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Sample records for functional elements required

  1. Functional changes appropriate for determining mineral element requirements.

    Science.gov (United States)

    Lukaski, H C; Penland, J G

    1996-09-01

    One factor limiting efforts to determine human requirements for dietary intakes of mineral elements has been the unavailability of acceptable standards for evaluating the effects of marginal and mild deficiencies. Traditional approaches, such as growth, longevity, chemical balance and measurement of concentrations of minerals in plasma or serum and cellular components of the blood, have not been sensitive indicators of mineral nutriture. One alternative that has been shown to be responsive to graded dietary mineral intake is the evaluation of functional responses to specific challenges or stressors. Aberrant responses, either exaggerated or attenuated, to controlled stressors have been observed in a variety of physiological, psychological and immunological parameters when mineral intakes have been suboptimal by conventional standards, compared with adequate responses. In comparison to static biochemical approaches for assessment of mineral nutritional status, functional tests may be sensitive and responsive to alterations in mineral intake in adult humans. Dynamic functional measures complement static biochemical measures and reflect the net effect of deficiencies on integrated biological systems. The application of some of these types of dynamic evaluations of function may be a useful and productive approach for proposing mineral element intakes to optimize human health and biological function and performance.

  2. Interstitial Functionalization in elemental Si

    Science.gov (United States)

    Kiefer, Boris; Fohtung, Edwin

    Societies in the 21st century will face many challenges. Materials science and materials design will be essential to address and master some if not all of these challenges. Semiconductors are among the most important technological material classes. Properties such as electrical transport are strongly affected by defects and a central goal continues to be the reduction of defect densities as much as possible in these compounds. Here we present results of interstitial Fe doping in elemental Si using first-principles DFT calculations. The preliminary results show that Fe will only occupy octahedral interstitial sites. The analysis of the electronic structure shows that the compounds are ferromagnetic and that a bandgap opens as interstitial Fe concentrations decrease, with a possible intermittent semi-metallic phase. The formation energy for interstitial Fe is unfavorable, as expected, by ~1.5 eV but becomes favorable as the chemical potential of Fe increases. Therefore, we expect that biasing the system with an external electrical field will lead to the formation of these materials. Thus, our results show that interstitial defects can be beneficial for the design of functionalities that differ significantly from those of the host material.

  3. Functional Metamirrors Using Bianisotropic Elements

    Science.gov (United States)

    Asadchy, V. S.; Ra'di, Y.; Vehmas, J.; Tretyakov, S. A.

    2015-03-01

    Conventional mirrors obey the simple reflection law that a plane wave is reflected as a plane wave, at the same angle. To engineer spatial distributions of fields reflected from a mirror, one can either shape the reflector or position some phase-correcting elements on top of a mirror surface. Here we show, both theoretically and experimentally, that full-power reflection with general control over the reflected wave phase is possible with a single-layer array of deeply subwavelength inclusions. These proposed artificial surfaces, metamirrors, provide various functions of shaped or nonuniform reflectors without utilizing any mirror. This can be achieved only if the forward and backward scattering of the inclusions in the array can be engineered independently, and we prove that it is possible using electrically and magnetically polarizable inclusions. The proposed subwavelength inclusions possess desired reflecting properties at the operational frequency band, while at other frequencies the array is practically transparent. The metamirror concept leads to a variety of applications over the entire electromagnetic spectrum, such as optically transparent focusing antennas for satellites, multifrequency reflector antennas for radio astronomy, low-profile conformal antennas for telecommunications, and nanoreflectarray antennas for integrated optics.

  4. GRID INFORMATION SECURITY FUNCTIONAL REQUIREMENT

    Directory of Open Access Journals (Sweden)

    Amy Poh Ai Ling

    2011-07-01

    Full Text Available This paper describes the background of smart information infrastructure and the needs for smart grid information security. It introduces the conceptual analysis to the methodology with the application ofhermeneutic circle and information security functional requirement identification. Information security for the grid market cover matters includes automation and communications industry that affects the operation of electric power systems and the functioning of the utilities that manage them and its awareness of this information infrastructure has become critical to the reliability of the power system. Community benefits from of cost savings, flexibility and deployment along with the establishment of wireless communications. However, concern revolves around the security protections for easily accessible devices such as the smart meter and the related communications hardware. On the other hand, the changing points between traditional versus smart grid networking trend and the information security importance on the communication field reflects the criticality of grid information security functional requirement identification. The goal of this paper is to identify the functional requirement and relate its significance addresses to the consumer requirement of an information security of a smart grid. Vulnerabilities may bring forth possibility for an attacker to penetrate a network, make headway admission to control software, alter it to load conditions that destabilize the grid in unpredictable ways. Focusing on the grid information security functional requirement is stepping ahead in developing consumer trust and satisfaction towardsmart grid completeness.

  5. Project X functional requirements specification

    CERN Document Server

    Holmes, S D; Kephart, R; Kerby, J; Kourbanis, I; Lebedev, V; Mishra, S; Nagaitsev, S; Solyak, N; Tschirhart, R

    2012-01-01

    Project X is a multi-megawatt proton facility being developed to support a world-leading program in Intensity Frontier physics at Fermilab. The facility is designed to support programs in elementary particle and nuclear physics, with possible applications to nuclear energy research. A Functional Requirements Specification has been developed in order to establish performance criteria for the Project X complex in support of these multiple missions, and to assure that the facility is designed with sufficient upgrade capability to provide U.S. leadership for many decades to come. This paper will briefly review the previously described Functional Requirements, and then discuss their recent evolution.

  6. Mixing Formal and Informal Model Elements for Tracing Requirements

    DEFF Research Database (Denmark)

    Jastram, Michael; Hallerstede, Stefan; Ladenberger, Lukas

    2011-01-01

    a system for traceability with a state-based formal method that supports refinement. We do not require all specification elements to be modelled formally and support incremental incorporation of new specification elements into the formal model. Refinement is used to deal with larger amounts of requirements......Tracing between informal requirements and formal models is challenging. A method for such tracing should permit to deal efficiently with changes to both the requirements and the model. A particular challenge is posed by the persisting interplay of formal and informal elements. In this paper, we...

  7. Design requirements for orbit maintenance of SPS elements

    Energy Technology Data Exchange (ETDEWEB)

    1980-11-01

    The objective of this study is to identify the design and operational requirements that will be imposed by the need to avoid unplanned reentry of SPS elements. The LEO Staging Base, Electric Orbit Transfer Vehicle, the LEO Construction Base, and SPS Self-Power Module are the SPS elements selected for this analysis. The orbit decay rates and attitude control/orbit maintenance propellant requirements for nominal and worst case conditions are defined. The sequence of events that could cause unplanned reentry are defined. The design and operational requirements that will be used to prevent the various elements from deorbiting are defined.

  8. Ab initio work function of elemental metals

    DEFF Research Database (Denmark)

    Skriver, Hans Lomholt; Rosengaard, N. M.

    1992-01-01

    We have used a recently developed self-consistent Green’s-function technique based on tight-binding linear-muffin-tin-orbital theory to calculate the work function for the close-packed surfaces of 37 elemental metals. The results agree with the limited experimental data obtained from single...... crystals to within 15%, and they explain the smooth behavior of the polycrystalline data as a function of atomic number....

  9. New functionalities in abundant element oxides: ubiquitous element strategy.

    Science.gov (United States)

    Hosono, Hideo; Hayashi, Katsuro; Kamiya, Toshio; Atou, Toshiyuki; Susaki, Tomofumi

    2011-06-01

    While most ceramics are composed of ubiquitous elements (the ten most abundant elements within the Earth's crust), many advanced materials are based on rare elements. A 'rare-element crisis' is approaching owing to the imbalance between the limited supply of rare elements and the increasing demand. Therefore, we propose a 'ubiquitous element strategy' for materials research, which aims to apply abundant elements in a variety of innovative applications. Creation of innovative oxide materials and devices based on conventional ceramics is one specific challenge. This review describes the concept of ubiquitous element strategy and gives some highlights of our recent research on the synthesis of electronic, thermionic and structural materials using ubiquitous elements.

  10. Matrix elements from moments of correlation functions

    CERN Document Server

    Bouchard, Chris; Orginos, Kostas; Richards, David

    2016-01-01

    Momentum-space derivatives of matrix elements can be related to their coordinate-space moments through the Fourier transform. We derive these expressions as a function of momentum transfer $Q^2$ for asymptotic in/out states consisting of a single hadron. We calculate corrections to the finite volume moments by studying the spatial dependence of the lattice correlation functions. This method permits the computation of not only the values of matrix elements at momenta accessible on the lattice, but also the momentum-space derivatives, providing {\\it a priori} information about the $Q^2$ dependence of form factors. As a specific application we use the method, at a single lattice spacing and with unphysically heavy quarks, to directly obtain the slope of the isovector form factor at various $Q^2$, whence the isovector charge radius. The method has potential application in the calculation of any hadronic matrix element with momentum transfer, including those relevant to hadronic weak decays.

  11. Matrix elements from moments of correlation functions

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Chia Cheng [SLAC National Accelerator Lab., Menlo Park, CA (United States); Bouchard, Chris [College of William and Mary, Williamsburg, VA (United States); Orginos, Konstantinos [Thomas Jefferson National Accelerator Facility (TJNAF), Newport News, VA (United States); College of William and Mary, Williamsburg, VA (United States); Richards, David G. [Thomas Jefferson National Accelerator Facility (TJNAF), Newport News, VA (United States)

    2016-10-01

    Momentum-space derivatives of matrix elements can be related to their coordinate-space moments through the Fourier transform. We derive these expressions as a function of momentum transfer Q2 for asymptotic in/out states consisting of a single hadron. We calculate corrections to the finite volume moments by studying the spatial dependence of the lattice correlation functions. This method permits the computation of not only the values of matrix elements at momenta accessible on the lattice, but also the momentum-space derivatives, providing {\\it a priori} information about the Q2 dependence of form factors. As a specific application we use the method, at a single lattice spacing and with unphysically heavy quarks, to directly obtain the slope of the isovector form factor at various Q2, whence the isovector charge radius. The method has potential application in the calculation of any hadronic matrix element with momentum transfer, including those relevant to hadronic weak decays.

  12. Membership Functions for Fuzzy Focal Elements

    Directory of Open Access Journals (Sweden)

    Porębski Sebastian

    2016-09-01

    Full Text Available The paper presents a study on data-driven diagnostic rules, which are easy to interpret by human experts. To this end, the Dempster-Shafer theory extended for fuzzy focal elements is used. Premises of the rules (fuzzy focal elements are provided by membership functions which shapes are changing according to input symptoms. The main aim of the present study is to evaluate common membership function shapes and to introduce a rule elimination algorithm. Proposed methods are first illustrated with the popular Iris data set. Next experiments with five medical benchmark databases are performed. Results of the experiments show that various membership function shapes provide different inference efficiency but the extracted rule sets are close to each other. Thus indications for determining rules with possible heuristic interpretation can be formulated.

  13. A Type System for Required/Excluded Elements in CLS

    Directory of Open Access Journals (Sweden)

    Mariangiola Dezani-Ciancaglini

    2009-11-01

    Full Text Available The calculus of looping sequences is a formalism for describing the evolution of biological systems by means of term rewriting rules. We enrich this calculus with a type discipline to guarantee the soundness of reduction rules with respect to some biological properties deriving from the requirement of certain elements, and the repellency of others. As an example, we model a toy system where the repellency of a certain element is captured by our type system and forbids another element to exit a compartment.

  14. Telomerase RNA stem terminus element affects template boundary element function, telomere sequence, and shelterin binding.

    Science.gov (United States)

    Webb, Christopher J; Zakian, Virginia A

    2015-09-08

    The stem terminus element (STE), which was discovered 13 y ago in human telomerase RNA, is required for telomerase activity, yet its mode of action is unknown. We report that the Schizosaccharomyces pombe telomerase RNA, TER1 (telomerase RNA 1), also contains a STE, which is essential for telomere maintenance. Cells expressing a partial loss-of-function TER1 STE allele maintained short stable telomeres by a recombination-independent mechanism. Remarkably, the mutant telomere sequence was different from that of wild-type cells. Generation of the altered sequence is explained by reverse transcription into the template boundary element, demonstrating that the STE helps maintain template boundary element function. The altered telomeres bound less Pot1 (protection of telomeres 1) and Taz1 (telomere-associated in Schizosaccharomyces pombe 1) in vivo. Thus, the S. pombe STE, although distant from the template, ensures proper telomere sequence, which in turn promotes proper assembly of the shelterin complex.

  15. Tolerancing analysis and functional requirement

    CERN Document Server

    Petit, Jean-Philippe

    2010-01-01

    The aim of this paper is to show through a simple assembly a method of tolerancing analysis (coherent with GPS) developed at LM\\'ecA and based on the model of clearance and deviation domains. Tolerancing is an important step in the product design because on it will depend the functionality of the mechanism its assemblibility but also its cost: manufacturing cost increases with the precision of tolerances values. In our model, each feature specification is translated into tolerance zone. This zone limits displacements of the toleranced feature. Limitations of this small displacements are expressed in a mathematical form by a 6-polytope in a 6 dimensions space (3 rotations and 3 translations). In the same way, contact conditions in joints allow to write linear inequalities which can be translated by 6-polytopes. Each domain is defined by a set of vertices and a system of inequalities. Considering a chosen tolerancing, the method allows to verify the mechanism assemblibility but also several functional requireme...

  16. Elements of the theory of functions

    CERN Document Server

    Knopp, Konrad

    2016-01-01

    Well-known book provides a clear, concise review of complex numbers and their geometric representation; linear functions and circular transformations; sets, sequences, and power series; analytic functions and conformal mapping; and elementary functions. 1952 edition.

  17. Are functional foods redefining nutritional requirements?

    Science.gov (United States)

    Jones, Peter J; Varady, Krista A

    2008-02-01

    Functional foods are increasing in popularity owing to their ability to confer health and physiological benefits. Nevertheless, the notion that functional foods improve health when providing nutrients at levels above and beyond existing recommended intakes is inconsistent with the definition of requirement. This disparity highlights the need for an alternative definition of nutrient requirement. The present objective is to examine distinctions between optimization of health, as defined by what we currently deem as required intakes, versus adding physiological benefit using bioactive agents found in functional foods. Presently, requirement is defined as the lowest amount of intake of a nutrient that will maintain a defined level of nourishment for a specific indicator of adequacy. In contrast, functional foods are described as ingredients that are not necessary for body function, yet provide added physiological benefit that confer better overall health. Plant sterols are one example of such an ingredient. Plant sterols lower plasma cholesterol concentrations, and may thus be considered essential nutrients in physiological situations where circulating cholesterol concentrations are high. Similarly, intakes of omega-3 fats beyond existing requirement may confer additional health benefits such as hypolipidemic and anti-diabetic effects. These examples underscore the inconsistencies between what is defined as a nutrient requirement versus what is identified as a health benefit of a functional food. Such discrepancies emphasize the need for a more all-encompassing definition of a nutrient requirement; that is, one that moves beyond the prevention of overt deficiency to encompass improved health and disease risk reduction.

  18. The Numerical Integration of Discrete Functions on a Triangular Element

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    With the application of Hammer integral formulas of a continuousfunction on a triangular element, the numerical integral formulas of some discrete functions on the element are derived by means of decomposition and recombination of base functions. Hammer integral formulas are the special examples of those of the paper.

  19. The Functional Requirements and Design Basis for Information Barriers

    Energy Technology Data Exchange (ETDEWEB)

    Fuller, James L.

    2012-05-01

    This report summarizes the results of the Information Barrier Working Group workshop held at Sandia National Laboratory in Albuquerque, NM, February 2-4, 1999. This workshop was convened to establish the functional requirements associated with warhead radiation signature information barriers, to identify the major design elements of any such system or approach, and to identify a design basis for each of these major elements. Such information forms the general design basis to be used in designing, fabricating, and evaluating the complete integrated systems developed for specific purposes.

  20. Elements and modulation of functional dynamics.

    Science.gov (United States)

    Gibbs, Alan C

    2014-10-09

    The existing structure-function paradigm of drug discovery has been evolving toward the essential incorporation of dynamics data. This new functional dynamics paradigm emphasizes conformational entropy as a driving force of protein function and intermolecular recognition. Conformational dynamics (a proxy of conformational entropy) impacts the degree of protein (dis)order and the constitution of the conformational ensemble, the mechanisms of allostery and drug resistance, and the free energy of ligand binding. Specific protein and ligand conformations facilitate favorable, reciprocal interactions. The number of protein and ligand conformers that exhibit favorable binding interactions will vary from system to system. All binding scenarios can modulate protein dynamics by various levels of enthalpic and entropic contribution, with significant influence on the functional dynamics of the system. Analysis and consideration of resulting changes of activity, signaling, catalysis, and subsequent phenotypic outcome are powerful motivations in the drug design process.

  1. Functional Foods Baseline and Requirements Analysis

    Science.gov (United States)

    Cooper, M. R.; Bermudez-Aguirre, L. D.; Douglas, G.

    2015-01-01

    Current spaceflight foods were evaluated to determine if their nutrient profile supports positioning as a functional food and if the stability of the bioactive compound within the food matrix over an extended shelf-life correlated with the expected storage duration during the mission. Specifically, the research aims were: Aim A. To determine the amount of each nutrient in representative spaceflight foods immediately after processing and at predetermined storage time to establish the current nutritional state. Aim B. To identify the requirements to develop foods that stabilize these nutrients such that required concentrations are maintained in the space food system throughout long duration missions (up to five years). Aim C. To coordinate collaborations with health and performance groups that may require functional foods as a countermeasure.

  2. Work function of elemental metals and its face dependence ...

    African Journals Online (AJOL)

    Journal of the Nigerian Association of Mathematical Physics. Journal Home ... Open Access DOWNLOAD FULL TEXT Subscription or Fee Access. Work function of elemental metals and its face dependence: Stabilized Jellium approach.

  3. Tunnelling matrix elements with Gutzwiller wave functions

    Energy Technology Data Exchange (ETDEWEB)

    Di Ciolo, Andrea; Tocchio, Luca F.; Gros, Claudius [Institut fuer Theoretische Physik, Goethe Universitaet Frankfurt, Frankfurt Am Main (Germany)

    2011-07-01

    We use a generalized Gutzwiller approach, in order to study projected particle (hole) excitations for superconducting systems and systems with antiferromagnetic (AFM) order. As in the standard Gutzwiller scheme the effects of the strong electronic correlations are given via the suppression of the site double occupancy; for our computations it is helpful to consider a lattice with a reservoir site unaffected by this suppression of the double occupancy. In this approach we obtain the probabilities for the tunnelling of a particle (hole) into the projected state. Our results are due only to the physical properties of the trial state and not to the choice of a specifical Hamiltonian: in this sense, they are model-independent but not universal, because they rely on the features of the chosen Gutzwiller wave function (projected Fermi Sea, BCS superconductor, AFM..) The accuracy and the reliability of our analytical approximation is tested using the Variational Monte Carlo. Possible comparisons with tunnelling experiments are discussed.

  4. Functional validation of a constitutive autonomous silencer element.

    Directory of Open Access Journals (Sweden)

    Heyuan Qi

    Full Text Available Sequences of the genome that are capable of silencing gene expression are thought to play a key role in gene regulation. However, very few silencer elements capable of functioning in mammalian cells have been described, and only a fraction of these have been tested for the ability to function in an autonomous fashion. We report here the characterization and functional validation of a constitutive autonomous silencer element from the human genome called T39, and the comparison of T39 to three other putative silencer elements previously described by others. Functional analysis included one assay for enhancer-blocking insulator activity and two independent assays for silencer activity, all based on stable transfection and comparison to a neutral spacer control. In erythroid K562 cells, T39 exhibited potent silencer activity, the previously described element PRE2-S5 exhibited modest silencer activity, and the two other previously described elements exhibited no silencer activity. T39 was further found to be capable of silencing three disparate promoters, of silencing gene expression in three disparate cell lines, and of functioning as a single copy in a topology-independent manner. Of the four elements analyzed, only T39 exhibits a constitutive pattern of DNase hypersensitivity and binding by CTCF. In its native location the T39 element also exhibits a unique interaction profile with a subset of distal putative regulatory elements. Taken together, these studies validate T39 as a constitutive autonomous silencer, identify T39 as a defined control for future studies of other regulatory elements such as insulators, and provide a basic chromatin profile for one highly potent silencer element.

  5. Mining functional elements in messenger RNAs: overview, challenges, and perspectives

    Directory of Open Access Journals (Sweden)

    Firoz eAhmed

    2011-11-01

    Full Text Available Eukaryotic messenger RNA contains not only protein-coding regions but also a plethora of functional cis-elements that influence or coordinate a number of regulatory aspects of gene expression, such as mRNA stability, splicing forms, and translation rates. Understanding the rules that apply to each of these element types (e.g., whether the element is defined by primary or higher-order structure allows for the discovery of novel mechanisms of gene expression as well as the design of transcripts with controlled expression. Bioinformatics plays a major role in creating databases and finding non-evident patterns governing each type of eukaryotic functional element. Much of what we currently know about mRNA regulatory elements in eukaryotes is derived from microorganism and animal systems, with the particularities of plant systems lagging behind. In this review, we provide a general introduction to the most well-known eukaryotic mRNA regulatory motifs (splicing regulatory elements, internal ribosome entry sites, iron-responsive elements, AU-rich elements, zipcodes, and polyadenylation signals and describe available bioinformatics resources (databases and analysis tools to analyze eukaryotic transcripts in search of functional elements, focusing on recent trends in bioinformatics methods and tool development. We also discuss future directions in the development of better computational tools based upon current knowledge of these functional elements. Improved computational tools would advance our understanding of the processes underlying gene regulations. We encourage plant bioinformaticians to turn their attention to this subject to help identify novel mechanisms of gene expression regulation using RNA motifs that have potentially evolved or diverged in plant species.

  6. A Finite Circular Arch Element Based on Trigonometric Shape Functions

    Directory of Open Access Journals (Sweden)

    H. Saffari

    2007-01-01

    Full Text Available The curved-beam finite element formulation by trigonometric function for curvature is presented. Instead of displacement function, trigonometric function is introduced for curvature to avoid the shear and membrane locking phenomena. Element formulation is carried out in polar coordinates. The element with three nodal parameters is chosen on curvature. Then, curvature field in the element is interpolated as the conventional trigonometric functions. Shape functions are obtained as usual by matrix operations. To consider the boundary conditions, a transformation matrix between nodal curvature and nodal displacement vectors is introduced. The equilibrium equation is written by minimizing the total potential energy in terms of the displacement components. In such equilibrium equation, the locking phenomenon is eliminated. The interesting point in this method is that for most problems, it is sufficient to use only one element to obtain the solution. Four examples are presented in order to verify the element formulation and to show the accuracy and efficiency of the method. The results are compared with those of other concepts.

  7. Schwann cell myelination requires Dynein function

    Directory of Open Access Journals (Sweden)

    Langworthy Melissa M

    2012-11-01

    Full Text Available Abstract Background Interaction of Schwann cells with axons triggers signal transduction that drives expression of Pou3f1 and Egr2 transcription factors, which in turn promote myelination. Signal transduction appears to be mediated, at least in part, by cyclic adenosine monophosphate (cAMP because elevation of cAMP levels can stimulate myelination in the absence of axon contact. The mechanisms by which the myelinating signal is conveyed remain unclear. Results By analyzing mutations that disrupt myelination in zebrafish, we learned that Dynein cytoplasmic 1 heavy chain 1 (Dync1h1, which functions as a motor for intracellular molecular trafficking, is required for peripheral myelination. In dync1h1 mutants, Schwann cell progenitors migrated to peripheral nerves but then failed to express Pou3f1 and Egr2 or make myelin membrane. Genetic mosaic experiments revealed that robust Myelin Basic Protein expression required Dync1h1 function within both Schwann cells and axons. Finally, treatment of dync1h1 mutants with a drug to elevate cAMP levels stimulated myelin gene expression. Conclusion Dync1h1 is required for retrograde transport in axons and mutations of Dync1h1 have been implicated in axon disease. Our data now provide evidence that Dync1h1 is also required for efficient myelination of peripheral axons by Schwann cells, perhaps by facilitating signal transduction necessary for myelination.

  8. Two-dimensional finite element neutron diffusion analysis using hierarchic shape functions

    Energy Technology Data Exchange (ETDEWEB)

    Carpenter, D.C.

    1997-04-01

    Recent advances have been made in the use of p-type finite element method (FEM) for structural and fluid dynamics problems that hold promise for reactor physics problems. These advances include using hierarchic shape functions, element-by-element iterative solvers and more powerful mapping techniques. Use of the hierarchic shape functions allows greater flexibility and efficiency in implementing energy-dependent flux expansions and incorporating localized refinement of the solution space. The irregular matrices generated by the p-type FEM can be solved efficiently using element-by-element conjugate gradient iterative solvers. These solvers do not require storage of either the global or local stiffness matrices and can be highly vectorized. Mapping techniques based on blending function interpolation allow exact representation of curved boundaries using coarse element grids. These features were implemented in a developmental two-dimensional neutron diffusion program based on the use of hierarchic shape functions (FEM2DH). Several aspects in the effective use of p-type analysis were explored. Two choices of elemental preconditioning were examined--the proper selection of the polynomial shape functions and the proper number of functions to use. Of the five shape function polynomials tested, the integral Legendre functions were the most effective. The serendipity set of functions is preferable over the full tensor product set. Two global preconditioners were also examined--simple diagonal and incomplete Cholesky. The full effectiveness of the finite element methodology was demonstrated on a two-region, two-group cylindrical problem but solved in the x-y coordinate space, using a non-structured element grid. The exact, analytic eigenvalue solution was achieved with FEM2DH using various combinations of element grids and flux expansions.

  9. Natural frequencies of cracked functionally graded material plates by the extended finite element method

    CERN Document Server

    Natarajan, S; Bordas, S; Rabczuk, T; Kerfriden, P

    2011-01-01

    In this paper, the linear free flexural vibration of cracked functionally graded material plates is studied using the extended finite element method. A 4-noded quadrilateral plate bending element based on field and edge consistency requirement with 20 degrees of freedom per element is used for this study. The natural frequencies and mode shapes of simply supported and clamped square and rectangular plates are computed as a function of gradient index, crack length, crack orientation and crack location. The effect of thickness and influence of multiple cracks is also studied.

  10. Glutathione S-transferase Ya subunit gene: identification of regulatory elements required for basal level and inducible expression.

    OpenAIRE

    Telakowski-Hopkins, C A; King, R. G.; Pickett, C B

    1988-01-01

    The function of the 5'-flanking region of a rat glutathione S-transferase Ya subunit structural gene has been examined in homologous and heterologous cells. By using the 5'-flanking region of the Ya subunit gene fused to the structural gene encoding chloramphenicol acetyltransferase, we have identified two cis-acting regulatory elements in the upstream region of the Ya gene. One element is required for maximum basal level expression in homologous cells, whereas maximum basal level expression ...

  11. DNA structural elements required for ERCC1-XPF endonuclease activity

    NARCIS (Netherlands)

    W.L. de Laat (Wouter); E. Appeldoorn (Esther); J.H.J. Hoeijmakers (Jan); N.G.J. Jaspers (Nicolaas)

    1998-01-01

    textabstractThe heterodimeric complex ERCC1-XPF is a structure-specific endonuclease responsible for the 5' incision during mammalian nucleotide excision repair (NER). Additionally, ERCC1-XPF is thought to function in the repair of interstrand DNA cross-links and, by analogy to the

  12. Green's function and boundary elements of multifield materials

    CERN Document Server

    Qin, Qing-Hua

    2007-01-01

    Green's Function and Boundary Elements of Multifield Materials contains a comprehensive treatment of multifield materials under coupled thermal, magnetic, electric, and mechanical loads. Its easy-to-understand text clarifies some of the most advanced techniques for deriving Green's function and the related boundary element formulation of magnetoelectroelastic materials: Radon transform, potential function approach, Fourier transform. Our hope in preparing this book is to attract interested readers and researchers to a new field that continues to provide fascinating and technologically important challenges. You will benefit from the authors' thorough coverage of general principles for each topic, followed by detailed mathematical derivation and worked examples as well as tables and figures where appropriate. In-depth explanations of the concept of Green's function Coupled thermo-magneto-electro-elastic analysis Detailed mathematical derivation for Green's functions.

  13. Algebraic evaluation of matrix elements in the Laguerre function basis

    Science.gov (United States)

    McCoy, A. E.; Caprio, M. A.

    2016-02-01

    The Laguerre functions constitute one of the fundamental basis sets for calculations in atomic and molecular electron-structure theory, with applications in hadronic and nuclear theory as well. While similar in form to the Coulomb bound-state eigenfunctions (from the Schrödinger eigenproblem) or the Coulomb-Sturmian functions (from a related Sturm-Liouville problem), the Laguerre functions, unlike these former functions, constitute a complete, discrete, orthonormal set for square-integrable functions in three dimensions. We construct the SU(1, 1) × SO(3) dynamical algebra for the Laguerre functions and apply the ideas of factorization (or supersymmetric quantum mechanics) to derive shift operators for these functions. We use the resulting algebraic framework to derive analytic expressions for matrix elements of several basic radial operators (involving powers of the radial coordinate and radial derivative) in the Laguerre function basis. We illustrate how matrix elements for more general spherical tensor operators in three dimensional space, such as the gradient, may then be constructed from these radial matrix elements.

  14. Clinical Aspects of Trace Elements: Zinc in Human Nutrition – Zinc Requirements

    Directory of Open Access Journals (Sweden)

    Michelle M Pluhator

    1995-01-01

    Full Text Available The body requires certain levels of essential nutrients, such as zinc, to maintain life. Intake less than the required levels can cause impaired function, disease and death. Every essential nutrient has a unique range of tissue concentration and intake necessary for proper physiological and biochemical functioning. Many criteria have been used to set dietary intake levels for nutrients. For trace elements, however, a limited number of investigative approaches are currently employed by researchers due to inadequate information on individual requirements and intake levels. Further, a clear lack of satisfactory biochemical methods to measure zinc nutritional status continues to hinder formulation of dietary guidelines. Thus, many assumptions have to be made, and large safety margins have to be added to assumed daily requirements in order to compensate for this absence of information. Numerous barriers to a full understanding of what constitutes an adequate dietary recommendation for zinc still exist. Zinc is incompletely absorbed, and this absorption can be greatly influenced by the chemical form in which zinc is bound; interactions with other nutrients also affect absorption. Part three of this five-part review presents the current Canadian recommended nutrient intakes for zinc for various sex and age categories and provides a rationale for the suggested values. The important nutrient interactions that affect the bioavailability of zinc, including those with phytates, copper, cadmium, tin and iron, are discussed.

  15. Exploring functional elements and genomic variation in the noncoding genome

    NARCIS (Netherlands)

    van Heesch, S.A.A.C.

    2014-01-01

    Gene expression regulation is a delicate process that depends on multiple aspects including genome structure and transcription factor binding to DNA elements. The majority of our genome consists of noncoding DNA, which was shown to be crucial in providing the correct context for genome function. Alt

  16. Finite element estimation of acoustical response functions in HID lamps

    Energy Technology Data Exchange (ETDEWEB)

    Baumann, Bernd; Wolff, Marcus [Department of Mechanical Engineering and Production, School of Engineering and Computer Science, Hamburg University of Applied Sciences, Berliner Tor 21, 20099 Hamburg (Germany); Hirsch, John; Antonis, Piet [Philips Lighting BV, Lightlabs, Mathildelaan 1, 5600 JM Eindhoven (Netherlands); Bhosle, Sounil [Universite de Toulouse (United States); Barrientos, Ricardo Valdivia, E-mail: bernd.baumann@haw-hamburg.d [National Nuclear Research Institute, Highway Mexico-Toluca s/n, La Marquesa, Ocoyoacac, CP 52750 (Mexico)

    2009-11-21

    High intensity discharge lamps can experience flickering and even destruction when operated at high frequency alternating current. The cause of these problems has been identified as acoustic resonances inside the lamp's arc tube. Here, a finite element approach for the calculation of the acoustic response function is described. The developed model does not include the plasma dynamics.

  17. Exploring functional elements and genomic variation in the noncoding genome

    NARCIS (Netherlands)

    van Heesch, S.A.A.C.|info:eu-repo/dai/nl/336463286

    2014-01-01

    Gene expression regulation is a delicate process that depends on multiple aspects including genome structure and transcription factor binding to DNA elements. The majority of our genome consists of noncoding DNA, which was shown to be crucial in providing the correct context for genome function. Alt

  18. Requirements for effective functional breast imaging

    Science.gov (United States)

    Weinberg, I. N.; Zawarzin, V.; Adler, L. P.; Pani, R.; DeVincentis, G.; Khalkhali, I.; Vargas, H.; Venegas, R.; Kim, S. C.; Bakale, G.; Levine, E.; Perrier, N.; Freimanis, R. I.; Lesko, N. M.; Newman, D. P.; Geisinger, K. R.; Berg, W. A.; Masood, S.

    2003-01-01

    Most nuclear medicine physicists were trained on devices aimed at functional neuroimaging. The clinical goals of brain-centered devices differ dramatically from the parameters needed to be useful in the breast clinic. We will discuss similarities and differences that impact on design considerations, and describe our latest generation of positron emission mammography and intraoperative products. Source of physiologic contrast: Clinical neuroimaging depends on flow agents to detect the presence of breaks in the blood-brain barrier. Breast flow agents are nonspecific, and may miss preinvasive lesions. Resolution: Brain cancers are generally diagnosed at late stages, so resolution is not so critical. Detecting early breast cancers, and specifying margins for surgery requires 3 mm spatial resolution or better. Prevalence: Primary brain cancer is uncommon, and lesions mimicking brain cancer are rare. Primary breast cancer is common, and benign lesions are even more common, so specificity and biopsy capability are very important. Anatomic references: Brain structure is standard, while breast structure is highly variable, requiring immobilization/compression for physiologic imaging and biopsy. Surgery: Complete cancer resections for brain are very rare, but are possible for breast with appropriate imaging guidance, implying the need for rapid and reliable imaging. To summarize, the breast clinic needs a rapid and highly sensitive method of assessing breast physiology, compatible with biopsy and surgery. Positron emission mammography devices, in handheld and X-ray platform based configurations, are ideal for this mission.

  19. Functional Nanofibers and Colloidal Gels: Key Elements to Enhance Functionality

    Science.gov (United States)

    Vogel, Nancy Amanda

    Nanomaterials bridge the gap between bulk materials and molecular structures and are known for their unique material properties and highly functional nature which make them attractive for a variety of potential applications, from energy storage and pollution sensors to agricultural and biomedical products. These potential applications, coupled with advances in nanotechnology, have generated considerable interest in nanostructure research. The work presented in this dissertation focuses on two such nanostructures, electrospun nanofibers and nanodiamond particles, with an overarching goal of tailoring the material behavior for a desired outcome. Our first research theme focuses on realizing the full potential of chitosan electrospinning by understanding the mechanism that enables fiber formation through cyclodextrin complexation as a function of solution properties, solvent types, and cyclodextrin content. We demonstrate that cyclodextrin addition not only enables chitosan fiber formation, but also extends the composition and solvent window for nanofiber synthesis while introducing a variety of mat topologies, including three-dimensional, self-supporting mats. These fiber formation improvements cannot be fully explained by conventional electrospinning parameters, but instead seem to be related to the molecular interactions between chitosan and cyclodextrin. Our second research theme entails the modification of highly water soluble, poly(vinyl alcohol) (PVA) nanofibers dissolution properties via atomic layer deposition (ALD) post treatments. In this work, we demonstrate that applying different thicknesses of aluminum oxide nano-coatings can improve the stability of PVA nanofibers in high humidity conditions and significantly decrease the solubility of electrospun PVA mats in water, from seconds to multiple weeks. Controlling mat dissolution allows for the unique opportunity to modulate small molecule, such as drug, release from nanofibers without altering the core

  20. Getting the balance right between functional and non-functional requirements: the case of requirement specification in IT procurement

    Directory of Open Access Journals (Sweden)

    Björn Johansson

    2013-01-01

    Full Text Available IT procurement represents a business process of high importance, including the ability to articulate requirements that the procurement deals with. Furthermore, specifying requirements is of importance for both procurer and potential supplier, as it functions as central contractual element between the two. The purpose of this article is two-fold: (i to show how established terminology for requirement specification is represented in current call for bids for the procurement of IT; and (ii to introduce an organizing framework that may assist procurers in actively addressing functional requirements and business requirements. Ten “call for bids” were examined from a Swedish national procurement database. From the analysis of the bids, it can be concluded that: (i the call for bids displays a high degree of precision regarding hardware aspects, but less precision regarding software; (ii supplier experience and competence is stressed, but rarely elaborated on in detail; and (iii call for bids vagueness may be used as a lock-in opportunity for suppliers. From the discussion on this, a tentative procurement framework is suggested, aiming on increasing the logical transparency for the procurement of IT.

  1. Modeling of sensor function for piezoelectric bender elements

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    An analytical sandwich beam model for piezoelectric bender elements is derived based on the first-order shear deformation theory (FSDT), which assumes a single rotation angle for the whole cross-section and a quadratic distribution for coupled electric potential in piezoelectric layers. Shear coefficient is introduced to correct the effect of transverse shear strain on shear force and the electric displacement integration. Static and free vibration analyses of simply-supported bender elements are carried out for the sensor function. The results illustrate the high accuracy of the present model compared with the exact 2D solutions.

  2. Element orbitals for Kohn-Sham density functional theory

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Lin; Ying, Lexing

    2012-05-08

    We present a method to discretize the Kohn-Sham Hamiltonian matrix in the pseudopotential framework by a small set of basis functions automatically contracted from a uniform basis set such as planewaves. Each basis function is localized around an element, which is a small part of the global domain containing multiple atoms. We demonstrate that the resulting basis set achieves meV accuracy for 3D densely packed systems with a small number of basis functions per atom. The procedure is applicable to insulating and metallic systems.

  3. Cross-species functionality of pararetroviral elements driving ribosome shunting.

    Directory of Open Access Journals (Sweden)

    Mikhail M Pooggin

    Full Text Available BACKGROUND: Cauliflower mosaic virus (CaMV and Rice tungro bacilliform virus (RTBV belong to distinct genera of pararetroviruses infecting dicot and monocot plants, respectively. In both viruses, polycistronic translation of pregenomic (pg RNA is initiated by shunting ribosomes that bypass a large region of the pgRNA leader with several short (sORFs and a stable stem-loop structure. The shunt requires translation of a 5'-proximal sORF terminating near the stem. In CaMV, mutations knocking out this sORF nearly abolish shunting and virus viability. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that two distant regions of the CaMV leader that form a minimal shunt configuration comprising the sORF, a bottom part of the stem, and a shunt landing sequence can be replaced by heterologous sequences that form a structurally similar configuration in RTBV without any dramatic effect on shunt-mediated translation and CaMV infectivity. The CaMV-RTBV chimeric leader sequence was largely stable over five viral passages in turnip plants: a few alterations that did eventually occur in the virus progenies are indicative of fine tuning of the chimeric sequence during adaptation to a new host. CONCLUSIONS/SIGNIFICANCE: Our findings demonstrate cross-species functionality of pararetroviral cis-elements driving ribosome shunting and evolutionary conservation of the shunt mechanism. We are grateful to Matthias Müller and Sandra Pauli for technical assistance. This work was initiated at Friedrich Miescher Institute (Basel, Switzerland. We thank Prof. Thomas Boller for hosting the group at the Institute of Botany.

  4. Basic functions of telecommunication channel elements for successful information transmission

    Directory of Open Access Journals (Sweden)

    Milorad S. Markagić

    2011-04-01

    the observed messages. Coder of messages generated by a message source should be transmitted to the recipient. For that purpose, an appropriate communication channel is used, with appropriate electrical signals as material bearers of the message. Definition of the code and the code system The set of combinations of digits that mirrors the elements of the set A is called a code. The established rule considers situations when each symbol from the set A is associated with the combination of elements of the set B. The function f defining this translation must be defined. This replacement is called a code replacement. Signal coder A coder performs signal transformation of coded messages to an electrical signal adapted for transmission via the transmission system. The most common signals are voltage transmission via cable connection or an electromagnetic field in the radio transmission. Modern systems for transferring discrete messages contain codecs and modems. Portable system A portable system is the medium for signal transmission from the source to the point of receipt. It can be wired and wireless. A wired transmission system is used in the stationary elements of communication systems. Wireless signal transmission is used in all conditions and it is more rational, efficient and economical. On their way through the transmission system, signals are subject to a variety of interferences. For a better insight into the interference impact, the source of interference is added to the whole system. Conclusion The model of the telecommunication channel is a complex system of a series of mutually dependent elements. Effectiveness of these elements is evaluated by the performances of the probability that the transfer of information through the channel will be successful. In a thus modeled telecommunication channel, regardless of the technical means used which is either a system or a circuit, the place and role of each element can be considered, which is the basis for consideration

  5. Non-Periodic Finite-Element Formulation of Orbital-Free Density Functional Theory

    Energy Technology Data Exchange (ETDEWEB)

    Gavini, V; Knap, J; Bhattacharya, K; Ortiz, M

    2006-10-06

    We propose an approach to perform orbital-free density functional theory calculations in a non-periodic setting using the finite-element method. We consider this a step towards constructing a seamless multi-scale approach for studying defects like vacancies, dislocations and cracks that require quantum mechanical resolution at the core and are sensitive to long range continuum stresses. In this paper, we describe a local real space variational formulation for orbital-free density functional theory, including the electrostatic terms and prove existence results. We prove the convergence of the finite-element approximation including numerical quadratures for our variational formulation. Finally, we demonstrate our method using examples.

  6. 41 CFR 60-2.17 - Additional required elements of affirmative action programs.

    Science.gov (United States)

    2010-07-01

    ... elements of affirmative action programs. 60-2.17 Section 60-2.17 Public Contracts and Property Management... EMPLOYMENT OPPORTUNITY, DEPARTMENT OF LABOR 2-AFFIRMATIVE ACTION PROGRAMS Purpose and Contents of Affirmative Action Programs § 60-2.17 Additional required elements of affirmative action programs. In addition to...

  7. Surface energy and work function of elemental metals

    DEFF Research Database (Denmark)

    Skriver, Hans Lomholt; Rosengaard, N. M.

    1992-01-01

    are in excellent agreement with a recent full-potential, all-electron, slab-supercell calculation of surface energies and work functions for the 4d metals. The present calculations explain the trend exhibited by the surface energies of the alkali, alkaline earth, divalent rare-earth, 3d, 4d, and 5d transition......We have performed an ab initio study of the surface energy and the work function for six close-packed surfaces of 40 elemental metals by means of a Green’s-function technique, based on the linear-muffin-tin-orbitals method within the tight-binding and atomic-sphere approximations. The results...... and noble metals, as derived from the surface tension of liquid metals. In addition, they give work functions which agree with the limited experimental data obtained from single crystals to within 15%, and explain the smooth behavior of the experimental work functions of polycrystalline samples...

  8. Key requirements for future control room functionality

    DEFF Research Database (Denmark)

    Tornelli, Carlo; Zuelli, Roberto; Marinelli, Mattia

    2016-01-01

    This internal report provides the key requirements for the future control centres. R8.1 represents the starting point of WP8 activities and wants to achieve a double objective. On the one hand it collects general requirements on future control centres emerging from the general trends in power...... system operation as well as experiences and results from other European projects. On the other hand, it analyses what requirements for future control rooms arise from the ELECTRA proposed control solutions. Hence, different points of view are taken into account. The ELECTRA Use Cases (UCs...... requirements for the future control centres discussed within this report. The analysis of what happened before the European system disturbance occurred on 4th November 2006 and of the existing trends by vendors helped T8.1 in the definition of the requirements for the future control centres. Volunteer...

  9. Understanding of Essential Elements Required in Informed Consent Form among Researchers and Institutional Review Board Members.

    Science.gov (United States)

    Koonrungsesomboon, Nut; Laothavorn, Junjira; Karbwang, Juntra

    2015-06-01

    The process of informed consent remains a constant challenge in clinical research. The aim of the present study was to evaluate the understanding of researchers and members of Institutional Review Boards (IRBs) regarding the essential elements of an Informed Consent Form (ICF) as required by internationally recognized regulations. Using eight case studies to illustrate basic ethical elements, the study involved 107 participants, mainly from the Asia Pacific and African regions. The results showed that most of the participants had general knowledge regarding the essential elements required in an ICF. However, the issues of confidentiality of data and payment for study participation proved to be problematic for some participants, accounting for 35% and 28% of all incorrect answers respectively. This suggests that participants' understanding of the underlying concepts of the required ICF elements is limited. Ethical training of researchers and IRB members, particularly in the Asia Pacific and African regions, concerning valid informed consent is still needed.

  10. Identification and functional analysis of a CDE/CHR element in the POLD1 promoter

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    DNA polymerase delta is encoded by the POLD1 gene,the transcription of which is strictly cell cycle-dependent.However,the means by which POLD1 transcription is regulated by the cell cycle mechanism is currently unknown.We discovered a novel element in the POLD1 promoter known as a CDE(cell cycle-dependent element)/CHR(cell cycle gene homology region) element.A series of luciferase reporter constructs containing various POLD1 promoter mutations were used to investigate the role of the CDE/CHR element in POLD1 transcription.When the CDE/CHR element was mutated,the promoter activity was up-regulated,and the cell-cycle related factors E2F1 and p21 stopped regulating the promoter.Furthermore,cell cycle-dependent changes in the promoter activity required the integrative CDE/CHR element.Electrophoretic mobility shift assay(EMSA) revealed the presence of at least three types of DNA/protein complexes binding to the CDE/CHR element.Our findings provide strong evidence that the CDE/CHR-like sequence is an active functional element in the POLD1 promoter,which is important for the cell cycle regulation of the POLD1 gene.

  11. Identification and functional analysis of a CDE/CHR element in the POLDI promoter

    Institute of Scientific and Technical Information of China (English)

    SONG NanMeng; ZHU XiaoYu; SHI Lei; AN Jing; WU YanWei; SANG JianLi

    2009-01-01

    Chinese Center for Disease Control and Prevention, Beijing 102206, China DNA polymerase delta is encoded by the POLD1 gene, the transcription of which is strictly cell cy-cle-dependent. However, the means by which POLD1 transcription is regulated by the cell cycle mechanism is currently unknown. We discovered a novel element in the POLD1 promoter known as a CDE(cell cycle-dependent element)lCHR(cell cycle gene homology region) element. A series of luci-ferase reporter constructs containing various POLD1 promoter mutations were used to investigate the role of the CDF_JCHR element in POLD1 transcription. When the CDE/CHR element was mutated, the promoter activity was up-regulated, and the cell-cycle related factors E2F1 and p21 stopped regulating the promoter. Furthermore, cell cycle-dependent changes in the promoter activity required the integra-tive CDE/CHR element. Electrophoretic mobility shift assay (EMSA) revealed the presence of at least three types of DNA/protein complexes binding to the CDE/CHR element. Our findings provide strong evidence that the CDE/CHR-like sequence is an active functional element in the POLD1 promoter, which is important for the cell cycle regulation of the POLD1 gene.

  12. Defining functional DNA elements in the human genome.

    Science.gov (United States)

    Kellis, Manolis; Wold, Barbara; Snyder, Michael P; Bernstein, Bradley E; Kundaje, Anshul; Marinov, Georgi K; Ward, Lucas D; Birney, Ewan; Crawford, Gregory E; Dekker, Job; Dunham, Ian; Elnitski, Laura L; Farnham, Peggy J; Feingold, Elise A; Gerstein, Mark; Giddings, Morgan C; Gilbert, David M; Gingeras, Thomas R; Green, Eric D; Guigo, Roderic; Hubbard, Tim; Kent, Jim; Lieb, Jason D; Myers, Richard M; Pazin, Michael J; Ren, Bing; Stamatoyannopoulos, John A; Weng, Zhiping; White, Kevin P; Hardison, Ross C

    2014-04-29

    With the completion of the human genome sequence, attention turned to identifying and annotating its functional DNA elements. As a complement to genetic and comparative genomics approaches, the Encyclopedia of DNA Elements Project was launched to contribute maps of RNA transcripts, transcriptional regulator binding sites, and chromatin states in many cell types. The resulting genome-wide data reveal sites of biochemical activity with high positional resolution and cell type specificity that facilitate studies of gene regulation and interpretation of noncoding variants associated with human disease. However, the biochemically active regions cover a much larger fraction of the genome than do evolutionarily conserved regions, raising the question of whether nonconserved but biochemically active regions are truly functional. Here, we review the strengths and limitations of biochemical, evolutionary, and genetic approaches for defining functional DNA segments, potential sources for the observed differences in estimated genomic coverage, and the biological implications of these discrepancies. We also analyze the relationship between signal intensity, genomic coverage, and evolutionary conservation. Our results reinforce the principle that each approach provides complementary information and that we need to use combinations of all three to elucidate genome function in human biology and disease.

  13. Density Functional Modelling of Elastic Properties of Elemental Semiconductors

    Directory of Open Access Journals (Sweden)

    M. Verma

    2011-01-01

    Full Text Available The expressions for bulk modulus, its first and second pressure derivatives for elemental semiconductors are derived using the ab initio pseudopotential approach to the total crystal energy within the framework of local Density Functional formalism. The expression for the second pressure derivative of the bulk modulus for four-fold crystal structures are derived for the first time within the pseudopotential framework. The computed results for the semiconductors under study are very close to the available experimental data and will be useful in the study of equation of states.

  14. Elements of a function analytic approach to probability.

    Energy Technology Data Exchange (ETDEWEB)

    Ghanem, Roger Georges (University of Southern California, Los Angeles, CA); Red-Horse, John Robert

    2008-02-01

    We first provide a detailed motivation for using probability theory as a mathematical context in which to analyze engineering and scientific systems that possess uncertainties. We then present introductory notes on the function analytic approach to probabilistic analysis, emphasizing the connections to various classical deterministic mathematical analysis elements. Lastly, we describe how to use the approach as a means to augment deterministic analysis methods in a particular Hilbert space context, and thus enable a rigorous framework for commingling deterministic and probabilistic analysis tools in an application setting.

  15. Scope Management of Non-Functional Requirements

    NARCIS (Netherlands)

    Kassab, M.; Daneva, M.; Ormandjieva, O.; Mueller, P.; Lyggesmeyer, P.; Maehle, E.

    2007-01-01

    In order to meet commitments in software projects, a realistic assessment must be made of project scope. Such an assessment relies on the availability of knowledge on the user-defined project requirements and their effort estimates and priorities, as well as their risk. This knowledge enables analys

  16. PDSS/IMC requirements and functional specifications

    Science.gov (United States)

    1983-01-01

    The system (software and hardware) requirements for the Payload Development Support System (PDSS)/Image Motion Compensator (IMC) are provided. The PDSS/IMC system provides the capability for performing Image Motion Compensator Electronics (IMCE) flight software test, checkout, and verification and provides the capability for monitoring the IMC flight computer system during qualification testing for fault detection and fault isolation.

  17. Scope Management of Non-Functional Requirements

    NARCIS (Netherlands)

    Kassab, M.; Daneva, Maia; Ormandjieva, O.; Mueller, P.; Lyggesmeyer, P.; Maehle, E.

    2007-01-01

    In order to meet commitments in software projects, a realistic assessment must be made of project scope. Such an assessment relies on the availability of knowledge on the user-defined project requirements and their effort estimates and priorities, as well as their risk. This knowledge enables

  18. Tank waste remediation system functions and requirements document

    Energy Technology Data Exchange (ETDEWEB)

    Carpenter, K.E

    1996-10-03

    This is the Tank Waste Remediation System (TWRS) Functions and Requirements Document derived from the TWRS Technical Baseline. The document consists of several text sections that provide the purpose, scope, background information, and an explanation of how this document assists the application of Systems Engineering to the TWRS. The primary functions identified in the TWRS Functions and Requirements Document are identified in Figure 4.1 (Section 4.0) Currently, this document is part of the overall effort to develop the TWRS Functional Requirements Baseline, and contains the functions and requirements needed to properly define the top three TWRS function levels. TWRS Technical Baseline information (RDD-100 database) included in the appendices of the attached document contain the TWRS functions, requirements, and architecture necessary to define the TWRS Functional Requirements Baseline. Document organization and user directions are provided in the introductory text. This document will continue to be modified during the TWRS life-cycle.

  19. Alu element-containing RNAs maintain nucleolar structure and function.

    Science.gov (United States)

    Caudron-Herger, Maïwen; Pankert, Teresa; Seiler, Jeanette; Németh, Attila; Voit, Renate; Grummt, Ingrid; Rippe, Karsten

    2015-11-12

    Non-coding RNAs play a key role in organizing the nucleus into functional subcompartments. By combining fluorescence microscopy and RNA deep-sequencing-based analysis, we found that RNA polymerase II transcripts originating from intronic Alu elements (aluRNAs) were enriched in the nucleolus. Antisense-oligo-mediated depletion of aluRNAs or drug-induced inhibition of RNA polymerase II activity disrupted nucleolar structure and impaired RNA polymerase I-dependent transcription of rRNA genes. In contrast, overexpression of a prototypic aluRNA sequence increased both nucleolus size and levels of pre-rRNA, suggesting a functional link between aluRNA, nucleolus integrity and pre-rRNA synthesis. Furthermore, we show that aluRNAs interact with nucleolin and target ectopic genomic loci to the nucleolus. Our study suggests an aluRNA-based mechanism that links RNA polymerase I and II activities and modulates nucleolar structure and rRNA production.

  20. New Generation Nuclear Plant -- High Level Functions and Requirements

    Energy Technology Data Exchange (ETDEWEB)

    J. M. Ryskamp; E. J. Gorski; E. A. Harvego; S. T. Khericha; G. A. Beitel

    2003-09-01

    This functions and requirements (F&R) document was prepared for the Next Generation Nuclear Plant (NGNP) Project. The highest-level functions and requirements for the NGNP preconceptual design are identified in this document, which establishes performance definitions for what the NGNP will achieve. NGNP designs will be developed based on these requirements by commercial vendor(s).

  1. Describing functional requirements for knowledge sharing communities

    Science.gov (United States)

    Garrett, Sandra; Caldwell, Barrett

    2002-01-01

    Human collaboration in distributed knowledge sharing groups depends on the functionality of information and communication technologies (ICT) to support performance. Since many of these dynamic environments are constrained by time limits, knowledge must be shared efficiently by adapting the level of information detail to the specific situation. This paper focuses on the process of knowledge and context sharing with and without mediation by ICT, as well as issues to be resolved when determining appropriate ICT channels. Both technology-rich and non-technology examples are discussed.

  2. Four Layered Approach to Non-Functional Requirements Analysis

    CERN Document Server

    Rao, A Ananda

    2012-01-01

    Identification of non-functional requirements is important for successful development and deployment of the software product. The acceptance of the software product by the customer depends on the non-functional requirements which are incorporated in the software. For this, we need to identify all the non-functional requirements required by all stakeholders. In the literature not many approaches are available for this purpose. Hence, we have proposed a four layered analysis approach for identification of non-functional requirements. The proposed layered approach has many advantages over non-layered approach. As part of this approach some rules are also proposed to be used in each layer. The approach is applied successfully on two case studies. The identified non-functional requirements are validated using a check list and in addition the completeness of the identified non-requirements is computed using a metric.

  3. Dynamic requirements for a functional protein hinge.

    Science.gov (United States)

    Kempf, James G; Jung, Ju-Yeon; Ragain, Christina; Sampson, Nicole S; Loria, J Patrick

    2007-04-20

    The enzyme triosephosphate isomerase (TIM) is a model of catalytic efficiency. The 11 residue loop 6 at the TIM active site plays a major role in this enzymatic prowess. The loop moves between open and closed states, which facilitate substrate access and catalysis, respectively. The N and C-terminal hinges of loop 6 control this motion. Here, we detail flexibility requirements for hinges in a comparative solution NMR study of wild-type (WT) TIM and a quintuple mutant (PGG/GGG). The latter contained glycine substitutions in the N-terminal hinge at Val167 and Trp168, which follow the essential Pro166, and in the C-terminal hinge at Lys174, Thr175, and Ala176. Previous work demonstrated that PGG/GGG has a tenfold higher Km value and 10(3)-fold reduced k(cat) relative to WT with either d-glyceraldehyde 3-phosphate or dihyrdroxyacetone phosphate as substrate. Our NMR results explain this in terms of altered loop-6 dynamics in PGG/GGG. In the mutant, loop 6 exhibits conformational heterogeneity with corresponding motional rates hinge design in proteins: structural rigidity is essential for focused motional freedom of active-site loops.

  4. 49 CFR 192.1007 - What are the required elements of an integrity management plan?

    Science.gov (United States)

    2010-10-01

    ...) PIPELINE SAFETY TRANSPORTATION OF NATURAL AND OTHER GAS BY PIPELINE: MINIMUM FEDERAL SAFETY STANDARDS Gas... 49 Transportation 3 2010-10-01 2010-10-01 false What are the required elements of an integrity management plan? 192.1007 Section 192.1007 Transportation Other Regulations Relating to Transportation...

  5. A functional gene array for detection of bacterial virulence elements.

    Directory of Open Access Journals (Sweden)

    Crystal Jaing

    Full Text Available Emerging known and unknown pathogens create profound threats to public health. Platforms for rapid detection and characterization of microbial agents are critically needed to prevent and respond to disease outbreaks. Available detection technologies cannot provide broad functional information about known or novel organisms. As a step toward developing such a system, we have produced and tested a series of high-density functional gene arrays to detect elements of virulence and antibiotic resistance mechanisms. Our first generation array targets genes from Escherichia coli strains K12 and CFT073, Enterococcus faecalis and Staphylococcus aureus. We determined optimal probe design parameters for gene family detection and discrimination. When tested with organisms at varying phylogenetic distances from the four target strains, the array detected orthologs for the majority of targeted gene families present in bacteria belonging to the same taxonomic family. In combination with whole-genome amplification, the array detects femtogram concentrations of purified DNA, either spiked in to an aerosol sample background, or in combinations from one or more of the four target organisms. This is the first report of a high density NimbleGen microarray system targeting microbial antibiotic resistance and virulence mechanisms. By targeting virulence gene families as well as genes unique to specific biothreat agents, these arrays will provide important data about the pathogenic potential and drug resistance profiles of unknown organisms in environmental samples.

  6. Enriched Element-Free Galerkin Method for Fracture Analysis of Functionally Graded Piezoelectric Materials

    Directory of Open Access Journals (Sweden)

    Guang Wei Meng

    2015-01-01

    Full Text Available A new method using the enriched element-free Galerkin method (EEFGM to model functionally graded piezoelectric materials (FGPMs with cracks was presented. To improve the solution accuracy, extended terms were introduced into the approximation function of the conventional element-free Galerkin method (EFGM to describe the displacement and electric fields near the crack. Compared with the conventional EFGM, the new approach requires smaller domain to describe the crack-tip singular field. Additionally, the domain of the nodes was not affected by the crack. Therefore, the visibility method and the diffraction method were no longer needed. The mechanical response of FGPM was discussed, when its material parameters changed exponentially in a certain direction. The modified J-integrals for FGPM were deduced, whose results were compared with the results of the conventional EFGM and the analytical solution. Numerical example results illustrated that this method is feasible and precise.

  7. Short interspersed element (SINE) depletion and long interspersed element (LINE) abundance are not features universally required for imprinting.

    Science.gov (United States)

    Cowley, Michael; de Burca, Anna; McCole, Ruth B; Chahal, Mandeep; Saadat, Ghazal; Oakey, Rebecca J; Schulz, Reiner

    2011-04-20

    Genomic imprinting is a form of gene dosage regulation in which a gene is expressed from only one of the alleles, in a manner dependent on the parent of origin. The mechanisms governing imprinted gene expression have been investigated in detail and have greatly contributed to our understanding of genome regulation in general. Both DNA sequence features, such as CpG islands, and epigenetic features, such as DNA methylation and non-coding RNAs, play important roles in achieving imprinted expression. However, the relative importance of these factors varies depending on the locus in question. Defining the minimal features that are absolutely required for imprinting would help us to understand how imprinting has evolved mechanistically. Imprinted retrogenes are a subset of imprinted loci that are relatively simple in their genomic organisation, being distinct from large imprinting clusters, and have the potential to be used as tools to address this question. Here, we compare the repeat element content of imprinted retrogene loci with non-imprinted controls that have a similar locus organisation. We observe no significant differences that are conserved between mouse and human, suggesting that the paucity of SINEs and relative abundance of LINEs at imprinted loci reported by others is not a sequence feature universally required for imprinting.

  8. Short interspersed element (SINE depletion and long interspersed element (LINE abundance are not features universally required for imprinting.

    Directory of Open Access Journals (Sweden)

    Michael Cowley

    Full Text Available Genomic imprinting is a form of gene dosage regulation in which a gene is expressed from only one of the alleles, in a manner dependent on the parent of origin. The mechanisms governing imprinted gene expression have been investigated in detail and have greatly contributed to our understanding of genome regulation in general. Both DNA sequence features, such as CpG islands, and epigenetic features, such as DNA methylation and non-coding RNAs, play important roles in achieving imprinted expression. However, the relative importance of these factors varies depending on the locus in question. Defining the minimal features that are absolutely required for imprinting would help us to understand how imprinting has evolved mechanistically. Imprinted retrogenes are a subset of imprinted loci that are relatively simple in their genomic organisation, being distinct from large imprinting clusters, and have the potential to be used as tools to address this question. Here, we compare the repeat element content of imprinted retrogene loci with non-imprinted controls that have a similar locus organisation. We observe no significant differences that are conserved between mouse and human, suggesting that the paucity of SINEs and relative abundance of LINEs at imprinted loci reported by others is not a sequence feature universally required for imprinting.

  9. Functional Requirements for an Electronic Work Package System

    Energy Technology Data Exchange (ETDEWEB)

    Oxstrand, Johanna H. [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2016-12-01

    This document provides a set of high level functional requirements for a generic electronic work package (eWP) system. The requirements have been identified by the U.S. nuclear industry as a part of the Nuclear Electronic Work Packages - Enterprise Requirements (NEWPER) initiative. The functional requirements are mainly applied to eWP system supporting Basic and Moderate types of smart documents, i.e., documents that have fields for recording input such as text, dates, numbers, and equipment status, and documents which incorporate additional functionalities such as form field data “type“ validation (e.g. date, text, number, and signature) of data entered and/or self-populate basic document information (usually from existing host application meta data) on the form when the user first opens it. All the requirements are categorized by the roles; Planner, Supervisor, Craft, Work Package Approval Reviewer, Operations, Scheduling/Work Control, and Supporting Functions. The categories Statistics, Records, Information Technology are also included used to group the requirements. All requirements are presented in Section 2 through Section 11. Examples of more detailed requirements are provided for the majority of high level requirements. These examples are meant as an inspiration to be used as each utility goes through the process of identifying their specific requirements. The report’s table of contents provides a summary of the high level requirements.

  10. Finite element strategies to satisfy clinical and engineering requirements in the field of percutaneous valves.

    Science.gov (United States)

    Capelli, Claudio; Biglino, Giovanni; Petrini, Lorenza; Migliavacca, Francesco; Cosentino, Daria; Bonhoeffer, Philipp; Taylor, Andrew M; Schievano, Silvia

    2012-12-01

    Finite element (FE) modelling can be a very resourceful tool in the field of cardiovascular devices. To ensure result reliability, FE models must be validated experimentally against physical data. Their clinical application (e.g., patients' suitability, morphological evaluation) also requires fast simulation process and access to results, while engineering applications need highly accurate results. This study shows how FE models with different mesh discretisations can suit clinical and engineering requirements for studying a novel device designed for percutaneous valve implantation. Following sensitivity analysis and experimental characterisation of the materials, the stent-graft was first studied in a simplified geometry (i.e., compliant cylinder) and validated against in vitro data, and then in a patient-specific implantation site (i.e., distensible right ventricular outflow tract). Different meshing strategies using solid, beam and shell elements were tested. Results showed excellent agreement between computational and experimental data in the simplified implantation site. Beam elements were found to be convenient for clinical applications, providing reliable results in less than one hour in a patient-specific anatomical model. Solid elements remain the FE choice for engineering applications, albeit more computationally expensive (>100 times). This work also showed how information on device mechanical behaviour differs when acquired in a simplified model as opposed to a patient-specific model.

  11. Derivation of an Efficient Non-Prismatic Thin Curved Beam Element Using Basic Displacement Functions

    Directory of Open Access Journals (Sweden)

    Ahmad Shahba

    2012-01-01

    Full Text Available The efficiency and accuracy of the elements proposed by the Finite Element Method (FEM considerably depend on the interpolating functions, namely shape functions, used to formulate the displacement field within an element. In this paper, a new insight is proposed for derivation of elements from a mechanical point of view. Special functions namely Basic Displacement Functions (BDFs are introduced which hold pure structural foundations. Following basic principles of structural mechanics, it is shown that exact shape functions for non-prismatic thin curved beams could be derived in terms of BDFs. Performing a limiting study, it is observed that the new curved beam element successfully becomes the straight Euler-Bernoulli beam element. Carrying out numerical examples, it is shown that the element provides exact static deformations. Finally efficiency of the method in free vibration analysis is verified through several examples. The results are in good agreement with those in the literature.

  12. Analysis of Dynamic Fracture Parameters in Functionally Graded Material Plates with Cracks by Graded Finite Element Method and Virtual Crack Closure Technique

    Directory of Open Access Journals (Sweden)

    Li Ming Zhou

    2016-01-01

    Full Text Available Based on the finite element software ABAQUS and graded element method, we developed a dummy node fracture element, wrote the user subroutines UMAT and UEL, and solved the energy release rate component of functionally graded material (FGM plates with cracks. An interface element tailored for the virtual crack closure technique (VCCT was applied. Fixed cracks and moving cracks under dynamic loads were simulated. The results were compared to other VCCT-based analyses. With the implementation of a crack speed function within the element, it can be easily expanded to the cases of varying crack velocities, without convergence difficulty for all cases. Neither singular element nor collapsed element was required. Therefore, due to its simplicity, the VCCT interface element is a potential tool for engineers to conduct dynamic fracture analysis in conjunction with commercial finite element analysis codes.

  13. The structure and function of the rous sarcoma virus RNA stability element.

    Science.gov (United States)

    Withers, Johanna B; Beemon, Karen L

    2011-11-01

    For simple retroviruses, such as the Rous sarcoma virus (RSV), post-transcriptional control elements regulate viral RNA splicing, export, stability, and packaging into virions. These RNA sequences interact with cellular host proteins to regulate and facilitate productive viral infections. One such element, known as the RSV stability element (RSE), is required for maintaining stability of the full-length unspliced RNA. This viral RNA serves as the mRNA for the Gag and Pol proteins and also as the genome packaged in progeny virions. When the RSE is deleted from the viral RNA, the unspliced RNA becomes unstable and is degraded in a Upf1-dependent manner. Current evidence suggests that the RSE inhibits recognition of the viral gag termination codon by the nonsense-mediated mRNA decay (NMD) pathway. We believe that the RSE acts as an insulator to NMD, thereby preventing at least one of the required functional steps that target an mRNA for degradation. Here, we discuss the history of the RSE and the current model of how the RSE is interacting with cellular NMD factors.

  14. Method of non-functional requirements balancing during service development

    Directory of Open Access Journals (Sweden)

    Larisa Globa

    2012-09-01

    Full Text Available Today, the list of telecom services, their functionality and requirements for Service Execu-tion Environment (SEE are changing extremely fast. Especially when it concerns require-ments for charging as they have a high influence on business. This results in the need for constant adaptation and reconfiguration of Online Charging System (OCS used in mobile operator networks. Moreover any new functionality requested from a service can have an impact on system behavior (performance, response time, delays which are in general non-functional requirements. Currently, this influence and reconfiguration strategies are poorly formalized and validated. Current state-of-the-art approaches are considered methodolo-gies that can model non-functional or functional requirements but these approaches don’t take into account interaction between functional and nonfunctional requirements and col-laboration between services. All these result in time and money consuming service devel-opment and testing, and cause delays during service deployment. The balancing method proposed in this paper fills this gap. It employs a well-defined workflow with predefined stages for development and deployment process for OCS. The applicability of this novel ap-proach is described in a separate section which contains an example of GPRS service charging. A tool, based on this method will be developed, providing automation of service functionality influence on non-functional requirements and allowing to provide a target de-ployment model for a particular customer. The reduction of development time and thus nec-essary financial input has been proved based on real-world experiments.

  15. 33 CFR 157.12f - Workshop functional test requirements.

    Science.gov (United States)

    2010-07-01

    ... CARRYING OIL IN BULK Design, Equipment, and Installation § 157.12f Workshop functional test requirements... the specific design of equipment. A completed workshop certificate including the delivery test...; (2) A check of the correct function of the signal processor and the recording equipment...

  16. Functions and requirements for single-shell tank leakage mitigation

    Energy Technology Data Exchange (ETDEWEB)

    Cruse, J.M.

    1994-09-22

    This document provides the initial functions and requirements for the leakage mitigation mission applicable to past and potential future leakage from the Hanford Site`s 149 single-shell high-level waste tanks. This mission is a part of the overall mission of the Westinghouse Hanford Company Tank Waste Remediation System division to remediate the tank waste in a safe and acceptable manner. Systems engineering principles are being applied to this effort. A Mission Analysis has been completed, this document reflects the next step in the systems engineering approach to decompose the mission into primary functions and requirements. The functions and requirements in this document apply to mitigative actions to be taken regarding below ground leaks from SST containment boundaries and the resulting soil contamination. Leakage mitigation is invoked in the TWRS Program in three fourth level functions: (1) Store Waste, (2) Retrieve Waste, and (3) Disposition Excess Facilities.

  17. Spatio-temporal requirements for transposable element piRNA-mediated silencing during Drosophila oogenesis.

    Science.gov (United States)

    Dufourt, Jérémy; Dennis, Cynthia; Boivin, Antoine; Gueguen, Nathalie; Théron, Emmanuelle; Goriaux, Coline; Pouchin, Pierre; Ronsseray, Stéphane; Brasset, Emilie; Vaury, Chantal

    2014-02-01

    During Drosophila oogenesis, transposable element (TE) repression involves the Piwi-interacting RNA (piRNA) pathway which ensures genome integrity for the next generation. We developed a transgenic model to study repression of the Idefix retrotransposon in the germline. Using a candidate gene KD-approach, we identified differences in the spatio-temporal requirements of the piRNA pathway components for piRNA-mediated silencing. Some of them (Aub, Vasa, Spn-E) are necessary in very early stages of oogenesis within the germarium and appear to be less important for efficient TE silencing thereafter. Others (Piwi, Ago3, Mael) are required at all stages of oogenesis. Moreover, during early oogenesis, in the dividing cysts within the germarium, Idefix anti-sense transgenes escape host control, and this is associated with very low piwi expression. Silencing of P-element-based transgenes is also strongly weakened in these cysts. This region, termed the 'Piwiless pocket' or Pilp, may ensure that new TE insertions occur and are transmitted to the next generation, thereby contributing to genome dynamics. In contrast, piRNA-mediated silencing is strong in germline stem cells in which TE mobilization is tightly repressed ensuring the continued production of viable germline cysts.

  18. Main functional elements having defects of illegal residential buildings: The case of Cova da Moura district

    NARCIS (Netherlands)

    Vilhena, A.; Costa Branco De Oliveira Pedro, J.A.; Baptista Coelho, A.; Vasconcelos Paiva, J.

    2011-01-01

    The purpose of the paper is to describe the main functional elements with defects in illegal residential buildings. Three research questions are addressed: What are the main functional elements with defects in buildings and in dwellings? What are the main defects found? In which way these defects af

  19. Main functional elements having defects of illegal residential buildings: The case of Cova da Moura district

    NARCIS (Netherlands)

    Vilhena, A.; Costa Branco De Oliveira Pedro, J.A.; Baptista Coelho, A.; Vasconcelos Paiva, J.

    2011-01-01

    The purpose of the paper is to describe the main functional elements with defects in illegal residential buildings. Three research questions are addressed: What are the main functional elements with defects in buildings and in dwellings? What are the main defects found? In which way these defects

  20. Equivalent Dynamic Stiffness Mapping technique for identifying nonlinear structural elements from frequency response functions

    Science.gov (United States)

    Wang, X.; Zheng, G. T.

    2016-02-01

    A simple and general Equivalent Dynamic Stiffness Mapping technique is proposed for identifying the parameters or the mathematical model of a nonlinear structural element with steady-state primary harmonic frequency response functions (FRFs). The Equivalent Dynamic Stiffness is defined as the complex ratio between the internal force and the displacement response of unknown element. Obtained with the test data of responses' frequencies and amplitudes, the real and imaginary part of Equivalent Dynamic Stiffness are plotted as discrete points in a three dimensional space over the displacement amplitude and the frequency, which are called the real and the imaginary Equivalent Dynamic Stiffness map, respectively. These points will form a repeatable surface as the Equivalent Dynamic stiffness is only a function of the corresponding data as derived in the paper. The mathematical model of the unknown element can then be obtained by surface-fitting these points with special functions selected by priori knowledge of the nonlinear type or with ordinary polynomials if the type of nonlinearity is not pre-known. An important merit of this technique is its capability of dealing with strong nonlinearities owning complicated frequency response behaviors such as jumps and breaks in resonance curves. In addition, this technique could also greatly simplify the test procedure. Besides there is no need to pre-identify the underlying linear parameters, the method uses the measured data of excitation forces and responses without requiring a strict control of the excitation force during the test. The proposed technique is demonstrated and validated with four classical single-degree-of-freedom (SDOF) numerical examples and one experimental example. An application of this technique for identification of nonlinearity from multiple-degree-of-freedom (MDOF) systems is also illustrated.

  1. Analysis of delayed convergence in the three-noded Timoshenko beam element using the function space approach

    Indian Academy of Sciences (India)

    Somenath Mukherjee; Gangan Prathap

    2002-10-01

    Despite satisfying only completeness and continuity requirements, elements often perform erroneously in a certain class of problems, called the locking situations, where they display spurious stress oscillations and enhanced stiffness properties. The function space approach that effectively substantiates the postulates of the field consistency paradigm is an efficient tool to reveal the fundamental cause of locking phenomena, and propose methods to eliminate this pathological problem. In this paper, we review the delayed convergence behaviour of three-noded Timoshenko beam elements using the rigorous function space approach. Explicit, closed form algebraic results for the element strains, stresses and errors have been derived using this method. The performance of the field-inconsistent three-noded Timoshenko beam element is compared with that of the field-inconsistent twonoded beam element. It is demonstrated that while the field-inconsistent two-noded linear element is prone to shear locking, the field-inconsistent three-noded element is not very vulnerable to this pathological problem, despite the resulting shear oscillations.

  2. Functional interferon system is required for clearance of lassa virus.

    Science.gov (United States)

    Yun, Nadezhda E; Poussard, Allison L; Seregin, Alexey V; Walker, Aida G; Smith, Jennifer K; Aronson, Judith F; Smith, Jeanon N; Soong, Lynn; Paessler, Slobodan

    2012-03-01

    Lassa virus (LASV) is the causative agent of Lassa hemorrhagic fever (LF) in humans, a deadly disease endemic to West Africa that results in 5,000 to 10,000 deaths annually. Here we present results demonstrating that functional type I and type II interferon (IFN) signaling is required for efficient control of LASV dissemination and clearance.

  3. Functional requirement specification in the packaging development chain

    NARCIS (Netherlands)

    Lutters, Diederick; ten Klooster, Roland

    2008-01-01

    As it is clear that the full packaging life cycle – at least partially – coincides with the product life cycle, both cycles are interwoven. Each has a network of functional requirements, with specific hierarchic propensities. These networks overlap, with prevailing hierarchies playing important

  4. New element for optimizing the functioning of sediment traps

    Science.gov (United States)

    Schwindt, Sebastian; Franca, Mário; Schleiss, Anton

    2017-04-01

    Sediment traps protect urban areas against excessive sediment transport during hazardous floods and consist typically of a retention basin with an open sediment check dam at the downstream end. The design, as well as the morphological processes within the retention basin, were analyzed by several authors. With regard to open sediment check dams two types of triggering mechanisms for the initiation of sediment retention can be distinguished: (1) mechanical and (2) hydraulic clogging of the structure. Recent studies have shown that outlet structures combining both clogging principles may be considered to avoid undesired self-flushing. Further elements of check dams are conceivable, e.g. for retaining or conveying driftwood. This study analyses experimentally working principles and design criteria of standard elements of sediment traps. Furthermore, it introduces a new structural element to the sediment trap design with a guiding channel in the retention reservoir. Taking into account the natural shape of mountain rivers, the guiding channel has a trapezoidal cross-section shape and a rough but fixed bed. The effect of the guiding channel on sediment deposition pattern and re-mobilization are studied by means of physical model experiments with a standardized hydrograph and variable sediment supply. The results are evaluated by means of zenithal pictures and bedload transport rate, measured at the downstream end of the model. Major advantages of the combined use of both clogging principles include an improved control of the initiation of sediment deposition in order to allow for sediment transfer for small floods and a reduction of hazards related to self-flushing.

  5. Model Penentuan Nilai Target Functional Requirement Berbasis Utilitas

    Directory of Open Access Journals (Sweden)

    Cucuk Nur Rosyidi

    2012-01-01

    Full Text Available In a product design and development process, a designer faces a problem to decide functional requirement (FR target values. That decision is made under a risk since it is conducted in the early design phase using incomplete information. Utility function can be used to reflect the decision maker attitude towards the risk in making such decision. In this research, we develop a utility-based model to determine FR target values using quadratic utility function and information from Quality Function Deployment (QFD. A pencil design is used as a numerical example using quadratic utility function for each FR. The model can be applied for balancing customer and designer interest in determining FR target values.

  6. Functional connection of didactical elements in teaching geography

    Directory of Open Access Journals (Sweden)

    Živković Ljiljana

    2010-01-01

    Full Text Available The aim of this work is to present complex relations within didactical triangle as well as review of the practical usage of relations of didactical polygon. Importance of subject of this work is, certainly, its constant actualization and irrepressible change which is happening within elements and in their mutual interaction. This kind of relation brings innovations and suffers changes from modern times. Starting from immediate ways of communication to closer and further perceive of their development, the subject gets dimension of expected and somewhat exciting. The theme ensued because of the need for logical separation of didactical elements and also to connect them through complex system of communication. Their imbues are coming to express daily while interaction is developing not only in historical period but in instantaneous stages. The media, today, gives grade to development of society and represent degree of progress. As such an important factor, the role of the media must be taken into consideration. Geographical achievement is represented by teaching methods of geography and in that way it represents significant media. Complicatedness of this theme also reflects in universality; geography has advanced as science and there is great expectation for methodical science to catch up with geography and to present new manners, ways of transferring knowledge. .

  7. A spider tRNA(Ala) requires a far upstream sequence element for expression.

    Science.gov (United States)

    Cintrón, I; Capó, L; Plazaola, A; Arroyo, G; Candelas, G C

    1999-04-29

    Within the series of timed differential accumulations of small RNAs we have shown to prelude the synthesis of fibroin in the large ampullate glands of Nephila clavipes (Nc), we are currently directing our attention to the alanine tRNAs. This work reports the subcloning of the members of a tRNAAla gene cluster and the optimization of their transcription in a heterologous cell-free system derived from Bombyx mori (Bm) silkglands. Our data show that the heterologous cell-free system supports the faithful and differential transcription of the individual spider alanine tRNA genes. We are thus making use of the extract to characterize the individual genes with respect to flank-contained regulatory elements through cell-free transcription of gene derivatives. The work has been initiated with pNTA3 because of its high transcriptional activity. Interestingly, the transcription of this gene requires a far upstream sequence, an uncommon modality in tRNA genes.

  8. What are the elements required to improve exposure estimates in life cycle assessments?

    DEFF Research Database (Denmark)

    Ernstoff, Alexi; Rosenbaum, Ralph K.; Margni, Manuele

    2016-01-01

    In this study we aim to identify and discuss priority elements required to improve exposure estimates in Life cycle assessment (LCA). LCA aims at guiding decision-support to minimize damages on resources, humans, and ecosystems which incur via providing society with products and services. Potential...... human toxicity and ecosystem toxicity of chemicals posed by different product life cycle stages are characterized in the life cycle impact assessment (LCIA) phase. Exposure and effect quantification as part of LCIA toxicity characterization faces numerous challenges related to inventory analysis (e.......g. number and quantity of chemicals emitted), substance-specific modelling (e.g. organics, inorganics, nano-materials) in various environments and time horizons, human and ecosystem exposure quantification (e.g. exposed organisms and exposure pathways), and toxicity end-points (e.g. carcinogenicity...

  9. Functional requirements for a central research imaging data repository.

    Science.gov (United States)

    Franke, Thomas; Gruetz, Romanus; Dickmann, Frank

    2013-01-01

    The current situation at many university medical centers regarding the management of biomedical research imaging data leaves much to be desired. In contrast to the recommendations of the German Research Foundation (DFG) and the German Council of Sciences and Humanities regarding the professional management of research data, there are commonly many individual data pools for research data in each institute and the management remains the responsibility of the researcher. A possible solution for this situation would be to install local central repositories for biomedical research imaging data. In this paper, we developed a scenario based on abstracted use-cases for institutional research undertakings as well as collaborative biomedical research projects and analyzed the functional requirements that a local repository would have to fulfill. We determined eight generic categories of functional requirements, which can be viewed as a basic guideline for the minimum functionality of a central repository for biomedical research imaging data.

  10. The interaction between the yeast telomerase RNA and the Est1 protein requires three structural elements.

    Science.gov (United States)

    Lubin, Johnathan W; Tucey, Timothy M; Lundblad, Victoria

    2012-09-01

    In the budding yeast Saccharomyces cerevisiae, the telomerase enzyme is composed of a 1.3-kb TLC1 RNA that forms a complex with Est2 (the catalytic subunit) and two regulatory proteins, Est1 and Est3. Previous work has identified a conserved 5-nt bulge, present in a long helical arm of TLC1, which mediates binding of Est1 to TLC1. However, increased expression of Est1 can bypass the consequences of removal of this RNA bulge, indicating that there are additional binding site(s) for Est1 on TLC1. We report here that a conserved single-stranded internal loop immediately adjacent to the bulge is also required for the Est1-RNA interaction; furthermore, a TLC1 variant that lacks this internal loop but retains the bulge cannot be suppressed by Est1 overexpression, arguing that the internal loop may be a more critical element for Est1 binding. An additional structural feature consisting of a single-stranded region at the base of the helix containing the bulge and internal loop also contributes to recognition of TLC1 by Est1, potentially by providing flexibility to this helical arm. Association of Est1 with each of these TLC1 motifs was assessed using a highly sensitive biochemical assay that simultaneously monitors the relative levels of the Est1 and Est2 proteins in the telomerase complex. The identification of three elements of TLC1 that are required for Est1 association provides a detailed view of this particular protein-RNA interaction.

  11. Cognitive-graphic method for constructing of hierarchical forms of basic functions of biquadratic finite element

    Science.gov (United States)

    Astionenko, I. O.; Litvinenko, O. I.; Osipova, N. V.; Tuluchenko, G. Ya.; Khomchenko, A. N.

    2016-10-01

    Recently the interpolation bases of the hierarchical type have been used for the problem solving of the approximation of multiple arguments functions (such as in the finite-element method). In this work the cognitive graphical method of constructing of the hierarchical form bases on the serendipity finite elements is suggested, which allowed to get the alternative bases on a biquadratic finite element from the serendipity family without internal knots' inclusion. The cognitive-graphic method allowed to improve the known interpolation procedure of Taylor and to get the modified elements with irregular arrangement of knots. The proposed procedures are universal and are spread in the area of finite-elements.

  12. Elements of mathematics functions of a real variable : elementary theory

    CERN Document Server

    Bourbaki, Nicolas

    2004-01-01

    This book is an English translation of the last French edition of Bourbaki’s Fonctions d'une Variable Réelle. The first chapter is devoted to derivatives, Taylor expansions, the finite increments theorem, convex functions. In the second chapter, primitives and integrals (on arbitrary intervals) are studied, as well as their dependence with respect to parameters. Classical functions (exponential, logarithmic, circular and inverse circular) are investigated in the third chapter. The fourth chapter gives a thorough treatment of differential equations (existence and unicity properties of solutions, approximate solutions, dependence on parameters) and of systems of linear differential equations. The local study of functions (comparison relations, asymptotic expansions) is treated in chapter V, with an appendix on Hardy fields. The theory of generalized Taylor expansions and the Euler-MacLaurin formula are presented in the sixth chapter, and applied in the last one to the study of the Gamma function on the real ...

  13. APPLICATION OF PENALTY FUNCTION METHOD IN ISOPARAMETRIC HYBRID FINITE ELEMENT ANALYSIS

    Institute of Scientific and Technical Information of China (English)

    CHEN Dao-zheng; JIAO Zhao-ping

    2005-01-01

    By the aid of the penalty function method, the equilibrium restriction conditions were introduced to the isoparametric hybrid finite element analysis, and the concrete application course of the penalty function method in three-dimensional isoparametric hybrid finite element was discussed. The separated penalty parameters method and the optimal hybrid element model with penalty balance were also presented.The penalty balance method can effectively refrain the parasitical stress on the premise of no additional degrees of freedom. The numeric experiment shows that the presented element not only is effective in improving greatly the numeric calculation precision of distorted grids but also has the universality.

  14. Squamous morules are functionally inert elements of premalignant endometrial neoplasia.

    Science.gov (United States)

    Lin, Ming-Chieh; Lomo, Lesley; Baak, Jan P A; Eng, Charis; Ince, Tan A; Crum, Christopher P; Mutter, George L

    2009-02-01

    Squamous morules are a common component of premalignant glandular lesions that are followed by glandular, rather than squamous, carcinomas. We tested the hypothesis that the appearance of glands associated with morules predicts cancer risk, and undertook molecular testing to determine the clonal and hormonal response properties of admixed squamous and glandular elements. A total of 66 patients with squamous morules in an index endometrial biopsy had follow-up clinical data (average follow-up: interval 31 months, 2.5 biopsies) showing development of carcinoma in 11% (7/66) of cases. The histological appearance of morule-associated glands in the index biopsy was significantly associated with this clinical outcome, with the majority (71%, 5/7) of cancer occurrences following an overtly premalignant lesion (endometrial intraepithelial neoplasia) with squamous morules. Eight endometrial intraepithelial neoplasias with squamous morules were examined by immunohistochemistry for estrogen and progesterone receptors and mitotic activity (Ki-67 antigen percent stained). Glandular components had abundant estrogen and progesterone receptors, and high levels of mitotic activity in all cases. In sharp contrast, all squamous morules were devoid of sex hormone receptors and had undetectable or extremely low-proliferation rates. When mutated, the same specific PTEN mutation was detected in squamous and glandular elements, indicating that both are of common lineage. The clinical and laboratory data are consistent with a model of morule biology in which squamous morules are a hormonally incompetent subpopulation of endometrial glandular lesions. Isolated morules might result from artifactual displacement from their native glandular context, or selective hormonally induced regression of the glandular but not squamous components over time. Subsequent cancer risk, as promoted by estrogens, is greatest when the glandular component has the appearance of endometrial intraepithelial

  15. Elemental and isotopic imaging to study biogeochemical functioning of intact soil micro-environments

    Science.gov (United States)

    Mueller, Carsten W.

    2017-04-01

    The complexity of soils extends from the ecosystem-scale to individual micro-aggregates, where nano-scale interactions between biota, organic matter (OM) and mineral particles are thought to control the long-term fate of soil carbon and nitrogen. It is known that such biogeochemical processes show disproportionally high reaction rates within nano- to micro-meter sized isolated zones ('hot spots') in comparison to surrounding areas. However, the majority of soil research is conducted on large bulk (> 1 g) samples, which are often significantly altered prior to analysis and analysed destructively. Thus it has previously been impossible to study elemental flows (e.g. C and N) between plants, microbes and soil in complex environments at the necessary spatial resolution within an intact soil system. By using nano-scale secondary ion mass spectrometry (NanoSIMS) in concert with other imaging techniques (e.g. scanning electron microscopy (SEM) and micro computed tomography (µCT)), classic analyses (isotopic and elemental analysis) and biochemical methods (e.g. GC-MS) it is possible to exhibit a more complete picture of soil processes at the micro-scale. I will present exemplarily results about the fate and distribution of organic C and N in complex micro-scale soil structures for a range of intact soil systems. Elemental imaging was used to study initial soil formation as an increase in the structural connectivity of micro-aggregates. Element distribution will be presented as a key to detect functional spatial patterns and biogeochemical hot spots in macro-aggregate functioning and development. In addition isotopic imaging will be demonstrated as a key to trace the fate of plant derived OM in the intact rhizosphere from the root to microbiota and mineral soil particles. Especially the use of stable isotope enrichment (e.g. 13CO2, 15NH4+) in conjunction with NanoSIMS allows to directly trace the fate of OM or nutrients in soils at the relevant scale (e.g. assimilate C

  16. Extensions of PDZ domains as important structural and functional elements

    OpenAIRE

    Wang, Conan K.; Pan, Lifeng; Chen, Jia; Zhang, Mingjie

    2010-01-01

    ‘Divide and conquer’ has been the guiding strategy for the study of protein structure and function. Proteins are divided into domains with each domain having a canonical structural definition depending on its type. In this review, we push forward with the interesting observation that many domains have regions outside of their canonical definition that affect their structure and function; we call these regions ‘extensions’. We focus on the highly abundant PDZ (PSD-95, DLG1 and ZO-1) domain. Us...

  17. Functional Requirements for Information Resource Provenance on the Web

    Energy Technology Data Exchange (ETDEWEB)

    McCusker, James P.; Lebo, Timothy; Graves, Alvaro; Difranzo, Dominic; Pinheiro da Silva, Paulo; McGuinness, Deborah L.

    2012-06-19

    We provide a means to formally explain the relationship between HTTP URLs and the representations returned when they are requested. According to existing World Wide Web architecture, the URL serves as an identier for a semiotic referent while the document returned via HTTP serves as a representation of the same referent. This begins with two sides of a semiotic triangle; the third side is the relationship between the URL and the representation received. We complete this description by extending the library science resource model Functional Requirements for Bibliographic Resources (FRBR) with cryptographic message and content digests to create a Functional Requirements for Information Resources (FRIR). We show how applying the FRIR model to HTTP GET and POST transactions disambiguates the many relationships between a given URL and all representations received from its request, provides fine-grained explanations that are complementary to existing explanations of web resources, and integrates easily into the emerging W3C provenance standard.

  18. Adapting ORAP to wind plants : industry value and functional requirements.

    Energy Technology Data Exchange (ETDEWEB)

    2010-08-01

    Strategic Power Systems (SPS) was contracted by Sandia National Laboratories to assess the feasibility of adapting their ORAP (Operational Reliability Analysis Program) tool for deployment to the wind industry. ORAP for Wind is proposed for use as the primary data source for the CREW (Continuous Reliability Enhancement for Wind) database which will be maintained by Sandia to enable reliability analysis of US wind fleet operations. The report primarily addresses the functional requirements of the wind-based system. The SPS ORAP reliability monitoring system has been used successfully for over twenty years to collect RAM (Reliability, Availability, Maintainability) and operations data for benchmarking and analysis of gas and steam turbine performance. This report documents the requirements to adapt the ORAP system for the wind industry. It specifies which existing ORAP design features should be retained, as well as key new requirements for wind. The latter includes alignment with existing and emerging wind industry standards (IEEE 762, ISO 3977 and IEC 61400). There is also a comprehensive list of thirty critical-to-quality (CTQ) functional requirements which must be considered and addressed to establish the optimum design for wind.

  19. An Ebox element in the proximal Gata4 promoter is required for Gata4 expression in vivo.

    Directory of Open Access Journals (Sweden)

    Alain Boulende Sab

    Full Text Available GATA4 is an essential transcription factor required for the development and function of multiple tissues, including a major role in gonadogenesis. Despite its crucial role, the molecular mechanisms that regulate Gata4 expression in vivo remain poorly understood. We recently found that the Gata4 gene is expressed as multiple transcripts with distinct 5' origins. These co-expressed alternative transcripts are generated by different non-coding first exons with transcripts E1a and E1b being the most prominent. Moreover, we previously showed that an Ebox element, located in Gata4 5' flanking sequences upstream of exon 1a, is important for the promoter activity of these sequences in cell lines. To confirm the importance of this element in vivo, we generated and characterized Gata4 Ebox knockout mice. Quantitative PCR analyses realized on gonads, heart and liver at three developmental stages (embryonic, pre-pubertal and adult revealed that the Ebox mutation leads to a robust and specific decrease (up to 89% of Gata4 E1a transcript expression in all tissues and stages examined. However, a detailed characterization of the gonads revealed normal morphology and GATA4 protein levels in these mutants. Our qPCR data further indicate that this outcome is most likely due to the presence of Gata4 E1b mRNA, whose expression levels were not decreased by the Ebox mutation. In conclusion, our work clearly confirms the importance of the proximal Ebox element and suggests that adequate GATA4 protein expression is likely protected by a compensation mechanism between Gata4 E1a and E1b transcripts operating at the translational level.

  20. Large-scale all-electron density functional theory calculations using an enriched finite element basis

    CERN Document Server

    Kanungo, Bikash

    2016-01-01

    We present a computationally efficient approach to perform large-scale all-electron density functional theory calculations by enriching the classical finite element basis with compactly supported atom-centered numerical basis functions that are constructed from the solution of the Kohn-Sham (KS) problem for single atoms. We term these numerical basis functions as enrichment functions, and the resultant basis as the enriched finite element basis. The enrichment functions are compactly supported through the use of smooth cutoff functions, which enhances the conditioning and maintains the locality of the basis. The integrals involved in the evaluation of the discrete KS Hamiltonian and overlap matrix in the enriched finite element basis are computed using an adaptive quadrature grid based on the characteristics of enrichment functions. Further, we propose an efficient scheme to invert the overlap matrix by using a block-wise matrix inversion in conjunction with special reduced-order quadrature rules to transform...

  1. Characterization of "cis"-regulatory elements ("c"RE) associated with mammary gland function

    Science.gov (United States)

    The Bos taurus genome assembly has propelled dairy science into a new era; still, most of the information encoded in the genome has not yet been decoded. The human Encyclopedia of DNA Elements (ENCODE) project has spearheaded the identification and annotation of functional genomic elements in the hu...

  2. Spent Nuclear Fuel Project Canister Storage Building Functions and Requirements

    Energy Technology Data Exchange (ETDEWEB)

    KLEM, M.J.

    2000-10-18

    In 1998, a major change in the technical strategy for managing Multi Canister Overpacks (MCO) while stored within the Canister Storage Building (CSB) occurred. The technical strategy is documented in Baseline Change Request (BCR) No. SNF-98-006, Simplified SNF Project Baseline (MCO Sealing) (FDH 1998). This BCR deleted the hot conditioning process initially adopted for the Spent Nuclear Fuel Project (SNF Project) as documented in WHC-SD-SNF-SP-005, Integrated Process Strategy for K Basins Spent Nuclear Fuel (WHC 199.5). In summary, MCOs containing Spent Nuclear Fuel (SNF) from K Basins would be placed in interim storage following processing through the Cold Vacuum Drying (CVD) facility. With this change, the needs for the Hot Conditioning System (HCS) and inerting/pressure retaining capabilities of the CSB storage tubes and the MCO Handling Machine (MHM) were eliminated. Mechanical seals will be used on the MCOs prior to transport to the CSB. Covers will be welded on the MCOs for the final seal at the CSB. Approval of BCR No. SNF-98-006, imposed the need to review and update the CSB functions and requirements baseline documented herein including changing the document title to ''Spent Nuclear Fuel Project Canister Storage Building Functions and Requirements.'' This revision aligns the functions and requirements baseline with the CSB Simplified SNF Project Baseline (MCO Sealing). This document represents the Canister Storage Building (CSB) Subproject technical baseline. It establishes the functions and requirements baseline for the implementation of the CSB Subproject. The document is organized in eight sections. Sections 1.0 Introduction and 2.0 Overview provide brief introductions to the document and the CSB Subproject. Sections 3.0 Functions, 4.0 Requirements, 5.0 Architecture, and 6.0 Interfaces provide the data described by their titles. Section 7.0 Glossary lists the acronyms and defines the terms used in this document. Section 8

  3. Surveying DNA Elements within Functional Genes of Heterocyst-Forming Cyanobacteria.

    Directory of Open Access Journals (Sweden)

    Jason A Hilton

    Full Text Available Some cyanobacteria are capable of differentiating a variety of cell types in response to environmental factors. For instance, in low nitrogen conditions, some cyanobacteria form heterocysts, which are specialized for N2 fixation. Many heterocyst-forming cyanobacteria have DNA elements interrupting key N2 fixation genes, elements that are excised during heterocyst differentiation. While the mechanism for the excision of the element has been well-studied, many questions remain regarding the introduction of the elements into the cyanobacterial lineage and whether they have been retained ever since or have been lost and reintroduced. To examine the evolutionary relationships and possible function of DNA sequences that interrupt genes of heterocyst-forming cyanobacteria, we identified and compared 101 interruption element sequences within genes from 38 heterocyst-forming cyanobacterial genomes. The interruption element lengths ranged from about 1 kb (the minimum able to encode the recombinase responsible for element excision, up to nearly 1 Mb. The recombinase gene sequences served as genetic markers that were common across the interruption elements and were used to track element evolution. Elements were found that interrupted 22 different orthologs, only five of which had been previously observed to be interrupted by an element. Most of the newly identified interrupted orthologs encode proteins that have been shown to have heterocyst-specific activity. However, the presence of interruption elements within genes with no known role in N2 fixation, as well as in three non-heterocyst-forming cyanobacteria, indicates that the processes that trigger the excision of elements may not be limited to heterocyst development or that the elements move randomly within genomes. This comprehensive analysis provides the framework to study the history and behavior of these unique sequences, and offers new insight regarding the frequency and persistence of interruption

  4. Surveying DNA Elements within Functional Genes of Heterocyst-Forming Cyanobacteria.

    Science.gov (United States)

    Hilton, Jason A; Meeks, John C; Zehr, Jonathan P

    2016-01-01

    Some cyanobacteria are capable of differentiating a variety of cell types in response to environmental factors. For instance, in low nitrogen conditions, some cyanobacteria form heterocysts, which are specialized for N2 fixation. Many heterocyst-forming cyanobacteria have DNA elements interrupting key N2 fixation genes, elements that are excised during heterocyst differentiation. While the mechanism for the excision of the element has been well-studied, many questions remain regarding the introduction of the elements into the cyanobacterial lineage and whether they have been retained ever since or have been lost and reintroduced. To examine the evolutionary relationships and possible function of DNA sequences that interrupt genes of heterocyst-forming cyanobacteria, we identified and compared 101 interruption element sequences within genes from 38 heterocyst-forming cyanobacterial genomes. The interruption element lengths ranged from about 1 kb (the minimum able to encode the recombinase responsible for element excision), up to nearly 1 Mb. The recombinase gene sequences served as genetic markers that were common across the interruption elements and were used to track element evolution. Elements were found that interrupted 22 different orthologs, only five of which had been previously observed to be interrupted by an element. Most of the newly identified interrupted orthologs encode proteins that have been shown to have heterocyst-specific activity. However, the presence of interruption elements within genes with no known role in N2 fixation, as well as in three non-heterocyst-forming cyanobacteria, indicates that the processes that trigger the excision of elements may not be limited to heterocyst development or that the elements move randomly within genomes. This comprehensive analysis provides the framework to study the history and behavior of these unique sequences, and offers new insight regarding the frequency and persistence of interruption elements in

  5. CONVERGENCE OF SIMPLIFIED AND STABILIZED MIXED ELEMENT FORMATS BASED ON BUBBLE FUNCTION FOR THE STOKES PROBLEM

    Institute of Scientific and Technical Information of China (English)

    罗振东; 朱江

    2002-01-01

    Two simplified and stabilized mixed element formats for the Stokes problem are derived by bubble function, and their convergence,i.e,error analysis, are proved.These formats can save more freedom degrees than other usual formats.

  6. The Innovative Bike Conceptual Design by Using Modified Functional Element Design Method

    Directory of Open Access Journals (Sweden)

    Nien-Te Liu

    2016-11-01

    Full Text Available The purpose of the study is to propose a new design process by modifying functional element design approach which can commence a large amount of innovative concepts within a short period of time. Firstly, the original creative functional elements design method is analyzed and the drawbacks are discussed. Then, the modified is proposed and is divided into 6 steps. The creative functional element representations, generalization, specialization, and particularization are used in this method. Every step is described clearly, and users could design by following the process easily. In this paper, a clear and accurate design process is proposed based on the creative functional element design method. By following this method, a lot of innovative bicycles will be created quickly.

  7. Ion-selective electrodes in organic elemental and functional group analysis: a review

    Energy Technology Data Exchange (ETDEWEB)

    Selig, W.

    1977-11-08

    The literature on the use of ion-selective electrodes in organic elemental and functional group analysis is surveyed in some detail. The survey is complete through Chemical Abstracts, Vol. 83 (1975). 40 figures, 52 tables, 236 references.

  8. Nonlinear Strain Measures, Shape Functions and Beam Elements for Dynamics of Flexible Beams

    Energy Technology Data Exchange (ETDEWEB)

    Sharf, I. [University of Victoria, Department of Mechanical Engineering (Canada)

    1999-05-15

    In this paper, we examine several aspects of the development of an explicit geometrically nonlinear beam element. These are: (i) linearization of the displacement field; (ii) the effect of a commonly adopted approximation for the nonlinear Lagrangian strain; and (iii) use of different-order shape functions for discretization. The issue of rigid-body check for a nonlinear beam element is also considered. An approximate check is introduced for an element based on an (approximate) intermediate strain measure. Several numerical examples are presented to support the analysis. The paper concludes with a discussion on the use of explicit nonlinear beam elements for multibody dynamics simulation.

  9. Non-Maxwellian probability density function of fibers with lumped polarization mode dispersion elements.

    Science.gov (United States)

    Antonelli, Cristian; Mecozzi, Antonio

    2004-05-15

    We give an analytical expression for the probability density function of the differential group delay for a concatenation of Maxwellian fiber sections and an arbitrary number of lumped elements with constant and isotropically oriented birefringence. When the contribution of the average squared of the constant birefringence elements is a significant fraction of the total, we show that the outage probability can be significantly overestimated if the probability density function of the differential group delay is approximated by a Maxwellian distribution.

  10. Finite Element Analysis of Functionally Graded Material to Reduce Crazing in Transparent Armor

    Science.gov (United States)

    2015-09-01

    UNCLASSIFIED AD-E403 681 Technical Report ARMET-TR-14042 FINITE ELEMENT ANALYSIS OF FUNCTIONALLY GRADED MATERIAL TO REDUCE...prevent disclosure of its contents or reconstruction of the document. Do not return to the originator. UNCLASSIFIED REPORT DOCUMENTATION PAGE Form...September 2012 to April 2013 4. TITLE AND SUBTITLE FINITE ELEMENT ANALYSIS OF FUNCTIONALLY GRADED MATERIAL TO REDUCE CRAZING IN TRANSPARENT ARMOR

  11. Patch test function for axisymmetric element of conventional and couple stress theory

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    The enhanced patch test proposed by Chen W J(2006) can be used to assess the convergence of the problem with non-homogeneous differential equations.Based on this theory,we establish the patch test function for axisymmetric elements of conventional and couple stress theories,and reach an important conclusion that the patch test function for axisymmetric elements cannot contain non-zero constant shear.

  12. Patch test function for axisymmetric element of conventional and couple stress theory

    Institute of Scientific and Technical Information of China (English)

    CHEN WanJi; ZHAO Jie; WANG JinZhi; JI Bian

    2009-01-01

    The enhanced patch test proposed by Chen W J (2006) can be used to assess the convergence of the problem with non-homogeneous differential equations. Based on this theory, we establish the patch test function for axisyrnrnetric elements of conventional and couple stress theories, and reach an im-portant conclusion that the patch test function for axisymrnetric elements cannot contain non-zero constant shear.

  13. A functional gene array for detection of bacterial virulence elements

    Energy Technology Data Exchange (ETDEWEB)

    Jaing, C

    2007-11-01

    We report our development of the first of a series of microarrays designed to detect pathogens with known mechanisms of virulence and antibiotic resistance. By targeting virulence gene families as well as genes unique to specific biothreat agents, these arrays will provide important data about the pathogenic potential and drug resistance profiles of unknown organisms in environmental samples. To validate our approach, we developed a first generation array targeting genes from Escherichia coli strains K12 and CFT073, Enterococcus faecalis and Staphylococcus aureus. We determined optimal probe design parameters for microorganism detection and discrimination, measured the required target concentration, and assessed tolerance for mismatches between probe and target sequences. Mismatch tolerance is a priority for this application, due to DNA sequence variability among members of gene families. Arrays were created using the NimbleGen Maskless Array Synthesizer at Lawrence Livermore National Laboratory. Purified genomic DNA from combinations of one or more of the four target organisms, pure cultures of four related organisms, and environmental aerosol samples with spiked-in genomic DNA were hybridized to the arrays. Based on the success of this prototype, we plan to design further arrays in this series, with the goal of detecting all known virulence and antibiotic resistance gene families in a greatly expanded set of organisms.

  14. Lymphatic function is required prenatally for lung inflation at birth

    Science.gov (United States)

    Jakus, Zoltán; Gleghorn, Jason P.; Enis, David R.; Sen, Aslihan; Chia, Stephanie; Liu, Xi; Rawnsley, David R.; Yang, Yiqing; Hess, Paul R.; Zou, Zhiying; Yang, Jisheng; Guttentag, Susan H.; Nelson, Celeste M.

    2014-01-01

    Mammals must inflate their lungs and breathe within minutes of birth to survive. A key regulator of neonatal lung inflation is pulmonary surfactant, a lipoprotein complex which increases lung compliance by reducing alveolar surface tension (Morgan, 1971). Whether other developmental processes also alter lung mechanics in preparation for birth is unknown. We identify prenatal lymphatic function as an unexpected requirement for neonatal lung inflation and respiration. Mice lacking lymphatic vessels, due either to loss of the lymphangiogenic factor CCBE1 or VEGFR3 function, appear cyanotic and die shortly after birth due to failure of lung inflation. Failure of lung inflation is not due to reduced surfactant levels or altered development of the lung but is associated with an elevated wet/dry ratio consistent with edema. Embryonic studies reveal active lymphatic function in the late gestation lung, and significantly reduced total lung compliance in late gestation embryos that lack lymphatics. These findings reveal that lymphatic vascular function plays a previously unrecognized mechanical role in the developing lung that prepares it for inflation at birth. They explain respiratory failure in infants with congenital pulmonary lymphangiectasia, and suggest that inadequate late gestation lymphatic function may also contribute to respiratory failure in premature infants. PMID:24733830

  15. Simplex finite element analysis of viscous incompressible flow with penalty function formulation

    Science.gov (United States)

    Allaire, P. E.; Rosen, M. C.; Rice, J. G.

    1985-01-01

    Viscous flow calculations are important for the determination of separated flows, recirculating flows, secondary flows and so on. This paper presents a penalty function approach for the finite element analysis of steady incompressible viscous flow. A simplex element is used with linear velocity and constant pressure in contrast to other works which usually employ higher order elements. Simplex elements yield analytical expressions for the element matrices which in turn lead to efficient solutions. Earlier works have partially indicated how constraint and lock-up problems might be avoided for simplex elements. This paper extends the earlier works by indicating the approach in detail and verifying that it is successful for several applications not discussed in the literature so far. Solution times and accuracy considerations are discussed for Couette flow, plane Poiseuille flow, a driven cavity problem, and laminar and turbulent flow over a step.

  16. Large-scale all-electron density functional theory calculations using an enriched finite-element basis

    Science.gov (United States)

    Kanungo, Bikash; Gavini, Vikram

    2017-01-01

    We present a computationally efficient approach to perform large-scale all-electron density functional theory calculations by enriching the classical finite element basis with compactly supported atom-centered numerical basis functions that are constructed from the solution of the Kohn-Sham (KS) problem for single atoms. We term these numerical basis functions as enrichment functions, and the resultant basis as the enriched finite element basis. The compact support for the enrichment functions is obtained by using smooth cutoff functions, which enhances the conditioning and maintains the locality of the enriched finite element basis. The integrals involved in the evaluation of the discrete KS Hamiltonian and overlap matrix in the enriched finite element basis are computed using an adaptive quadrature grid that is constructed based on the characteristics of enrichment functions. Further, we propose an efficient scheme to invert the overlap matrix by using a blockwise matrix inversion in conjunction with special reduced-order quadrature rules, which is required to transform the discrete Kohn-Sham problem to a standard eigenvalue problem. Finally, we solve the resulting standard eigenvalue problem, in each self-consistent field iteration, by using a Chebyshev polynomial based filtering technique to compute the relevant eigenspectrum. We demonstrate the accuracy, efficiency, and parallel scalability of the proposed method on semiconducting and heavy-metallic systems of various sizes, with the largest system containing 8694 electrons. We obtain accuracies in the ground-state energies that are ˜1 mHa with reference ground-state energies employing classical finite element as well as Gaussian basis sets. Using the proposed formulation based on enriched finite element basis, for accuracies commensurate with chemical accuracy, we observe a staggering 50 -300 -fold reduction in the overall computational time when compared to classical finite element basis. Further, we find a

  17. Uncertainty Analysis via Failure Domain Characterization: Polynomial Requirement Functions

    Science.gov (United States)

    Crespo, Luis G.; Munoz, Cesar A.; Narkawicz, Anthony J.; Kenny, Sean P.; Giesy, Daniel P.

    2011-01-01

    This paper proposes an uncertainty analysis framework based on the characterization of the uncertain parameter space. This characterization enables the identification of worst-case uncertainty combinations and the approximation of the failure and safe domains with a high level of accuracy. Because these approximations are comprised of subsets of readily computable probability, they enable the calculation of arbitrarily tight upper and lower bounds to the failure probability. A Bernstein expansion approach is used to size hyper-rectangular subsets while a sum of squares programming approach is used to size quasi-ellipsoidal subsets. These methods are applicable to requirement functions whose functional dependency on the uncertainty is a known polynomial. Some of the most prominent features of the methodology are the substantial desensitization of the calculations from the uncertainty model assumed (i.e., the probability distribution describing the uncertainty) as well as the accommodation for changes in such a model with a practically insignificant amount of computational effort.

  18. The 3'-terminal 55 nucleotides of bovine coronavirus defective interfering RNA harbor cis-acting elements required for both negative- and positive-strand RNA synthesis.

    Directory of Open Access Journals (Sweden)

    Wei-Yu Liao

    Full Text Available The synthesis of the negative-strand [(--strand] complement of the ∼30 kilobase, positive-strand [(+-strand] coronaviral genome is a necessary early step for genome replication. The identification of cis-acting elements required for (--strand RNA synthesis in coronaviruses, however, has been hampered due to insufficiencies in the techniques used to detect the (--strand RNA species. Here, we employed a method of head-to-tail ligation and real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR to detect and quantitate the synthesis of bovine coronavirus (BCoV defective interfering (DI RNA (- strands. Furthermore, using the aforementioned techniques along with Northern blot assay, we specifically defined the cis-acting RNA elements within the 3'-terminal 55 nucleotides (nts which function in the synthesis of (-- or (+-strand BCoV DI RNA. The major findings are as follows: (i nts from -5 to -39 within the 3'-terminal 55 nts are the cis-acting elements responsible for (--strand BCoV DI RNA synthesis, (ii nts from -3 to -34 within the 3'-terminal 55 nts are cis-acting elements required for (+-strand BCoV DI RNA synthesis, and (iii the nucleotide species at the 3'-most position (-1 is important, but not critical, for both (-- and (+-strand BCoV DI RNA synthesis. These results demonstrate that the 3'-terminal 55 nts in BCoV DI RNA harbor cis-acting RNA elements required for both (-- and (+-strand DI RNA synthesis and extend our knowledge on the mechanisms of coronavirus replication. The method of head-to-tail ligation and qRT-PCR employed in the study may also be applied to identify other cis-acting elements required for (--strand RNA synthesis in coronaviruses.

  19. User Requirements Analysis For Digital Library Application Using Quality Function Deployment.

    Science.gov (United States)

    Wulandari, Lily; Sularto, Lana; Yusnitasari, Tristyanti; Ikasari, Diana

    2017-03-01

    This study attemp to build Smart Digital Library to be used by the wider community wherever they are. The system is built in the form of Smart Digital Library portal which uses semantic similarity method (Semantic Similarity) to search journals, articles or books by title or author name. This method is also used to determine the recommended books to be read by visitors of Smart Digital Library based on testimony from a previous reader automatically. Steps being taken in the development of Smart Digital Library system is the analysis phase, design phase, testing and implementation phase. At this stage of the analysis using WebQual for the preparation of the instruments to be distributed to the respondents and the data obtained from the respondents will be processed using Quality Function Deployment. In the analysis phase has the purpose of identifying consumer needs and technical requirements. The analysis was performed to a digital library on the web digital library Gunadarma University, Bogor Institute of Agriculture, University of Indonesia, etc. The questionnaire was distributed to 200 respondents. The research methodology begins with the collection of user requirements and analyse it using QFD. Application design is funded by the government through a program of Featured Universities Research by the Directorate General of Higher Education (DIKTI). Conclusions from this research are identified which include the Consumer Requirements of digital library application. The elements of the consumers requirements consists of 13 elements and 25 elements of Engineering Characteristics digital library requirements. Therefore the design of digital library applications that will be built, is designed according to the findings by eliminating features that are not needed by restaurant based on QFD House of Quality.

  20. Toeplitz Matrices Whose Elements Are the Coefficients of Functions with Bounded Boundary Rotation

    Directory of Open Access Journals (Sweden)

    V. Radhika

    2016-01-01

    Full Text Available Let R denote the family of functions f(z=z+∑n=2∞anzn of bounded boundary rotation so that Ref′(z>0 in the open unit disk U={z:z<1}. We obtain sharp bounds for Toeplitz determinants whose elements are the coefficients of functions f∈R.

  1. Higher-order adaptive finite-element methods for Kohn-Sham density functional theory

    CERN Document Server

    Motamarri, Phani; Leiter, Kenneth; Knap, Jaroslaw; Gavini, Vikram

    2012-01-01

    We present an efficient computational approach to perform real-space electronic structure calculations using an adaptive higher-order finite-element discretization of Kohn-Sham density-functional theory (DFT).To this end, we develop an \\emph{a priori} mesh adaption technique to construct a close to optimal finite-element discretization of the problem. We further propose an efficient solution strategy for solving the discrete eigenvalue problem by using spectral finite-elements in conjunction with Gauss-Lobatto quadrature, and a Chebyshev acceleration technique for computing the occupied eigenspace. Using the proposed solution procedure, we investigate the computational efficiency afforded by higher-order finite-element discretizations of the Kohn-Sham DFT problem. Our studies suggest that staggering computational savings---of the order of $1000-$fold---can be realized, for both all-electron and pseudopotential calculations, by using higher-order finite-element discretizations. On all the benchmark systems stu...

  2. Modelling Thermal Shock in Functionally Graded Plates with Finite Element Method

    Directory of Open Access Journals (Sweden)

    Vyacheslav N. Burlayenko

    2016-01-01

    Full Text Available Thermomechanical behavior and crack propagation in a functionally graded metal/ceramic plate undergoing thermal shock are analyzed by using the finite element method. A two-dimensional plane strain functionally graded finite element has been developed within the ABAQUS software environment for this purpose. An actual material gradation has been accomplished by sampling material quantities directly at the Gauss points of the element via programming appropriate user-defined subroutines. The virtual crack closure technique is used to model a crack growth under thermal loading. Contact possible between crack lips during the crack advance is taken into account in thermomechanical simulations as well. The paper shows that the presented finite element model can be applied to provide an insight into the thermomechanical respond and failure of the metal/ceramic plate.

  3. Sterol Regulatory Element Binding Protein (Srb1) Is Required for Hypoxic Adaptation and Virulence in the Dimorphic Fungus Histoplasma capsulatum

    Science.gov (United States)

    DuBois, Juwen C.; Smulian, A. George

    2016-01-01

    The Histoplasma capsulatum sterol regulatory element binding protein (SREBP), Srb1 is a member of the basic helix-loop-helix (bHLH), leucine zipper DNA binding protein family of transcription factors that possess a unique tyrosine (Y) residue instead of an arginine (R) residue in the bHLH region. We have determined that Srb1 message levels increase in a time dependent manner during growth under oxygen deprivation (hypoxia). To further understand the role of Srb1 during infection and hypoxia, we silenced the gene encoding Srb1 using RNA interference (RNAi); characterized the resulting phenotype, determined its response to hypoxia, and its ability to cause disease within an infected host. Silencing of Srb1 resulted in a strain of H. capsulatum that is incapable of surviving in vitro hypoxia. We found that without complete Srb1 expression, H. capsulatum is killed by murine macrophages and avirulent in mice given a lethal dose of yeasts. Additionally, silencing Srb1 inhibited the hypoxic upregulation of other known H. capsulatum hypoxia-responsive genes (HRG), and genes that encode ergosterol biosynthetic enzymes. Consistent with these regulatory functions, Srb1 silenced H. capsulatum cells were hypersensitive to the antifungal azole drug itraconazole. These data support the theory that the H. capsulatum SREBP is critical for hypoxic adaptation and is required for H. capsulatum virulence. PMID:27711233

  4. Functional Requirements for Fab-7 Boundary Activity in the Bithorax Complex.

    Science.gov (United States)

    Wolle, Daniel; Cleard, Fabienne; Aoki, Tsutomu; Deshpande, Girish; Schedl, Paul; Karch, Francois

    2015-11-01

    Chromatin boundaries are architectural elements that determine the three-dimensional folding of the chromatin fiber and organize the chromosome into independent units of genetic activity. The Fab-7 boundary from the Drosophila bithorax complex (BX-C) is required for the parasegment-specific expression of the Abd-B gene. We have used a replacement strategy to identify sequences that are necessary and sufficient for Fab-7 boundary function in the BX-C. Fab-7 boundary activity is known to depend on factors that are stage specific, and we describe a novel ∼700-kDa complex, the late boundary complex (LBC), that binds to Fab-7 sequences that have insulator functions in late embryos and adults. We show that the LBC is enriched in nuclear extracts from late, but not early, embryos and that it contains three insulator proteins, GAF, Mod(mdg4), and E(y)2. Its DNA binding properties are unusual in that it requires a minimal sequence of >65 bp; however, other than a GAGA motif, the three Fab-7 LBC recognition elements display few sequence similarities. Finally, we show that mutations which abrogate LBC binding in vitro inactivate the Fab-7 boundary in the BX-C.

  5. Thyroid hormone is required for hypothalamic neurons regulating cardiovascular functions.

    Science.gov (United States)

    Mittag, Jens; Lyons, David J; Sällström, Johan; Vujovic, Milica; Dudazy-Gralla, Susi; Warner, Amy; Wallis, Karin; Alkemade, Anneke; Nordström, Kristina; Monyer, Hannah; Broberger, Christian; Arner, Anders; Vennström, Björn

    2013-01-01

    Thyroid hormone is well known for its profound direct effects on cardiovascular function and metabolism. Recent evidence, however, suggests that the hormone also regulates these systems indirectly through the central nervous system. While some of the molecular mechanisms underlying the hormone's central control of metabolism have been identified, its actions in the central cardiovascular control have remained enigmatic. Here, we describe a previously unknown population of parvalbuminergic neurons in the anterior hypothalamus that requires thyroid hormone receptor signaling for proper development. Specific stereotaxic ablation of these cells in the mouse resulted in hypertension and temperature-dependent tachycardia, indicating a role in the central autonomic control of blood pressure and heart rate. Moreover, the neurons exhibited intrinsic temperature sensitivity in patch-clamping experiments, providing a new connection between cardiovascular function and core temperature. Thus, the data identify what we believe to be a novel hypothalamic cell population potentially important for understanding hypertension and indicate developmental hypothyroidism as an epigenetic risk factor for cardiovascular disorders. Furthermore, the findings may be beneficial for treatment of the recently identified patients that have a mutation in thyroid hormone receptor α1.

  6. A new method of heart sound signal analysis based on independent function element

    Directory of Open Access Journals (Sweden)

    Cheng Xie-feng

    2014-09-01

    Full Text Available In this paper, a new method is presented for heart sound signal processing in statistical domain. The multiple components obtained from the conventional linear transformation are possibly irrelevant, but usually do not possess the characteristics of statistical independence. First, the definition and obtaining method of independent function element are discussed; the method of signal decomposition and reconstruction based on the independent function element, not only inherits the advantages of linear transformation, but also has the capability of signal representation in the statistical domain. After that, the application of independent function element in heart sound signal analysis is analyzed in detail. The validity and practicability of the method are demonstrated through two experiments.

  7. Identification of functional elements and regulatory circuits by Drosophila modENCODE.

    Science.gov (United States)

    Roy, Sushmita; Ernst, Jason; Kharchenko, Peter V; Kheradpour, Pouya; Negre, Nicolas; Eaton, Matthew L; Landolin, Jane M; Bristow, Christopher A; Ma, Lijia; Lin, Michael F; Washietl, Stefan; Arshinoff, Bradley I; Ay, Ferhat; Meyer, Patrick E; Robine, Nicolas; Washington, Nicole L; Di Stefano, Luisa; Berezikov, Eugene; Brown, Christopher D; Candeias, Rogerio; Carlson, Joseph W; Carr, Adrian; Jungreis, Irwin; Marbach, Daniel; Sealfon, Rachel; Tolstorukov, Michael Y; Will, Sebastian; Alekseyenko, Artyom A; Artieri, Carlo; Booth, Benjamin W; Brooks, Angela N; Dai, Qi; Davis, Carrie A; Duff, Michael O; Feng, Xin; Gorchakov, Andrey A; Gu, Tingting; Henikoff, Jorja G; Kapranov, Philipp; Li, Renhua; MacAlpine, Heather K; Malone, John; Minoda, Aki; Nordman, Jared; Okamura, Katsutomo; Perry, Marc; Powell, Sara K; Riddle, Nicole C; Sakai, Akiko; Samsonova, Anastasia; Sandler, Jeremy E; Schwartz, Yuri B; Sher, Noa; Spokony, Rebecca; Sturgill, David; van Baren, Marijke; Wan, Kenneth H; Yang, Li; Yu, Charles; Feingold, Elise; Good, Peter; Guyer, Mark; Lowdon, Rebecca; Ahmad, Kami; Andrews, Justen; Berger, Bonnie; Brenner, Steven E; Brent, Michael R; Cherbas, Lucy; Elgin, Sarah C R; Gingeras, Thomas R; Grossman, Robert; Hoskins, Roger A; Kaufman, Thomas C; Kent, William; Kuroda, Mitzi I; Orr-Weaver, Terry; Perrimon, Norbert; Pirrotta, Vincenzo; Posakony, James W; Ren, Bing; Russell, Steven; Cherbas, Peter; Graveley, Brenton R; Lewis, Suzanna; Micklem, Gos; Oliver, Brian; Park, Peter J; Celniker, Susan E; Henikoff, Steven; Karpen, Gary H; Lai, Eric C; MacAlpine, David M; Stein, Lincoln D; White, Kevin P; Kellis, Manolis

    2010-12-24

    To gain insight into how genomic information is translated into cellular and developmental programs, the Drosophila model organism Encyclopedia of DNA Elements (modENCODE) project is comprehensively mapping transcripts, histone modifications, chromosomal proteins, transcription factors, replication proteins and intermediates, and nucleosome properties across a developmental time course and in multiple cell lines. We have generated more than 700 data sets and discovered protein-coding, noncoding, RNA regulatory, replication, and chromatin elements, more than tripling the annotated portion of the Drosophila genome. Correlated activity patterns of these elements reveal a functional regulatory network, which predicts putative new functions for genes, reveals stage- and tissue-specific regulators, and enables gene-expression prediction. Our results provide a foundation for directed experimental and computational studies in Drosophila and related species and also a model for systematic data integration toward comprehensive genomic and functional annotation.

  8. Efficient LEC2 activation of OLEOSIN expression requires two neighboring RY elements on its promoter

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    As the main structural protein of oil body,OLEOSIN is highly expressed only during seed development. OLEOSIN promoter is a very useful tool for seed-specific gene engineering and seed bioreactor designing. The B3 domain transcription factor leafy cotyledon2 (LEC2) plays an important role in regulating seed development and seed-specific gene expression. Here,we first report how seed-specific B3 domain transcription factor leafy cotyledon2 (LEC2) efficiently activates OLEOSIN expression. The central promoter region of OLEOSIN,responsible for seed specificity and LEC2 activation,was determined by 5’-deletion analysis. Binding experiments in yeast cells and electrophoretic mobility shift assays showed that LEC2 specifically bound to two conserved RY elements in this region. In transient expression assays,mutation in either RY element dramatically reduced LEC2 activation of OLEOSIN promoter activity,while double mutation abolished it. Analysis of the distribution of RY elements in seed-specific genes activated by LEC2 also supported the idea that genes containing neighboring RY elements responded strongly to LEC2 activation. Therefore,we conclude that two neighboring RY elements are essential for efficient LEC2 activation of OLEOSIN expression. These findings will help us better utilize seed-specific promoter activity.

  9. Efficient LEC2 activation of OLEOSIN expression requires two neighboring RY elements on its promoter

    Institute of Scientific and Technical Information of China (English)

    CHE NanYing; YANG Yang; LI YanDong; WANG LiLi; HUANG Ping; GAO Yin; An ChengCai

    2009-01-01

    As the main structural protein of oil body, OLEOSIN is highly expressed only during seed development. OLEOSIN promoter is a very useful tool for seed-specific gene engineering and seed bioreactor designing. The B3 domain transcription factor leafy cotyledon2 (LEC2) plays an important role in regulating seed development and seed-specific gene expression. Here, we first report how seed-specific B3 domain transcription factor leafy cotyledon2 (LEC2) efficiently activates OLEOSIN expression. The central promoter region of OLEOSIN, responsible for seed specificity and LEC2 activation, was determined by 5'-deletion analysis. Binding experiments in yeast cells and electrophoretic mobility shift assays showed that LEC2 specifically bound to two conserved RY elements in this region, in transient expression assays, mutation in either RY element dramatically reduced LEC2 activation of OLEOSIN promoter activity, while double mutation abolished it. Analysis of the distribution of RY elements in seed-specific genes activated by LEC2 also supported the idea that genes containing neighboring RY elements responded strongly to LEC2 activation. Therefore, we conclude that two neighboring RY elements are essential for efficient LEC2 activation of OLEOSIN expression. These findings will help us better utilize seed-specific promoter activity.

  10. Towards an Early Software Effort Estimation Based on Functional and Non-Functional Requirements

    NARCIS (Netherlands)

    Kassab, M.; Daneva, Maia; Ormanjieva, Olga; Abran, A.; Braungarten, R.; Dumke, R.; Cuadrado-Gallego, J.; Brunekreef, J.

    2009-01-01

    The increased awareness of the non-functional requirements as a key to software project and product success makes explicit the need to include them in any software project effort estimation activity. However, the existing approaches to defining size-based effort relationships still pay insufficient

  11. Higher-order adaptive finite-element methods for Kohn–Sham density functional theory

    Energy Technology Data Exchange (ETDEWEB)

    Motamarri, P. [Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI 48109 (United States); Nowak, M.R. [Department of Electrical Engineering, University of Michigan, Ann Arbor, MI 48109 (United States); Leiter, K.; Knap, J. [U.S. Army Research Labs, Aberdeen Proving Ground, Aberdeen, MD 21001 (United States); Gavini, V., E-mail: vikramg@umich.edu [Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI 48109 (United States)

    2013-11-15

    We present an efficient computational approach to perform real-space electronic structure calculations using an adaptive higher-order finite-element discretization of Kohn–Sham density-functional theory (DFT). To this end, we develop an a priori mesh-adaption technique to construct a close to optimal finite-element discretization of the problem. We further propose an efficient solution strategy for solving the discrete eigenvalue problem by using spectral finite-elements in conjunction with Gauss–Lobatto quadrature, and a Chebyshev acceleration technique for computing the occupied eigenspace. The proposed approach has been observed to provide a staggering 100–200-fold computational advantage over the solution of a generalized eigenvalue problem. Using the proposed solution procedure, we investigate the computational efficiency afforded by higher-order finite-element discretizations of the Kohn–Sham DFT problem. Our studies suggest that staggering computational savings—of the order of 1000-fold—relative to linear finite-elements can be realized, for both all-electron and local pseudopotential calculations, by using higher-order finite-element discretizations. On all the benchmark systems studied, we observe diminishing returns in computational savings beyond the sixth-order for accuracies commensurate with chemical accuracy, suggesting that the hexic spectral-element may be an optimal choice for the finite-element discretization of the Kohn–Sham DFT problem. A comparative study of the computational efficiency of the proposed higher-order finite-element discretizations suggests that the performance of finite-element basis is competing with the plane-wave discretization for non-periodic local pseudopotential calculations, and compares to the Gaussian basis for all-electron calculations to within an order of magnitude. Further, we demonstrate the capability of the proposed approach to compute the electronic structure of a metallic system containing 1688

  12. Epigenetic regulation of transcription and possible functions of mammalian short interspersed elements, SINEs.

    Science.gov (United States)

    Ichiyanagi, Kenji

    2013-01-01

    Short interspersed elements (SINEs) are a class of retrotransposons, which amplify their copy numbers in their host genomes by retrotransposition. More than a million copies of SINEs are present in a mammalian genome, constituting over 10% of the total genomic sequence. In contrast to the other two classes of retrotransposons, long interspersed elements (LINEs) and long terminal repeat (LTR) elements, SINEs are transcribed by RNA polymerase III. However, like LINEs and LTR elements, the SINE transcription is likely regulated by epigenetic mechanisms such as DNA methylation, at least for human Alu and mouse B1. Whereas SINEs and other transposable elements have long been thought as selfish or junk DNA, recent studies have revealed that they play functional roles at their genomic locations, for example, as distal enhancers, chromatin boundaries and binding sites of many transcription factors. These activities imply that SINE retrotransposition has shaped the regulatory network and chromatin landscape of their hosts. Whereas it is thought that the epigenetic mechanisms were originated as a host defense system against proliferation of parasitic elements, this review discusses a possibility that the same mechanisms are also used to regulate the SINE-derived functions.

  13. Electronic coupling matrix elements from charge constrained density functional theory calculations using a plane wave basis set

    Science.gov (United States)

    Oberhofer, Harald; Blumberger, Jochen

    2010-12-01

    We present a plane wave basis set implementation for the calculation of electronic coupling matrix elements of electron transfer reactions within the framework of constrained density functional theory (CDFT). Following the work of Wu and Van Voorhis [J. Chem. Phys. 125, 164105 (2006)], the diabatic wavefunctions are approximated by the Kohn-Sham determinants obtained from CDFT calculations, and the coupling matrix element calculated by an efficient integration scheme. Our results for intermolecular electron transfer in small systems agree very well with high-level ab initio calculations based on generalized Mulliken-Hush theory, and with previous local basis set CDFT calculations. The effect of thermal fluctuations on the coupling matrix element is demonstrated for intramolecular electron transfer in the tetrathiafulvalene-diquinone (Q-TTF-Q-) anion. Sampling the electronic coupling along density functional based molecular dynamics trajectories, we find that thermal fluctuations, in particular the slow bending motion of the molecule, can lead to changes in the instantaneous electron transfer rate by more than an order of magnitude. The thermal average, ( { } )^{1/2} = 6.7 {mH}, is significantly higher than the value obtained for the minimum energy structure, | {H_ab } | = 3.8 {mH}. While CDFT in combination with generalized gradient approximation (GGA) functionals describes the intermolecular electron transfer in the studied systems well, exact exchange is required for Q-TTF-Q- in order to obtain coupling matrix elements in agreement with experiment (3.9 mH). The implementation presented opens up the possibility to compute electronic coupling matrix elements for extended systems where donor, acceptor, and the environment are treated at the quantum mechanical (QM) level.

  14. Promiscuity of enhancer, coding and non-coding transcription functions in ultraconserved elements

    Directory of Open Access Journals (Sweden)

    Sanges Remo

    2010-03-01

    Full Text Available Abstract Background Ultraconserved elements (UCEs are highly constrained elements of mammalian genomes, whose functional role has not been completely elucidated yet. Previous studies have shown that some of them act as enhancers in mouse, while some others are expressed in both normal and cancer-derived human tissues. Only one UCE element so far was shown to present these two functions concomitantly, as had been observed in other isolated instances of single, non ultraconserved enhancer elements. Results We used a custom microarray to assess the levels of UCE transcription during mouse development and integrated these data with published microarray and next-generation sequencing datasets as well as with newly produced PCR validation experiments. We show that a large fraction of non-exonic UCEs is transcribed across all developmental stages examined from only one DNA strand. Although the nature of these transcripts remains a mistery, our meta-analysis of RNA-Seq datasets indicates that they are unlikely to be short RNAs and that some of them might encode nuclear transcripts. In the majority of cases this function overlaps with the already established enhancer function of these elements during mouse development. Utilizing several next-generation sequencing datasets, we were further able to show that the level of expression observed in non-exonic UCEs is significantly higher than in random regions of the genome and that this is also seen in other regions which act as enhancers. Conclusion Our data shows that the concurrent presence of enhancer and transcript function in non-exonic UCE elements is more widespread than previously shown. Moreover through our own experiments as well as the use of next-generation sequencing datasets, we were able to show that the RNAs encoded by non-exonic UCEs are likely to be long RNAs transcribed from only one DNA strand.

  15. Modeling shock waves using exponential interpolation functions with the Least-Squares Finite Element method

    Science.gov (United States)

    Smith, Bradford Scott, Jr.

    The hypothesis of this research is that exponential interpolation functions will approximate fluid properties at shock waves with less error than polynomial interpolation functions. Exponential interpolation functions are derived for the purpose of modeling sharp gradients. General equations for conservation of mass, momentum, and energy for an inviscid flow of a perfect gas are converted to finite element equations using the least-squares method. Boundary conditions and a mesh adaptation scheme are also presented. An oblique shock reflection problem is used as a benchmark to determine whether or not exponential interpolation provides any advantages over Lagrange polynomial interpolation. Using exponential interpolation in elements downstream of a shock and having edges coincident with the shock showed a slight reduction in the solution error. However there was very little qualitative difference between solutions using polynomial and exponential interpolation. Regardless of the type of interpolation used, the shocks were smeared and oscillations were present both upstream and downstream of the shock waves. When a mesh adaptation scheme was implemented, exponential elements adjacent to the shock waves became much smaller and the numerical solution diverged. Changing the exponential elements to polynomial elements yielded a convergent solution. There appears to be no significant advantage to using exponential interpolation in comparison to Lagrange polynomial interpolation.

  16. Band-limited Green's Functions for Quantitative Evaluation of Acoustic Emission Using the Finite Element Method

    Science.gov (United States)

    Leser, William P.; Yuan, Fuh-Gwo; Leser, William P.

    2013-01-01

    A method of numerically estimating dynamic Green's functions using the finite element method is proposed. These Green's functions are accurate in a limited frequency range dependent on the mesh size used to generate them. This range can often match or exceed the frequency sensitivity of the traditional acoustic emission sensors. An algorithm is also developed to characterize an acoustic emission source by obtaining information about its strength and temporal dependence. This information can then be used to reproduce the source in a finite element model for further analysis. Numerical examples are presented that demonstrate the ability of the band-limited Green's functions approach to determine the moment tensor coefficients of several reference signals to within seven percent, as well as accurately reproduce the source-time function.

  17. Dissection of the beta-globin replication-initiation region reveals specific requirements for replicator elements during gene amplification.

    Directory of Open Access Journals (Sweden)

    Naoya Okada

    Full Text Available Gene amplification plays a pivotal role in malignant transformation of human cells. A plasmid with both a mammalian replication-initiation region (IR/origin/replicator and a nuclear matrix-attachment region (MAR is spontaneously amplified in transfected cells by a mechanism that involves amplification at the extrachromosomal site, followed by amplification at the chromosomal arm, ultimately generating a long homogeneously staining region (HSR. Several observations suggest that replication initiation from IR sequences might mediate amplification. To test this idea, we previously dissected c-myc and DHFR IRs to identify the minimum sequence required to support amplification. In this study, we applied an improved analysis that discriminates between two amplification steps to the ß-globin RepP IR, which contains separate elements already known to be essential for initiation on the chromosome arm. The IR sequence was required at least for the extrachromosomal amplification step. In addition to the vector-encoded MAR, amplification also required an AT-rich region and a MAR-like element, consistent with the results regarding replicator activity on the chromosome. However, amplification did not require the AG-rich tract necessary for replicator activity, but instead required a novel sequence containing another AG-rich tract. The differential sequence requirement might be a consequence of extrachromosomal replication.

  18. IMPORTANCE OF ACTIVATED CARBON'S OXYGEN SURFACE FUNCTIONAL GROUPS ON ELEMENTAL MERCURY ADSORPTION

    Science.gov (United States)

    The effect of varying physical and chemical properties of activated carbons on adsorption of elemental mercury [Hg(0)] was studied by treating two activated carbons to modify their surface functional groups and pore structures. Heat treatment (1200 K) in nitrogen (N2), air oxidat...

  19. Space station data system analysis/architecture study. Task 1: Functional requirements definition, DR-5. Appendix: Requirements data base

    Science.gov (United States)

    1985-01-01

    Appendix A contains data that characterize the system functions in sufficient depth as to determine the requirements for the Space Station Data System (SSDS). This data is in the form of: (1) top down traceability report; (2) bottom up traceability report; (3) requirements data sheets; and (4) cross index of requirements paragraphs of the source documents and the requirements numbers. A data base users guide is included that interested parties can use to access the requirements data base and get up to date information about the functions.

  20. Non-linear shape functions over time in the space-time finite element method

    Directory of Open Access Journals (Sweden)

    Kacprzyk Zbigniew

    2017-01-01

    Full Text Available This work presents a generalisation of the space-time finite element method proposed by Kączkowski in his seminal of 1970’s and early 1980’s works. Kączkowski used linear shape functions in time. The recurrence formula obtained by Kączkowski was conditionally stable. In this paper, non-linear shape functions in time are proposed.

  1. Test functions for three-dimensional control-volume mixed finite-element methods on irregular grids

    Science.gov (United States)

    Naff, R.L.; Russell, T.F.; Wilson, J.D.; ,; ,; ,; ,; ,

    2000-01-01

    Numerical methods based on unstructured grids, with irregular cells, usually require discrete shape functions to approximate the distribution of quantities across cells. For control-volume mixed finite-element methods, vector shape functions are used to approximate the distribution of velocities across cells and vector test functions are used to minimize the error associated with the numerical approximation scheme. For a logically cubic mesh, the lowest-order shape functions are chosen in a natural way to conserve intercell fluxes that vary linearly in logical space. Vector test functions, while somewhat restricted by the mapping into the logical reference cube, admit a wider class of possibilities. Ideally, an error minimization procedure to select the test function from an acceptable class of candidates would be the best procedure. Lacking such a procedure, we first investigate the effect of possible test functions on the pressure distribution over the control volume; specifically, we look for test functions that allow for the elimination of intermediate pressures on cell faces. From these results, we select three forms for the test function for use in a control-volume mixed method code and subject them to an error analysis for different forms of grid irregularity; errors are reported in terms of the discrete L2 norm of the velocity error. Of these three forms, one appears to produce optimal results for most forms of grid irregularity.

  2. Clustered Protocadherins Are Required for Building Functional Neural Circuits

    Directory of Open Access Journals (Sweden)

    Takeshi Yagi

    2017-04-01

    Full Text Available Neuronal identity is generated by the cell-surface expression of clustered protocadherin (Pcdh isoforms. In mice, 58 isoforms from three gene clusters, Pcdhα, Pcdhβ, and Pcdhγ, are differentially expressed in neurons. Since cis-heteromeric Pcdh oligomers on the cell surface interact homophilically with that in other neurons in trans, it has been thought that the Pcdh isoform repertoire determines the binding specificity of synapses. We previously described the cooperative functions of isoforms from all three Pcdh gene clusters in neuronal survival and synapse formation in the spinal cord. However, the neuronal loss and the following neonatal lethality prevented an analysis of the postnatal development and characteristics of the clustered-Pcdh-null (Δαβγ neural circuits. Here, we used two methods, one to generate the chimeric mice that have transplanted Δαβγ neurons into mouse embryos, and the other to generate double mutant mice harboring null alleles of both the Pcdh gene and the proapoptotic gene Bax to prevent neuronal loss. First, our results showed that the surviving chimeric mice that had a high contribution of Δαβγ cells exhibited paralysis and died in the postnatal period. An analysis of neuronal survival in postnatally developing brain regions of chimeric mice clarified that many Δαβγ neurons in the forebrain were spared from apoptosis, unlike those in the reticular formation of the brainstem. Second, in Δαβγ/Bax null double mutants, the central pattern generator (CPG for locomotion failed to create a left-right alternating pattern even in the absence of neurodegeneraton. Third, calcium imaging of cultured hippocampal neurons showed that the network activity of Δαβγ neurons tended to be more synchronized and lost the variability in the number of simultaneously active neurons observed in the control network. Lastly, a comparative analysis for trans-homophilic interactions of the exogenously introduced single

  3. Technology requirements for an orbiting fuel depot: A necessary element of a space infrastructure

    Science.gov (United States)

    Stubbs, R. M.; Corban, R. R.; Willoughby, A. J.

    1988-01-01

    Advanced planning within NASA has identified several bold space exploration initiatives. The successful implementation of these missions will require a supporting space infrastructure which would include a fuel depot, an orbiting facility to store, transfer and process large quantities of cryogenic fluids. In order to adequately plan the technology development programs required to enable the construction and operation of a fuel depot, a multidisciplinary workshop was convened to assess critical technologies and their state of maturity. Since technology requirements depend strongly on the depot design assumptions, several depot concepts are presented with their effect on criticality ratings. Over 70 depot-related technology areas are addressed.

  4. Technology requirements for an orbiting fuel depot - A necessary element of a space infrastructure

    Science.gov (United States)

    Stubbs, R. M.; Corban, R. R.; Willoughby, A. J.

    1988-01-01

    Advanced planning within NASA has identified several bold space exploration initiatives. The successful implementation of these missions will require a supporting space infrastructure which would include a fuel depot, an orbiting facility to store, transfer and process large quantities of cryogenic fluids. In order to adequately plan the technology development programs required to enable the construction and operation of a fuel depot, a multidisciplinary workshop was convened to assess critical technologies and their state of maturity. Since technology requirements depend strongly on the depot design assumptions, several depot concepts are presented with their effect of criticality ratings. Over 70 depot-related technology areas are addressed.

  5. Elemental carbon exposure and lung function in school children from Mexico City.

    Science.gov (United States)

    Barraza-Villarreal, A; Escamilla-Nuñez, M C; Hernández-Cadena, L; Texcalac-Sangrador, J L; Sienra-Monge, J J; Del Río-Navarro, B E; Cortez-Lugo, M; Sly, P D; Romieu, I

    2011-09-01

    Though exposure to air pollution has a detrimental effect on respiratory health, few studies have examined the association between elemental carbon exposure and lung function among schoolchildren. The aim of the present study was to present the association between short-term elemental carbon exposure and lung function in schoolchildren from Mexico City. 55 asthmatic and 40 non-asthmatic children were followed for an average of 22 weeks. A spirometry test was performed every 15 days during follow-up. Portable air samplers collected particulate matter onto Teflon filters. Gravimetric analysis was conducted and elemental carbon was quantified using transmission densitometry. The association between the main variables was analysed using linear mixed effects models. The mean ± sd of elemental carbon light absorption was 92.7 ± 54.7 Mm(-1). An increase of one interquartile range in the 24-h average of elemental carbon (100.93 Mm(-1)) was associated with a significant negative impact on forced expiratory volume in 1 s (FEV(1)) (-62.0 (95% CI -123.3- -1.2) mL) and forced expiratory flow at 25-75% of forced vital capacity (FVC) (FEF(25-75%)) (-111 (95% CI -228.3- -4.1) mL) among asthmatic children, equal to 3.3% and 5.5%, respectively; and on FEV(1) (-95.0 (95% CI -182.3- -8.5) mL) and FVC (-105.0 (95% CI -197.0- -13.7) mL) among non-asthmatic children. Exposure to elemental carbon resulted in an important negative effect on lung function in atopic schoolchildren, regardless of asthma status.

  6. A Fortran program to calculate the matrix elements of the Coulomb interaction involving hydrogenic wave functions

    Science.gov (United States)

    Sarkadi, L.

    2017-03-01

    The program MTRXCOUL [1] calculates the matrix elements of the Coulomb interaction between a charged particle and an atomic electron, ∫ ψf∗ (r) | R - r | - 1ψi(r) d r. Bound-free transitions are considered, and non-relativistic hydrogenic wave functions are used. In this revised version a bug discovered in the F3Y CPC Program Library (PL) subprogram [2] is fixed. Furthermore, the COULCC CPC PL subprogram [3] applied for the calculations of the radial wave functions of the free states and the Bessel functions is replaced by the CPC PL subprogram DCOUL [4].

  7. Correlation functions of scattering matrix elements in microwave cavities with strong absorption

    Energy Technology Data Exchange (ETDEWEB)

    Schaefer, R [Fachbereich Physik, Philipps-Universitaet Marburg, Renthof 5, D-35032 Marburg (Germany); Gorin, T [Theoretische Quantendynamik, Fakultaet fuer Physik, Universitaet Freiburg, Hermann-Herder-Str. 3, D-79104 Freiburg (Germany); Seligman, T H [Centro de Ciencias Fisicas, Universidad Nacional Autonoma de Mexico, Campus Morelos, CP 62251, Cuernavaca, Morelos (Mexico); Stoeckmann, H-J [Fachbereich Physik, Philipps-Universitaet Marburg, Renthof 5, D-35032 Marburg (Germany)

    2003-03-28

    The scattering matrix was measured for microwave cavities with two antennae. It was analysed in the regime of overlapping resonances. The theoretical description in terms of a statistical scattering matrix and the rescaled Breit-Wigner approximation has been applied to this regime. The experimental results for the auto-correlation function show that the absorption in the cavity walls yields an exponential decay. This behaviour can only be modelled using a large number of weakly coupled channels. In comparison to the auto-correlation functions, the cross-correlation functions of the diagonal S-matrix elements display a more pronounced difference between regular and chaotic systems.

  8. Correlation functions of scattering matrix elements in microwave cavities with strong absorption

    Science.gov (United States)

    Schäfer, R.; Gorin, T.; Seligman, T. H.; Stöckmann, H.-J.

    2003-03-01

    The scattering matrix was measured for microwave cavities with two antennae. It was analysed in the regime of overlapping resonances. The theoretical description in terms of a statistical scattering matrix and the rescaled Breit-Wigner approximation has been applied to this regime. The experimental results for the auto-correlation function show that the absorption in the cavity walls yields an exponential decay. This behaviour can only be modelled using a large number of weakly coupled channels. In comparison to the auto-correlation functions, the cross-correlation functions of the diagonal S-matrix elements display a more pronounced difference between regular and chaotic systems.

  9. Micro-optical elements functioning in non-visible spectral range

    Science.gov (United States)

    Wang, Qin; Zhang, Andy Z. Z.; Bergström, Andreas; Huo, Vicky Z. J.; Almqvist, Susanne; Kaplan, Wlodek; Andersson, Jan Y.

    2010-05-01

    Nowadays novel micro-fabrication and wafer-based manufacturing approach allows realizing micro-optics in a way scientists have dreamt for generations, in particular, utilizing nano-imprint lithography as fabrication tooling enables greatly accelerating the micro-optics technology to its frontier. In this report, we present wafer-scale fabrication of various types of micro-optical elements based on photoresist, benzocyclobutene, photocurable imprint resist, and semiconductor materials by using thermal reflow, reactive ion etching, and imprint techniques. Especially, several concave or convex 3-dimensional micro-optical structures shaped by imprint method are detailed. These micro-optical elements can be monolithically or hybrid integrated onto optoelectronics devices, such as photodetectors and emitters as optical beam focuser, collimator, filter, or anti-reflectance elements. As application examples, polymer microlenses were integrated directly on the top of UV dual functional devices and quantum dot long wavelength infrared photodetectors, respectively.

  10. Hybrid graded element model for transient heat conduction in functionally graded materials

    Institute of Scientific and Technical Information of China (English)

    Lei-Lei Cao; Qing-Hua Qin; Ning Zhao

    2012-01-01

    This paper presents a hybrid graded element model for the transient heat conduction problem in functionally graded materials (FGMs).First,a Laplace transform approach is used to handle the time variable.Then,a fundamental solution in Laplace space for FGMs is constructed.Next,a hybrid graded element is formulated based on the obtained fundamental solution and a frame field.As a result,the graded properties of FGMs are naturally reflected by using the fundamental solution to interpolate the intra-element field.Further,Stefest's algorithm is employed to convert the results in Laplace space back into the time-space domain.Finally,the performance of the proposed method is assessed by several benchmark examples.The results demonstrate well the efficiency and accuracy of the proposed method.

  11. Identification of functional glucocorticoid response elements in the mouse FoxO1 promoter.

    Science.gov (United States)

    Qin, Weiping; Pan, Jiangping; Qin, Yiwen; Lee, David N; Bauman, William A; Cardozo, Christopher

    2014-07-25

    Glucocorticoids stimulate muscle atrophy through a cascade of signals that includes activation of FoxO transcription factors which then upregulate multiple genes to promote degradation of myofibrillar and other muscle proteins and inhibit protein synthesis. Our previous finding that glucocorticoids upregulate mRNA levels for FoxO1 in skeletal muscle led us to hypothesize that the FoxO1 gene contains one or more glucocorticoid response elements (GREs). Here we show that upregulation of FoxO1 expression by glucocorticoids requires the glucocorticoid receptor (GR) and binding of hormones to it. In cultured C2C12 myoblasts dexamethasone did not alter FoxO1 mRNA stability. Computational analysis predicted that the proximal promoter of the FoxO1 gene contained a cluster of eight GRE half sites and one highly conserved near-consensus SRE; the cluster is found between -800 and -2000bp upstream of the first codon of the FoxO1 gene. A reporter gene constructed using the first 2kb of the FoxO1 promoter was stimulated by dexamethasone. Removal of a 5' domain containing half of the GREs reduced reporter gene activity and removal of all GREs in this region ablated activation by dexamethasone. Restriction fragments of the cluster of 8 upstream GREs bound recombinant GR in gel shift assays. Collectively, the data demonstrate that the proximal promoter of the FoxO1 gene contains multiple functional GREs, indicating that upregulation of FoxO1 expression by glucocorticoids through GREs represents an additional mechanism by which the GR drives glucocorticoid-mediated muscle atrophy. These findings are also relevant to other physiological roles of FoxO1 such as regulation of hepatic metabolism. Published by Elsevier Inc.

  12. Do consumption of Kargi Tulum cheese meet daily requirements for minerals and trace elements?

    Directory of Open Access Journals (Sweden)

    Seval Sevgi Kirdar

    2015-07-01

    Full Text Available The mineral and trace elements of Kargı Tulum cheese are investigated during the ripening period of 90 days. Calcium, potassium, phosphorus, sodium, magnesium, manganese, copper, zinc and iron quantities were determined by simultaneous inductively coupled plasma optical emission spectrometry (ICP-OES. The effect of maturation time on the sodium, phosphor and potassium content of cheese samples has been found to be statistically significant (p<0.05. Magnesium and calcium levels during ripening period showed significant statistical difference (p<0.01. Copper values of cheese samples demonstrated an increase throughout 90-day maturation time. The effect of maturation time on manganese and zinc value has been found to be statistically significant (p<0.05. According to obtained data, by consuming 100 g Kargı Tulum cheese in daily period, an adult can provide a remarkable portion of his/her minerals needs.

  13. Finite element analysis (FEA): applying an engineering method to functional morphology in anthropology and human biology.

    Science.gov (United States)

    Panagiotopoulou, O

    2009-01-01

    A fundamental research question for morphologists is how morphological variation in the skeleton relates to function. Traditional approaches have advanced our understanding of form-function relationships considerably but have limitations. Strain gauges can only record strains on a surface, and the geometry of the structure can limit where they can be bonded. Theoretical approaches, such as geometric abstractions, work well on problems with simple geometries and material properties but biological structures typically have neither of these. Finite element analysis (FEA) is a method that overcomes these problems by reducing a complex geometry into a finite number of elements with simple geometries. In addition, FEA allows strain to be modelled across the entire surface of the structure and throughout the internal structure. With advances in the processing power of computers, FEA has become more accessible and as such is becoming an increasingly popular tool to address questions about form-function relationships in development and evolution, as well as human biology generally. This paper provides an introduction to FEA including a review of the sequence of steps needed for the generation of biologically accurate finite element models that can be used for the testing of biological and functional morphology hypotheses.

  14. Expert Opinion on Elements Required to Develop a Base Support Plan Training Guide

    Science.gov (United States)

    1989-09-01

    transiting or deploying forces is critica . The reception of forces refer to meeting short term requirements of the forces. Temporary billeting and... crisis for the logistician to fix anyway. Question G: The emphasis must be placed on continuing mission support and integration of effort. This seems to be

  15. Analysis of Tactical Automation Requirements for the Maneuver Functional Area.

    Science.gov (United States)

    1987-11-06

    BT. N 3 - ESSEN’TIAL CD.TR:B’:.’ I-II-2 lL IDENIFICATION OF HARDWARE REQUIREMENTS CANDIDATE SOLUTIONS TYPE UNIT: COMBAT ENGR ECHELON: BN OPERATOR: BN...STORAGE REQ7IREMENT FOR FOG OIL X 2~ i lET PERSONNEL REQ TO DO DECON TIASKS - F ORE-CAST IiECON MATER:Al- x.QRMN 33 1V --TORAGE REQ FOR DECrNTA.YMNAN... FOG OIL RE.’IRE X :0 DETERMINE SMOKE POT REQUIREMENTS X 11 DEV STORAGE REQUIREMENT FOR FOG OIL x x 2 DET PERSONNEL REQ TO DO DECON -ASKS XX 13

  16. An arthropod cis-regulatory element functioning in sensory organ precursor development dates back to the Cambrian

    Directory of Open Access Journals (Sweden)

    Simpson Pat

    2010-09-01

    Full Text Available Abstract Background An increasing number of publications demonstrate conservation of function of cis-regulatory elements without sequence similarity. In invertebrates such functional conservation has only been shown for closely related species. Here we demonstrate the existence of an ancient arthropod regulatory element that functions during the selection of neural precursors. The activity of genes of the achaete-scute (ac-sc family endows cells with neural potential. An essential, conserved characteristic of proneural genes is their ability to restrict their own activity to single or a small number of progenitor cells from their initially broad domains of expression. This is achieved through a process called lateral inhibition. A regulatory element, the sensory organ precursor enhancer (SOPE, is required for this process. First identified in Drosophila, the SOPE contains discrete binding sites for four regulatory factors. The SOPE of the Drosophila asense gene is situated in the 5' UTR. Results Through a manual comparison of consensus binding site sequences we have been able to identify a SOPE in UTR sequences of asense-like genes in species belonging to all four arthropod groups (Crustacea, Myriapoda, Chelicerata and Insecta. The SOPEs of the spider Cupiennius salei and the insect Tribolium castaneum are shown to be functional in transgenic Drosophila. This would place the origin of this regulatory sequence as far back as the last common ancestor of the Arthropoda, that is, in the Cambrian, 550 million years ago. Conclusions The SOPE is not detectable by inter-specific sequence comparison, raising the possibility that other ancient regulatory modules in invertebrates might have escaped detection.

  17. Advanced functional materials in solid phase extraction for ICP-MS determination of trace elements and their species - A review.

    Science.gov (United States)

    He, Man; Huang, Lijin; Zhao, Bingshan; Chen, Beibei; Hu, Bin

    2017-06-22

    For the determination of trace elements and their species in various real samples by inductively coupled plasma mass spectrometry (ICP-MS), solid phase extraction (SPE) is a commonly used sample pretreatment technique to remove complex matrix, pre-concentrate target analytes and make the samples suitable for subsequent sample introduction and measurements. The sensitivity, selectivity/anti-interference ability, sample throughput and application potential of the methodology of SPE-ICP-MS are greatly dependent on SPE adsorbents. This article presents a general overview of the use of advanced functional materials (AFMs) in SPE for ICP-MS determination of trace elements and their species in the past decade. Herein the AFMs refer to the materials featuring with high adsorption capacity, good selectivity, fast adsorption/desorption dynamics and satisfying special requirements in real sample analysis, including nanometer-sized materials, porous materials, ion imprinting polymers, restricted access materials and magnetic materials. Carbon/silica/metal/metal oxide nanometer-sized adsorbents with high surface area and plenty of adsorption sites exhibit high adsorption capacity, and porous adsorbents would provide more adsorption sites and faster adsorption dynamics. The selectivity of the materials for target elements/species can be improved by using physical/chemical modification, ion imprinting and restricted accessed technique. Magnetic adsorbents in conventional batch operation offer unique magnetic response and high surface area-volume ratio which provide a very easy phase separation, greater extraction capacity and efficiency over conventional adsorbents, and chip-based magnetic SPE provides a versatile platform for special requirement (e.g. cell analysis). The performance of these adsorbents for the determination of trace elements and their species in different matrices by ICP-MS is discussed in detail, along with perspectives and possible challenges in the future

  18. Genetic evidence for conserved non-coding element function across species--the ears have it

    Directory of Open Access Journals (Sweden)

    Eric E Turner

    2014-01-01

    Full Text Available Comparison of genomic sequences from diverse vertebrate species has revealed numerous highly conserved regions that do not appear to encode proteins or functional RNAs. Often these conserved non-coding elements, or CNEs, direct gene expression to specific tissues in transgenic models, demonstrating they have regulatory function. CNEs are frequently found near ‘developmental’ genes, particularly transcription factors, implying that these elements have essential regulatory roles in development. However, actual examples demonstrating CNE regulatory functions across species have been few, and recent loss-of-function studies of several CNEs in mice have shown relatively minor effects. In this Perspectives article, we discuss new findings in fancy rats and Highland cattle demonstrating that function of a CNE near the Hmx1 gene is crucial for normal external ear development and resembles loss-of function Hmx1 coding mutations in mice and humans. These findings provide important support for similar developmental roles of CNEs in divergent species, and reinforce the concept that CNEs should be examined systematically in the ongoing search for genetic causes of human developmental disorders in the era of genome-scale sequencing.

  19. CRTC2 is required for β-cell function and proliferation.

    Science.gov (United States)

    Eberhard, Chandra E; Fu, Accalia; Reeks, Courtney; Screaton, Robert A

    2013-07-01

    Previous work in insulinoma cell lines has established that calcineurin plays a critical role in the activation of cAMP-responsive element binding protein (Creb), a key transcription factor required for β-cell function and survival, by dephosphorylating the Creb coactivator Creb-regulated transcription coactivator (Crtc)2 at 2 regulatory sites, Ser171 and Ser275. Here, we report that Crtc2 is essential both for glucose-stimulated insulin secretion and cell survival in the β-cell. Endogenous Crtc2 activation is achieved via increasing glucose levels to the physiological feeding range, indicating that Crtc2 is a sensor that couples ambient glucose concentrations to Creb activity in the β-cell. Immunosuppressant drugs such as cyclosporin A and tacrolimus that target the protein phosphatase calcineurin are commonly administered after organ transplantation. Chronic use is associated with reduced insulin secretion and new onset diabetes, suggestive of pancreatic β-cell dysfunction. Importantly, we show that overexpression of a Crtc2 mutant rendered constitutively active by introduction of nonphosphorylatable alanine residues at Ser171 and Ser275 permits Creb target gene activation under conditions when calcineurin is inhibited. Taken together, these data suggest that promoting Crtc2-Creb activity is required for β-cell function and proliferation and promoting this pathway could ameliorate symptoms of new onset diabetes after transplantation.

  20. Intermediate elemental image reconstruction for refocused three-dimensional images in integral imaging by convolution with δ-function sequences

    Science.gov (United States)

    Yoo, Hoon; Jang, Jae-Young

    2017-10-01

    We propose a novel approach for intermediate elemental image reconstruction in integral imaging. To reconstruct intermediate elemental images, we introduce a null elemental image whose pixels are all zero. In the proposed method a number of null elemental images are inserted into a given elemental image array. The elemental image array with null elemental images is convolved with the δ-function sequence. The convolution result shows that the proposed method provides an efficient structure to expand an elemental image array. The resulting elemental image array from the proposed method can supply three-dimensional information for an object at a specific depth. In addition, the proposed method provides adjustable parameters, which can be utilized in design of integral imaging systems. The feasibility of the proposed method has been confirmed through preliminary experiments and theoretical analysis.

  1. Acoustic Transfer Functions Derived from Finite Element Modeling for Thermoacoustic Stability Predictions of Gas Turbine Engines

    OpenAIRE

    Black, Paul Randall

    2007-01-01

    Acoustic Transfer Functions Derived from Finite Element Modeling for Thermoacoustic Stability Predictions of Gas Turbine Engines Design and prediction of thermoacoustic instabilities is a major challenge in aerospace propulsion and the operation of power generating gas turbine engines. This is a complex problem in which multiple physical systems couple together. Traditionally, thermoacoustic models can be reduced to dominant physics which depend only on flame dynamics and acoustics. Th...

  2. Calculation of the matrix elements of the Coulomb interaction involving relativistic hydrogenic wave functions

    Science.gov (United States)

    Sarkadi, L.

    2017-03-01

    The program MTRDCOUL [1] calculates the matrix elements of the Coulomb interaction between a charged particle and an atomic electron, ∫ ψf∗ (r) ∣ R - r∣-1ψi(r) d r. Bound-free transitions are considered, and relativistic hydrogenic wave functions are used. In this revised version a bug discovered in the F3Y CPC Program Library subprogram [2] is fixed.

  3. Elements required for an efficient NADP-malic enzyme type C4 photosynthesis.

    Science.gov (United States)

    Wang, Yu; Long, Stephen P; Zhu, Xin-Guang

    2014-04-01

    C4 photosynthesis has higher light, nitrogen, and water use efficiencies than C3 photosynthesis. Although the basic anatomical, cellular, and biochemical features of C4 photosynthesis are well understood, the quantitative significance of each element of C4 photosynthesis to the high photosynthetic efficiency are not well defined. Here, we addressed this question by developing and using a systems model of C4 photosynthesis, which includes not only the Calvin-Benson cycle, starch synthesis, sucrose synthesis, C4 shuttle, and CO₂ leakage, but also photorespiration and metabolite transport between the bundle sheath cells and mesophyll cells. The model effectively simulated the CO₂ uptake rates, and the changes of metabolite concentrations under varied CO₂ and light levels. Analyses show that triose phosphate transport and CO₂ leakage can help maintain a high photosynthetic rate by balancing ATP and NADPH amounts in bundle sheath cells and mesophyll cells. Finally, we used the model to define the optimal enzyme properties and a blueprint for C4 engineering. As such, this model provides a theoretical framework for guiding C4 engineering and studying C4 photosynthesis in general.

  4. [Estimates of trace elements requirements of children receiving total parenteral nutrition].

    Science.gov (United States)

    Ricour, C; Duhamel, J F; Gros, J; Mazière, B; Comar, D

    1977-01-01

    Ten children on total parenteral nutrition were studied. Plasma copper, zinc, manganese and selenium levels were determined by neutron activation and gamma spectrometry, every 10 days. With a copper intake of 20 microgram/kg/24 h, the average level 120 microgram% (94-144) was normal (N: 118 microgram +/- 11%). With a manganese intake of 40 microgram/kg/24 h, the level increased to 2.6 microgram% (1.3-4.5) (N: 1.1 microgram +/- 0.2%). With a zinc intake of 30 microgram/kg/24 h, the level decreased to 45.9 microgram % (20-63) (N: 83 microgram +/- 28%); with an intake of 50 microgram/kg/24 h the level remained under normal. With a selenium intake of 1 microgram/kg/24 h, the level decreased to 10.6 ng/ml (3.6-21.6) (N: 38.2 ng/ml +/- 11.9), but was normalized with an intake of 3 microgram/kg/24 h. From these results, with all reserves that estimation implies, the authors suggest that the disorders due to deficit or excess of trace elements could be avoided by daily intakes per kg of body weight: copper 20 microgram, zinc 100 microgram, manganese 10 microgram and selenium 3 microgram, with supplementation of iron, iodine and fluoride.

  5. High conservation of a 5' element required for RNA editing of a C target in chloroplast psbE transcripts.

    Science.gov (United States)

    Hayes, Michael L; Hanson, Maureen R

    2008-09-01

    C-to-U editing modifies 30-40 distinct nucleotides within higher-plant chloroplast transcripts. Many C targets are located at the same position in homologous genes from different plants; these either could have emerged independently or could share a common origin. The 5' sequence GCCGUU, required for editing of C214 in tobacco psbE in vitro, is one of the few identified editing cis-elements. We investigated psbE sequences from many plant species to determine in what lineage(s) editing of psbE C214 emerged and whether the cis-element identified in tobacco is conserved in plants with a C214. The GCCGUU sequence is present at a high frequency in plants that carry a C214 in psbE. However, Sciadopitys verticillata (Pinophyta) edits C214 despite the presence of nucleotide differences compared to the conserved cis-element. The C214 site in psbE genes is represented in members of four branches of spermatophytes but not in gnetophytes, resulting in the parsimonious prediction that editing of psbE C214 was present in the ancestor of spermatophytes. Extracts from chloroplasts from a species that has a difference in the motif and lacks the C target are incapable of editing tobacco psbE C214 substrates, implying that the critical trans-acting protein factors were not retained without a C target. Because noncoding sequences are less constrained than coding regions, we analyzed sequences 5' to two C editing targets located within coding regions to search for possible editing-related conserved elements. Putative editing cis-elements were uncovered in the 5' UTRs near editing sites psbL C2 and ndhD C2.

  6. Robust design requirements specification: a quantitative method for requirements development using quality loss functions

    DEFF Research Database (Denmark)

    Pedersen, Søren Nygaard; Christensen, Martin Ebro; Howard, Thomas J.

    2016-01-01

    Product requirements serve many purposes in the product development process. Most importantly, they are meant to capture and facilitate product goals and acceptance criteria, as defined by stakeholders. Accurately communicating stakeholder goals and acceptance criteria can be challenging and more...

  7. Towards a Scope Management of Non-Functional Requirements in Requirements Engineering

    NARCIS (Netherlands)

    Kassab, M.; Ormandjieva, O.; Daneva, Maia; Ebert, C.; Herrmann, A.; Rupp, C.

    Getting business stakeholders’ goals formulated clearly and project scope defined realistically increases the chance of success for any application development process. As a consequence, stakeholders at early project stages acquire as much as possible knowledge about the requirements, their risk

  8. All-electron Kohn–Sham density functional theory on hierarchic finite element spaces

    Energy Technology Data Exchange (ETDEWEB)

    Schauer, Volker [Institute of Applied Mechanics (CE) Chair I, University of Stuttgart, 70550 Stuttgart, Pfaffenwaldring 7 (Germany); Linder, Christian, E-mail: linder@stanford.edu [Department of Civil and Environmental Engineering, Stanford University, Stanford, CA 94305 (United States)

    2013-10-01

    In this work, a real space formulation of the Kohn–Sham equations is developed, making use of the hierarchy of finite element spaces from different polynomial order. The focus is laid on all-electron calculations, having the highest requirement onto the basis set, which must be able to represent the orthogonal eigenfunctions as well as the electrostatic potential. A careful numerical analysis is performed, which points out the numerical intricacies originating from the singularity of the nuclei and the necessity for approximations in the numerical setting, with the ambition to enable solutions within a predefined accuracy. In this context the influence of counter-charges in the Poisson equation, the requirement of a finite domain size, numerical quadratures and the mesh refinement are examined as well as the representation of the electrostatic potential in a high order finite element space. The performance and accuracy of the method is demonstrated in computations on noble gases. In addition the finite element basis proves its flexibility in the calculation of the bond-length as well as the dipole moment of the carbon monoxide molecule.

  9. Functional Requirements for SIERRA Version 1.0 Beta

    Energy Technology Data Exchange (ETDEWEB)

    EDWARDS, HAROLD C.; STEWART, JAMES R.; TAYLOR, LEE M.

    1999-10-01

    The objective of the SIERRA framework is to provide a common software infrastructure for massively parallel computational mechanics applications. The SIERRA framework consolidates the mechanics-independent computational services required by a diverse set of mechanics applications into a shared framework. Consolidation of these computational services eliminates their redundant development and maintenance efforts and streamlines the coupling of independently developed computational mechanics capabilities into integrated multi-mechanics applications.

  10. Hippocampal-dependent learning requires a functional circadian system.

    Science.gov (United States)

    Ruby, Norman F; Hwang, Calvin E; Wessells, Colin; Fernandez, Fabian; Zhang, Pei; Sapolsky, Robert; Heller, H Craig

    2008-10-01

    Decades of studies have shown that eliminating circadian rhythms of mammals does not compromise their health or longevity in the laboratory in any obvious way. These observations have raised questions about the functional significance of the mammalian circadian system, but have been difficult to address for lack of an appropriate animal model. Surgical ablation of the suprachiasmatic nucleus (SCN) and clock gene knockouts eliminate rhythms, but also damage adjacent brain regions or cause developmental effects that may impair cognitive or other physiological functions. We developed a method that avoids these problems and eliminates rhythms by noninvasive means in Siberian hamsters (Phodopus sungorus). The present study evaluated cognitive function in arrhythmic animals by using a hippocampal-dependent learning task. Control hamsters exhibited normal circadian modulation of performance in a delayed novel-object recognition task. By contrast, arrhythmic animals could not discriminate a novel object from a familiar one only 20 or 60 min after training. Memory performance was not related to prior sleep history as sleep manipulations had no effect on performance. The GABA antagonist pentylenetetrazol restored learning without restoring circadian rhythms. We conclude that the circadian system is involved in memory function in a manner that is independent of sleep. Circadian influence on learning may be exerted via cyclic GABA output from the SCN to target sites involved in learning. Arrhythmic hamsters may have failed to perform this task because of chronic inhibitory signaling from the SCN that interfered with the plastic mechanisms that encode learning in the hippocampus.

  11. Functional Internet Literacy: Required Cognitive Skills with Implications for Instruction

    Science.gov (United States)

    Johnson, Genevieve Marie

    2007-01-01

    Patterns of typical Internet use provide the basis for defining "functional Internet literacy." Internet use commonly includes communication, information, recreation, and commercial activities. Technical competence with connectivity, security, and downloads is a prerequisite for using the Internet for such activities. Bloom's taxonomy of cognitive…

  12. Thyroid hormone is required for hypothalamic neurons regulating cardiovascular functions

    NARCIS (Netherlands)

    Mittag, J.; Lyons, D.J.; Sällström, J.; Vujoviv, M.; Dudazy-Gralla, S.; Warner, A.; Wallis, K.; Alkemade, A.; Nordström, K.; Monyer, H.; Broberger, C.; Arner, A.; Vennström, B.

    2013-01-01

    Thyroid hormone is well known for its profound direct effects on cardiovascular function and metabolism. Recent evidence, however, suggests that the hormone also regulates these systems indirectly through the central nervous system. While some of the molecular mechanisms underlying the hormone’s

  13. Matrix elements for sum of power-law potentials in quantum mechanic using generalized hypergeometric functions

    Directory of Open Access Journals (Sweden)

    Ma'zoozeh E. Abu-Amra

    2008-04-01

    Full Text Available In this paper we derive close form for the matrix elements for $hat H=-Delta +V$, where $V$ is a pure power-law potential. We use trial functions of the form $$ psi _n(r= sqrt{{frac{2eta ^{gamma/2}(gamma _n} {n!Gamma(gamma }}} r^{gamma - 1/2} e^{-frac{sqrt{eta }}{2}r^q} _pF_1 ( -n,a_2,ldots ,a_p;gamma;sqrt {eta } r^q, $$ for $eta, q,gamma >0$ to obtain the matrix elements for $hat H$. These formulas are then optimized with respect to variational parameters $eta ,q$ and $gamma $ to obtain accurate upper bounds for the given nonsolvable eigenvalue problem in quantum mechanics. Moreover, we write the matrix elements in terms of the generalized hypergeomtric functions. These results are generalization of those found earlier in [2], [8-16] for power-law potentials. Applications and comparisons with earlier work are presented.

  14. Home Blood Pressure Telemonitoring: Rationale for Use, Required Elements, and Barriers to Implementation in Canada.

    Science.gov (United States)

    Wood, Peter W; Boulanger, Pierre; Padwal, Raj S

    2017-05-01

    Contemporary hypertension guidelines strongly endorse the use of home blood pressure (BP) monitoring for hypertension diagnosis and management. However, barriers exist that prevent optimal use of home BP measurements. Patients might not follow the recommended home BP measurement protocol, might not take the required number of readings, and/or might report only selected readings to their providers. Providers might not calculate the mean (used for clinical decision-making) and/or incorporate home BP measurements into the medical record. Use of home BP telemonitoring, defined as the process by which home BP readings are securely teletransmitted and summarized within a health care portal or electronic medical record for provider use, might overcome these barriers. Telemonitoring, especially when combined with protocolized case management, leads to statistically significant and clinically important BP reductions, and improvements in overall BP control. Despite evidence supporting its use, home BP telemonitoring is not widely used in Canada. Barriers to adoption can be classified as structural and financial. Although technological advancements have made telemonitoring highly feasible, infrastructure is lacking, and implementation remains a challenge; this is especially true with respect to creating simple and cost-effective systems that are user-friendly and acceptable to patients as well as to providers. Ensuring data security is crucial to successful implementation, as is developing appropriate reimbursement models for providers. If these barriers can be overcome, home BP telemonitoring has the potential to make care provision easier and more convenient for patients and providers, while improving BP control in Canadians with hypertension. Copyright © 2017 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  15. Study on the Explicit Formula of the Triangular Flat Shell Element Based on the Analytical Trial Functions for Anisotropy Material

    Directory of Open Access Journals (Sweden)

    Xiang-Rong Fu

    2013-01-01

    Full Text Available This paper presents a novel way to formulate the triangular flat shell element. The basic analytical solutions of membrane and bending plate problem for anisotropy material are studied separately. Combining with the conforming displacement along the sides and hybrid element strategy, the triangular flat shell elements based on the analytical trial functions (ATF for anisotropy material are formulated. By using the explicit integral formulae of the triangular element, the matrices used in proposed shell element are calculated efficiently. The benchmark examples showed the high accuracy and high efficiency.

  16. Multiscale finite element methods for high-contrast problems using local spectral basis functions

    KAUST Repository

    Efendiev, Yalchin

    2011-02-01

    In this paper we study multiscale finite element methods (MsFEMs) using spectral multiscale basis functions that are designed for high-contrast problems. Multiscale basis functions are constructed using eigenvectors of a carefully selected local spectral problem. This local spectral problem strongly depends on the choice of initial partition of unity functions. The resulting space enriches the initial multiscale space using eigenvectors of local spectral problem. The eigenvectors corresponding to small, asymptotically vanishing, eigenvalues detect important features of the solutions that are not captured by initial multiscale basis functions. Multiscale basis functions are constructed such that they span these eigenfunctions that correspond to small, asymptotically vanishing, eigenvalues. We present a convergence study that shows that the convergence rate (in energy norm) is proportional to (H/Λ*)1/2, where Λ* is proportional to the minimum of the eigenvalues that the corresponding eigenvectors are not included in the coarse space. Thus, we would like to reach to a larger eigenvalue with a smaller coarse space. This is accomplished with a careful choice of initial multiscale basis functions and the setup of the eigenvalue problems. Numerical results are presented to back-up our theoretical results and to show higher accuracy of MsFEMs with spectral multiscale basis functions. We also present a hierarchical construction of the eigenvectors that provides CPU savings. © 2010.

  17. Functions for patch test in finite element analysis of the Mindlin plate and the thin cylindrical shell

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Current patch test for Mindlin plate element only satisfies the zero shear deformation condition.The patch test of non-zero constant shear for Mindlin plate problem cannot be performed.For shell element, the patch test does not even exist.Based on the theory of enhanced patch test proposed by Chen W J (2006),the authors proposed the enhanced patch test function for Mindlin plate and thin cylindrical shell elements.This enhanced patch test function can be used to assess the convergence of the Mindlin plate and cylindrical thin shell elements.

  18. Casing of preinsulated district heating pipes. Functional Requirements. Scientific report

    Energy Technology Data Exchange (ETDEWEB)

    Bryder, K.L.; Feld, T.; Randloev, P.; Vestergaard, J.B.; Noergaard Pedersen, H.; Palle, S.; Amby, L.

    1996-10-01

    Requirements for the wall thickness of the casing pipes in Europe were formulated to clarify the laying conditions, representative for the European district heating areas. We achieved a broad estimate by defining four scenarios for the laying of district heating pipes. It is common to the four scenarios that that all bends, branches etc. are always laid in sand. The four scenarios are differentiated by soil types. The soil types include: Uniform sand, Well graded gravel, Sand with fines and Sand with crushed stone. In the following analysis it was possible to examine the influence from following parameters: Casing thickness; Diameter of steel pipe; Diameter of casing; Material properties (PUR and PE); Soil type. The results from the model showed that uniform sand is the absolute best soil type. Based on the results from and earlier project a laboratory method has been developed. The result was a test method based on the indentation of three mandrels with a diameter of {phi}30 mm with a taper with an angle of 45 deg. and with roundings on the apex of R5 mm, R10 mm and R15 mm, respectively. The mandrels simulate stones. The examinations among other things showed that even a 1.5 mm casing demands an indentation of 20 mm with a R5 mm mandrel before it is perforated. The demanded force is 1.6 kN, which is considerably higher than the theoretically highest force in an actual situation. On this background it is recommended that the minimum requirement for the wall thickness of the casings with diameters less than 200 mm should still follow the EN 253, whereas the minimum requirement for the larger casing pipes securely can be reduced. Based on the tests and an evaluation of the safety factors it is proposed that the wall thickness for the largest pipes can be reduced 50%. Thus the wall thickness of an 800 mm casing should be 6.6 mm with a linear reduction down to 3 mm for 180 mm casing. (EG)

  19. Identification of functional elements and regulatory circuits by Drosophila modENCODE

    Energy Technology Data Exchange (ETDEWEB)

    Roy, Sushmita; Ernst, Jason; Kharchenko, Peter V.; Kheradpour, Pouya; Negre, Nicolas; Eaton, Matthew L.; Landolin, Jane M.; Bristow, Christopher A.; Ma, Lijia; Lin, Michael F.; Washietl, Stefan; Arshinoff, Bradley I.; Ay, Ferhat; Meyer, Patrick E.; Robine, Nicolas; Washington, Nicole L.; Stefano, Luisa Di; Berezikov, Eugene; Brown, Christopher D.; Candeias, Rogerio; Carlson, Joseph W.; Carr, Adrian; Jungreis, Irwin; Marbach, Daniel; Sealfon, Rachel; Tolstorukov, Michael Y.; Will, Sebastian; Alekseyenko, Artyom A.; Artieri, Carlo; Booth, Benjamin W.; Brooks, Angela N.; Dai, Qi; Davis, Carrie A.; Duff, Michael O.; Feng, Xin; Gorchakov, Andrey A.; Gu, Tingting; Henikoff, Jorja G.; Kapranov, Philipp; Li, Renhua; MacAlpine, Heather K.; Malone, John; Minoda, Aki; Nordman, Jared; Okamura, Katsutomo; Perry, Marc; Powell, Sara K.; Riddle, Nicole C.; Sakai, Akiko; Samsonova, Anastasia; Sandler, Jeremy E.; Schwartz, Yuri B.; Sher, Noa; Spokony, Rebecca; Sturgill, David; van Baren, Marijke; Wan, Kenneth H.; Yang, Li; Yu, Charles; Feingold, Elise; Good, Peter; Guyer, Mark; Lowdon, Rebecca; Ahmad, Kami; Andrews, Justen; Berger, Bonnie; Brenner, Steven E.; Brent, Michael R.; Cherbas, Lucy; Elgin, Sarah C. R.; Gingeras, Thomas R.; Grossman, Robert; Hoskins, Roger A.; Kaufman, Thomas C.; Kent, William; Kuroda, Mitzi I.; Orr-Weaver, Terry; Perrimon, Norbert; Pirrotta, Vincenzo; Posakony, James W.; Ren, Bing; Russell, Steven; Cherbas, Peter; Graveley, Brenton R.; Lewis, Suzanna; Micklem, Gos; Oliver, Brian; Park, Peter J.; Celniker, Susan E.; Henikoff, Steven; Karpen, Gary H.; Lai, Eric C.; MacAlpine, David M.; Stein, Lincoln D.; White, Kevin P.; Kellis, Manolis

    2010-12-22

    To gain insight into how genomic information is translated into cellular and developmental programs, the Drosophila model organism Encyclopedia of DNA Elements (modENCODE) project is comprehensively mapping transcripts, histone modifications, chromosomal proteins, transcription factors, replication proteins and intermediates, and nucleosome properties across a developmental time course and in multiple cell lines. We have generated more than 700 data sets and discovered protein-coding, noncoding, RNA regulatory, replication, and chromatin elements, more than tripling the annotated portion of the Drosophila genome. Correlated activity patterns of these elements reveal a functional regulatory network, which predicts putative new functions for genes, reveals stage- and tissue-specific regulators, and enables gene-expression prediction. Our results provide a foundation for directed experimental and computational studies in Drosophila and related species and also a model for systematic data integration toward comprehensive genomic and functional annotation. Several years after the complete genetic sequencing of many species, it is still unclear how to translate genomic information into a functional map of cellular and developmental programs. The Encyclopedia of DNA Elements (ENCODE) (1) and model organism ENCODE (modENCODE) (2) projects use diverse genomic assays to comprehensively annotate the Homo sapiens (human), Drosophila melanogaster (fruit fly), and Caenorhabditis elegans (worm) genomes, through systematic generation and computational integration of functional genomic data sets. Previous genomic studies in flies have made seminal contributions to our understanding of basic biological mechanisms and genome functions, facilitated by genetic, experimental, computational, and manual annotation of the euchromatic and heterochromatic genome (3), small genome size, short life cycle, and a deep knowledge of development, gene function, and chromosome biology. The functions

  20. Avoiding coral reef functional collapse requires local and global action.

    Science.gov (United States)

    Kennedy, Emma V; Perry, Chris T; Halloran, Paul R; Iglesias-Prieto, Roberto; Schönberg, Christine H L; Wisshak, Max; Form, Armin U; Carricart-Ganivet, Juan P; Fine, Maoz; Eakin, C Mark; Mumby, Peter J

    2013-05-20

    Coral reefs face multiple anthropogenic threats, from pollution and overfishing to the dual effects of greenhouse gas emissions: rising sea temperature and ocean acidification. While the abundance of coral has declined in recent decades, the implications for humanity are difficult to quantify because they depend on ecosystem function rather than the corals themselves. Most reef functions and ecosystem services are founded on the ability of reefs to maintain their three-dimensional structure through net carbonate accumulation. Coral growth only constitutes part of a reef's carbonate budget; bioerosion processes are influential in determining the balance between net structural growth and disintegration. Here, we combine ecological models with carbonate budgets and drive the dynamics of Caribbean reefs with the latest generation of climate models. Budget reconstructions using documented ecological perturbations drive shallow (6-10 m) Caribbean forereefs toward an increasingly fragile carbonate balance. We then projected carbonate budgets toward 2080 and contrasted the benefits of local conservation and global action on climate change. Local management of fisheries (specifically, no-take marine reserves) and the watershed can delay reef loss by at least a decade under "business-as-usual" rises in greenhouse gas emissions. However, local action must be combined with a low-carbon economy to prevent degradation of reef structures and associated ecosystem services. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. The edge-based face element method for 3D-stream function and flux calculations in porous media flow

    NARCIS (Netherlands)

    Zijl, W.; Nawalany, M.

    2004-01-01

    We present a velocity-oriented discrete analog of the partial differential equations governing porous media flow: the edge-based face element method. Conventional finite element techniques calculate pressures in the nodes of the grid. However, such methods do not satisfy the requirement of flux cont

  2. Targeted deletion of multiple CTCF-binding elements in the human C-MYC gene reveals a requirement for CTCF in C-MYC expression.

    Directory of Open Access Journals (Sweden)

    Wendy M Gombert

    Full Text Available BACKGROUND: Insulators and domain boundaries both shield genes from adjacent enhancers and inhibit intrusion of heterochromatin into transgenes. Previous studies examined the functional mechanism of the MYC insulator element MINE and its CTCF binding sites in the context of transgenes that were randomly inserted into the genome by transfection. However, the contribution of CTCF binding sites to both gene regulation and maintenance of chromatin has not been tested at the endogenous MYC gene. METHODOLOGY/PRINCIPAL FINDINGS: To determine the impact of CTCF binding on MYC expression, a series of mutant human chromosomal alleles was prepared in homologous recombination-efficient DT40 cells and individually transferred by microcell fusion into murine cells. Functional tests reported here reveal that deletion of CTCF binding elements within the MINE does not impact the capacity of this locus to correctly organize an 'accessible' open chromatin domain, suggesting that these sites are not essential for the formation of a competent, transcriptionally active locus. Moreover, deletion of the CTCF site at the MYC P2 promoter reduces transcription but does not affect promoter acetylation or serum-inducible transcription. Importantly, removal of either CTCF site leads to DNA methylation of flanking sequences, thereby contributing to progressive loss of transcriptional activity. CONCLUSIONS: These findings collectively demonstrate that CTCF-binding at the human MYC locus does not repress transcriptional activity but is required for protection from DNA methylation.

  3. SIRT6 is required for normal retinal function.

    Directory of Open Access Journals (Sweden)

    Dafne M Silberman

    Full Text Available The retina is one of the major energy consuming tissues within the body. In this context, synaptic transmission between light-excited rod and cone photoreceptors and downstream ON-bipolar neurons is a highly demanding energy consuming process. Sirtuin 6 (SIRT6, a NAD-dependent deacylase, plays a key role in regulating glucose metabolism. In this study, we demonstrate that SIRT6 is highly expressed in the retina, controlling levels of histone H3K9 and H3K56 acetylation. Notably, despite apparent normal histology, SIRT6 deficiency caused major retinal transmission defects concomitant to changes in expression of glycolytic genes and glutamate receptors, as well as elevated levels of apoptosis in inner retina cells. Our results identify SIRT6 as a critical modulator of retinal function, likely through its effects on chromatin.

  4. SIRT6 is required for normal retinal function.

    Science.gov (United States)

    Silberman, Dafne M; Ross, Kenneth; Sande, Pablo H; Kubota, Shunsuke; Ramaswamy, Sridhar; Apte, Rajendra S; Mostoslavsky, Raul

    2014-01-01

    The retina is one of the major energy consuming tissues within the body. In this context, synaptic transmission between light-excited rod and cone photoreceptors and downstream ON-bipolar neurons is a highly demanding energy consuming process. Sirtuin 6 (SIRT6), a NAD-dependent deacylase, plays a key role in regulating glucose metabolism. In this study, we demonstrate that SIRT6 is highly expressed in the retina, controlling levels of histone H3K9 and H3K56 acetylation. Notably, despite apparent normal histology, SIRT6 deficiency caused major retinal transmission defects concomitant to changes in expression of glycolytic genes and glutamate receptors, as well as elevated levels of apoptosis in inner retina cells. Our results identify SIRT6 as a critical modulator of retinal function, likely through its effects on chromatin.

  5. The Function,Future and Support Elements of Farmer Cooperative Economy Organization

    Institute of Scientific and Technical Information of China (English)

    Jing; GAO; Peng; XIE

    2014-01-01

    The nature of farmer cooperative economy organization( known as FCEO) determines the fact that the economic effects of farmer cooperative economy organization are as important as its social effects. Many experts,however,now would only focus on its economic function, and either neglect or weaken its social influence. Therefore,this paper introduces the theoretical foundation of the farmer cooperative economy organization,and studies the nature of cooperative economics. Based on those typical cases,the future of cooperative organization and four supporting elements were put forward in this paper.

  6. Finite Element Quadrature of Regularized Discontinuous and Singular Level Set Functions in 3D Problems

    Directory of Open Access Journals (Sweden)

    Nicola Ponara

    2012-11-01

    Full Text Available Regularized Heaviside and Dirac delta function are used in several fields of computational physics and mechanics. Hence the issue of the quadrature of integrals of discontinuous and singular functions arises. In order to avoid ad-hoc quadrature procedures, regularization of the discontinuous and the singular fields is often carried out. In particular, weight functions of the signed distance with respect to the discontinuity interface are exploited. Tornberg and Engquist (Journal of Scientific Computing, 2003, 19: 527–552 proved that the use of compact support weight function is not suitable because it leads to errors that do not vanish for decreasing mesh size. They proposed the adoption of non-compact support weight functions. In the present contribution, the relationship between the Fourier transform of the weight functions and the accuracy of the regularization procedure is exploited. The proposed regularized approach was implemented in the eXtended Finite Element Method. As a three-dimensional example, we study a slender solid characterized by an inclined interface across which the displacement is discontinuous. The accuracy is evaluated for varying position of the discontinuity interfaces with respect to the underlying mesh. A procedure for the choice of the regularization parameters is proposed.

  7. Spherically symmetric volume elements as basis functions for image reconstructions in computed laminography.

    Science.gov (United States)

    Trampert, Patrick; Vogelgesang, Jonas; Schorr, Christian; Maisl, Michael; Bogachev, Sviatoslav; Marniok, Nico; Louis, Alfred; Dahmen, Tim; Slusallek, Philipp

    2017-03-21

    Laminography is a tomographic technique that allows three-dimensional imaging of flat and elongated objects that stretch beyond the extent of a reconstruction volume. Laminography images can be reconstructed using iterative algorithms based on the Kaczmarz method. This study aims to develop and demonstrate a new reconstruction algorithm that may provide superior image reconstruction quality for this challenged imaging application. The images are initially represented using the coefficients over basis functions, which are typically piecewise constant functions (voxels). By replacing voxels with spherically symmetric volume elements (blobs) based on the generalized Kaiser-Bessel window functions, the images are reconstructed using this new adapted version of the algebraic image reconstruction technique. Band-limiting properties of blob functions are beneficial particular in the case of noisy projections and with only a limited number of available projections. Study showed that using blob basis functions improved full-width-at-half-maximum resolution from 10.2±1.0 to 9.9±0.9 (p functions, especially if noisy data is expected.

  8. Functional evolution of the p53 regulatory network through its target response elements

    Science.gov (United States)

    Jegga, Anil G.; Inga, Alberto; Menendez, Daniel; Aronow, Bruce J.; Resnick, Michael A.

    2008-01-01

    Transcriptional network evolution is central to the development of complex biological systems. Networks can evolve through variation of master regulators and/or by changes in regulation of genes within networks. To gain insight into meaningful evolutionary differences in large networks, it is essential to address the functional consequences of sequence differences in response elements (REs) targeted by transcription factors. Using a combination of custom bioinformatics and multispecies alignment of promoter regions, we investigated the functional evolution of REs in terms of responsiveness to the sequence-specific transcription factor p53, a tumor suppressor and master regulator of stress responses. We identified REs orthologous to known p53 targets in human and rodent cells or alternatively REs related to the established p53 consensus. The orthologous REs were assigned p53 transactivation capabilities based on rules determined from model systems, and a functional heat map was developed to visually summarize conservation of sequence and relative level of responsiveness to p53 for 47 REs in 14 species. Individual REs exhibited marked differences in transactivation potentials and widespread evolutionary turnover. Functional differences were often not predicted from consensus sequence evaluations. Of the established human p53 REs analyzed, 91% had sequence conservation in at least one nonprimate species compared with 67.5% for functional conservation. Surprisingly, there was almost no conservation of functional REs for genes involved in DNA metabolism or repair between humans and rodents, suggesting important differences in p53 stress responses and cancer development. PMID:18187580

  9. TMJ development and growth require primary cilia function.

    Science.gov (United States)

    Kinumatsu, T; Shibukawa, Y; Yasuda, T; Nagayama, M; Yamada, S; Serra, R; Pacifici, M; Koyama, E

    2011-08-01

    Primary cilia regulate limb and axial skeletal formation and hedgehog signaling, but their roles in temporomandibular joint (TMJ) development are unknown. Thus, we created conditional mouse mutants deficient in ciliary transport protein Kif3a in cartilage. In post-natal wild-type mice, primary cilia were occasionally observed on the superior, inferior, or lateral side of condylar cells. Cilia were barely detectable in mutant chondrocytes but were evident in surrounding tissues, attesting to the specificity of chondrocyte Kif3a ablation. Mutant condyles from 3-month-old mice were narrow and flat along their antero-posterior and medio-lateral axes, were often fused with the articular disc, and displayed an irregular bony surface. The polymorphic layer in P15 mutants contained fewer Sox9-expressing chondroprogenitor cells because of reduced mitotic activity, and newly differentiated chondrocytes underwent precocious hypertrophic enlargement accompanied by early activation of Indian hedgehog (Ihh). Interestingly, there was excessive intramembranous ossification along the perichondrium, accompanied by local expression of the hedgehog receptor Patched-1 and up-regulation of Osterix and Collagen I. In summary, Kif3a and primary cilia are required for coordination of chondrocyte maturation, intramembranous bone formation, and chondrogenic condylar growth. Defects in these processes in Kif3a condylar cartilage are likely to reflect abnormal hedgehog signaling topography and dysfunction.

  10. Functions and requirements document for interim store solidified high-level and transuranic waste

    Energy Technology Data Exchange (ETDEWEB)

    Smith-Fewell, M.A., Westinghouse Hanford

    1996-05-17

    The functions, requirements, interfaces, and architectures contained within the Functions and Requirements (F{ampersand}R) Document are based on the information currently contained within the TWRS Functions and Requirements database. The database also documents the set of technically defensible functions and requirements associated with the solidified waste interim storage mission.The F{ampersand}R Document provides a snapshot in time of the technical baseline for the project. The F{ampersand}R document is the product of functional analysis, requirements allocation and architectural structure definition. The technical baseline described in this document is traceable to the TWRS function 4.2.4.1, Interim Store Solidified Waste, and its related requirements, architecture, and interfaces.

  11. Functional elements in the minimal promoter of the human proton-coupled folate transporter

    Energy Technology Data Exchange (ETDEWEB)

    Stark, Michal; Gonen, Nitzan [The Fred Wyszkowski Cancer Research Laboratory, Dept. of Biology, Technion-Israel Institute of Technology, Haifa 32000 (Israel); Assaraf, Yehuda G., E-mail: assaraf@tx.technion.ac.il [The Fred Wyszkowski Cancer Research Laboratory, Dept. of Biology, Technion-Israel Institute of Technology, Haifa 32000 (Israel)

    2009-10-09

    The proton-coupled folate transporter (PCFT) is the dominant intestinal folate transporter, however, its promoter has yet to be revealed. Hence, we here cloned a 3.1 kb fragment upstream to the first ATG of the human PCFT gene and generated sequential deletion constructs evaluated in luciferase reporter assay. This analysis mapped the minimal promoter to 157 bp upstream to the first ATG. Crucial GC-box sites were identified within the minimal promoter and in its close vicinity which substantially contribute to promoter activity, as their disruption resulted in 94% loss of luciferase activity. We also identified upstream enhancer elements including YY1 and AP1 which, although distantly located, prominently transactivated the minimal promoter, as their inactivation resulted in 50% decrease in reporter activity. This is the first functional identification of the minimal PCFT promoter harboring crucial GC-box elements that markedly contribute to its transcriptional activation via putative interaction with distal YY1 and AP1 enhancer elements.

  12. A density-functional-theory-based finite element model to study the mechanical properties of zigzag phosphorene nanotubes

    Science.gov (United States)

    Ansari, R.; Shahnazari, A.; Rouhi, S.

    2017-04-01

    In this paper, the density functional theory calculations are used to obtain the elastic properties of zigzag phosphorene nanotubes. Besides, based on the similarity between phosphorene nanotubes and a space-frame structure, a three-dimensional finite element model is proposed in which the atomic bonds are simulated by beam elements. The results of density functional theory are employed to compute the properties of the beam elements. Finally, using the proposed finite element model, the elastic modulus of the zigzag phosphorene nanotubes is computed. It is shown that phosphorene nanotubes with larger radii have larger Young's modulus. Comparing the results of finite element model with those of density functional theory, it is concluded that the proposed model can predict the elastic modulus of phosphorene nanotubes with a good accuracy.

  13. New induction relations for homogeneous functions in Jucys-Murphy elements

    CERN Document Server

    Feray, Valentin

    2010-01-01

    The problem of computing the class expansion of some symmetric function evaluated in Jucys-Murphy elements appears in different contexts, for instance in the computation of matrix integrals. Recently, M. Lassalle gave a unified algebraic method to obtain some induction relations on the coefficients in this kind of expansion. In this paper, we give a simple purely combinatorial proof of its result. Using the same type of argument, we also obtain new simpler formulas. We also prove an analogous formula in the double class algebra and use it to prove a conjecture of S. Matsumoto on the subleading term of orthogonal Weingarten function. Finally, we formulate a conjecture for a continuous interpolation between the two problems.

  14. Adsorption enhancement of elemental mercury onto sulphur-functionalized silica gel adsorbents.

    Science.gov (United States)

    Johari, Khairiraihanna; Saman, Norasikin; Mat, Hanapi

    2014-01-01

    In this study, elemental mercury (EM) adsorbents were synthesized using tetraethyl orthosilicate (TEOS) and 3-mercaptopropyl trimethoxysilane as silica precursors. The synthesized silica gel (SG)-TEOS was further functionalized through impregnation with elemental sulphur and carbon disulphide (CS2). The SG adsorbents were then characterized by using scanning electron microscope, Fourier transform infra-red spectrophotometer, nitrogen adsorption/desorption, and energy-dispersive X-ray diffractometer. The EM adsorption of the SG adsorbents was determined using fabricated fixed-bed adsorber. The EM adsorption results showed that the sulphur-functionalized SG adsorbents had a greater Hgo breakthrough adsorption capacity, confirming that the presence of sulphur in silica matrices can improve Hgo adsorption performance due to their high affinity towards mercury. The highest Hgo adsorption capacity was observed for SG-TEOS(CS2) (82.62 microg/g), which was approximately 2.9 times higher than SG-TEOS (28.47 microg/g). The rate of Hgo adsorption was observed higher for sulphur-impregnated adsorbents, and decreased with the increase in the bed temperatures.

  15. Creating the finite element models of car seats with passive head restraints to meet the requirements of passive safety

    Directory of Open Access Journals (Sweden)

    D. Yu. Solopov

    2014-01-01

    Full Text Available A problem solution to create the car chairs using modern software complexes (CAE based on the finite elements is capable to increase an efficiency of designing process significantly. Designing process is complicated by the fact that at present there are no available techniques focused on this sort of tasks.This article shows the features to create the final element models (FEM of the car chairs having three levels of complexity. It assesses a passive safety, which is ensured by the developed chair models with passive head restraints according to requirements of UNECE No 25 Regulations, and an accuracy of calculation results compared with those of full-scale experiments.This work is part of the developed technique, which allows effective development of the car chair designs both with passive, and with active head restraints, meeting the requirements of passive safety.By results of calculations and experiments it was established that at assessment by an UNECE No 25 technique the "rough" FEM (the 1st and 2nd levels can be considered as rational (in terms of effort to its creation and task solution and by the errors of results, and it is expedient to use them for preliminary and multiple calculations. Detailed models (the 3rd level provide the greatest accuracy (for accelerations the relative error makes 10%, for movements it is 11%, while in comparison with calculations, the relative error for a model of head restraint only decreases by 5% for accelerations and for 9% for movements.The materials presented in the article are used both in research activities and in training students at the Chair of Wheel Vehicles of the Scientific and Educational Complex "Special Mechanical Engineering" of Bauman Moscow State Technical University.

  16. An algorithm for computing an element of the Clarke generalized Jacobian of a difference of max-type functions

    CERN Document Server

    Horta, Ana

    2011-01-01

    We show that the algorithm for computing an element of the Clarke generalized Jacobian of a max-type function proposed by Zheng-da Huang and Guo-chun Ma can be extended to a much wider class of functions representable as a difference of max-type functions.

  17. Three-dimensional finite element analysis of Eustachian tube function under normal and pathological conditions.

    Science.gov (United States)

    Sheer, F J; Swarts, J D; Ghadiali, S N

    2012-06-01

    A primary etiological factor underlying chronic middle ear disease is an inability to open the collapsible Eustachian tube (ET). However, the structure-function relationships responsible for ET dysfunction in patient populations at risk for developing otitis media (OM) are not known. In this study, three-dimensional (3D) finite element (FE) modeling techniques were used to investigate how changes in biomechanical and anatomical properties influence opening phenomena in three populations: normal adults, young children and infants with cleft palate. Histological data was used to create anatomically accurate models and FE techniques were used to simulate tissue deformation and ET opening. Lumen dilation was quantified using a computational fluid dynamic (CFD) technique and a sensitivity analysis was performed to ascertain the relative importance of the different anatomical and tissue mechanical properties. Results for adults suggest that ET function is highly sensitive to tensor veli palatini muscle (TVPM) forces and to periluminal mucosal tissue (PMT) elasticity. Young children and cleft palate subjects exhibited reduced sensitivity to TVPM forces while changes in PMT stiffness continued to have a significant impact on ET function. These results suggest that reducing PMT stiffness might be an effective way to restore ET function in these populations. Varying TVPM force vector relationships via changes in hamulus location had no effect on ET opening in young children and cleft palate subjects but did alter force transmission to the ET lumen during conditions of elevated adhesion. These models have therefore provided important new insights into the biomechanical mechanisms responsible for ET dysfunction.

  18. 3D finite element model of the chinchilla ear for characterizing middle ear functions.

    Science.gov (United States)

    Wang, Xuelin; Gan, Rong Z

    2016-10-01

    Chinchilla is a commonly used animal model for research of sound transmission through the ear. Experimental measurements of the middle ear transfer function in chinchillas have shown that the middle ear cavity greatly affects the tympanic membrane (TM) and stapes footplate (FP) displacements. However, there is no finite element (FE) model of the chinchilla ear available in the literature to characterize the middle ear functions with the anatomical features of the chinchilla ear. This paper reports a recently completed 3D FE model of the chinchilla ear based on X-ray micro-computed tomography images of a chinchilla bulla. The model consisted of the ear canal, TM, middle ear ossicles and suspensory ligaments, and the middle ear cavity. Two boundary conditions of the middle ear cavity wall were simulated in the model as the rigid structure and the partially flexible surface, and the acoustic-mechanical coupled analysis was conducted with these two conditions to characterize the middle ear function. The model results were compared with experimental measurements reported in the literature including the TM and FP displacements and the middle ear input admittance in chinchilla ear. An application of this model was presented to identify the acoustic role of the middle ear septa-a unique feature of chinchilla middle ear cavity. This study provides the first 3D FE model of the chinchilla ear for characterizing the middle ear functions through the acoustic-mechanical coupled FE analysis.

  19. Australopithecus anamensis: a finite-element approach to studying the functional adaptations of extinct hominins.

    Science.gov (United States)

    Macho, Gabriele A; Shimizu, Daisuke; Jiang, Yong; Spears, Iain R

    2005-04-01

    Australopithecus anamensis is the stem species of all later hominins and exhibits the suite of characters traditionally associated with hominins, i.e., bipedal locomotion when on the ground, canine reduction, and thick-enameled teeth. The functional consequences of its thick enamel are, however, unclear. Without appropriate structural reinforcement, these thick-enameled teeth may be prone to failure. This article investigates the mechanical behavior of A. anamensis enamel and represents the first in a series that will attempt to determine the functional adaptations of hominin teeth. First, the microstructural arrangement of enamel prisms in A. anamensis teeth was reconstructed using recently developed software and was compared with that of extant hominoids. Second, a finite-element model of a block of enamel containing one cycle of prism deviation was reconstructed for Homo, Pan, Gorilla, and A. anamensis and the behavior of these tissues under compressive stress was determined. Despite similarities in enamel microstructure between A. anamensis and the African great apes, the structural arrangement of prismatic enamel in A. anamensis appears to be more effective in load dissipation under these compressive loads. The findings may imply that this hominin species was well adapted to puncture crushing and are in some respects contrary to expectations based on macromorphology of teeth. Taking together, information obtained from both finite-element analyses and dental macroanatomy leads us to suggest that A. anamensis was probably adapted for habitually consuming a hard-tough diet. However, additional tests are needed to understand the functional adaptations of A. anamensis teeth fully.

  20. Functional characterization of an alkaline exonuclease and single strand annealing protein from the SXT genetic element of Vibrio cholerae

    Directory of Open Access Journals (Sweden)

    Huang Jian-dong

    2011-04-01

    Full Text Available Abstract Background SXT is an integrating conjugative element (ICE originally isolated from Vibrio cholerae, the bacterial pathogen that causes cholera. It houses multiple antibiotic and heavy metal resistance genes on its ca. 100 kb circular double stranded DNA (dsDNA genome, and functions as an effective vehicle for the horizontal transfer of resistance genes within susceptible bacterial populations. Here, we characterize the activities of an alkaline exonuclease (S066, SXT-Exo and single strand annealing protein (S065, SXT-Bet encoded on the SXT genetic element, which share significant sequence homology with Exo and Bet from bacteriophage lambda, respectively. Results SXT-Exo has the ability to degrade both linear dsDNA and single stranded DNA (ssDNA molecules, but has no detectable endonuclease or nicking activities. Adopting a stable trimeric arrangement in solution, the exonuclease activities of SXT-Exo are optimal at pH 8.2 and essentially require Mn2+ or Mg2+ ions. Similar to lambda-Exo, SXT-Exo hydrolyzes dsDNA with 5'- to 3'-polarity in a highly processive manner, and digests DNA substrates with 5'-phosphorylated termini significantly more effectively than those lacking 5'-phosphate groups. Notably, the dsDNA exonuclease activities of both SXT-Exo and lambda-Exo are stimulated by the addition of lambda-Bet, SXT-Bet or a single strand DNA binding protein encoded on the SXT genetic element (S064, SXT-Ssb. When co-expressed in E. coli cells, SXT-Bet and SXT-Exo mediate homologous recombination between a PCR-generated dsDNA fragment and the chromosome, analogous to RecET and lambda-Bet/Exo. Conclusions The activities of the SXT-Exo protein are consistent with it having the ability to resect the ends of linearized dsDNA molecules, forming partially ssDNA substrates for the partnering SXT-Bet single strand annealing protein. As such, SXT-Exo and SXT-Bet may function together to repair or process SXT genetic elements within infected V

  1. Density functional calculations of large systems containing heavy elements by means of the regionalization algorithm

    Institute of Scientific and Technical Information of China (English)

    HU Xiangqian; LI Lemin

    2004-01-01

    The regionalized computational method is extended to the non-relativistic, scalar and 2-component relativistic density functional calculation of large systems containing transition series or heavy main-group metal elements. A large system is divided into several regions which can be considered as relatively independent quantum mechanical subsystems. Taking into account the Coulomb and exchange-correlation potentials as well as the Pauli repulsion exerted by the other subsystems, the Kohn-Sham equation related to subsystem K can be written as: (FK+FKP)CK =SKCKεK K=A,B,C,…,where FK,CK,SK,εK are the Fock matrix, the matrix of combination coefficients of orbitals, the overlap matrix of basis sets and the energy eigenvalue matrix, respectively. The matrix FKP reflects the Pauli repulsion from the other subsystems.FK may be non-relativistic, scalar or 2-component relativistic Fock matrix determined by the theoretical method related to the density functional calculations. The other matrices are mated with FK. Solving the Kohn-Sham equation for every subsystem and combining the results from the subsystem calculations, the electronic structural information of the whole system is derived. The density functional calculation of several molecules containing transition metal Ni or heavy main-group metal Tl or Bi is performed by the afore-mentioned regionalization algorithm. The obtained results for each molecule are compared with those from the density functional calculation of that molecule in its entirety in order to check the feasibility of the regionalization algorithm. It is found that with sufficiently large regional basis set in the subsystem calculation the accuracy of the results calculated by the regionalization algorithm is essentially the same as that from the calculation of the molecule in its entirety. With proper smaller regional basis sets the accuracy of the results calculated with the regionalization algorithm can still match the actual accuracy of the

  2. Effect of duct obstruction on structure, elemental composition, and function of rat submandibular glands

    Energy Technology Data Exchange (ETDEWEB)

    Sagstroem, S.S.; Sagulin, G.B.; Roomans, G.M. (Univ. of Uppsala (Sweden))

    1989-06-01

    Obstruction of salivary glands occurs in association with a number of pathological conditions. It has been suggested that the major changes found in the salivary glands of patients with cystic fibrosis are due to obstruction of the excretory duct by viscous mucus. In the present study, the effect of excretory duct obstruction on structure, elemental composition and function of rat submandibular gland was investigated. Obstruction was effected by infusion of a fast-hardening protein emulsion in the main excretory duct. After 1 week, and more pronounced after 2 weeks of obstruction the number of granular duct cells had decreased in the obstructed gland. X-ray microanalysis showed an increase in Mg, Ca and K, and a decrease in Na levels in the acinar cells, compared to normal glands. The contralateral glands apparently underwent compensatory hypertrophy and showed a similar pattern of changes in elemental composition. The composition of pilocarpine-induced submandibular saliva was neither in the obstructed nor in the contralateral gland significantly different from that in control glands. However, the flow rate was somewhat lower. Hence, increase in cellular Ca levels in submandibular gland acinar cells in cystic fibrosis could be secondary to duct obstruction, but the present study does not support the hypothesis that duct obstruction would result in changes in the composition of saliva.

  3. FARE-CAFE: a database of functional and regulatory elements of cancer-associated fusion events.

    Science.gov (United States)

    Korla, Praveen Kumar; Cheng, Jack; Huang, Chien-Hung; Tsai, Jeffrey J P; Liu, Yu-Hsuan; Kurubanjerdjit, Nilubon; Hsieh, Wen-Tsong; Chen, Huey-Yi; Ng, Ka-Lok

    2015-01-01

    Chromosomal translocation (CT) is of enormous clinical interest because this disorder is associated with various major solid tumors and leukemia. A tumor-specific fusion gene event may occur when a translocation joins two separate genes. Currently, various CT databases provide information about fusion genes and their genomic elements. However, no database of the roles of fusion genes, in terms of essential functional and regulatory elements in oncogenesis, is available. FARE-CAFE is a unique combination of CTs, fusion proteins, protein domains, domain-domain interactions, protein-protein interactions, transcription factors and microRNAs, with subsequent experimental information, which cannot be found in any other CT database. Genomic DNA information including, for example, manually collected exact locations of the first and second break points, sequences and karyotypes of fusion genes are included. FARE-CAFE will substantially facilitate the cancer biologist's mission of elucidating the pathogenesis of various types of cancer. This database will ultimately help to develop 'novel' therapeutic approaches. Database URL: http://ppi.bioinfo.asia.edu.tw/FARE-CAFE.

  4. Elemental and compound semiconductor surface chemistry: Intelligent interfacial design facilitated through novel functionalization and deposition strategies

    Science.gov (United States)

    Porter, Lon Alan, Jr.

    The fundamental understanding of silicon surface chemistry is an essential tool for silicon's continued dominance of the semiconductor industry in the years to come. By tapping into the vast library of organic functionalities, the synthesis of organic monolayers may be utilized to prepare interfaces, tailored to a myriad of applications ranging from silicon VLSI device optimization and MEMS to physiological implants and chemical sensors. Efforts in our lab to form stable organic monolayers on porous silicon through direct silicon-carbon linkages have resulted in several efficient functionalization methods. In the first chapter of this thesis a comprehensive review of these methods, and many others is presented. The following chapter and the appendix serve to demonstrate both potential applications and studies aimed at developing a fundamental understanding of the chemistry behind the organic functionalization of silicon surfaces. The remainder of this thesis attempts to demonstrate new methods of metal deposition onto both elemental and compound semiconductor surfaces. Currently, there is considerable interest in producing patterned metallic structures with reduced dimensions for use in technologies such as ULSI device fabrication, MEMS, and arrayed nanosensors, without sacrificing throughput or cost effectiveness. Research in our laboratory has focused on the preparation of precious metal thin films on semiconductor substrates via electroless deposition. Continuous metallic films form spontaneously under ambient conditions, in the absence of a fluoride source or an externally applied current. In order to apply this metallization method toward the development of useful technologies, patterning utilizing photolithography, microcontact printing, and scanning probe nanolithography has been demonstrated.

  5. Finite element analysis on longitudinal and radial functionally graded femoral prosthesis.

    Science.gov (United States)

    Oshkour, Azim Ataollahi; Abu Osman, N A; Davoodi, M M; Yau, Y H; Tarlochan, F; Wan Abas, W A B; Bayat, M

    2013-12-01

    This study focused on developing a 3D finite element model of functionally graded femoral prostheses to decrease stress shielding and to improve total hip replacement performance. The mechanical properties of the modeled functionally graded femoral prostheses were adjusted in the sagittal and transverse planes by changing the volume fraction gradient exponent. Prostheses with material changes in the sagittal and transverse planes were considered longitudinal and radial prostheses, respectively. The effects of cemented and noncemented implantation methods were also considered in this study. Strain energy and von Mises stresses were determined at the femoral proximal metaphysis and interfaces of the implanted femur components, respectively. Results demonstrated that the strain energy increased proportionally with increasing volume fraction gradient exponent, whereas the interface stresses decreased on the prostheses surfaces. A limited increase was also observed at the surfaces of the bone and cement. The periprosthetic femur with a noncemented prosthesis exhibited higher strain energy than with a cemented prosthesis. Radial prostheses implantation displayed more strain energy than longitudinal prostheses implantation in the femoral proximal part. Functionally graded materials also increased strain energy and exhibited promising potentials as substitutes of conventional materials to decrease stress shielding and to enhance total hip replacement lifespan.

  6. Three-Dimensional Finite Element Modeling of Thermomechanical Problems in Functionally Graded Hydroxyapatite/Titanium Plate

    Directory of Open Access Journals (Sweden)

    S. N. S. Jamaludin

    2014-01-01

    Full Text Available The composition of hydroxyapatite (HA as the ceramic phase and titanium (Ti as the metallic phase in HA/Ti functionally graded materials (FGMs shows an excellent combination of high biocompatibility and high mechanical properties in a structure. Because the gradation of these properties is one of the factors that affects the response of the functionally graded (FG plates, this paper is presented to show the domination of the grading parameter on the displacement and stress distribution of the plates. A three-dimensional (3D thermomechanical model of a 20-node brick quadratic element is used in the simulation of the thermoelastic behaviors of HA/Ti FG plates subjected to constant and functional thermal, mechanical, and thermomechanical loadings. The convergence properties of the present results are examined thoroughly in order to assess the accuracy of the theory applied and to compare them with the established research results. Instead of the grading parameter, this study reveals that the loading field distribution can be another factor that reflects the thermoelastic properties of the HA/Ti FG plates. The FG structure is found to be able to withstand the thermal stresses while preserving the high toughness properties and thus shows its ability to operate at high temperature.

  7. Numerical simulation of thermal fracture in functionally graded materials using element-free Galerkin method

    Indian Academy of Sciences (India)

    SAHIL GARG; MOHIT PANT

    2017-03-01

    In the present work, element-free Galerkin method (EFGM) has been extended and implemented to simulate thermal fracture in functionally graded materials. The thermo-elastic fracture problem is decoupled into two separate parts. Initially, the temperature distribution over the domain is obtained by solving the heat transfer problem. The temperature field so obtained is then employed as input for the mechanical problem to determine the displacement and stress fields. The crack surfaces are modelled as non-insulated boundaries; hence the temperature field remains undisturbed by the presence of crack. A modified conservative M-integral technique has been used in order to extract the stress intensity factors for the simulated problems. The present analysisshows that the results obtained by EFGM are in good agreement with those available in the literature.

  8. High-resolution interrogation of functional elements in the noncoding genome.

    Science.gov (United States)

    Sanjana, Neville E; Wright, Jason; Zheng, Kaijie; Shalem, Ophir; Fontanillas, Pierre; Joung, Julia; Cheng, Christine; Regev, Aviv; Zhang, Feng

    2016-09-30

    The noncoding genome affects gene regulation and disease, yet we lack tools for rapid identification and manipulation of noncoding elements. We developed a CRISPR screen using ~18,000 single guide RNAs targeting >700 kilobases surrounding the genes NF1, NF2, and CUL3, which are involved in BRAF inhibitor resistance in melanoma. We find that noncoding locations that modulate drug resistance also harbor predictive hallmarks of noncoding function. With a subset of regions at the CUL3 locus, we demonstrate that engineered mutations alter transcription factor occupancy and long-range and local epigenetic environments, implicating these sites in gene regulation and chemotherapeutic resistance. Through our expansion of the potential of pooled CRISPR screens, we provide tools for genomic discovery and for elucidating biologically relevant mechanisms of gene regulation. Copyright © 2016, American Association for the Advancement of Science.

  9. Chemical footprinting of structural and functional elements of dhfr oribeta during the CHOC 400 cell cycle.

    Science.gov (United States)

    Schroll, Alayne L; Heintz, Nicholas H

    2004-05-12

    Oribeta, an origin of replication 3' to Chinese hamster dihydrofolate reductase (dhfr) gene, contains several sequence elements that function as components of a chromosomal replicator. Here we have examined sensitivity to KMnO(4) in vitro and in living cells of three regions within dhfr oribeta which contribute to replicator function: the origin of bidirectional DNA replication (OBR) that serves as an initiation site for DNA synthesis, a stably bent DNA region that binds activator protein one (AP-1) and RIP60 in vitro, and an AT-rich region that contains a dA/dT(23) dinucleotide repeat that has properties of a DNA unwinding element. The in vitro patterns of KMnO(4) modification in linear plasmid differed from that in supercoiled plasmid most prominently in the dA/dT(23) repeat, with evidence of palindrome extrusion in supercoiled plasmid. Although palindrome extrusion was not detected in genomic DNA during the cell cycle, the pattern of genomic DNA modification within the dA/dT(23) repeat differed substantially from that of either linear or plasmid DNA in vitro. An AT-rich region that borders the dA/dT repeat was also highly sensitive to modification by KMnO(4) in cells. Within the bent DNA region, the patterns of chemical modification of both the AP-1 and RIP60 sites differed between plasmid and genomic DNA, and minor differences in the in vitro and cellular modification patterns also were observed for the OBR. Nonetheless, there was little evidence of cell cycle-specific modifications in any sequence examined. These studies suggest that sequences within dhfr oribeta adopt specific conformations in cells, with the most prominent changes in the AT-rich region associated with the dA/dT(23) repeat and DNA unwinding.

  10. Sequence requirements for viral RNA replication and VPg uridylylation directed by the internal cis-acting replication element (cre) of human rhinovirus type 14.

    Science.gov (United States)

    Yang, Yan; Rijnbrand, Rene; McKnight, Kevin L; Wimmer, Eckard; Paul, Aniko; Martin, Annette; Lemon, Stanley M

    2002-08-01

    Until recently, the cis-acting signals required for replication of picornaviral RNAs were believed to be restricted to the 5' and 3' noncoding regions of the genome. However, an RNA stem-loop in the VP1-coding sequence of human rhinovirus type 14 (HRV-14) is essential for viral minus-strand RNA synthesis (K. L. McKnight and S. M. Lemon, RNA 4:1569-1584, 1998). The nucleotide sequence of the apical loop of this internal cis-acting replication element (cre) was critical for RNA synthesis, while secondary RNA structure, but not primary sequence, was shown to be important within the duplex stem. Similar cres have since been identified in other picornaviral genomes. These RNA segments appear to serve as template for the uridylylation of the genome-linked protein, VPg, providing the VPg-pUpU primer required for viral RNA transcription (A. V. Paul et al., J. Virol. 74:10359-10370, 2000). Here, we show that the minimal functional HRV-14 cre resides within a 33-nucleotide (nt) RNA segment that is predicted to form a simple stem-loop with a 14-nt loop sequence. An extensive mutational analysis involving every possible base substitution at each position within the loop segment defined the sequence that is required within this loop for efficient replication of subgenomic HRV-14 replicon RNAs. These results indicate that three consecutive adenosine residues (nt 2367 to 2369) within the 5' half of this loop are critically important for cre function and suggest that a common RNNNAARNNNNNNR loop motif exists among the cre sequences of enteroviruses and rhinoviruses. We found a direct, positive correlation between the capacity of mutated cres to support RNA replication and their ability to function as template in an in vitro VPg uridylylation reaction, suggesting that these functions are intimately linked. These data thus define more precisely the sequence and structural requirements of the HRV-14 cre and provide additional support for a model in which the role of the cre in RNA

  11. Functions and requirements for Project W-236B, Initial Pretreatment Module: Revision 1

    Energy Technology Data Exchange (ETDEWEB)

    Swanson, L.M.

    1994-11-22

    Hanford Site tank waste supernatants will be pretreated to separate the low-level and high-level fractions. The low-level waste fraction, containing the bulk of the chemical constituents, must be processed into a vitrified waste product which will be disposed of onsite, in a safe, environmentally sound, and cost effective manner. The high-level waste fraction separated during supernatant pretreatment (primarily cesium) will be recombined with an additional high-level waste fraction generated from pretreatment of the tank waste sludges and solids. This combined high-level waste fraction will be immobilized as glass and disposed in a geological repository. The purpose of this document is to establish the functional requirements baseline for Project W-236B, Initial Pretreatment Module, by defining the level 5 and 6 functions and requirements for the project. A functional analysis approach has been used to break down the program functions and associated physical requirements that each function must meet. As the systems engineering process evolves, the design requirements document will replace this preliminary functions and requirements document. The design requirements document (DRD) will identify key decisions and associated uncertainties that impact the project. A revision of this document to a DRD is not expected to change the performance requirements or open issues. However, additional requirements and issues may be identified.

  12. Design of new generation femoral prostheses using functionally graded materials: a finite element analysis.

    Science.gov (United States)

    Oshkour, A A; Abu Osman, N A; Yau, Y H; Tarlochan, F; Abas, W A B Wan

    2013-01-01

    This study aimed to develop a three-dimensional finite element model of a functionally graded femoral prosthesis. The model consisted of a femoral prosthesis created from functionally graded materials (FGMs), cement, and femur. The hip prosthesis was composed of FGMs made of titanium alloy, chrome-cobalt, and hydroxyapatite at volume fraction gradient exponents of 0, 1, and 5, respectively. The stress was measured on the femoral prosthesis, cement, and femur. Stress on the neck of the femoral prosthesis was not sensitive to the properties of the constituent material. However, stress on the stem and cement decreased proportionally as the volume fraction gradient exponent of the FGM increased. Meanwhile, stress became uniform on the cement mantle layer. In addition, stress on the femur in the proximal part increased and a high surface area of the femoral part was involved in absorbing the stress. As such, the stress-shielding area decreased. The results obtained in this study are significant in the design and longevity of new prosthetic devices because FGMs offer the potential to achieve stress distribution that more closely resembles that of the natural bone in the femur.

  13. Function of the vegetative elements in contemporaneous interpretation of the architectonic work

    Directory of Open Access Journals (Sweden)

    Markéta Krejčí

    2008-01-01

    Full Text Available The creative process during which a vegetation element finds itself in the position of a fundamental part of material design of the building can be found in the field of modern architectural production. Along with other building materials, it has its own task to participate in the composition of architectural space. This represents an authentic approach of the current production where the do­mi­na­ting position of the vegetation material determines the unique character of the final work. In these exis­ting factors of practice, the vegetation material is treated, according to the three branches of purposefulness after Friedrich Schinkel, as fundamental part of structural composition of the architectural work. In considered cases, when the vegetation material is removed, the building loses its functional qualities or basic value of expression. Studied cases have proved the existing application of vegetation motives and their combinations the garden art has worked with for centuries. However, mo­dern architectural production adapts them to fields of application that are completely new. It develops these original sources of inspiration that lead modern architecture to totally inventive and new results. The above-mentioned factors are the subject of this paper the purpose of which is to provide basic determination of real applicability of the green mass in the materials applied in the building construction and give examples of current leading finished examples. On the one hand, ar­chi­tec­tu­ral objects restore, with the application of vegetation elements, natural form of greenery in urban interior on the individual level of human dimension. On the other hand, with their help, when siting a project in open space you can also prevent building of a totalitarian wall in the form of a building mass. Thus contextuality of the executed project is achieved in relation to its surroundings. In the presented architectural initiatives the vegetation

  14. Pattern-Driven Architectural Partitioning. Balancing Functional and Non-functional Requirements

    NARCIS (Netherlands)

    Harrison, Neil; Avgeriou, Paris

    2007-01-01

    One of the vexing challenges of software architecture is the problem of satisfying the functional specifications of the system to be created while at the same time meeting its non-functional needs. In this work we focus on the early stages of the software architecture process, when initial

  15. A static analysis of three-dimensional functionally graded beams through hierarchical one-dimensional finite elements

    Energy Technology Data Exchange (ETDEWEB)

    Giunta, G.; Belouettar, S. [Centre de Recherche Public Henri Tudor, 29, av. John F. Kennedy, L-1855, Luxembourg-Kirchberg, Luxembourg (Belgium)

    2015-03-10

    In this paper, the static response of three-dimensional beams made of functionally graded materials is investigated through a family of hierarchical one-dimensional finite elements. A wide variety of elements is proposed differing by the kinematic formulation and the number of nodes per elements along the beam axis. Elements’ stiffness matrix and load vector are derived in a unified nuclear form that does not depend upon the a priori expansion order over the cross-section nor the finite element approximation along the beam axis. Results are validated towards three-dimensional finite element models as well as equivalent Navier-type analytical solutions. The numerical investigations show that accurate and efficient solutions (when compared with full three-dimensional FEM solutions) can be obtained by the proposed family of hierarchical one-dimensional elements’ family.

  16. An Approach for Integrating the Prioritization of Functional and Nonfunctional Requirements

    Directory of Open Access Journals (Sweden)

    Mohammad Dabbagh

    2014-01-01

    Full Text Available Due to the budgetary deadlines and time to market constraints, it is essential to prioritize software requirements. The outcome of requirements prioritization is an ordering of requirements which need to be considered first during the software development process. To achieve a high quality software system, both functional and nonfunctional requirements must be taken into consideration during the prioritization process. Although several requirements prioritization methods have been proposed so far, no particular method or approach is presented to consider both functional and nonfunctional requirements during the prioritization stage. In this paper, we propose an approach which aims to integrate the process of prioritizing functional and nonfunctional requirements. The outcome of applying the proposed approach produces two separate prioritized lists of functional and non-functional requirements. The effectiveness of the proposed approach has been evaluated through an empirical experiment aimed at comparing the approach with the two state-of-the-art-based approaches, analytic hierarchy process (AHP and hybrid assessment method (HAM. Results show that our proposed approach outperforms AHP and HAM in terms of actual time-consumption while preserving the quality of the results obtained by our proposed approach at a high level of agreement in comparison with the results produced by the other two approaches.

  17. "Braingame Brian": Toward an Executive Function Training Program with Game Elements for Children with ADHD and Cognitive Control Problems.

    Science.gov (United States)

    Prins, Pier J M; Brink, Esther Ten; Dovis, Sebastiaan; Ponsioen, Albert; Geurts, Hilde M; de Vries, Marieke; van der Oord, Saskia

    2013-02-01

    In the area of childhood attention-deficit hyperactivity disorder, there is an urgent need for new, innovative, and child-focused treatments. A computerized executive functioning training with game elements aimed at enhancing self-control was developed. The first results are promising, and the next steps involve replication with larger samples, evaluating transfer of training effects to daily life, and enhancing motivation through more gaming elements.

  18. Distinct functional constraints partition sequence conservation in a cis-regulatory element.

    Directory of Open Access Journals (Sweden)

    Antoine Barrière

    2011-06-01

    Full Text Available Different functional constraints contribute to different evolutionary rates across genomes. To understand why some sequences evolve faster than others in a single cis-regulatory locus, we investigated function and evolutionary dynamics of the promoter of the Caenorhabditis elegans unc-47 gene. We found that this promoter consists of two distinct domains. The proximal promoter is conserved and is largely sufficient to direct appropriate spatial expression. The distal promoter displays little if any conservation between several closely related nematodes. Despite this divergence, sequences from all species confer robustness of expression, arguing that this function does not require substantial sequence conservation. We showed that even unrelated sequences have the ability to promote robust expression. A prominent feature shared by all of these robustness-promoting sequences is an AT-enriched nucleotide composition consistent with nucleosome depletion. Because general sequence composition can be maintained despite sequence turnover, our results explain how different functional constraints can lead to vastly disparate rates of sequence divergence within a promoter.

  19. Multiple functions of Osterix are required for bone growth and homeostasis in postnatal mice

    National Research Council Canada - National Science Library

    Xin Zhou; Zhaoping Zhang; Jian Q. Feng; Vladmir M. Dusevich; Krishna Sinha; Hua Zhang; Bryant G. Darnay; Benoit de Crombrugghe; Eric N. Olson

    2010-01-01

    The transcription factor Osterix (Osx) is required for osteoblast differentiation and bone formation during embryonic development, but it is not known whether Osx has an essential function in postnatal bone growth and in bone homeostasis...

  20. An 8-Node Shell Element for Nonlinear Analysis of Shells Using the Refined Combination of Membrane and Shear Interpolation Functions

    Directory of Open Access Journals (Sweden)

    Woo-Young Jung

    2013-01-01

    Full Text Available An improved 8-node shell finite element applicable for the geometrically linear and nonlinear analyses of plates and shells is presented. Based on previous first-order shear deformation theory, the finite element model is further improved by the combined use of assumed natural strains and different sets of collocation points for the interpolation of the different strain components. The influence of the shell element with various conditions such as locations, number of enhanced membranes, and shear interpolation is also identified. By using assumed natural strain method with proper interpolation functions, the present shell element generates neither membrane nor shear locking behavior even when full integration is used in the formulation. Furthermore, to characterize the efficiency of these modifications of the 8-node shell finite elements, numerical studies are carried out for the geometrically linear and non-linear analysis of plates and shells. In comparison to some other shell elements, numerical examples for the methodology indicate that the modified element described locking-free behavior and better performance. More specifically, the numerical examples of annular plate presented herein show good validity, efficiency, and accuracy to the developed nonlinear shell element.

  1. Workshop on Functional Requirements for the Modeling of Fate and Transport of Waterborne CBRN Materials

    Energy Technology Data Exchange (ETDEWEB)

    Giles, GE

    2005-02-03

    The purpose of this Workshop on ''Functional Requirements for the Modeling of Fate and Transport of Waterborne CBRN Materials'' was to solicit functional requirements for tools that help Incident Managers plan for and deal with the consequences of industrial or terrorist releases of materials into the nation's waterways and public water utilities. Twenty representatives attended and several made presentations. Several hours of discussions elicited a set of requirements. These requirements were summarized in a form for the attendees to vote on their highest priority requirements. These votes were used to determine the prioritized requirements that are reported in this paper and can be used to direct future developments.

  2. Subunit architecture of the Golgi Dsc E3 ligase required for sterol regulatory element-binding protein (SREBP) cleavage in fission yeast.

    Science.gov (United States)

    Lloyd, S Julie-Ann; Raychaudhuri, Sumana; Espenshade, Peter J

    2013-07-19

    The membrane-bound sterol regulatory element-binding protein (SREBP) transcription factors regulate lipogenesis in mammalian cells and are activated through sequential cleavage by the Golgi-localized Site-1 and Site-2 proteases. The mechanism of fission yeast SREBP cleavage is less well defined and, in contrast, requires the Golgi-localized Dsc E3 ligase complex. The Dsc E3 ligase consists of five integral membrane subunits, Dsc1 through Dsc5, and resembles membrane E3 ligases that function in endoplasmic reticulum-associated degradation. Using immunoprecipitation assays and blue native electrophoresis, we determined the subunit architecture for the complex of Dsc1 through Dsc5, showing that the Dsc proteins form subcomplexes and display defined connectivity. Dsc2 is a rhomboid pseudoprotease family member homologous to mammalian UBAC2 and a central component of the Dsc E3 ligase. We identified conservation in the architecture of the Dsc E3 ligase and the multisubunit E3 ligase gp78 in mammals. Specifically, Dsc1-Dsc2-Dsc5 forms a complex resembling gp78-UBAC2-UBXD8. Further characterization of Dsc2 revealed that its C-terminal UBA domain can bind to ubiquitin chains but that the Dsc2 UBA domain is not essential for yeast SREBP cleavage. Based on the ability of rhomboid superfamily members to bind transmembrane proteins, we speculate that Dsc2 functions in SREBP recognition and binding. Homologs of Dsc1 through Dsc4 are required for SREBP cleavage and virulence in the human opportunistic pathogen Aspergillus fumigatus. Thus, these studies advance our organizational understanding of multisubunit E3 ligases involved in endoplasmic reticulum-associated degradation and fungal pathogenesis.

  3. Combinatorial interactions are required for the efficient recruitment of pho repressive complex (PhoRC to polycomb response elements.

    Directory of Open Access Journals (Sweden)

    Tatyana G Kahn

    2014-07-01

    Full Text Available Polycomb Group (PcG proteins are epigenetic repressors that control metazoan development and cell differentiation. In Drosophila, PcG proteins form five distinct complexes targeted to genes by Polycomb Response Elements (PREs. Of all PcG complexes PhoRC is the only one that contains a sequence-specific DNA binding subunit (PHO or PHOL, which led to a model that places PhoRC at the base of the recruitment hierarchy. Here we demonstrate that in vivo PHO is preferred to PHOL as a subunit of PhoRC and that PHO and PHOL associate with PREs and a subset of transcriptionally active promoters. Although the binding to the promoter sites depends on the quality of recognition sequences, the binding to PREs does not. Instead, the efficient recruitment of PhoRC to PREs requires the SFMBT subunit and crosstalk with Polycomb Repressive Complex 1. We find that human YY1 protein, the ortholog of PHO, binds sites at active promoters in the human genome but does not bind most PcG target genes, presumably because the interactions involved in the targeting to Drosophila PREs are lost in the mammalian lineage. We conclude that the recruitment of PhoRC to PREs is based on combinatorial interactions and propose that such a recruitment strategy is important to attenuate the binding of PcG proteins when the target genes are transcriptionally active. Our findings allow the appropriate placement of PhoRC in the PcG recruitment hierarchy and provide a rationale to explain why YY1 is unlikely to serve as a general recruiter of mammalian Polycomb complexes despite its reported ability to participate in PcG repression in flies.

  4. Business Process Quality Computation: Computing Non-Functional Requirements to Improve Business Processes

    NARCIS (Netherlands)

    Heidari, F.

    2015-01-01

    Business process modelling is an important part of system design. When designing or redesigning a business process, stakeholders specify, negotiate, and agree on business requirements to be satisfied, including non-functional requirements that concern the quality of the business process. This thesis

  5. 78 FR 9802 - Payout Requirements for Type III Supporting Organizations That Are Not Functionally Integrated...

    Science.gov (United States)

    2013-02-12

    ... requirements to qualify as a Type III supporting organization that is operated in connection with one or more... Internal Revenue Service 26 CFR Part 1 RIN 1545-BG31; 1545-BL38 Payout Requirements for Type III Supporting Organizations That Are Not Functionally Integrated; Correction AGENCY: Internal Revenue Service (IRS),...

  6. Business Process Quality Computation: Computing Non-Functional Requirements to Improve Business Processes

    NARCIS (Netherlands)

    Heidari, F.

    2015-01-01

    Business process modelling is an important part of system design. When designing or redesigning a business process, stakeholders specify, negotiate, and agree on business requirements to be satisfied, including non-functional requirements that concern the quality of the business process. This thesis

  7. Comparison of various functionally graded femoral prostheses by finite element analysis.

    Science.gov (United States)

    Oshkour, Azim Ataollahi; Talebi, Hossein; Shirazi, Seyed Farid Seyed; Bayat, Mehdi; Yau, Yat Huang; Tarlochan, Faris; Abu Osman, Noor Azuan

    2014-01-01

    This study is focused on finite element analysis of a model comprising femur into which a femoral component of a total hip replacement was implanted. The considered prosthesis is fabricated from a functionally graded material (FGM) comprising a layer of a titanium alloy bonded to a layer of hydroxyapatite. The elastic modulus of the FGM was adjusted in the radial, longitudinal, and longitudinal-radial directions by altering the volume fraction gradient exponent. Four cases were studied, involving two different methods of anchoring the prosthesis to the spongy bone and two cases of applied loading. The results revealed that the FG prostheses provoked more SED to the bone. The FG prostheses carried less stress, while more stress was induced to the bone and cement. Meanwhile, less shear interface stress was stimulated to the prosthesis-bone interface in the noncemented FG prostheses. The cement-bone interface carried more stress compared to the prosthesis-cement interface. Stair climbing induced more harmful effects to the implanted femur components compared to the normal walking by causing more stress. Therefore, stress shielding, developed stresses, and interface stresses in the THR components could be adjusted through the controlling stiffness of the FG prosthesis by managing volume fraction gradient exponent.

  8. Thermal-mechanical study of functionally graded dental implants with the finite element method.

    Science.gov (United States)

    Wang, F; Lee, H P; Lu, C

    2007-01-01

    This article investigates the thermal-mechanical performance of hydroxyapatite/titanium (HA/Ti) functionally graded (FG) dental implants with the three-dimensional finite element method. The stresses induced by occlusal force for the present HA/Ti FG implant are calculated to compare with the corresponding stresses for the titanium dental implant. Thermal-mechanical effect of temperature variation due to daily oral activity is also studied. The HA/Ti FG dental implant performance is evaluated against the maximum von Mises stress, which is the general performance indicator, the first principal/tensile stress for mechanical failure of implant-bone-bond and the third principal/compressive stress for bone absorption. Simulation results indicate that under the influence of occlusal force only, the FG implants with different HA fraction along the implant length perform almost equally well, while the titanium implant sustains much higher von Mises stress. However, when thermal stress is also considered, the FG implant having HA fraction exponential index of m = 2 with temperature decrease of 20 degrees C yields the highest first principal and von Mises stresses among all the FG and titanium implants.

  9. Comparison of Various Functionally Graded Femoral Prostheses by Finite Element Analysis

    Directory of Open Access Journals (Sweden)

    Azim Ataollahi Oshkour

    2014-01-01

    Full Text Available This study is focused on finite element analysis of a model comprising femur into which a femoral component of a total hip replacement was implanted. The considered prosthesis is fabricated from a functionally graded material (FGM comprising a layer of a titanium alloy bonded to a layer of hydroxyapatite. The elastic modulus of the FGM was adjusted in the radial, longitudinal, and longitudinal-radial directions by altering the volume fraction gradient exponent. Four cases were studied, involving two different methods of anchoring the prosthesis to the spongy bone and two cases of applied loading. The results revealed that the FG prostheses provoked more SED to the bone. The FG prostheses carried less stress, while more stress was induced to the bone and cement. Meanwhile, less shear interface stress was stimulated to the prosthesis-bone interface in the noncemented FG prostheses. The cement-bone interface carried more stress compared to the prosthesis-cement interface. Stair climbing induced more harmful effects to the implanted femur components compared to the normal walking by causing more stress. Therefore, stress shielding, developed stresses, and interface stresses in the THR components could be adjusted through the controlling stiffness of the FG prosthesis by managing volume fraction gradient exponent.

  10. The NERV Methodology: Non-Functional Requirements Elicitation, Reasoning and Validation in Agile Processes

    Science.gov (United States)

    Domah, Darshan

    2013-01-01

    Agile software development has become very popular around the world in recent years, with methods such as Scrum and Extreme Programming (XP). Literature suggests that functionality is the primary focus in Agile processes while non-functional requirements (NFR) are either ignored or ill-defined. However, for software to be of good quality both…

  11. Non-functional requirements: size measurement and testing with COSMIC-FFP

    NARCIS (Netherlands)

    Kassab, M.; Ormandjieva, O.; Daneva, M.; Abran, A.; Abran, A.; Dumke, R.; Mas, A.

    2007-01-01

    The non-functional requirements (NFRs) of software systems are well known to add a degree of uncertainty to process of estimating the cost of any project. This paper contributes to the achievement of more precise project size measurement through incorporating NFRs into the functional size quantifica

  12. The NERV Methodology: Non-Functional Requirements Elicitation, Reasoning and Validation in Agile Processes

    Science.gov (United States)

    Domah, Darshan

    2013-01-01

    Agile software development has become very popular around the world in recent years, with methods such as Scrum and Extreme Programming (XP). Literature suggests that functionality is the primary focus in Agile processes while non-functional requirements (NFR) are either ignored or ill-defined. However, for software to be of good quality both…

  13. Justification of the technical requirements of a fully functional modular robot

    Directory of Open Access Journals (Sweden)

    Shlyakhov Nikita

    2017-01-01

    Full Text Available Modular robots are characterized by limited built-in resources necessary for communication, connection and movement of modules, when performing reconfiguration tasks at rigidly interconnected elements. In developing the technological fundamentals of designing modular robots with pairwise connection mechanisms, we analysed modern hardware and model algorithms typical of a fully functional robot, which provide independent locomotion, communication, navigation, decentralized power and control. A survey of actuators, batteries, sensors, communication means, suitable for modular robotics is presented.

  14. Functional genomics reveals relationships between the retrovirus-like Ty1 element and its host Saccharomyces cerevisiae.

    Science.gov (United States)

    Griffith, Jacqulyn L; Coleman, Laura E; Raymond, Adam S; Goodson, Summer G; Pittard, William S; Tsui, Circe; Devine, Scott E

    2003-07-01

    Retroviruses and their relatives, the long terminal repeat (LTR) retrotransposons, carry out complex life cycles within the cells of their hosts. We have exploited a collection of gene deletion mutants developed by the Saccharomyces Genome Deletion Project to perform a functional genomics screen for host factors that influence the retrovirus-like Ty1 element in yeast. A total of 101 genes that presumably influence many different aspects of the Ty1 retrotransposition cycle were identified from our analysis of 4483 homozygous diploid deletion strains. Of the 101 identified mutants, 46 had significantly altered levels of Ty1 cDNA, whereas the remaining 55 mutants had normal levels of Ty1 cDNA. Thus, approximately half of the mutants apparently affected the early stages of retrotransposition leading up to the assembly of virus-like particles and cDNA replication, whereas the remaining half affected steps that occur after cDNA replication. Although most of the mutants retained the ability to target Ty1 integration to tRNA genes, 2 mutants had reduced levels of tRNA gene targeting. Over 25% of the gene products identified in this study were conserved in other organisms, suggesting that this collection of host factors can serve as a starting point for identifying host factors that influence LTR retroelements and retroviruses in other organisms. Overall, our data indicate that Ty1 requires a large number of cellular host factors to complete its retrotransposition cycle efficiently.

  15. Conservation of Fold and Topology of Functional Elements in Thiamin Pyrophosphate Enzymes

    Science.gov (United States)

    Dominiak, P.; Ciszak, E. M.

    2005-01-01

    Thiamin pyrophosphate (TPP)-dependent enzymes are a highly divergent family of proteins binding both TPP and metal ions. They perform decarboxylation-hydroxyaldehydes. Prior -ketoacids and of a common - (O=)C-C(OH)- fragment of to knowledge of three-dimensional structures of these enzmes, the GDGY25-30NN sequence was used to identify these enzymes. Subsequently, a number of structural studies on those enzymes revealed multi-subunit organization and the features of the two duplicate cofactor binding sites. Analyzing the structures of 44 structurally known enzymes, we found that the common structure of these enzymes is reduced to 180-220 amino acid long fragments of two PP and two PYR domains that form the [PP:PYR]2 binding center of two cofactor molecules. The structures of PP and PYR are arranged in a similar fold-sheet with triplets of helices on both sides.Dconsisting of a six-stranded Residues surrounding the cofactors are not strictly conserved, but they provide the same interatomic contacts required for the catalytic functions that these enzymes perform while maintaining interactive structural integrity. These structural and functional amino acids are topological counterparts located in the same positions of the conserved fold of sets of PP and PYR domains. Additional parallels include short fragments of sequences that link these amino acids to the fold and function. This report on the structural commonalities amongst TPP dependent enzymes is thought to contribute new approaches to annotation that may assist in advancing the functional proteomics of TPP dependent enzymes, and trace their complexity within evolutionary context.

  16. Development of utility generic functional requirements for electronic work packages and computer-based procedures

    Energy Technology Data Exchange (ETDEWEB)

    Oxstrand, Johanna [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2017-06-01

    The Nuclear Electronic Work Packages - Enterprise Requirements (NEWPER) initiative is a step toward a vision of implementing an eWP framework that includes many types of eWPs. This will enable immediate paper-related cost savings in work management and provide a path to future labor efficiency gains through enhanced integration and process improvement in support of the Nuclear Promise (Nuclear Energy Institute 2016). The NEWPER initiative was organized by the Nuclear Information Technology Strategic Leadership (NITSL) group, which is an organization that brings together leaders from the nuclear utility industry and regulatory agencies to address issues involved with information technology used in nuclear-power utilities. NITSL strives to maintain awareness of industry information technology-related initiatives and events and communicates those events to its membership. NITSL and LWRS Program researchers have been coordinating activities, including joint organization of NEWPER-related meetings and report development. The main goal of the NEWPER initiative was to develop a set of utility generic functional requirements for eWP systems. This set of requirements will support each utility in their process of identifying plant-specific functional and non-functional requirements. The NEWPER initiative has 140 members where the largest group of members consists of 19 commercial U.S. nuclear utilities and eleven of the most prominent vendors of eWP solutions. Through the NEWPER initiative two sets of functional requirements were developed; functional requirements for electronic work packages and functional requirements for computer-based procedures. This paper will describe the development process as well as a summary of the requirements.

  17. A FINITE-ELEMENTS APPROACH TO THE STUDY OF FUNCTIONAL ARCHITECTURE IN SKELETAL-MUSCLE

    NARCIS (Netherlands)

    OTTEN, E; HULLIGER, M

    1994-01-01

    A mathematical model that simulates the mechanical processes inside a skeletal muscle under various conditions of muscle recruitment was formulated. The model is based on the finite-elements approach and simulates both contractile and passive elastic elements. Apart from the classic strategy of solv

  18. A FINITE-ELEMENTS APPROACH TO THE STUDY OF FUNCTIONAL ARCHITECTURE IN SKELETAL-MUSCLE

    NARCIS (Netherlands)

    OTTEN, E; HULLIGER, M

    1994-01-01

    A mathematical model that simulates the mechanical processes inside a skeletal muscle under various conditions of muscle recruitment was formulated. The model is based on the finite-elements approach and simulates both contractile and passive elastic elements. Apart from the classic strategy of solv

  19. ESL Based Cylindrical Shell Elements with Hierarchical Shape Functions for Laminated Composite Shells

    Directory of Open Access Journals (Sweden)

    Jae S. Ahn

    2015-01-01

    Full Text Available We introduce higher-order cylindrical shell element based on ESL (equivalent single-layer theory for the analysis of laminated composite shells. The proposed elements are formulated by the dimensional reduction technique from three-dimensional solid to two-dimensional cylindrical surface with plane stress assumption. It allows the first-order shear deformation and considers anisotropic materials due to fiber orientation. The element displacement approximation is established by the integrals of Legendre polynomials with hierarchical concept to ensure the C0-continuity at the interface between adjacent elements as well as C1-continuity at the interface between adjacent layers. For geometry mapping, cylindrical coordinate is adopted to implement the exact mapping of curved shell configuration with a constant curvature with respect to any direction in the plane. The verification and characteristics of the proposed element are investigated through the analyses of three cylindrical shell problems with different shapes, loadings, and boundary conditions.

  20. DDX3 RNA helicase is required for HIV-1 Tat function.

    Science.gov (United States)

    Yasuda-Inoue, Mariko; Kuroki, Misao; Ariumi, Yasuo

    2013-11-22

    Host RNA helicase has been involved in human immunodeficiency virus type 1 (HIV-1) replication, since HIV-1 does not encode an RNA helicase. Indeed, DDX1 and DDX3 DEAD-box RNA helicases are known to be required for efficient HIV-1 Rev-dependent RNA export. However, it remains unclear whether DDX RNA helicases modulate the HIV-1 Tat function. In this study, we demonstrate, for the first time, that DDX3 is required for the HIV-1 Tat function. Notably, DDX3 colocalized and interacted with HIV-1 Tat in cytoplasmic foci. Indeed, DDX3 localized in the cytoplasmic foci P-bodies or stress granules under stress condition after the treatment with arsenite. Importantly, only DDX3 enhanced the Tat function, while various distinct DEAD-box RNA helicases including DDX1, DDX3, DDX5, DDX17, DDX21, and DDX56, stimulated the HIV-1 Rev-dependent RNA export function, indicating a specific role of DDX3 in Tat function. Indeed, the ATPase-dependent RNA helicase activity of DDX3 seemed to be required for the Tat function as well as the colocalization with Tat. Furthermore, the combination of DDX3 with other distinct DDX RNA helicases cooperated to stimulate the Rev but not Tat function. Thus, DDX3 seems to interact with the HIV-1 Tat and facilitate the Tat function.

  1. Functions and requirements for Hanford single-shell tank leakage detection and monitoring

    Energy Technology Data Exchange (ETDEWEB)

    Cruse, J.M.; Ohl, P.C.

    1995-04-19

    This document provides the initial functions and requirements for leakage detection and monitoring applicable to past and potential future leakage from the Hanford Site`s 149 single-shell high-level waste tanks. This mission is a part of the overall mission of the Westinghouse Hanford Company Tank Waste Remediation System division to remediate the tank waste in a safe and acceptable manner. Systems engineering principles are being applied to this effort. This document reflects the an initial step in the systems engineering approach to decompose the mission into primary functions and requirements. The document is considered approximately 30% complete relative to the effort required to produce a final version that can be used to support demonstration and/or procurement of technologies. The functions and requirements in this document apply to detection and monitoring of below ground leaks from SST containment boundaries and the resulting soil contamination. Leakage detection and monitoring is invoked in the TWRS Program in three fourth level functions: (1) Store Waste, (2) Retrieve Waste, and (3) Disposition Excess Facilities (as identified in DOE/RL-92-60 Rev. 1, Tank Waste Remediation System Functions and Requirements).

  2. The leaching of major and trace elements from MSWI bottom ash as a function of pH and time

    NARCIS (Netherlands)

    Dijkstra, J.J.; Sloot, van der H.A.; Comans, R.N.J.

    2006-01-01

    In this paper, the leaching behaviour of major components (Al, Ca, SO4, Mg, Si, Fe, Na and DOC) and trace elements (Ni, Zn, Cd, Cu, Pb, Mo and Sb) from MSWI bottom ash is studied as a function of time over a wide range of pH, under pH-controlled conditions. Equilibrium geochemical modelling using th

  3. Wigner Function:from Ensemble Average of Density Operator to Its One Matrix Element in Entangled Pure States

    Institute of Scientific and Technical Information of China (English)

    FAN Hong-Yi

    2002-01-01

    We show that the Wigner function W = Tr(△ρ) (an ensemble average of the density operator ρ, △ is theWigner operator) can be expressed as a matrix element of ρ in the entangled pure states. In doing so, converting fromquantum master equations to time-evolution equation of the Wigner functions seems direct and concise. The entangledstates are defined in the enlarged Fock space with a fictitious freedom.

  4. THE DISPLACEMENT FUNCTION OF QUASI-CONFORMING ELEMENT AND ITS NODE ERROR

    Institute of Scientific and Technical Information of China (English)

    何东升; 唐立民

    2002-01-01

    Based on the strain formulation of the quasi-conforming finite element,displacement finctions are constructed which have definite physical meaning, and a conclusion can be obtained that the coefficients of the constant and the linear strain are uniquely determined, and the quasi-conforming finite element method is convergent to constant strain. There are different methods for constructing the rigid displacement items,and different methods correspond to different order node errors, and this is different fiom ordinary displacement method finite element.

  5. Quantitative estimation of activity and quality for collections of functional genetic elements.

    Science.gov (United States)

    Mutalik, Vivek K; Guimaraes, Joao C; Cambray, Guillaume; Mai, Quynh-Anh; Christoffersen, Marc Juul; Martin, Lance; Yu, Ayumi; Lam, Colin; Rodriguez, Cesar; Bennett, Gaymon; Keasling, Jay D; Endy, Drew; Arkin, Adam P

    2013-04-01

    The practice of engineering biology now depends on the ad hoc reuse of genetic elements whose precise activities vary across changing contexts. Methods are lacking for researchers to affordably coordinate the quantification and analysis of part performance across varied environments, as needed to identify, evaluate and improve problematic part types. We developed an easy-to-use analysis of variance (ANOVA) framework for quantifying the performance of genetic elements. For proof of concept, we assembled and analyzed combinations of prokaryotic transcription and translation initiation elements in Escherichia coli. We determined how estimation of part activity relates to the number of unique element combinations tested, and we show how to estimate expected ensemble-wide part activity from just one or two measurements. We propose a new statistic, biomolecular part 'quality', for tracking quantitative variation in part performance across changing contexts.

  6. Discovery of functional elements in 12 Drosophila genomes using evolutionary signatures

    DEFF Research Database (Denmark)

    Stark, Alexander; Lin, Michael F; Kheradpour, Pouya

    2007-01-01

    element shows characteristic patterns of change, or 'evolutionary signatures', dictated by its precise selective constraints. Such signatures enable recognition of new protein-coding genes and exons, spurious and incorrect gene annotations, and numerous unusual gene structures, including abundant stop...

  7. Thermal analysis of a functionally graded material subject to a thermal gradient using the boundary element method

    Science.gov (United States)

    Goldberg, Robert K.; Hopkins, Dale A.

    1994-01-01

    The boundary element method is utilized in this study to conduct thermal analysis of functionally graded composites, materials in which the internal microstructure or properties are explicitly tailored in order to obtain an optimal response, on the micromechanical (constituent) scale. A unique feature of the boundary element formulations used here is the use of circular shape functions to convert the two-dimensional integrations of the composite fibers to one dimensional integrations. Using the computer code BEST-CMS, the through the thickness temperature profiles are computed for a representative material with varying numbers of fibers and fiber spacing in the thickness direction. The computed temperature profiles are compared to those obtained using an alternate analytical theory which explicitly couples the heterogeneous microstructure to the global analysis. The boundary element results compared favorably to the analytical calculations, with discrepancies that are explainable based on the boundary element formulation. The results serve both to demonstrate the ability of the boundary element method to analyze these types of materials, and to verify the accuracy of the analytical theory.

  8. Scanning sequences after Gibbs sampling to find multiple occurrences of functional elements

    Directory of Open Access Journals (Sweden)

    Landsman David

    2006-09-01

    Full Text Available Abstract Background Many DNA regulatory elements occur as multiple instances within a target promoter. Gibbs sampling programs for finding DNA regulatory elements de novo can be prohibitively slow in locating all instances of such an element in a sequence set. Results We describe an improvement to the A-GLAM computer program, which predicts regulatory elements within DNA sequences with Gibbs sampling. The improvement adds an optional "scanning step" after Gibbs sampling. Gibbs sampling produces a position specific scoring matrix (PSSM. The new scanning step resembles an iterative PSI-BLAST search based on the PSSM. First, it assigns an "individual score" to each subsequence of appropriate length within the input sequences using the initial PSSM. Second, it computes an E-value from each individual score, to assess the agreement between the corresponding subsequence and the PSSM. Third, it permits subsequences with E-values falling below a threshold to contribute to the underlying PSSM, which is then updated using the Bayesian calculus. A-GLAM iterates its scanning step to convergence, at which point no new subsequences contribute to the PSSM. After convergence, A-GLAM reports predicted regulatory elements within each sequence in order of increasing E-values, so users have a statistical evaluation of the predicted elements in a convenient presentation. Thus, although the Gibbs sampling step in A-GLAM finds at most one regulatory element per input sequence, the scanning step can now rapidly locate further instances of the element in each sequence. Conclusion Datasets from experiments determining the binding sites of transcription factors were used to evaluate the improvement to A-GLAM. Typically, the datasets included several sequences containing multiple instances of a regulatory motif. The improvements to A-GLAM permitted it to predict the multiple instances.

  9. Improved Element Erosion Function for Concrete-Like Materials with the SPH Method

    Directory of Open Access Journals (Sweden)

    Jiří Kala

    2016-01-01

    Full Text Available The subject of the paper is a description of a simple test from the field of terminal ballistics and the handling of issues arising during its simulation using the numerical techniques of the finite element method. With regard to the possible excessive reshaping of the finite element mesh there is a danger that problems will arise such as the locking of elements or the appearance of negative volumes. It is often necessary to introduce numerical extensions so that the simulations can be carried out at all. When examining local damage to structures, such as the penetration of the outer shell or its perforation, it is almost essential to introduce the numerical erosion of elements into the simulations. However, when using numerical erosion, the dissipation of matter and energy from the computational model occurs in the mathematical background to the calculation. It is a phenomenon which can reveal itself in the final result when a discrepancy appears between the simulations and the experiments. This issue can be solved by transforming the eroded elements into smoothed particle hydrodynamics particles. These newly created particles can then assume the characteristics of the original elements and preserve the matter and energy of the numerical model.

  10. What are the key elements required for a successful and effective word of mouth tourism marketing campaign? – Case analysis

    OpenAIRE

    Piltonen, Anna

    2016-01-01

    The purpose of this thesis was to further study what are the key elements for successful and effective word of mouth marketing campaign in tourism. The objective was to identify the key elements by analysing a real life case provided for this thesis where a tourism board used word of mouth as part of their marketing campaign to increase awareness of the destination and drive tourism in the destination. The case was analysed with the support of secondary research conducted around the topics of...

  11. Refining Behavioral Specification for Satisfying Non-functional Requirements of Stakeholders

    OpenAIRE

    Kaiya, H; Kaijiri, k

    2002-01-01

    System specifications should be refined to meet stakeholders' requirements as much as possible, because the first specification does not satisfy all stakeholders in general. This paper presents a procedure to refine behavioral specification to satisfy stakeholders. Non-functional requirements are used for checking stakeholders' satisfaction. With this procedure, stakeholder-dissatisfaction can be reduced and new possibilities to satisfy or dissatisfy other stakeholders can be found, since a m...

  12. Formal Verification of Complex Systems based on SysML Functional Requirements

    Science.gov (United States)

    2014-12-23

    functional, and structural modeling, etc. Those with particu- lar focus on requirements engineering are the Unified Model- ing Language ( UML ) (OMG, 2007) to...requirements through design and implementation. UML is developed by the Object Management Group (OMG) in co- operation with the International Council of...Systems Engi- neering (INCOSE). UML is an Object-oriented modeling lan- guage that allows hierarchical organization of system compo- nent models, which in

  13. HIV-1 and Human PEG10 Frameshift Elements Are Functionally Distinct and Distinguished by Novel Small Molecule Modulators.

    Directory of Open Access Journals (Sweden)

    Tony S Cardno

    Full Text Available Frameshifting during translation of viral or in rare cases cellular mRNA results in the synthesis of proteins from two overlapping reading frames within the same mRNA. In HIV-1 the protease, reverse transcriptase, and integrase enzymes are in a second reading frame relative to the structural group-specific antigen (gag, and their synthesis is dependent upon frameshifting. This ensures that a strictly regulated ratio of structural proteins and enzymes, which is critical for HIV-1 replication and viral infectivity, is maintained during protein synthesis. The frameshift element in HIV-1 RNA is an attractive target for the development of a new class of anti HIV-1 drugs. However, a number of examples are now emerging of human genes using -1 frameshifting, such as PEG10 and CCR5. In this study we have compared the HIV-1 and PEG10 frameshift elements and shown they have distinct functional characteristics. Frameshifting occurs at several points within each element. Moreover, frameshift modulators that were isolated by high-throughput screening of a library of 114,000 lead-like compounds behaved differently with the PEG10 frameshift element. The most effective compounds affecting the HIV-1 element enhanced frameshifting by 2.5-fold at 10 μM in two different frameshift reporter assay systems. HIV-1 protease:gag protein ratio was affected by a similar amount in a specific assay of virally-infected cultured cell, but the modulation of frameshifting of the first-iteration compounds was not sufficient to show significant effects on viral infectivity. Importantly, two compounds did not affect frameshifting with the human PEG10 element, while one modestly inhibited rather than enhanced frameshifting at the human element. These studies indicate that frameshift elements have unique characteristics that may allow targeting of HIV-1 and of other viruses specifically for development of antiviral therapeutic molecules without effect on human genes like PEG10 that

  14. OPUS-Ca: a knowledge-based potential function requiring only Calpha positions.

    Science.gov (United States)

    Wu, Yinghao; Lu, Mingyang; Chen, Mingzhi; Li, Jialin; Ma, Jianpeng

    2007-07-01

    In this paper, we report a knowledge-based potential function, named the OPUS-Ca potential, that requires only Calpha positions as input. The contributions from other atomic positions were established from pseudo-positions artificially built from a Calpha trace for auxiliary purposes. The potential function is formed based on seven major representative molecular interactions in proteins: distance-dependent pairwise energy with orientational preference, hydrogen bonding energy, short-range energy, packing energy, tri-peptide packing energy, three-body energy, and solvation energy. From the testing of decoy recognition on a number of commonly used decoy sets, it is shown that the new potential function outperforms all known Calpha-based potentials and most other coarse-grained ones that require more information than Calpha positions. We hope that this potential function adds a new tool for protein structural modeling.

  15. Physical properties of the 6d-series elements from density functional theory: Close similarity to lighter transition metals

    Science.gov (United States)

    Gyanchandani, Jyoti; Sikka, S. K.

    2011-05-01

    We have calculated some of the physical properties of the recently discovered 6d elements by density functional theory. Comparison with those of the 5d metals shows that there is a close analogy for the crystal structures, for parabolic variation of equilibrium atomic volumes and bulk moduli, and an almost linearly increasing behavior of the pressure derivative of the bulk modulus across the 6d series. The Friedel model that is used to explain these trends for homologous series also holds for 6d metals. These elements also seem to be placed correctly in the Periodic Table.

  16. New Requirements of the Voltage/VAR Function for Smart Inverter in Distributed Generation Control

    Directory of Open Access Journals (Sweden)

    Yun-Su Kim

    2016-11-01

    Full Text Available International Electronical Committee (IEC 61850-90-7 is a part of the IEC 61850 series which specifies the advanced functions and object models for power converter based Distributed Energy Resources (DERs. One of its functions, the Voltage/VAR (V/V control function, is used to enhance the stability and the reliability of the voltage in the distribution system. The conventional V/V function acts mainly for flattening the voltage profile as for a basic grid support function. Currently, other objectives such as the minimization of line loss and the operational costs reduction are coming into the spotlight. In order to attain these objectives, the V/V function and hence the DER units shall actively respond to the change of distribution system conditions. In this paper, the modification of V/V function and new requirements are proposed. To derive new requirements of V/V function, loss minimization is applied to a particle swarm optimization (PSO algorithm where the condition of voltage constraint is considered not to deteriorate the voltage stability of the distribution system.

  17. Distribution of trace elements in selected pulverized coals as a function of particle size and density

    Science.gov (United States)

    Senior, C.L.; Zeng, T.; Che, J.; Ames, M.R.; Sarofim, A.F.; Olmez, I.; Huggins, Frank E.; Shah, N.; Huffman, G.P.; Kolker, A.; Mroczkowski, S.; Palmer, C.; Finkelman, R.

    2000-01-01

    Trace elements in coal have diverse modes of occurrence that will greatly influence their behavior in many coal utilization processes. Mode of occurrence is important in determining the partitioning during coal cleaning by conventional processes, the susceptibility to oxidation upon exposure to air, as well as the changes in physical properties upon heating. In this study, three complementary methods were used to determine the concentrations and chemical states of trace elements in pulverized samples of four US coals: Pittsburgh, Illinois No. 6, Elkhorn and Hazard, and Wyodak coals. Neutron Activation Analysis (NAA) was used to measure the absolute concentration of elements in the parent coals and in the size- and density-fractionated samples. Chemical leaching and X-ray absorption fine structure (XAFS) spectroscopy were used to provide information on the form of occurrence of an element in the parent coals. The composition differences between size-segregated coal samples of different density mainly reflect the large density difference between minerals, especially pyrite, and the organic portion of the coal. The heavy density fractions are therefore enriched in pyrite and the elements associated with pyrite, as also shown by the leaching and XAFS methods. Nearly all the As is associated with pyrite in the three bituminous coals studied. The sub-bituminous coal has a very low content of pyrite and arsenic; in this coal arsenic appears to be primarily organically associated. Selenium is mainly associated with pyrite in the bituminous coal samples. In two bituminous coal samples, zinc is mostly in the form of ZnS or associated with pyrite, whereas it appears to be associated with other minerals in the other two coals. Zinc is also the only trace element studied that is significantly more concentrated in the smaller (45 to 63 ??m) coal particles.

  18. Identification and characterization of functionally important elements in the multidrug resistance protein 1 COOH-terminal region.

    Science.gov (United States)

    Westlake, Christopher J; Payen, Lea; Gao, Mian; Cole, Susan P C; Deeley, Roger G

    2004-12-17

    The ATP binding cassette (ABC) transporter, multidrug resistance protein 1 (MRP1/ABCC1), transports a broad spectrum of conjugated and unconjugated compounds, including natural product chemotherapeutic agents. In this study, we have investigated the importance of the COOH-terminal region of MRP1 for transport activity and basolateral plasma membrane trafficking. The COOH-terminal regions of some ABCC proteins have been implicated in protein trafficking, but the function of this region of MRP1 has not been defined. In contrast to results obtained with other ABCC proteins, we found that the COOH-proximal 30 amino acids of MRP1 can be removed without affecting trafficking to basolateral membranes. However, the truncated protein is inactive. Furthermore, removal of as few as 4 COOH-terminal amino acids profoundly decreases transport activity. Although amino acid sequence conservation of the COOH-terminal regions of ABC proteins is low, secondary structure predictions indicate that they consist of a broadly conserved helix-sheet-sheet-helix-helix structure. Consistent with a conservation of secondary and tertiary structure, MRP1 hybrids containing the COOH-terminal regions of either the homologous MRP2 or the distantly related P-glycoprotein were fully active and trafficked normally. Using mutated proteins, we have identified structural elements containing five conserved hydrophobic amino acids that are required for activity. We show that these are important for binding and hydrolysis of ATP by nucleotide binding domain 2. Based on crystal structures of several ABC proteins, we suggest that the conserved amino acids may stabilize a helical bundle formed by the COOH-terminal three helices and may contribute to interactions between the COOH-terminal region and the protein's two nucleotide binding domains.

  19. The Automation of Government Publications: Functional Requirements and Selected Software Systems for Serials Controls.

    Science.gov (United States)

    Stephenson, Mary Sue; Purcell, Gary R.

    1985-01-01

    Describes computer-based software and network systems for application to serials and government publications. General and specific functional requirements (hardware, software, file structure) are discussed, and descriptive information about commercially available serials control systems and a list of distributors are provided. (CLB)

  20. Does work-related training reduce the discrepancy between function requirements and competencies?

    NARCIS (Netherlands)

    E.R. Kappe; G.E. Bijwaard (Govert)

    2005-01-01

    textabstractThe issue of lifelong learning is high on the political agenda. However, despite this political interest and the large economic literature on human capital, the impact of work-related training on the discrepancy between function requirements and the skills of the employee has been ignore

  1. Guidance on the scientific requirements for health claims related to gut and immune function

    DEFF Research Database (Denmark)

    Tetens, Inge

    2011-01-01

    The European Food Safety Authority (EFSA) asked the Panel on Dietetic Products Nutrition and Allergies (NDA) to draft guidance on scientific requirements for health claims related to gut and immune function. This guidance has been drawn from scientific opinions of the NDA Panel on such health...

  2. Understanding functional reuse of ERP requirements in the telecommunication sector: an empirical study

    NARCIS (Netherlands)

    Daneva, Maya

    2014-01-01

    This paper is an empirical study on the application of Function Points (FP) and a FP-based reuse measurement model in Enterprise Resource Planning (ERP) projects in three organizations in the telecommunication sector. The findings of the study are used to compare the requirements reuse for one parti

  3. 77 FR 76426 - Payout Requirements for Type III Supporting Organizations That Are Not Functionally Integrated

    Science.gov (United States)

    2012-12-28

    ... organizations that are not functionally integrated. The withdrawal affects Type III supporting organizations... ``Type III Supporting Organizations''). Those regulations reflect changes to the law made by the Pension... Revenue Service 26 CFR Part 1 [REG 155929-06] RIN 1545-BL44 Payout Requirements for Type III...

  4. Peculiarities of cognitive functions in urban children with mental retardation in relation to the chemical elements content in a hair

    Directory of Open Access Journals (Sweden)

    Yevstafyeva E.V.

    2012-06-01

    Full Text Available

    In 30 children in the age of 12,8±0,3 with mental retardation and 30 healthy children of the same age an element balance of organism and state of cognitive functions were related. The content of elements (Ca, Fe, Mn, Mo, Ni, Sr, Pb in the hair was determined by a method of X-ray fuorescent spectroscopy. The content of Ca, Ni and Mn in 55 % of children and the defciency of Fe in 21 % of children with mental retardation were established. The defciency of Ca, Fe and Mn of healthy children was displayed. The value of Sr and Pb in organism in children of booth group was normal. The content of Mo in hair in 40 % of children with mental retardation and in 30 % of children of a check-group were established. The relationship between the content of chemical elements in organisms and state of cognitive functions was analyzed by non-parametric analysis by Spearmen. The excess of Ni in organism of children with mental retardation and defciency of Fe in organism of children in booth groups negatively infuenced the characteristics of cognitive functions (0,34functions of Mn was not reveled.

  5. Energy and energy gradient matrix elements with N-particle explicitly correlated complex Gaussian basis functions with L=1.

    Science.gov (United States)

    Bubin, Sergiy; Adamowicz, Ludwik

    2008-03-21

    In this work we consider explicitly correlated complex Gaussian basis functions for expanding the wave function of an N-particle system with the L=1 total orbital angular momentum. We derive analytical expressions for various matrix elements with these basis functions including the overlap, kinetic energy, and potential energy (Coulomb interaction) matrix elements, as well as matrix elements of other quantities. The derivatives of the overlap, kinetic, and potential energy integrals with respect to the Gaussian exponential parameters are also derived and used to calculate the energy gradient. All the derivations are performed using the formalism of the matrix differential calculus that facilitates a way of expressing the integrals in an elegant matrix form, which is convenient for the theoretical analysis and the computer implementation. The new method is tested in calculations of two systems: the lowest P state of the beryllium atom and the bound P state of the positronium molecule (with the negative parity). Both calculations yielded new, lowest-to-date, variational upper bounds, while the number of basis functions used was significantly smaller than in previous studies. It was possible to accomplish this due to the use of the analytic energy gradient in the minimization of the variational energy.

  6. Genetic organisation, mobility and predicted functions of genes on integrated, mobile genetic elements in sequenced strains of Clostridium difficile.

    Directory of Open Access Journals (Sweden)

    Michael S M Brouwer

    Full Text Available BACKGROUND: Clostridium difficile is the leading cause of hospital-associated diarrhoea in the US and Europe. Recently the incidence of C. difficile-associated disease has risen dramatically and concomitantly with the emergence of 'hypervirulent' strains associated with more severe disease and increased mortality. C. difficile contains numerous mobile genetic elements, resulting in the potential for a highly plastic genome. In the first sequenced strain, 630, there is one proven conjugative transposon (CTn, Tn5397, and six putative CTns (CTn1, CTn2 and CTn4-7, of which, CTn4 and CTn5 were capable of excision. In the second sequenced strain, R20291, two further CTns were described. RESULTS: CTn1, CTn2 CTn4, CTn5 and CTn7 were shown to excise from the genome of strain 630 and transfer to strain CD37. A putative CTn from R20291, misleadingly termed a phage island previously, was shown to excise and to contain three putative mobilisable transposons, one of which was capable of excision. In silico probing of C. difficile genome sequences with recombinase gene fragments identified new putative conjugative and mobilisable transposons related to the elements in strains 630 and R20291. CTn5-like elements were described occupying different insertion sites in different strains, CTn1-like elements that have lost the ability to excise in some ribotype 027 strains were described and one strain was shown to contain CTn5-like and CTn7-like elements arranged in tandem. Additionally, using bioinformatics, we updated previous gene annotations and predicted novel functions for the accessory gene products on these new elements. CONCLUSIONS: The genomes of the C. difficile strains examined contain highly related CTns suggesting recent horizontal gene transfer. Several elements were capable of excision and conjugative transfer. The presence of antibiotic resistance genes and genes predicted to promote adaptation to the intestinal environment suggests that CTns play a

  7. Generic functional requirements for a NASA general-purpose data base management system

    Science.gov (United States)

    Lohman, G. M.

    1981-01-01

    Generic functional requirements for a general-purpose, multi-mission data base management system (DBMS) for application to remotely sensed scientific data bases are detailed. The motivation for utilizing DBMS technology in this environment is explained. The major requirements include: (1) a DBMS for scientific observational data; (2) a multi-mission capability; (3) user-friendly; (4) extensive and integrated information about data; (5) robust languages for defining data structures and formats; (6) scientific data types and structures; (7) flexible physical access mechanisms; (8) ways of representing spatial relationships; (9) a high level nonprocedural interactive query and data manipulation language; (10) data base maintenance utilities; (11) high rate input/output and large data volume storage; and adaptability to a distributed data base and/or data base machine configuration. Detailed functions are specified in a top-down hierarchic fashion. Implementation, performance, and support requirements are also given.

  8. A recent assessment of the elemental composition of New Zealand pastures in relation to meeting the dietary requirements of grazing livestock.

    Science.gov (United States)

    Knowles, S O; Grace, N D

    2014-01-01

    An understanding of the benefits and limitations of pasture feeding underpins sustainable grazing systems that produce milk and meat from ruminant livestock. We evaluated the mineral composition of 1,106 pasture samples collected independently from locations across New Zealand from 2001 to 2006. About half were submitted during 2002 and 2003, and 87% came from the North Island. Most herbage was from ryegrass and clover-dominated swards. The concentrations of Ca, Co, Cu, Fe, K, Mg, Mn, Mo, Na, P, S, Se, or Zn were measured by nitric acid digestion followed by inductively coupled plasma optical emission spectroscopy or atomic absorption spectroscopy. Median concentrations for the macro elements were Ca 5.5, K 33, Mg 2.2, Na 2.0, P 4.0, and S 3.6 g/kg DM and for the trace elements were Co 0.10, Cu 8.4, Fe 131, Mn 74, Mo 0.66, Se 0.050, and Zn 43 mg/kg DM. Frequency histograms of concentrations revealed distributions ranging from near-normal to bottom-heavy skew with a long tail of high values. The minerals required for good plant growth were found at adequate concentrations in the majority of pastures. The exception was P; only 74% of pastures contained the recommended 3.5 mg P/kg DM. Results of the pasture survey were compared to the dietary intake requirements of cattle and sheep. For 7 elements, >95% of the pastures contained sufficiently high concentrations to meet the needs of unsupplemented animals. Exceptions were the Se dietary requirement, which was met by only 76% of pastures, the Co requirement of sheep met by only 54% of pastures, and the Cu, Na, and P requirements of cattle met by 25, 78, and 87% of pastures, respectively. Pasture analysis is an essential tool for identifying dietary insufficiency as well as unfavorable mineral balances where interactions could induce a deficiency, such as Cu × Mo and Mg × K. Monitoring of animals' nutritional status is also required to manage complex metabolic disorders related to peripartum flux of Ca and Mg. This

  9. Discontinuous Galerkin finite element method for solving population density functions of cortical pyramidal and thalamic neuronal populations.

    Science.gov (United States)

    Huang, Chih-Hsu; Lin, Chou-Ching K; Ju, Ming-Shaung

    2015-02-01

    Compared with the Monte Carlo method, the population density method is efficient for modeling collective dynamics of neuronal populations in human brain. In this method, a population density function describes the probabilistic distribution of states of all neurons in the population and it is governed by a hyperbolic partial differential equation. In the past, the problem was mainly solved by using the finite difference method. In a previous study, a continuous Galerkin finite element method was found better than the finite difference method for solving the hyperbolic partial differential equation; however, the population density function often has discontinuity and both methods suffer from a numerical stability problem. The goal of this study is to improve the numerical stability of the solution using discontinuous Galerkin finite element method. To test the performance of the new approach, interaction of a population of cortical pyramidal neurons and a population of thalamic neurons was simulated. The numerical results showed good agreement between results of discontinuous Galerkin finite element and Monte Carlo methods. The convergence and accuracy of the solutions are excellent. The numerical stability problem could be resolved using the discontinuous Galerkin finite element method which has total-variation-diminishing property. The efficient approach will be employed to simulate the electroencephalogram or dynamics of thalamocortical network which involves three populations, namely, thalamic reticular neurons, thalamocortical neurons and cortical pyramidal neurons.

  10. Cis-regulatory elements in the primate brain: from functional specialization to neurodegeneration

    NARCIS (Netherlands)

    Vermunt, Marit W.

    2017-01-01

    Over the last decade, the noncoding part of the genome has been shown to harbour thousands of cis-regulatory elements, such as enhancers, that activate well-defined gene expression programs. Here, we charted active enhancers in a multiplicity of human brain regions to understand the role of

  11. Organizational Culture: Elements in its Portraiture and Some Implications for Organization Functioning.

    Science.gov (United States)

    Marshall, Judi

    1982-01-01

    Charts significant elements of organizational culture centering on four "dimensions of difference": a company's stock of managers, the conceptual job model managers used, significant influences on job performance, and managers' perceptions of freedom. Portrays two organizations in these terms, exploring factors that appear to have influenced their…

  12. Implementation of a finite-element approximation of the Mumford-Shah functional

    DEFF Research Database (Denmark)

    Bourdin, Blaise; Chambolle, Antonin

    1999-01-01

    We present and detail a method for the numerical solving of the Mumford-Shah problem, based on a finite element method and on adaptive meshes. We start with a formulation introduced by A. Chambolle and G. Dal Maso, detail its numerical implementation and then propose a variant which is proved to ...

  13. Are protected areas required to maintain functional diversity in human-modified landscapes?

    Directory of Open Access Journals (Sweden)

    H Eden W Cottee-Jones

    Full Text Available The conversion of forest to agriculture across the world's tropics, and the limited space for protected areas, has increased the need to identify effective conservation strategies in human-modified landscapes. Isolated trees are believed to conserve elements of ecological structure, providing micro-sites for conservation in matrix landscapes, and facilitating seed dispersal and forest restoration. Here we investigate the role of isolated Ficus trees, which are of critical importance to tropical forest ecosystems, in conserving frugivore composition and function in a human-modified landscape in Assam, India. We surveyed the frugivorous birds feeding at 122 isolated Ficus trees, 33 fruit trees, and 31 other large trees across a range of 32 km from the nearest intact forest. We found that Ficus trees attracted richer and more abundant assemblages of frugivores than the other tree categories. However, incidence function estimates revealed that forest specialist species decreased dramatically within the first kilometre of the forest edge. Despite this, species richness and functional diversity remained consistent across the human-modified landscape, as habitat generalists replaced forest-dependent frugivores, and accounted for most of the ecological function found in Ficus trees near the forest edge. We recommend that isolated Ficus trees are awarded greater conservation status, and suggest that their conservation can support ecologically functional networks of frugivorous bird communities.

  14. A functional selection of viral genetic elements in cultured cells to identify hepatitis C virus RNA translation inhibitors †

    OpenAIRE

    Jaffrelo, Loic; Chabas, Sandrine; Reigadas, Sandrine; Pflieger, Aude; Wychowski, Czeslaw; Rumi, Julie; Ventura, Michel; Toulmé, Jean-Jacques; Staedel, Cathy

    2008-01-01

    We developed a functional selection system based on randomized genetic elements (GE) to identify potential regulators of hepatitis C virus (HCV) RNA translation, a process initiated by an internal ribosomal entry site (IRES). A retroviral HCV GE library was introduced into HepG2 cells, stably expressing the Herpes simplex virus thymidine kinase (HSV-TK) under the control of the HCV IRES. Cells that expressed transduced GEs inhibiting HSV-TK were selected via their resistance to ganciclovir. S...

  15. 13 CFR 120.425 - What are the minimum elements that SBA will require before consenting to a securitization?

    Science.gov (United States)

    2010-01-01

    ... Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Lenders Participating Lender Financings § 120.425... any securitization pools. Each nondepository institution must submit annual audited financial statements demonstrating that it has met SBA's capital requirement. (b) Subordinated Tranche—A securitizer...

  16. Cement Dust Exposure and Perturbations in Some Elements and Lung and Liver Functions of Cement Factory Workers

    Science.gov (United States)

    Richard, Egbe Edmund; Augusta Chinyere, Nsonwu-Anyanwu; Jeremaiah, Offor Sunday; Opara, Usoro Chinyere Adanna; Henrieta, Etukudo Maise; Ifunanya, Egbe Deborah

    2016-01-01

    Background. Cement dust inhalation is associated with deleterious health effects. The impact of cement dust exposure on the peak expiratory flow rate (PEFR), liver function, and some serum elements in workers and residents near cement factory were assessed. Methods. Two hundred and ten subjects (50 workers, 60 residents, and 100 controls) aged 18–60 years were studied. PEFR, liver function {aspartate and alanine transaminases (AST and ALT) and total and conjugated bilirubin (TB and CB)}, and serum elements {lead (Pb), copper (Cu), manganese (Mn), iron (Fe), cadmium (Cd), selenium (Se), chromium (Cr), zinc (Zn), and arsenic (As)} were determined using peak flow meter, colorimetry, and atomic absorption spectrometry, respectively. Data were analysed using ANOVA and correlation at p = 0.05. Results. The ALT, TB, CB, Pb, As, Cd, Cr, Se, Mn, and Cu were significantly higher and PEFR, Fe, and Zn lower in workers and residents compared to controls (p < 0.05). Higher levels of ALT, AST, and Fe and lower levels of Pb, Cd, Cr, Se, Mn, and Cu were seen in cement workers compared to residents (p < 0.05). Negative correlation was observed between duration of exposure and PEFR (r = −0.416, p = 0.016) in cement workers. Conclusions. Cement dust inhalation may be associated with alterations in serum elements levels and lung and liver functions while long term exposure lowers peak expiratory flow rate. PMID:26981118

  17. Cement Dust Exposure and Perturbations in Some Elements and Lung and Liver Functions of Cement Factory Workers

    Directory of Open Access Journals (Sweden)

    Egbe Edmund Richard

    2016-01-01

    Full Text Available Background. Cement dust inhalation is associated with deleterious health effects. The impact of cement dust exposure on the peak expiratory flow rate (PEFR, liver function, and some serum elements in workers and residents near cement factory were assessed. Methods. Two hundred and ten subjects (50 workers, 60 residents, and 100 controls aged 18–60 years were studied. PEFR, liver function {aspartate and alanine transaminases (AST and ALT and total and conjugated bilirubin (TB and CB}, and serum elements {lead (Pb, copper (Cu, manganese (Mn, iron (Fe, cadmium (Cd, selenium (Se, chromium (Cr, zinc (Zn, and arsenic (As} were determined using peak flow meter, colorimetry, and atomic absorption spectrometry, respectively. Data were analysed using ANOVA and correlation at p=0.05. Results. The ALT, TB, CB, Pb, As, Cd, Cr, Se, Mn, and Cu were significantly higher and PEFR, Fe, and Zn lower in workers and residents compared to controls (p<0.05. Higher levels of ALT, AST, and Fe and lower levels of Pb, Cd, Cr, Se, Mn, and Cu were seen in cement workers compared to residents (p<0.05. Negative correlation was observed between duration of exposure and PEFR (r=-0.416, p=0.016 in cement workers. Conclusions. Cement dust inhalation may be associated with alterations in serum elements levels and lung and liver functions while long term exposure lowers peak expiratory flow rate.

  18. The NIMA Kinase Is Required To Execute Stage-Specific Mitotic Functions after Initiation of Mitosis

    Science.gov (United States)

    Govindaraghavan, Meera; Lad, Alisha A.

    2014-01-01

    The G2-M transition in Aspergillus nidulans requires the NIMA kinase, the founding member of the Nek kinase family. Inactivation of NIMA results in a late G2 arrest, while overexpression of NIMA is sufficient to promote mitotic events independently of cell cycle phase. Endogenously tagged NIMA-GFP has dynamic mitotic localizations appearing first at the spindle pole body and then at nuclear pore complexes before transitioning to within nuclei and the mitotic spindle and back at the spindle pole bodies at mitotic exit, suggesting that it functions sequentially at these locations. Since NIMA is indispensable for mitotic entry, it has been difficult to determine the requirement of NIMA for subaspects of mitosis. We show here that when NIMA is partially inactivated, although mitosis can be initiated, a proportion of cells fail to successfully generate two daughter nuclei. We further define the mitotic defects to show that normal NIMA function is required for the formation of a bipolar spindle, nuclear pore complex disassembly, completion of chromatin segregation, and the normal structural rearrangements of the nuclear envelope required to generate two nuclei from one. In the remaining population of cells that enter mitosis with inadequate NIMA, two daughter nuclei are generated in a manner dependent on the spindle assembly checkpoint, indicating highly penetrant defects in mitotic progression without sufficient NIMA activity. This study shows that NIMA is required not only for mitotic entry but also sequentially for successful completion of stage-specific mitotic events. PMID:24186954

  19. Kinetic-energy matrix elements for atomic Hylleraas-CI wave functions.

    Science.gov (United States)

    Harris, Frank E

    2016-05-28

    Hylleraas-CI is a superposition-of-configurations method in which each configuration is constructed from a Slater-type orbital (STO) product to which is appended (linearly) at most one interelectron distance rij. Computations of the kinetic energy for atoms by this method have been difficult due to the lack of formulas expressing these matrix elements for general angular momentum in terms of overlap and potential-energy integrals. It is shown here that a strategic application of angular-momentum theory, including the use of vector spherical harmonics, enables the reduction of all atomic kinetic-energy integrals to overlap and potential-energy matrix elements. The new formulas are validated by showing that they yield correct results for a large number of integrals published by other investigators.

  20. Thyroid functions and trace elements in pediatric patients with exogenous obesity.

    Science.gov (United States)

    Cayir, Atilla; Doneray, Hakan; Kurt, Nezahat; Orbak, Zerrin; Kaya, Avni; Turan, Mehmet Ibrahim; Yildirim, Abdulkadir

    2014-02-01

    Obesity is a multifactorial disease developing following impairment of the energy balance. The endocrine system is known to be affected by the condition. Serum thyroid hormones and trace element levels have been shown to be affected in obese children. Changes in serum thyroid hormones may result from alterations occurring in serum trace element levels. The aim of this study was to evaluate whether or not changes in serum thyroid hormone levels in children with exogenous obesity are associated with changes in trace element levels. Eighty-five children diagnosed with exogenous obesity constituted the study group, and 24 age- and sex-matched healthy children made up the control group. Serum thyroid stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3), thyroglobulin (TG), selenium (Se), zinc (Zn), copper (Cu), and manganese (Mn) levels in the study group were measured before and at the third and sixth months of treatment, and once only in the control group. Pretreatment fT4 levels in the study group rose significantly by the sixth month (p = 0.006). Zn levels in the patient group were significantly low compared to the control group (p = 0.009). Mn and Se levels in the obese children before and at the third and sixth months of treatment were significantly higher than those of the control group (p = 0.001, p = 0.001). In conclusion, fT4, Zn, Cu, Mn, and Se levels are significantly affected in children diagnosed with exogenous obesity. The change in serum fT4 levels is not associated with changes in trace element concentrations.

  1. The Functions of China Marginal Sea Sediments in the Cycle of Biogenic Elements

    Institute of Scientific and Technical Information of China (English)

    Sun Yunming; Song Jinming

    2002-01-01

    The contents of biogenic elements in China marginal sea sediments are related to their grain sizes, river transport, et al. In general, the finer the grain size is, the higher the contents of organic matter and OC, N, P are, the lower the contents of S and Si are. The biogeochemical environments of sediments are related to Eh, pH, temperature content of OC,Fe3+/Fe2+ radio, water dynamics condition, grain size of sediment, S system in sediment interstitial waters, et al., and they influence the early diageneses and cycle of biogenic elements in sediments. In most regions of China marginal sea, the flux directions of S2-, HS-,3- NH4+H4SiO4, PO4 , across the sediment-water interface are from sediment to the overlying seawater, the flux directions of SO42-, HCO3-, NO3-, NO2- across the sediment-water interface are from the overlying seawater to sediment. The irrigation of living things is important in the cycle of the biogenic elements across sediment-water interfaces.

  2. Replicating function of the RS1 element associated with Vibrio cholerae CTX phi prophage.

    Science.gov (United States)

    Campos, J; Fando, R; Silva, A; Rodriguez, B L; Benitez, J A

    1998-07-01

    The RS1 element associated with Vibrio cholerae CTX phi prophage was cloned from an E1 Tor biotype Vibrio cholerae strain. We used the recA- vaccine strain Peru-15, that lacks the target for RS-mediated site-specific integration, to show that RS1 promotes autonomous replication of a suicide vector. A linker insertion in the rstR open reading frame abolished autonomous replication in Peru-15 but not in a strain containing an RS1 in the chromosome. An AT-rich region containing cis-acting elements involved in autonomous replication was identified by deletion. This region was sufficient to support autonomous replication in a strain containing an RS1 in the chromosome. DNA sequence analysis of a region present in RS1 and not RS2 revealed the presence of putative binding sites for host proteins involved in plasmid replication. These results indicate that RS1 contains a replicon distinct from RS2 which could be involved in replicative recombination events associated with tandem amplification of the CTX element.

  3. Temporal and Spatial Distribution of Elements in a Small Catchment, and Buffer Function of Wetland in Longgan Lake, China

    Institute of Scientific and Technical Information of China (English)

    WU Yanhong(吴艳宏); WANG Sumin(王苏民); R. W. Barttarbee; ZHU Yuxin(朱育新)

    2004-01-01

    Wetland is the conjunction of lake and terrene where human activities are concentrated. From the viewpoints of material transport and cycling in the terrene-lake system, wetland is the buffer where sand and mud, heavy metals, pollutants and nutrients are tarried. In this paper, we provide a case study based on the temporal and spatial distribution of elements in the Wangling River catchment, a small sub-catchment of Longgan Lake in the middle reaches of the Yangtze River. We have found that wetland can buffer major heavy metals such as Cr, Cu, etc.significantly, but has a little buffer function to some active elements such as Fe and Mn, which are always transported as solutions. Human activities not only influence the distribution of elements, but also weaken the buffer function of wetland. Intensive human activities in the Longgan Lake area in the past 70 years have been recorded in stream, wetland and lake sediments, especially the human activity events such as deforesting and reclaiming on a large scale in 1958 and the 1980' s. Human activities caused the increase of sedimentation rates since the 1950' s, as well as the increase of elements' concentrations. The extensive use of fertilizers and pesticides since the 1960' s have led to the increase of total P concentrations. Increasing SO2 emission accelerate the process of cation exchange in soil, and enhance the leaching of Mn out of soils. Permanent storing of water causes the soil gleyification that also intensifies the leaching of Mn.These are two major reasons for the obvious increase of manganese concentrations in recent 20 years in Longgan Lake. Intensive human activities since the 1950s' have intensified the population in this region and thus destroyed the buffer function of wetland.

  4. Shoulder Strength Requirements for Upper Limb Functional Tasks: Do age and Rotator Cuff Tear Status Matter?

    Science.gov (United States)

    Santago, Anthony C; Vidt, Meghan E; Li, Xiaotong; Tuohy, Christopher J; Poehling, Gary G; Freehill, Michael T; Saul, Katherine R

    2017-07-17

    Understanding upper limb strength requirements for daily tasks is imperative for early detection of strength loss that may progress to disability due to age or rotator cuff tear. We quantified shoulder strength requirements for five upper limb tasks performed by three groups: uninjured young adults and older adults, and older adults with a degenerative supraspinatus tear prior to repair. Musculoskeletal models were developed for each group representing age, sex, and tear-related strength losses. Percentage of available strength used was quantified for the subset of tasks requiring the largest amount of shoulder strength. Significant differences in strength requirements existed across tasks: upward reach 105° required the largest average strength; axilla wash required the largest peak strength. However, there were limited differences across participant groups. Older adults with and without a tear used a larger percentage of their shoulder elevation (p<.001, p<.001) and external rotation (p<.001, p=.017) strength than the young adults respectively. Presence of a tear signficantly increased percentage of internal rotation strength compared to young (p<.001) and uninjured older adults (p=.008). Marked differences in strength demand across tasks indicate the need for evaluating a diversity of functional tasks to effectively detect early strength loss which may lead to disability.

  5. Computational Methodology for the Prediction of Functional Requirement Variations Across the Product Life-Cycle

    CERN Document Server

    Mandil, Guillaume; Rivière, Alain

    2009-01-01

    The great majority of engineered products are subject to thermo-mechanical loads which vary with the product environment during the various phases of its life-cycle (machining, assembly, intended service use...). Those load variations may result in different values of the parts nominal dimensions, which in turn generate corresponding variation of the effective clearance (functional requirement) in the assembly. Usually, and according to the contractual drawings, the parts are measured after the machining stage, whereas the interesting measurement values are the ones taken in service for they allow the prediction of clearance value under operating conditions. Unfortunately, measurement in operating conditions may not be practical to obtain. Hence, the main purpose of this research is to create, through computations and simulations, links between the values of the loads, dimensions and functional requirements during the successive phases of the life cycle of some given product. [...

  6. High-Level Functional and Operational Requirements for the Advanced Fuel Cycle Facilty

    Energy Technology Data Exchange (ETDEWEB)

    Charles Park

    2006-12-01

    High-Level Functional & Operational Requirements for the AFCF -This document describes the principal functional and operational requirements for the proposed Advanced Fuel Cycle Facility (AFCF). The AFCF is intended to be the world's foremost facility for nuclear fuel cycle research, technology development, and demonstration. The facility will also support the near-term mission to develop and demonstrate technology in support of fuel cycle needs identified by industry, and the long-term mission to retain and retain U.S. leadership in fuel cycle operations. The AFCF is essential to demonstrate a more proliferation-resistant fuel cycle and make long-term improvements in fuel cycle effectiveness, performance and economy.

  7. Whole genome functional analysis identifies novel components required for mitotic spindle integrity in human cells

    OpenAIRE

    Rines, Daniel R; Gomez-Ferreria, Maria Ana; Zhou, Yingyao; DeJesus, Paul; Grob,Seanna; Batalov, Serge; Labow, Marc; Huesken, Dieter; Mickanin, Craig; Hall, Jonathan; Reinhardt, Mischa; Natt, Francois; Lange, Joerg; Sharp, David J.; Chanda, Sumit K.

    2008-01-01

    Background The mitotic spindle is a complex mechanical apparatus required for accurate segregation of sister chromosomes during mitosis. We designed a genetic screen using automated microscopy to discover factors essential for mitotic progression. Using a RNA interference library of 49,164 double-stranded RNAs targeting 23,835 human genes, we performed a loss of function screen to look for small interfering RNAs that arrest cells in metaphase. Results Here we report the identification of gene...

  8. Systems Engineering functions and requirements for the Hanford Cleanup mission: First issue

    Energy Technology Data Exchange (ETDEWEB)

    Holmes, J.J.

    1994-01-01

    This report documents the top-level SE mission analysis, functions analysis, and requirements analysis for the Hanford Site cleanup mission. Because SE is an iterative process, this document will be continuously updated as the mission evolves. This first issue will be subject to change as lower-level work is conducted or primary system architecture is changed as a result of public involvement, NEPA processes, or changes in DOE/HQ direction.

  9. Directional resolution of head-related transfer functions required in binaural synthesis

    DEFF Research Database (Denmark)

    Minnaar, Pauli; Plogsties, Jan; Christensen, Flemming

    2005-01-01

    In binaural synthesis a virtual sound source is implemented by convolving an anechoic signal with a pair of head-related transfer functions (HRTFs). In order to represent all possible directions of the sound source with respect to the listener a discrete number of HRTFs are measured...... and moving sound sources. A criterion was found that predicts the experimental results. This criterion was used to estimate the directional resolution required in binaural synthesis for all directions on the sphere around the head....

  10. 76 FR 14812 - Final Regulation Extending the Reporting Deadline for Year 2010 Data Elements Required Under the...

    Science.gov (United States)

    2011-03-18

    ... Review B. Paperwork Reduction Act C. Regulatory Flexibility Act (RFA) D. Unfunded Mandates Reform Act... facilities. 331492 Zinc dust reclaiming facilities, recovering from scrap and/or alloying purchased metals... addition of facility- and parent-level reporting requirements (75 FR 57669, September 22, 2010); technical...

  11. The rapidly evolving centromere-specific histone has stringent functional requirements in Arabidopsis thaliana.

    Science.gov (United States)

    Ravi, Maruthachalam; Kwong, Pak N; Menorca, Ron M G; Valencia, Joel T; Ramahi, Joseph S; Stewart, Jodi L; Tran, Robert K; Sundaresan, Venkatesan; Comai, Luca; Chan, Simon W-L

    2010-10-01

    Centromeres control chromosome inheritance in eukaryotes, yet their DNA structure and primary sequence are hypervariable. Most animals and plants have megabases of tandem repeats at their centromeres, unlike yeast with unique centromere sequences. Centromere function requires the centromere-specific histone CENH3 (CENP-A in human), which replaces histone H3 in centromeric nucleosomes. CENH3 evolves rapidly, particularly in its N-terminal tail domain. A portion of the CENH3 histone-fold domain, the CENP-A targeting domain (CATD), has been previously shown to confer kinetochore localization and centromere function when swapped into human H3. Furthermore, CENP-A in human cells can be functionally replaced by CENH3 from distantly related organisms including Saccharomyces cerevisiae. We have used cenh3-1 (a null mutant in Arabidopsis thaliana) to replace endogenous CENH3 with GFP-tagged variants. A H3.3 tail domain-CENH3 histone-fold domain chimera rescued viability of cenh3-1, but CENH3's lacking a tail domain were nonfunctional. In contrast to human results, H3 containing the A. thaliana CATD cannot complement cenh3-1. GFP-CENH3 from the sister species A. arenosa functionally replaces A. thaliana CENH3. GFP-CENH3 from the close relative Brassica rapa was targeted to centromeres, but did not complement cenh3-1, indicating that kinetochore localization and centromere function can be uncoupled. We conclude that CENH3 function in A. thaliana, an organism with large tandem repeat centromeres, has stringent requirements for functional complementation in mitosis.

  12. Lead Coolant Test Facility Technical and Functional Requirements, Conceptual Design, Cost and Construction Schedule

    Energy Technology Data Exchange (ETDEWEB)

    Soli T. Khericha

    2006-09-01

    This report presents preliminary technical and functional requirements (T&FR), thermal hydraulic design and cost estimate for a lead coolant test facility. The purpose of this small scale facility is to simulate lead coolant fast reactor (LFR) coolant flow in an open lattice geometry core using seven electrical rods and liquid lead or lead-bismuth eutectic. Based on review of current world lead or lead-bismuth test facilities and research need listed in the Generation IV Roadmap, five broad areas of requirements of basis are identified: Develop and Demonstrate Prototype Lead/Lead-Bismuth Liquid Metal Flow Loop Develop and Demonstrate Feasibility of Submerged Heat Exchanger Develop and Demonstrate Open-lattice Flow in Electrically Heated Core Develop and Demonstrate Chemistry Control Demonstrate Safe Operation and Provision for Future Testing. These five broad areas are divided into twenty-one (21) specific requirements ranging from coolant temperature to design lifetime. An overview of project engineering requirements, design requirements, QA and environmental requirements are also presented. The purpose of this T&FRs is to focus the lead fast reactor community domestically on the requirements for the next unique state of the art test facility. The facility thermal hydraulic design is based on the maximum simulated core power using seven electrical heater rods of 420 kW; average linear heat generation rate of 300 W/cm. The core inlet temperature for liquid lead or Pb/Bi eutectic is 420oC. The design includes approximately seventy-five data measurements such as pressure, temperature, and flow rates. The preliminary estimated cost of construction of the facility is $3.7M. It is also estimated that the facility will require two years to be constructed and ready for operation.

  13. An evaluation of a coupled microstructural approach for the analysis of functionally graded composites via the finite-element method

    Science.gov (United States)

    Pindera, Marek-Jerzy; Dunn, Patrick

    1995-01-01

    A comparison is presented between the predictions of the finite-element analysis and a recently developed higher-order theory for functionally graded materials subjected to a thorough-thickness temperature gradient. In contrast to existing micromechanical theories that utilize classical (i.e., uncoupled) homogenization schemes to calculate micro-level and macro-level stress and displacement fields in materials with uniform or nonuniform fiber spacing (i.e., functionally graded materials), the new theory explicitly couples the microstructural details with the macrostructure of the composite. Previous thermo-elastic analysis has demonstrated that such coupling is necessary when: the temperature gradient is large with respect to the dimension of the reinforcement; the characteristic dimension of the reinforcement is large relative to the global dimensions of the composite and the number of reinforcing fibers or inclusions is small. In these circumstances, the standard micromechanical analyses based on the concept of the representative volume element used to determine average composite properties produce questionable results. The comparison between the predictions of the finite-element method and the higher-order theory presented herein establish the theory's accuracy in predicting thermal and stress fields within composites with a finite number of fibers in the thickness direction subjected to a thorough-thickness thermal gradient.

  14. Transcriptional repression of frequency by the IEC-1-INO80 complex is required for normal Neurospora circadian clock function.

    Science.gov (United States)

    Gai, Kexin; Cao, Xuemei; Dong, Qing; Ding, Zhaolan; Wei, Yashang; Liu, Yingchun; Liu, Xiao; He, Qun

    2017-04-01

    Rhythmic activation and repression of the frequency (frq) gene are essential for normal function of the Neurospora circadian clock. WHITE COLLAR (WC) complex, the positive element of the Neurospora circadian system, is responsible for stimulation of frq transcription. We report that a C2H2 finger domain-containing protein IEC-1 and its associated chromatin remodeling complex INO80 play important roles in normal Neurospora circadian clock function. In iec-1KO strains, circadian rhythms are abolished, and the frq transcript levels are increased compared to that of the wild-type strain. Similar results are observed in mutant strains of the INO80 subunits. Furthermore, ChIP data show that recruitment of the INO80 complex to the frq promoter is IEC-1-dependent. WC-mediated transcription of frq contributes to the rhythmic binding of the INO80 complex at the frq promoter. As demonstrated by ChIP analysis, the INO80 complex is required for the re-establishment of the dense chromatin environment at the frq promoter. In addition, WC-independent frq transcription is present in ino80 mutants. Altogether, our data indicate that the INO80 complex suppresses frq transcription by re-assembling the suppressive mechanisms at the frq promoter after transcription of frq.

  15. Multiple Functions of Let-23, a Caenorhabditis Elegans Receptor Tyrosine Kinase Gene Required for Vulval Induction

    Science.gov (United States)

    Aroian, R. V.; Sternberg, P. W.

    1991-01-01

    The let-23 gene, which encodes a putative tyrosine kinase of the epidermal growth factor (EGF) receptor subfamily, has multiple functions during Caenorhabditis elegans development. We show that let-23 function is required for vulval precursor cells (VPCs) to respond to the signal that induces vulval differentiation: a complete loss of let-23 function results in no induction. However, some let-23 mutations that genetically reduce but do not eliminate let-23 function result in VPCs apparently hypersensitive to inductive signal: as many as five of six VPCs can adopt vulval fates, in contrast to the three that normally do. These results suggest that the let-23 receptor tyrosine kinase controls two opposing pathways, one that stimulates vulval differentiation and another that negatively regulates vulval differentiation. Furthermore, analysis of 16 new let-23 mutations indicates that the let-23 kinase functions in at least five tissues. Since various let-23 mutant phenotypes can be obtained independently, the let-23 gene is likely to have tissue-specific functions. PMID:2071015

  16. A discussion of higher order software concepts as they apply to functional requirements and specifications. [space shuttles and guidance

    Science.gov (United States)

    Hamilton, M.

    1973-01-01

    The entry guidance software functional requirements (requirements design phase), its architectural requirements (specifications design phase), and the entry guidance software verified code are discussed. It was found that the proper integration of designs at both the requirements and specifications levels are of high priority consideration.

  17. Rapid mapping of functional cis-acting RNA elements by recovery of virus from a degenerate RNA population: application to genome segment 10 of bluetongue virus.

    Science.gov (United States)

    Boyce, M; McCrae, M A

    2015-10-01

    The regulatory elements which control the processes of virus replication and gene expression in the Orbivirus genus are uncharacterized in terms of both their locations within genome segments and their specific functions. The reverse genetics system for the type species, Bluetongue virus, has been used in combination with RNA secondary structure prediction to identify and map the positions of cis-acting regions within genome segment 10. Through the simultaneous introduction of variability at multiple nucleotide positions in the rescue RNA population, the functional contribution of these positions was used to map regions containing cis-acting elements essential for virus viability. Nucleotides that were individually lethal when varied mapped within a region of predicted secondary structure involving base pairing between the 5' and 3' ends of the transcript. An extended region of predicted perfect base pairing located within the 3' untranslated region of the genome segment was also found to be required for virus viability. In contrast to the identification of individually lethal mutations, gross alteration of the composition of this predicted stem region was possible, providing the base-pairing potential between the two strands was maintained, identifying a structural feature predicted to be conserved throughout the Orbivirus genus. The approach of identifying cis-acting sequences through sequencing the recovered virus following the rescue of a degenerate RNA population is broadly applicable to viruses where reverse genetics is available.

  18. Elements Required for an Efficient NADP-Malic Enzyme Type C4 Photosynthesis1[C][W][OPEN

    Science.gov (United States)

    Wang, Yu; Long, Stephen P.; Zhu, Xin-Guang

    2014-01-01

    C4 photosynthesis has higher light, nitrogen, and water use efficiencies than C3 photosynthesis. Although the basic anatomical, cellular, and biochemical features of C4 photosynthesis are well understood, the quantitative significance of each element of C4 photosynthesis to the high photosynthetic efficiency are not well defined. Here, we addressed this question by developing and using a systems model of C4 photosynthesis, which includes not only the Calvin-Benson cycle, starch synthesis, sucrose synthesis, C4 shuttle, and CO2 leakage, but also photorespiration and metabolite transport between the bundle sheath cells and mesophyll cells. The model effectively simulated the CO2 uptake rates, and the changes of metabolite concentrations under varied CO2 and light levels. Analyses show that triose phosphate transport and CO2 leakage can help maintain a high photosynthetic rate by balancing ATP and NADPH amounts in bundle sheath cells and mesophyll cells. Finally, we used the model to define the optimal enzyme properties and a blueprint for C4 engineering. As such, this model provides a theoretical framework for guiding C4 engineering and studying C4 photosynthesis in general. PMID:24521879

  19. 3D finite element and experimental study of the size requirements for measuring toughness on tempered martensitic steels

    Energy Technology Data Exchange (ETDEWEB)

    Mueller, P. [Fusion Technology-Materials, CRPP-EPFL, Association EURATOM-Confederation Suisse, 5232 Villigen PSI (Switzerland)], E-mail: pablo.mueller@psi.ch; Spaetig, P. [Fusion Technology-Materials, CRPP-EPFL, Association EURATOM-Confederation Suisse, 5232 Villigen PSI (Switzerland)

    2009-06-01

    The fracture properties of the tempered martensitic steel Eurofer97, which is among the main candidates for fusion power plant structural applications, were studied with two sizes of pre-cracked compact specimens (0.35T C(T) and 0.87T C(T)). The fracture toughness behavior was characterized within the temperature range -80 to -40 deg. C. The ductile-to-brittle transition reference temperature, as defined in the ASTM standard E1921, was around T{sub 0} {approx} -75 deg. C. At -60 deg. C, it was found that two sets of toughness data obtained with 0.35T and 0.87T C(T) specimens are not consistent with the size adjustments recommended in the ASTM standard. It was then shown that the underlying reason of this inconsistency is an inappropriate specimen size limit of the ASTM standard for this type of steel. From published fracture toughness data on the tempered martensitic steel F82H steel, similar results were also highlighted. 3D finite elements simulations of the compact specimens were performed to compare the stresses and deformations at the onset of fracture. A local approach model based on the attainment of a critical stress and a critical volume was used to study the constraint loss phenomenon. Within the framework of this model, the strong toughness increase by reducing the specimen size could be satisfactorily explained.

  20. 3D finite element and experimental study of the size requirements for measuring toughness on tempered martensitic steels

    Science.gov (United States)

    Mueller, P.; Spätig, P.

    2009-06-01

    The fracture properties of the tempered martensitic steel Eurofer97, which is among the main candidates for fusion power plant structural applications, were studied with two sizes of pre-cracked compact specimens (0.35T C(T) and 0.87T C(T)). The fracture toughness behavior was characterized within the temperature range -80 to -40 °C. The ductile-to-brittle transition reference temperature, as defined in the ASTM standard E1921, was around T0 ≈ -75 °C. At -60 °C, it was found that two sets of toughness data obtained with 0.35T and 0.87T C(T) specimens are not consistent with the size adjustments recommended in the ASTM standard. It was then shown that the underlying reason of this inconsistency is an inappropriate specimen size limit of the ASTM standard for this type of steel. From published fracture toughness data on the tempered martensitic steel F82H steel, similar results were also highlighted. 3D finite elements simulations of the compact specimens were performed to compare the stresses and deformations at the onset of fracture. A local approach model based on the attainment of a critical stress and a critical volume was used to study the constraint loss phenomenon. Within the framework of this model, the strong toughness increase by reducing the specimen size could be satisfactorily explained.

  1. Visual Functions and TraceElement Metabolism in Tobacco-toxic Optic Neuropathy

    Institute of Scientific and Technical Information of China (English)

    1992-01-01

    Visual functions and nutrition metabolic characteristics werestudied in 8 subjects(16 eyes)with tobacco-toxic optic neuropathy(TTON).Their visual functions tested by psychophysical and electrophysiologicmethods showed that:1.central vision diminished in 16 eyes,2.dyschromatopsias were found in 14 tested eyes,3.bilateral symmetricalcentral or cecocentral scotomas were the visual field characteristics in allcases,4.PVEP were severe abnormal in 3 spatial frequencies in all cases and56.3% of 15' checkboard ...

  2. Effects of chemical functional groups on elemental mercury adsorption on carbonaceous surfaces.

    Science.gov (United States)

    Liu, Jing; Cheney, Marcos A; Wu, Fan; Li, Meng

    2011-02-15

    A systematic theoretical study using density functional theory is performed to provide molecular-level understanding of the effects of chemical functional groups on mercury adsorption on carbonaceous surfaces. The zigzag and armchair edges were used in modeling the carbonaceous surfaces to simulate different adsorption sites. The edge atoms on the upper side of the models are unsaturated to simulate active sites. All calculations (optimizations, energies, and frequencies) were made at B3PW91 density functional theory level, using RCEP60VDZ basis set for mercury and 6-31G(d) pople basis set for other atoms. The results indicate that the embedding of halogen atom can increase the activity of its neighboring site which in turn increases the adsorption capacity of the carbonaceous surface for Hg(0). The adsorption belongs to chemisorptions, which is in good agreement with the experimental results. For the effects of oxygen functional groups, lactone, carbonyl and semiquinone favor Hg(0) adsorption because they increase the neighboring site's activity for mercury adsorption. On the contrary, phenol and carboxyl functional groups show a physisorption of Hg(0), and reduce Hg capture. This result can explain the seemingly conflicting experimental results reported in the literature concerning the influence of oxygen functional groups on mercury adsorption on carbonaceous surface.

  3. A novel human polycomb binding site acts as a functional polycomb response element in Drosophila.

    Directory of Open Access Journals (Sweden)

    Suresh Cuddapah

    Full Text Available Polycomb group (PcG proteins are key chromatin regulators implicated in multiple processes including embryonic development, tissue homeostasis, genomic imprinting, X-chromosome inactivation, and germ cell differentiation. The PcG proteins recognize target genomic loci through cis DNA sequences known as Polycomb Response Elements (PREs, which are well characterized in Drosophila. However, mammalian PREs have been elusive until two groups reported putative mammalian PREs recently. Consistent with the existence of mammalian PREs, here we report the identification and characterization of a potential PRE from human T cells. The putative human PRE has enriched binding of PcG proteins, and such binding is dependent on a key PcG component SUZ12. We demonstrate that the putative human PRE carries both genetic and molecular features of Drosophila PRE in transgenic flies, implying that not only the trans PcG proteins but also certain features of the cis PREs are conserved between mammals and Drosophila.

  4. Characteristics and trends in required home care by GPs in Austria: diseases and functional status of patients

    Directory of Open Access Journals (Sweden)

    Pichler Ingrid

    2006-10-01

    Full Text Available Abstract Background Almost all societies carry responsibility towards patients who require continuous medical care at home. In many health systems the general practitioner cooperates with community based services of home care and coordinates all medical and non medical activities. In Austria the general practitioner together and in cooperation with relatives of the patient and professional organisations usually takes on this task by visiting his patients. This study was carried out to identify diseases that need home care and to describe the functional profile of home care patients in eastern Austria. Methods Cross sectional observational study with 17 GP practices participating during 2 study periods in 1997 and in 2004 in eastern Austria. Each GP identified patients requiring home care and assessed their underlying diseases and functional status by filling in a questionnaire personally after an encounter. Patients in nursing homes were excluded. Statistical tests used were t-tests, contingency tables, nonparametric Wilcoxon signed rank sum test and Fisher-combination test. Results Patients with degenerative diseases of the central nervous system (65% caused by Alzheimer's disease and cerebrovascular occlusive disease and patients with degenerative diseases of the skeletal system (53% were the largest groups among the 198 (1997 and 261 (2004 home care cases of the 11 (1997 and 13 (2004 practices. Malignant diseases in a terminal state constituted only 5% of the cases. More than two thirds of all cases were female with an average age of 80 years. Slightly more than 70% of the patients were at least partially mobile. Conclusion Home care and home visits for patients with degenerative diseases of the central nervous and skeletal system are important elements of GP's work. Further research should therefore focus on effective methods of training and rehabilitation to better the mental and physical status of patients living in their private homes.

  5. Basic Program Elements for Federal employee Occupational Safety and Health Programs and related matters; Subpart I for Recordkeeping and Reporting Requirements. Final rule.

    Science.gov (United States)

    2013-08-05

    OSHA is issuing a final rule amending the Basic Program Elements to require Federal agencies to submit their occupational injury and illness recordkeeping information to the Bureau of Labor Statistics (BLS) and OSHA on an annual basis. The information, which is already required to be created and maintained by Federal agencies, will be used by BLS to aggregate injury and illness information throughout the Federal government. OSHA will use the information to identify Federal establishments with high incidence rates for targeted inspection, and assist in determining the most effective safety and health training for Federal employees. The final rule also interprets several existing basic program elements in our regulations to clarify requirements applicable to Federal agencies, amends the date when Federal agencies must submit to the Secretary of Labor their annual report on occupational safety and health programs, amends the date when the Secretary of Labor must submit to the President the annual report on Federal agency safety and health, and clarifies that Federal agencies must include uncompensated volunteers when reporting and recording occupational injuries and illnesses.

  6. Divergent picornavirus IRES elements

    DEFF Research Database (Denmark)

    Belsham, Graham

    2009-01-01

    Internal ribosome entry site (IRES) elements were first identified about 20 years ago within the 5' untranslated region of picornavirus RNAs. They direct a cap-independent mechanism of translation initiation on the viral RNA. Within the picornavirus family it is now known that there are four...... classes of IRES element which vary in size (450-270nt), they also have different, complex, secondary structures and distinct requirements for cellular proteins to allow them to function. This review describes the features of each class of picornavirus IRES element but focuses on the characteristics...... of the most recently described group, initially identified within the porcine teschovirus-1 RNA, which has strong similarities to the IRES elements from within the genomes of hepatitis C virus and the pestiviruses which are members of the flavivirus family. The selection of the initiation codon...

  7. Identification of a functional antioxidant responsive element in the promoter of the Chinese hamster carbonyl reductase 3 (Chcr3) gene.

    Science.gov (United States)

    Miura, Takeshi; Taketomi, Ayako; Nakabayashi, Toshikatsu; Nishinaka, Toru; Terada, Tomoyuki

    2015-07-01

    CHCR3, a member of the short-chain dehydrogenase/reductase superfamily, is a carbonyl reductase 3 enzyme in Chinese hamsters. Carbonyl reductase 3 in humans has been believed to involve the metabolism and/or pharmacokinetics of anthracycline drugs, and the mechanism underlying the gene regulation has been investigated. In this study, the nucleotide sequence of the Chcr3 promoter was originally determined, and its promoter activity was characterised. The proximal promoter region is TATA-less and GC-rich, similar to the promoter region of human carbonyl reductase 3. Cobalt stimulated the transcriptional activity of the Chcr3 gene. The results of a luciferase gene reporter assay demonstrated that cobalt-induced stimulation required an antioxidant responsive element. Forced expression of Nrf2, the transcription factor that binds to antioxidant responsive elements, enhanced the transcriptional activity of the Chcr3 gene. These results suggest that cobalt induces the expression of the Chcr3 gene via the Nrf2-antioxidant responsive element pathway.

  8. cAMP response element binding protein is required for differentiation of respiratory epithelium during murine development.

    Directory of Open Access Journals (Sweden)

    A Daniel Bird

    Full Text Available The cAMP response element binding protein 1 (Creb1 transcription factor regulates cellular gene expression in response to elevated levels of intracellular cAMP. Creb1(-/- fetal mice are phenotypically smaller than wildtype littermates, predominantly die in utero and do not survive after birth due to respiratory failure. We have further investigated the respiratory defect of Creb1(-/- fetal mice during development. Lungs of Creb1(-/- fetal mice were pale in colour and smaller than wildtype controls in proportion to their reduced body size. Creb1(-/- lungs also did not mature morphologically beyond E16.5 with little or no expansion of airway luminal spaces, a phenotype also observed with the Creb1(-/- lung on a Crem(-/- genetic background. Creb1 was highly expressed throughout the lung at all stages examined, however activation of Creb1 was detected primarily in distal lung epithelium. Cell differentiation of E17.5 Creb1(-/- lung distal epithelium was analysed by electron microscopy and showed markedly reduced numbers of type-I and type-II alveolar epithelial cells. Furthermore, immunomarkers for specific lineages of proximal epithelium including ciliated, non-ciliated (Clara, and neuroendocrine cells showed delayed onset of expression in the Creb1(-/- lung. Finally, gene expression analyses of the E17.5 Creb1(-/- lung using whole genome microarray and qPCR collectively identified respiratory marker gene profiles and provide potential novel Creb1-regulated genes. Together, these results demonstrate a crucial role for Creb1 activity for the development and differentiation of the conducting and distal lung epithelium.

  9. Liver safety assessment: required data elements and best practices for data collection and standardization in clinical trials.

    Science.gov (United States)

    Avigan, Mark I; Bjornsson, Einar S; Pasanen, Markku; Cooper, Charles; Andrade, Raul J; Watkins, Paul B; Lewis, James H; Merz, Michael

    2014-11-01

    A workshop was convened to discuss best practices for the assessment of drug-induced liver injury (DILI) in clinical trials. In a breakout session, workshop attendees discussed necessary data elements and standards for the accurate measurement of DILI risk associated with new therapeutic agents in clinical trials. There was agreement that in order to achieve this goal the systematic acquisition of protocol-specified clinical measures and lab specimens from all study subjects is crucial. In addition, standard DILI terms that address the diverse clinical and pathologic signatures of DILI were considered essential. There was a strong consensus that clinical and lab analyses necessary for the evaluation of cases of acute liver injury should be consistent with the US Food and Drug Administration (FDA) guidance on pre-marketing risk assessment of DILI in clinical trials issued in 2009. A recommendation that liver injury case review and management be guided by clinicians with hepatologic expertise was made. Of note, there was agreement that emerging DILI signals should prompt the systematic collection of candidate pharmacogenomic, proteomic and/or metabonomic biomarkers from all study subjects. The use of emerging standardized clinical terminology, CRFs and graphic tools for data review to enable harmonization across clinical trials was strongly encouraged. Many of the recommendations made in the breakout session are in alignment with those made in the other parallel sessions on methodology to assess clinical liver safety data, causality assessment for suspected DILI, and liver safety assessment in special populations (hepatitis B, C, and oncology trials). Nonetheless, a few outstanding issues remain for future consideration.

  10. Identification of Cis-Acting Elements on Positive-Strand Subgenomic mRNA Required for the Synthesis of Negative-Strand Counterpart in Bovine Coronavirus

    Directory of Open Access Journals (Sweden)

    Po-Yuan Yeh

    2014-07-01

    Full Text Available It has been demonstrated that, in addition to genomic RNA, sgmRNA is able to serve as a template for the synthesis of the negative-strand [(−-strand] complement. However, the cis-acting elements on the positive-strand [(+-strand] sgmRNA required for (−-strand sgmRNA synthesis have not yet been systematically identified. In this study, we employed real-time quantitative reverse transcription polymerase chain reaction to analyze the cis-acting elements on bovine coronavirus (BCoV sgmRNA 7 required for the synthesis of its (−-strand counterpart by deletion mutagenesis. The major findings are as follows. (1 Deletion of the 5'-terminal leader sequence on sgmRNA 7 decreased the synthesis of the (−-strand sgmRNA complement. (2 Deletions of the 3' untranslated region (UTR bulged stem-loop showed no effect on (−-strand sgmRNA synthesis; however, deletion of the 3' UTR pseudoknot decreased the yield of (−-strand sgmRNA. (3 Nucleotides positioned from −15 to −34 of the sgmRNA 7 3'-terminal region are required for efficient (−-strand sgmRNA synthesis. (4 Nucleotide species at the 3'-most position (−1 of sgmRNA 7 is correlated to the efficiency of (−-strand sgmRNA synthesis. These results together suggest, in principle, that the 5'- and 3'-terminal sequences on sgmRNA 7 harbor cis-acting elements are critical for efficient (−-strand sgmRNA synthesis in BCoV.

  11. Finite Element Modeling and Free Vibration Analysis of Functionally Graded Nanocomposite Beams Reinforced by Randomly Oriented Carbon Nanotubes

    Directory of Open Access Journals (Sweden)

    Benedict Thomas

    2013-12-01

    Full Text Available This article deals with the finite element modeling and free vibration analysis of functionally graded nanocomposite beams reinforced by randomly oriented straight single-walled carbon nanotubes (SWCNTs. Nanostructural materials can be used to alter mechanical, thermal and electrical properties of polymer-based composite materials, because of their superior properties and perfect atom arrangement. Timoshenko beam theory is used to evaluate dynamic characteristics of the beam. The Eshelby–Mori–Tanaka approach based on an equivalent fiber is used to investigate the material properties of the beam. The equations of motion are derived by using Hamilton’s principle. The finite element method is employed to discretize the model and obtain a numerical approximation of the motion equation. Different SWCNTs distributions in the thickness direction are introduced to improve fundamental natural frequency and dynamic behavior of uniform functionally graded nanocomposite beam. Results are presented in tabular and graphical forms to show the effects of various material distributions, carbon nanotube orientations, shear deformation, slenderness ratios and boundary conditions on the dynamic behavior of the beam. The first five normalized mode shapes for functionally graded carbon nanotube reinforced composite (FG-CNTRC beams with different boundary conditions and different carbon nanotubes (CNTs orientation are presented. The results show that the above mentioned effects play very important role on the dynamic behavior of the beam.

  12. Finite element analysis of the dynamic behavior of radially polarized Functionally Graded Piezoelectric (FGP) structures

    Science.gov (United States)

    Kandasamy, Ramkumar; Cui, Fangsen

    2016-04-01

    In the traditional layered piezoelectric structures, high stress concentrations could cause the structural failure in interlayer surfaces due to repeated strain reversals. To overcome the performance limitations of these structures, the concept of Functionally Graded Materials (FGMs) has been introduced to improve the lifetime, integrity, and reliability of these structures. In this paper, the free and forced vibration of radially polarized Functionally Graded Piezoelectric (FGP) cylinders under different sets of loading are studied. Material properties such as piezoelectric, elastic and permittivity are assumed to change along its thickness, based on a specific gradation function. Four-parameter power law distribution is used to grade the volume fraction of the constituents comprising of PZT-5A and PZT-5H. Material property is assumed to be temperature dependent for a few numerical studies. The present modeling approach is validated by comparing the free and forced vibration of radially polarized Functionally Graded Piezoelectric (FGP) cylinders with those reported in the literature. The effects of material composition, loading and boundary conditions on the dynamic behavior of FGP cylinder are described. Since the modeling of functionally graded piezoelectric systems is challenging, the present study can help in the design and analysis of FGP cylinders.

  13. Neuro-cognition and social cognition elements of social functioning and social quality of life.

    Science.gov (United States)

    Hasson-Ohayon, Ilanit; Mashiach-Eizenberg, Michal; Arnon-Ribenfeld, Nitzan; Kravetz, Shlomo; Roe, David

    2017-09-06

    Previous studies have shown that deficits in social cognition mediate the association between neuro-cognition and functional outcome. Based on these findings, the current study presents an examination of the mediating role of social cognition and includes two different outcomes: social functioning assessed by objective observer and social quality of life assessed by subjective self-report. Instruments measuring different aspects of social cognition, cognitive ability, social functioning and social quality of life were administered to 131 participants who had a diagnosis of a serious mental illness. Results showed that emotion recognition and attributional bias were significant mediators such that cognitive assessment was positively related to both, which in turn, were negatively related to SQoL. While one interpretation of the data suggests that deficits in emotion recognition may serve as a possible defense mechanism, future studies should re-assess this idea. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. TYK2 kinase activity is required for functional type I interferon responses in vivo.

    Directory of Open Access Journals (Sweden)

    Michaela Prchal-Murphy

    Full Text Available Tyrosine kinase 2 (TYK2 is a member of the Janus kinase (JAK family and is involved in cytokine signalling. In vitro analyses suggest that TYK2 also has kinase-independent, i.e., non-canonical, functions. We have generated gene-targeted mice harbouring a mutation in the ATP-binding pocket of the kinase domain. The Tyk2 kinase-inactive (Tyk2(K923E mice are viable and show no gross abnormalities. We show that kinase-active TYK2 is required for full-fledged type I interferon- (IFN induced activation of the transcription factors STAT1-4 and for the in vivo antiviral defence against viruses primarily controlled through type I IFN actions. In addition, TYK2 kinase activity was found to be required for the protein's stability. An inhibitory function was only observed upon over-expression of TYK2(K923Ein vitro. Tyk2(K923E mice represent the first model for studying the kinase-independent function of a JAK in vivo and for assessing the consequences of side effects of JAK inhibitors.

  15. Survival and functional outcome of children requiring endotracheal intubation during therapy for severe traumatic brain injury.

    Science.gov (United States)

    Thakker, J C; Splaingard, M; Zhu, J; Babel, K; Bresnahan, J; Havens, P L

    1997-08-01

    To determine the predictors of survival and functional outcome of pediatric patients with traumatic brain injury severe enough to require endotracheal intubation and mechanical ventilation. Retrospective, observational cohort study. Pediatric intensive care unit (ICU) at a tertiary care children's hospital. All children (n = 105) admitted over a 5-yr period with traumatic brain injury severe enough to require endotracheal intubation and mechanical ventilation. The median age was 43 months (range 1 month to 14 yrs). Of these children, 74% were male and 70% were white. None. Variables studied included vital signs during the first 24 hrs of admission, Pediatric Risk of Mortality (PRISM) score, Glasgow Coma Score, duration of mechanical ventilation, and number of pediatric ICU and hospital days. Functional status was graded as normal, independent, partially dependent, or dependent in the areas of locomotion, self-care, and communication. This status was assessed at hospital discharge by chart review and at follow-up by telephone interview. The median Glasgow Coma Score was 6 (range 3 to 14) and the median PRISM score was 13 (range 1 to 51). There were 19 (18.1%) deaths, 17 in the pediatric ICU and two after hospital discharge. Of the patients who survived to hospital discharge, 39 (37.1%) patients were completely normal or independent, 42 (40%) patients were partially dependent, and seven (6.7%) patients were dependent in all three areas of function. Follow-up evaluations were available for 80 patients, with a median follow-up time of 24.5 months (range 8 to 70). Of the 78 patients who survived and were available for follow-up, the number who were functionally normal or independent increased to 69 (65.7%). At follow-up, there were eight (7.6%) patients remaining with partial dependency in at least one area of function while one (0.9%) patient continued to be dependent in all three areas of function. Mortality and dependent functional outcome were more likely in

  16. A single diffractive optical element implementing spectrum-splitting and beam-concentration functions simultaneously with high diffraction efficiency

    Institute of Scientific and Technical Information of China (English)

    Ye Jia-Sheng; Wang Jin-Ze; Huang Qing-Li; Dong Bi-Zhen; Zhang Yan; Yang Guo-Zhen

    2013-01-01

    In this paper,a novel method is proposed and employed to design a single diffractive optical element (DOE) for implementing spectrum-splitting and beam-concentration (SSBC) functions simultaneously.We develop an optimization algorithm,through which the SSBC DOE can be optimized within an arbitrary thickness range according to the limitations of modem photolithography technology.Theoretical simulation results reveal that the designed SSBC DOE has a high optical focusing efficiency.It is expected that the designed SSBC DOE should have practical applications in high-efficiency solar cell systems.

  17. A single diffractive optical element for implementing spectrum-splitting and beam-concentration functions simultaneously with high diffraction efficiency

    CERN Document Server

    Ye, Jia-Sheng; Huang, Qing-Li; Dong, Bi-Zhen; Zhang, Yan; Yang, Guo-Zhen

    2013-01-01

    In this paper, a novel method is proposed, and employed to design a single diffractive optical element (DOE) for implementing spectrum-splitting and beam-concentration (SSBC) functions simultaneously. We develop an optimization algorithm, through which the SSBC DOE can be optimized within an arbitrary thickness range, according to the limitations of modern photolithography technology. Theoretical simulation results reveal that the designed SSBC DOE has a high optical focusing efficiency. It is expected that the designed SSBC DOE should have practical applications in high-efficiency solar cell systems.

  18. Transition elements based on transfinite interpolation

    Science.gov (United States)

    Odabas, Onur R.; Sarigul-Klijn, Nesrin

    1993-01-01

    In this study the transfinite interpolation methodology, a 'blending-function' method in particular, is utilized for the formulation of transition elements. The method offers a formal way of meeting continuity requirements in a transition element. Element shape functions are derived by blending the continuity requirements of individual boundary segments. The blending directions are naturally orthogonal in rectangular domains therefore interpolation of the boundaries over rectangular 2D and 3D elements can be performed with minimal effort. In triangular domains, however, the choice of blending directions and interpolants is not straightforward. For that reason, two interpolation techniques are proposed for blending of the boundaries of triangular domains. A series of transition elements of various classes compatible with elements of different orders and dimensions is developed and the full potential of the transfinite interpolation, as it applies to element formulation, is explored.

  19. Accurate and Efficient Analysis of Printed Reflectarrays With Arbitrary Elements Using Higher-Order Hierarchical Legendre Basis Functions

    DEFF Research Database (Denmark)

    Zhou, Min; Jørgensen, Erik; Kim, Oleksiy S.;

    2012-01-01

    , thus providing the flexibility required in the analysis of printed reflectarrays. A comparison to DTU-ESA Facility measurements of a reference offset reflectarray shows that higher-order hierarchical Legendre basis functions produce results of the same accuracy as those obtained using singular basis...

  20. Finite Element Analysis of the Deformation of Functionally Graded Plates under Thermomechanical Loads

    Directory of Open Access Journals (Sweden)

    A. E. Alshorbagy

    2013-01-01

    Full Text Available The first-order shear deformation plate model, accounting for the exact neutral plane position, is exploited to investigate the uncoupled thermomechanical behavior of functionally graded (FG plates. Functionally graded materials are mainly constructed to operate in high temperature environments. Also, FG plates are used in many applications (such as mechanical, electrical, and magnetic, where an amount of heat may be generated into the FG plate whenever other forms of energy (electrical, magnetic, etc. are converted into thermal energy. Several simulations are performed to study the behavior of FG plates, subjected to thermomechanical loadings, and focus the attention on the effect of the heat source intensity. Most of the previous studies have considered the midplane neutral one, while the actual position of neutral plane for functionally graded plates is shifted and should be firstly determined. A comparative study is performed to illustrate the effect of considering the neutral plane position. The volume fraction of the two constituent materials of the FG plate is varied smoothly and continuously, as a continuous power function of the material position, along the thickness of the plate.

  1. Federalism. Theory and Neo-Functionalism: Elements for an analytical framework

    DEFF Research Database (Denmark)

    Dosenrode, Søren

    2010-01-01

    -McKayian way, is able to explain the cases of ‘big bang’ integration (USA, Australia, Canada), but not an ‘organic’ integration process. Neo-functionalism, on the other hand, is not able to explain this relatively fast form of integration, but it is – in its new version - able to analyze and explain...

  2. Federalism. Theory and Neo-Functionalism: Elements for an analytical framework

    DEFF Research Database (Denmark)

    Dosenrode, Søren

    2010-01-01

    -McKayian way, is able to explain the cases of ‘big bang’ integration (USA, Australia, Canada), but not an ‘organic’ integration process. Neo-functionalism, on the other hand, is not able to explain this relatively fast form of integration, but it is – in its new version - able to analyze and explain...

  3. Higher-Order Adaptive Finite-Element Methods for Kohn-Sham Density Functional Theory

    Science.gov (United States)

    2012-07-03

    equation (25)). The constants c1 and c2 which correspond to the scaling and shifting are determined such that the unwanted eigen-spectrum is mapped into...U. Gross, A. Rubio, Octopus : A tool for the application of time- dependent density functional theory, Phys. Status Solidi B 243 (2006) 24652488. [12

  4. Caliciviruses differ in their functional requirements for eIF4F components

    DEFF Research Database (Denmark)

    Chaudhry, Y.; Nayak, A.; Bordeleau, M-E.

    2006-01-01

    Two classes of viruses, namely members of the Potyviridae and Caliciviridae, use a novel mechanism for the initiation of protein synthesis that involves the interaction of translation initiation factors with a viral protein covalently linked to the viral RNA, known as VPg. The calicivirus VPg...... proteins can interact directly with the initiation factors eIF4E and eIF3. Translation initiation on feline calicivirus (FCV) RNA requires eIF4E because it is inhibited by recombinant 4E-BP1. However, to date, there have been no functional studies carried out with respect to norovirus translation...... translation require the RNA helicase component of the eIF4F complex, namely eIF4A, because translation was sensitive (albeit to different degrees) to a dominant negative form and to a small molecule inhibitor of eIF4A (hippuristanol). These results suggest that calicivirus RNAs differ with respect...

  5. An experimental study of the partitioning of trace elements between rutile and silicate melt as a function of oxygen fugacity

    Directory of Open Access Journals (Sweden)

    GUILHERME MALLMANN

    2014-12-01

    Full Text Available Subduction zone or arc magmas are known to display a characteristic depletion of High Field Strength Elements (HFSE relative to other similarly incompatible elements, which can be attributed to the presence of the accessory mineral rutile (TiO2 in the residual slab. Here we show that the partitioning behavior of vanadium between rutile and silicate melt varies from incompatible (∼0.1 to compatible (∼18 as a function of oxygen fugacity. We also confirm that the HFSE are compatible in rutile, with D(Ta> D(Nb>> (D(Hf>/∼ D(Zr, but that the level of compatibility is strongly dependent on melt composition, with partition coefficients increasing about one order of magnitude with increasing melt polymerization (or decreasing basicity. Our partitioning results also indicate that residual rutile may fractionate U from Th due to the contrasting (over 2 orders of magnitude partitioning between these two elements. We confirm that, in addition to the HFSE, Cr, Cu, Zn and W are compatible in rutile at all oxygen fugacity conditions.

  6. Unusual 5'-regulatory structure and regulation of the murine Mlc1 gene: Lack of promoter-specific functional elements

    Directory of Open Access Journals (Sweden)

    Darja Henseler

    2011-10-01

    Full Text Available Normal 0 21 false false false MicrosoftInternetExplorer4 The MLC1 gene is involved in an autosomal recessive neurological disorder, megalencephalic leucoencephalopathy with subcortical cysts (MLC, which is characterized by macrocephaly during the first year of life and swollen white matter (leucoencephaly. Variants of MLC1 have also been associated with psychiatric disorders such as schizophrenia, major depression and bipolar disorder. Currently, little is known about the encoded protein (MLC1. Judging from its similarity to other known proteins, it may serve as a trans-membrane transporter. However, the function of the encoded protein and its gene regulation has not been investigated successfully so far. We investigated the 5’ region of the murine Mlc1 with respect to regulatory elements for gene expression. A promoter search and an in silico analysis were conducted. Luciferase reporter gene constructs with potential promoter regions were created to study promoter activity in vitro. We found two alternative first exons for the murine Mlc1 but were not able to detect any promoter activity for the investigated reporter gene constructs in different cell lines, thus pointing to the presence of essential cis-acting elements far outside of the region. In silico analysis indicated an uncommon promoter structure for Mlc1, with CCAAT-boxes representing the only noticeable elements.

  7. Shape memory alloy smart knee spacer to enhance knee functionality: model design and finite element analysis.

    Science.gov (United States)

    Gautam, Arvind; Rani, A Bhargavi; Callejas, Miguel A; Acharyya, Swati Ghosh; Acharyya, Amit; Biswas, Dwaipayan; Bhandari, Vasundhra; Sharma, Paresh; Naik, Ganesh R; Gautam, Arvind; Rani, A Bhargavi; Callejas, Miguel A; Acharyya, Swati Ghosh; Acharyya, Amit; Biswas, Dwaipayan; Bhandari, Vasundhra; Sharma, Paresh; Naik, Ganesh R; Acharyya, Swati Ghosh; Sharma, Paresh; Bhandari, Vasundhra; Rani, A Bhargavi; Gautam, Arvind; Biswas, Dwaipayan; Callejas, Miguel A; Acharyya, Amit

    2016-08-01

    In this paper we introduce Shape Memory Alloy (SMA) for designing the tibial part of Total Knee Arthroplasty (TKA) by exploiting the shape-memory and pseudo-elasticity property of the SMA (e.g. NiTi). This would eliminate the drawbacks of the state-of-the art PMMA based knee-spacer including fracture, sustainability, dislocation, tilting, translation and subluxation for tackling the Osteoarthritis especially for the aged people of 45-plus or the athletes. In this paper a Computer Aided Design (CAD) model using SolidWorks for the knee-spacer is presented based on the proposed SMA adopting the state-of-the art industry-standard geometry that is used in the PMMA based spacer design. Subsequently Ansys based Finite Element Analysis is carried out to measure and compare the performance between the proposed SMA based model with the state-of-the art PMMA ones. 81% more bending is noticed in the PMMA based spacer compared to the proposed SMA that would eventually cause fracture and tilting or translation of spacer. Permanent shape deformation of approximately 58.75% in PMMA based spacer is observed compared to recoverable 11% deformation in SMA when same load is applied on both separately.

  8. Retroviral hybrid LTR vector strategy: functional analysis of LTR elements and generation of endothelial cell specificity.

    Science.gov (United States)

    Richardson, T B; Kaspers, J; Porter, C D

    2004-05-01

    Transcriptional targeting is an important aspect of developing gene therapy vectors in order to restrict transgene expression to selected target cells. One approach, when using retroviral vectors, is to replace viral transcriptional control elements within the long terminal repeat (LTR) with sequences imparting the desired specificity. We have developed such hybrid LTR retroviruses, incorporating sequences from each of the human promoters for flt-1, ICAM-2 and KDR, as part of our antivascular cancer gene therapy strategy targeting tumour endothelial cells. The chosen fragments were used to replace the enhancer or combined enhancer and proximal promoter regions of the viral LTR. All showed activity in primary human breast microvascular endothelial cells, with viruses incorporating ICAM-2 sequences exhibiting the greatest specificity versus nonendothelial cells in vitro and a marked alteration of specificity towards endothelial cells in a subcutaneous xenograft model in vivo. Moreover, our study documents the effect of enhancer and/or proximal promoter deletion on LTR activity and reports that differential dependence in different cell lines can give the false impression of specificity if experiments are not adequately controlled. This finding also has implications for other retroviral vector designs seeking to provide transcriptional specificity and for their safety with respect to prevention of gene activation at sites of proviral integration.

  9. 3D Finite element analysis of functionally graded multilayered dental ceramic cores.

    Science.gov (United States)

    Al-Maqtari, Ali Abdullah; Razak, Abdul Aziz Abdul; Hamdi, Mohd

    2014-01-01

    This study aimed at investigating and establishing stress distributions in graded multilayered zirconia/alumina ceramic cores and at veneer-core-cement-dentin interfaces, using finite element analysis (FEA), to facilitate the structural design of ceramic cores through computer modeling. An intact maxillary premolar was digitized using CT scanning. An imaging software, Mimics, was used to reconstruct 3D models based on computed tomography (CT) data saved in DICOM format. Eight different 3D models were created for FEA, where each 3D model was meshed and its bottom boundaries constrained. A static load was applied in the oblique direction. The materials were assumed to be isotropic and homogeneous. Highest von Mises stress values were found in areas directly below the load application point, and stress gradually decreased in occlusal loading direction from the external surface toward the dentin. Stress levels occurring at veneer-ceramic core-cement-dentin interfaces were shown to be lower in multilayered ceramic cores than in single-layer models.

  10. A study to develop the domestic functional requirements of the specific safety systems of CANDU

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Man Woong [Korea Institute of Nuclear Safety, Taejon (Korea, Republic of); Lee, Jae Young; Park, Kun Chul [Handong Global Univ., Pohang (Korea, Republic of)] (and others)

    2003-03-15

    The present research has been made to develop and review critically the functional requirements of the specific safety systems of CANDU such as SDS-1, SDS2, ECCS, and containment. Based on R documents for this, a systematic study was made to develop the domestic regulation statements. Also, the conventional laws are carefully reviewed to see the compatibility to CANDU. Also, the safety assessment method for CANDU was studied by reviewing C documents and recommendation of IAEA. Through the present works, the vague policy in the CANDU safety regulation is cleaning up in a systematic form and a new frame to measure the objective risk of nuclear power plants was developed.

  11. Guidance on the scientific requirements for health claims related to gut and immune function

    DEFF Research Database (Denmark)

    Tetens, Inge

    2011-01-01

    The European Food Safety Authority (EFSA) asked the Panel on Dietetic Products Nutrition and Allergies (NDA) to draft guidance on scientific requirements for health claims related to gut and immune function. This guidance has been drawn from scientific opinions of the NDA Panel on such health...... claims. Thus, this guidance document represents the views of the NDA Panel based on the experience gained to date with the evaluation of health claims in these areas. It is not intended that the document will include an exhaustive list of beneficial effects and studies/outcome measures which...

  12. A study to develop the domestic functional requirements of the specific safety systems of CANDU

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Man Woong; Lee, Jae Young; Bang, Kwang Hyun [Handong Global Univ., Pohang (Korea, Republic of)] (and others)

    2001-03-15

    The present research has been made to develop and review critically the functional requirements of the specific safety systems of CANDU such as SOS-1, SOS-2, ECCS and containment. Based on R documents for this, a systematic study was made to develop the domestic regulation statements. Also, the conventional laws are carefully reviewed to see the compatibility to CANDU. Also, the safety assessment method for CANDU was studied by reviewing C documents and recommendation of IAEA. Through the present works, the vague policy in the CANDU safety regulation is cleaning up in a systematic form and a new frame to measure the objective risk of nuclear power plants was developed.

  13. Grid Information Security Functional Requirement - Fulfilling Information Security of a Smart Grid System

    CERN Document Server

    Ling, Amy Poh Ai; 10.5121/ijgca.2011.2201

    2011-01-01

    This paper describes the background of smart information infrastructure and the needs for smart grid information security. It introduces the conceptual analysis to the methodology with the application of hermeneutic circle and information security functional requirement identification. Information security for the grid market cover matters includes automation and communications industry that affects the operation of electric power systems and the functioning of the utilities that manage them and its awareness of this information infrastructure has become critical to the reliability of the power system. Community benefits from of cost savings, flexibility and deployment along with the establishment of wireless communications. However, concern revolves around the security protections for easily accessible devices such as the smart meter and the related communications hardware. On the other hand, the changing points between traditional versus smart grid networking trend and the information security importance on...

  14. Functions and requirements for tank farm restoration and safe operations, Project W-314. Revision 3

    Energy Technology Data Exchange (ETDEWEB)

    Garrison, R.C.

    1995-02-01

    This Functions and Requirements document (FRD) establishes the basic performance criteria for Project W-314, in accordance with the guidance outlined in the letter from R.W. Brown, RL, to President, WHC, ``Tank Waste Remediation System (TWRS) Project Documentation Methodology,`` 94-PRJ-018, dated 3/18/94. The FRD replaces the Functional Design Criteria (FDC) as the project technical baseline documentation. Project W-314 will improve the reliability of safety related systems, minimize onsite health and safety hazards, and support waste retrieval and disposal activities by restoring and/or upgrading existing Tank Farm facilities and systems. The scope of Project W-314 encompasses the necessary restoration upgrades of the Tank Farms` instrumentation, ventilation, electrical distribution, and waste transfer systems.

  15. Expansion of the Kano model to identify relevant customer segments and functional requirements

    DEFF Research Database (Denmark)

    Atlason, Reynir Smari; Stefansson, Arnaldur Smari; Wietz, Miriam

    2017-01-01

    or a service. A current limitation of the Kano model is that it does not allow developers to visualise which combined sets of FRs would provide the highest satisfaction between different customer segments. In this paper, a stepwise method to address this particular shortcoming is presented. First......The Kano model of customer satisfaction has been widely used to analyse perceived needs of customers. The model provides product developers valuable information about if, and then how much a given functional requirement (FR) will impact customer satisfaction if implemented within a product, system...... are identified. At last, the functions of the chosen segments with the smallest interval, define the FRs appealing to the biggest target group. The proposed extension to the model should assist product developers within various fields to more effectively evaluate which FRs should be implemented when considering...

  16. A Study of the Function of Musical Elements in Entezar Poetry (in Contemporary Period

    Directory of Open Access Journals (Sweden)

    z Bahramian

    2012-09-01

    Full Text Available Literature of “Waiting” (Entezar is one of the motives which was considered by poets and literary critiques especially in early sixties but the approach of critiques to it has been mainly journalistic and not academic. Hence, there is space for academic and scientific researches. For studying such genre, it is valuable to explore and investigate it from different perspectives. The main questions of this article are how the musical function of this kind of poetry works and how this function and the theme of the poem are related. Accordingly, the authors analyze statistically ninety poems of this genre written by twenty great poets to find out the answers of these questions. In analyzing external music of waiting poetry, functions of rhythm in this kind of poetry, harmony between rhythm and theme, rising and falling rhythms, and transparent and opaque rhythms are investigated. Then, investigating marginal music of waiting poetry, the function of rhyme and its relation with the theme of waiting, the word rhyme and its musical link with other words of the verse, rhetorical and spiritual rhymes in this kind of poetry and dynamic and static radifs and their relation with the theme are all studied. Finally, internal music of waiting poetry and repetition and music in the titles of this poetry are explored. One of the results and findings of this article is that the poet of waiting poems unconsciously establishes a deep link between the sad concept of waiting and the form of such poems at the moment of composition.

  17. Analytic function theory of several variables elements of Oka’s coherence

    CERN Document Server

    Noguchi, Junjiro

    2016-01-01

    The purpose of this book is to present the classical analytic function theory of several variables as a standard subject in a course of mathematics after learning the elementary materials (sets, general topology, algebra, one complex variable). This includes the essential parts of Grauert–Remmert's two volumes, GL227(236) (Theory of Stein spaces) and GL265 (Coherent analytic sheaves) with a lowering of the level for novice graduate students (here, Grauert's direct image theorem is limited to the case of finite maps). The core of the theory is "Oka's Coherence", found and proved by Kiyoshi Oka. It is indispensable, not only in the study of complex analysis and complex geometry, but also in a large area of modern mathematics. In this book, just after an introductory chapter on holomorphic functions (Chap. 1), we prove Oka's First Coherence Theorem for holomorphic functions in Chap. 2. This defines a unique character of the book compared with other books on this subject, in which the notion of coherence appear...

  18. The AP-3 adaptor complex is required for vacuolar function in Arabidopsis

    Institute of Scientific and Technical Information of China (English)

    Maria Zwiewka; Elena Feraru; Barbara M(o)ller; Inhwan Hwang; Mugurel I Feraru; Jürgen Kleine-Vehn; Dolf Weijers; Ji(n) Friml

    2011-01-01

    Subcellular trafficking is required for a multitude of functions in eukaryotic cells.It involves regulation of cargo sorting,vesicle formation,trafficking and fusion processes at multiple levels.Adaptor protein (AP) complexes are key regulators of cargo sorting into vesicles in yeast and mammals but their existence and function in plants have not been demonstrated.Here we report the identification of the protein-affected trafficking 4 (pat4) mutant defective in the putative δ subunit of the AP-3 complex.pat4 and pat2,a mutant isolated from the same GFP imaging-based forward genetic screen that lacks a functional putative AP-3 β,as well as dominant negative AP-3 μ transgenic lines display undistinguishable phenotypes characterized by largely normal morphology and development,but strong intracellular accumulation of membrane proteins in aberrant vacuolar structures.All mutants are defective in morphology and function of lytic and protein storage vacuoles (PSVs) but show normal sorting of reserve proteins to PSVs.Immunoprecipitation experiments and genetic studies revealed tight functional and physical associations of putative AP-3 β and AP-3 δ subunits.Furthermore,both proteins are closely linked with putative AP-3 μ and σ subunits and several components of the clathrin and dynamin machineries.Taken together,these results demonstrate that AP complexes,similar to those in other eukaryotes,exist in plants,and that AP-3 plays a specific role in the regulation of biogenesis and function of vacuoles in plant cells.

  19. Finite Element Analysis of Shrinkage in the Interface of Functionally Graded Concrete Segment Used in Shield Tunneling

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    In functionally graded materials (FGM), the problem of interface stability caused by the volume deformation is commonly regarded as the key factor for its performance. Based on test results, in terms of finite element method (FEM) this paper analyzed problems in the shrinkage of functionally graded material interface of shield concrete segment, which was designed and produced by the principle of functionally graded materials. In the analysis model, the total shrinkage of concrete was converted into the thermal shrinkage by means of the method of "Equivalent Temperature Difference". Consequently, the shrinkage stress of interface layer was calculated and compared with the bond strength of interface layer.The results indicated that the volume deformation of two-phase materials of functionally graded concrete (FGC) segment, which were the concrete cover and the concrete structure layer, showed better compatibility and the tension stress of interface layer, which was resulted from the shrinkage of concrete and calculated by ANSYS, was less than the bond strength of interface layer. Therefore, the interface stability of functionally graded concrete segment was good and the sliding deformation of interface layer would not generate.

  20. Combined effects of simulated acid rain and lanthanum chloride on chloroplast structure and functional elements in rice.

    Science.gov (United States)

    Hu, Huiqing; Wang, Lihong; Zhou, Qing; Huang, Xiaohua

    2016-05-01

    Acid rain and rare earth element (REE) pollution exist simultaneously in many agricultural regions. However, how REE pollution and acid rain affect plant growth in combination remains largely unknown. In this study, the combined effects of simulated acid rain and lanthanum chloride (LaCl3) on chloroplast morphology, chloroplast ultrastructure, functional element contents, chlorophyll content, and the net photosynthetic rate (P n) in rice (Oryza sativa) were investigated by simulating acid rain and rare earth pollution. Under the combined treatment of simulated acid rain at pH 4.5 and 0.08 mM LaCl3, the chloroplast membrane was smooth, proteins on this membrane were uniform, chloroplast structure was integrated, and the thylakoids were orderly arranged, and simulated acid rain and LaCl3 exhibited a mild antagonistic effect; the Mg, Ca, Mn contents, the chlorophyll content, and the P n increased under this combined treatment, with a synergistic effect of simulated acid rain and LaCl3. Under other combined treatments of simulated acid rain and LaCl3, the chloroplast membrane surface was uneven, a clear "hole" was observed on the surface of chloroplasts, and the thylakoids were dissolved and loose; and the P n and contents of functional elements (P, Mg, K, Ca, Mn, Fe, Ni, Cu, Zn and Mo) and chlorophyll decreased. Under these combined treatments, simulated acid rain and LaCl3 exhibited a synergistic effect. Based on the above results, a model of the combined effects of simulated acid rain and LaCl3 on plant photosynthesis was established in order to reveal the combined effects on plant photosynthesis, especially on the photosynthetic organelle-chloroplast. Our results would provide some references for further understanding the mechanism of the combined effects of simulated acid rain and LaCl3 on plant photosynthesis.

  1. Differing Requirements for MALT1 Function in Peripheral B Cell Survival and Differentiation.

    Science.gov (United States)

    Lee, Peishan; Zhu, Zilu; Hachmann, Janna; Nojima, Takuya; Kitamura, Daisuke; Salvesen, Guy; Rickert, Robert C

    2017-02-01

    During a T cell-dependent immune response, formation of the germinal center (GC) is essential for the generation of high-affinity plasma cells and memory B cells. The canonical NF-κB pathway has been implicated in the initiation of GC reaction, and defects in this pathway have been linked to immune deficiencies. The paracaspase MALT1 plays an important role in regulating NF-κB activation upon triggering of Ag receptors. Although previous studies have reported that MALT1 deficiency abrogates the GC response, the relative contribution of B cells and T cells to the defective phenotype remains unclear. We used chimeric mouse models to demonstrate that MALT1 function is required in B cells for GC formation. This role is restricted to BCR signaling where MALT1 is critical for B cell proliferation and survival. Moreover, the proapoptotic signal transmitted in the absence of MALT1 is dominant to the prosurvival effects of T cell-derived stimuli. In addition to GC B cell differentiation, MALT1 is required for plasma cell differentiation, but not mitogenic responses. Lastly, we show that ectopic expression of Bcl-2 can partially rescue the GC phenotype in MALT1-deficient animals by prolonging the lifespan of BCR-activated B cells, but plasma cell differentiation and Ab production remain defective. Thus, our data uncover previously unappreciated aspects of MALT1 function in B cells and highlight its importance in humoral immunity.

  2. Structure-function analysis of myomaker domains required for myoblast fusion.

    Science.gov (United States)

    Millay, Douglas P; Gamage, Dilani G; Quinn, Malgorzata E; Min, Yi-Li; Mitani, Yasuyuki; Bassel-Duby, Rhonda; Olson, Eric N

    2016-02-23

    During skeletal muscle development, myoblasts fuse to form multinucleated myofibers. Myomaker [Transmembrane protein 8c (TMEM8c)] is a muscle-specific protein that is essential for myoblast fusion and sufficient to promote fusion of fibroblasts with muscle cells; however, the structure and biochemical properties of this membrane protein have not been explored. Here, we used CRISPR/Cas9 mutagenesis to disrupt myomaker expression in the C2C12 muscle cell line, which resulted in complete blockade to fusion. To define the functional domains of myomaker required to direct fusion, we established a heterologous cell-cell fusion system, in which fibroblasts expressing mutant versions of myomaker were mixed with WT myoblasts. Our data indicate that the majority of myomaker is embedded in the plasma membrane with seven membrane-spanning regions and a required intracellular C-terminal tail. We show that myomaker function is conserved in other mammalian orthologs; however, related family members (TMEM8a and TMEM8b) do not exhibit fusogenic activity. These findings represent an important step toward deciphering the cellular components and mechanisms that control myoblast fusion and muscle formation.

  3. Topography of thalamic projections requires attractive and repulsive functions of Netrin-1 in the ventral telencephalon.

    Directory of Open Access Journals (Sweden)

    Ashton W Powell

    2008-05-01

    Full Text Available Recent studies have demonstrated that the topography of thalamocortical (TC axon projections is initiated before they reach the cortex, in the ventral telencephalon (VTel. However, at this point, the molecular mechanisms patterning the topography of TC projections in the VTel remains poorly understood. Here, we show that a long-range, high-rostral to low-caudal gradient of Netrin-1 in the VTel is required in vivo for the topographic sorting of TC axons to distinct cortical domains. We demonstrate that Netrin-1 is a chemoattractant for rostral thalamic axons but functions as a chemorepulsive cue for caudal thalamic axons. In accordance with this model, DCC is expressed in a high-rostromedial to low-caudolateral gradient in the dorsal thalamus (DTh, whereas three Unc5 receptors (Unc5A-C show graded expression in the reverse orientation. Finally, we show that DCC is required for the attraction of rostromedial thalamic axons to the Netrin-1-rich, anterior part of the VTel, whereas DCC and Unc5A/C receptors are required for the repulsion of caudolateral TC axons from the same Netrin-1-rich region of the VTel. Our results demonstrate that a long-range gradient of Netrin-1 acts as a counteracting force from ephrin-A5 to control the topography of TC projections before they enter the cortex.

  4. Cookie- versus cracker-baking--what's the difference? Flour functionality requirements explored by SRC and alveography.

    Science.gov (United States)

    Kweon, Meera; Slade, Louise; Levine, Harry; Gannon, Diane

    2014-01-01

    The many differences between cookie- and cracker-baking are discussed and described in terms of the functionality, and functional requirements, of the major biscuit ingredients--flour and sugar. Both types of products are similar in their major ingredients, but different in their formulas and processes. One of the most important and consequential differences between traditional cracker and cookie formulas is sugar (i.e., sucrose) concentration: usually lower than 30% in a typical cracker formula and higher than 30% in a typical cookie formula. Gluten development is facilitated in lower-sugar cracker doughs during mixing and sheeting; this is a critical factor linked to baked-cracker quality. Therefore, soft wheat flours with greater gluten quality and strength are typically preferred for cracker production. In contrast, the concentrated aqueous sugar solutions existing in high-sugar cookie doughs generally act as an antiplasticizer, compared with water alone, so gluten development during dough mixing and starch gelatinization/pasting during baking are delayed or prevented in most cookie systems. Traditional cookies and crackers are low-moisture baked goods, which are desirably made from flours with low water absorption [low water-holding capacity (WHC)], and low levels of damaged starch and water-soluble pentosans (i.e., water-accessible arabinoxylans). Rheological (e.g., alveography) and baking tests are often used to evaluate flour quality for baked-goods applications, but the solvent retention capacity (SRC) method (AACC 56-11) is a better diagnostic tool for predicting the functional contribution of each individual flour functional component, as well as the overall functionality of flours for cookie- and/or cracker-baking.

  5. The role of reserves and anthropogenic elements for functional connectivity and resilience of ephemeral habitats

    Science.gov (United States)

    Uden, Daniel R.; Hellman, Michelle L.; Angeler, David G.; Allen, Craig R.

    2014-01-01

    Ecological reserves provide important wildlife habitat in many landscapes, and the functional connectivity of reserves and other suitable habitat patches is crucial for the persistence and resilience of spatially structured populations. To maintain or increase connectivity at spatial scales larger than individual patches, conservation actions may focus on creating and maintaining reserves and/or influencing management on non-reserves. Using a graph-theoretic approach, we assessed the functional connectivity and spatial distribution of wetlands in the Rainwater Basin of Nebraska, USA, an intensively cultivated agricultural matrix, at four assumed, but ecologically realistic, anuran dispersal distances. We compared connectivity in the current landscape to the historical landscape and putative future landscapes, and evaluated the importance of individual and aggregated reserve and non-reserve wetlands for maintaining connectivity. Connectivity was greatest in the historical landscape, where wetlands were also the most densely distributed. The construction of irrigation reuse pits for water storage has maintained connectivity in the current landscape by replacing destroyed wetlands, but these pits likely provide suboptimal habitat. Also, because there are fewer total wetlands (i.e., wetlands and irrigation reuse pits) in the current landscape than the historical landscape, and because the distribution of current wetlands is less clustered than that of historical wetlands, larger and longer dispersing, sometimes nonnative species may be favored over smaller, shorter dispersing species of conservation concern. Because of their relatively low number, wetland reserves do not affect connectivity as greatly as non-reserve wetlands or irrigation reuse pits; however, they likely provide the highest quality anuran habitat. To improve future levels of resilience in this wetland habitat network, management could focus on continuing to improve the conservation status of non

  6. Streptococcal group B integrative and mobilizable element IMESag-rpsI encodes a functional relaxase involved in its transfer

    Science.gov (United States)

    Lorenzo-Diaz, Fabian; Fernández-Lopez, Cris; Douarre, Pierre-Emmanuel; Baez-Ortega, Adrian; Flores, Carlos; Glaser, Philippe

    2016-01-01

    Streptococcus agalactiae or Group B Streptococcus (GBS) are opportunistic bacteria that can cause lethal sepsis in children and immuno-compromised patients. Their genome is a reservoir of mobile genetic elements that can be horizontally transferred. Among them, integrative and conjugative elements (ICEs) and the smaller integrative and mobilizable elements (IMEs) primarily reside in the bacterial chromosome, yet have the ability to be transferred between cells by conjugation. ICEs and IMEs are therefore a source of genetic variability that participates in the spread of antibiotic resistance. Although IMEs seem to be the most prevalent class of elements transferable by conjugation, they are poorly known. Here, we have studied a GBS-IME, termed IMESag-rpsI, which is widely distributed in GBS despite not carrying any apparent virulence trait. Analyses of 240 whole genomes showed that IMESag-rpsI is present in approximately 47% of the genomes, has a roughly constant size (approx. 9 kb) and is always integrated at a single location, the 3′-end of the gene encoding the ribosomal protein S9 (rpsI). Based on their genetic variation, several IMESag-rpsI types were defined (A–J) and classified in clonal complexes (CCs). CC1 was the most populated by IMESag-rpsI (more than 95%), mostly of type-A (71%). One CC1 strain (S. agalactiae HRC) was deep-sequenced to understand the rationale underlying type-A IMESag-rpsI enrichment in GBS. Thirteen open reading frames were identified, one of them encoding a protein (MobSag) belonging to the broadly distributed family of relaxases MOBV1. Protein MobSag was purified and, by a newly developed method, shown to cleave DNA at a specific dinucleotide. The S. agalactiae HRC-IMESag-rpsI is able to excise from the chromosome, as shown by the presence of circular intermediates, and it harbours a fully functional mobilization module. Further, the mobSag gene encoded by this mobile element is able to promote plasmid transfer among pneumococcal

  7. The Analysis of Thin Wires Using Higher-Order Elements and Basis Functions

    Energy Technology Data Exchange (ETDEWEB)

    Champagne, N J; Wilton, D R; Rockway, J W

    2006-01-23

    Thin wire analysis was applied to curved wire segments in [1], but a special procedure was needed to evaluate the self and near-self terms. The procedure involved associating the singular behavior with a straight segment tangent to the curved source segment, permitting use of algorithms for straight wires. Recently, a procedure that avoids the singularity extraction for straight wires was presented in [2-4]. In this paper, the approach in [4] is applied to curved (or higher-order) wires using a procedure similar to that used in [1] for singularity extraction. Here, the straight tangent segment is used to determine the quadrature rules to be used on the curved segment. The result is a formulation that allows for a general mixture of higher-order basis functions [5] and higher-order wire segments.

  8. The Drosophila Translational Control Element (TCE) is required for high-level transcription of many genes that are specifically expressed in testes.

    Science.gov (United States)

    Katzenberger, Rebeccah J; Rach, Elizabeth A; Anderson, Ashley K; Ohler, Uwe; Wassarman, David A

    2012-01-01

    To investigate the importance of core promoter elements for tissue-specific transcription of RNA polymerase II genes, we examined testis-specific transcription in Drosophila melanogaster. Bioinformatic analyses of core promoter sequences from 190 genes that are specifically expressed in testes identified a 10 bp A/T-rich motif that is identical to the translational control element (TCE). The TCE functions in the 5' untranslated region of Mst(3)CGP mRNAs to repress translation, and it also functions in a heterologous gene to regulate transcription. We found that among genes with focused initiation patterns, the TCE is significantly enriched in core promoters of genes that are specifically expressed in testes but not in core promoters of genes that are specifically expressed in other tissues. The TCE is variably located in core promoters and is conserved in melanogaster subgroup species, but conservation dramatically drops in more distant species. In transgenic flies, short (300-400 bp) genomic regions containing a TCE directed testis-specific transcription of a reporter gene. Mutation of the TCE significantly reduced but did not abolish reporter gene transcription indicating that the TCE is important but not essential for transcription activation. Finally, mutation of testis-specific TFIID (tTFIID) subunits significantly reduced the transcription of a subset of endogenous TCE-containing but not TCE-lacking genes, suggesting that tTFIID activity is limited to TCE-containing genes but that tTFIID is not an obligatory regulator of TCE-containing genes. Thus, the TCE is a core promoter element in a subset of genes that are specifically expressed in testes. Furthermore, the TCE regulates transcription in the context of short genomic regions, from variable locations in the core promoter, and both dependently and independently of tTFIID. These findings set the stage for determining the mechanism by which the TCE regulates testis-specific transcription and understanding the

  9. Requirement for ergosterol in V-ATPase function underlies antifungal activity of azole drugs.

    Directory of Open Access Journals (Sweden)

    Yong-Qiang Zhang

    Full Text Available Ergosterol is an important constituent of fungal membranes. Azoles inhibit ergosterol biosynthesis, although the cellular basis for their antifungal activity is not understood. We used multiple approaches to demonstrate a critical requirement for ergosterol in vacuolar H(+-ATPase function, which is known to be essential for fungal virulence. Ergosterol biosynthesis mutants of S. cerevisiae failed to acidify the vacuole and exhibited multiple vma(- phenotypes. Extraction of ergosterol from vacuolar membranes also inactivated V-ATPase without disrupting membrane association of its subdomains. In both S. cerevisiae and the fungal pathogen C. albicans, fluconazole impaired vacuolar acidification, whereas concomitant ergosterol feeding restored V-ATPase function and cell growth. Furthermore, fluconazole exacerbated cytosolic Ca(2+ and H(+ surges triggered by the antimicrobial agent amiodarone, and impaired Ca(2+ sequestration in purified vacuolar vesicles. These findings provide a mechanistic basis for the synergy between azoles and amiodarone observed in vitro. Moreover, we show the clinical potential of this synergy in treatment of systemic fungal infections using a murine model of Candidiasis. In summary, we demonstrate a new regulatory component in fungal V-ATPase function, a novel role for ergosterol in vacuolar ion homeostasis, a plausible cellular mechanism for azole toxicity in fungi, and preliminary in vivo evidence for synergism between two antifungal agents. New insights into the cellular basis of azole toxicity in fungi may broaden therapeutic regimens for patient populations afflicted with systemic fungal infections.

  10. Balancing functional and nutritional quality of oils and fats: Current requirements and future trends

    Directory of Open Access Journals (Sweden)

    Van den Bremt Karen

    2012-03-01

    Full Text Available Oils and fats play an important role in the structure, aroma and stability of a wide variety of food products, as well as in their nutritional properties. For Puratos, a producer of ingredients for bakery, patisserie and chocolate sector, functionality and taste are of utmost importance, but the company also wants to contribute to the balanced diet of consumers. Vegetable oils and fats are used in margarines and releasing agents, vegetable creams, compound chocolate, fillings and emulsifiers. Each application requires an oil or fat with specific physicochemical properties in order to ensure the optimal structure, stability and taste of the end product. Traditionally, (partially hydrogenated vegetable oils deliver important functional characteristics concerning crystallization behaviour, directly linked with the workability, melting properties, stability and mouth feel of the food product. However, due to negative nutritional implications, trans fats are to be replaced by healthier alternatives, preferably not by saturated fats. Consumers – and in some regions, legal instances – demand transfree or hydro-free products while not compromising on taste. Alternative fats and oils will be discussed concerning their functional and nutritional properties.

  11. Androgen Receptor Coactivator ARID4B Is Required for the Function of Sertoli Cells in Spermatogenesis.

    Science.gov (United States)

    Wu, Ray-Chang; Zeng, Yang; Pan, I-Wen; Wu, Mei-Yi

    2015-09-01

    Defects in spermatogenesis, a process that produces spermatozoa inside seminiferous tubules of the testis, result in male infertility. Spermatogenic progression is highly dependent on a microenvironment provided by Sertoli cells, the only somatic cells and epithelium of seminiferous tubules. However, genes that regulate such an important activity of Sertoli cells are poorly understood. Here, we found that AT-rich interactive domain 4B (ARID4B), is essential for the function of Sertoli cells to regulate spermatogenesis. Specifically, we generated Sertoli cell-specific Arid4b knockout (Arid4bSCKO) mice, and showed that the Arid4bSCKO male mice were completely infertile with impaired testis development and significantly reduced testis size. Importantly, severe structural defects accompanied by loss of germ cells and Sertoli cell-only phenotype were found in many seminiferous tubules of the Arid4bSCKO testes. In addition, maturation of Sertoli cells was significantly delayed in the Arid4bSCKO mice, associated with delayed onset of spermatogenesis. Spermatogenic progression was also defective, showing an arrest at the round spermatid stage in the Arid4bSCKO testes. Interestingly, we showed that ARID4B functions as a "coactivator" of androgen receptor and is required for optimal transcriptional activation of reproductive homeobox 5, an androgen receptor target gene specifically expressed in Sertoli cells and critical for spermatogenesis. Together, our study identified ARID4B to be a key regulator of Sertoli cell function important for male germ cell development.

  12. From Elements to Function: Toward Unifying Ecological Stoichiometry and Trait-Based Ecology

    Directory of Open Access Journals (Sweden)

    Cédric L. Meunier

    2017-05-01

    Full Text Available The theories developed in ecological stoichiometry (ES are fundamentally based on traits. Traits directly linked to cell/body stoichiometry, such as nutrient uptake and storage, as well as the associated trade-offs, have the potential to shape ecological interactions such as competition and predation within ecosystems. Further, traits that indirectly influence and are influenced by nutritional requirements, such as cell/body size and growth rate, are tightly linked to organismal stoichiometry. Despite their physiological and ecological relevance, traits are rarely explicitly integrated in the framework of ES and, currently, the major challenge is to more closely inter-connect ES with trait-based ecology (TBE. Here, we highlight four interconnected nutrient trait groups, i.e., acquisition, body stoichiometry, storage, and excretion, which alter interspecific competition in autotrophs and heterotrophs. We also identify key differences between producer-consumer interactions in aquatic and terrestrial ecosystems. For instance, our synthesis shows that, in contrast to aquatic ecosystems, traits directly influencing herbivore stoichiometry in forested ecosystems should play only a minor role in the cycling of nutrients. We furthermore describe how linking ES and TBE can help predict the ecosystem consequences of global change. The concepts we highlight here allow us to predict that increasing N:P ratios in ecosystems should shift trait dominances in communities toward species with higher optimal N:P ratios and higher P uptake affinity, while decreasing N retention and increasing P storage.

  13. The methodical approach to determining the heterogeneity of cognitive function in preschool children requiring correction of speech impediments

    Directory of Open Access Journals (Sweden)

    Petrenko N.B.

    2016-02-01

    Full Text Available Introduction. It has been confirmed that children who suffer from speech impediments may experience difficulties in their cognitive activity, limitations in communication, asociality and sense detachment. It is also clear that these children require not only logopedic treatment, but also assistance in developing functions of their cognitive and mental activities. Aims. To identify the case of uniformity lack of cognitive and somatomental functions of 5-6 year old children with speech impediments in a group; to evaluate the method used for this research. Methods. Use estimates of major mental and cognitive activities by means of tests increases the difficulty. Scores from 1 to 10 were given. Such factors as movement coordination, musicality and body plasticity were taken into consideration too. StatSoft STATISTICA10.0. programme was used to run the statistical analysis. Results. The changes of the group with uniformity of physical, cognitive, somatomental and dance abilities were analysed and estimated at the beginning and at the end of the academic year. The results of the claster analysis have shown that the children managed to develop their cognitive and somatomental abilities. Also it was estimated that the level of uniformity has increased in the group. Conclusions. Having done the research we can state that with the help of cluster analysis children with speech impediments can be grouped according to their physical, cognitive, somatomental and dance abilities. With the help of the results of the claster analysis that notifies that the children managed to develop their cognitive and somatomental abilities, we can observe the positivie effects of the suggested dance-cognitive teaching elements in an educational programme.

  14. Sulfur Atom in its Bound State Is a Unique Element Involved in Physiological Functions in Mammals

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    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.

  15. Vibration Prediction Method of Electric Machines by using Experimental Transfer Function and Magnetostatic Finite Element Analysis

    Science.gov (United States)

    Saito, A.; Kuroishi, M.; Nakai, H.

    2016-09-01

    This paper concerns the noise and structural vibration caused by rotating electric machines. Special attention is given to the magnetic-force induced vibration response of interior-permanent magnet machines. In general, to accurately predict and control the vibration response caused by the electric machines, it is inevitable to model not only the magnetic force induced by the fluctuation of magnetic fields, but also the structural dynamic characteristics of the electric machines and surrounding structural components. However, due to complicated boundary conditions and material properties of the components, such as laminated magnetic cores and varnished windings, it has been a challenge to compute accurate vibration response caused by the electric machines even after their physical models are available. In this paper, we propose a highly-accurate vibration prediction method that couples experimentally-obtained discrete structural transfer functions and numerically-obtained distributed magnetic-forces. The proposed vibration synthesis methodology has been applied to predict vibration responses of an interior permanent magnet machine. The results show that the predicted vibration response of the electric machine agrees very well with the measured vibration response for several load conditions, for wide frequency ranges.

  16. Dsc E3 ligase localization to the Golgi requires the ATPase Cdc48 and cofactor Ufd1 for activation of Sterol Regulatory Element-binding Protein in fission yeast.

    Science.gov (United States)

    Burr, Risa; Ribbens, Diedre; Raychaudhuri, Sumana; Stewart, Emerson V; Ho, Jason; Espenshade, Peter J

    2017-08-18

    Sterol regulatory element-binding proteins (SREBPs) in the fission yeast Schizosaccharomyces pombe regulate lipid homeostasis and the hypoxic response under conditions of low sterol or oxygen availability. SREBPs are cleaved in the Golgi through the combined action of the Dsc E3 ligase complex, the rhomboid protease Rbd2, and the essential ATPases Associated with diverse cellular Activities (AAA+) ATPase Cdc48. The soluble SREBP N-terminal transcription factor domain is then released in the cytosol to enter the nucleus and regulate gene expression. Previously, we reported that Cdc48 binding to Rbd2 is required for Rbd2-mediated SREBP cleavage. Here, using affinity chromatography and mass spectrometry experiments, we identified Cdc48-binding proteins in S. pombe, generating a list of many previously unknown potential Cdc48 binding partners. We show that the established Cdc48 cofactor Ufd1 is required for SREBP cleavage but does not interact with the Cdc48-Rbd2 complex. Cdc48-Ufd1 is instead required at a step prior to Rbd2 function, during Golgi localization of the Dsc E3 ligase complex. Together, these findings demonstrate that two distinct Cdc48 complexes - Cdc48-Ufd1 and Cdc48-Rbd2 - are required for SREBP activation and low-oxygen adaptation in S. pombe. Copyright © 2017, The American Society for Biochemistry and Molecular Biology.

  17. Tsunami waveform inversion by numerical finite-elements Green’s functions

    Directory of Open Access Journals (Sweden)

    A. Piatanesi

    2001-01-01

    Full Text Available During the last few years, the steady increase in the quantity and quality of the data concerning tsunamis has led to an increasing interest in the inversion problem for tsunami data. This work addresses the usually ill-posed problem of the hydrodynamical inversion of tsunami tide-gage records to infer the initial sea perturbation. We use an inversion method for which the data space consists of a given number of waveforms and the model parameter space is represented by the values of the initial water elevation field at a given number of points. The forward model, i.e. the calculation of the synthetic tide-gage records from an initial water elevation field, is based on the linear shallow water equations and is simply solved by applying the appropriate Green’s functions to the known initial state. The inversion of tide-gage records to determine the initial state results in the least square inversion of a rectangular system of linear equations. When the inversions are unconstrained, we found that in order to attain good results, the dimension of the data space has to be much larger than that of the model space parameter. We also show that a large number of waveforms is not sufficient to ensure a good inversion if the corresponding stations do not have a good azimuthal coverage with respect to source directivity. To improve the inversions we use the available a priori information on the source, generally coming from the inversion of seismological data. In this paper we show how to implement very common information about a tsunamigenic seismic source, i.e. the earthquake source region, as a set of spatial constraints. The results are very satisfactory, since even a rough localisation of the source enables us to invert correctly the initial elevation field.

  18. Steam Reforming, 6-in. Bench-Scale Design and Testing Project -- Technical and Functional Requirements Description

    Energy Technology Data Exchange (ETDEWEB)

    Losinski, Sylvester John; Marshall, Douglas William

    2002-08-01

    Feasibility studies and technology development work are currently being performed on several processes to treat radioactive liquids and solids currently stored at the Idaho Nuclear Technology and Engineering Center (INTEC), located within the Idaho National Engineering and Environmental Laboratory (INEEL). These studies and development work will be used to select a treatment process for treatment of the radioactive liquids and solids to meet treatment milestones of the Settlement Agreement between the Department of Energy and the State of Idaho. One process under consideration for treating the radioactive liquids and solids, specifically Sodium-Bearing Waste (SBW) and tank heel solids, is fluid bed steam reforming (FBSR). To support both feasibility and development studies a bench-scale FBSR is being designed and constructed. This report presents the technical and functional requirements, experimental objectives, process flow sheets, and equipment specifications for the bench-scale FBSR.

  19. Palmitoylation of TEAD Transcription Factors Is Required for Their Stability and Function in Hippo Pathway Signaling.

    Science.gov (United States)

    Noland, Cameron L; Gierke, Sarah; Schnier, Paul D; Murray, Jeremy; Sandoval, Wendy N; Sagolla, Meredith; Dey, Anwesha; Hannoush, Rami N; Fairbrother, Wayne J; Cunningham, Christian N

    2016-01-05

    The Hippo signaling pathway is responsible for regulating the function of TEAD family transcription factors in metazoans. TEADs, with their co-activators YAP/TAZ, are critical for controlling cell differentiation and organ size through their transcriptional activation of genes involved in cell growth and proliferation. Dysregulation of the Hippo pathway has been implicated in multiple forms of cancer. Here, we identify a novel form of regulation of TEAD family proteins. We show that human TEADs are palmitoylated at a universally conserved cysteine, and report the crystal structures of the human TEAD2 and TEAD3 YAP-binding domains in their palmitoylated forms. These structures show a palmitate bound within a highly conserved hydrophobic cavity at each protein's core. Our findings also demonstrate that this modification is required for proper TEAD folding and stability, indicating a potential new avenue for pharmacologically regulating the Hippo pathway through the modulation of TEAD palmitoylation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Effects of rare earth elements La and Yb on the morphological and functional development of zebrafish embryos

    Institute of Scientific and Technical Information of China (English)

    Jun'an Cui; Zhiyong Zhang; Wei Bai; Ligang Zhang; Xiao He; Yuhui Ma; Yan Liu; Zhifang Chai

    2012-01-01

    In recent years,with the wide applications and mineral exploitation of rare earth elements,their potential environmental and health effects have caused increasing public concern.Effect of rare earth elements La and Yb on the morphological and functional development of zebrafish embryos were studied.The embryos were exposed to La3+ or Yb3+ at 0,0.01,0.1,0.3,0.5 and 1.0 mmol/L,respectively.Early life stage parameters such as egg and embryo mortality,gastrula development,tail detachment,eyes,somite formation,circulatory system,pigmentation,malformations,hatching rate,length of larvae and mortality were investigated.The results showed La3+ and Yb3+ delayed zebrafish embryo and larval development,decreased survival and hatching rates,and caused tail malformation in a concentration-dependent way.Moreover,heavy rare-earth ytterbium led to more severe acute toxicity of zebrafish embryo than light rare-earth lanthanum.

  1. A functional selection of viral genetic elements in cultured cells to identify hepatitis C virus RNA translation inhibitors.

    Science.gov (United States)

    Jaffrelo, Loic; Chabas, Sandrine; Reigadas, Sandrine; Pflieger, Aude; Wychowski, Czeslaw; Rumi, Julie; Ventura, Michel; Toulmé, Jean-Jacques; Staedel, Cathy

    2008-09-01

    We developed a functional selection system based on randomized genetic elements (GE) to identify potential regulators of hepatitis C virus (HCV) RNA translation, a process initiated by an internal ribosomal entry site (IRES). A retroviral HCV GE library was introduced into HepG2 cells, stably expressing the Herpes simplex virus thymidine kinase (HSV-TK) under the control of the HCV IRES. Cells that expressed transduced GEs inhibiting HSV-TK were selected via their resistance to ganciclovir. Six major GEs were rescued by PCR on the selected cell DNA and identified as HCV elements. We validated our strategy by further studying the activity of one of them, GE4, encoding the 5' end of the viral NS5A gene. GE4 inhibited HCV IRES-, but not cap-dependent, reporter translation in human hepatic cell lines and inhibited HCV infection at a post-entry step, decreasing by 85% the number of viral RNA copies. This method can be applied to the identification of gene expression regulators.

  2. Functional elements associated with hepatic regeneration in living donors after right hepatic lobectomy.

    Science.gov (United States)

    Everson, Gregory T; Hoefs, John C; Niemann, Claus U; Olthoff, Kim M; Dupuis, Robert; Lauriski, Shannon; Herman, Andrea; Milne, Norah; Gillespie, Brenda W; Goodrich, Nathan P; Everhart, James E

    2013-03-01

    We quantified the rates of hepatic regeneration and functional recovery for 6 months after right hepatic lobectomy in living donors for liver transplantation. Twelve donors were studied pre-donation (baseline); 8 were retested at a mean ± SD of 11±3 days after donation (T1), 10 were retested at a mean of 91±9 days after donation (T2), and 10 were retested at a mean of 185±17 days after donation (T3). Liver and spleen volumes were measured with computed tomography (CT) and single-photon emission computed tomography (SPECT). Hepatic metabolism was assessed with caffeine and erythromycin, and hepatic blood flow (HBF) was assessed with cholates, galactose, and the perfused hepatic mass (PHM) by SPECT. The regeneration rates (mL kg(-1) of body weight day(-1)) by CT were 0.60±0.22 mL from the baseline to T1, 0.05±0.02 mL from T1 to T2, and 0.01±0.01 from T2 to T3; by SPECT they were 0.54±0.20, 0.04±0.01, and 0.01±0.02, respectively. At T3, the liver volumes were 84%±7% of the baseline according to CT and 92%±13% of the baseline according to SPECT. Changes in the hepatic metabolism did not achieve statistical significance. At T1, the unadjusted clearance ratios with respect to the baseline were 0.75±0.07 for intravenous cholate (Pliver were up to 50% greater than the baseline values, suggesting recruitment of HBF by the regenerating liver. Increased cholate shunt, increased spleen volume, and decreased platelet count, were consistent with an altered portal circulation. In conclusion, initial hepatic regeneration is rapid, accounts for nearly two-thirds of total regeneration, and is associated with increases in HBF and cholate uptake. Right lobe donation alters the portal circulation of living donors, but the long-term clinical consequences, if there are any, are unknown.

  3. Host ESCRT proteins are required for bromovirus RNA replication compartment assembly and function.

    Directory of Open Access Journals (Sweden)

    Arturo Diaz

    2015-03-01

    Full Text Available Positive-strand RNA viruses genome replication invariably is associated with vesicles or other rearranged cellular membranes. Brome mosaic virus (BMV RNA replication occurs on perinuclear endoplasmic reticulum (ER membranes in ~70 nm vesicular invaginations (spherules. BMV RNA replication vesicles show multiple parallels with membrane-enveloped, budding retrovirus virions, whose envelopment and release depend on the host ESCRT (endosomal sorting complexes required for transport membrane-remodeling machinery. We now find that deleting components of the ESCRT pathway results in at least two distinct BMV phenotypes. One group of genes regulate RNA replication and the frequency of viral replication complex formation, but had no effect on spherule size, while a second group of genes regulate RNA replication in a way or ways independent of spherule formation. In particular, deleting SNF7 inhibits BMV RNA replication > 25-fold and abolishes detectable BMV spherule formation, even though the BMV RNA replication proteins accumulate and localize normally on perinuclear ER membranes. Moreover, BMV ESCRT recruitment and spherule assembly depend on different sets of protein-protein interactions from those used by multivesicular body vesicles, HIV-1 virion budding, or tomato bushy stunt virus (TBSV spherule formation. These and other data demonstrate that BMV requires cellular ESCRT components for proper formation and function of its vesicular RNA replication compartments. The results highlight growing but diverse interactions of ESCRT factors with many viruses and viral processes, and potential value of the ESCRT pathway as a target for broad-spectrum antiviral resistance.

  4. Host ESCRT proteins are required for bromovirus RNA replication compartment assembly and function.

    Science.gov (United States)

    Diaz, Arturo; Zhang, Jiantao; Ollwerther, Abigail; Wang, Xiaofeng; Ahlquist, Paul

    2015-03-01

    Positive-strand RNA viruses genome replication invariably is associated with vesicles or other rearranged cellular membranes. Brome mosaic virus (BMV) RNA replication occurs on perinuclear endoplasmic reticulum (ER) membranes in ~70 nm vesicular invaginations (spherules). BMV RNA replication vesicles show multiple parallels with membrane-enveloped, budding retrovirus virions, whose envelopment and release depend on the host ESCRT (endosomal sorting complexes required for transport) membrane-remodeling machinery. We now find that deleting components of the ESCRT pathway results in at least two distinct BMV phenotypes. One group of genes regulate RNA replication and the frequency of viral replication complex formation, but had no effect on spherule size, while a second group of genes regulate RNA replication in a way or ways independent of spherule formation. In particular, deleting SNF7 inhibits BMV RNA replication > 25-fold and abolishes detectable BMV spherule formation, even though the BMV RNA replication proteins accumulate and localize normally on perinuclear ER membranes. Moreover, BMV ESCRT recruitment and spherule assembly depend on different sets of protein-protein interactions from those used by multivesicular body vesicles, HIV-1 virion budding, or tomato bushy stunt virus (TBSV) spherule formation. These and other data demonstrate that BMV requires cellular ESCRT components for proper formation and function of its vesicular RNA replication compartments. The results highlight growing but diverse interactions of ESCRT factors with many viruses and viral processes, and potential value of the ESCRT pathway as a target for broad-spectrum antiviral resistance.

  5. LRGUK-1 is required for basal body and manchette function during spermatogenesis and male fertility.

    Directory of Open Access Journals (Sweden)

    Yan Liu

    2015-03-01

    Full Text Available Male infertility affects at least 5% of reproductive age males. The most common pathology is a complex presentation of decreased sperm output and abnormal sperm shape and motility referred to as oligoasthenoteratospermia (OAT. For the majority of OAT men a precise diagnosis cannot be provided. Here we demonstrate that leucine-rich repeats and guanylate kinase-domain containing isoform 1 (LRGUK-1 is required for multiple aspects of sperm assembly, including acrosome attachment, sperm head shaping and the initiation of the axoneme growth to form the core of the sperm tail. Specifically, LRGUK-1 is required for basal body attachment to the plasma membrane, the appropriate formation of the sub-distal appendages, the extension of axoneme microtubules and for microtubule movement and organisation within the manchette. Manchette dysfunction leads to abnormal sperm head shaping. Several of these functions may be achieved in association with the LRGUK-1 binding partner HOOK2. Collectively, these data establish LRGUK-1 as a major determinant of microtubule structure within the male germ line.

  6. Functional genomics identifies a requirement of pre-mRNA splicing factors for sister chromatid cohesion.

    Science.gov (United States)

    Sundaramoorthy, Sriramkumar; Vázquez-Novelle, María Dolores; Lekomtsev, Sergey; Howell, Michael; Petronczki, Mark

    2014-11-18

    Sister chromatid cohesion mediated by the cohesin complex is essential for chromosome segregation during cell division. Using functional genomic screening, we identify a set of 26 pre-mRNA splicing factors that are required for sister chromatid cohesion in human cells. Loss of spliceosome subunits increases the dissociation rate of cohesin from chromatin and abrogates cohesion after DNA replication, ultimately causing mitotic catastrophe. Depletion of splicing factors causes defective processing of the pre-mRNA encoding sororin, a factor required for the stable association of cohesin with chromatin, and an associated reduction of sororin protein level. Expression of an intronless version of sororin and depletion of the cohesin release protein WAPL suppress the cohesion defect in cells lacking splicing factors. We propose that spliceosome components contribute to sister chromatid cohesion and mitotic chromosome segregation through splicing of sororin pre-mRNA. Our results highlight the loss of cohesion as an early cellular consequence of compromised splicing. This may have clinical implications because SF3B1, a splicing factor that we identify to be essential for cohesion, is recurrently mutated in chronic lymphocytic leukaemia.

  7. Survey of proposed functional requirements for a disturbance analysis and surveillance system

    Energy Technology Data Exchange (ETDEWEB)

    Sides, W.H. Jr.; Oh, C.B.; Knight, P.F.

    1980-10-01

    A program to enhance the capabilities of operators of nuclear power plants is being pursued by the US Nuclear Regulatory Commission (NRC). The program includes improvements in plant monitoring, diagnostic and corrective action aids, operator-process communication, and operator training. Concerning diagnostic aids, a disturbance analysis and surveillance system (DASS) was considered which would monitor the plant for the approach or occurrence of disturbance conditions and would assist the operator in returning the plant to normal operation or to help mitigate the consequences of a failure condition or misoperation. The NRC had requested Oak Ridge National Laboratory to survey the functional requirements being proposed for a DASS. In fulfilling this task, the proposed requirements were categorized according to whether they could be realized in the short term and backfitted to existing plants or whether they could be realized only in the long term by incorporation into new plant designs. In addition, several recommendations concerning DASS development were made for consideration by the NRC. Finally, the effects of human factors on a DASS were evaluated, and the results are discussed in this report. 12 refs., 6 figs.

  8. THE ANALYSIS OF THIN WALLED COMPOSITE LAMINATED HELICOPTER ROTOR WITH HIERARCHICAL WARPING FUNCTIONS AND FINITE ELEMENT METHOD

    Institute of Scientific and Technical Information of China (English)

    诸德超; 邓忠民; 王荇卫

    2001-01-01

    In the present paper, a series of hierarchical warping functions is developed to analyze the static and dynamic problems of thin walled composite laminated helicopter rotors composed of several layers with single closed cell. This ethod is the development and extension of the traditional constrained warping theory of thin walled metallic beams, which had been proved very successful since 1940s. The warping distribution along the perimeter of each layer is expanded into a series of successively corrective warping functions with the traditional warping function caused by free torsion or free bending as the first term, and is assumed to be piecewise linear along the thickness direction of layers. The governing equations are derived based upon the variational principle of minimum potential energy for static analysis and Rayleigh Quotient for free vibration analysis. Then the hierarchical finite element method is introduced to form a numerical algorithm. Both static and natural vibration problems of sample box beams are analyzed with the present method to show the main mechanical behavior of the thin walled composite laminated helicopter rotor.

  9. [Mechanism of differential effect of low dose adaptogens on the functional activity of normal and transformed cellular elements in vitro].

    Science.gov (United States)

    Udintsev, S N; Shakhov, V P; Borovskoĭ, I G

    1991-01-01

    Influence of water solutions of chemically pure adaptogen--synthetic analog of Rhodiola Rosea extract phenol composition (SAR) on functional activity of hemopoietic and tumor cells of mice with Ehrlich ascite cancer was studied in vitro. The periodical character of SAR effects was shown to be different for both types of cells, and at 1 x 10(-2) and 1 x 10(-26) M concentrations simultaneous stimulation of blood marrow cells colony-forming activity and inhibition of the latter in tumor elements was revealed. Essential changes of reactions of both cell types after adding the DNA-dependent RNA polymerase blocker Actinomycin D permit to suggest SAR effects to be connected with drug influence on the membrane RNA of the target cells.

  10. Timing specific requirement of microRNA function is essential for embryonic and postnatal hippocampal development.

    Directory of Open Access Journals (Sweden)

    Qingsong Li

    Full Text Available The adult hippocampus consists of the dentate gyrus (DG and the CA1, CA2 and CA3 regions and is essential for learning and memory functions. During embryonic development, hippocampal neurons are derived from hippocampal neuroepithelial cells and dentate granular progenitors. The molecular mechanisms that control hippocampal progenitor proliferation and differentiation are not well understood. Here we show that noncoding microRNAs (miRNAs are essential for early hippocampal development in mice. Conditionally ablating the RNAase III enzyme Dicer at different embryonic time points utilizing three Cre mouse lines causes abnormal hippocampal morphology and affects the number of hippocampal progenitors due to altered proliferation and increased apoptosis. Lack of miRNAs at earlier stages causes early differentiation of hippocampal neurons, in particular in the CA1 and DG regions. Lack of miRNAs at a later stage specifically affects neuronal production in the CA3 region. Our results reveal a timing requirement of miRNAs for the formation of specific hippocampal regions, with the CA1 and DG developmentally hindered by an early loss of miRNAs and the CA3 region to a late loss of miRNAs. Collectively, our studies indicate the importance of the Dicer-mediated miRNA pathway in hippocampal development and functions.

  11. Whole genome functional analysis identifies novel components required for mitotic spindle integrity in human cells

    Science.gov (United States)

    Rines, Daniel R; Gomez-Ferreria, Maria Ana; Zhou, Yingyao; DeJesus, Paul; Grob, Seanna; Batalov, Serge; Labow, Marc; Huesken, Dieter; Mickanin, Craig; Hall, Jonathan; Reinhardt, Mischa; Natt, Francois; Lange, Joerg; Sharp, David J; Chanda, Sumit K; Caldwell, Jeremy S

    2008-01-01

    Background The mitotic spindle is a complex mechanical apparatus required for accurate segregation of sister chromosomes during mitosis. We designed a genetic screen using automated microscopy to discover factors essential for mitotic progression. Using a RNA interference library of 49,164 double-stranded RNAs targeting 23,835 human genes, we performed a loss of function screen to look for small interfering RNAs that arrest cells in metaphase. Results Here we report the identification of genes that, when suppressed, result in structural defects in the mitotic spindle leading to bent, twisted, monopolar, or multipolar spindles, and cause cell cycle arrest. We further describe a novel analysis methodology for large-scale RNA interference datasets that relies on supervised clustering of these genes based on Gene Ontology, protein families, tissue expression, and protein-protein interactions. Conclusion This approach was utilized to classify functionally the identified genes in discrete mitotic processes. We confirmed the identity for a subset of these genes and examined more closely their mechanical role in spindle architecture. PMID:18302737

  12. PRMT1 mediated methylation of TAF15 is required for its positive gene regulatory function

    Energy Technology Data Exchange (ETDEWEB)

    Jobert, Laure; Argentini, Manuela [Institut de Genetique et de Biologie Moleculaire et Cellulaire (IGBMC), CNRS UMR 7104, INSERM U 596, Universite Louis Pasteur de Strasbourg, BP 10142 - 67404 Illkirch Cedex, CU de Strasbourg (France); Tora, Laszlo, E-mail: laszlo@igbmc.u-strasbg.fr [Institut de Genetique et de Biologie Moleculaire et Cellulaire (IGBMC), CNRS UMR 7104, INSERM U 596, Universite Louis Pasteur de Strasbourg, BP 10142 - 67404 Illkirch Cedex, CU de Strasbourg (France)

    2009-04-15

    TAF15 (formerly TAF{sub II}68) is a nuclear RNA-binding protein that is associated with a distinct population of TFIID and RNA polymerase II complexes. TAF15 harbours an N-terminal activation domain, an RNA recognition motif (RRM) and many Arg-Gly-Gly (RGG) repeats at its C-terminal end. The N-terminus of TAF15 serves as an essential transforming domain in the fusion oncoprotein created by chromosomal translocation in certain human chondrosarcomas. Post-transcriptional modifications (PTMs) of proteins are known to regulate their activity, however, nothing is known on how PTMs affect TAF15 function. Here we demonstrate that endogenous human TAF15 is methylated in vivo at its numerous RGG repeats. Furthermore, we identify protein arginine N-methyltransferase 1 (PRMT1) as a TAF15 interactor and the major PRMT responsible for its methylation. In addition, the RGG repeat-containing C-terminus of TAF15 is responsible for the shuttling between the nucleus and the cytoplasm and the methylation of RGG repeats affects the subcellular localization of TAF15. The methylation of TAF15 by PRMT1 is required for the ability of TAF15 to positively regulate the expression of the studied endogenous TAF15-target genes. Our findings demonstrate that arginine methylation of TAF15 by PRMT1 is a crucial event determining its proper localization and gene regulatory function.

  13. ADAM10 regulates transcription factor expression required for plasma cell function.

    Directory of Open Access Journals (Sweden)

    Natalia S Chaimowitz

    Full Text Available A disintegrin and metalloprotease 10 (ADAM10 is a key regulator of cellular processes by shedding extracellular domains of transmembrane proteins. We have previously demonstrated that deletion of B cell expressed ADAM10 results in changes in lymphoid tissue architecture and impaired germinal center (GC formation. In this study, mice were generated in which ADAM10 is deleted in B cells following class switch recombination (ADAM10(Δ/ΔIgG1-cre(+/- mice. Despite normal GC formation, antibody responses were impaired in ADAM10(Δ/ΔIgG1-cre(+/- mice, implicating ADAM10 in post-GC and extrafollicular B cell terminal differentiation. Surprisingly, plasma cell (PC numbers were normal in ADAM10(Δ/ΔIgG1-cre(+/- mice when compared to controls. However, PCs isolated from ADAM10(Δ/ΔIgG1-cre(+/- mice exhibited decreased expression of transcription factors important for PC function: Prdm1, Xbp1 and Irf4. Bcl6 is a GC transcriptional repressor that inhibits the PC transcriptional program and thus must be downregulated for PC differentiation to occur. Bcl6 expression was increased in PCs isolated from ADAM10(Δ/ΔIgG1-cre(+/- mice at both the mRNA and protein level. These results demonstrate that ADAM10 is required for proper transcription factor expression in PCs and thus, for normal PC function.

  14. The functional requirements of mammalian hair: a compromise between crypsis and thermoregulation?

    Science.gov (United States)

    Wacker, Chris B.; McAllan, Bronwyn M.; Körtner, Gerhard; Geiser, Fritz

    2016-08-01

    Mammalian fur often shows agouti banding with a proximal dark band near the skin and a lighter distal band. We examined the function of both bands in relation to camouflage, thermal properties of pelts, and thermal energetics of dunnarts ( Sminthopsis crassicaudata), which are known to use torpor and basking. Although the distal band of dunnart fur darkened with increasing latitude, which is important for camouflage, it did not affect the thermal properties and the length of the dark band and total hair length were not correlated. In contrast, the length of the proximal dark band of preserved pelts exposed to sunlight was positively correlated ( r 2 = 0.59) with the temperature underneath the pelt ( T pelt). All dunnarts offered radiant heat basked by exposing the dark band of the hair during both rest and torpor. Basking dunnarts with longer dark bands had lower resting metabolism ( r 2 = 0.69), warmed faster from torpor ( r 2 = 0.77), required less energy to do so ( r 2 = 0.32), and reached a higher subcutaneous temperature ( T sub) at the end of rewarming ( r 2 = 0.75). We provide the first experimental evidence on the possible dual function of the color banding of mammalian fur. The distal colored band appears to be important for camouflage, whereas the length of the dark proximal hair band facilitates heat gain for energy conservation and allows animals to rewarm quickly and economically from torpor.

  15. Functional Requirements for Heparan Sulfate Biosynthesis in Morphogenesis and Nervous System Development in C. elegans

    Science.gov (United States)

    Blanchette, Cassandra R.; Thackeray, Andrea; Perrat, Paola N.; Hekimi, Siegfried; Bénard, Claire Y.

    2017-01-01

    The regulation of cell migration is essential to animal development and physiology. Heparan sulfate proteoglycans shape the interactions of morphogens and guidance cues with their respective receptors to elicit appropriate cellular responses. Heparan sulfate proteoglycans consist of a protein core with attached heparan sulfate glycosaminoglycan chains, which are synthesized by glycosyltransferases of the exostosin (EXT) family. Abnormal HS chain synthesis results in pleiotropic consequences, including abnormal development and tumor formation. In humans, mutations in either of the exostosin genes EXT1 and EXT2 lead to osteosarcomas or multiple exostoses. Complete loss of any of the exostosin glycosyltransferases in mouse, fish, flies and worms leads to drastic morphogenetic defects and embryonic lethality. Here we identify and study previously unavailable viable hypomorphic mutations in the two C. elegans exostosin glycosyltransferases genes, rib-1 and rib-2. These partial loss-of-function mutations lead to a severe reduction of HS levels and result in profound but specific developmental defects, including abnormal cell and axonal migrations. We find that the expression pattern of the HS copolymerase is dynamic during embryonic and larval morphogenesis, and is sustained throughout life in specific cell types, consistent with HSPGs playing both developmental and post-developmental roles. Cell-type specific expression of the HS copolymerase shows that HS elongation is required in both the migrating neuron and neighboring cells to coordinate migration guidance. Our findings provide insights into general principles underlying HSPG function in development. PMID:28068429

  16. Characterization of the TRBP domain required for Dicer interaction and function in RNA interference

    Directory of Open Access Journals (Sweden)

    El Far Mohamed

    2009-05-01

    Full Text Available Abstract Background Dicer, Ago2 and TRBP are the minimum components of the human RNA-induced silencing complex (RISC. While Dicer and Ago2 are RNases, TRBP is the double-stranded RNA binding protein (dsRBP that loads small interfering RNA into the RISC. TRBP binds directly to Dicer through its C-terminal domain. Results We show that the TRBP binding site in Dicer is a 165 amino acid (aa region located between the ATPase and the helicase domains. The binding site in TRBP is a 69 aa domain, called C4, located at the C-terminal end of TRBP. The TRBP1 and TRBP2 isoforms, but not TRBPs lacking the C4 site (TRBPsΔC4, co-immunoprecipitated with Dicer. The C4 domain is therefore necessary to bind Dicer, irrespective of the presence of RNA. Immunofluorescence shows that while full-length TRBPs colocalize with Dicer, TRBPsΔC4 do not. tarbp2-/- cells, which do not express TRBP, do not support RNA interference (RNAi mediated by short hairpin or micro RNAs against EGFP. Both TRBPs, but not TRBPsΔC4, were able to rescue RNAi function. In human cells with low RNAi activity, addition of TRBP1 or 2, but not TRBPsΔC4, rescued RNAi function. Conclusion The mapping of the interaction sites between TRBP and Dicer show unique domains that are required for their binding. Since TRBPsΔC4 do not interact or colocalize with Dicer, we suggest that TRBP and Dicer, both dsRBPs, do not interact through bound dsRNA. TRBPs, but not TRBPsΔC4, rescue RNAi activity in RNAi-compromised cells, indicating that the binding of Dicer to TRBP is critical for RNAi function.

  17. Identifying Functional Requirements for Flexible Airspace Management Concept Using Human-In-The-Loop Simulations

    Science.gov (United States)

    Lee, Paul U.; Bender, Kim; Pagan, Danielle

    2011-01-01

    Flexible Airspace Management (FAM) is a mid- term Next Generation Air Transportation System (NextGen) concept that allows dynamic changes to airspace configurations to meet the changes in the traffic demand. A series of human-in-the-loop (HITL) studies have identified procedures and decision support requirements needed to implement FAM. This paper outlines a suggested FAM procedure and associated decision support functionality based on these HITL studies. A description of both the tools used to support the HITLs and the planned NextGen technologies available in the mid-term are presented and compared. The mid-term implementation of several NextGen capabilities, specifically, upgrades to the Traffic Management Unit (TMU), the initial release of an en route automation system, the deployment of a digital data communication system, a more flexible voice communications network, and the introduction of a tool envisioned to manage and coordinate networked ground systems can support the implementation of the FAM concept. Because of the variability in the overall deployment schedule of the mid-term NextGen capabilities, the dependency of the individual NextGen capabilities are examined to determine their impact on a mid-term implementation of FAM. A cursory review of the different technologies suggests that new functionality slated for the new en route automation system is a critical enabling technology for FAM, as well as the functionality to manage and coordinate networked ground systems. Upgrades to the TMU are less critical but important nonetheless for FAM to be fully realized. Flexible voice communications network and digital data communication system could allow more flexible FAM operations but they are not as essential.

  18. Basic residues within the ebolavirus VP35 protein are required for its viral polymerase cofactor function.

    Science.gov (United States)

    Prins, Kathleen C; Binning, Jennifer M; Shabman, Reed S; Leung, Daisy W; Amarasinghe, Gaya K; Basler, Christopher F

    2010-10-01

    The ebolavirus (EBOV) VP35 protein binds to double-stranded RNA (dsRNA), inhibits host alpha/beta interferon (IFN-α/β) production, and is an essential component of the viral polymerase complex. Structural studies of the VP35 C-terminal IFN inhibitory domain (IID) identified specific structural features, including a central basic patch and a hydrophobic pocket, that are important for dsRNA binding and IFN inhibition. Several other conserved basic residues bordering the central basic patch and a separate cluster of basic residues, called the first basic patch, were also identified. Functional analysis of alanine substitution mutants indicates that basic residues outside the central basic patch are not required for dsRNA binding or for IFN inhibition. However, minigenome assays, which assess viral RNA polymerase complex function, identified these other basic residues to be critical for viral RNA synthesis. Of these, a subset located within the first basic patch is important for VP35-nucleoprotein (NP) interaction, as evidenced by the inability of alanine substitution mutants to coimmunoprecipitate with NP. Therefore, first basic patch residues are likely critical for replication complex formation through interactions with NP. Coimmunoprecipitation studies further demonstrate that the VP35 IID is sufficient to interact with NP and that dsRNA can modulate VP35 IID interactions with NP. Other basic residue mutations that disrupt the VP35 polymerase cofactor function do not affect interaction with NP or with the amino terminus of the viral polymerase. Collectively, these results highlight the importance of conserved basic residues from the EBOV VP35 C-terminal IID and validate the VP35 IID as a potential therapeutic target.

  19. A Functional Core of IncA Is Required for Chlamydia trachomatis Inclusion Fusion.

    Science.gov (United States)

    Weber, Mary M; Noriea, Nicholas F; Bauler, Laura D; Lam, Jennifer L; Sager, Janet; Wesolowski, Jordan; Paumet, Fabienne; Hackstadt, Ted

    2016-04-01

    Chlamydia trachomatis is an obligate intracellular pathogen that is the etiological agent of a variety of human diseases, including blinding trachoma and sexually transmitted infections. Chlamydiae replicate within a membrane-bound compartment, termed an inclusion, which they extensively modify by the insertion of type III secreted proteins called Inc proteins. IncA is an inclusion membrane protein that encodes two coiled-coil domains that are homologous to eukaryotic SNARE (soluble N-ethylmaleimide-sensitive factor attachment receptor) motifs. Recent biochemical evidence suggests that a functional core, composed of SNARE-like domain 1 (SLD-1) and part of SNARE-like domain 2 (SLD-2), is required for the characteristic homotypic fusion of C. trachomatis inclusions in multiply infected cells. To verify the importance of IncA in homotypic fusion in Chlamydia, we generated an incA::bla mutant. Insertional inactivation of incA resulted in the formation of nonfusogenic inclusions, a phenotype that was completely rescued by complementation with full-length IncA. Rescue of homotypic inclusion fusion was dependent on the presence of the functional core consisting of SLD-1 and part of SLD-2. Collectively, these results confirm in vitro membrane fusion assays identifying functional domains of IncA and expand the genetic tools available for identification of chlamydia with a method for complementation of site-specific mutants. Chlamydia trachomatis replicates within a parasitophorous vacuole termed an inclusion. The chlamydial inclusions are nonfusogenic with vesicles in the endocytic pathway but, in multiply infected cells, fuse with each other to form a single large inclusion. This homotypic fusion is dependent upon the presence of a chlamydial inclusion membrane-localized protein, IncA. Specificity of membrane fusion in eukaryotic cells is regulated by SNARE (soluble N-ethylmaleimide sensitive factor attachment receptor) proteins on the cytosolic face of vesicles and target

  20. Surveillance Radar Design Options as a Function of Cataloguing Performance Requirements

    Science.gov (United States)

    Krag, H.; Klinkrad, H.

    2009-03-01

    Europe is preparing for the development of an autonomous space surveillance and situational awareness system. First concept and capability analysis studies have led to a draft proposal for the surveillance and tracking part of the system. This foresees, in a first deployment step, ground-based surveillance and tracking radar systems, a network of optical telescopes and a data centre. In a second step the system is planned to be extended by adding space-based assets and the associated ground-segment. The terrestrial part of the system will be responsible for the build-up and maintenance of a catalogue of space objects. Studies showed that one large phased array radar alone could act as the single means for the generation of a catalogue of LEO objects (apogee altitudes radar search window for a minimum time span to enable orbit determination of sufficient accuracy. Catalogue maintenance requires objects to be re-observable after limited time spans so that they can be clearly correlated. Today, the user requirements on the performance of the system are under definition. Different options to specify the desired system performance in terms of the resulting object catalogue have been proposed. One of them is to specify a certain coverage level of the existing NORAD catalogue. A second one is to request full coverage of all objects above a certain diameter threshold. Both approaches have certain advantages (e.g. the first one being verifiable by tests and the second one leading to an unbiased/independent catalogue). However, these requirements might impose different system designs in terms of the sensor location, and the dimensions and the orientation of the search field. This paper outlines the consequences of the cataloguing performance requirements on the high-level system design. Simulation tools are used to investigate key parameters such as the optimum radar wavelength, the viewing direction and search field dimensions as a function of these specifications. First

  1. Tardigrade workbench: comparing stress-related proteins, sequence-similar and functional protein clusters as well as RNA elements in tardigrades

    Directory of Open Access Journals (Sweden)

    Frohme Marcus

    2009-10-01

    Full Text Available Abstract Background Tardigrades represent an animal phylum with extraordinary resistance to environmental stress. Results To gain insights into their stress-specific adaptation potential, major clusters of related and similar proteins are identified, as well as specific functional clusters delineated comparing all tardigrades and individual species (Milnesium tardigradum, Hypsibius dujardini, Echiniscus testudo, Tulinus stephaniae, Richtersius coronifer and functional elements in tardigrade mRNAs are analysed. We find that 39.3% of the total sequences clustered in 58 clusters of more than 20 proteins. Among these are ten tardigrade specific as well as a number of stress-specific protein clusters. Tardigrade-specific functional adaptations include strong protein, DNA- and redox protection, maintenance and protein recycling. Specific regulatory elements regulate tardigrade mRNA stability such as lox P DICE elements whereas 14 other RNA elements of higher eukaryotes are not found. Further features of tardigrade specific adaption are rapidly identified by sequence and/or pattern search on the web-tool tardigrade analyzer http://waterbear.bioapps.biozentrum.uni-wuerzburg.de. The work-bench offers nucleotide pattern analysis for promotor and regulatory element detection (tardigrade specific; nrdb as well as rapid COG search for function assignments including species-specific repositories of all analysed data. Conclusion Different protein clusters and regulatory elements implicated in tardigrade stress adaptations are analysed including unpublished tardigrade sequences.

  2. Tardigrade workbench: comparing stress-related proteins, sequence-similar and functional protein clusters as well as RNA elements in tardigrades.

    Science.gov (United States)

    Förster, Frank; Liang, Chunguang; Shkumatov, Alexander; Beisser, Daniela; Engelmann, Julia C; Schnölzer, Martina; Frohme, Marcus; Müller, Tobias; Schill, Ralph O; Dandekar, Thomas

    2009-10-12

    Tardigrades represent an animal phylum with extraordinary resistance to environmental stress. To gain insights into their stress-specific adaptation potential, major clusters of related and similar proteins are identified, as well as specific functional clusters delineated comparing all tardigrades and individual species (Milnesium tardigradum, Hypsibius dujardini, Echiniscus testudo, Tulinus stephaniae, Richtersius coronifer) and functional elements in tardigrade mRNAs are analysed. We find that 39.3% of the total sequences clustered in 58 clusters of more than 20 proteins. Among these are ten tardigrade specific as well as a number of stress-specific protein clusters. Tardigrade-specific functional adaptations include strong protein, DNA- and redox protection, maintenance and protein recycling. Specific regulatory elements regulate tardigrade mRNA stability such as lox P DICE elements whereas 14 other RNA elements of higher eukaryotes are not found. Further features of tardigrade specific adaption are rapidly identified by sequence and/or pattern search on the web-tool tardigrade analyzer http://waterbear.bioapps.biozentrum.uni-wuerzburg.de. The work-bench offers nucleotide pattern analysis for promotor and regulatory element detection (tardigrade specific; nrdb) as well as rapid COG search for function assignments including species-specific repositories of all analysed data. Different protein clusters and regulatory elements implicated in tardigrade stress adaptations are analysed including unpublished tardigrade sequences.

  3. Tardigrade workbench: comparing stress-related proteins, sequence-similar and functional protein clusters as well as RNA elements in tardigrades

    OpenAIRE

    Frohme Marcus; Schnölzer Martina; Engelmann Julia C; Beisser Daniela; Shkumatov Alexander; Liang Chuanguang; Förster Frank; Müller Tobias; Schill Ralph O; Dandekar Thomas

    2009-01-01

    Abstract Background Tardigrades represent an animal phylum with extraordinary resistance to environmental stress. Results To gain insights into their stress-specific adaptation potential, major clusters of related and similar proteins are identified, as well as specific functional clusters delineated comparing all tardigrades and individual species (Milnesium tardigradum, Hypsibius dujardini, Echiniscus testudo, Tulinus stephaniae, Richtersius coronifer) and functional elements in tardigrade ...

  4. Tardigrade workbench: comparing stress-related proteins, sequence-similar and functional protein clusters as well as RNA elements in tardigrades

    OpenAIRE

    Frohme Marcus; Schnölzer Martina; Engelmann Julia C; Beisser Daniela; Shkumatov Alexander; Liang Chuanguang; Förster Frank; Müller Tobias; Schill Ralph O; Dandekar Thomas

    2009-01-01

    Abstract Background Tardigrades represent an animal phylum with extraordinary resistance to environmental stress. Results To gain insights into their stress-specific adaptation potential, major clusters of related and similar proteins are identified, as well as specific functional clusters delineated comparing all tardigrades and individual species (Milnesium tardigradum, Hypsibius dujardini, Echiniscus testudo, Tulinus stephaniae, Richtersius coronifer) and functional elements in tardigrade ...

  5. Electric dipole moment function of the X1 Sigma/+/ state of CO - Vibration-rotation matrix elements for transitions of gas laser and astrophysical interest

    Science.gov (United States)

    Chackerian, C., Jr.

    1976-01-01

    The electric dipole moment function of the ground electronic state of carbon monoxide has been determined by combining numerical solutions of the radial Schrodinger equation with absolute intensity data of vibration-rotation bands. The derived dipole moment function is used to calculate matrix elements of interest to stellar astronomy and of importance in the carbon monoxide laser.

  6. The Drosophila Translational Control Element (TCE is required for high-level transcription of many genes that are specifically expressed in testes.

    Directory of Open Access Journals (Sweden)

    Rebeccah J Katzenberger

    Full Text Available To investigate the importance of core promoter elements for tissue-specific transcription of RNA polymerase II genes, we examined testis-specific transcription in Drosophila melanogaster. Bioinformatic analyses of core promoter sequences from 190 genes that are specifically expressed in testes identified a 10 bp A/T-rich motif that is identical to the translational control element (TCE. The TCE functions in the 5' untranslated region of Mst(3CGP mRNAs to repress translation, and it also functions in a heterologous gene to regulate transcription. We found that among genes with focused initiation patterns, the TCE is significantly enriched in core promoters of genes that are specifically expressed in testes but not in core promoters of genes that are specifically expressed in other tissues. The TCE is variably located in core promoters and is conserved in melanogaster subgroup species, but conservation dramatically drops in more distant species. In transgenic flies, short (300-400 bp genomic regions containing a TCE directed testis-specific transcription of a reporter gene. Mutation of the TCE significantly reduced but did not abolish reporter gene transcription indicating that the TCE is important but not essential for transcription activation. Finally, mutation of testis-specific TFIID (tTFIID subunits significantly reduced the transcription of a subset of endogenous TCE-containing but not TCE-lacking genes, suggesting that tTFIID activity is limited to TCE-containing genes but that tTFIID is not an obligatory regulator of TCE-containing genes. Thus, the TCE is a core promoter element in a subset of genes that are specifically expressed in testes. Furthermore, the TCE regulates transcription in the context of short genomic regions, from variable locations in the core promoter, and both dependently and independently of tTFIID. These findings set the stage for determining the mechanism by which the TCE regulates testis-specific transcription and

  7. Bioinformatic and functional analysis of RNA secondary structure elements among different genera of human and animal caliciviruses

    Science.gov (United States)

    Simmonds, Peter; Karakasiliotis, Ioannis; Bailey, Dalan; Chaudhry, Yasmin; Evans, David J.; Goodfellow, Ian G.

    2008-01-01

    The mechanism and role of RNA structure elements in the replication and translation of Caliciviridae remains poorly understood. Several algorithmically independent methods were used to predict secondary structures within the Norovirus, Sapovirus, Vesivirus and Lagovirus genera. All showed profound suppression of synonymous site variability (SSSV) at genomic 5′ ends and the start of the sub-genomic (sg) transcript, consistent with evolutionary constraints from underlying RNA structure. A newly developed thermodynamic scanning method predicted RNA folding mapping precisely to regions of SSSV and at the genomic 3′ end. These regions contained several evolutionarily conserved RNA secondary structures, of variable size and positions. However, all caliciviruses contained 3′ terminal hairpins, and stem–loops in the anti-genomic strand invariably six bases upstream of the sg transcript, indicating putative roles as sg promoters. Using the murine norovirus (MNV) reverse-genetics system, disruption of 5′ end stem–loops produced ∼15- to 20-fold infectivity reductions, while disruption of the RNA structure in the sg promoter region and at the 3′ end entirely destroyed replication ability. Restoration of infectivity by repair mutations in the sg promoter region confirmed a functional role for the RNA secondary structure, not the sequence. This study provides comprehensive bioinformatic resources for future functional studies of MNV and other caliciviruses. PMID:18319285

  8. Evidence for functional heterogeneity of sieve element-companion cell complexes in minor vein phloem of Alonsoa meridionalis.

    Science.gov (United States)

    Voitsekhovskaja, Olga V; Rudashevskaya, Elena L; Demchenko, Kirill N; Pakhomova, Marina V; Batashev, Denis R; Gamalei, Yuri V; Lohaus, Gertrud; Pawlowski, Katharina

    2009-01-01

    Two modes of phloem loading have been proposed, apoplastic and symplastic, depending on the structure of sieve element-companion cell complexes (SE-CCCs) in minor vein phloem. Species are usually classified as either apoplastic or symplastic loaders although the cytology of SE-CCCs in minor veins of the majority of plants indicates that both mechanisms can be simultaneously involved in phloem loading. The functions of structurally different SE-CCCs in minor veins of the stachyose-translocating plant Alonsoa meridionalis were examined. A stachyose synthase gene, AmSTS1, was expressed in intermediary cells but not in the ordinary companion cell of the same vein. In contrast, sucrose transporter AmSUT1 protein was present in ordinary companion cells but not in the neighbouring intermediary cells. These data reveal the principles of phloem sap formation in A. meridionalis and, probably, in many other dicots. The two types of SE-CCCs within one and the same minor vein load different carbohydrates, using contrasting mechanisms for their delivery into the phloem. Lateral sieve pores in the minor vein phloem lead to mixing of the carbohydrates soon after loading. While symplastic and apoplastic pathways can function simultaneously during phloem loading, they are separated at the level of different SE-CCCs combined in phloem endings.

  9. A monomer is the minimum functional unit required for channel and ATPase activity of the cystic fibrosis transmembrane conductance regulator.

    Science.gov (United States)

    Ramjeesingh, M; Li, C; Kogan, I; Wang, Y; Huan, L J; Bear, C E

    2001-09-04

    The cystic fibrosis transmembrane conductance regulator (CFTR) normally functions as a phosphorylation-regulated chloride channel on the apical surface of epithelial cells, and lack of this function is the primary cause for the fatal disease cystic fibrosis (CF). Previous studies showed that purified, reconstituted CFTR can function as a chloride channel and, further, that its intrinsic ATPase activity is required to regulate opening and closing of the channel gate. However, these previous studies did not identify the quaternary structure required to mediate conduction and catalysis. Our present studies show that CFTR molecules may self-associate in CHO and Sf9 membranes, as complexes close to the predicted size of CFTR dimers can be captured by chemical cross-linking reagents and detected using nondissociative PAGE. However, CFTR function does not require a multimeric complex for function as we determined that purified, reconstituted CFTR monomers are sufficient to mediate regulated chloride conduction and ATPase activity.

  10. Ezrin is required for the functional regulation of the epithelial sodium proton exchanger, NHE3.

    Directory of Open Access Journals (Sweden)

    Hisayoshi Hayashi

    Full Text Available The sodium hydrogen exchanger isoform 3 (NHE3 mediates absorption of sodium, bicarbonate and water from renal and intestinal lumina. This activity is fundamental to the maintenance of a physiological plasma pH and blood pressure. To perform this function NHE3 must be present in the apical membrane of renal tubular and intestinal epithelia. The molecular determinants of this localization have not been conclusively determined, although linkage to the apical actin cytoskeleton through ezrin has been proposed. We set out to evaluate this hypothesis. Functional studies of NHE3 activity were performed on ezrin knockdown mice (Vil2(kd/kd and NHE3 activity similar to wild-type animals detected. Interpretation of this finding was difficult as other ERM (ezrin/radixin/moesin proteins were present. We therefore generated an epithelial cell culture model where ezrin was the only detectable ERM. After knockdown of ezrin expression with siRNA, radixin and moesin expression remained undetectable. Consistent with the animal ultrastructural data, cells lacking ezrin retained an epithelial phenotype but had shortened and thicker microvilli. NHE3 localization was identical to cells transfected with non-targeting siRNA. The attachment of NHE3 to the apical cytoskeleton was unaltered as assessed by fluorescent recovery after photobleaching (FRAP and the solubility of NHE3 in Triton X-100. Baseline NHE3 activity was unaltered, however, cAMP-dependent inhibition of NHE3 was largely lost even though NHE3 was phosphorylated at serines 552 and 605. Thus, ezrin is not necessary for the apical localization, attachment to the cytoskeleton, baseline activity or cAMP induced phosphrylation of NHE3, but instead is required for cAMP mediated inhibition.

  11. Functional Analysis of Multiple Transcription Factor Sites in a Regulatory Element of Human ε-Globin Gene

    Institute of Scientific and Technical Information of China (English)

    Chun-Hui HOU; Jian HUANG; Ruo-Lan QIAN

    2004-01-01

    The developmental control of the human ε-globin gene expression is mediated by transcriptional regulatory elements in the 5' flanking DNA of this gene. A previously identified negative regulatory element (-3028 to -2902 bp, termed ε-NRAII) was analyzed and one putative NF-κB site and two GATA sites locate at -3004 bp, -2975 bp and -2948 bp were characterized. Electrophoresis mobility shift assay (EMSA)showed that the putative NF-κB site was specifically bound by nuclear proteins of K562 cells. Data obtained from transient transfection showed that the expression of reporter gene could be upregulated about 50% or 100% respectively when ε-NRAII was inserted upstream of the SV40 promoter or ε-globin gene proximal promoter (-177 bp to +1 bp), suggesting that ε-NRAII might not be a classic silencer. Mutation in the putative NF-κB site or in the GATA site (at-2975 bp) slightly reduced the expression of reporter gene driven by SV40 promoter or ε-globin gene proximal promoter. However, the mutation of GATA site at -2948 bp remarkably reduced the reporter gene activity driven by SV40 promoter, but not by ε-globin gene proximal promoter. Further mutation analysis showed that the negative effect of mutation in GATA site at -2948 bp on SV40 promoter was not affected by the mutation of the putative NF-κB site, whereas it could be abolished by the mutation of GATA site at -2975 bp. Furthermore, the mutation of both GATA sites could synergistically reduce the reporter gene activity driven by ε-globin gene proximal promoter. Those results suggested that ε-NRAII might function differently on the SV40 promoter and ε-globin gene proximal promoter.

  12. A Rice Ca2+ Binding Protein Is Required for Tapetum Function and Pollen Formation.

    Science.gov (United States)

    Yu, Jing; Meng, Zhaolu; Liang, Wanqi; Behera, Smrutisanjita; Kudla, Jörg; Tucker, Matthew R; Luo, Zhijing; Chen, Mingjiao; Xu, Dawei; Zhao, Guochao; Wang, Jie; Zhang, Siyi; Kim, Yu-Jin; Zhang, Dabing

    2016-11-01

    In flowering plants, successful male reproduction requires the sophisticated interaction between somatic anther wall layers and reproductive cells. Timely degradation of the innermost tissue of the anther wall layer, the tapetal layer, is critical for pollen development. Ca(2+) is a well-known stimulus for plant development, but whether it plays a role in affecting male reproduction remains elusive. Here we report a role of Defective in Exine Formation 1 (OsDEX1) in rice (Oryza sativa), a Ca(2+) binding protein, in regulating rice tapetal cell degradation and pollen formation. In osdex1 anthers, tapetal cell degeneration is delayed and degradation of the callose wall surrounding the microspores is compromised, leading to aborted pollen formation and complete male sterility. OsDEX1 is expressed in tapetal cells and microspores during early anther development. Recombinant OsDEX1 is able to bind Ca(2+) and regulate Ca(2+) homeostasis in vitro, and osdex1 exhibited disturbed Ca(2+) homeostasis in tapetal cells. Phylogenetic analysis suggested that OsDEX1 may have a conserved function in binding Ca(2+) in flowering plants, and genetic complementation of pollen wall defects of an Arabidopsis (Arabidopsis thaliana) dex1 mutant confirmed its evolutionary conservation in pollen development. Collectively, these findings suggest that OsDEX1 plays a fundamental role in the development of tapetal cells and pollen formation, possibly via modulating the Ca(2+) homeostasis during pollen development.

  13. Eight genes are required for functional reconstitution of the Caenorhabditis elegans levamisole-sensitive acetylcholine receptor

    Science.gov (United States)

    Boulin, Thomas; Gielen, Marc; Richmond, Janet E.; Williams, Daniel C.; Paoletti, Pierre; Bessereau, Jean-Louis

    2008-01-01

    Levamisole-sensitive acetylcholine receptors (L-AChRs) are ligand-gated ion channels that mediate excitatory neurotransmission at the neuromuscular junctions of nematodes. They constitute a major drug target for anthelminthic treatments because they can be activated by nematode-specific cholinergic agonists such as levamisole. Genetic screens conducted in Caenorhabditis elegans for resistance to levamisole toxicity identified genes that are indispensable for the biosynthesis of L-AChRs. These include 5 genes encoding distinct AChR subunits and 3 genes coding for ancillary proteins involved in assembly and trafficking of the receptors. Despite extensive analysis of L-AChRs in vivo, pharmacological and biophysical characterization of these receptors has been greatly hampered by the absence of a heterologous expression system. Using Xenopus laevis oocytes, we were able to reconstitute functional L-AChRs by coexpressing the 5 distinct receptor subunits and the 3 ancillary proteins. Strikingly, this system recapitulates the genetic requirements for receptor expression in vivo because omission of any of these 8 genes dramatically impairs L-AChR expression. We demonstrate that 3 α- and 2 non-α-subunits assemble into the same receptor. Pharmacological analysis reveals that the prototypical cholinergic agonist nicotine is unable to activate L-AChRs but rather acts as a potent allosteric inhibitor. These results emphasize the role of ancillary proteins for efficient expression of recombinant neurotransmitter receptors and open the way for in vitro screening of novel anthelminthic agents. PMID:19020092

  14. Joint Service Common Operating Environment (COE) Common Geographic Information System functional requirements

    Energy Technology Data Exchange (ETDEWEB)

    Meitzler, W.D.

    1992-06-01

    In the context of this document and COE, the Geographic Information Systems (GIS) are decision support systems involving the integration of spatially referenced data in a problem solving environment. They are digital computer systems for capturing, processing, managing, displaying, modeling, and analyzing geographically referenced spatial data which are described by attribute data and location. The ability to perform spatial analysis and the ability to combine two or more data sets to create new spatial information differentiates a GIS from other computer mapping systems. While the CCGIS allows for data editing and input, its primary purpose is not to prepare data, but rather to manipulate, analyte, and clarify it. The CCGIS defined herein provides GIS services and resources including the spatial and map related functionality common to all subsystems contained within the COE suite of C4I systems. The CCGIS, which is an integral component of the COE concept, relies on the other COE standard components to provide the definition for other support computing services required.

  15. Genome-wide functional profiling reveals genes required for tolerance to benzene metabolites in yeast.

    Directory of Open Access Journals (Sweden)

    Matthew North

    Full Text Available Benzene is a ubiquitous environmental contaminant and is widely used in industry. Exposure to benzene causes a number of serious health problems, including blood disorders and leukemia. Benzene undergoes complex metabolism in humans, making mechanistic determination of benzene toxicity difficult. We used a functional genomics approach to identify the genes that modulate the cellular toxicity of three of the phenolic metabolites of benzene, hydroquinone (HQ, catechol (CAT and 1,2,4-benzenetriol (BT, in the model eukaryote Saccharomyces cerevisiae. Benzene metabolites generate oxidative and cytoskeletal stress, and tolerance requires correct regulation of iron homeostasis and the vacuolar ATPase. We have identified a conserved bZIP transcription factor, Yap3p, as important for a HQ-specific response pathway, as well as two genes that encode putative NAD(PH:quinone oxidoreductases, PST2 and YCP4. Many of the yeast genes identified have human orthologs that may modulate human benzene toxicity in a similar manner and could play a role in benzene exposure-related disease.

  16. Joint Service Common Operating Environment (COE) Common Geographic Information System functional requirements

    Energy Technology Data Exchange (ETDEWEB)

    Meitzler, W.D.

    1992-06-01

    In the context of this document and COE, the Geographic Information Systems (GIS) are decision support systems involving the integration of spatially referenced data in a problem solving environment. They are digital computer systems for capturing, processing, managing, displaying, modeling, and analyzing geographically referenced spatial data which are described by attribute data and location. The ability to perform spatial analysis and the ability to combine two or more data sets to create new spatial information differentiates a GIS from other computer mapping systems. While the CCGIS allows for data editing and input, its primary purpose is not to prepare data, but rather to manipulate, analyte, and clarify it. The CCGIS defined herein provides GIS services and resources including the spatial and map related functionality common to all subsystems contained within the COE suite of C4I systems. The CCGIS, which is an integral component of the COE concept, relies on the other COE standard components to provide the definition for other support computing services required.

  17. Mapping and functional characterisation of a CTCF-dependent insulator element at the 3' border of the murine Scl transcriptional domain.

    Directory of Open Access Journals (Sweden)

    George A Follows

    Full Text Available The Scl gene encodes a transcription factor essential for haematopoietic development. Scl transcription is regulated by a panel of cis-elements spread over 55 kb with the most distal 3' element being located downstream of the neighbouring gene Map17, which is co-regulated with Scl in haematopoietic cells. The Scl/Map17 domain is flanked upstream by the ubiquitously expressed Sil gene and downstream by a cluster of Cyp genes active in liver, but the mechanisms responsible for delineating the domain boundaries remain unclear. Here we report identification of a DNaseI hypersensitive site at the 3' end of the Scl/Map17 domain and 45 kb downstream of the Scl transcription start site. This element is located at the boundary of active and inactive chromatin, does not function as a classical tissue-specific enhancer, binds CTCF and is both necessary and sufficient for insulator function in haematopoietic cells in vitro. Moreover, in a transgenic reporter assay, tissue-specific expression of the Scl promoter in brain was increased by incorporation of 350 bp flanking fragments from the +45 element. Our data suggests that the +45 region functions as a boundary element that separates the Scl/Map17 and Cyp transcriptional domains, and raise the possibility that this element may be useful for improving tissue-specific expression of transgenic constructs.

  18. The varicella-zoster virus ORFS/L (ORF0) gene is required for efficient viral replication and contains an element involved in DNA cleavage.

    Science.gov (United States)

    Kaufer, Benedikt B; Smejkal, Benjamin; Osterrieder, Nikolaus

    2010-11-01

    The genome of varicella-zoster virus (VZV), a human alphaherpesvirus, consists of two unique regions, unique long (U(L)) and unique short (U(S)), each of which is flanked by inverted repeats. During replication, four isomers of the viral DNA are generated which are distinguished by the relative orientations of U(L) and U(S). VZV virions predominantly package two isomeric forms of the genome that have a fixed orientation of U(L). An open reading frame (ORF) of unknown function, ORFS/L, also referred to as ORF0, is located at the extreme terminus of U(L), directly adjacent to the a-like sequences, which are known to be involved in cleavage and packaging of viral DNA. We demonstrate here that the ORFS/L protein localizes to the Golgi network in infected and transfected cells. Furthermore, we were able to demonstrate that deletion of the predicted ORFS/L gene is lethal, while retention of the N-terminal 28 amino acid residues resulted in viable yet replication-impaired virus. The growth defect was only partially attributable to the expression of the ORFS/L product, suggesting that the 5' region of ORFS/L contains a sequence element crucial for cleavage/packaging of viral DNA. Consequently, mutations introduced into the extreme 5' terminus of ORFS/L resulted in a defect in DNA cleavage, indicating that the region is indeed involved in the processing of viral DNA. Since the sequence element has no counterpart at the other end of U(L), we concluded that our results can provide an explanation for the almost exclusive orientation of the U(L) seen in packaged VZV DNA.

  19. Evaluation of group electronegativities and hardness (softness) of group 14 elements and containing functional groups through density functional theory and correlation with NMR spectra data

    Energy Technology Data Exchange (ETDEWEB)

    Vivas-Reyes, R.; Aria, A. [Universidad de Cartagena, Cartagena (Colombia). Facultad de Ciencias Naturales y Exactas. Grupo de Quimica Cuantica y Computacional]. E-mail: rvivasr@unicartagena.edu.co

    2008-07-01

    Quantum Chemical calculations for group 14 elements of Periodic Table (C, Si, Ge, Sn, Pb) and their functional groups have been carried out using Density Functional Theory (DFT) based reactivity descriptors such as group electronegativities, hardness and softness. DFT calculations were performed for a large series of tetra coordinated Sn compounds of the CH{sub 3}SnRR'X type, where X is a halogen and R and R' are alkyl, halogenated alkyl, alkoxy, or alkyl thio groups. The results were interpreted in terms of calculated electronegativity and hardness of the SnRR'X groups, applying a methodology previously developed by Geerlings and coworkers (J. Phys. Chem. 1993, 97, 1826). These calculations allowed to see the regularities concerning the influence of the nature of organic groups RR' and inorganic group X on electronegativities and hardness of the SnRR'X groups; in this case, it was found a very good correlation between the electronegativity of the fragment and experimental {sup 119}Sn chemical shifts, a property that sensitively reflects the change in the valence electronic structure of molecules. This work was complemented with the study of some compounds of the EX and ER types, where E= C, Si, Ge, Sn and R= CH{sub 3}, H, which was performed to study the influence that the central atom has on the electronegativity and hardness of molecules, or whether these properties are mainly affected for the type of ligand bound to the central atom. All these calculations were performed using the B3PW91 functional together with the 6-3 1 1 + + G basis set level for H, C, Si, Ge, F, Cl and Br atoms and the 3-21G for Sn and I atoms. (author)

  20. Direct and indirect effects of nutritional status, physical function and cognitive function on activities of daily living in Japanese older adults requiring long-term care.

    Science.gov (United States)

    Kamo, Tomohiko; Nishida, Yuusuke

    2014-10-01

    To identify the direct and indirect effects of nutritional status, physical function, and cognitive function on activities of daily living in Japanese older adults requiring long-term care. In total, 179 participants aged ≥ 65 years who were eligible for long-term care insurance (mean age 85.5 ± 7.8 years) were recruited for this study. Nutritional status (Mini Nutritional Assessment, Short Form) and physical function (Short Physical Performance Battery) were examined. Activities of daily living, cognitive function and frailty were assessed using the Barthel Index, Mini-Mental State Examination and Clinical Frailty Scale, respectively. Path analysis was used to determine relationships between these factors and the activities of daily living. For Japanese older adults requiring long-term care, pathways were modeled for nutritional status, physical function and the activities of daily living. The total effect of nutritional status was 0.516 (Pnutritional status through physical function on the activities of daily living was 0.458 (Pnutritional status on activities of daily living was observed (b=0.058, P=0.258). The present study identified the complex pathway from nutritional status to the activities of daily living through physical function in aged Japanese people requiring long-term care. These findings suggest that maintaining good nutritional status and nutritional support might delay physical function decline, and prolong the activities of daily living. © 2013 Japan Geriatrics Society.

  1. Differential nuclease sensitivity profiling of chromatin reveals biochemical footprints coupled to gene expression and functional DNA elements in maize.

    Science.gov (United States)

    Vera, Daniel L; Madzima, Thelma F; Labonne, Jonathan D; Alam, Mohammad P; Hoffman, Gregg G; Girimurugan, S B; Zhang, Jinfeng; McGinnis, Karen M; Dennis, Jonathan H; Bass, Hank W

    2014-10-01

    The eukaryotic genome is organized into nucleosomes, the fundamental units of chromatin. The positions of nucleosomes on DNA regulate protein-DNA interactions and in turn influence DNA-templated events. Despite the increasing number of genome-wide maps of nucleosome position, how global changes in gene expression relate to changes in nucleosome position is poorly understood. We show that in nucleosome occupancy mapping experiments in maize (Zea mays), particular genomic regions are highly susceptible to variation introduced by differences in the extent to which chromatin is digested with micrococcal nuclease (MNase). We exploited this digestion-linked variation to identify protein footprints that are hypersensitive to MNase digestion, an approach we term differential nuclease sensitivity profiling (DNS-chip). Hypersensitive footprints were enriched at the 5' and 3' ends of genes, associated with gene expression levels, and significantly overlapped with conserved noncoding sequences and the binding sites of the transcription factor KNOTTED1. We also found that the tissue-specific regulation of gene expression was linked to tissue-specific hypersensitive footprints. These results reveal biochemical features of nucleosome organization that correlate with gene expression levels and colocalize with functional DNA elements. This approach to chromatin profiling should be broadly applicable to other species and should shed light on the relationships among chromatin organization, protein-DNA interactions, and genome regulation.

  2. Dependence of the functional characteristics of thermomechanically processed titanium nickelide on the size of the structural elements of austenite

    Science.gov (United States)

    Polyakova-Vachiyan, K. A.; Ryklina, E. P.; Prokoshkin, S. D.; Dubinskii, S. M.

    2016-08-01

    Effect of the size of the elements of the mixed structure of B2 austenite, which consists of nanosized grains and subgrains of a polygonized substructure, on the functional properties of the Ti-50.7 at % Ni alloy preliminarily subjected to a low-temperature thermomechanical treatment (LTMT) and post-deformation annealing (PDA), has been investigated. The generation of the shape-memory effect (SME) and reversible two-way SME (TWSME) was performed using bending deformation. A maximum (for the Ti-Ni alloys) value of the recovery strain ɛr = 15.5 ± 0.5% has been obtained after annealing at 600°C for 1 h (recrystallized structure) and after LTMT + PDA at 430°C for 10 h (mixed nanocrystalline and nanosubgrain structure). The behavior of the parameters of the SME and TWSME in different structural states has been considered. A comparative study of the effect of the temperature and time of holding at a temperature upon the PDA on the formation of the microstructure and submicrostructure of the B2 austenite has been performed.

  3. Object localization within turbid slab media using time-resolved transillumination contrast functions: a finite element approach

    Science.gov (United States)

    Piron, V.; L'Huillier, J. P.; Mansouri, C.

    2007-07-01

    In the last few years, the propagation of diffuse photons in scattering media has become an important field of interest. This is mainly due to the possibility offered by the low absorption of light in the range 700 to 900nm. Indeed, this property leads to a potential deep penetration. But a non negligible limitation appears: the scattering processes strongly reduce both the contrast and the resolution. In this paper, the time-dependent light propagation in highly scattering media containing an inclusion is solved by means of a finite element method, tacking into account Robin type air-tissue boundary conditions. This study is devoted to the depth localization of a tumor enclosed into a breast-like slab. The tissue is modeled by a rectangular meshed domain that mimics a breast compressed between two transparent plates. Cartesian coordinates are used in order to solve the time-dependent diffusion approximation. A short laser pulse of 1ps is considered. The transillumination technique is able to laterally detect the object when the source and detector are moved together on the same axis. In order to perform the localization of the inclusion in this study, the optical properties of the object were varied. Knowing the lateral position of the inclusion, we derive interesting temporal contrast functions based on the mean time of flight of photons. These functions allow to localize in depth the inclusion under the assumption that the object is very diffusing. To conclude, our study demonstrates the possibility to detect laterally and axially a tumor-like inclusion enclosed in breast-like tissues.

  4. The TAK1-JNK cascade is required for IRF3 function in the innate immune response

    Institute of Scientific and Technical Information of China (English)

    Bianhong Zhang; Meng Li; Liang Chen; Kai Yang; Yufei Shan; Lianhui Zhu; Shaogang Sun; Lin Li; Chen Wang

    2009-01-01

    Interferon regulatory factor (IRF)3 is critical for the transcriptional induction of chemokines and cytokines during viral or bacterial invasion. The kinases Tank binding kinase (TBK)1 and Ikappa B kinase (IKK)ε can phosphorylate the C-terminal part of IRF3 and play important roles in IRF3 activation. In this study, we show that another kinase, c-Jun-NH2-terminal kinase (JNK), phosphorylates IRF3 on its N-terminal serine 173 residue, and TAK1 can stimulate IRF3 phosphorylation via JNK. JNK specific inhibitor SP600125 inhibits the N-terminal phosphorylation without affecting the C-terminal phosphorylation. In addition, IRF3-mediated gene expressions on lipopolysaccharide (LPS) or polyinosinic-cytidylic acid (polyI:C) treatment are severely impaired by SP600125, as well as for reporter gene assay of IRF3 activation. Knockdown of TAK1 further confirmed these observations. Interestingly, constitutive active IRF3(5D) can be inhibited by SP600125; JNK1 can synergize the action of IRF3(5D), but not the S173A-IRF3(5D) mutant. More importantly, polyI:C failed to induce the phosphorylation of mutant S173A and SP600125 dramatically abrogated IRF3 phosphorylation and dimerization that was stimulated by polyI:C. Thus, this study demonstrates that the TAK1-JNK cascade is required for IRF3 function, in addition to TBK1/IKKε, uncovering a new mechanism for mitogen-activated protein (MAP) kinase to regulate the innate immunity.

  5. Programmed cell death activated by Rose Bengal in Arabidopsis thaliana cell suspension cultures requires functional chloroplasts.

    Science.gov (United States)

    Gutiérrez, Jorge; González-Pérez, Sergio; García-García, Francisco; Daly, Cara T; Lorenzo, Oscar; Revuelta, José L; McCabe, Paul F; Arellano, Juan B

    2014-07-01

    Light-grown Arabidopsis thaliana cell suspension culture (ACSC) were subjected to mild photooxidative damage with Rose Bengal (RB) with the aim of gaining a better understanding of singlet oxygen-mediated defence responses in plants. Additionally, ACSC were treated with H2O2 at concentrations that induced comparable levels of protein oxidation damage. Under low to medium light conditions, both RB and H2O2 treatments activated transcriptional defence responses and inhibited photosynthetic activity, but they differed in that programmed cell death (PCD) was only observed in cells treated with RB. When dark-grown ACSC were subjected to RB in the light, PCD was suppressed, indicating that the singlet oxygen-mediated signalling pathway in ACSC requires functional chloroplasts. Analysis of up-regulated transcripts in light-grown ACSC, treated with RB in the light, showed that both singlet oxygen-responsive transcripts and transcripts with a key role in hormone-activated PCD (i.e. ethylene and jasmonic acid) were present. A co-regulation analysis proved that ACSC treated with RB exhibited higher correlation with the conditional fluorescence (flu) mutant than with other singlet oxygen-producing mutants or wild-type plants subjected to high light. However, there was no evidence for the up-regulation of EDS1, suggesting that activation of PCD was not associated with the EXECUTER- and EDS1-dependent signalling pathway described in the flu mutant. Indigo Carmine and Methylene Violet, two photosensitizers unable to enter chloroplasts, did not activate transcriptional defence responses in ACSC; however, whether this was due to their location or to their inherently low singlet oxygen quantum efficiencies was not determined.

  6. Reserpine-induced reduction in norepinephrine transporter function requires catecholamine storage vesicles.

    Science.gov (United States)

    Mandela, Prashant; Chandley, Michelle; Xu, Yao-Yu; Zhu, Meng-Yang; Ordway, Gregory A

    2010-01-01

    Treatment of rats with reserpine, an inhibitor of the vesicular monoamine transporter (VMAT), depletes norepinephrine (NE) and regulates NE transporter (NET) expression. The present study examined the molecular mechanisms involved in regulation of the NET by reserpine using cultured cells. Exposure of rat PC12 cells to reserpine for a period as short as 5min decreased [(3)H]NE uptake capacity, an effect characterized by a robust decrease in the V(max) of the transport of [(3)H]NE. As expected, reserpine did not displace the binding of [(3)H]nisoxetine from the NET in membrane homogenates. The potency of reserpine for reducing [(3)H]NE uptake was dramatically lower in SK-N-SH cells that have reduced storage capacity for catecholamines. Reserpine had no effect on [(3)H]NE uptake in HEK-293 cells transfected with the rat NET (293-hNET), cells that lack catecholamine storage vesicles. NET regulation by reserpine was independent of trafficking of the NET from the cell surface. Pre-exposure of cells to inhibitors of several intracellular signaling cascades known to regulate the NET, including Ca(2+)/Ca(2+)-calmodulin dependent kinase and protein kinases A, C and G, did not affect the ability of reserpine to reduce [(3)H]NE uptake. Treatment of PC12 cells with the catecholamine depleting agent, alpha-methyl-p-tyrosine, increased [(3)H]NE uptake and eliminated the inhibitory effects of reserpine on [(3)H]NE uptake. Reserpine non-competitively inhibits NET activity through a Ca(2+)-independent process that requires catecholamine storage vesicles, revealing a novel pharmacological method to modify NET function. Further characterization of the molecular nature of reserpine's action could lead to the development of alternative therapeutic strategies for treating disorders known to be benefitted by treatment with traditional competitive NET inhibitors.

  7. DNA element downstream of the κB site in the Lcn2 promoter is required for transcriptional activation by IκBζ and NF-κB p50.

    Science.gov (United States)

    Kohda, Akira; Yamazaki, Soh; Sumimoto, Hideki

    2014-08-01

    The nuclear protein IκBζ activates transcription of a subset of NF-κB-dependent innate immune genes such as Lcn2 encoding the antibacterial protein lipocalin-2. IκBζ functions as a coactivator via its interaction with NF-κB p50, which contains a DNA-binding Rel-homology domain but lacks a transcriptional activation domain. However cis-regulatory elements involved in IκBζ function have remained unknown. Here, we show that, although IκBζ by itself is unable to associate with the Lcn2 promoter, IκBζ interacts with the promoter via p50 binding to the NF-κB-binding site (κB site) and the interaction also requires the pyrimidine-rich site (CCCCTC) that localizes seven bases downstream of the κB site. The pyrimidine-rich site is also essential for IκBζ-mediated activation of the Lcn2 gene. Introduction of both sites into an IκBζ-independent gene culminates in IκBζ-p50-DNA complex formation and transcriptional activation. Furthermore, spacing between the two sites is crucial for both IκBζ-DNA interaction and IκBζ-mediated gene activation. Thus, the pyrimidine-rich IκBζ-responsive site plays an essential role in productive interaction of IκBζ with the p50-DNA complex.

  8. Identifying the Functional Requirements for an Arizona Astronomy Data Hub (AADH)

    Science.gov (United States)

    Stahlman, G.; Heidorn, P. B.

    2015-12-01

    Astronomy data represent a curation challenge for information managers, as well as for astronomers. Extracting knowledge from these heterogeneous and complex datasets is particularly complicated and requires both interdisciplinary and domain expertise to accomplish true curation, with an overall goal of facilitating reproducible science through discoverability and persistence. A group of researchers and professional staff at the University of Arizona held several meetings during the spring of 2015 about astronomy data and the role of the university in curation of that data. The group decided that it was critical to obtain a broader consensus on the needs of the community. With assistance from a Start for Success grant provided by the University of Arizona Office of Research and Discovery and funding from the American Astronomical Society (AAS), a workshop was held in early July 2015, with 28 participants plus 4 organizers in attendance. Representing University researchers as well as astronomical facilities and a scholarly society, the group verified that indeed there is a problem with the long-term curation of some astronomical data not associated with major facilities, and that a repository or "data hub" with the correct functionality could facilitate research and the preservation and use of astronomy data. The workshop members also identified a set of next steps, including the identification of possible data and metadata to be included in the Hub. The participants further helped to identify additional information that must be gathered before construction of the AADH could begin, including identifying significant datasets that do not currently have sufficient preservation and dissemination infrastructure, as well as some data associated with journal publications and the broader context of the data beyond that directly published in the journals. Workshop participants recommended that a set of grant proposal should be developed that ensures community buy-in and

  9. Executive function training with game elements for obese children: A novel treatment to enhance self-regulatory abilities for weight-control

    NARCIS (Netherlands)

    Verbeken, S.; Braet, C.; Goossens, L.; van der Oord, S.

    2013-01-01

    For obese children behavioral treatment results in only small changes in relative weight and frequent relapse. The current study investigated the effects of an Executive Functioning (EF) training with game-elements on weight loss maintenance in obese children, over and above the care as usual in an

  10. Accumulation of germanium and rare earth elements in functional groups of selected energy crops cultivated on two different soils

    Science.gov (United States)

    Wiche, Oliver; Székely, Balázs

    2016-04-01

    A field experiment was conducted to investigate the uptake of Ge and selected REEs in functional groups of selected crop species. Five species belonging to the functional group of grasses (Hordeum vulgare, Zea mays, Avena sativa, Panicum miliaceum and Phalaris arundinacea) and four species from the group of herbs (Lupinus albus, Lupinus angustifolius, Fagopyrum esculentum and Brassica napus) were cultivated in parallel on two soils with slightly alkaline (soil A: pH = 7.8) and slightly acidic (soil B: pH = 6.8) conditions. After harvest, concentrations of Ge, La, Nd, Gd, Er, P, Fe, Mn and Si in shoot tissues were determined with ICP-MS. Concentrations of Ge were significantly higher in grasses than in herbs. Conversely, concentrations of La and Nd were significantly higher in herbs, than in grasses. Highest concentrations were measured in Brassica napus (REEs) and Zea mays (Ge). Concentrations of Ge significantly correlated with that of Si in the shoots showing low concentrations in herbs and high concentrations in grasses, indicating a common mechanism during the uptake in grasses. Concentrations of REEs correlated significantly with that of Fe, indicating increasing concentrations of REEs with increasing concentrations of Fe. Cultivation of species on the slightly acidic soil significantly increased the uptake Ge in Lupinus albus and Phalaris arundinacea and the uptake of La and Nd in all species except of Phalaris arundinacea. This study demonstrated that commonly used field crops could be regarded as suitable candidates for a phytomining of Ge and REEs, since these species develop high yields of shoots, high concentrations of elements and are widely used in agricultural practice. Under soil conditions where bioavailability of Ge and REEs is expected to be low (soil A) accumulation can be estimated at 1.8 g/ha Ge in Z. mays and 3.7 g/ha REEs (1.5 g/ha La, 1.4 g/ha Nd, 0.6 g/ha Gd, 0.3 g/ha Er), respectively, in B. napus, assuming a constant high efficiency of

  11. Determining Consistency of Tillage Direction with Soil Erosion Protection Requirements as The Element of Decision-Making Process in Planning and Applying Land Consolidation

    Science.gov (United States)

    Bozek, Piotr; Janus, Jaroslaw; Taszakowski, Jaroslaw; Glowacka, Agnieszka

    2016-10-01

    Water erosion is one of the factors which have negative effect on soil productivity. It often leads to irreversible soil degradation, making soil worthless for agricultural activities. One way of preventing water erosion is making the direction of cultivation perpendicular to the direction of rainwater run-off. Matching the direction with the shape of parcels boundaries in small and extended ones is often possible only through changes in the configuration of property boundaries, which is possible only in the process of land consolidation. The article presents methodology of qualifying the areas for changes in boundaries configuration and cultivation direction in view of existing erosion risk. A computation process was suggested that uses, among others, LIDAR data to model the terrain shape precisely as well as cadastral data that defines the geometry of parcels and, resulting from it, the direction of cultivation and form of use. The suggested process includes also the information on the texture of soil upper horizons from soil agricultural maps. The RUSLE erosion model was applied and the computation process took place in ArcGIS environment with the use of dedicated algorithms suggested and implemented to solve the formulated problem. Computations were conducted for test area of several hundred hectares which was characterized by vast diversity of soil types and landforms. The results prove the usefulness of the suggested method as an element of systems that support decision-making processes used in the stage of determining objects chosen for the realization of consolidating processes (including local consolidation, which covers only chosen fragment of a village). They can also be used in the stage of completing detailed plans of parcels distribution in land consolidation process. The importance of the method is particularly seen in the analysis of areas where land fragmentation indices are unfavourable. Especially in these cases, without the reorganization of

  12. C2 Link Security for UAS: Technical Literature Study and Preliminary Functional Requirements. Version 0.9 (Working Draft)

    Science.gov (United States)

    2005-01-01

    This document provides a study of the technical literature related to Command and Control (C2) link security for Unmanned Aircraft Systems (UAS) for operation in the National Airspace System (NAS). Included is a preliminary set of functional requirements for C2 link security.

  13. Adaptive behavior, functional outcomes, and quality of life outcomes of children requiring urgent ICU admission.

    Science.gov (United States)

    Ebrahim, Shanil; Singh, Simran; Hutchison, Jamie S; Kulkarni, Abhaya V; Sananes, Renee; Bowman, Kerry W; Parshuram, Christopher S

    2013-01-01

    To describe the adaptive behavior and functional outcomes, and health-related quality of life of children who were urgently admitted to the ICU. Prospective observational study. Critical Care Medicine program at a University-affiliated pediatric institution. Urgently admitted patients, aged 1 month to 18 yrs. None. We evaluated children's adaptive behavior functioning with the Vineland Adaptive Behavior Scale-2, functional outcomes with the pediatric cerebral performance category and pediatric overall performance category, and health-related quality of life with the Pediatric Quality of Life Inventory 4 and Visual Analogue Scale. We enrolled 91 children and 65 (71%) completed the 1-month assessment. Patients had a mean (SD) Vineland Adaptive Behavior Scale-2 rating of 83.2 (± 24.8), considered to be moderate-low adaptive behavior functioning. From baseline to 1 month, pediatric cerebral performance category ratings did not significantly change (p = 0.59) and pediatric overall performance category ratings significantly improved (p = 0.03). Visual Analogue Scale ratings significantly worsened from baseline to 1 wk (p adaptive behavior functioning. Neurological admissions, worse pediatric cerebral performance category score at baseline, longer ICU stay, and longer duration of extracorporeal membrane oxygenation were independently associated with worse functional outcome. Worse pediatric cerebral performance category score at baseline, longer ICU stay, and longer duration of extracorporeal membrane oxygenation were independently associated with worse health-related quality of life. Children surviving PICU have significant adaptive behavior functioning and functional morbidity and reduced health-related quality of life. Although neurologic morbidity following ICU was associated with baseline state, we found that resuscitation intensity and illness severity factors were independently associated with the development of acquired brain injury and reduced quality of life.

  14. Functional requirements of computer systems for the U.S. Geological Survey, Water Resources Division, 1988-97

    Science.gov (United States)

    Hathaway, R.M.; McNellis, J.M.

    1989-01-01

    Investigating the occurrence, quantity, quality, distribution, and movement of the Nation 's water resources is the principal mission of the U.S. Geological Survey 's Water Resources Division. Reports of these investigations are published and available to the public. To accomplish this mission, the Division requires substantial computer technology to process, store, and analyze data from more than 57,000 hydrologic sites. The Division 's computer resources are organized through the Distributed Information System Program Office that manages the nationwide network of computers. The contract that provides the major computer components for the Water Resources Division 's Distributed information System expires in 1991. Five work groups were organized to collect the information needed to procure a new generation of computer systems for the U. S. Geological Survey, Water Resources Division. Each group was assigned a major Division activity and asked to describe its functional requirements of computer systems for the next decade. The work groups and major activities are: (1) hydrologic information; (2) hydrologic applications; (3) geographic information systems; (4) reports and electronic publishing; and (5) administrative. The work groups identified 42 functions and described their functional requirements for 1988, 1992, and 1997. A few new functions such as Decision Support Systems and Executive Information Systems, were identified, but most are the same as performed today. Although the number of functions will remain about the same, steady growth in the size, complexity, and frequency of many functions is predicted for the next decade. No compensating increase in the Division 's staff is anticipated during this period. To handle the increased workload and perform these functions, new approaches will be developed that use advanced computer technology. The advanced technology is required in a unified, tightly coupled system that will support all functions simultaneously

  15. HDAC Activity Is Required for Efficient Core Promoter Function at the Mouse Mammary Tumor Virus Promoter

    Directory of Open Access Journals (Sweden)

    Sang C. Lee

    2011-01-01

    Full Text Available Histone deacetylases (HDACs have been shown to be required for basal or inducible transcription at a variety of genes by poorly understood mechanisms. We demonstrated previously that HDAC inhibition rapidly repressed transcription from the mouse mammary tumor virus (MMTV promoter by a mechanism that does not require the binding of upstream transcription factors. In the current study, we find that HDACs work through the core promoter sequences of MMTV as well as those of several cellular genes to facilitate transcriptional initiation through deacetylation of nonhistone proteins.

  16. Functional requirements for the Automated Transportation Management System: TTP number: RL 439002

    Energy Technology Data Exchange (ETDEWEB)

    Portsmouth, J.H. [Westinghouse Hanford Co., Richland, WA (United States)

    1992-12-31

    This requirements analysis, documents Department of Energy (DOE) transportation management procedures for the purpose of providing a clear and mutual understanding between users and designers of the proposed Automated Transportation Management System (ATMS). It is imperative that one understand precisely how DOE currently performs traffic management tasks; only then can an integrated system be proposed that successfully satisfies the major requirements of transportation managers and other system users. Accordingly, this report describes the current workings of DOE transportation organizations and then proposes a new system which represents a synthesis of procedures (both current and desired) which forms the basis for further systems development activities.

  17. Elemental Chemical Puzzlers

    Science.gov (United States)

    Thomas, Nicholas C.

    2009-01-01

    This paper provides nine short chemically based puzzles or problems extensible for use with students from middle school to college. Some of these will strengthen students' recognition of individual elements and element names. Others require students to focus on the salient properties of given chemical elements.

  18. Expression and secretion of Salmonella pathogenicity island-2 virulence genes in response to acidification exhibit differential requirements of a functional type III secretion apparatus and SsaL.

    Science.gov (United States)

    Coombes, Brian K; Brown, Nat F; Valdez, Yanet; Brumell, John H; Finlay, B Brett

    2004-11-26

    Salmonella pathogenicity island (SPI)-2 is pivotal to the intracellular survival of Salmonella and for virulence in mammals. SPI-2 encodes virulence factors (called effectors) that are translocated into the host cell, a type III secretion apparatus and a two-component regulatory system that regulates intracellular expression of SPI-2. Salmonella SPI-2 secretion activity appears to be induced in response to acidification of the vacuole in which it replicates. Here we show that the expression of the SPI-2 proteins, SseB and SseD (filament and pore forming components of the secretion apparatus, respectively) in response to acidification requires an intact secretion system and SsaL, a Salmonella homologue of SepL, a regulator required for type III-dependent secretion of translocators but not effectors in attaching and effacing gastrointestinal pathogens. We show that the expression of SPI-2-encoded effectors is acid-regulated but can be uncoupled from the expression of filament and translocon components, thus showing a differential requirement of SsaL for expression. The secretion and translocation of SPI-2-encoded effectors requires SsaL, but SsaL is dispensable for the secretion of SPI-2 effectors encoded in other pathogenicity loci, suggesting a secretion regulation function for SsaL. Further, we demonstrate that the differential expression of adjacent genes within the sseA operon (sseD and sseE) occurs at the transcriptional level. These data indicate that a Salmonella SPI-2 activation state is achieved by an acidregulated response that requires SsaL. These data also suggest the existence of a previously unrecognized regulatory element within SPI-2 for the "effector operon" region downstream of sseD that might demarcate the expression of translocators and effectors.

  19. Functions and requirements of conserved RNA structures in the 3’ untranslated region of Flaviviruses

    NARCIS (Netherlands)

    Agostinho Gonçalves Costa da Silva, Patrícia

    2011-01-01

    The Flavivirus genus contains nearly 80 viruses, including many important human pathogens such as dengue virus, yellow fever virus, West Nile virus and tick-borne encephalitis virus. To reduce and prevent the impact of flavivirus infection on society, vaccines and effective therapies are required. H

  20. PR72, a novel regulator of Wnt signaling required for Naked cuticle function

    NARCIS (Netherlands)

    Creyghton, M.P.; Roël, G.; Eichhorn, P.J.A.; Hijmans, E.M.; Maurer, I.; Destrée, O.; Bernards, R.A.

    2005-01-01

    The Wnt signaling cascade is a central regulator of cell fate determination during embryonic development, whose deregulation contributes to oncogenesis. Naked cuticle is the first Wnt-induced antagonist found in this pathway, establishing a negative-feedback loop that limits the Wnt signal required

  1. Using a Functional Architecture to Identify Human-Automation Trust Needs and Design Requirements

    Science.gov (United States)

    2016-12-01

    Intelligence , Surveillance, and Reconnaissance (ISR) mission without a continuous communication link to human operators for trust needs. The factors that affect...performance link to human knowledge, perception and beliefs. From the analysis , automation design requirements that link to the identified trust...performing an Intelligence , Surveillance, and Reconnaissance (ISR) mission without a continuous communication link to human operators for trust needs

  2. Functional Mobility Testing: A Novel Method to Establish Human System Interface Design Requirements

    Science.gov (United States)

    England, Scott A.; Benson, Elizabeth A.; Rajulu, Sudhakar

    2008-01-01

    Across all fields of human-system interface design it is vital to posses a sound methodology dictating the constraints on the system based on the capabilities of the human user. These limitations may be based on strength, mobility, dexterity, cognitive ability, etc. and combinations thereof. Data collected in an isolated environment to determine, for example, maximal strength or maximal range of motion would indeed be adequate for establishing not-to-exceed type design limitations, however these restraints on the system may be excessive over what is basally needed. Resources may potentially be saved by having a technique to determine the minimum measurements a system must accommodate. This paper specifically deals with the creation of a novel methodology for establishing mobility requirements for a new generation of space suit design concepts. Historically, the Space Shuttle and the International Space Station vehicle and space hardware design requirements documents such as the Man-Systems Integration Standards and International Space Station Flight Crew Integration Standard explicitly stated that the designers should strive to provide the maximum joint range of motion capabilities exhibited by a minimally clothed human subject. In the course of developing the Human-Systems Integration Requirements (HSIR) for the new space exploration initiative (Constellation), an effort was made to redefine the mobility requirements in the interest of safety and cost. Systems designed for manned space exploration can receive compounded gains from simplified designs that are both initially less expensive to produce and lighter, thereby, cheaper to launch.

  3. PR72, a novel regulator of Wnt signaling required for Naked cuticle function

    NARCIS (Netherlands)

    Creyghton, M.P.; Roël, G.; Eichhorn, P.J.A.; Hijmans, E.M.; Maurer, I.; Destrée, O.; Bernards, R.A.

    2005-01-01

    The Wnt signaling cascade is a central regulator of cell fate determination during embryonic development, whose deregulation contributes to oncogenesis. Naked cuticle is the first Wnt-induced antagonist found in this pathway, establishing a negative-feedback loop that limits the Wnt signal required

  4. Substance of Presentation on The J-Coefficient and Job-Element Procedure as a Means of Integrating All Evidences of Ability to Meet Educational or Job Requirements.

    Science.gov (United States)

    Primoff, Ernest S.

    This paper concerns two features of a project on the assessment of job potential: the J-Coefficient, and the J-Scale. The J-Coefficient is a means of determining the validity of a test for a position on the basis of (1) the Beta Weights for predicting test scores from a set of elements and (2) estimates of importance of each element in the…

  5. Functional and operational requirements document : building 1012, Battery and Energy Storage Device Test Facility, Sandia National Laboratories, New Mexico.

    Energy Technology Data Exchange (ETDEWEB)

    Johns, William H.

    2013-11-01

    This report provides an overview of information, prior studies, and analyses relevant to the development of functional and operational requirements for electrochemical testing of batteries and energy storage devices carried out by Sandia Organization 2546, Advanced Power Sources R&D. Electrochemical operations for this group are scheduled to transition from Sandia Building 894 to a new Building located in Sandia TA-II referred to as Building 1012. This report also provides background on select design considerations and identifies the Safety Goals, Stakeholder Objectives, and Design Objectives required by the Sandia Design Team to develop the Performance Criteria necessary to the design of Building 1012. This document recognizes the Architecture-Engineering (A-E) Team as the primary design entity. Where safety considerations are identified, suggestions are provided to provide context for the corresponding operational requirement(s).

  6. A Monte Carlo investigation of experimental data requirements for fitting polynomial functions

    Science.gov (United States)

    Canavos, G. C.

    1974-01-01

    This report examines the extent to which sample size affects the accuracy of a low order polynomial approximation of an experimentally observed quantity and establishes a trend toward improvement in the accuracy of the approximation as a function of sample size. The task is made possible through a simulated analysis carried out by the Monte Carlo method, in which data are generated by using several transcendental or algebraic functions as models. Contaminated data of varying amounts are fitted to linear quadratic or cubic polynomials, and the behavior of the mean-squared error of the residual variance is determined as a function of sample size. Results indicate that the effect of the size of the sample is significant only for relatively small sample sizes and diminishes drastically for moderate and large amounts of experimental data.

  7. Kyphoplasty increases vertebral height, decreases both pain score and opiate requirements while improving functional status.

    Science.gov (United States)

    Tolba, Reda; Bolash, Robert B; Shroll, Joshua; Costandi, Shrif; Dalton, Jarrod E; Sanghvi, Chirag; Mekhail, Nagy

    2014-03-01

    Vertebral compression fractures can result from advanced osteoporosis, or less commonly from metastatic or traumatic insults to the vertebral column, and result in disabling pain and decreased functional capacity. Various vertebral augmentation options including kyphoplasty aim at preventing the sequelae of pain and immobility that can develop as the result of the vertebral fractures. The mechanism for pain relief following kyphoplasty is not entirely understood, and the restoration of a portion of the lost vertebral height is a subject of debate. We retrospectively reviewed radiographic imaging, pain relief, analgesic intake and functional outcomes in 67 consecutive patients who underwent single- or multilevel kyphoplasty with the primary goal of quantifying the restoration of lost vertebral height. We observed a mean of 45% of the lost vertebral height restored postprocedurally. Secondarily, kyphoplasty was associated with significant decreases in pain scores, daily morphine consumption and improvement in patient-reported functional measures.

  8. Antibody-Mediated Targeting of Tau In Vivo Does Not Require Effector Function and Microglial Engagement

    Directory of Open Access Journals (Sweden)

    Seung-Hye Lee

    2016-08-01

    Full Text Available The spread of tau pathology correlates with cognitive decline in Alzheimer’s disease. In vitro, tau antibodies can block cell-to-cell tau spreading. Although mechanisms of anti-tau function in vivo are unknown, effector function might promote microglia-mediated clearance. In this study, we investigated whether antibody effector function is required for targeting tau. We compared efficacy in vivo and in vitro of two versions of the same tau antibody, with and without effector function, measuring tau pathology, neuron health, and microglial function. Both antibodies reduced accumulation of tau pathology in Tau-P301L transgenic mice and protected cultured neurons against extracellular tau-induced toxicity. Only the full-effector antibody enhanced tau uptake in cultured microglia, which promoted release of proinflammatory cytokines. In neuron-microglia co-cultures, only effectorless anti-tau protected neurons, suggesting full-effector tau antibodies can induce indirect toxicity via microglia. We conclude that effector function is not required for efficacy, and effectorless tau antibodies may represent a safer approach to targeting tau.

  9. A functional cutin matrix is required for plant protection against water loss

    OpenAIRE

    Chen, Guoxiong; Komatsuda, Takao; Ma, Jian Feng; Li, Chao; Yamaji, Naoki; Nevo, Eviatar

    2011-01-01

    The plant cuticle, a cutin matrix embedded with and covered by wax, seals the aerial organ's surface to protect the plant against uncontrolled water loss. The cutin matrix is essential for the cuticle to function as a barrier to water loss. Recently, we identified from wild barley a drought supersensitive mutant, eibi1, which is caused by a defective cutin matrix as the result of the loss of function of HvABCG31, an ABCG full transporter. Here, we report that eibi1 epidermal cells contain lip...

  10. Conserved aspartic acid 233 and alanine 231 are not required for poliovirus polymerase function in replicons

    Directory of Open Access Journals (Sweden)

    Freistadt Marion S

    2007-03-01

    Full Text Available Abstract Nucleic acid polymerases have similar structures and motifs. The function of an aspartic acid (conserved in all classes of nucleic acid polymerases in motif A remains poorly understood in RNA-dependent RNA polymerases. We mutated this residue to alanine in a poliovirus replicon. The resulting mutant could still replicate, although at a reduced level. In addition, mutation A231C (also in motif A yielded high levels of replication. Taken together these results show that poliovirus polymerase conserved residues D233 and A231 are not essential to poliovirus replicon function.

  11. Conserved aspartic acid 233 and alanine 231 are not required for poliovirus polymerase function in replicons

    Science.gov (United States)

    Freistadt, Marion S; Eberle, Karen E

    2007-01-01

    Nucleic acid polymerases have similar structures and motifs. The function of an aspartic acid (conserved in all classes of nucleic acid polymerases) in motif A remains poorly understood in RNA-dependent RNA polymerases. We mutated this residue to alanine in a poliovirus replicon. The resulting mutant could still replicate, although at a reduced level. In addition, mutation A231C (also in motif A) yielded high levels of replication. Taken together these results show that poliovirus polymerase conserved residues D233 and A231 are not essential to poliovirus replicon function. PMID:17352827

  12. Systems engineering functions and requirements for the Hanford cleanup mission. First issue, Addendum 2

    Energy Technology Data Exchange (ETDEWEB)

    Holmes, J.J.

    1994-01-01

    This addendum provides the technical detail of a systems engineering functional analysis for the Hanford cleanup mission. Details of the mission analysis including mission statement, scope, problem statement, initial state definition, and final state definition are provided in the parent document. The functional analysis consists of Input Computer Automated Manufacturing Definition (IDEFO) diagrams an definitions, which will be understood by systems engineers, but which may be difficult for others to comprehend. For a more complete explanation of this work, refer to the parent document. The analysis covers the total Hanford cleanup mission including the decomposition levels at which the various Hanford programs or integrated activities are encountered.

  13. Definition of Specific Functions and Procedural Skills Required by Cuban Specialists in Intensive Care and Emergency Medicine.

    Science.gov (United States)

    Véliz, Pedro L; Berra, Esperanza M; Jorna, Ana R

    2015-07-01

    INTRODUCTION Medical specialties' core curricula should take into account functions to be carried out, positions to be filled and populations to be served. The functions in the professional profile for specialty training of Cuban intensive care and emergency medicine specialists do not include all the activities that they actually perform in professional practice. OBJECTIVE Define the specific functions and procedural skills required of Cuban specialists in intensive care and emergency medicine. METHODS The study was conducted from April 2011 to September 2013. A three-stage methodological strategy was designed using qualitative techniques. By purposive maximum variation sampling, 82 professionals were selected. Documentary analysis and key informant criteria were used in the first stage. Two expert groups were formed in the second stage: one used various group techniques (focus group, oral and written brainstorming) and the second used a three-round Delphi method. In the final stage, a third group of experts was questioned in semistructured in-depth interviews, and a two-round Delphi method was employed to assess priorities. RESULTS Ultimately, 78 specific functions were defined: 47 (60.3%) patient care, 16 (20.5%) managerial, 6 (7.7%) teaching, and 9 (11.5%) research. Thirty-one procedural skills were identified. The specific functions and procedural skills defined relate to the profession's requirements in clinical care of the critically ill, management of patient services, teaching and research at the specialist's different occupational levels. CONCLUSIONS The specific functions and procedural skills required of intensive care and emergency medicine specialists were precisely identified by a scientific method. This product is key to improving the quality of teaching, research, administration and patient care in this specialty in Cuba. The specific functions and procedural skills identified are theoretical, practical, methodological and social contributions to

  14. Tissue Engineering of Blood Vessels: Functional Requirements, Progress, and Future Challenges.

    Science.gov (United States)

    Kumar, Vivek A; Brewster, Luke P; Caves, Jeffrey M; Chaikof, Elliot L

    2011-09-01

    Vascular disease results in the decreased utility and decreased availability of autologus vascular tissue for small diameter (engineered replacement vessels represent an ideal solution to this clinical problem. Ongoing progress requires combined approaches from biomaterials science, cell biology, and translational medicine to develop feasible solutions with the requisite mechanical support, a non-fouling surface for blood flow, and tissue regeneration. Over the past two decades interest in blood vessel tissue engineering has soared on a global scale, resulting in the first clinical implants of multiple technologies, steady progress with several other systems, and critical lessons-learned. This review will highlight the current inadequacies of autologus and synthetic grafts, the engineering requirements for implantation of tissue-engineered grafts, and the current status of tissue-engineered blood vessel research.

  15. Are hummingbirds facultatively ammonotelic? Nitrogen excretion and requirements as a function of body size.

    Science.gov (United States)

    McWhorter, Todd J; Powers, Donald R; Martínez Del Rio, Carlos

    2003-01-01

    Most birds are uricotelic. An exception to this rule may be nectar-feeding birds, which excrete significant amounts of ammonia under certain conditions. Although ammonia is toxic, because it is highly water soluble its excretion may be facilitated in animals that ingest and excrete large amounts of water. Bird-pollinated plants secrete carbohydrate- and water-rich floral nectars that contain exceedingly little protein. Thus, nectar-feeding birds are faced with the dual challenge of meeting nitrogen requirements while disposing of large amounts of water. The peculiar diet of nectar-feeding birds suggests two hypotheses: (1) these birds must have low protein requirements, and (2) when they ingest large quantities of water their primary nitrogen excretion product may be ammonia. To test these hypotheses, we measured maintenance nitrogen requirements (MNR) and total endogenous nitrogen losses (TENL) in three hummingbird species (Archilochus alexandri, Eugenes fulgens, and Lampornis clemenciae) fed on diets with varying sugar, protein, and water content. We also quantified the form in which the by-products of nitrogen metabolism were excreted. The MNR and TENL of the hummingbirds examined were exceptionally low. However, no birds excreted more than 50% of nitrogen as ammonia or more nitrogen as ammonia than urates. Furthermore, ammonia excretion was not influenced by either water or protein intake. The smallest species (A. alexandri) excreted a significantly greater proportion (>25%) of their nitrogenous wastes as ammonia than the larger hummingbirds ( approximately 4%). Our results support the hypothesis that nectar-feeding birds have low protein requirements but cast doubt on the notion that they are facultatively ammonotelic. Our data also hint at a possible size-dependent dichotomy in hummingbirds, with higher ammonia excretion in smaller species. Differences in proportionate water loads and/or postrenal modification of urine may explain this dichotomy.

  16. A functional cutin matrix is required for plant protection against water loss.

    Science.gov (United States)

    Chen, Guoxiong; Komatsuda, Takao; Ma, Jian Feng; Li, Chao; Yamaji, Naoki; Nevo, Eviatar

    2011-09-01

    The plant cuticle, a cutin matrix embedded with and covered by wax, seals the aerial organ's surface to protect the plant against uncontrolled water loss. The cutin matrix is essential for the cuticle to function as a barrier to water loss. Recently, we identified from wild barley a drought supersensitive mutant, eibi1, which is caused by a defective cutin matrix as the result of the loss of function of HvABCG31, an ABCG full transporter. Here, we report that eibi1 epidermal cells contain lipid-like droplets, which are supposed to consist of cutin monomers that have not been transported out of the cells. The eibi1 cuticle is fragile due to a defective cutin matrix. The rice ortholog of the EIBI1 gene has a similar pattern of expression, young shoot but not flag leaf blade, as the barley gene. The model of the function of Eibi1 is discussed. The HvABCG31 full transporter functions in the export of cutin components and contributed to land plant colonization, hence also to terrestrial life evolution.

  17. Visual Pattern Memory Requires "Foraging" Function in the Central Complex of "Drosophila"

    Science.gov (United States)

    Wang, Zhipeng; Pan, Yufeng; Li, Weizhe; Jiang, Huoqing; Chatzimanolis, Lazaros; Chang, Jianhong; Gong, Zhefeng; Liu, Li

    2008-01-01

    The role of the "foraging" ("for)" gene, which encodes a cyclic guanosine-3',5'-monophosphate (cGMP)-dependent protein kinase (PKG), in food-search behavior in "Drosophila" has been intensively studied. However, its functions in other complex behaviors have not been well-characterized. Here, we show experimentally in "Drosophila" that the "for"…

  18. Directional resolution of head-related transfer functions required in binaural synthesis

    DEFF Research Database (Denmark)

    Minnaar, Pauli; Plogsties, Jan; Christensen, Flemming

    2005-01-01

    In binaural synthesis a virtual sound source is implemented by convolving an anechoic signal with a pair of head-related transfer functions (HRTFs). In order to represent all possible directions of the sound source with respect to the listener a discrete number of HRTFs are measured...

  19. Functional requirements for assistive technology for people with cognitive impairments and dementia

    NARCIS (Netherlands)

    Meiland, F.J.M.; Boer, M.E. de; Hoof, J. van; Leeuw, J. van der; Witte, L. de; Blom, M.; Karkowski, I.P.; Mulvenna, M.D.; Droes, R.M.

    2012-01-01

    The amount of technological aids on the market to support people in their everyday functioning is increasing. For example mobile telephone, electronic diary, skyping and domotics. Many of these aids are too complicated to operate for people with cognitive impairments, like dementia. For technology

  20. Functional dissection of the alphavirus capsid protease: sequence requirements for activity

    Directory of Open Access Journals (Sweden)

    Pützer Brigitte M

    2010-11-01

    Full Text Available Abstract Background The alphavirus capsid is multifunctional and plays a key role in the viral life cycle. The nucleocapsid domain is released by the self-cleavage activity of the serine protease domain within the capsid. All alphaviruses analyzed to date show this autocatalytic cleavage. Here we have analyzed the sequence requirements for the cleavage activity of Chikungunya virus capsid protease of genus alphavirus. Results Amongst alphaviruses, the C-terminal amino acid tryptophan (W261 is conserved and found to be important for the cleavage. Mutating tryptophan to alanine (W261A completely inactivated the protease. Other amino acids near W261 were not having any effect on the activity of this protease. However, serine protease inhibitor AEBSF did not inhibit the activity. Through error-prone PCR we found that isoleucine 227 is important for the effective activity. The loss of activity was analyzed further by molecular modelling and comparison of WT and mutant structures. It was found that lysine introduced at position 227 is spatially very close to the catalytic triad and may disrupt electrostatic interactions in the catalytic site and thus inactivate the enzyme. We are also examining other sequence requirements for this protease activity. Conclusions We analyzed various amino acid sequence requirements for the activity of ChikV capsid protease and found that amino acids outside the catalytic triads are important for the activity.

  1. Truncation of the membrane-spanning domain of human immunodeficiency virus type 1 envelope glycoprotein defines elements required for fusion, incorporation, and infectivity.

    Science.gov (United States)

    Yue, Ling; Shang, Liang; Hunter, Eric

    2009-11-01

    The membrane-spanning domain (MSD) of the envelope (Env) glycoprotein from human (HIV) and simian immunodeficiency viruses plays a key role in anchoring the Env complex into the viral membrane but also contributes to its biological function in fusion and virus entry. In HIV type 1 (HIV-1), it has been predicted to span 27 amino acids, from lysine residue 681 to arginine 707, and encompasses an internal arginine at residue 694. By examining a series of C-terminal-truncation mutants of the HIV-1 gp41 glycoprotein that substituted termination codons for amino acids 682 to 708, we show that this entire region is required for efficient viral infection of target cells. Truncation to the arginine at residue 694 resulted in an Env complex that was secreted from the cells. In contrast, a region from residues 681 to 698, which contains highly conserved hydrophobic residues and glycine motifs and extends 4 amino acids beyond 694R, can effectively anchor the protein in the membrane, allow efficient transport to the plasma membrane, and mediate wild-type levels of cell-cell fusion. However, these fusogenic truncated Env mutants are inefficiently incorporated into budding virions. Based on the analysis of these mutants, a "snorkeling" model, in which the flanking charged amino acid residues at 681 and 694 are buried in the lipid while their side chains interact with polar head groups, is proposed for the HIV-1 MSD.

  2. Science and Measurement Requirements for a Plant Physiology and Functional Types Mission: Measuring the Composition, Function and Health of Global Land and Coastal Ocean Ecosystems

    Science.gov (United States)

    Green, Robert O.; Rogez, Francois; Green, Rob; Ungar, Steve; Knox, Robert; Asner, Greg; Muller-Karger, Frank; Bissett, Paul; Chekalyuk, Alex; Dierssen, Heidi; Gamon, John; Hook, Simon; Meister, Gerhard; Middleton, Betsy; Ollinger, Scott; Roberts, Dar; Siegel, Dave; Townsend, Phil; Saatchi, Sassan; Unstin, Susan; Turner, Woody; Wickland, Diane; Bontempi, Paula; Emanuel, Bill

    2007-01-01

    This slide presentation reviews the proposed Plant Physiology and Functional Types (PPFT) Mission. The National Academy of Sciences Decadal Survey, placed a critical priority on a Mission to observe distribution and changes in ecosystem functions. The PPFT satellite mission provides the essential measurements needed to assess drivers of change in biodiversity and ecosystem services that affect human welfare. The presentation reviews the science questions that the mission will be designed to answer, the science rationale, the science measurements, the mission concept, the planned instrumentation, the calibration method, and key signal to noise ratios and uniformity requirements.

  3. [Effects of TiO₂ nanoparticles on antioxidant function and element content of liver and kidney tissues in young and adult rats].

    Science.gov (United States)

    Wang, Yun; Chen, Zhang-jian; Ba, Te; Pu, Ji; Cui, Xiao-xing; Jia, Guang

    2014-06-18

    To compare the effect of TiO₂ nanoparticles on antioxidant function and element content of liver and kidney tissues in young and adult rats. Forty-eight SD male rats, half in 4-week (youth) old and half in 9-week (adult) old rats, were randomly divided into 8 groups, which were exposed to TiO₂ nanoparticles [(75 ± 15) nm, anatase] through intragastric administration at 0, 10, 50 and 200 mg/kg body weight every day for 30 days. The liver and kidney tissues were collected for antioxidant function and element content analysis. 200 mg/kg TiO₂ nanoparticles exposure significantly increased the liver total superoxide dismutase (T-SOD) activity and the kidney reduced glutathione (GSH)/oxidized glutathione (GSSG) ratios in young rats, and significantly decreased the liver Mo, Co, Mn and P contents and the kidney Rb and Na contents in young rats. 200 mg/kg TiO₂ nanoparticles exposure significantly increased GSH/GSSG ratios and Rb contents and decreased Na contents in the liver of adult rats. No significantly difference was found in antioxidant indexes and elements content in the kidney of adult rats between three experimental groups and control group. TiO₂ nanoparticles can enhance the antioxidant capacity and decrease the elements content in rat liver and kidney tissues. The liver is the more sensitive target organ and the young animals are more susceptible to TiO₂ nanoparticles toxicity by the oral routes.

  4. The Function of the Conserved Regulatory Element within the Second Intron of the Mammalian Csf1r Locus

    Science.gov (United States)

    O’Neal, Julie; Sester, David P.; Tagoh, Hiromi; Ingram, Richard M.; Pridans, Clare; Bonifer, Constanze; Hume, David A.

    2013-01-01

    The gene encoding the receptor for macrophage colony-stimulating factor (CSF-1R) is expressed exclusively in cells of the myeloid lineages as well as trophoblasts. A conserved element in the second intron, Fms-Intronic Regulatory Element (FIRE), is essential for macrophage-specific transcription of the gene. However, the molecular details of how FIRE activity is regulated and how it impacts the Csf1r promoter have not been characterised. Here we show that agents that down-modulate Csf1r mRNA transcription regulated promoter activity altered the occupancy of key FIRE cis-acting elements including RUNX1, AP1, and Sp1 binding sites. We demonstrate that FIRE acts as an anti-sense promoter in macrophages and reversal of FIRE orientation within its native context greatly reduced enhancer activity in macrophages. Mutation of transcription initiation sites within FIRE also reduced transcription. These results demonstrate that FIRE is an orientation-specific transcribed enhancer element. PMID:23383005

  5. The function of the conserved regulatory element within the second intron of the mammalian Csf1r locus.

    Directory of Open Access Journals (Sweden)

    Kristin A Sauter

    Full Text Available The gene encoding the receptor for macrophage colony-stimulating factor (CSF-1R is expressed exclusively in cells of the myeloid lineages as well as trophoblasts. A conserved element in the second intron, Fms-Intronic Regulatory Element (FIRE, is essential for macrophage-specific transcription of the gene. However, the molecular details of how FIRE activity is regulated and how it impacts the Csf1r promoter have not been characterised. Here we show that agents that down-modulate Csf1r mRNA transcription regulated promoter activity altered the occupancy of key FIRE cis-acting elements including RUNX1, AP1, and Sp1 binding sites. We demonstrate that FIRE acts as an anti-sense promoter in macrophages and reversal of FIRE orientation within its native context greatly reduced enhancer activity in macrophages. Mutation of transcription initiation sites within FIRE also reduced transcription. These results demonstrate that FIRE is an orientation-specific transcribed enhancer element.

  6. NEW ALGORITHM OF COUPLING ELEMENT-FREE GALERKIN WITH FINITE ELEMENT METHOD

    Institute of Scientific and Technical Information of China (English)

    ZHAO Guang-ming; SONG Shun-cheng

    2005-01-01

    Through the construction of a new ramp function, the element-free Galerkin method and finite element coupling method were applied to the whole field, and was made fit for the structure of element nodes within the interface regions, both satisfying the essential boundary conditions and deploying meshless nodes and finite elements in a convenient and flexible way, which can meet the requirements of computation for complicated field. The comparison between the results of the present study and the corresponding analytical solutions shows this method is feasible and effective.

  7. Arabidopsis MKS1 is involved in basal immunity and requires an intact N-terminal domain for proper function.

    Directory of Open Access Journals (Sweden)

    Klaus Petersen

    Full Text Available BACKGROUND: Innate immune signaling pathways in animals and plants are regulated by mitogen-activated protein kinase (MAPK cascades. MAP kinase 4 (MPK4 functions downstream of innate immune receptors via a nuclear substrate MKS1 to regulate the activity of the WRKY33 transcription factor, which in turn controls the production of anti-microbial phytoalexins. METHODOLOGY/PRINCIPAL FINDINGS: We investigate the role of MKS1 in basal resistance and the importance of its N- and C-terminal domains for MKS1 function. We used the information that mks1 loss-of-function partially suppresses the mpk4 loss-of-function phenotype, and that transgenic expression of functional MKS1 in mpk4/mks1 double mutants reverted the mpk4 dwarf phenotype. Transformation of mks1/mpk4 with mutant versions of MKS1 constructs showed that a single amino acid substitution in a putative MAP kinase docking domain, MKS1-L32A, or a truncated MKS1 version unable to interact with WRKY33, were deficient in reverting the double mutant to the mpk4 phenotype. These results demonstrate functional requirement in MKS1 for the interaction with MPK4 and WRKY33. In addition, nuclear localization of MKS1 was shown to depend on an intact N-terminal domain. Furthermore, loss-of-function mks1 mutants exhibited increased susceptibility to strains of Pseudomonas syringae and Hyaloperonospora arabidopsidis, indicating that MKS1 plays a role in basal defense responses. CONCLUSIONS: Taken together, our results indicate that MKS1 function and subcellular location requires an intact N-terminus important for both MPK4 and WRKY33 interactions.

  8. Sphingomyelin homeostasis is required to form functional enzymatic domains at the trans-Golgi network.

    Science.gov (United States)

    van Galen, Josse; Campelo, Felix; Martínez-Alonso, Emma; Scarpa, Margherita; Martínez-Menárguez, José Ángel; Malhotra, Vivek

    2014-09-01

    Do lipids such as sphingomyelin (SM) that are known to assemble into specific membrane domains play a role in the organization and function of transmembrane proteins? In this paper, we show that disruption of SM homeostasis at the trans-Golgi network (TGN) by treatment of HeLa cells with d-ceramide-C6, which was converted together with phosphatidylcholine to short-chain SM and diacylglycerol by SM synthase, led to the segregation of Golgi-resident proteins from each other. We found that TGN46, which cycles between the TGN and the plasma membrane, was not sialylated by a sialyltransferase at the TGN and that this enzyme and its substrate TGN46 could not physically interact with each other. Our results suggest that SM organizes transmembrane proteins into functional enzymatic domains at the TGN.

  9. RNA Replication and Membrane Modification Require the Same Functions of Alphavirus Nonstructural Proteins.

    Science.gov (United States)

    Kallio, Katri; Hellström, Kirsi; Jokitalo, Eija; Ahola, Tero

    2015-11-18

    The alphaviruses induce membrane invaginations known as spherules as their RNA replication sites. Here, we show that inactivation of any function (polymerase, helicase, protease, or membrane association) essential for RNA synthesis also prevents the generation of spherule structures in a Semliki Forest virus trans-replication system. Mutants capable of negative-strand synthesis, including those defective in RNA capping, gave rise to spherules. Recruitment of RNA to membranes in the absence of spherule formation was not detected.

  10. Galnt1 is required for normal heart valve development and cardiac function.

    Directory of Open Access Journals (Sweden)

    E Tian

    Full Text Available Congenital heart valve defects in humans occur in approximately 2% of live births and are a major source of compromised cardiac function. In this study we demonstrate that normal heart valve development and cardiac function are dependent upon Galnt1, the gene that encodes a member of the family of glycosyltransferases (GalNAc-Ts responsible for the initiation of mucin-type O-glycosylation. In the adult mouse, compromised cardiac function that mimics human congenital heart disease, including aortic and pulmonary valve stenosis and regurgitation; altered ejection fraction; and cardiac dilation, was observed in Galnt1 null animals. The underlying phenotype is aberrant valve formation caused by increased cell proliferation within the outflow tract cushion of developing hearts, which is first detected at developmental stage E11.5. Developing valves from Galnt1 deficient animals displayed reduced levels of the proteases ADAMTS1 and ADAMTS5, decreased cleavage of the proteoglycan versican and increased levels of other extracellular matrix proteins. We also observed increased BMP and MAPK signaling. Taken together, the ablation of Galnt1 appears to disrupt the formation/remodeling of the extracellular matrix and alters conserved signaling pathways that regulate cell proliferation. Our study provides insight into the role of this conserved protein modification in cardiac valve development and may represent a new model for idiopathic valve disease.

  11. Identification of genes required for neural-specific glycosylation using functional genomics.

    Directory of Open Access Journals (Sweden)

    Miki Yamamoto-Hino

    Full Text Available Glycosylation plays crucial regulatory roles in various biological processes such as development, immunity, and neural functions. For example, α1,3-fucosylation, the addition of a fucose moiety abundant in Drosophila neural cells, is essential for neural development, function, and behavior. However, it remains largely unknown how neural-specific α1,3-fucosylation is regulated. In the present study, we searched for genes involved in the glycosylation of a neural-specific protein using a Drosophila RNAi library. We obtained 109 genes affecting glycosylation that clustered into nine functional groups. Among them, members of the RNA regulation group were enriched by a secondary screen that identified genes specifically regulating α1,3-fucosylation. Further analyses revealed that an RNA-binding protein, second mitotic wave missing (Swm, upregulates expression of the neural-specific glycosyltransferase FucTA and facilitates its mRNA export from the nucleus. This first large-scale genetic screen for glycosylation-related genes has revealed novel regulation of fucTA mRNA in neural cells.

  12. The Wiskott-Aldrich syndrome protein is required for iNKT cell maturation and function

    Science.gov (United States)

    Locci, Michela; Draghici, Elena; Marangoni, Francesco; Bosticardo, Marita; Catucci, Marco; Aiuti, Alessandro; Cancrini, Caterina; Marodi, Laszlo; Espanol, Teresa; Bredius, Robbert G.M.; Thrasher, Adrian J.; Schulz, Ansgar; Litzman, Jiri; Roncarolo, Maria Grazia; Casorati, Giulia; Dellabona, Paolo

    2009-01-01

    The Wiskott-Aldrich syndrome (WAS) protein (WASp) is a regulator of actin cytoskeleton in hematopoietic cells. Mutations of the WASp gene cause WAS. Although WASp is involved in various immune cell functions, its role in invariant natural killer T (iNKT) cells has never been investigated. Defects of iNKT cells could indeed contribute to several WAS features, such as recurrent infections and high tumor incidence. We found a profound reduction of circulating iNKT cells in WAS patients, directly correlating with the severity of clinical phenotype. To better characterize iNKT cell defect in the absence of WASp, we analyzed was−/− mice. iNKT cell numbers were significantly reduced in the thymus and periphery of was−/− mice as compared with wild-type controls. Moreover analysis of was−/− iNKT cell maturation revealed a complete arrest at the CD44+ NK1.1− intermediate stage. Notably, generation of BM chimeras demonstrated a was−/− iNKT cell-autonomous developmental defect. was−/− iNKT cells were also functionally impaired, as suggested by the reduced secretion of interleukin 4 and interferon γ upon in vivo activation. Altogether, these results demonstrate the relevance of WASp in integrating signals critical for development and functional differentiation of iNKT cells and suggest that defects in these cells may play a role in WAS pathology. PMID:19307326

  13. SIRT1 is required for AMPK activation and the beneficial effects of resveratrol on mitochondrial function

    Science.gov (United States)

    Price, Nathan L.; Gomes, Ana P.; Ling, Alvin J.Y.; Duarte, Filipe V.; Martin-Montalvo, Alejandro; North, Brian J.; Agarwal, Beamon; Ye, Lan; Ramadori, Giorgio; Teodoro, Joao S.; Hubbard, Basil P.; Varela, Ana T.; Davis, James G.; Varamini, Behzad; Hafner, Angela; Moaddel, Ruin; Rolo, Anabela P.; Coppari, Roberto; Palmeira, Carlos M.; de Cabo, Rafael; Baur, Joseph A.; Sinclair, David A.

    2012-01-01

    SUMMARY Resveratrol induces mitochondrial biogenesis and protects against metabolic decline but whether SIRT1 mediates these benefits is the subject of debate. To circumvent the developmental defects of germ-line SIRT1 knockouts, we have developed the first inducible system that permits whole-body deletion of SIRT1 in adult mice. Mice treated with a moderate dose of resveratrol showed increased mitochondrial biogenesis and function, AMPK activation and increased NAD+ levels in skeletal muscle, whereas SIRT1 knockouts displayed none of these benefits. A mouse overexpressing SIRT1 mimicked these effects. A high dose of resveratrol activated AMPK in a SIRT1-independent manner, demonstrating that resveratrol dosage is a critical factor. Importantly, at both doses of resveratrol no improvements in mitochondrial function were observed in animals lacking SIRT1. Together these data indicate that SIRT1 plays an essential role in the ability of moderate doses of resveratrol to stimulate AMPK and improve mitochondrial function both in vitro and in vivo. PMID:22560220

  14. Early development of Drosophila embryos requires Smc5/6 function during oogenesis.

    Science.gov (United States)

    Tran, Martin; Tsarouhas, Vasilios; Kegel, Andreas

    2016-07-15

    Mutations in structural maintenance of chromosomes (Smc) proteins are frequently associated with chromosomal abnormalities commonly observed in developmental disorders. However, the role of Smc proteins in development still remains elusive. To investigate Smc5/6 function during early embryogenesis we examined smc5 and smc6 mutants of the fruit fly Drosophila melanogaster using a combination of reverse genetics and microscopy approaches. Smc5/6 exhibited a maternally contributed function in maintaining chromosome stability during early embryo development, which manifested as female subfertility in its absence. Loss of Smc5/6 caused an arrest and a considerable delay in embryo development accompanied by fragmented nuclei and increased anaphase-bridge formation, respectively. Surprisingly, early embryonic arrest was attributable to the absence of Smc5/6 during oogenesis, which resulted in insufficient repair of pre-meiotic and meiotic DNA double-strand breaks. Thus, our findings contribute to the understanding of Smc proteins in higher eukaryotic development by highlighting a maternal function in chromosome maintenance and a link between oogenesis and early embryogenesis.

  15. Drosophila spastin regulates synaptic microtubule networks and is required for normal motor function.

    Directory of Open Access Journals (Sweden)

    Nina Tang Sherwood

    2004-12-01

    Full Text Available The most common form of human autosomal dominant hereditary spastic paraplegia (AD-HSP is caused by mutations in the SPG4 (spastin gene, which encodes an AAA ATPase closely related in sequence to the microtubule-severing protein Katanin. Patients with AD-HSP exhibit degeneration of the distal regions of the longest axons in the spinal cord. Loss-of-function mutations in the Drosophila spastin gene produce larval neuromuscular junction (NMJ phenotypes. NMJ synaptic boutons in spastin mutants are more numerous and more clustered than in wild-type, and transmitter release is impaired. spastin-null adult flies have severe movement defects. They do not fly or jump, they climb poorly, and they have short lifespans. spastin hypomorphs have weaker behavioral phenotypes. Overexpression of Spastin erases the muscle microtubule network. This gain-of-function phenotype is consistent with the hypothesis that Spastin has microtubule-severing activity, and implies that spastin loss-of-function mutants should have an increased number of microtubules. Surprisingly, however, we observed the opposite phenotype: in spastin-null mutants, there are fewer microtubule bundles within the NMJ, especially in its distal boutons. The Drosophila NMJ is a glutamatergic synapse that resembles excitatory synapses in the mammalian spinal cord, so the reduction of organized presynaptic microtubules that we observe in spastin mutants may be relevant to an understanding of human Spastin's role in maintenance of axon terminals in the spinal cord.

  16. Early development of Drosophila embryos requires Smc5/6 function during oogenesis

    Directory of Open Access Journals (Sweden)

    Martin Tran

    2016-07-01

    Full Text Available Mutations in structural maintenance of chromosomes (Smc proteins are frequently associated with chromosomal abnormalities commonly observed in developmental disorders. However, the role of Smc proteins in development still remains elusive. To investigate Smc5/6 function during early embryogenesis we examined smc5 and smc6 mutants of the fruit fly Drosophila melanogaster using a combination of reverse genetics and microscopy approaches. Smc5/6 exhibited a maternally contributed function in maintaining chromosome stability during early embryo development, which manifested as female subfertility in its absence. Loss of Smc5/6 caused an arrest and a considerable delay in embryo development accompanied by fragmented nuclei and increased anaphase-bridge formation, respectively. Surprisingly, early embryonic arrest was attributable to the absence of Smc5/6 during oogenesis, which resulted in insufficient repair of pre-meiotic and meiotic DNA double-strand breaks. Thus, our findings contribute to the understanding of Smc proteins in higher eukaryotic development by highlighting a maternal function in chromosome maintenance and a link between oogenesis and early embryogenesis.

  17. The Polybasic Juxtamembrane Region of Sso1p Is Required for SNARE Function In Vivo†

    OpenAIRE

    Van Komen, Jeffrey S.; Bai, Xiaoyang; Rodkey, Travis L.; Schaub, Johanna; MCNEW, JAMES A.

    2005-01-01

    Exocytosis in Saccharomyces cerevisiae requires the specific interaction between the plasma membrane t-SNARE complex (Sso1/2p;Sec9p)and a vesicular v-SNARE (Snc1/2p). While SNARE proteins drive membrane fusion, many aspects of SNARE assembly and regulation are ill defined. Plasma membrane syntaxin homologs (including Sso1p) contain a highly charged juxtamembrane region between the transmembrane helix and the “SNARE domain” or core complex domain. We examined this region in vitro and in vivo b...

  18. Identification of evolutionarily conserved, functional noncoding elements in the promoter region of the sodium channel gene SCN8A.

    Science.gov (United States)

    Drews, Valerie L; Shi, Kehui; de Haan, Georgius; Meisler, Miriam H

    2007-10-01

    SCN8A is a major neuronal sodium channel gene expressed throughout the central and peripheral nervous systems. Mutations of SCN8A result in movement disorders and impaired cognition. To investigate the basis for the tissue-specific expression of SCN8A, we located conserved, potentially regulatory sequences in the human, mouse, chicken, and fish genes by 5' RACE of brain RNA and genomic sequence comparison. A highly conserved 5' noncoding exon, exon 1c, is present in vertebrates from fish to mammals and appears to define the ancestral promoter region. The distance from exon 1c to the first coding exon increased tenfold during vertebrate evolution, largely by insertion of repetitive elements. The mammalian gene acquired three novel, mutually exclusive noncoding exons that are not represented in the lower vertebrates. Within the shared exon 1c, we identified four short sequence elements of 10-20 bp with an unusually high level of evolutionary conservation. The conserved elements are most similar to consensus sites for the transcription factors Pou6f1/Brn5, YY1, and REST/NRSF. Introduction of mutations into the predicted Pou6f1 and REST sites reduced promoter activity in transfected neuronal cells. A 470-bp promoter fragment containing all of the conserved elements directed brain-specific expression of the LacZ reporter in transgenic mice. Transgene expression was highest in hippocampal neurons and cerebellar Purkinje cells, consistent with the expression of the endogenous gene. The compact cluster of conserved regulatory elements in SCN8A provides a useful target for molecular analysis of neuronal gene expression.

  19. Functional Analysis of Mutations in Exon 9 of NF1 Reveals the Presence of Several Elements Regulating Splicing.

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    Elisabete Hernández-Imaz

    Full Text Available Neurofibromatosis type 1 (NF1 is one of the most common human hereditary disorders, predisposing individuals to the development of benign and malignant tumors in the nervous system, as well as other clinical manifestations. NF1 is caused by heterozygous mutations in the NF1 gene and around 25% of the pathogenic changes affect pre-mRNA splicing. Since the molecular mechanisms affected by these mutations are poorly understood, we have analyzed the splicing mutations identified in exon 9 of NF1, which is particularly prone to such changes, to better define the possible splicing regulatory elements. Using a minigene approach, we studied the effect of five splicing mutations in this exon described in patients. These highlighted three regulatory motifs within the exon. An in vivo splicing analysis of an extensive collection of changes generated in the minigene demonstrated that the CG motif at c.910-911 is critical for the recognition of exon 9. We also found that the GC motif at c.945-946 is involved in exon recognition through SRSF2 and that this motif is part of a Composite Exon Splicing Regulatory Element made up of physically overlapping enhancer and silencer elements. Finally, through an in vivo splicing analysis and in vitro binding assays, we demonstrated that the c.1007G>A mutation creates an Exonic Splicing Silencer element that binds the hnRNPA1 protein. The complexity of the splicing regulatory elements present in exon 9 is most likely responsible for the fact that mutations in this region represent 25% of all exonic changes that affect splicing in the NF1 gene.

  20. Calmodulin Methyltransferase Is Required for Growth, Muscle Strength, Somatosensory Development and Brain Function.

    Science.gov (United States)

    Haziza, Sitvanit; Magnani, Roberta; Lan, Dima; Keinan, Omer; Saada, Ann; Hershkovitz, Eli; Yanay, Nurit; Cohen, Yoram; Nevo, Yoram; Houtz, Robert L; Sheffield, Val C; Golan, Hava; Parvari, Ruti

    2015-08-01

    Calmodulin lysine methyl transferase (CaM KMT) is ubiquitously expressed and highly conserved from plants to vertebrates. CaM is frequently trimethylated at Lys-115, however, the role of CaM methylation in vertebrates has not been studied. CaM KMT was found to be homozygously deleted in the 2P21 deletion syndrome that includes 4 genes. These patients present with cystinuria, severe intellectual disabilities, hypotonia, mitochondrial disease and facial dysmorphism. Two siblings with deletion of three of the genes included in the 2P21 deletion syndrome presented with cystinuria, hypotonia, a mild/moderate mental retardation and a respiratory chain complex IV deficiency. To be able to attribute the functional significance of the methylation of CaM in the mouse and the contribution of CaM KMT to the clinical presentation of the 2p21deletion patients, we produced a mouse model lacking only CaM KMT with deletion borders as in the human 2p21deletion syndrome. No compensatory activity for CaM methylation was found. Impairment of complexes I and IV, and less significantly III, of the mitochondrial respiratory chain was more pronounced in the brain than in muscle. CaM KMT is essential for normal body growth and somatosensory development, as well as for the proper functioning of the adult mouse brain. Developmental delay was demonstrated for somatosensory function and for complex behavior, which involved both basal motor function and motivation. The mutant mice also had deficits in motor learning, complex coordination and learning of aversive stimuli. The mouse model contributes to the evaluation of the role of methylated CaM. CaM methylation appears to have a role in growth, muscle strength, somatosensory development and brain function. The current study has clinical implications for human patients. Patients presenting slow growth and muscle weakness that could result from a mitochondrial impairment and mental retardation should be considered for sequence analysis of the Ca

  1. A novel sterol regulatory element-binding protein gene (sreA identified in penicillium digitatum is required for prochloraz resistance, full virulence and erg11 (cyp51 regulation.

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    Jing Liu

    Full Text Available Penicillium digitatum is the most destructive postharvest pathogen of citrus fruits, causing fruit decay and economic loss. Additionally, control of the disease is further complicated by the emergence of drug-resistant strains due to the extensive use of triazole antifungal drugs. In this work, an orthologus gene encoding a putative sterol regulatory element-binding protein (SREBP was identified in the genome of P. digitatum and named sreA. The putative SreA protein contains a conserved domain of unknown function (DUF2014 at its carboxyl terminus and a helix-loop-helix (HLH leucine zipper DNA binding domain at its amino terminus, domains that are functionally associated with SREBP transcription factors. The deletion of sreA (ΔsreA in a prochloraz-resistant strain (PdHS-F6 by Agrobacterium tumefaciens-mediated transformation led to increased susceptibility to prochloraz and a significantly lower EC50 value compared with the HS-F6 wild-type or complementation strain (COsreA. A virulence assay showed that the ΔsreA strain was defective in virulence towards citrus fruits, while the complementation of sreA could restore the virulence to a large extent. Further analysis by quantitative real-time PCR demonstrated that prochloraz-induced expression of cyp51A and cyp51B in PdHS-F6 was completely abolished in the ΔsreA strain. These results demonstrate that sreA is a critical transcription factor gene required for prochloraz resistance and full virulence in P. digitatum and is involved in the regulation of cyp51 expression.

  2. A novel sterol regulatory element-binding protein gene (sreA) identified in penicillium digitatum is required for prochloraz resistance, full virulence and erg11 (cyp51) regulation.

    Science.gov (United States)

    Liu, Jing; Yuan, Yongze; Wu, Zhi; Li, Na; Chen, Yuanlei; Qin, Tingting; Geng, Hui; Xiong, Li; Liu, Deli

    2015-01-01

    Penicillium digitatum is the most destructive postharvest pathogen of citrus fruits, causing fruit decay and economic loss. Additionally, control of the disease is further complicated by the emergence of drug-resistant strains due to the extensive use of triazole antifungal drugs. In this work, an orthologus gene encoding a putative sterol regulatory element-binding protein (SREBP) was identified in the genome of P. digitatum and named sreA. The putative SreA protein contains a conserved domain of unknown function (DUF2014) at its carboxyl terminus and a helix-loop-helix (HLH) leucine zipper DNA binding domain at its amino terminus, domains that are functionally associated with SREBP transcription factors. The deletion of sreA (ΔsreA) in a prochloraz-resistant strain (PdHS-F6) by Agrobacterium tumefaciens-mediated transformation led to increased susceptibility to prochloraz and a significantly lower EC50 value compared with the HS-F6 wild-type or complementation strain (COsreA). A virulence assay showed that the ΔsreA strain was defective in virulence towards citrus fruits, while the complementation of sreA could restore the virulence to a large extent. Further analysis by quantitative real-time PCR demonstrated that prochloraz-induced expression of cyp51A and cyp51B in PdHS-F6 was completely abolished in the ΔsreA strain. These results demonstrate that sreA is a critical transcription factor gene required for prochloraz resistance and full virulence in P. digitatum and is involved in the regulation of cyp51 expression.

  3. Enhanced patch test of finite element methods

    Institute of Scientific and Technical Information of China (English)

    CHEN; Wanji

    2006-01-01

    Theoretically, the constant stress patch test is not rigorous. Also, either the patch test of non-zero constant shear for Mindlin plate problem or non-zero strain gradient curvature of the microstructures cannot be performed. To improve the theory of the patch test, in this paper, based on the variational principle with relaxed continuity requirement of nonconforming element for homogeneous differential equations, the author proposed the individual element condition for passing the patch test and the convergence condition of the element: besides passing the patch test, the element function should include the rigid body modes and constant strain modes and satisfy the weak continuity condition, and no extra zero energy modes occur. Moreover, the author further established a variational principle with relaxed continuity requirement of nonconforming element for inhomogeneous differential equations, the enhanced patch test condition and the individual element condition. To assure the convergence of the element that should pass the enhanced patch test, the element function should include the rigid body modes and non-zero strain modes which satisfied the equilibrium equations, and no spurious zero energy modes occur and should satisfy new weak continuity condition. The theory of the enhanced patch test proposed in this paper can be applied to both homogeneous and inhomogeneous differential equations. Based on this theory, the patch test of the non-zero constant shear stress for Mindlin plate and the C0-1 patch test of the non-zero constant curvature for the couple stress/strain gradient theory were established.

  4. Shared Enhancer Activity in the Limbs and Phallus and Functional Divergence of a Limb-Genital cis-Regulatory Element in Snakes.

    Science.gov (United States)

    Infante, Carlos R; Mihala, Alexandra G; Park, Sungdae; Wang, Jialiang S; Johnson, Kenji K; Lauderdale, James D; Menke, Douglas B

    2015-10-12

    The amniote phallus and limbs differ dramatically in their morphologies but share patterns of signaling and gene expression in early development. Thus far, the extent to which genital and limb transcriptional networks also share cis-regulatory elements has remained unexplored. We show that many limb enhancers are retained in snake genomes, suggesting that these elements may function in non-limb tissues. Consistent with this, our analysis of cis-regulatory activity in mice and Anolis lizards reveals that patterns of enhancer activity in embryonic limbs and genitalia overlap heavily. In mice, deletion of HLEB, an enhancer of Tbx4, produces defects in hindlimbs and genitalia, establishing the importance of this limb-genital enhancer for development of these different appendages. Further analyses demonstrate that the HLEB of snakes has lost hindlimb enhancer function while retaining genital activity. Our findings identify roles for Tbx4 in genital development and highlight deep similarities in cis-regulatory activity between limbs and genitalia.

  5. Bending and free vibration analysis of functionally graded plates using new eight-unknown shear deformation theory by finite-element method

    Science.gov (United States)

    Van Long, Nguyen; Quoc, Tran Huu; Tu, Tran Minh

    2016-12-01

    In this paper, a new eight-unknown shear deformation theory is developed for bending and free vibration analysis of functionally graded plates by finite-element method. The theory based on full 12-unknown higher order shear deformation theory simultaneously satisfies zeros transverse stresses at top and bottom surfaces of FG plates. A four-node rectangular element with 16 degrees of freedom per node is used. Poisson's ratios, Young's moduli, and material densities vary continuously in thickness direction according to the volume fraction of constituents which is modeled as power-law functions. Results are verified with available results in the literature. Parametric studies are performed for different power-law indices, side-to-thickness ratios.

  6. Two-component relativistic density-functional calculations of the dimers of the halogens from bromine through element 117 using effective core potential and all-electron methods.

    Science.gov (United States)

    Mitin, Alexander V; van Wüllen, Christoph

    2006-02-14

    A two-component quasirelativistic Hamiltonian based on spin-dependent effective core potentials is used to calculate ionization energies and electron affinities of the heavy halogen atom bromine through the superheavy element 117 (eka-astatine) as well as spectroscopic constants of the homonuclear dimers of these atoms. We describe a two-component Hartree-Fock and density-functional program that treats spin-orbit coupling self-consistently within the orbital optimization procedure. A comparison with results from high-order Douglas-Kroll calculations--for the superheavy systems also with zeroth-order regular approximation and four-component Dirac results--demonstrates the validity of the pseudopotential approximation. The density-functional (but not the Hartree-Fock) results show very satisfactory agreement with theoretical coupled cluster as well as experimental data where available, such that the theoretical results can serve as an estimate for the hitherto unknown properties of astatine, element 117, and their dimers.

  7. Intraflagellar Transport and Functional Analysis of Genes Required for Flagellum Formation in Trypanosomes

    Science.gov (United States)

    Absalon, Sabrina; Blisnick, Thierry; Kohl, Linda; Toutirais, Géraldine; Doré, Gwénola; Julkowska, Daria; Tavenet, Arounie

    2008-01-01

    Intraflagellar transport (IFT) is the bidirectional movement of protein complexes required for cilia and flagella formation. We investigated IFT by analyzing nine conventional IFT genes and five novel putative IFT genes (PIFT) in Trypanosoma brucei that maintain its existing flagellum while assembling a new flagellum. Immunostaining against IFT172 or expression of tagged IFT20 or green fluorescent protein GFP::IFT52 revealed the presence of IFT proteins along the axoneme and at the basal body and probasal body regions of both old and new flagella. IFT particles were detected by electron microscopy and exhibited a strict localization to axonemal microtubules 3–4 and 7–8, suggesting the existence of specific IFT tracks. Rapid (>3 μm/s) bidirectional intraflagellar movement of GFP::IFT52 was observed in old and new flagella. RNA interference silencing demonstrated that all individual IFT and PIFT genes are essential for new flagellum construction but the old flagellum remained present. Inhibition of IFTB proteins completely blocked axoneme construction. Absence of IFTA proteins (IFT122 and IFT140) led to formation of short flagella filled with IFT172, indicative of defects in retrograde transport. Two PIFT proteins turned out to be required for retrograde transport and three for anterograde transport. Finally, flagellum membrane elongation continues despite the absence of axonemal microtubules in all IFT/PIFT mutant. PMID:18094047

  8. Functional diversification of hsp40: distinct j-protein functional requirements for two prions allow for chaperone-dependent prion selection.

    Science.gov (United States)

    Harris, Julia M; Nguyen, Phil P; Patel, Milan J; Sporn, Zachary A; Hines, Justin K

    2014-07-01

    Yeast prions are heritable amyloid aggregates of functional yeast proteins; their propagation to subsequent cell generations is dependent upon fragmentation of prion protein aggregates by molecular chaperone proteins. Mounting evidence indicates the J-protein Sis1 may act as an amyloid specificity factor, recognizing prion and other amyloid aggregates and enabling Ssa and Hsp104 to act in prion fragmentation. Chaperone interactions with prions, however, can be affected by variations in amyloid-core structure resulting in distinct prion variants or 'strains'. Our genetic analysis revealed that Sis1 domain requirements by distinct variants of [PSI+] are strongly dependent upon overall variant stability. Notably, multiple strong [PSI+] variants can be maintained by a minimal construct of Sis1 consisting of only the J-domain and glycine/phenylalanine-rich (G/F) region that was previously shown to be sufficient for cell viability and [RNQ+] prion propagation. In contrast, weak [PSI+] variants are lost under the same conditions but maintained by the expression of an Sis1 construct that lacks only the G/F region and cannot support [RNQ+] propagation, revealing mutually exclusive requirements for Sis1 function between these two prions. Prion loss is not due to [PSI+]-dependent toxicity or dependent upon a particular yeast genetic background. These observations necessitate that Sis1 must have at least two distinct functional roles that individual prions differentially require for propagation and which are localized to the glycine-rich domains of the Sis1. Based on these distinctions, Sis1 plasmid-shuffling in a [PSI+]/[RNQ+] strain permitted J-protein-dependent prion selection for either prion. We also found that, despite an initial report to the contrary, the human homolog of Sis1, Hdj1, is capable of [PSI+] prion propagation in place of Sis1. This conservation of function is also prion-variant dependent, indicating that only one of the two Sis1-prion functions may have

  9. Functional relevance of microbiome signatures: The correlation era requires tools for consolidation.

    Science.gov (United States)

    Buttó, Ludovica F; Haller, Dirk

    2017-04-01

    Compelling research over the past decade identified a fundamental role of the intestinal microbiome on human health. Compositional and functional changes of this microbial ecosystem are correlated with a variety of human pathologies. Metagenomic resolution and bioinformatic tools considerably improved, allowing even strain-level analysis. However, the search for microbial risk patterns in human cohorts is often confounded by environmental factors (eg, medication) and host status (eg, disease relapse), questioning the prognostic and therapeutic value of the currently available information. In addition to a better stratification of human phenotypes, the implementation of standardized protocols for sampling and analysis is needed to improve the reproducibility and comparability of microbiome signatures at a meaningful taxonomic resolution. At the level of mechanistic understanding, the molecular integration of pleiotropic signals coming from this complex and dynamically changing ecosystem is one of the biggest challenges in this field. The first successful attempts to apply reverse genetics based on the available metagenomic information yielded identification of small molecules and metabolites with functional relevance for microbe-host interactions. Further expansion on the isolation of bacteria from the "unculturable biomass" will help characterize microbiome signatures in model systems, finally aiming at the development of clinically relevant synthetic consortia with safe and functionally well-defined strains. In conclusion and beyond reasonable enthusiasm, the mechanistic implementation and clinical relevance of microbiome alterations on disease susceptibility is still in its infancy, but the integration of all the above-mentioned strategies will help overcome the correlation era in microbiome research and lead to a rational evaluation of clinical strategies relevant for targeted microbial intervention. Copyright © 2017 American Academy of Allergy, Asthma

  10. A Trypanosomatid Iron Transporter that Regulates Mitochondrial Function Is Required for Leishmania amazonensis Virulence.

    Directory of Open Access Journals (Sweden)

    Bidyottam Mittra

    2016-01-01

    Full Text Available Iron, an essential co-factor of respiratory chain proteins, is critical for mitochondrial function and maintenance of its redox balance. We previously reported a role for iron uptake in differentiation of Leishmania amazonensis into virulent amastigotes, by a mechanism that involves reactive oxygen species (ROS production and is independent of the classical pH and temperature cues. Iron import into mitochondria was proposed to be essential for this process, but evidence supporting this hypothesis was lacking because the Leishmania mitochondrial iron transporter was unknown. Here we describe MIT1, a homolog of the mitochondrial iron importer genes mrs3 (yeast and mitoferrin-1 (human that is highly conserved among trypanosomatids. MIT1 expression was essential for the survival of Trypanosoma brucei procyclic but not bloodstream forms, which lack functional respiratory complexes. L. amazonensis LMIT1 null mutants could not be generated, suggesting that this mitochondrial iron importer is essential for promastigote viability. Promastigotes lacking one LMIT1 allele (LMIT1/Δlmit1 showed growth defects and were more susceptible to ROS toxicity, consistent with the role of iron as the essential co-factor of trypanosomatid mitochondrial superoxide dismutases. LMIT1/Δlmit1 metacyclic promastigotes were unable to replicate as intracellular amastigotes after infecting macrophages or cause cutaneous lesions in mice. When induced to differentiate axenically into amastigotes, LMIT1/Δlmit1 showed strong defects in iron content and function of mitochondria, were unable to upregulate the ROS-regulatory enzyme FeSOD, and showed mitochondrial changes suggestive of redox imbalance. Our results demonstrate the importance of mitochondrial iron uptake in trypanosomatid parasites, and highlight the role of LMIT1 in the iron-regulated process that orchestrates differentiation of L. amazonensis into infective amastigotes.

  11. What advances in microscopy are required for combined MRI and optical functional brain imaging? (Conference Presentation)

    Science.gov (United States)

    Kleinfeld, David

    2016-03-01

    This overview talk will focus on forward-looking scientific needs and physical limits to images of neuronal processes. The challenge in nervous systems is that the basic unit for "switching" events in the nervous system occurs on the one micrometer scale of synaptic spines, while computations involve communication between individual neurons across the full expanse of cortex, which is ten millimeters for mouse cortex. I will address hoped-for advances in optical microscopy, within the context of existing and proposed contrast mechanisms of neuronal function, that span the four orders of magnitude of length scales for neuronal processing

  12. Human placenta as a 'dual' biomarker for monitoring fetal and maternal environment with special reference to potentially toxic trace elements. Part 1: physiology, function and sampling of placenta for elemental characterisation.

    Science.gov (United States)

    Iyengar, G V; Rapp, A

    2001-12-03

    Choice of specimen from human subjects for monitoring pollutants proven to be detrimental to human health depends on the criteria chosen, namely real-time monitoring (RTM) or long-term monitoring (LTM). Specimens such as whole blood, urine, saliva and breast milk are commonly used from living subjects for RTM of toxic metals. However, sampling blood requires an invasive procedure. On the other hand, hair (with some limitations), bone (especially for the assessment of bone seeking elements), adipose tissue (mainly for organic pollutants) and liver (for both organic and inorganic toxicants) are used as specimens for LTM. With the exception of hair, generally these specimens are obtained at post-mortem. In context of health-related biomonitoring, placenta as a specimen has not received as much attention as it deserves. It is a unique sample requiring no invasive procedure, and offers possibilities for RTM, in particular as a dual purpose specimen for evaluating the pollutant burden exerted on the mother as well as on the fetus. Obtaining representative samples of placenta for elemental composition studies is a difficult task, because of heterogeneous mix of placental cells and decidual matter tainted with maternal and fetal blood. Therefore, the present sampling practices for placental tissue, and guidelines to safeguard the validity of the sampled material have been reviewed in part 1 with the following conclusions: medico-legal and ethical matters should be properly addressed before collecting the placenta; it is advisable to collect the entire placenta even if it includes the umbilical cord; further preparatory work is to be carried out in a clean laboratory and depends upon the purpose of the investigation; homogenising the entire sample may prove to be technically challenging but this step is crucial to obtain representative samples, handling the entire sample may be unavoidable; and an alternative method of procuring representative samples would require random

  13. Ascl1 is a required downstream effector of Gsx gene function in the embryonic mouse telencephalon

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    Allen Zegary J

    2009-02-01

    Full Text Available Abstract Background The homeobox gene Gsx2 (formerly Gsh2 is known to regulate patterning in the lateral ganglionic eminence (LGE of the embryonic telencephalon. In its absence, the closely related gene Gsx1 (previously known as Gsh1 can partially compensate in the patterning and differentiation of ventral telencephalic structures, such as the striatum. However, the cellular and molecular mechanisms underlying this compensation remain unclear. Results We show here that in the Gsx2 mutants Gsx1 is expressed in only a subset of the ventral telencephalic progenitors that normally express Gsx2. Based on the similarities in the expression of Gsx1 and Ascl1 (Mash1 within the Gsx2 mutant LGE, we examined whether Ascl1 plays an integral part in the Gsx1-based recovery. Ascl1 mutants show only modest alterations in striatal development; however, in Gsx2;Ascl1 double mutants, striatal development is severely affected, similar to that seen in the Gsx1;Gsx2 double mutants. This is despite the fact that Gsx1 is expressed, and even expands, in the Gsx2;Ascl1 mutant LGE, comparable to that seen in the Gsx2 mutant. Finally, Notch signaling has recently been suggested to be required for normal striatal development. In spite of the fact that Notch signaling is severely disrupted in Ascl1 mutants, it actually appears to be improved in the Gsx2;Ascl1 double mutants. Conclusion These results, therefore, reveal a non-proneural requirement of Ascl1 that together with Gsx1 compensates for the loss of Gsx2 in a subset of LGE progenitors.

  14. Aldehyde dehydrogenases in Arabidopsis thaliana: Biochemical requirements, metabolic pathways and functional analysis

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    Naim eStiti

    2011-10-01

    Full Text Available Aldehyde dehydrogenases (ALDHs are a family of enzymes which catalyze the oxidation of reactive aldehydes to their corresponding carboxylic acids. Here we summarize molecular genetic and biochemical analyses of selected Arabidopsis ALDH genes. Aldehyde molecules are very reactive and are involved in many metabolic processes but when they accumulate in excess they become toxic. Thus activity of aldehyde dehydrogenases is important in regulating the homeostasis of aldehydes. Overexpression of some ALDH genes demonstrated an improved abiotic stress tolerance. Despite the fact that several reports are available describing a role for specific ALDHs, their precise physiological roles are often still unclear. Therefore a number of genetic and biochemical tools have been generated to address the function with an emphasis on stress-related ALDHs. ALDHs exert their functions in different cellular compartments and often in a developmental and tissue specific manner. To investigate substrate specificity, catalytic efficiencies have been determined using a range of substrates varying in carbon chain length and degree of carbon oxidation. Mutational approaches identified amino acid residues critical for coenzyme usage and enzyme activities.

  15. Aldehyde Dehydrogenases in Arabidopsis thaliana: Biochemical Requirements, Metabolic Pathways, and Functional Analysis.

    Science.gov (United States)

    Stiti, Naim; Missihoun, Tagnon D; Kotchoni, Simeon O; Kirch, Hans-Hubert; Bartels, Dorothea

    2011-01-01

    Aldehyde dehydrogenases (ALDHs) are a family of enzymes which catalyze the oxidation of reactive aldehydes to their corresponding carboxylic acids. Here we summarize molecular genetic and biochemical analyses of selected ArabidopsisALDH genes. Aldehyde molecules are very reactive and are involved in many metabolic processes but when they accumulate in excess they become toxic. Thus activity of aldehyde dehydrogenases is important in regulating the homeostasis of aldehydes. Overexpression of some ALDH genes demonstrated an improved abiotic stress tolerance. Despite the fact that several reports are available describing a role for specific ALDHs, their precise physiological roles are often still unclear. Therefore a number of genetic and biochemical tools have been generated to address the function with an emphasis on stress-related ALDHs. ALDHs exert their functions in different cellular compartments and often in a developmental and tissue specific manner. To investigate substrate specificity, catalytic efficiencies have been determined using a range of substrates varying in carbon chain length and degree of carbon oxidation. Mutational approaches identified amino acid residues critical for coenzyme usage and enzyme activities.

  16. Requirement of DDX3 DEAD box RNA helicase for HIV-1 Rev-RRE export function.

    Science.gov (United States)

    Yedavalli, Venkat S R K; Neuveut, Christine; Chi, Ya-Hui; Kleiman, Lawrence; Jeang, Kuan-Teh

    2004-10-29

    A single transcript in its unspliced and spliced forms directs the synthesis of all HIV-1 proteins. Although nuclear export of intron-containing cellular transcripts is restricted in mammalian cells, HIV-1 has evolved the viral Rev protein to overcome this restriction for viral transcripts. Previously, CRM1 was identified as a cellular cofactor for Rev-dependent export of intron-containing HIV-1 RNA. Here, we present evidence that Rev/CRM1 activity utilizes the ATP-dependent DEAD box RNA helicase, DDX3. We show that DDX3 is a nucleo-cytoplasmic shuttling protein, which binds CRM1 and localizes to nuclear membrane pores. Knockdown of DDX3 using either antisense vector or dominant-negative mutants suppressed Rev-RRE-function in the export of incompletely spliced HIV-1 RNAs. Plausibly, DDX3 is the human RNA helicase which functions in the CRM1 RNA export pathway analogously to the postulated role for Dbp5p in yeast mRNA export.

  17. The tumor suppressor gene retinoblastoma-1 is required for retinotectal development and visual function in zebrafish.

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    Michael Gyda

    Full Text Available Mutations in the retinoblastoma tumor suppressor gene (rb1 cause both sporadic and familial forms of childhood retinoblastoma. Despite its clinical relevance, the roles of rb1 during normal retinotectal development and function are not well understood. We have identified mutations in the zebrafish space cadet locus that lead to a premature truncation of the rb1 gene, identical to known mutations in sporadic and familial forms of retinoblastoma. In wild-type embryos, axons of early born retinal ganglion cells (RGC pioneer the retinotectal tract to guide later born RGC axons. In rb1 deficient embryos, these early born RGCs show a delay in cell cycle exit, causing a transient deficit of differentiated RGCs. As a result, later born mutant RGC axons initially fail to exit the retina, resulting in optic nerve hypoplasia. A significant fraction of mutant RGC axons eventually exit the retina, but then frequently project to the incorrect optic tectum. Although rb1 mutants eventually establish basic retinotectal connectivity, behavioral analysis reveals that mutants exhibit deficits in distinct, visually guided behaviors. Thus, our analysis of zebrafish rb1 mutants reveals a previously unknown yet critical role for rb1 during retinotectal tract development and visual function.

  18. The adapter protein ADAP is required for selected dendritic cell functions

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    Togni Mauro

    2012-06-01

    Full Text Available Abstract Background The cytosolic adaptor protein ADAP (adhesion and degranulation promoting adapter protein is expressed by T cells, natural killer cells, myeloid cells and platelets. ADAP is involved in T-cell-receptor-mediated inside-out signaling, which leads to integrin activation, adhesion and reorganization of the actin cytoskeleton. However, little is known about the role of ADAP in myeloid cells. In the present study, we analyzed the function of ADAP in bone-marrow-derived dendritic cells (BMDCs from ADAP-deficient mice. Results ADAP-deficient BMDCs showed almost normal levels of antigen uptake, adhesion, maturation, migration from the periphery to the draining lymph nodes, antigen-specific T-cell activation, and production of the proinflammatory cytokines IL-6 and TNF-∝. Furthermore, we provide evidence that the activation of signaling pathways after lipopolysaccharide (LPS stimulation are not affected by the loss of ADAP. In contrast, ADAP-deficient BMDCs showed defects in CD11c-mediated cellular responses, with significantly diminished production of IL-6, TNF-∝ and IL-10. Actin polymerization was enhanced after CD11c integrin stimulation. Conclusions In summary, we propose that the adapter molecule ADAP is critical for selected CD11c integrin-mediated functions of dendritic cells.

  19. Pineal gland function is required for colon antipreneoplastic effects of physical exercise in rats.

    Science.gov (United States)

    Frajacomo, F T T; de Paula Garcia, W; Fernandes, C R; Garcia, S B; Kannen, V

    2015-10-01

    Light-at-night exposure enhances the risk of cancer. Colon cancer is among the most dangerous tumors affecting humankind. Physical exercise has shown positive effects against colon cancer. Here, we investigated whether pineal gland modulates antipreneoplastic effects of physical exercise in the colon. Surgical and non-surgical pineal impairments were performed to clarify the relationship between the pineal gland activity and manifestation of colonic preneoplastic lesions. Next, a progressive swimming training was applied in rats exposed or not to either non-surgical pineal impairment or carcinogen treatment for 10 weeks. Both surgical and non-surgical pineal impairments increased the development of colon preneoplasia. It was further found that impairing the pineal gland function, higher rates of DNA damage were induced in colonic epithelial and enteric glial cells. Physical exercise acted positively against preneoplasia, whereas impairing the pineal function with constant light exposure disrupts its positive effects on the development of preneoplastic lesions in the colon. This was yet related to increased DNA damage in glial cells and enteric neuronal activation aside from serum melatonin levels. Our findings suggest that protective effects of physical exercise against colon cancer are dependent on the pineal gland activity.

  20. SMN is required for sensory-motor circuit function in Drosophila.

    Science.gov (United States)

    Imlach, Wendy L; Beck, Erin S; Choi, Ben Jiwon; Lotti, Francesco; Pellizzoni, Livio; McCabe, Brian D

    2012-10-12

    Spinal muscular atrophy (SMA) is a lethal human disease characterized by motor neuron dysfunction and muscle deterioration due to depletion of the ubiquitous survival motor neuron (SMN) protein. Drosophila SMN mutants have reduced muscle size and defective locomotion, motor rhythm, and motor neuron neurotransmission. Unexpectedly, restoration of SMN in either muscles or motor neurons did not alter these phenotypes. Instead, SMN must be expressed in proprioceptive neurons and interneurons in the motor circuit to nonautonomously correct defects in motor neurons and muscles. SMN depletion disrupts the motor system subsequent to circuit development and can be mimicked by the inhibition of motor network function. Furthermore, increasing motor circuit excitability by genetic or pharmacological inhibition of K(+) channels can correct SMN-dependent phenotypes. These results establish sensory-motor circuit dysfunction as the origin of motor system deficits in this SMA model and suggest that enhancement of motor neural network activity could ameliorate the disease.

  1. The implications of user requirements for the functionality and content of a future EGDI

    Science.gov (United States)

    Pedersen, Mikael; Tulstrup, Jørgen

    2014-05-01

    The FP7 co-funded EGDI-Scope project is conducting analyses, which forms the basis for the development of an implementation plan for a future European Geological Data Infrastructure (EGDI) the aim of which will be to serve pan-European geological information from the European geological survey organisations. An important aspect of the project has been to consult stakeholders in order to deduce requirements, which is a fundamental prerequisite for making recommendations on the content and technical design of the system. It is indisputable that EGDI will have to build on international standards such as OGC and CGI and take into account legislative requirements from e.g. the INSPIRE directive. This will support the tasks of data providers and facilitate integration with other e-Infrastructures, but will not in itself lever the end user experiences. In order to make the future EGDI a successful online contributor of geological information, EGDI-Scope has therefore been looking very concretely into the needs and expectations of various user groups Most people have clear expectations anno 2014. They want to be able to search the web for information, and once found, they expect fast-performing, intuitive web applications with buttons to click, maps to navigate and reliable content to fulfil their immediate needs. In order for the EGDI to handle such requirements, a number of use cases for various thematic areas have been assessed. The use cases reveal (for example) that information about the geological composition of the ground is critical for the assessment of things like ecosystems or ground water quality. But where ecosystem assessment relies on the composition of the surface layers, groundwater geochemistry rely on the lithology of subsurface layers. For both scenarios, harmonised, pan-European geological maps are very important, but the harmonisation should not only relate to lithological classes, but also to the depth representation. The use cases also make clear

  2. Endogenous mesenchymal stromal cells in bone marrow are required to preserve muscle function in mdx mice.

    Science.gov (United States)

    Fujita, Ryo; Tamai, Katsuto; Aikawa, Eriko; Nimura, Keisuke; Ishino, Saki; Kikuchi, Yasushi; Kaneda, Yasufumi

    2015-03-01

    The physiological role of "endogenous" bone marrow (BM) mesenchymal stromal cells (MSCs) in tissue regeneration is poorly understood. Here, we show the significant contribution of unique endogenous BM-MSC populations to muscle regeneration in Duchenne muscular dystrophy (DMD) mice (mdx). Transplantation of BM cells (BMCs) from 10-week-old mdx into 3-4-week-old mdx mice increased inflammation and fibrosis and reduced muscle function compared with mdx mice that received BMCs from 10-week-old wild-type mice, suggesting that the alteration of BMC populations in mdx mice affects the progression of muscle pathology. Two distinct MSC populations in BM, that is, hematopoietic lineage (Lin)(-) /ckit(-) /CD106(+) /CD44(+) and Lin(-) /ckit(-) /CD106(+) /CD44(-) cells, were significantly reduced in 10-week-old mdx mice in disease progression. The results of a whole-transcriptome analysis indicated that these two MSC populations have distinct gene expression profiles, indicating that the Lin(-) /ckit(-) /CD106(+) /CD44(+) and Lin(-) /ckit(-) /CD106(+) /CD44(-) MSC populations are proliferative- and dormant-state populations in BM, respectively. BM-derived Lin(-) /CD106(+) /CD44(+) MSCs abundantly migrated to damaged muscles and highly expressed tumor necrosis factor-alpha-stimulated gene/protein-6 (TSG-6), an anti-inflammatory protein, in damaged muscles. We also demonstrated that TSG-6 stimulated myoblast proliferation. The injection of Lin(-) /ckit(-) /CD106(+) /CD44(+) MSCs into the muscle of mdx mice successfully ameliorated muscle dysfunction by decreasing inflammation and enhancing muscle regeneration through TSG-6-mediated activities. Thus, we propose a novel function of the unique endogenous BM-MSC population, which countered muscle pathology progression in a DMD model.

  3. Amyloid precursor protein is required for normal function of the rod and cone pathways in the mouse retina.

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    Tracy Ho

    Full Text Available Amyloid precursor protein (APP is a transmembrane glycoprotein frequently studied for its role in Alzheimer's disease. Our recent study in APP knockout (KO mice identified an important role for APP in modulating normal neuronal development in the retina. However the role APP plays in the adult retina and whether it is required for vision is unknown. In this study we evaluated the role of APP in retinal function and morphology comparing adult wildtype (WT and APP-KO mice. APP was expressed on neuronal cells of the inner retina, including horizontal, cone bipolar, amacrine and ganglion cells in WT mice. The function of the retina was assessed using the electroretinogram and although the rod photoreceptor responses were similar in APP-KO and WT mice, the post-photoreceptor, inner retinal responses of both the rod and cone pathways were reduced in APP-KO mice. These changes in inner retinal function did not translate to a substantial change in visual acuity as assessed using the optokinetic response or to changes in the gross cellular structure of the retina. These findings indicate that APP is not required for basic visual function, but that it is involved in modulating inner retinal circuitry.

  4. SIENA Customer Problem Statement and Requirements

    Energy Technology Data Exchange (ETDEWEB)

    L. Sauer; R. Clay; C. Adams; H. Walther; B. Allan; R. Mariano; C. Poore; B. Whiteside; B. Boughton; J. Dike; E. Hoffman; R. Hogan; C. LeGall

    2000-08-01

    This document describes the problem domain and functional requirements of the SIENA framework. The software requirements and system architecture of SIENA are specified in separate documents (called SIENA Software Requirement Specification and SIENA Software Architecture, respectively). While currently this version of the document describes the problems and captures the requirements within the Analysis domain (concentrating on finite element models), it is our intention to subsequent y expand this document to describe problems and capture requirements from the Design and Manufacturing domains. In addition, SIENA is designed to be extendible to support and integrate elements from the other domains (see SIENA Software Architecture document).

  5. Astrocytic Ca2+ signals are required for the functional integrity of tripartite synapses

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    Tanaka Mika

    2013-01-01

    Full Text Available Abstract Background Neuronal activity alters calcium ion (Ca2+ dynamics in astrocytes, but the physiologic relevance of these changes is controversial. To examine this issue further, we generated an inducible transgenic mouse model in which the expression of an inositol 1,4,5-trisphosphate absorbent, “IP3 sponge”, attenuates astrocytic Ca2+ signaling. Results Attenuated Ca2+ activity correlated with reduced astrocytic coverage of asymmetric synapses in the hippocampal CA1 region in these animals. The decreased astrocytic ‘protection’ of the synapses facilitated glutamate ‘spillover’, which was reflected by prolonged glutamate transporter currents in stratum radiatum astrocytes and enhanced N-methyl-D-aspartate receptor currents in CA1 pyramidal neurons in response to burst stimulation. These mice also exhibited behavioral impairments in spatial reference memory and remote contextual fear memory, in which hippocampal circuits are involved. Conclusions Our findings suggest that IP3-mediated astrocytic Ca2+ signaling correlates with the formation of functional tripartite synapses in the hippocampus.

  6. Phosphorylation of nucleoporin Tpr governs its differential localization and is required for its mitotic function.

    Science.gov (United States)

    Rajanala, Kalpana; Sarkar, Anshuk; Jhingan, Gagan Deep; Priyadarshini, Raina; Jalan, Manisha; Sengupta, Sagar; Nandicoori, Vinay Kumar

    2014-08-15

    A major constituent of the nuclear basket region of the nuclear pore complex (NPC), nucleoporin Tpr, plays roles in regulating multiple important processes. We have previously established that Tpr is phosphorylated in both a MAP-kinase-dependent and MAP-kinase-independent manner, and that Tpr acts as both a substrate and as a scaffold for ERK2 (also known as MAPK1). Here, we report the identification of S2059 and S2094 as the major novel ERK-independent phosphorylation sites and T1677, S2020, S2023 and S2034 as additional ERK-independent phosphorylation sites found in the Tpr protein in vivo. Our results suggest that protein kinase A phosphorylates the S2094 residue and that the site is hyperphosphorylated during mitosis. Furthermore, we find that Tpr is phosphorylated at the S2059 residue by CDK1 and the phosphorylated form distinctly localizes with chromatin during telophase. Abrogation of S2059 phosphorylation abolishes the interaction of Tpr with Mad1, thus compromising the localization of both Mad1 and Mad2 proteins, resulting in cell cycle defects. The identification of novel phosphorylation sites on Tpr and the observations presented in this study allow better understanding of Tpr functions.

  7. Mitochondrial Sulfide Detoxification Requires a Functional Isoform O-Acetylserine(thiol)lyase C in Arabidopsis thaliana

    Institute of Scientific and Technical Information of China (English)

    Consolación (A)lvarez; Irene García; Luis C.Romero; Cecilia Gotor

    2012-01-01

    In non-cyanogenic species,the main source of cyanide derives from ethylene and camalexin biosyntheses.In mitochondria,cyanide is a potent inhibitor of the cytochrome c oxidase and is metabolized bythe β-cyanoalanine synthase CYS-C1,catalyzing the conversion of cysteine and cyanide to hydrogen sulfide and β-cyanoalanine.The hydrogen sulfide released also inhibits the cytochrome c oxidase and needs to be detoxified by the O-acetylserine(thiol)lyase mitochondrial isoform,OAS-C,which catalyzes the incorporation of sulfide to O-acetylserine to produce cysteine,thus generating a cyclic pathway in the mitochondria.The loss of functional OAS-C isoforms causes phenotypic characteristics very similar to the loss of the CYS-C1 enzyme,showing defects in root hair formation.Genetic complementation with the OAS-C gene rescues the impairment of root hair elongation,restoring the wild-type phenotype.The mitochondria compromise their capacity to properly detoxify cyanide and the resulting sulfide because the latter cannot re-assimilate into cysteine in the oas-c null mutant.Consequently,we observe an accumulation of sulfide and cyanide and of the alternative oxidase,which is unable to prevent the production of reactive oxygen species probably due to the accumulation of both toxic molecules.Our results allow us to suggest that the significance of OAS-C is related to its role in the proper sulfide and cyanide detoxification in mitochondria.

  8. Smad3 signaling is required for satellite cell function and myogenic differentiation of myoblasts

    Institute of Scientific and Technical Information of China (English)

    Xiaojia Ge; Ravi Kambadur; Craig McFarlane; Anuradha Vajjala; Sudarsanareddy Lokireddy; Zhi Hui Ng; Chek Kun Tan; Nguan Soon Tan; Walter Wahli; Mridula Sharma

    2011-01-01

    TGF-β and myostatin are the two most important regulators of muscle growth.Both growth factors have been shown to signal through a Smad3-dependent pathway.However to date,the role of Smad3 in muscle growth and differentiation is not investigated.Here,we demonstrate that Smad3-null mice have decreased muscle mass and pronounced skeletal muscle atrophy.Consistent with this,we also find increased protein ubiquitination and elevated levels of the ubiquitin E3 ligase MuRF1 in muscle tissue isolated from Smad3-null mice.Loss of Smad3 also led to defective satellite cell (SC) functionality.Smad3-null SCs showed reduced propensity for self-renewal,which may lead to a progressive loss of SC number.Indeed,decreased SC number was observed in skeletal muscle from Smad3- null mice showing signs of severe muscle wasting.Further in vitro analysis of primary myoblast cultures identified that Smad3-nuil myoblasts exhibit impaired proliferation,differentiation and fusion,resulting in the formation of atrophied myotubes.A search for the molecular mechanism revealed that loss of Smad3 results in increased myostatin expression in Smad3-null muscle and myoblasts.Given that myostatin is a negative regulator,we hypothesize that increased myostatin levels are responsible for the atrophic phenotype in Smad3-null mice.Consistent with this theory,inactivation of myostatin in Smad3-null mice rescues the muscle atrophy phenotype.

  9. Soft robotic arm inspired by the octopus: I. From biological functions to artificial requirements.

    Science.gov (United States)

    Margheri, L; Laschi, C; Mazzolai, B

    2012-06-01

    Octopuses are molluscs that belong to the group Cephalopoda. They lack joints and rigid links, and as a result, their arms possess virtually limitless freedom of movement. These flexible appendages exhibit peculiar biomechanical features such as stiffness control, compliance, and high flexibility and dexterity. Studying the capabilities of the octopus arm is a complex task that presents a challenge for both biologists and roboticists, the latter of whom draw inspiration from the octopus in designing novel technologies within soft robotics. With this idea in mind, in this study, we used new, purposively developed methods of analysing the octopus arm in vivo to create new biologically inspired design concepts. Our measurements showed that the octopus arm can elongate by 70% in tandem with a 23% diameter reduction and exhibits an average pulling force of 40 N. The arm also exhibited a 20% mean shortening at a rate of 17.1 mm s(-1) and a longitudinal stiffening rate as high as 2 N (mm s)(-1). Using histology and ultrasounds, we investigated the functional morphology of the internal tissues, including the sinusoidal arrangement of the nerve cord and the local insertion points of the longitudinal and transverse muscle fibres. The resulting information was used to create novel design principles and specifications that can in turn be used in developing a new soft robotic arm.

  10. Hippocampal function is not required for the precision of remote place memory

    Directory of Open Access Journals (Sweden)

    Kitamura Takashi

    2012-02-01

    Full Text Available Abstract Background During permanent memory formation, recall of acquired place memories initially depends on the hippocampus and eventually become hippocampus-independent with time. It has been suggested that the quality of original place memories also transforms from a precise form to a less precise form with similar time course. The question arises of whether the quality of original place memories is determined by brain regions on which the memory depends. Results To directly test this idea, we introduced a new procedure: a non-associative place recognition memory test in mice. Combined with genetic and pharmacological approaches, our analyses revealed that place memory is precisely maintained for 28 days, although the recall of place memory shifts from hippocampus-dependent to hippocampus-independent with time. Moreover, the inactivation of the hippocampal function does not inhibit the precision of remote place memory. Conclusion These results indicate that the quality of place memories is not determined by brain regions on which the memory depends.

  11. Nutritional control of immunity: Balancing the metabolic requirements with an appropriate immune function.

    Science.gov (United States)

    De Rosa, Veronica; Galgani, Mario; Santopaolo, Marianna; Colamatteo, Alessandra; Laccetti, Roberta; Matarese, Giuseppe

    2015-09-01

    The immune system is a highly integrated network of cells sensitive to a number of environmental factors. Interestingly, recent years have seen a dramatic increase in our understanding of how diet makes a crucial contribution to human health, affecting the immune system, secretion of adipocytokines and metabolic pathways. Recent experimental evidence indicates that diet and its components are able to profoundly influence immune responses, thus affecting the development of inflammatory and autoimmune diseases. This review aims to discuss some of the main topics concerning the impact of nutrients and their relative composition on immune cell development and function that may be particularly important for regulating the balance between inflammatory and tolerogenic processes. We also highlight the effects of diet on commensal bacteria and how changes in the composition of the microbiota alter intestinal and systemic immune homeostasis. Finally, we summarize the effects of dietary compounds on epigenetic mechanisms involved in the regulation of several immune related genes. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Vibrio cholerae ensures function of host proteins required for virulence through consumption of luminal methionine sulfoxide

    Science.gov (United States)

    Vanhove, Audrey S.; Hang, Saiyu; Wong, Adam CN; Asara, John M.

    2017-01-01

    Vibrio cholerae is a diarrheal pathogen that induces accumulation of lipid droplets in enterocytes, leading to lethal infection of the model host Drosophila melanogaster. Through untargeted lipidomics, we provide evidence that this process is the product of a host phospholipid degradation cascade that induces lipid droplet coalescence in enterocytes. This infection-induced cascade is inhibited by mutation of the V. cholerae glycine cleavage system due to intestinal accumulation of methionine sulfoxide (MetO), and both dietary supplementation with MetO and enterocyte knock-down of host methionine sulfoxide reductase A (MsrA) yield increased resistance to infection. MsrA converts both free and protein-associated MetO to methionine. These findings support a model in which dietary MetO competitively inhibits repair of host proteins by MsrA. Bacterial virulence strategies depend on functional host proteins. We propose a novel virulence paradigm in which an intestinal pathogen ensures the repair of host proteins essential for pathogenesis through consumption of dietary MetO. PMID:28586382

  13. Investigation of Spectral Band Requirements for Improving Retrievals of Phytoplankton Functional Types

    Directory of Open Access Journals (Sweden)

    Aleksandra Wolanin

    2016-10-01

    Full Text Available Studying phytoplankton functional types (PFTs from space is possible due to recent advances in remote sensing. Though a variety of products are available, the limited number of wavelengths available compared to the number of model parameters needed to be retrieved is still a major problem in using ocean-color data for PFT retrievals. Here, we investigated which band placement could improve retrievals of three particular PFTs (diatoms, coccolithophores and cyanobacteria. In addition to analyzing dominant spectral features in the absorption spectra of the target PFTs, two previously-developed methods using measured spectra were applied to simulated data. Such a synthetic dataset allowed for significantly increasing the number of scenarios and enabled a full control over parameters causing spectral changes. We evaluated the chosen band placement by applying an adapted ocean reflectance inversion, as utilized in the generalized inherent optical properties (GIOP retrieval. Results show that the optimal band settings depend on the method applied to determine the bands placement, as well as on the internal variability of the dataset investigated. Therefore, continuous hyperspectral instruments would be most beneficial for discriminating multiple PFTs, though a small improvement in spectral sampling and resolution does not significantly modify the results. Bands, which could be added to future instruments (e.g., Ocean and Land Colour Instrument (OLCI instrument on the upcoming Sentinel-3B,-3C,-3D, etc., and further satellites in order to enhance PFT retrieval capabilities, were also determined.

  14. Dissection of transcription factor TFIIF functional domains required for initiation and elongation.

    Science.gov (United States)

    Tan, S; Conaway, R C; Conaway, J W

    1995-06-20

    TFIIF is unique among the general transcription factors because of its ability to control the activity of RNA polymerase II at both the initiation and elongation stages of transcription. Mammalian TFIIF, a heterodimer of approximately 30-kDa (RAP30) and approximately 70-kDa (RAP74) subunits, assists TFIIB in recruiting RNA polymerase II into the preinitiation complex and activates the overall rate of RNA chain elongation by suppressing transient pausing by polymerase at many sites on DNA templates. A major objective of efforts to understand how TFIIF regulates transcription has been to establish the relationship between its initiation and elongation activities. Here we establish this relationship by demonstrating that TFIIF transcriptional activities are mediated by separable functional domains. To accomplish this, we sought and identified distinct classes of RAP30 mutations that selectively block TFIIF activity in transcription initiation and elongation. We propose that (i) TFIIF initiation activity is mediated at least in part by RAP30 C-terminal sequences that include a cryptic DNA-binding domain similar to conserved region 4 of bacterial sigma factors and (ii) TFIIF elongation activity is mediated in part by RAP30 sequences located immediately upstream of the C terminus in a region proposed to bind RNA polymerase II and by additional sequences located in the RAP30 N terminus.

  15. Three Members of the LC8/DYNLL Family Are Required for Outer Arm Dynein Motor Function

    Science.gov (United States)

    Tanner, Christopher A.; Rompolas, Panteleimon; Patel-King, Ramila S.; Gorbatyuk, Oksana; Wakabayashi, Ken-ichi; Pazour, Gregory J.

    2008-01-01

    The highly conserved LC8/DYNLL family proteins were originally identified in axonemal dyneins and subsequently found to function in multiple enzyme systems. Genomic analysis uncovered a third member (LC10) of this protein class in Chlamydomonas. The LC10 protein is extracted from flagellar axonemes with 0.6 M NaCl and cofractionates with the outer dynein arm in sucrose density gradients. Furthermore, LC10 is specifically missing only from axonemes of those strains that fail to assemble outer dynein arms. Previously, the oda12-1 insertional allele was shown to lack the Tctex2-related dynein light chain LC2. The LC10 gene is located ∼2 kb from that of LC2 and is also completely missing from this mutant but not from oda12-2, which lacks only the 3′ end of the LC2 gene. Although oda12-1 cells assemble outer arms that lack only LC2 and LC10, this strain exhibits a flagellar beat frequency that is consistently less than that observed for strains that fail to assemble the entire outer arm and docking complex (e.g., oda1). These results support a key regulatory role for the intermediate chain/light chain complex that is an integral and highly conserved feature of all oligomeric dynein motors. PMID:18579685

  16. Functional phosphatome requirement for protein homeostasis, networked mitochondria, and sarcomere structure in C. elegans muscle.

    Science.gov (United States)

    Lehmann, Susann; Bass, Joseph J; Barratt, Thomas F; Ali, Mohammed Z; Szewczyk, Nathaniel J

    2017-08-01

    Skeletal muscle is central to locomotion and metabolic homeostasis. The laboratory worm Caenorhabditis elegans has been developed into a genomic model for assessing the genes and signals that regulate muscle development and protein degradation. Past work has identified a receptor tyrosine kinase signalling network that combinatorially controls autophagy, nerve signal to muscle to oppose proteasome-based degradation, and extracellular matrix-based signals that control calpain and caspase activation. The last two discoveries were enabled by following up results from a functional genomic screen of known regulators of muscle. Recently, a screen of the kinome requirement for muscle homeostasis identified roughly 40% of kinases as required for C. elegans muscle health; 80 have identified human orthologues and 53 are known to be expressed in skeletal muscle. To complement this kinome screen, here, we screen most of the phosphatases in C. elegans. RNA interference was used to knockdown phosphatase-encoding genes. Knockdown was first conducted during development with positive results also knocked down only in fully developed adult muscle. Protein homeostasis, mitochondrial structure, and sarcomere structure were assessed using transgenic reporter proteins. Genes identified as being required to prevent protein degradation were also knocked down in conditions that blocked proteasome or autophagic degradation. Genes identified as being required to prevent autophagic degradation were also assessed for autophagic vesicle accumulation using another transgenic reporter. Lastly, bioinformatics were used to look for overlap between kinases and phosphatases required for muscle homeostasis, and the prediction that one phosphatase was required to prevent mitogen-activated protein kinase activation was assessed by western blot. A little over half of all phosphatases are each required to prevent abnormal development or maintenance of muscle. Eighty-six of these phosphatases have known

  17. Requirement-specific use of trace element biogas additives under consideration of the bioavailability; Bedarfsgerechter Einsatz von Spurenelement-Biogasadditiven unter Beruecksichtigung der Bioverfuegbarkeit

    Energy Technology Data Exchange (ETDEWEB)

    Feher, Adam; Fritz, Thomas; Loewen, Achim; Nelles, Michael [HAWK Hochschule fuer Angewandte Wissenschaft und Kunst Hildesheim/Holzminden/Goettingen, Goettingen (Germany). Fachgebiet Nachhaltige Energie- und Umwelttechnik (NEUTec)

    2013-10-01

    A highly efficient utilisation of substrates and operational stability at the same time is essential for the efficiency of a biogas plant. The research project SequEx of HAWK and /SF GmbH investigates the increase of efficiency of biogas plants by targeted use of trace elements taking into account bio-availability. Based on sequential extraction diagrams a method for the determination of bio-availability of macro- and micro-nutrients is developed. Within this context, different trace element compounds are analysed during the fermentation process on their share of bioavailable micro-nutrients as well as their effect on the biological activity of microorganisms. The actual knowledge gap between common practice of nutrients' supply and real impact shall be closed by the knowledge base enhancement of the bio-availability of nutrients. (orig.)

  18. Analysis of connection element classes and locations and of some structural requirements for the mounting of different superstructure types on transport vehicles

    Directory of Open Access Journals (Sweden)

    Zoran Đ. Majkić

    2011-04-01

    Full Text Available The paper presents the basic requirements for transport vehicles. A special request regarding the adaptation of transport vehicles for the transport of various types of cargo was taken into consideration. Superstructures and the situation arising after mounting superstructures on wheeled transport vehicles were analyzed and the following was described: console coupling, stirrups, simplex elastic coupling, two-way elastic and rigid connection elements. Vehicle torsional elasticity is provided by a proper choice of the type of connection between the superstructure and the vehicle chassis. Applying the instructions of vehicle manufacturers for using appropriate connections between the truck superstructure and the vehicle chassis provides positive torsional elasticity of the vehicle. The paper gives the general recommendations of the Volvo, Mercedes and Renault transport vehicle producers for the use of particular connection types of locations as well as structural requirements for the mounting of concrete mixers, tippers and truck tanks on their vehicles. Introduction Achieving a high level of transport effectiveness depends on a number of factors. One of the most important ones is the possibility to increase the payload share in the gross vehicle weight. This share depends on the net vehicle weight, a method of coupling the truck superstructure with the chassis frame as well as on the truck superstructure construction. Realization of this requirement is of significant importance, particularly for large business systems since it results in the reduction of number of necessary vehicles, more economic fleet maintenance and the fleet capacity increase. It is also relatively easy to adapt the vehicle for the transportation of other loads, depending on user's current needs. The adaptation is correctly performed if manufacturer's recommendations are followed during the mounting of the superstructure on the chassis. This paper gives the analysis of the

  19. p27kip1 Is Required for Functionally Relevant Adult Hippocampal Neurogenesis in Mice.

    Science.gov (United States)

    Hörster, Henrik; Garthe, Alexander; Walker, Tara L; Ichwan, Muhammad; Steiner, Barbara; Khan, Muhammad Amir; Lie, Dieter Chichung; Nicola, Zeina; Ramirez-Rodriguez, Gerardo; Kempermann, Gerd

    2017-03-01

    We asked whether cell-cycle associated protein p27kip1 might be involved in the transition of precursor cells to postmitotic maturation in adult hippocampal neurogenesis. p27kip1 was expressed throughout the dentate gyrus with a strong nuclear expression in early postmitotic, calretinin-positive neurons and neuronally determined progenitor cells (type-3 and some type-2b), lower or absent expression in radial glia-like precursor cells (type-1) and type-2a cells and essentially no expression in granule cells. This suggested a transitory role in late proliferative and early postmitotic phases of neurogenesis. Inconsistent with a role limited to cell cycle arrest the acute stimuli, voluntary wheel running (RUN), environmental enrichment (ENR) and kainate-induced seizures increased p27kip1 expressing cells. Sequential short-term combination of RUN and ENR yielded more p27kip1 cells than either stimulus alone, indicating an additive effect. In vitro, p27kip1 was lowly expressed by proliferating precursor cells but increased upon differentiation. In p27kip1-/- mice neurogenesis was reduced in vivo, whereas the number of proliferating cells was increased. Accordingly, the microdissected dentate gyrus of p27kip1-/- mice generated more colonies in the neurosphere assay and an increased number of larger spheres with the differentiation potential unchanged. In p27kip1-/- monolayer cultures, proliferation was increased and cell cycle genes were upregulated. In the Morris water maze p27kip1-/- mice learned the task but were specifically impaired in the reversal phase explainable by the decrease in adult neurogenesis. We conclude that p27kip1 is involved in the decisive step around cell-cycle exit and plays an important role in activity-regulated and functionally relevant adult hippocampal neurogenesis. Stem Cells 2017;35:787-799.

  20. High isoproterenol doses are required to activate beta3-adrenoceptor-mediated functions in dogs.

    Science.gov (United States)

    Pelat, Michel; Verwaerde, Patrick; Galitzky, Jean; Lafontan, Max; Berlan, Michel; Senard, Jean-Michel; Montastruc, Jean-Louis

    2003-01-01

    The "in vivo" conditions for beta3-adrenoceptors (beta-AR) activation by isoproterenol were investigated in dog. Experiments were carried out in anesthetized dogs using isoproterenol as a nonselective beta-AR agonist. Intravenous infusion of isoproterenol (0.4 nmol/kg/min) induced arterial hypotension and tachycardia with a slight decrease in cutaneous blood flow. At this dose, isoproterenol increased glucose, glycerol, and nonesterified fatty acid plasma levels. The changes in cardiovascular and endocrine-metabolic parameters, induced by the low dose of isoproterenol, were suppressed by pretreatment with nadolol (1 mg/kg, i.v.). After nadolol administration, however, a 10-fold higher dose (4 nmol/kg/min) of isoproterenol was able to induce a decrease in arterial blood pressure with a slight tachycardia and an increase in cutaneous blood flow. This high dose of isoproterenol increased nonesterified fatty acid and glycerol plasma levels but failed to change glucose plasma levels. All these effects were abolished by a pretreatment with nadolol (1 mg/kg, i.v.) plus SR59230A [a selective beta3-adrenoceptor antagonist; (3-(2-ethylphenoxy)-1(1S)-1,2,3,4-tetrahydronaphth-1-ylaminol-(2S)2-propanol oxalate); 1 mg/kg, i.v.]. Moreover, as observed with the high dose of isoproterenol under nadolol pretreatment, an infusion of SR58611A [a selective beta3-adrenoceptor agonist; ((N2S)-7-carbethoxymethoxy-1,2,3,4-tetrahydronaphth-2-yl-(2R)-2-hydroxy-2-chlorophenyl) ethanamine hydrochloride] induces a decrease in mean arterial blood pressure associated with an increase in heart rate, cutaneous blood flow, and nonesterified fatty acid and glycerol plasma levels. These results demonstrate that the in vivo activation of beta3-adrenoceptors requires higher doses of catecholamine than those necessary for beta1- and/or beta2-adrenoceptor stimulation. These results also argue for the lack of a beta3-AR involvement in the control of heart rate and glycogenolysis in dogs.