison of the address region of the {delta}-OR with other GPCRs reveals that this structural organization may be a more general phenomenon, extending to other GPCR families as well.

  17. Detailed analysis of variation at and around mitochondrial position 16189 in a large Finnish cohort reveals no significant associations with early growth or metabolic phenotypes at age 31 years.

    Science.gov (United States)

    Das, Sreena; Bennett, Amanda J; Sovio, Ulla; Ruokonen, Aimo; Martikainen, Hannu; Pouta, Anneli; Hartikainen, Anna-Liisa; Franks, Stephen; Elliott, Paul; Poulton, Joanna; Järvelin, Marjo-Riitta; McCarthy, Mark I

    2007-08-01

    Mitochondrial dysfunction is increasingly implicated in pathogenesis of adult metabolic disease. Rare mitochondrial (mt) DNA mutations impair glucose homeostasis, but the contribution of common variants is unclear. In small studies, variation within the OriB origin of replication (at mt16189 in particular) has been associated with both early growth and adult metabolic phenotypes and may contribute to life-course relationships between the two. The aim was to study a large well-characterized cohort to determine whether previously reported small-scale associations between OriB sequence variation and early growth and adult metabolic phenotypes are robust. This was a genetic association study of 5470 individuals from the population-based Northern Finland Birth Cohort of 1966, followed prospectively from pregnancy to age 31 yr. We measured indices of early growth (including birth weight, placental weight, and ponderal index) and adult metabolic homeostasis (including body mass index, fasting glucose and insulin, indices of insulin action and secretion) and their relationship to variation in the OriB region. Previously reported associations could not be confirmed. There were no significant (P < 0.01, uncorrected) associations between OriB sequence variation and measures of early growth including birth weight (P = 0.52, comparing individuals with mt16189T to those with a homopolymeric C-tract) and placental weight (P = 0.49). There were no significant associations with adult metabolic phenotypes including fasting glucose (P = 0.07), fasting insulin (P = 0.42), and homeostatic model assessment-derived measures of insulin sensitivity or secretion (P = 0.45 and P = 0.56, respectively). Despite substantial power to detect previously reported effects, mtDNA variations around OriB are not major contributors to variation in early growth and metabolic phenotypes during early adulthood.

  18. Tight bounds on computing error-correcting codes by bounded-depth circuits with arbitrary gates

    DEFF Research Database (Denmark)

    Gál, Anna; Hansen, Kristoffer Arnsfelt; Koucký, Michal

    2012-01-01

    We bound the minimum number w of wires needed to compute any (asymptotically good) error-correcting code C:{0,1}Ω(n) -> {0,1}n with minimum distance Ω(n), using unbounded fan-in circuits of depth d with arbitrary gates. Our main results are: (1) If d=2 then w = Θ(n ({log n/ log log n})2). (2) If d...... on a superconcentrator-like condition that the graphs of circuits computing good codes must satisfy. This condition is provably intermediate between superconcentrators and their weakenings considered before....

  19. Bounds of Certain Dynamic Inequalities on Time Scales

    Directory of Open Access Journals (Sweden)

    Deepak B. Pachpatte

    2014-10-01

    Full Text Available In this paper we study explicit bounds of certain dynamic integral inequalities on time scales. These estimates give the bounds on unknown functions which can be used in studying the qualitative aspects of certain dynamic equations. Using these inequalities we prove the uniqueness of some partial integro-differential equations on time scales.

  20. Optimal Two Parameter Bounds for the Seiffert Mean

    Directory of Open Access Journals (Sweden)

    Hui Sun

    2013-01-01

    Full Text Available We obtain sharp bounds for the Seiffert mean in terms of a two parameter family of means. Our results generalize and extend the recent bounds presented in the Journal of Inequalities and Applications (2012 and Abstract and Applied Analysis (2012.

  1. Sum rule expressions for bounds on Van der Waals coefficients

    NARCIS (Netherlands)

    Luyckx, R.; Coulon, P.; Lekkerkerker, H.N.W.

    1979-01-01

    We present a simple matrix solution for the moment equations that occur in recently discovered bounds on van der Waals coefficients. Using this matrix solution it is possible to express these new bounds directly in terms of the oscillator strength sum rules of the interacting systems.

  2. Bounded Baire functions and the Henstock-Stieltjes integral

    Science.gov (United States)

    Tantrawan, Made; Indrati, Ch. Rini

    2016-02-01

    In this paper, we give a sufficient condition for bounded Baire functions to be integrable in the sense of the Henstock-Stieltjes integral. By considering the space of all bounded Baire class α functions (α theorem for two-norm continuous linear functionals defined on bℬα [a, b] in terms of the Henstock-Stieltjes integral.

  3. On parallel Branch and Bound frameworks for Global Optimization

    NARCIS (Netherlands)

    Herrera, Juan F.R.; Salmerón, José M.G.; Hendrix, Eligius M.T.; Asenjo, Rafael; Casado, Leocadio G.

    2017-01-01

    Branch and Bound (B&B) algorithms are known to exhibit an irregularity of the search tree. Therefore, developing a parallel approach for this kind of algorithms is a challenge. The efficiency of a B&B algorithm depends on the chosen Branching, Bounding, Selection, Rejection, and Termination

  4. Entropy Bounds for Constrained Two-Dimensional Fields

    DEFF Research Database (Denmark)

    Forchhammer, Søren Otto; Justesen, Jørn

    1999-01-01

    The maximum entropy and thereby the capacity of 2-D fields given by certain constraints on configurations are considered. Upper and lower bounds are derived.......The maximum entropy and thereby the capacity of 2-D fields given by certain constraints on configurations are considered. Upper and lower bounds are derived....

  5. Improved Space Bounds for Cache-Oblivious Range Reporting

    DEFF Research Database (Denmark)

    Afshani, Peyman; Zeh, Norbert

    2011-01-01

    second main result shows that any cache-oblivious 2-d three-sided range reporting data structure with the optimal query bound has to use Ω(N logε N) space, thereby improving on a recent lower bound for the same problem. Using known transformations, the lower bound extends to 3-d dominance reporting and 3......We provide improved bounds on the size of cacheoblivious range reporting data structures that achieve the optimal query bound of O(logB N + K/B) block transfers. Our first main result is an O(N √ logN log logN)-space data structure that achieves this query bound for 3-d dominance reporting and 2-d...... three-sided range reporting. No cache-oblivious o(N log N/ log logN)-space data structure for these problems was known before, even when allowing a query bound of O(logO(1) 2 N + K/B) block transfers.1 Our result also implies improved space bounds for general 2-d and 3-d orthogonal range reporting. Our...

  6. Higgs interchange and bound states of superheavy fermions

    Indian Academy of Sciences (India)

    Hypothetical superheavy fourth-generation fermions with a very small coupling with the rest of the Standard Model can give rise to long enough lived bound states. The production and the detection of these bound states would be experimentally feasible at the LHC. Extending, in the present study, the analysis of other ...

  7. A Partitioning and Bounded Variable Algorithm for Linear Programming

    Science.gov (United States)

    Sheskin, Theodore J.

    2006-01-01

    An interesting new partitioning and bounded variable algorithm (PBVA) is proposed for solving linear programming problems. The PBVA is a variant of the simplex algorithm which uses a modified form of the simplex method followed by the dual simplex method for bounded variables. In contrast to the two-phase method and the big M method, the PBVA does…

  8. Holographic bounds on the UV cutoff scale in inflationary cosmology

    DEFF Research Database (Denmark)

    Keski-Vakkuri, Esko; Sloth, Martin Snoager

    2003-01-01

    We discuss how holographic bounds can be applied to the quantum fluctuations of the inflaton. In general the holographic principle will lead to a bound on the UV cutoff scale of the effective theory of inflation, but it will depend on the coarse-graining prescription involved in calculating the e...

  9. A bounds on the resonant frequency of rectangular microstrip antennas

    Science.gov (United States)

    Bailey, M. C.

    1980-01-01

    The calculation of currents induced by a transverse electric plane wave normally incident upon an infinite strip embedded in a grounded dielectric slab is used to infer a lower bound on the resonant frequency (or resonant-E-plane dimension) for rectangular microstrip antennas. An upper bound is provided by the frequency for which the E-plane dimension is a half-wavelength.

  10. Quasi-bound states, resonance tunnelling, and tunnelling times ...

    Indian Academy of Sciences (India)

    Abstract. In analogy with the definition of resonant or quasi-bound states used in three-dimensional quantal scattering, we define the quasi-bound states that occur in one- dimensional transmission generated by twin symmetric potential barriers and evaluate their energies and widths using two typical examples: (i) twin ...

  11. Bound states in a hyperbolic asymmetric double-well

    Energy Technology Data Exchange (ETDEWEB)

    Hartmann, R. R., E-mail: richard.hartmann@dlsu.edu.ph [Physics Department, De La Salle University, 2401 Taft Avenue, Manila (Philippines)

    2014-01-15

    We report a new class of hyperbolic asymmetric double-well whose bound state wavefunctions can be expressed in terms of confluent Heun functions. An analytic procedure is used to obtain the energy eigenvalues and the criterion for the potential to support bound states is discussed.

  12. Monetary and fiscal policy under bounded rationality and heterogeneous expectations

    NARCIS (Netherlands)

    Lustenhouwer, J.E.

    2017-01-01

    The goal of this thesis is to use plausible and intuitive models of bounded rationality to give new insights in monetary and fiscal policy. Particular focus is put on the zero lower bound on the nominal interest rate, forward guidance, and fiscal consolidations. The thesis considers different forms

  13. Asymptotic-bound-state model for Feshbach resonances

    NARCIS (Netherlands)

    Tiecke, T.G.; Goosen, M.R.; Walraven, J.T.M.; Kokkelmans, S.J.J.M.F.

    2010-01-01

    We present an asymptotic-bound-state model which can be used to accurately describe all Feshbach resonance positions and widths in a two-body system. With this model we determine the coupled bound states of a particular two-body system. The model is based on analytic properties of the two-body

  14. Bounding W-W ' Mixing with Spin Asymmetries at RHIC

    NARCIS (Netherlands)

    Boer, Daniel; den Dunnen, Wilco J.

    2010-01-01

    The W boson can obtain a small right-handed coupling to quarks and leptons through mixing with a hypothetical W' boson that appears in many extensions of the standard model. Measuring or even bounding this coupling to the light quarks is very challenging. Only one model independent bound on the

  15. On the Feng-Rao bound for generalized hamming weights

    DEFF Research Database (Denmark)

    Geil, Hans Olav; Thommesen, Christian

    2006-01-01

    The Feng-Rao bound gives good estimates of the minimum distance of a large class of codes. In this work we are concerned with the problem of how to extend the Feng-Rao bound so that it deals with all the generalized Hamming weights. The problem was solved by Heijnen and Pellikaan in [7] for a lar...

  16. Parity lifetime of bound states in a proximitized semiconductor nanowire

    DEFF Research Database (Denmark)

    Higginbotham, Andrew Patrick; Albrecht, Sven Marian; Kirsanskas, Gediminas

    2015-01-01

    superconductor layer, yielding an isolated, proximitized nanowire segment. We identify Andreev-like bound states in the semiconductor via bias spectroscopy, determine the characteristic temperatures and magnetic fields for quasiparticle excitations, and extract a parity lifetime (poisoning time) of the bound...... state in the semiconductor exceeding 10 ms....

  17. Bounds on the Effect of Progressive Structural Degradation

    DEFF Research Database (Denmark)

    Achtziger, Wolfgang; Bendsøe, Martin P; Taylor, John E.

    1997-01-01

    Problem formulations are presented for the evaluation of upper and lower bounds on the effect of progressive structural degradation. For the purposes of this study, degradation effect is measured by an increase in global structural compliance (flexibility). Thus the stated bounds are given simply...

  18. Detecting Majorana nonlocality using strongly coupled Majorana bound states

    NARCIS (Netherlands)

    Rubbert, S.H.P.; Akhmerov, A.R.

    2016-01-01

    Majorana bound states (MBS) differ from the regular zero energy Andreev bound states in their nonlocal properties, since two MBS form a single fermion. We design strategies for detection of this nonlocality by using the phenomenon of Coulomb-mediated Majorana coupling in a setting which still

  19. College Bound with the Office of Educational Programs

    Science.gov (United States)

    Neal, Brittany D.

    2004-01-01

    The Educational Programs Office at NASA Glenn Research Center hosts a variety of programs that takes on the hard task of getting students of all ages interested in pursuing careers in science, mathematics, and engineering. To help assist students along the way there are many programs to participate in such as: the explorers, shadowing opportunities, and paid internships. The Educational Programs Office not only creates learning opportunities for students, they also host workshops to help educators enhance their knowledge these fields. This summer I assisted Marie Borowski in the Educational Programs Office with the Tennessee State University College Bound Program. The Tennessee state University College Bound Program is an intensive two-week summer academic workshop designed to introduce minority students to the profession of engineering. NASA Glenn Research Center sent forty dedicated students on a bus to Nashville, Tennessee to experience college life as a whole. At the college the students day consisted of a math class, aeronautics, ACT/SAT preparation, writing and research, African American Culture, computer science, and study sessions. The students also went on educational field trips to the Fisk Museum, the Space and Rocket Center, and the Parthenon Museum. On the last day of the program the students competed in an oratorical contest where the students made a Powerpoint presentation on the class that they enjoyed the most. There were many processes that had to be put into action for the college bound program to run smoothly. The process started in early January with the preparation of applications. Once prepared, the applications were then sent to schools and past participants in hopes of receiving a well-qualified pool of applicants. Once the applications were received, a prescreening is done which ensures all of the information is complete. Then, they are reviewed by a panel, using a rubric to evaluate them, and the semifinalists are then selected

  20. Insight into partial agonism by observing multiple equilibria for ligand-bound and Gs-mimetic nanobody-bound β1-adrenergic receptor.

    Science.gov (United States)

    Solt, Andras S; Bostock, Mark J; Shrestha, Binesh; Kumar, Prashant; Warne, Tony; Tate, Christopher G; Nietlispach, Daniel

    2017-11-27

    A complex conformational energy landscape determines G-protein-coupled receptor (GPCR) signalling via intracellular binding partners (IBPs), e.g., Gs and β-arrestin. Using 13C methyl methionine NMR for the β1-adrenergic receptor, we identify ligand efficacy-dependent equilibria between an inactive and pre-active state and, in complex with Gs-mimetic nanobody, between more and less active ternary complexes. Formation of a basal activity complex through ligand-free nanobody-receptor interaction reveals structural differences on the cytoplasmic receptor side compared to the full agonist-bound nanobody-coupled form, suggesting that ligand-induced variations in G-protein interaction underpin partial agonism. Significant differences in receptor dynamics are observed ranging from rigid nanobody-coupled states to extensive μs-to-ms timescale dynamics when bound to a full agonist. We suggest that the mobility of the full agonist-bound form primes the GPCR to couple to IBPs. On formation of the ternary complex, ligand efficacy determines the quality of the interaction between the rigidified receptor and an IBP and consequently the signalling level.