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Sample records for promotes doubling functionality

  1. The double jeopardy of sales promotions.

    Science.gov (United States)

    Jones, J P

    1990-01-01

    The maturing of most consumer markets in the United States has put great pressure on manufacturers in their search for growth. They have concentrated on building sales and expanding share proportions in the stagnant markets with devices like niche products, product extensions, mergers, and international ventures. They have shifted emphasis to sales promotions at the expense of advertising. But promotions, when you come right down to it, mean price reductions. Trade promotions are almost always rebates, and consumer promotions are usually temporary price reductions or coupons. The cost in reduced profit, demonstrated mathematically through calculations of price elasticity, is severe. Besides, when the promotion is over, the manufacturer has not moved forward an inch in shoring up the brand franchise. Promotions bring volatile demand, whereas the producer seeks stable demand. By sustaining a brand image and building customer loyalty, on the other hand, theme advertising can stabilize demand. Moreover, this type of advertising is less likely than promotion is to invite destructive competitive retaliation. Calculation of the advertising elasticity of a brand indicates that sometimes even modest sales increases can produce healthy profit improvement. In a well-planned marketing campaign, there is often good reason to include trade or consumer promotion--to counter a leading competitor's moves, for example. But there is no point in carrying out wild swings at rivals in a struggle for market share. Mathematical techniques can aid the efficiency of marketing planning and put on a more rational basis the decision on where to put the dollars.

  2. Functional Analysis for Double Shell Tank (DST) Subsystems

    International Nuclear Information System (INIS)

    SMITH, D.F.

    2000-01-01

    This functional analysis identifies the hierarchy and describes the subsystem functions that support the Double-Shell Tank (DST) System described in HNF-SD-WM-TRD-007, System Specification for the Double-Shell Tank System. Because of the uncertainty associated with the need for upgrades of the existing catch tanks supporting the Waste Feed Delivery (WFD) mission, catch tank functions are not addressed in this document. The functions identified herein are applicable to the Phase 1 WFD mission only

  3. Double-continuum wave functions and double-photoionization cross sections of two-electron systems

    International Nuclear Information System (INIS)

    Tiwary, S.N.

    1996-09-01

    The present review briefly presents the growing experimental as well as theoretical interests in recent years in the double-continuum wave functions and double-photoionization cross sections of two-electron systems. The validity of existing double-continuum wave functions is analyzed and the importance of electronic correlations in both the initial as well as final states wave functions involved in the transition amplitude for double-photoionization process is demonstrated. At present, we do not have comprehensive and practical double-continuum wave functions which account the full correlation of two-electron in the continuum. Basic difficulties in making accurate theoretical calculations of double ionization by a single high energy photon especially in the vicinity of the threshold, where the correlation plays an important role, are discussed. Illuminating, illustrative and representative examples are presented in order to show the present status and the progress in this field. Future challenges and directions, in high-precision double-photoionization cross sections calculations, have been discussed and suggested. (author). 133 refs, 9 figs

  4. Toscana virus NSs protein promotes degradation of double-stranded RNA-dependent protein kinase.

    Science.gov (United States)

    Kalveram, Birte; Ikegami, Tetsuro

    2013-04-01

    Toscana virus (TOSV), which is transmitted by Phlebotomus spp. sandflies, is a major etiologic agent of aseptic meningitis and encephalitis in the Mediterranean. Like other members of the genus Phlebovirus of the family Bunyaviridae, TOSV encodes a nonstructural protein (NSs) in its small RNA segment. Although the NSs of Rift Valley fever virus (RVFV) has been identified as an important virulence factor, which suppresses host general transcription, inhibits transcription from the beta interferon promoter, and promotes the proteasomal degradation of double-stranded RNA-dependent protein kinase (PKR), little is known about the functions of NSs proteins encoded by less-pathogenic members of this genus. In this study we report that TOSV is able to downregulate PKR with similar efficiency as RVFV, while infection with the other phleboviruses-i.e., Punta Toro virus, sandfly fever Sicilian virus, or Frijoles virus-has no effect on cellular PKR levels. In contrast to RVFV, however, cellular transcription remains unaffected during TOSV infection. TOSV NSs protein promotes the proteasome-dependent downregulation of PKR and is able to interact with kinase-inactive PKR in infected cells.

  5. Promoters of Escherichia coli versus promoter islands: function and structure comparison.

    Directory of Open Access Journals (Sweden)

    Valeriy V Panyukov

    Full Text Available Expression of bacterial genes takes place under the control of RNA polymerase with exchangeable σ-subunits and multiple transcription factors. A typical promoter region contains one or several overlapping promoters. In the latter case promoters have the same or different σ-specificity and are often subjected to different regulatory stimuli. Genes, transcribed from multiple promoters, have on average higher expression levels. However, recently in the genome of Escherichia coli we found 78 regions with an extremely large number of potential transcription start points (promoter islands, PIs. It was shown that all PIs interact with RNA polymerase in vivo and are able to form transcriptionally competent open complexes both in vitro and in vivo but their transcriptional activity measured by oligonucleotide microarrays was very low, if any. Here we confirmed transcriptional defectiveness of PIs by analyzing the 5'-end specific RNA-seq data, but showed their ability to produce short oligos (9-14 bases. This combination of functional properties indicated a deliberate suppression of transcriptional activity within PIs. According to our data this suppression may be due to a specific conformation of the DNA double helix, which provides an ideal platform for interaction with both RNA polymerase and the histone-like nucleoid protein H-NS. The genomic DNA of E.coli contains therefore several dozen sites optimized by evolution for staying in a heterochromatin-like state. Since almost all promoter islands are associated with horizontally acquired genes, we offer them as specific components of bacterial evolution involved in acquisition of foreign genetic material by turning off the expression of toxic or useless aliens or by providing optimal promoter for beneficial genes. The putative molecular mechanism underlying the appearance of promoter islands within recipient genomes is discussed.

  6. Asymptotically double lacunry equivalent sequences defined by Orlicz functions

    Directory of Open Access Journals (Sweden)

    Ayhan Esi

    2014-04-01

    Full Text Available This paper presents the following definition which is natural combition of the definition for asymptotically equivalent and Orlicz function. The two nonnegative double sequences x=(x_{k,l} and y=(y_{k,l} are said to be M-asymptotically double equivalent to multiple L provided that for every ε>0, P-lim_{k,l}M(((|((x_{k,l}/(y_{k,l}-L|/ρ=0, for some ρ>0, (denoted by x∽y and simply M-asymptotically double equivalent if L=1. Also we give some new concepts related to this definition and some inclusion theorems.

  7. Double photoionization of helium: A new correlated double continuum wave function

    Energy Technology Data Exchange (ETDEWEB)

    Macri, P.A.; Kornberg, M.A.; Miraglia, J.E. [Consejo Nacional de Investigaciones Cientificas y Tecnicas, Buenos Aires (Argentina). Inst. de Astron. y Fisica del Espacio; Garibotti, C.R.; Gasaneo, G.; Colavecchia, F.D. [Centro Atomico Bariloche, Comision Nacional de Energia Atomica, 8400 S.C. de Bariloche, Rio Negro (Argentina)

    1997-10-01

    In this work we discuss the failures and goodness of using the product of two and three Coulomb waves to represent the double-continuum wave function of two electrons in the field of an ion. Furthermore, we present a new wave function for the double continuum, which takes into account the non-diagonal part of the kinetic energy. It satisfies the correct boundary conditions for large particle separations, and treats the electronic interaction in a more realistic way than the previously enunciated models. (orig.). 14 refs.

  8. Reduction of Double Clausenian Hypergeometric Functions

    DEFF Research Database (Denmark)

    Karlsson, Per W.

    1996-01-01

    The reduction formulas under consideration are those for which the conditions upon the variables are other than 'fixed values'. Known results are discussed, and some new formulas are derived by series manipulations from various known summation and transformation theorems. The ten functions in thi...

  9. Psychedelics Promote Structural and Functional Neural Plasticity

    Directory of Open Access Journals (Sweden)

    Calvin Ly

    2018-06-01

    Full Text Available Summary: Atrophy of neurons in the prefrontal cortex (PFC plays a key role in the pathophysiology of depression and related disorders. The ability to promote both structural and functional plasticity in the PFC has been hypothesized to underlie the fast-acting antidepressant properties of the dissociative anesthetic ketamine. Here, we report that, like ketamine, serotonergic psychedelics are capable of robustly increasing neuritogenesis and/or spinogenesis both in vitro and in vivo. These changes in neuronal structure are accompanied by increased synapse number and function, as measured by fluorescence microscopy and electrophysiology. The structural changes induced by psychedelics appear to result from stimulation of the TrkB, mTOR, and 5-HT2A signaling pathways and could possibly explain the clinical effectiveness of these compounds. Our results underscore the therapeutic potential of psychedelics and, importantly, identify several lead scaffolds for medicinal chemistry efforts focused on developing plasticity-promoting compounds as safe, effective, and fast-acting treatments for depression and related disorders. : Ly et al. demonstrate that psychedelic compounds such as LSD, DMT, and DOI increase dendritic arbor complexity, promote dendritic spine growth, and stimulate synapse formation. These cellular effects are similar to those produced by the fast-acting antidepressant ketamine and highlight the potential of psychedelics for treating depression and related disorders. Keywords: neural plasticity, psychedelic, spinogenesis, synaptogenesis, depression, LSD, DMT, ketamine, noribogaine, MDMA

  10. Promotion of health and human functionality

    Directory of Open Access Journals (Sweden)

    Ana Cristhina de Oliveira Brasil

    2013-08-01

    Full Text Available For the development of public health policies in Brazil, two aspects should be taken into consideration, namely, the demographic transition and the epidemiological transition. More and more, it is perceivable an increase in the number of elderly people living with numerous disabilities and also an epidemiological profile. National Household Sample Survey (Pesquisa Nacional por Amostra de Domicílios - PNAD 1998-2003 indicates a distribution of chronic diseases that, consequently, has generated an expressive number of disabilities. These people with disabilities need health services, and use them when they manage to access them. However, the current models of healthcare for the elderly or people with disabilities are expensive and, in some aspects, are not efficient, requiring preventive strategies and health equipment for the maintenance or recovery of health of an aged population. Thus, the public policy agenda of Brazil should give priority to the maintenance of the functionality of the aged, with monitoring of health status, specific preventive actions on health and education, and care seeking an integral and multidimensional attention, not necessarily focused on disease(1. The need to develop policies and strategies, particularly on health promotion, with a look detached from the disease is justified because health problems come not only from the disease, but from any other circumstance or health condition, such as, pregnancy , aging, stress, genetic predisposition – all classified by D-10, nevertheless, not being able to measure the status alterations related to health, and much less to sort and describe the context in which these problems occur, which complicates and jeopardizes the planning and solvability of actions and services in health, unlike the data by means of qualifiers that the International Classification of Functioning, Disability and Health (ICF has the potential to generate(2. Brazil is a member country of the World Health

  11. Promotion of Health and Human Functionality

    Directory of Open Access Journals (Sweden)

    Ana Cristhina de Oliveira Brasil

    2013-03-01

    Full Text Available For the development of public health policies in Brazil, two aspects should be taken into consideration, namely, the demographic transition and the epidemiological transition. More and more, it is perceivable an increase in the number of elderly people living with numerous disabilities and also an epidemiological profile. National Household Sample Survey (Pesquisa Nacional por Amostra de Domicílios - PNAD 1998-2003 indicates a distribution of chronic diseases that, consequently, has generated an expressive number of disabilities. These people with disabilities need health services, and use them when they manage to access them. However, the current models of healthcare for the elderly or people with disabilities are expensive and, in some aspects, are not efficient, requiring preventive strategies and health equipment for the maintenance or recovery of health of an aged population. Thus, the public policy agenda of Brazil should give priority to the maintenance of the functionality of the aged, with monitoring of health status, specific preventive actions on health and education, and care seeking an integral and multidimensional attention, not necessarily focused on disease(1.The need to develop policies and strategies, particularly on health promotion, with a look detached from the disease is justified because health problems come not only from the disease, but from any other circumstance or health condition, such as, pregnancy , aging, stress, genetic predisposition – all classified by D-10, nevertheless, not being able to measure the status alterations related to health, and much less to sort and describe the context in which these problems occur, which complicates and jeopardizes the planning and solvability of actions and services in health, unlike the data by means of qualifiers that the International Classification of Functioning, Disability and Health (ICF has the potential to generate(2.Brazil is a member country of the World Health

  12. Three-dimensional coupled double-distribution-function lattice ...

    Indian Academy of Sciences (India)

    Ruo-Fan Qiu

    2017-11-14

    Nov 14, 2017 ... Abstract. Two three-dimensional (3D) lattice Boltzmann models in the framework of coupled double-distribution- function approach for compressible flows, in which specific-heat ratio and Prandtl number can be adjustable, are developed in this paper. The main differences between the two models are ...

  13. Psychedelics Promote Structural and Functional Neural Plasticity.

    Science.gov (United States)

    Ly, Calvin; Greb, Alexandra C; Cameron, Lindsay P; Wong, Jonathan M; Barragan, Eden V; Wilson, Paige C; Burbach, Kyle F; Soltanzadeh Zarandi, Sina; Sood, Alexander; Paddy, Michael R; Duim, Whitney C; Dennis, Megan Y; McAllister, A Kimberley; Ori-McKenney, Kassandra M; Gray, John A; Olson, David E

    2018-06-12

    Atrophy of neurons in the prefrontal cortex (PFC) plays a key role in the pathophysiology of depression and related disorders. The ability to promote both structural and functional plasticity in the PFC has been hypothesized to underlie the fast-acting antidepressant properties of the dissociative anesthetic ketamine. Here, we report that, like ketamine, serotonergic psychedelics are capable of robustly increasing neuritogenesis and/or spinogenesis both in vitro and in vivo. These changes in neuronal structure are accompanied by increased synapse number and function, as measured by fluorescence microscopy and electrophysiology. The structural changes induced by psychedelics appear to result from stimulation of the TrkB, mTOR, and 5-HT2A signaling pathways and could possibly explain the clinical effectiveness of these compounds. Our results underscore the therapeutic potential of psychedelics and, importantly, identify several lead scaffolds for medicinal chemistry efforts focused on developing plasticity-promoting compounds as safe, effective, and fast-acting treatments for depression and related disorders. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  14. Certain Subclasses of Analytic and Bi-Univalent Functions Involving Double Zeta Functions

    OpenAIRE

    Siregar, Saibah; Raman, Sintuja

    2012-01-01

    In the present paper, we introduce two new subclasses of the functions class Σ of bi-univalent functions involving double zeta functions in the open unit disc U={z:zEC, |z|<1}. The estimates on the coefficients |a2| and |a3| for functions in these new subclasses of the function class Σ are obtained in our investigation.

  15. Energy demand with the flexible double-logarithmic functional form

    International Nuclear Information System (INIS)

    Nan, G.D.; Murry, D.A.

    1992-01-01

    A flexible double-logarithmic function form is developed to meet assumptions of consumer behavior. Then annual residential and commercial data (1970-87) are applied to this functional form to examine demand for petroleum products, electricity, and natural gas in California. The traditional double log-linear functional form has shortcomings of constant elasticities. The regression equations in this study, with varied estimated elasticities, overcome some of these shortcomings. All short-run own-price elasticities are inelastic and all income elasticities are close to unity in this study. According to the short-run time-trend elasticities, consumers' fuel preference in California is electricity. The long-run income elasticities also indicate that the residential consumers will consume more electricity and natural gas as their energy budgets increase in the long run. 14 refs., 5 tabs

  16. Functional Molecular Junctions Derived from Double Self-Assembled Monolayers.

    Science.gov (United States)

    Seo, Sohyeon; Hwang, Eunhee; Cho, Yunhee; Lee, Junghyun; Lee, Hyoyoung

    2017-09-25

    Information processing using molecular junctions is becoming more important as devices are miniaturized to the nanoscale. Herein, we report functional molecular junctions derived from double self-assembled monolayers (SAMs) intercalated between soft graphene electrodes. Newly assembled molecular junctions are fabricated by placing a molecular SAM/(top) electrode on another molecular SAM/(bottom) electrode by using a contact-assembly technique. Double SAMs can provide tunneling conjugation across the van der Waals gap between the terminals of each monolayer and exhibit new electrical functions. Robust contact-assembled molecular junctions can act as platforms for the development of equivalent contact molecular junctions between top and bottom electrodes, which can be applied independently to different kinds of molecules to enhance either the structural complexity or the assembly properties of molecules. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Unified double- and single-sided homogeneous Green's function representations

    Science.gov (United States)

    Wapenaar, Kees; van der Neut, Joost; Slob, Evert

    2016-06-01

    In wave theory, the homogeneous Green's function consists of the impulse response to a point source, minus its time-reversal. It can be represented by a closed boundary integral. In many practical situations, the closed boundary integral needs to be approximated by an open boundary integral because the medium of interest is often accessible from one side only. The inherent approximations are acceptable as long as the effects of multiple scattering are negligible. However, in case of strongly inhomogeneous media, the effects of multiple scattering can be severe. We derive double- and single-sided homogeneous Green's function representations. The single-sided representation applies to situations where the medium can be accessed from one side only. It correctly handles multiple scattering. It employs a focusing function instead of the backward propagating Green's function in the classical (double-sided) representation. When reflection measurements are available at the accessible boundary of the medium, the focusing function can be retrieved from these measurements. Throughout the paper, we use a unified notation which applies to acoustic, quantum-mechanical, electromagnetic and elastodynamic waves. We foresee many interesting applications of the unified single-sided homogeneous Green's function representation in holographic imaging and inverse scattering, time-reversed wave field propagation and interferometric Green's function retrieval.

  18. Density functional theory of the electrical double layer: the RFD functional

    International Nuclear Information System (INIS)

    Gillespie, Dirk; Valisko, Monika; Boda, Dezso

    2005-01-01

    Density functional theory (DFT) of electrolytes is applied to the electrical double layer under a wide range of conditions. The ions are charged, hard spheres of different size and valence, and the wall creating the double layer is uncharged, weakly charged, and strongly charged. Under all conditions, the density and electrostatic potential profiles calculated using the recently proposed RFD electrostatic functional (Gillespie et al 2002 J. Phys.: Condens. Matter 14 12129; 2003 Phys. Rev. E 68 031503) compare well to Monte Carlo simulations. When the wall is strongly charged, the RFD functional results agree with the results of a simpler perturbative electrostatic DFT, but the two functionals' results qualitatively disagree when the wall is uncharged or weakly charged. The RFD functional reproduces these phenomena of weakly charged double layers. It also reproduces bulk thermodynamic quantities calculated from pair correlation functions

  19. Generation of new solutions of the stationary axisymmetric Einstein equations by a double complex function method

    International Nuclear Information System (INIS)

    Zhong, Z.

    1985-01-01

    A new approach to the solution of certain differential equations, the double complex function method, is developed, combining ordinary complex numbers and hyperbolic complex numbers. This method is applied to the theory of stationary axisymmetric Einstein equations in general relativity. A family of exact double solutions, double transformation groups, and n-soliton double solutions are obtained

  20. Functional analysis of human and chimpanzee promoters.

    Science.gov (United States)

    Heissig, Florian; Krause, Johannes; Bryk, Jaroslaw; Khaitovich, Philipp; Enard, Wolfgang; Pääbo, Svante

    2005-01-01

    It has long been argued that changes in gene expression may provide an additional and crucial perspective on the evolutionary differences between humans and chimpanzees. To investigate how often expression differences seen in tissues are caused by sequence differences in the proximal promoters, we tested the expression activity in cultured cells of human and chimpanzee promoters from genes that differ in mRNA expression between human and chimpanzee tissues. Twelve promoters for which the corresponding gene had been shown to be differentially expressed between humans and chimpanzees in liver or brain were tested. Seven showed a significant difference in activity between the human promoter and the orthologous chimpanzee promoter in at least one of the two cell lines used. However, only three of them showed a difference in the same direction as in the tissues. Differences in proximal promoter activity are likely to be common between humans and chimpanzees, but are not linked in a simple fashion to gene-expression levels in tissues. This suggests that several genetic differences between humans and chimpanzees might be responsible for a single expression difference and thus that relevant expression differences between humans and chimpanzees will be difficult to predict from cell culture experiments or DNA sequences.

  1. Singlet structure function F_1 in double-logarithmic approximation

    Science.gov (United States)

    Ermolaev, B. I.; Troyan, S. I.

    2018-03-01

    The conventional ways to calculate the perturbative component of the DIS singlet structure function F_1 involve approaches based on BFKL which account for the single-logarithmic contributions accompanying the Born factor 1 / x. In contrast, we account for the double-logarithmic (DL) contributions unrelated to 1 / x and because of that they were disregarded as negligibly small. We calculate the singlet F_1 in the double-logarithmic approximation (DLA) and account at the same time for the running α _s effects. We start with a total resummation of both quark and gluon DL contributions and obtain the explicit expression for F_1 in DLA. Then, applying the saddle-point method, we calculate the small- x asymptotics of F_1, which proves to be of the Regge form with the leading singularity ω _0 = 1.066. Its large value compensates for the lack of the factor 1 / x in the DLA contributions. Therefore, this Reggeon can be identified as a new Pomeron, which can be quite important for the description of all QCD processes involving the vacuum (Pomeron) exchanges at very high energies. We prove that the expression for the small- x asymptotics of F_1 scales: it depends on a single variable Q^2/x^2 only instead of x and Q^2 separately. Finally, we show that the small- x asymptotics reliably represent F_1 at x ≤ 10^{-6}.

  2. The Role of RANTES Promoter Polymorphism in Functional Dyspepsia

    OpenAIRE

    Tahara, Tomomitsu; Shibata, Tomoyuki; Yamashita, Hiromi; Hirata, Ichiro; Arisawa, Tomiyasu

    2009-01-01

    Altered inflammatory immune responses have been shown to be associated with functional gastro intestinal disorder. We aimed to clarify the effect of functional promoter polymorphism of RANTES, which is a potent chemoattractant peptide for memory T lymphocytes and eosinophils, on the risk of functional dyspepsia in a Japanese population. RANTES promoter C-28G polymorphism was genotyped in 246 subjects including 134 FD patients according to Roma III criteria and 112 non-symptomatic healthy cont...

  3. Electrochemical double-layer capacitors based on functionalized graphene

    Science.gov (United States)

    Pope, Michael Allan

    Graphene is a promising electrode material for electrochemical double-layer capacitors (EDLCs) used for energy storage due to its high electrical conductivity and theoretical specific surface area. However, the intrinsic capacitance of graphene is known to be low and governed by the electronic side of the interface. Furthermore, graphene tends to aggregate and stack together when processed into thick electrode films. This significantly lowers the ion-accessible specific surface area (SSA). Maximizing both the SSA and the intrinsic capacitance are the main problems addressed in this thesis in an effort to improve the specific capacitance and energy density of EDLCs. In contrast to pristine graphene, functionalized graphene produced by the thermal exfoliation of graphite oxide contains residual functional groups and lattice defects. To study how these properties affect the double-layer capacitance, a model electrode system capable of measuring the intrinsic electrochemical properties of functionalized graphene was developed. To prevent artifacts and uncertainties related to measurements on porous electrodes, the functionalized graphene sheets (FGSs) were assembled as densely tiled monolayers using a Langmuir-Blodgett technique. In this way, charging can be studied in a well-defined 2D geometry. The possibility of measuring and isolating the intrinsic electrochemical properties of FGS monolayers was first demonstrated by comparing capacitance and redox probe measurements carried out on coatings deposited on passivated gold and single crystal graphite substrates. This monolayer system was then used to follow the double-layer capacitance of the FGS/electrolyte interface as the structure and chemistry of graphene was varied by thermal treatments ranging from 300 °C to 2100 °C. Elemental analysis and Raman spectroscopy were used to determine the resulting chemical and structural transformation upon heat treatment. It was demonstrated that intrinsically defective

  4. Some double sequence spaces of interval numbers defined by Orlicz function

    Directory of Open Access Journals (Sweden)

    Ayhan Esi

    2014-10-01

    Full Text Available In this paper we introduce some interval valued double sequence spaces defined by Orlicz function and study different properties of these spaces like inclusion relations, solidity, etc. We establish some inclusion relations among them. Also we introduce the concept of double statistical convergence for interval number sequences and give an inclusion relation between interval valued double sequence spaces.

  5. Promoting Efficacy Research on Functional Analytic Psychotherapy

    Science.gov (United States)

    Maitland, Daniel W. M.; Gaynor, Scott T.

    2012-01-01

    Functional Analytic Psychotherapy (FAP) is a form of therapy grounded in behavioral principles that utilizes therapist reactions to shape target behavior. Despite a growing literature base, there is a paucity of research to establish the efficacy of FAP. As a general approach to psychotherapy, and how the therapeutic relationship produces change,…

  6. Does partial occlusion promote normal binocular function?

    Science.gov (United States)

    Li, Jingrong; Thompson, Benjamin; Ding, Zhaofeng; Chan, Lily Y L; Chen, Xiang; Yu, Minbin; Deng, Daming; Hess, Robert F

    2012-10-03

    There is growing evidence that abnormal binocular interactions play a key role in the amblyopia syndrome and represent a viable target for treatment interventions. In this context the use of partial occlusion using optical devices such as Bangerter filters as an alternative to complete occlusion is of particular interest. The aims of this study were to understand why Bangerter filters do not result in improved binocular outcomes compared to complete occlusion, and to compare the effects of Bangerter filters, optical blur and neutral density (ND) filters on normal binocular function. The effects of four strengths of Bangerter filters (0.8, 0.6, 0.4, 0.2) on letter and vernier acuity, contrast sensitivity, stereoacuity, and interocular suppression were measured in 21 observers with normal vision. In a subset of 14 observers, the partial occlusion effects of Bangerter filters, ND filters and plus lenses on stereopsis and interocular suppression were compared. Bangerter filters did not have graded effect on vision and induced significant disruption to binocular function. This disruption was greater than that of monocular defocus but weaker than that of ND filters. The effect of the Bangerter filters on stereopsis was more pronounced than their effect on monocular acuity, and the induced monocular acuity deficits did not predict the induced deficits in stereopsis. Bangerter filters appear to be particularly disruptive to binocular function. Other interventions, such as optical defocus and those employing computer generated dichoptic stimulus presentation, may be more appropriate than partial occlusion for targeting binocular function during amblyopia treatment.

  7. Conceptualizing Parental Autonomy Support: Adolescent Perceptions of Promotion of Independence versus Promotion of Volitional Functioning

    Science.gov (United States)

    Soenens, Bart; Vansteenkiste, Maarten; Lens, Willy; Luyckx, Koen; Goossens, Luc; Beyers, Wim; Ryan, Richard M.

    2007-01-01

    In current research on parenting, 2 ways of conceptualizing perceived parental autonomy support can be distinguished. Parental autonomy support can be defined in terms of promotion of independence (PI) or in terms of promotion of volitional functioning (PVF). This study aimed to establish the empirical distinctiveness of both conceptualizations…

  8. OPTIMIZATION OF PROMOTION EXPENSES USING A PRODUCTION FUNCTION

    Directory of Open Access Journals (Sweden)

    Gleb V. Kamenskiy

    2013-01-01

    Full Text Available This article describes an opportunity of application of the production function for optimization of promotion expenses. Second part of the article contains a data of a real enterprise to calculate an optimal advertising budget.

  9. APOBEC3 cytidine deaminases in double-strand DNA break repair and cancer promotion.

    Science.gov (United States)

    Nowarski, Roni; Kotler, Moshe

    2013-06-15

    High frequency of cytidine to thymidine conversions was identified in the genome of several types of cancer cells. In breast cancer cells, these mutations are clustered in long DNA regions associated with single-strand DNA (ssDNA), double-strand DNA breaks (DSB), and genomic rearrangements. The observed mutational pattern resembles the deamination signature of cytidine to uridine carried out by members of the APOBEC3 family of cellular deaminases. Consistently, APOBEC3B (A3B) was recently identified as the mutational source in breast cancer cells. A3G is another member of the cytidine deaminases family predominantly expressed in lymphoma cells, where it is involved in mutational DSB repair following ionizing radiation treatments. This activity provides us with a new paradigm for cancer cell survival and tumor promotion and a mechanistic link between ssDNA, DSBs, and clustered mutations. Cancer Res; 73(12); 3494-8. ©2013 AACR. ©2013 AACR.

  10. Conditional punishment is a double-edged sword in promoting cooperation.

    Science.gov (United States)

    Huang, Feng; Chen, Xiaojie; Wang, Long

    2018-01-11

    Punishment is widely recognized as an effective approach for averting from exploitation by free-riders in human society. However, punishment is costly, and thus rational individuals are unwilling to take the punishing action, resulting in the second-order free-rider problem. Recent experimental study evidences that individuals prefer conditional punishment, and their punishing decision depends on other members' punishing decisions. In this work, we thus propose a theoretical model for conditional punishment and investigate how such conditional punishment influences cooperation in the public goods game. Considering conditional punishers only take the punishing action when the number of unconditional punishers exceeds a threshold number, we demonstrate that such conditional punishment induces the effect of a double-edged sword on the evolution of cooperation both in well-mixed and structured populations. Specifically, when it is relatively easy for conditional punishers to engage in the punishment activity corresponding to a low threshold value, cooperation can be promoted in comparison with the case without conditional punishment. Whereas when it is relatively difficult for conditional punishers to engage in the punishment activity corresponding to a high threshold value, cooperation is inhibited in comparison with the case without conditional punishment. Moreover, we verify that such double-edged sword effect exists in a wide range of model parameters and can be still observed in other different punishment regimes.

  11. Identification of functional DNA variants in the constitutive promoter region of MDM2

    Directory of Open Access Journals (Sweden)

    Lalonde Marie-Eve

    2012-09-01

    Full Text Available Abstract Although mutations in the oncoprotein murine double minute 2 (MDM2 are rare, MDM2 gene overexpression has been observed in several human tumors. Given that even modest changes in MDM2 levels might influence the p53 tumor suppressor signaling pathway, we postulated that sequence variation in the promoter region of MDM2 could lead to disregulated expression and variation in gene dosage. Two promoters have been reported for MDM2; an internal promoter (P2, which is located near the end of intron 1 and is p53-responsive, and an upstream constitutive promoter (P1, which is p53-independent. Both promoter regions contain DNA variants that could influence the expression levels of MDM2, including the well-studied single nucleotide polymorphism (SNP SNP309, which is located in the promoter P2; i.e., upstream of exon 2. In this report, we screened the promoter P1 for DNA variants and assessed the functional impact of the corresponding SNPs. Using the dbSNP database and genotyping validation in individuals of European descent, we identified three common SNPs (−1494 G > A; indel 40 bp; and −182 C > G. Three major promoter haplotypes were inferred by using these three promoter SNPs together with rs2279744 (SNP309. Following subcloning into a gene reporter system, we found that two of the haplotypes significantly influenced MDM2 promoter activity in a haplotype-specific manner. Site-directed mutagenesis experiments indicated that the 40 bp insertion/deletion variation is causing the observed allelic promoter activity. This study suggests that part of the variability in the MDM2 expression levels could be explained by allelic p53-independent P1 promoter activity.

  12. Hydrocracking of Cerbera manghas Oil with Co-Ni/HZSM-5 as Double Promoted Catalyst

    Directory of Open Access Journals (Sweden)

    Lenny Marlinda

    2017-05-01

    Full Text Available The effect of various reaction temperature on the hydrocracking of Cerbera manghas oil to produce a paraffin-rich mixture of hydrocarbons with Co-Ni/HZSM-5 as doubled promoted catalyst were studied. The Co-Ni/HZSM-5 catalyst with various metal loading and metal ratio was prepared by incipient wetness impregnation. The catalysts were characterized by XRD, AAS, and N2 adsorption-desorption. Surface area, pore diameter, and pore volume of catalysts decreased with the increasing of metals loading. The hydrocracking process was conducted under hydrogen initial pressure in batch reactor equipped with a mechanical stirrer. The reaction was carried out at a temperature of 300-375 oC for 2 h.  Depending on the experimental condition, the reaction pressure changed between 10 bar and 15 bar.   Several parameters were used to evaluate biofuel produced, including oxygen removal, hydrocarbon composition and gasoline/kerosene/diesel yields. Biofuel was analyzed by Fourier Transform Infrared Spectroscopic (FTIR and gas chromatography-mass spectrometry (GC-MS. The composition of hydrocarbon compounds in liquid products was similar to the compounds in the gasoil sold in unit of Pertamina Gas Stations, namely pentadecane, hexadecane, heptadecane, octadecane, and nonadecane with different amounts for each biofuel produced at different reaction temperatures. However, isoparaffin compounds were not formed at all operating conditions. Pentadecane (n-C15 and heptadecane (n-C17 were the most abundant composition in gasoil when Co-Ni/HZSM-5 catalyst was used. Cerbera Manghas oil can be recommended as the source of non-edible vegetable oil to produce gasoil as an environmentally friendly transportation fuel. Copyright © 2017 BCREC Group. All rights reserved Received: 20th May 2016; Revised: 30th January 2017; Accepted: 10th February 2017 How to Cite: Marlinda, L., Al-Muttaqii, M., Gunardi, I., Roesyadi, A., Prajitno, D.H. (2017. Hydrocracking of Cerbera manghas Oil

  13. Functional analysis of the OCA-B promoter.

    Science.gov (United States)

    Stevens, S; Wang, L; Roeder, R G

    2000-06-15

    OCA-B was identified as a B cell-specific coactivator that functions with either Oct-1 or Oct-2 to mediate efficient cell type-specific transcription via the octamer site (ATGCAAAT) both in vivo and in vitro. Mice lacking OCA-B exhibit normal Ag-independent B cell maturation. In contrast, Ag-dependent functions, including production of secondary Ig isotypes and germinal center formation, are greatly affected. To better understand OCA-B expression and, ultimately, the defects observed in the OCA-B knockout mice, we have cloned the OCA-B promoter and examined its function in both transformed and primary B cells. We show here that the OCA-B promoter is developmentally regulated, with activity increasing throughout B cell differentiation. Through physical and functional assays, we have found an activating transcription factor/cAMP response element binding protein binding site (or cAMP response element) that is crucial for OCA-B promoter activity. Furthermore, we demonstrate that IL-4 and anti-CD40 induce both the OCA-B promoter and octamer-dependent promoters, thus implicating OCA-B in B cell signaling events in the nucleus.

  14. A Sharp Double Inequality for Trigonometric Functions and Its Applications

    Directory of Open Access Journals (Sweden)

    Zhen-Hang Yang

    2014-01-01

    Full Text Available We present the best possible parameters p and q such that the double inequality (2/3cos2p(t/2+1/31/p

  15. Functional significance of SPINK1 promoter variants in chronic pancreatitis.

    Science.gov (United States)

    Derikx, Monique H M; Geisz, Andrea; Kereszturi, Éva; Sahin-Tóth, Miklós

    2015-05-01

    Chronic pancreatitis is a progressive inflammatory disorder of the pancreas, which often develops as a result of genetic predisposition. Some of the most frequently identified risk factors affect the serine protease inhibitor Kazal type 1 (SPINK1) gene, which encodes a trypsin inhibitor responsible for protecting the pancreas from premature trypsinogen activation. Recent genetic and functional studies indicated that promoter variants in the SPINK1 gene might contribute to disease risk in carriers. Here, we investigated the functional effects of 17 SPINK1 promoter variants using luciferase reporter gene expression assay in four different cell lines, including three pancreatic acinar cell lines (rat AR42J with or without dexamethasone-induced differentiation and mouse 266-6) and human embryonic kidney 293T cells. We found that most variants caused relatively small changes in promoter activity. Surprisingly, however, we observed significant variations in the effects of the promoter variants in the different cell lines. Only four variants exhibited consistently reduced promoter activity in all acinar cell lines, confirming previous reports that variants c.-108G>T, c.-142T>C, and c.-147A>G are risk factors for chronic pancreatitis and identifying c.-52G>T as a novel risk variant. In contrast, variant c.-215G>A, which is linked with the disease-associated splice-site mutation c.194 + 2T>C, caused increased promoter activity, which may mitigate the overall effect of the pathogenic haplotype. Our study lends further support to the notion that sequence evaluation of the SPINK1 promoter region in patients with chronic pancreatitis is justified as part of the etiological investigation. Copyright © 2015 the American Physiological Society.

  16. Assembly and function of DNA double-strand break repair foci in mammalian cells

    DEFF Research Database (Denmark)

    Bekker-Jensen, Simon; Mailand, Niels

    2010-01-01

    DNA double-strand breaks (DSBs) are among the most cytotoxic types of DNA damage, which if left unrepaired can lead to mutations or gross chromosomal aberrations, and promote the onset of diseases associated with genomic instability such as cancer. One of the most discernible hallmarks...

  17. Modifying Lipid Rafts Promotes Regeneration and Functional Recovery

    Directory of Open Access Journals (Sweden)

    Nardos G. Tassew

    2014-08-01

    Full Text Available Ideal strategies to ameliorate CNS damage should promote both neuronal survival and axon regeneration. The receptor Neogenin promotes neuronal apoptosis. Its ligand prevents death, but the resulting repulsive guidance molecule a (RGMa-Neogenin interaction also inhibits axonal growth, countering any prosurvival benefits. Here, we explore strategies to inhibit Neogenin, thus simultaneously enhancing survival and regeneration. We show that bone morphogenetic protein (BMP and RGMa-dependent recruitment of Neogenin into lipid rafts requires an interaction between RGMa and Neogenin subdomains. RGMa or Neogenin peptides that prevent this interaction, BMP inhibition by Noggin, or reduction of membrane cholesterol all block Neogenin raft localization, promote axon outgrowth, and prevent neuronal apoptosis. Blocking Neogenin raft association influences axonal pathfinding, enhances survival in the developing CNS, and promotes survival and regeneration in the injured adult optic nerve and spinal cord. Moreover, lowering cholesterol disrupts rafts and restores locomotor function after spinal cord injury. These data reveal a unified strategy to promote both survival and regeneration in the CNS.

  18. SCAI promotes DNA double-strand break repair in distinct chromosomal contexts

    DEFF Research Database (Denmark)

    Hansen, Rebecca Kring; Mund, Andreas; Poulsen, Sara Lund

    2016-01-01

    cell invasion) as a 53BP1-interacting chromatin-associated protein that promotes the functionality of several DSB repair pathways in mammalian cells. SCAI undergoes prominent enrichment at DSB sites through dual mechanisms involving 53BP1-dependent recruitment to DSB-surrounding chromatin and 53BP1...... in repressive chromatin environments. Moreover, we establish an important role of SCAI in meiotic recombination, as SCAI deficiency in mice leads to germ cell loss and subfertility associated with impaired retention of the DMC1 recombinase on meiotic chromosomes. Collectively, our findings uncover SCAI...... as a physiologically important component of both NHEJ- and HR-mediated pathways that potentiates DSB repair efficiency in specific chromatin contexts....

  19. Brisk walking can promote functional recovery in chronic stroke patients

    OpenAIRE

    Batcho, Sèbiyo Charles; Stoquart, Gaëtan; Thonnard, Jean-Louis

    2013-01-01

    Objective: To determine whether regular brisk walking can promote functional recovery in community-dwelling stroke patients. Patients: A total of 44 chronic stroke patients, recruited in Belgium and Benin, respectively European high-income and African low-income countries. Methods: This longitudinal, single-cohort, observational study with 1 intervention period and 4 time-points of assessments (2 baseline, 1 post-intervention and 1 follow-up) was structured in 3 periods: pre-intervention peri...

  20. Functional effectiveness of threat appeals in exercise promotion messages

    Directory of Open Access Journals (Sweden)

    Olivier Mairesse

    2010-01-01

    Full Text Available As more than 70% of individuals in Western societies can be categorized as sedentary and inactivity has been recognized to lead to a series of serious physical and psychological disorders, the importance of physical activity promotion is ever more emphasized. Many social marketing campaigns use threat (or fear appeals to promote healthy behaviors. Theoretical models, such as the Extended Parallel Process Model integrate concepts as 'perceived threat' and 'perceived efficacy' to explain how such messages operate and can cause diverse behavioral reactions. It is however still not entirely clear how these different aspects are valuated and combined to determine desired versus undesired response behaviors in individuals. In a functional integration task, threat-appeal based exercise promotion messages varying in psychological threat and efficacy content were shown to sedentary employees in order to assess how they affect their intention to engage in physical exercise. Our results show that individuals can be categorized in 4 different clusters depending on the way they valuate threat and efficacy appeals: i.e. individuals sensitive to both types of cues, those sensitive to either the threat or the efficacy component in the message and those insensitive to either one of them. As different segments of receivers of the message react differently to threat and efficacy combinations, it is concluded that different approaches to designing effective mass media campaigns may be required for effective exercise promotion.

  1. Chopped or long roughage: what do calves prefer? Using cross point analysis of double demand functions.

    Directory of Open Access Journals (Sweden)

    Laura E Webb

    Full Text Available The present study aimed to quantify calves' (Bos taurus preference for long versus chopped hay and straw, and hay versus straw, using cross point analysis of double demand functions, in a context where energy intake was not a limiting factor. Nine calves, fed milk replacer and concentrate, were trained to work for roughage rewards from two simultaneously available panels. The cost (number of muzzle presses required on the panels varied in each session (left panel/right panel: 7/35, 14/28, 21/21, 28/14, 35/7. Demand functions were estimated from the proportion of rewards achieved on one panel relative to the total number of rewards achieved in one session. Cross points (cp were calculated as the cost at which an equal number of rewards was achieved from both panels. The deviation of the cp from the midpoint (here 21 indicates the strength of the preference. Calves showed a preference for long versus chopped hay (cp = 14.5; P = 0.004, and for hay versus straw (cp = 38.9; P = 0.004, both of which improve rumen function. Long hay may stimulate chewing more than chopped hay, and the preference for hay versus straw could be related to hedonic characteristics. No preference was found for chopped versus long straw (cp = 20.8; P = 0.910. These results could be used to improve the welfare of calves in production systems; for example, in systems where calves are fed hay along with high energy concentrate, providing long hay instead of chopped could promote roughage intake, rumen development, and rumination.

  2. Chopped or Long Roughage: What Do Calves Prefer? Using Cross Point Analysis of Double Demand Functions

    Science.gov (United States)

    Webb, Laura E.; Bak Jensen, Margit; Engel, Bas; van Reenen, Cornelis G.; Gerrits, Walter J. J.; de Boer, Imke J. M.; Bokkers, Eddie A. M.

    2014-01-01

    The present study aimed to quantify calves'(Bos taurus) preference for long versus chopped hay and straw, and hay versus straw, using cross point analysis of double demand functions, in a context where energy intake was not a limiting factor. Nine calves, fed milk replacer and concentrate, were trained to work for roughage rewards from two simultaneously available panels. The cost (number of muzzle presses) required on the panels varied in each session (left panel/right panel): 7/35, 14/28, 21/21, 28/14, 35/7. Demand functions were estimated from the proportion of rewards achieved on one panel relative to the total number of rewards achieved in one session. Cross points (cp) were calculated as the cost at which an equal number of rewards was achieved from both panels. The deviation of the cp from the midpoint (here 21) indicates the strength of the preference. Calves showed a preference for long versus chopped hay (cp  = 14.5; P  = 0.004), and for hay versus straw (cp  = 38.9; P = 0.004), both of which improve rumen function. Long hay may stimulate chewing more than chopped hay, and the preference for hay versus straw could be related to hedonic characteristics. No preference was found for chopped versus long straw (cp  = 20.8; P = 0.910). These results could be used to improve the welfare of calves in production systems; for example, in systems where calves are fed hay along with high energy concentrate, providing long hay instead of chopped could promote roughage intake, rumen development, and rumination. PMID:24558426

  3. Double-dealing behavior potentially promotes cooperation in evolutionary prisoner's dilemma games

    Science.gov (United States)

    Dai, Qionglin; Li, Haihong; Cheng, Hongyan; Li, Yuting; Yang, Junzhong

    2010-11-01

    We investigate the effects of double-dealing behavior on cooperation in evolutionary games. Each individual in a population has two attributes: character and action. One's action may be consistent with one's character or not. We provide analytical results by a mean-field description of evolutionary prisoner's dilemma games (PDGs). Moreover, we give numerical results on different networks, ranging from square lattices to scale-free networks (SFNs). Two important conclusions have been drawn from the results on SFNs. Firstly, if only non-influential individuals (those with low degrees) have chances of becoming double-dealers, cooperation is certain to deteriorate. Secondly, when influential individuals (those with high degrees) adopt double-dealing behavior moderately, cooperation would be enhanced, which is in opposition to the traditional belief. These results help us to understand better the social phenomenon of the existence of double-dealers. In addition to the PDG, other types of games including the snowdrift game, the stag-hunt game and the harmony game have also been studied on our model. The results for these three games are also presented, which are consistent with the results for the PDG qualitatively. Furthermore, we consider our model under the co-evolution framework, in which the probability of an individual changing into a double-dealer and the individual strategy both could evolve during the evolutionary process.

  4. Experimental strategies to promote functional recovery after peripheral nerve injuries.

    Science.gov (United States)

    Gordon, Tessa; Sulaiman, Olawale; Boyd, J Gordon

    2003-12-01

    The capacity of Schwann cells (SCs) in the peripheral nervous system to support axonal regeneration, in contrast to the oligodendrocytes in the central nervous system, has led to the misconception that peripheral nerve regeneration always restores function. Here, we consider how prolonged periods of time that injured neurons remain without targets during axonal regeneration (chronic axotomy) and that SCs in the distal nerve stumps remain chronically denervated (chronic denervation) progressively reduce the number of motoneurons that regenerate their axons. We demonstrate the effectiveness of low-dose, brain-derived neurotrophic and glial-derived neurotrophic factors to counteract the effects of chronic axotomy in promoting axonal regeneration. High-dose brain-derived neurotrophic factor (BDNF) on the other hand, acting through the p75 receptor, inhibits axonal regeneration and may be a factor in stopping regenerating axons from forming neuromuscular connections in skeletal muscle. The immunophilin, FK506, is also effective in promoting axonal regeneration after chronic axotomy. Chronic denervation of SCs (>1 month) severely deters axonal regeneration, although the few motor axons that do regenerate to reinnervate muscles become myelinated and form enlarged motor units in the reinnervated muscles. We found that in vitro incubation of chronically denervated SCs with transforming growth factor-beta re-established their growth-supportive phenotype in vivo, consistent with the idea that the interaction between invading macrophages and denervated SCs during Wallerian degeneration is essential to sustain axonal regeneration by promoting the growth-supportive SC phenotype. Finally, we consider the effectiveness of a brief period of 20 Hz electrical stimulation in promoting the regeneration of axons across the surgical gap after nerve repair.

  5. Structure and functional regulation of the CD38 promoter

    International Nuclear Information System (INIS)

    Sun Li; Iqbal, Jameel; Zaidi, Samir; Zhu Linglng; Zhang Xuefeng; Peng Yuanzheng; Moonga, Baljit S.; Zaidi, Mone

    2006-01-01

    CD38 has multiple roles in biology, including T lymphocyte signaling, neutrophil migration, neurotransmission, cell proliferation, apoptosis, and bone remodeling. To study the transcriptional control of the CD38 gene, we cloned a putative 1.8 kb promoter fragment from a rabbit genomic DNA library. Primer extension analysis indicated two transcription start sites consistent with the absence of a TATA box. Sequence analysis revealed several AP-1, AP-4, myo-D, GATA, and SP-1 sequences. MC3T3.E1 (osteoblast) or RAW-C3 (osteoclast precursor macrophage) cells were then transfected with the CD38 promoter or its deletion fragments ligated to the luciferase reporter gene. Except for the shortest 41 bp fragment, all fragments showed significant luciferase activity. There was a marked stimulation of basal activity in the 93 bp fragment that contained a GC box and SP-1 site. Furthermore, there were significant differences in the activity of the fragments in MC3T3.E1 and RAW-C3 cells. Intracellular Ca 2+ elevations by ionomycin (10 μM) in MC3T3.E1 cells inhibited promoter activity, except in the short 41 bp. In contrast, cAMP elevation by exposure to forskolin (100 μM) inhibited activation of all fragments, except the 0.6 and 1.2 kb fragments. Finally, TNF-α stimulated promoter activity in RAW-C3 cells transfected with the 93 bp and 1.0 kb fragments, consistent with the stimulation of CD38 mRNA by TNF-α. Physiologically, therefore, modulation of the expression of the NAD + -sensing enzyme, CD38, by Ca 2+ , cAMP, and cytokines, such as TNF-α may contribute to coupling the intense metabolic activity of osteoclasts and osteoblasts to their respective bone-resorbing and bone-forming functions

  6. Period doubling for trapezoid function iteration: metric theory

    International Nuclear Information System (INIS)

    Beyer, W.A.; Stein, P.R.

    1982-01-01

    Iterations of a one-parameter family F(lambda,x) = lambda f(x) of endomorphisms of [0,2] having the form of a trapezoid f(x) = x/e for x belongs to [0,e], f(x) = 1 for x belongs to (e,2 - e) and f(x) = (2 - x)/e for x belongs to [2 - e,2], are investigated. Here lambda belongs to [1,2] and e belongs to (0,1). Let lambda/sub n/ be the smallest value of lambda > 1 for which x = 1 is a periodic point of period 2/sup n/. It is proved that for e < 0.99, lambda/sub n/ - lambda/sub n-1/ approx. = k(lambda/sub infinity//e)/sup -2n/, where k is some constant and lambda/sub infinity/ = lim/sub n→infinity/lambda/sub n/. The same conclusion probably holds for any e < 1. This behavior is substantially different from that found by Feigenbaum and others for the case where f(x) assumes its maximum value for a unique x. Numerical investigations are reported for functions related to the trapezoid function

  7. The double bromodomain protein Brd2 promotes B cell expansion and mitogenesis.

    Science.gov (United States)

    Belkina, Anna C; Blanton, Wanda P; Nikolajczyk, Barbara S; Denis, Gerald V

    2014-03-01

    Bromodomain-containing transcriptional regulators represent new epigenetic targets in different hematologic malignancies. However, bromodomain-mediated mechanisms that couple histone acetylation to transcription in lymphopoiesis and govern mature lymphocyte mitogenesis are poorly understood. Brd2, a transcriptional coregulator that contains dual bromodomains and an extraterminal domain (the BET family), couples chromatin to cell-cycle progression. We reported previously the first functional characterization of a BET protein as an effector of mammalian mitogenic signal transduction: Eμ-Brd2 Tg mice develop "activated B cell" diffuse large B cell lymphoma. No other animal models exist for genetic or lentiviral expression of BET proteins, hampering testing of novel anti-BET anticancer drugs, such as JQ1. We transduced HSCs with Brd2 lentivirus and reconstituted recipient mice to test the hypothesis that Brd2 regulates hematopoiesis in BM and mitogenesis in the periphery. Forced expression of Brd2 provides an expansion advantage to the donor-derived B cell compartment in BM and increases mature B cell mitogenic responsiveness in vitro. Brd2 binds the cyclin A promoter in B cells, shown by ChIP, and increases cyclin A mRNA and protein levels, and S-phase progression in vitro in mitogen-stimulated primary B cells, but not T cells, reinforcing results from Eμ-Brd2 mice. The small molecule BET inhibitor JQ1 reduces B cell mitogenesis, consistent with the interpretation that BET inhibitors are antiproliferative. Brd2-specific knockdown experiments show that Brd2 is also required for hematopoiesis. We conclude that Brd2 plays a critical, independent role in regulation of mitogenic response genes, particularly cyclin A, in B cells.

  8. Construction and expression of secreting type human TRAIL gene vector mediated by hypoxia/radiation double sensitive promoter

    International Nuclear Information System (INIS)

    Yang Yanming; Jia Xiaojing; Qu Yaqin; Li Yanbo

    2009-01-01

    Objective: To construct secreting type human TRAIL (shTRAIL) gene vector pcDNA3.1-HRE/Egr1-shTRAIL mediated by hypoxia/radiation double sensitive promoter, and observe the effect of hypoxia and radiation on shTRAIL. Methods: HRE upper and lower strands were gotten by chemical synthesis, double strands HRE was gotten by PCR; pMD19T-Egr1 was digested by Sac I and Hind III, then Egr1 was obtained, pshuttle-shTRAIL was digested by Kpn I and BamH I, then shTRAIL was obtained; HRE/Egr1 double sensitive promoter mediated shTRAIL expression vector pcDNA3.1-HRE/Egr1-shTRAIL was constructed by gene recombination technique, it was identified correctly by enzyme digestion, PCR and sequencing. A549 cells were divided into normal, hypoxia (0.1%), irradiation (6 Gy) and hypoxia + irradiation groups. Results: After enzyme digestion by BamH I and Sma I, the fragments which lengths were 1284 bp and 4 998 bp, 2 292 bp and 3 990 bp were obtained; the vector was amplified by PCR with Egr1 and shTRAIL primer, the products which lengthens were 469 bp and 820 bp were obtained; pcDNA3.1-HRE/Egr1-shTRAIL was sequenced, the result was same to designed, this demonstrated that the construction was right. The vectors were transfected into A549 cells of adenocarcinoma of lung, the expression levels of shTRAIL mRNA and protein were increased after treated with hypoxia and radiation, it had statistically significant differences compared with normal group (P<0.05), and when they were combinated, the effect was more obvious. Conclusion: Secreting type human TRAIL gene vector pcDNA3.1-HRE/Egr1-shTRAIL mediated by hypoxia/radiation double sensitive promoter is constructed successfully, and hypoxia and radiation could increase the expression of TRAIL, and they have synergetic effect. (authors)

  9. Examining quality function deployment in safety promotion in Sweden.

    Science.gov (United States)

    Kullberg, Agneta; Nordqvist, Cecilia; Lindqvist, Kent; Timpka, Toomas

    2014-09-01

    The first-hand needs and demands of laypersons are not always considered when safety promotion programmes are being developed. We compared focal areas for interventions identified from residents' statements of safety needs with focal areas for interventions identified by local government professionals in a Swedish urban community certified by the international Safe Community movement supported by the World Health Organization. Quantitative and qualitative data on self-expressed safety needs from 787 housing residents were transformed into an intervention design, using the quality function deployment (QFD) technique and compared with the safety intervention programme developed by professionals at the municipality administrative office. The outcome of the comparison was investigated with regard to implications for the Safe Community movement. The QFD analysis identified the initiation and maintenance of social integrative processes in housing areas as the most highly prioritized interventions among the residents, but failed to highlight the safety needs of several vulnerable groups (the elderly, infants and persons with disabilities). The intervention programme designed by the public health professionals did not address the social integrative processes, but it did highlight the vulnerable groups. This study indicates that the QFD technique is suitable for providing residential safety promotion efforts with a quality orientation from the layperson's perspective. Views of public health professionals have to be included to ascertain that the needs of socially deprived residents are adequately taken into account. QFD can augment the methodological toolbox for safety promotion programmes, including interventions in residential areas. © The Author (2013). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  10. Selective Androgen Receptor Modulators (SARMs) as Function Promoting Therapies

    Science.gov (United States)

    Bhasin, Shalender; Jasuja, Ravi

    2010-01-01

    Purpose of review The last decade has witnessed unprecedented discovery effort to develop selective androgen receptor modulators (SARMs) that improve physical function and bone health without adversely affecting the prostate and cardiovascular outcomes. This review describes the historical evolution, the rationale for SARM development, and the mechanisms of testosterone action and SARM selectivity. Recent Findings While steroidal SARMs have been around since the 1940s, a number of nonsteroidal SARMs that do not serve as substrates for CYP19 aromatase or 5α-reductase, act as full agonists in muscle and bone and as partial agonists in prostate are in development. The differing interactions of steroidal and nonsteroidal compounds with AR contribute to their unique pharmacologic actions. Ligand binding induces specific conformational changes in the ligand binding domain, which could modulate surface topology and protein-protein interactions between AR and coregulators, resulting in tissue-specific gene regulation. Preclinical studies have demonstrated the ability of SARMs to increase muscle and bone mass in preclinical rodent models with varying degree of prostate sparing. Phase I trials of SARMs in humans have reported modest increments in fat-free mass. Summary SARMs hold promise as a new class of function promoting anabolic therapies for a number of clinical indications, including functional limitations associated with aging and chronic disease, frailty, cancer cachexia, and osteoporosis. PMID:19357508

  11. Selective androgen receptor modulators as function promoting therapies.

    Science.gov (United States)

    Bhasin, Shalender; Jasuja, Ravi

    2009-05-01

    The past decade has witnessed an unprecedented discovery effort to develop selective androgen receptor modulators (SARMs) that improve physical function and bone health without adversely affecting the prostate and cardiovascular outcomes. This review describes the historical evolution, the rationale for SARM development, and the mechanisms of testosterone action and SARM selectivity. Although steroidal SARMs have been around since the 1940s, a number of nonsteroidal SARMs that do not serve as substrates for CYP19 aromatase or 5alpha-reductase, act as full agonists in muscle and bone and as partial agonists in prostate are in development. The differing interactions of steroidal and nonsteroidal compounds with androgen receptor (AR) contribute to their unique pharmacologic actions. Ligand binding induces specific conformational changes in the ligand-binding domain, which could modulate surface topology and protein-protein interactions between AR and coregulators, resulting in tissue-specific gene regulation. Preclinical studies have demonstrated the ability of SARMs to increase muscle and bone mass in preclinical rodent models with varying degree of prostate sparing. Phase I trials of SARMs in humans have reported modest increments in fat-free mass. SARMs hold promise as a new class of function promoting anabolic therapies for a number of clinical indications, including functional limitations associated with aging and chronic disease, frailty, cancer cachexia, and osteoporosis.

  12. Promoting the development of resilient academic functioning in maltreated children.

    Science.gov (United States)

    Holmes, Megan R; Yoon, Susan; Berg, Kristen A; Cage, Jamie L; Perzynski, Adam T

    2018-01-01

    This study examined (a) the extent of heterogeneity in the patterns of developmental trajectories of language development and academic functioning in children who have experienced maltreatment, (b) how maltreatment type (i.e., neglect or physical abuse) and timing of abuse explained variation in developmental trajectories, and (c) the extent to which individual protective factors (i.e., preschool attendance, prosocial skills), relationship protective factors (i.e., parental warmth, absence of past-year depressive episode, cognitive/verbal responsiveness) and community protective factors (i.e., neighborhood safety) promoted the development of resilient language/academic functioning trajectories. Longitudinal data analyses were conducted using cohort sequential Growth Mixture Model (CS-GMM) with a United States national representative sample of children reported to Child Protective Services (n=1,776). Five distinct developmental trajectories from birth to age 10 were identified including two resilient groups. Children who were neglected during infancy/toddlerhood or physically abused during preschool age were more likely to be in the poorer language/academic functioning groups (decreasing/recovery/decreasing and high decreasing) than the resilient high stable group. Child prosocial skills, caregiver warmth, and caregiver cognitive stimulation significantly predicted membership in the two resilient academic functioning groups (low increasing and high stable), after controlling for demographics and child physical abuse and neglect. Results suggest that it is possible for a maltreated child to successfully achieve competent academic functioning, despite the early adversity, and identifies three possible avenues of intervention points. This study also makes a significant contribution to the field of child development research through the novel use of CS-GMM, which has implications for future longitudinal data collection methodology. Copyright © 2017 Elsevier Ltd. All

  13. (Re)framing school as a setting for promoting health and wellbeing: a double translation process

    DEFF Research Database (Denmark)

    Nordin, Lone Lindegard; Jourdan, Didier; Simovska, Venka

    2018-01-01

    , but entangled, processes of translation. At the national level, despite resistance by a number of actors with differing priorities, the translation resulted in the integration of selected key principles of the setting approach to health promotion in the national curriculum for health education. At the municipal......The aim of this article is to discuss the ways in which the setting approach to health promotion in schools, as part of knowledge-based international policies and guidelines, is embedded in the Danish policy landscape and enacted at the local governance level. The study draws on the sociology...... level, however, the principles seem to be ‘lost in translation’, as the treatment of schools as settings for promoting health and wellbeing remains largely subordinate to the discourses of disease prevention and individual behaviour regulation, dominated by the agenda of actors in the health sector....

  14. Chopped or long roughage: what do calves prefer? Using cross point analysis of double demand functions

    NARCIS (Netherlands)

    Webb, L.E.; Bak Jensen, M.; Engel, B.; Reenen, van C.G.; Gerrits, W.J.J.; Boer, de I.J.M.; Bokkers, E.A.M.

    2014-01-01

    The present study aimed to quantify calves'(Bos taurus) preference for long versus chopped hay and straw, and hay versus straw, using cross point analysis of double demand functions, in a context where energy intake was not a limiting factor. Nine calves, fed milk replacer and concentrate, were

  15. Analytical expression for the nonsinglet structure functions at small x in the double logarithmic approximation

    International Nuclear Information System (INIS)

    Lublinsky, Michael

    2004-01-01

    A simple analytic expression for the nonsinglet structure function f NS is given. The expression is derived from the result of Ermolaev, Manaenkov, and Ryskin obtained by low x resummation of the quark ladder diagrams in the double logarithmic approximation of perturbative QCD

  16. Transfer functions of double- and multiple-cavity Fabry-Perot filters driven by Lorentzian sources.

    Science.gov (United States)

    Marti, J; Capmany, J

    1996-12-20

    We derive expressions for the transfer functions of double- and multiple-cavity Fabry-Perot filters driven by laser sources with Lorentzian spectrum. These are of interest because of their applications in sensing and channel filtering in optical frequency-division multiplexing networks.

  17. Brisk walking can promote functional recovery in chronic stroke patients.

    Science.gov (United States)

    Batcho, Charles Sèbiyo; Stoquart, Gaëtan; Thonnard, Jean-Louis

    2013-09-01

    To determine whether regular brisk walking can promote functional recovery in community-dwelling stroke patients. A total of 44 chronic stroke patients, recruited in Belgium and Benin, respectively European high-income and African low-income countries. This longitudinal, single-cohort, observational study with 1 intervention period and 4 time-points of assessments (2 baseline, 1 post-intervention and 1 follow-up) was structured in 3 periods: pre-intervention period (1 month), intervention period (3 months) and follow-up period (3 month). Intervention consisted of a 3 times/week group-based brisk walking programme. Primary outcome measures were ACTIVLIM-Stroke questionnaire and the 6-minute walk test (6MWT). Secondary outcome measures were the Stroke Impairment Assessment Set (SIAS), the Hospital Anxiety and Depression Scale (HADS), and the Berg Balance Scale (BBS). All outcome measures were stable during the pre-intervention period (p ≥ 0.16). They all improved significantly after intervention (p ≤ 0.01), except the HADS (p = 0.058). However, during the follow-up period, SIAS (p = 0.002) and BBS (p = 0.001) decreased, while ACTIVLIM-Stroke, 6MWT and HADS showed no significant change (p ≥ 0.13). This study suggests regular brisk walking as an effective approach to promote functional recovery in chronic stroke survivors. However, further studies are required before generalizing these results to the whole stroke population.

  18. Coupled double-distribution-function lattice Boltzmann method for the compressible Navier-Stokes equations.

    Science.gov (United States)

    Li, Q; He, Y L; Wang, Y; Tao, W Q

    2007-11-01

    A coupled double-distribution-function lattice Boltzmann method is developed for the compressible Navier-Stokes equations. Different from existing thermal lattice Boltzmann methods, this method can recover the compressible Navier-Stokes equations with a flexible specific-heat ratio and Prandtl number. In the method, a density distribution function based on a multispeed lattice is used to recover the compressible continuity and momentum equations, while the compressible energy equation is recovered by an energy distribution function. The energy distribution function is then coupled to the density distribution function via the thermal equation of state. In order to obtain an adjustable specific-heat ratio, a constant related to the specific-heat ratio is introduced into the equilibrium energy distribution function. Two different coupled double-distribution-function lattice Boltzmann models are also proposed in the paper. Numerical simulations are performed for the Riemann problem, the double-Mach-reflection problem, and the Couette flow with a range of specific-heat ratios and Prandtl numbers. The numerical results are found to be in excellent agreement with analytical and/or other solutions.

  19. Functional Connectivity and Genetic Profile of a “Double-Cortex”-Like Malformation

    Science.gov (United States)

    Sprugnoli, Giulia; Vatti, Giampaolo; Rossi, Simone; Cerase, Alfonso; Renieri, Alessandra; Mencarelli, Maria A.; Zara, Federico; Rossi, Alessandro; Santarnecchi, Emiliano

    2018-01-01

    Laminar heterotopia is a rare condition consisting in an extra layer of gray matter under properly migrated cortex; it configures an atypical presentation of periventricular nodular heterotopia (PNH) or a double cortex (DC) syndrome. We conducted an original functional MRI (fMRI) analysis in a drug-resistant epilepsy patient with “double-cortex”-like malformation to reveal her functional connectivity (FC) as well as a wide genetic analysis to identify possible genetic substrates. Heterotopias were segmented into region of interests (ROIs), whose voxel-wise FC was compared to that of (i) its normally migrated counterpart, (ii) its contralateral homologous, and (iii) those of 30 age-matched healthy controls. Extensive genetic analysis was conducted to screen cortical malformations-associated genes. Compared to healthy controls, both laminar heterotopias and the overlying cortex showed significant reduction of FC with the contralateral hemisphere. Two heterozygous variants of uncertain clinical significance were found, involving autosomal recessive disease-causing genes, FAT4 and COL18A1. This first FC analysis of a unique case of “double-cortex”-like malformation revealed a hemispheric connectivity segregation both in the laminar cortex as in the correctly migrated one, with a new pattern of genes’ mutations. Our study suggests the altered FC could have an electrophysiological and functional impact on large-scale brain networks, and the involvement of not yet identified genes in “double-cortex”-like malformation with a possible role of rare variants in recessive genes as pathogenic cofactors. PMID:29946244

  20. Exosomes from eosinophils autoregulate and promote eosinophil functions.

    Science.gov (United States)

    Cañas, José Antonio; Sastre, Beatriz; Mazzeo, Carla; Fernández-Nieto, Mar; Rodrigo-Muñoz, José Manuel; González-Guerra, Andrés; Izquierdo, Manuel; Barranco, Pilar; Quirce, Santiago; Sastre, Joaquín; Del Pozo, Victoria

    2017-05-01

    Eosinophils are able to secrete exosomes that have an undefined role in asthma pathogenesis. We hypothesized that exosomes released by eosinophils autoregulate and promote eosinophil function. Eosinophils of patients with asthma ( n = 58) and healthy volunteers ( n = 16) were purified from peripheral blood, and exosomes were isolated and quantified from eosinophils of the asthmatic and healthy populations. Apoptosis, adhesion, adhesion molecules expression, and migration assays were performed with eosinophils in the presence or absence of exosomes from healthy and asthmatic individuals. Reactive oxygen species (ROS) were evaluated by flow cytometry with an intracellular fluorescent probe and nitric oxide (NO) and a colorimetric kit. In addition, exosomal proteins were analyzed by mass spectrometry. Eosinophil-derived exosomes induced an increase in NO and ROS production on eosinophils. Moreover, exosomes could act as a chemotactic factor on eosinophils, and they produced an increase in cell adhesion, giving rise to a specific augmentation of adhesion molecules, such as ICAM-1 and integrin α2. Protein content between exosomes from healthy and asthmatic individuals seems to be similar in both groups. In conclusion, we found that exosomes from the eosinophils of patients with asthma could modify several specific eosinophil functions related to asthma pathogenesis and that they could contribute fundamentally to the development and maintenance of asthma. © Society for Leukocyte Biology.

  1. Functional and structural outcomes of single-row versus double-row versus combined double-row and suture-bridge repair for rotator cuff tears.

    Science.gov (United States)

    Mihata, Teruhisa; Watanabe, Chisato; Fukunishi, Kunimoto; Ohue, Mutsumi; Tsujimura, Tomoyuki; Fujiwara, Kenta; Kinoshita, Mitsuo

    2011-10-01

    Although previous biomechanical research has demonstrated the superiority of the suture-bridge rotator cuff repair over double-row repair from a mechanical point of view, no articles have described the structural and functional outcomes of this type of procedure. The structural and functional outcomes after arthroscopic rotator cuff repair may be different between the single-row, double-row, and combined double-row and suture-bridge (compression double-row) techniques. Cohort study; Level of evidence, 3. There were 206 shoulders in 201 patients with full-thickness rotator cuff tears that underwent arthroscopic rotator cuff repair. Eleven patients were lost to follow-up. Sixty-five shoulders were repaired using the single-row, 23 shoulders using the double-row, and 107 shoulders using the compression double-row techniques. Clinical outcomes were evaluated at an average of 38.5 months (range, 24-74 months) after rotator cuff repair. Postoperative cuff integrity was determined using Sugaya's classification of magnetic resonance imaging (MRI). The retear rates after arthroscopic rotator cuff repair were 10.8%, 26.1%, and 4.7%, respectively, for the single-row, double-row, and compression double-row techniques. In the subcategory of large and massive rotator cuff tears, the retear rate in the compression double-row group (3 of 40 shoulders, 7.5%) was significantly less than those in the single-row group (5 of 8 shoulders, 62.5%, P row group (5 of 12 shoulders, 41.7%, P row and suture-bridge techniques, which had the lowest rate of postoperative retear, is an effective option for arthroscopic repair of the rotator cuff tendons because the postoperative functional outcome in patients with a retear is inferior to that without retear.

  2. Promotion of double-duplex invasion of peptide nucleic acids through conjugation with nuclear localization signal peptide.

    Science.gov (United States)

    Aiba, Yuichiro; Honda, Yuta; Komiyama, Makoto

    2015-03-02

    Pseudo-complementary peptide nucleic acid (pcPNA), as one of the most widely used synthetic DNA analogues, invades double-stranded DNA according to Watson-Crick rules to form invasion complexes. This unique mode of DNA recognition induces structural changes at the invasion site and can be used for a range of applications. In this paper, pcPNA is conjugated with a nuclear localization signal (NLS) peptide, and its invading activity is notably promoted both thermodynamically and kinetically. Thus, the double-duplex invasion complex is formed promptly at low pcPNA concentrations under high salt conditions, where the invasion otherwise never occurs. Furthermore, NLS-modified pcPNA is successfully employed for site-selective DNA scission, and the targeted DNA is selectively cleaved under conditions that are not conducive for DNA cutters using unmodified pcPNAs. This strategy of pcPNA modification is expected to be advantageous and promising for a range of in vitro and in vivo applications. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Development of double chain phosphatidylcholine functionalized polymeric monoliths for immobilized artificial membrane chromatography.

    Science.gov (United States)

    Wang, Qiqin; Peng, Kun; Chen, Weijia; Cao, Zhen; Zhu, Peijie; Zhao, Yumei; Wang, Yuqiang; Zhou, Haibo; Jiang, Zhengjin

    2017-01-06

    This study described a simple synthetic methodology for preparing biomembrane mimicking monolithic column. The suggested approach not only simplifies the preparation procedure but also improves the stability of double chain phosphatidylcholine (PC) functionalized monolithic column. The physicochemical properties of the optimized monolithic column were characterized by scanning electron microscopy, energy-dispersive X-ray spectrometry, and nano-LC. Satisfactory column permeability, efficiency, stability and reproducibility were obtained on this double chain PC functionalized monolithic column. It is worth noting that the resulting polymeric monolith exhibits great potential as a useful alternative of commercial immobilized artificial membrane (IAM) columns for in vitro predication of drug-membrane interactions. Furthermore, the comparative study of both double chain and single chain PC functionalized monoliths indicates that the presence or absence of glycerol backbone and the number of acyl chains are not decisive for the predictive ability of IAM monoliths on drug-membrane interactions. This novel PC functionalized monolithic column also exhibited good selectivity for a protein mixture and a set of pharmaceutical compounds. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Double standards for community sports: promoting active lifestyles but unhealthy diets.

    Science.gov (United States)

    Kelly, Bridget; Chapman, Kathy; King, Lesley; Hardy, Louise; Farrell, Louise

    2008-12-01

    Overweight and obesity in Australia is an emerging health concern. Obesity prevention initiatives must consider both physical activity and nutrition to be effective. Community sports venues have the capacity to promote healthy lifestyles through physical activity as well as healthy food choices. A telephone survey was conducted on parents of children aged 5-17 years in NSW to determine the nature of food and beverages purchased by children at community sporting venues and to determine parent's perception of the role that government should play in regulating the types of food and beverages sold at these outlets. The majority of canteens at children's sporting venues were considered to sell mostly unhealthy food and beverages (53%). Very few parents reported that canteens sold mostly healthy food and beverages. Parents reported that their child's most frequently purchased food and beverage items at outdoor sports fields were water, chocolate and confectionery, soft drink and sports drinks, and ice cream. At community swimming pools the most frequently purchased items were ice cream, followed by snack foods, including chips, cakes and biscuits. Most parents (63%) agreed that government should restrict the types of food and beverages that can be sold at children's sporting venues. Children are receiving inconsistent health messages at sporting venues, with healthy lifestyles being promoted through sports participation, but unhealthy dietary choices being provided at sports canteens.

  5. The promotional functionality of evaluative language in tourism discourse

    Directory of Open Access Journals (Sweden)

    R. Mocini

    2013-10-01

    Full Text Available This study intends to investigate the use of evaluation in a corpus of British tourist brochures produced by tour operators specializing in the promotion of Italy. The theoretical framework is the Appraisal System developed mainly by White (1998, 2001 and Martin (2000 in order to study the discourse functions of evaluative resources. The creators of brochures resort mainly to two categories of Appraisal. The first concerns the expression of emotions (Affect, both in an implicit and explicit way, while the second category (Appreciation includes aesthetic assessments. Evaluation can be amplified by several linguistic devices which either sharpen the margins of an experiential category or intensify the meaning of a word, like those lexical items which include an assessment of intensity as part of their semantic load. The iteration of evalua­tive meanings constructs a prosody, bringing an emotional and aesthetic colour to the whole text which in­volves the reader and increases the perceived value of a tourist destination.

  6. The double-soft limit in cosmological correlation functions and graviton exchange effects

    Energy Technology Data Exchange (ETDEWEB)

    Alinea, Allan L.; Kubota, Takahiro; Misumi, Nobuhiko, E-mail: alinea@het.phys.sci.osaka-u.ac.jp, E-mail: kubota@celas.osaka-u.ac.jp, E-mail: misumi.nobu@gmail.com [Department of Physics, Osaka University, Toyonaka, Osaka 560-0043 (Japan)

    2017-01-01

    The graviton exchange effect on cosmological correlation functions is examined by employing the double-soft limit technique. A new relation among correlation functions that contain the effects due to graviton exchange diagrams in addition to those due to scalar-exchange and scalar-contact-interaction, is derived by using the background field method and independently by the method of Ward identities associated with dilatation symmetry. We compare these three terms, putting small values for the slow-roll parameters and (1− n {sub s} ) ≈ 0.042, where n {sub s} is the scalar spectral index. It is argued that the graviton exchange effects are more dominant than the other two and could be observed in the trispectrum in the double-soft limit. Our observation strengthens the previous work by Seery, Sloth and Vernizzi, in which it has been argued that the graviton exchange dominates in the counter-collinear limit for single field slow-roll inflation.

  7. Synergy between pair coupled cluster doubles and pair density functional theory

    Energy Technology Data Exchange (ETDEWEB)

    Garza, Alejandro J.; Bulik, Ireneusz W. [Department of Chemistry, Rice University, Houston, Texas 77251-1892 (United States); Henderson, Thomas M. [Department of Chemistry and Department of Physics and Astronomy, Rice University, Houston, Texas 77251-1892 (United States); Scuseria, Gustavo E. [Department of Chemistry and Department of Physics and Astronomy, Rice University, Houston, Texas 77251-1892 (United States); Chemistry Department, Faculty of Science, King Abdulaziz University, Jeddah 21589 (Saudi Arabia)

    2015-01-28

    Pair coupled cluster doubles (pCCD) has been recently studied as a method capable of accounting for static correlation with low polynomial cost. We present three combinations of pCCD with Kohn–Sham functionals of the density and on-top pair density (the probability of finding two electrons on top of each other) to add dynamic correlation to pCCD without double counting. With a negligible increase in computational cost, these pCCD+DFT blends greatly improve upon pCCD in the description of typical problems where static and dynamic correlations are both important. We argue that—as a black-box method with low scaling, size-extensivity, size-consistency, and a simple quasidiagonal two-particle density matrix—pCCD is an excellent match for pair density functionals in this type of fusion of multireference wavefunctions with DFT.

  8. Unified double- and single-sided homogeneous Green’s function representations

    Science.gov (United States)

    van der Neut, Joost; Slob, Evert

    2016-01-01

    In wave theory, the homogeneous Green’s function consists of the impulse response to a point source, minus its time-reversal. It can be represented by a closed boundary integral. In many practical situations, the closed boundary integral needs to be approximated by an open boundary integral because the medium of interest is often accessible from one side only. The inherent approximations are acceptable as long as the effects of multiple scattering are negligible. However, in case of strongly inhomogeneous media, the effects of multiple scattering can be severe. We derive double- and single-sided homogeneous Green’s function representations. The single-sided representation applies to situations where the medium can be accessed from one side only. It correctly handles multiple scattering. It employs a focusing function instead of the backward propagating Green’s function in the classical (double-sided) representation. When reflection measurements are available at the accessible boundary of the medium, the focusing function can be retrieved from these measurements. Throughout the paper, we use a unified notation which applies to acoustic, quantum-mechanical, electromagnetic and elastodynamic waves. We foresee many interesting applications of the unified single-sided homogeneous Green’s function representation in holographic imaging and inverse scattering, time-reversed wave field propagation and interferometric Green’s function retrieval. PMID:27436983

  9. The function of single containment and double containment of PWR nuclear power plant

    International Nuclear Information System (INIS)

    Chen Weijing.

    1985-01-01

    The function and structures of single containment and double containment of PWR nuclear power plant were described briefiy. The dissimilarites of diffent type of containments, which effects the impact of environment are discused. The impact of environment, effected by 'source term', containment gas leak rate and diffusion pattern of the released gas, under different operating condition is analysed. Especially, the impact of environment under LOCA accident is fully analysed

  10. Functional Effectiveness of Threat Appeals in Exercise Promotion Messages

    Science.gov (United States)

    Brengman, Malaika; Wauters, Birgit; Macharis, Cathy; Mairesse, Olivier

    2010-01-01

    As more than 70% of individuals in Western societies can be categorized as sedentary and inactivity has been recognized to lead to a series of serious physical and psychological disorders, the importance of physical activity promotion is ever more emphasized. Many social marketing campaigns use threat (or fear) appeals to promote healthy…

  11. Molecular and functional assessment of multicellular cancer spheroids produced in double emulsions enabled by efficient airway resistance based selective surface treatment

    Science.gov (United States)

    Ma, Xiao; Leth Jepsen, Morten; Ivarsen, Anne Kathrine R.; Knudsen, Birgitta R.; Ho, Yi-Ping

    2017-09-01

    Multicellular spheroids have garnered significant attention as an in vitro three-dimensional cancer model which can mimick the in vivo microenvironmental features. While microfluidics generated double emulsions have become a potential method to generate spheroids, challenges remain on the tedious procedures. Enabled by a novel ‘airway resistance’ based selective surface treatment, this study presents an easy and facile generation of double emulsions for the initiation and cultivation of multicellular spheroids in a scaffold-free format. Combining with our previously developed DNA nanosensors, intestinal spheroids produced in the double emulsions have shown an elevated activities of an essential DNA modifying enzyme, the topoisomerase I. The observed molecular and functional characteristics of spheroids produced in double emulsions are similar to the counterparts produced by the commercially available ultra-low attachment plates. However, the double emulsions excel for their improved uniformity, and the consistency of the results obtained by subsequent analysis of the spheroids. The presented technique is expected to ease the burden of producing spheroids and to promote the spheroids model for cancer or stem cell study.

  12. Towards double-functionalized small diamondoids: selective electronic band-gap tuning

    International Nuclear Information System (INIS)

    Adhikari, Bibek; Fyta, Maria

    2015-01-01

    Diamondoids are nanoscale diamond-like cage structures with hydrogen terminations, which can occur in various sizes and with a diverse type of modifications. In this work, we focus on the structural alterations and the effect of doping and functionalization on the electronic properties of diamondoids, from the smallest adamantane to heptamantane. The results are based on quantum mechanical calculations. We perform a self-consistent study, starting with doping the smallest diamondoid, adamantane. Boron, nitrogen, silicon, oxygen, and phosphorus are chosen as dopants at sites which have been previously optimized and are also consistent with the literature. At a next step, an amine- and a thiol- group are separately used to functionalize the adamantane molecule. We mainly focus on a double functionalization of diamondoids up to heptamantane using both these atomic groups. The effect of isomeration in the case of tetramantane is also studied. We discuss the higher efficiency of a double-functionalization compared to doping or a single-functionalization of diamondoids in tuning the electronic properties, such as the electronic band-gap, of modified small diamondoids in view of their novel nanotechnological applications. (paper)

  13. A general range-separated double-hybrid density-functional theory.

    Science.gov (United States)

    Kalai, Cairedine; Toulouse, Julien

    2018-04-28

    A range-separated double-hybrid (RSDH) scheme which generalizes the usual range-separated hybrids and double hybrids is developed. This scheme consistently uses a two-parameter Coulomb-attenuating-method (CAM)-like decomposition of the electron-electron interaction for both exchange and correlation in order to combine Hartree-Fock exchange and second-order Møller-Plesset (MP2) correlation with a density functional. The RSDH scheme relies on an exact theory which is presented in some detail. Several semi-local approximations are developed for the short-range exchange-correlation density functional involved in this scheme. After finding optimal values for the two parameters of the CAM-like decomposition, the RSDH scheme is shown to have a relatively small basis dependence and to provide atomization energies, reaction barrier heights, and weak intermolecular interactions globally more accurate or comparable to range-separated MP2 or standard MP2. The RSDH scheme represents a new family of double hybrids with minimal empiricism which could be useful for general chemical applications.

  14. EXPERIMENTAL DETERMINATION OF DOUBLE VIBE FUNCTION PARAMETERS IN DIESEL ENGINES WITH BIODIESEL

    Directory of Open Access Journals (Sweden)

    Radivoje B Pešić

    2010-01-01

    Full Text Available A zero-dimensional, one zone model of engine cycle for steady-state regimes of engines and a simplified procedure for indicator diagrams analysis have been developed at the Laboratory for internal combustion engines, fuels and lubricants of the Faculty of Mechanical Engineering in Kragujevac. In addition to experimental research, thermodynamic modeling of working process of diesel engine with direct injection has been presented in this paper. The simplified procedure for indicator diagrams analysis has been applied, also. The basic problem, a selection of shape parameters of double Vibe function used for modeling the engine operation process, has been solved. The influence of biodiesel fuel and engine working regimes on the start of combustion, combustion duration and shape parameter of double Vibe was determined by a least square fit of experimental heat release curve.

  15. On calculating double logarithmical asymptotics of vertex functions defined on the mass shell

    International Nuclear Information System (INIS)

    Belokurov, V.V.; Usyukina, N.I.

    1981-01-01

    The essence of the calculation method of double logarithmical asymptotics of vertex functions defined on the mass shell is presented. Using the method the asymptotics of the form-factor of electron is calculated. The ladder and cross-ladder diagrams are asymptotically considerable in every order of the perturbation theory. The way in which the asymptotics of the 4-order diagrams is calculated has been shown. The diagrams of this order and reduction procedures for them are given in a graphic form. The photon mass μ 2 not equal to 0 plays the role of a regulator, removing infrared divergencies. The double logarithmical asymptotics of the form-factor of electron on the mass shell is calculated rigorously in an arbitrary order of the perturbation theory [ru

  16. Functional analysis of bipartite begomovirus coat protein promoter sequences

    International Nuclear Information System (INIS)

    Lacatus, Gabriela; Sunter, Garry

    2008-01-01

    We demonstrate that the AL2 gene of Cabbage leaf curl virus (CaLCuV) activates the CP promoter in mesophyll and acts to derepress the promoter in vascular tissue, similar to that observed for Tomato golden mosaic virus (TGMV). Binding studies indicate that sequences mediating repression and activation of the TGMV and CaLCuV CP promoter specifically bind different nuclear factors common to Nicotiana benthamiana, spinach and tomato. However, chromatin immunoprecipitation demonstrates that TGMV AL2 can interact with both sequences independently. Binding of nuclear protein(s) from different crop species to viral sequences conserved in both bipartite and monopartite begomoviruses, including TGMV, CaLCuV, Pepper golden mosaic virus and Tomato yellow leaf curl virus suggests that bipartite begomoviruses bind common host factors to regulate the CP promoter. This is consistent with a model in which AL2 interacts with different components of the cellular transcription machinery that bind viral sequences important for repression and activation of begomovirus CP promoters

  17. Layered double hydroxide nanoparticles promote self-renewal of mouse embryonic stem cells through the PI3K signaling pathway

    Science.gov (United States)

    Wu, Youjun; Zhu, Rongrong; Zhou, Yang; Zhang, Jun; Wang, Wenrui; Sun, Xiaoyu; Wu, Xianzheng; Cheng, Liming; Zhang, Jing; Wang, Shilong

    2015-06-01

    Embryonic stem cells (ESCs) hold great potential for regenerative medicine due to their two unique characteristics: self-renewal and pluripotency. Several groups of nanoparticles have shown promising applications in directing the stem cell fate. Herein, we investigated the cellular effects of layered double hydroxide nanoparticles (LDH NPs) on mouse ESCs (mESCs) and the associated molecular mechanisms. Mg-Al-LDH NPs with an average diameter of ~100 nm were prepared by hydrothermal methods. To determine the influences of LDH NPs on mESCs, cellular cytotoxicity, self-renewal, differentiation potential, and the possible signaling pathways were explored. Evaluation of cell viability, lactate dehydrogenase release, ROS generation and apoptosis demonstrated the low cytotoxicity of LDH NPs. The alkaline phosphatase activity and the expression of pluripotency genes in mESCs were examined, which indicated that exposure to LDH NPs could support self-renewal and inhibit spontaneous differentiation of mESCs under feeder-free culture conditions. The self-renewal promotion was further proved to be independent of the leukemia inhibitory factor (LIF). Furthermore, cells treated with LDH NPs maintained the potential to differentiate into all three germ layers both in vitro and in vivo through formation of embryoid bodies and teratomas. In addition, we observed that LDH NPs initiated the activation of the PI3K/Akt pathway, while treatment with the PI3K inhibitor LY294002 could block the effects of LDH NPs on mESCs. The results confirmed that the promotion of self-renewal by LDH NPs was associated with activation of the PI3K/Akt signaling pathway. Altogether, our studies identified a new role of LDH NPs in maintaining self-renewal of mouse ES cells which could potentially be applied in stem cell research.Embryonic stem cells (ESCs) hold great potential for regenerative medicine due to their two unique characteristics: self-renewal and pluripotency. Several groups of nanoparticles

  18. NODAL and SHH dose-dependent double inhibition promotes an HPE-like phenotype in chick embryos

    Directory of Open Access Journals (Sweden)

    Sandra Mercier

    2013-03-01

    Holoprosencephaly (HPE is a common congenital defect that results from failed or incomplete forebrain cleavage. HPE is characterized by a wide clinical spectrum, with inter- and intrafamilial variability. This heterogeneity is not well understood and it has been suggested that HPE involves a combination of multiple gene mutations. In this model, several mutated alleles or modifying factors are presumed to act in synergy to cause and determine the severity of HPE. This could explain the various clinical phenotypes. Screening for HPE-associated genes in humans suggests the involvement of NODAL or SHH signaling, or both. To test this multigenic hypothesis, we investigated the effects of chemical inhibition of these two main HPE signaling pathways in a chick embryo model. SB-505124, a selective inhibitor of transforming growth factor-B type I receptors was used to inhibit the NODAL pathway. Cyclopamine was used to inhibit the SHH pathway. We report that both inhibitors caused HPE-like defects that were dependent on the drug concentration and on the developmental stage at the time of treatment. We also investigated double inhibition of NODAL and SHH pathways from the onset of gastrulation by using subthreshold inhibitor concentrations. The inhibitors of the NODAL and SHH pathways, even at low concentration, acted synergistically to promote an HPE-like phenotype. These findings support the view that genetic heterogeneity is important in the etiology of HPE and may contribute to the phenotypic variability.

  19. Lyn tyrosine kinase promotes silencing of ATM-dependent checkpoint signaling during recovery from DNA double-strand breaks

    International Nuclear Information System (INIS)

    Fukumoto, Yasunori; Kuki, Kazumasa; Morii, Mariko; Miura, Takahito; Honda, Takuya; Ishibashi, Kenichi; Hasegawa, Hitomi; Kubota, Sho; Ide, Yudai; Yamaguchi, Noritaka; Nakayama, Yuji; Yamaguchi, Naoto

    2014-01-01

    Highlights: • Inhibition of Src family kinases decreased γ-H2AX signal. • Inhibition of Src family increased ATM-dependent phosphorylation of Chk2 and Kap1. • shRNA-mediated knockdown of Lyn increased phosphorylation of Kap1 by ATM. • Ectopic expression of Src family kinase suppressed ATM-mediated Kap1 phosphorylation. • Src is involved in upstream signaling for inactivation of ATM signaling. - Abstract: DNA damage activates the DNA damage checkpoint and the DNA repair machinery. After initial activation of DNA damage responses, cells recover to their original states through completion of DNA repair and termination of checkpoint signaling. Currently, little is known about the process by which cells recover from the DNA damage checkpoint, a process called checkpoint recovery. Here, we show that Src family kinases promote inactivation of ataxia telangiectasia mutated (ATM)-dependent checkpoint signaling during recovery from DNA double-strand breaks. Inhibition of Src activity increased ATM-dependent phosphorylation of Chk2 and Kap1. Src inhibition increased ATM signaling both in G2 phase and during asynchronous growth. shRNA knockdown of Lyn increased ATM signaling. Src-dependent nuclear tyrosine phosphorylation suppressed ATM-mediated Kap1 phosphorylation. These results suggest that Src family kinases are involved in upstream signaling that leads to inactivation of the ATM-dependent DNA damage checkpoint

  20. Multiple zeta functions and double wrapping in planar N=4 SYM

    Science.gov (United States)

    Leurent, Sébastien; Volin, Dmytro

    2013-10-01

    Using the FiNLIE solution of the AdS/CFT Y-system, we compute the anomalous dimension of the Konishi operator in planar N=4 SYM up to eight loops, i.e. up to the leading double wrapping order. At this order a non-reducible Euler-Zagier sum, ζ1,2,8, appears for the first time. We find that at all orders in perturbation, every spectral-dependent quantity of the Y-system is expressed through multiple Hurwitz zeta functions, hence we provide a Mathematica package to manipulate these functions, including the particular case of Euler-Zagier sums. Furthermore, we conjecture that only Euler-Zagier sums can appear in the answer for the anomalous dimension at any order in perturbation theory. We also resum the leading transcendentality terms of the anomalous dimension at all orders, obtaining a simple result in terms of Bessel functions. Finally, we demonstrate that exact Bethe equations should be related to an absence of poles condition that becomes especially non-trivial at double wrapping.

  1. Production of a double-humped ion velocity distribution function in a single-ended Q-machine

    DEFF Research Database (Denmark)

    Andersen, S.A.; Jensen, Vagn Orla; Michelsen, Poul

    1970-01-01

    An experimental method of producing a double-humped velocity distribution function for the ions in a Q-machine is described. The method is based on charge exchange processes between neutral ceasium and the ions in a ceasium plasma.......An experimental method of producing a double-humped velocity distribution function for the ions in a Q-machine is described. The method is based on charge exchange processes between neutral ceasium and the ions in a ceasium plasma....

  2. Analytic derivatives for perturbatively corrected ''double hybrid'' density functionals: Theory, implementation, and applications

    International Nuclear Information System (INIS)

    Neese, Frank; Schwabe, Tobias; Grimme, Stefan

    2007-01-01

    A recently proposed new family of density functionals [S. Grimme, J. Chem. Phys. 124, 34108 (2006)] adds a fraction of nonlocal correlation as a new ingredient to density functional theory (DFT). This fractional correlation energy is calculated at the level of second-order many-body perturbation theory (PT2) and replaces some of the semilocal DFT correlation of standard hybrid DFT methods. The new ''double hybrid'' functionals (termed, e.g., B2-PLYP) contain only two empirical parameters that have been adjusted in thermochemical calculations on parts of the G2/3 benchmark set. The methods have provided the lowest errors ever obtained by any DFT method for the full G3 set of molecules. In this work, the applicability of the new functionals is extended to the exploration of potential energy surfaces with analytic gradients. The theory of the analytic gradient largely follows the standard theory of PT2 gradients with some additional subtleties due to the presence of the exchange-correlation terms in the self-consistent field operator. An implementation is reported for closed-shell as well as spin-unrestricted reference determinants. Furthermore, the implementation includes external point charge fields and also accommodates continuum solvation models at the level of the conductor like screening model. The density fitting resolution of the identity (RI) approximation can be applied to the evaluation of the PT2 part with large gains in computational efficiency. For systems with ∼500-600 basis functions the evaluation of the double hybrid gradient is approximately four times more expensive than the calculation of the standard hybrid DFT gradient. Extensive test calculations are provided for main group elements and transition metal containing species. The results reveal that the B2-PLYP functional provides excellent molecular geometries that are superior compared to those from standard DFT and MP2

  3. Investigation of the adsorption of polymer chains on amine-functionalized double-walled carbon nanotubes.

    Science.gov (United States)

    Ansari, R; Ajori, S; Rouhi, S

    2015-12-01

    Molecular dynamics (MD) simulations were used to study the adsorption of different polymer chains on functionalized double-walled carbon nanotubes (DWCNTs). The nanotubes were functionalized with two different amines: NH2 (a small amine) and CH2-NH2 (a large amine). Considering three different polymer chains, all with the same number of atoms, the effect of polymer type on the polymer-nanotube interaction was studied. In general, it was found that covalent functionalization considerably improved the polymer-DWCNT interaction. By comparing the results obtained with different polymer chains, it was observed that, unlike polyethylene and polyketone, poly(styrene sulfonate) only weakly interacts with the functionalized DWCNTs. Accordingly, the smallest radius of gyration was obtained with adsorbed poly(styrene sulfonate). It was also observed that the DWCNTs functionalized with the large amine presented more stable interactions with polyketone and poly(styrene sulfonate) than with polyethylene, whereas the DWCNTs functionalized with the small amine showed better interfacial noncovalent bonding with polyethylene.

  4. Double-section curvature tunable functional actuator with micromachined buckle and grid wire for electricity delivery

    Science.gov (United States)

    Feng, Guo-Hua; Hou, Sheng-You

    2015-09-01

    This paper presents an ionic polymer metal composite (IPMC)-driven tentacle-like biocompatible flexible actuator with double-section curvature tunability. This actuator, possessing an embedded electrical transmission ability that mimics skeletal muscle nerves in the human body, affords versatile device functions. Novel micromachined copper buckles and grid wires are fabricated and their superiority in electricity delivery and driving the IPMC component with less flexural rigidity is demonstrated. In addition, soft conductive wires realized on a polydimethylsiloxane structure function as electrical signal transmitters. A light-emitting diode integrated with the developed actuator offers directional guiding light ability while the actuator performs a snake-like motion. The electrical conductivity and Young’s modulus of the key actuator components are investigated, and flexural rigidity and dynamic behavior analyses of the actuator under electrical manipulation are elaborated.

  5. Double-section curvature tunable functional actuator with micromachined buckle and grid wire for electricity delivery

    International Nuclear Information System (INIS)

    Feng, Guo-Hua; Hou, Sheng-You

    2015-01-01

    This paper presents an ionic polymer metal composite (IPMC)-driven tentacle-like biocompatible flexible actuator with double-section curvature tunability. This actuator, possessing an embedded electrical transmission ability that mimics skeletal muscle nerves in the human body, affords versatile device functions. Novel micromachined copper buckles and grid wires are fabricated and their superiority in electricity delivery and driving the IPMC component with less flexural rigidity is demonstrated. In addition, soft conductive wires realized on a polydimethylsiloxane structure function as electrical signal transmitters. A light-emitting diode integrated with the developed actuator offers directional guiding light ability while the actuator performs a snake-like motion. The electrical conductivity and Young’s modulus of the key actuator components are investigated, and flexural rigidity and dynamic behavior analyses of the actuator under electrical manipulation are elaborated. (paper)

  6. Suitability of the double Langevin function for description of anhysteretic magnetization curves in NO and GO electrical steel grades

    Directory of Open Access Journals (Sweden)

    Simon Steentjes

    2017-05-01

    Full Text Available This paper compares the match obtained using the classical Langevin function, the tanh function as well as a recently by the authors proposed double Langevin function with the measured anhysteretic magnetization curve of three different non-oriented electrical steel grades and one grain-oriented grade. Two standard non-oriented grades and a high-silicon grade (Si content of 6.5% made by CVD are analyzed. An excellent match is obtained using the double Langevin function, whereas the classical solutions are less appropriate. Thereby, problems such as those due to propagation of approximation errors observed in hysteresis modeling can be bypassed.

  7. Amine functionalized nanodiamond promotes cellular adhesion, proliferation and neurite outgrowth

    International Nuclear Information System (INIS)

    Hopper, A P; Dugan, J M; Gill, A A; Haycock, J W; Claeyssens, F; Fox, O J L; May, P W

    2014-01-01

    In this study, we report the production of amine functionalized nanodiamond. The amine functionalized nanodiamond forms a conformal monolayer on a negatively charged surface produced via plasma polymerization of acrylic acid. Nanodiamond terminated surfaces were studied as substrates for neuronal cell culture. NG108-15 neuroblastoma-glyoma hybrid cells were successfully cultured upon amine functionalized nanodiamond coated surfaces for between 1 and 7 d. Additionally, primary dorsal root ganglion (DRG) neurons and Schwann cells isolated from Wistar rats were also successfully cultured over a period of 21 d illustrating the potential of the coating for applications in the treatment of peripheral nerve injury. (paper)

  8. New platforms for multi-functional ocular lenses: engineering double-sided functionalized nano-coatings

    DEFF Research Database (Denmark)

    Mehta, Prina; Justo, Lucas; Walsh, Susannah

    2015-01-01

    rates variable between 5 and 10 µL/min, applied voltage 4–11 kV). Each side was coated (using a specially designed flip-able well) selectively with a pre-determined morphology and model drug substance. PVP nanoparticles (inner side, to be in contact with the cornea, mean size ... encapsulated with a probe (flourescein dye) and PVP nanofibres (outer side, to be exposed to air and eye lid, mean width size ... on rapid dissolution and contact of PVP model substance matrix. Adapting these findings further for advanced EHDA technologies (encapsulation layering, controllable size and deposition and multi-phase media deposition options) and intrinsic material properties (functional polymers/excipients and advanced...

  9. Thermostability promotes the cooperative function of split adenylate kinases.

    Science.gov (United States)

    Nguyen, Peter Q; Liu, Shirley; Thompson, Jeremy C; Silberg, Jonathan J

    2008-05-01

    Proteins can often be cleaved to create inactive polypeptides that associate into functional complexes through non-covalent interactions, but little is known about what influences the cooperative function of the ensuing protein fragments. Here, we examine whether protein thermostability affects protein fragment complementation by characterizing the function of split adenylate kinases from the mesophile Bacillus subtilis (AKBs) and the hyperthermophile Thermotoga neapolitana (AKTn). Complementation studies revealed that the split AKTn supported the growth of Escherichia coli with a temperature-sensitive AK, but not the fragmented AKBs. However, weak complementation occurred when the AKBs fragments were fused to polypeptides that strongly associate, and this was enhanced by a Q16L mutation that thermostabilizes the full-length protein. To examine how the split AK homologs differ in structure and function, their catalytic activity, zinc content, and circular dichroism spectra were characterized. The reconstituted AKTn had higher levels of zinc, greater secondary structure, and >10(3)-fold more activity than the AKBs pair, albeit 17-fold less active than full-length AKTn. These findings provide evidence that the design of protein fragments that cooperatively function can be improved by choosing proteins with the greatest thermostability for bisection, and they suggest that this arises because hyperthermophilic protein fragments exhibit greater residual structure compared to their mesophilic counterparts.

  10. Short-term tibolone does not interfere with endothelial function: a double-blinded, randomized, controlled trial.

    Science.gov (United States)

    Celani, M F S; Hurtado, R; Brandão, A H F; Maciel da Fonseca, A M R; Geber, S

    2016-06-01

    Objective To evaluate the effect of short-term hormone replacement therapy with tibolone 2.5 mg daily on endothelial function of healthy postmenopausal women, using flow-mediated dilation (FMD) of the brachial artery. Methods We performed a randomized, double-blinded, placebo-controlled study. A total of 100 healthy postmenopausal women were randomly allocated to receive tibolone (n = 50) or placebo (n = 50) for 28 days. Measurement of the FMD of the brachial artery was performed before and after the use of tibolone and placebo. Results A total of 31 women completed the study in the tibolone group, and 32 women completed the study in the control group. The results of the FMD measurements obtained from the women in the two groups before treatment were similar (0.018 and 0.091, for tibolone and placebo, p = 0.57). The values of the FMD in women who used tibolone and placebo, before and after the treatment, were similar in both groups. The numbers of women who presented an increase in the values of the FMD in both groups were also similar. Conclusion Our results demonstrate that the administration of 2.5 mg tibolone to healthy postmenopausal women for 28 days does not promote endothelial-dependent vasodilation, measured by FMD of the brachial artery.

  11. A model for the electrical double layer combining integral equation techniques with quantum density functional theory

    International Nuclear Information System (INIS)

    Luque, N.B.; Woelki, S.; Henderson, D.; Schmickler, W.

    2011-01-01

    Highlights: · We augment a double-layer model based on integral equations by calculating the interaction parameters with the electrode from quantum density functional theory · Explicit model calculations for Ag(1 1 1) in aqueous solutions give at least qualitatively good results for the particle profiles · Ours is the only method which allows the calculation of capacity-charge characteristics. · We obtain reasonable values for the Helmholtz (inner-layer) capacity. - Abstract: We have complemented the singlet reference interaction site model for the electric double layer by quantum chemical calculations for the interaction of ions and solvents with an electrode. Specific calculations have been performed for an aqueous solution of NaCl in contact with a Ag(1 1 1) electrode. The particle profiles near the electrode show the specific adsorption of Cl - ions, but not of Na + , and are at least in qualitative agreement with those obtained by molecular dynamics. Including the electronic response of the silver surface into the model results in reasonable capacity-charge characteristics.

  12. Ab initio density functional theory investigation of structural and electronic properties of double-walled silicon carbide nanotubes

    Science.gov (United States)

    Moradian, Rostam; Behzad, Somayeh; Chegel, Raad

    2009-12-01

    By using ab initio density functional theory, the structural and electronic properties of (n,n)@(11,11) double-walled silicon carbide nanotubes (SiCNTs) are investigated. Our calculations reveal the existence of an energetically favorable double-walled nanotube whose interwall distance is about 4.3 Å. Interwall spacing and curvature difference are found to be essential for the electronic states around the Fermi level.

  13. Calculation of the pion-nucleon double spectral functions and applications

    International Nuclear Information System (INIS)

    Grether, D.

    1986-01-01

    In the present thesis the latest results from pion-pion and pion-nucleon phase analyses are applied in order to calculate the pion-nucleon double spectral functions which belong to the elastic unitarity in the t-channel. The equivalence of the partial wave projection of these spectral functions in the s-channel with the elastic t-channel unitarity is extensively discussed. After we summarize the aspects of the pion-nucleon system seeming in this connection interesting we discuss the Mandelstam method for the calculation of the spectral functions by means of the elastic t-channel unitarity as well as the applied input and present the results. Thereafter we use these results in order to calculate by means of a fixed t-channel dispersion relation the real parts of the t-channel cuts. Partial wave projections into the t-channel are proved as equivalent to the elastic t-channel unitarity. We study the compatibility of the asymptotic behaviour of the spectral functions relative to the energy with current Regge pole models. Finally we use our results in order to calculate the pion-nucleon partial waves by means of their Froissart-Gribov representations which follow from their analyticity at fixed energy. (orig./HSI) [de

  14. The promotion and control functions of atomic energy law

    International Nuclear Information System (INIS)

    Roser, T.

    1998-01-01

    The question about the purpose of atomic energy law may sound superfluous in Germany, a country where a highly differential legal framework for the peaceful utilization of nuclear power has existed for nearly 40 years in the Basic Law, the Atomic Energy Act, and its ordinances, and a comprehensive body of case laws. Yet, it is justified in view of the declared intention of the German federal government to establish an environmental code into which atomic energy law, hitherto an independent branch of the law, would be integrated, and it is justified also in view of persistent complaints that the present rules and regulations stifled investment activities. A look into some codes of law may help answer the question. Already in 1959, the authors of the Atomic Energy Act outlined the purposes of the legislation in relatively clear terms in Section 1. Besides the two foreign policy aspects of security and loyalty under treaties, which do not concern us in this connection, the key purposes of atomic energy law are stated there as promotion and protection. The protection purpose, which implies the need to protect life, health, and property from the hazards of nuclear energy and harmful effects of ionizing radiation, ranks second in the Act. In accordance with the ruling in 1972 of the Federal Administrative Court, however, it should rank at the top. (orig.) [de

  15. A Randomized Double-Blind Placebo-Controlled Trial of Lactobacillus reuteri for Chronic Functional Abdominal Pain in Children

    OpenAIRE

    Kambiz Eftekhari; Zahra Vahedi; Mojtaba Kamali Aghdam; Diana Noemi Diaz

    2015-01-01

    Background: Functional abdominal pain (FAP) is one of the most common diseases, and large percentages of children suffer from it. Objectives: The purpose of the study was to evaluate the effect of Lactobacillus reuteri in treatment of children with functional abdominal pain. Patients and Methods: This study was a randomized double-blind placebo-controlled trial. Children aged 4 to ...

  16. Comparison of density functional and modified Poisson-Boltzmann structural properties for a spherical double layer

    Directory of Open Access Journals (Sweden)

    L.B.Bhuiyan

    2005-01-01

    Full Text Available The density functional and modified Poisson-Boltzmann descriptions of a spherical (electric double layer are compared and contrasted vis-a-vis existing Monte Carlo simulation data (for small ion diameter 4.25·10-10 m from the literature for a range of physical parameters such as macroion surface charge, macroion radius, valencies of the small ions, and electrolyte concentration. Overall, the theoretical predictions are seen to be remarkably consistent between themselves, being also in very good agreement with the simulations. Some modified Poisson-Boltzmann results for the zeta potential at small ion diameters of 3 and 2·10-10 m are also reported.

  17. Improving Survival and Promoting Respiratory Motor Function After Cervical Spinal Cord Injury

    Science.gov (United States)

    2017-09-01

    AWARD NUMBER: W81XWH-15-1-0378 TITLE: Improving Survival and Promoting Respiratory Motor Function After Cervical Spinal Cord Injury PRINCIPAL...TITLE AND SUBTITLE CordCorInjury 5a. CONTRACT NUMBER Improvi g Survival and Promoting Respiratory Motor Function After Cervical Spinal Cord...care. However, despite these drastic interventions, the cervical injured patient is still susceptible to death due to respiratory complications

  18. Promoting consistent use of the communication function classification system (CFCS).

    Science.gov (United States)

    Cunningham, Barbara Jane; Rosenbaum, Peter; Hidecker, Mary Jo Cooley

    2016-01-01

    We developed a Knowledge Translation (KT) intervention to standardize the way speech-language pathologists working in Ontario Canada's Preschool Speech and Language Program (PSLP) used the Communication Function Classification System (CFCS). This tool was being used as part of a provincial program evaluation and standardizing its use was critical for establishing reliability and validity within the provincial dataset. Two theoretical foundations - Diffusion of Innovations and the Communication Persuasion Matrix - were used to develop and disseminate the intervention to standardize use of the CFCS among a cohort speech-language pathologists. A descriptive pre-test/post-test study was used to evaluate the intervention. Fifty-two participants completed an electronic pre-test survey, reviewed intervention materials online, and then immediately completed an electronic post-test survey. The intervention improved clinicians' understanding of how the CFCS should be used, their intentions to use the tool in the standardized way, and their abilities to make correct classifications using the tool. Findings from this work will be shared with representatives of the Ontario PSLP. The intervention may be disseminated to all speech-language pathologists working in the program. This study can be used as a model for developing and disseminating KT interventions for clinicians in paediatric rehabilitation. The Communication Function Classification System (CFCS) is a new tool that allows speech-language pathologists to classify children's skills into five meaningful levels of function. There is uncertainty and inconsistent practice in the field about the methods for using this tool. This study used combined two theoretical frameworks to develop an intervention to standardize use of the CFCS among a cohort of speech-language pathologists. The intervention effectively increased clinicians' understanding of the methods for using the CFCS, ability to make correct classifications, and

  19. Communication: Evaluating non-empirical double hybrid functionals for spin-state energetics in transition-metal complexes

    Science.gov (United States)

    Wilbraham, Liam; Adamo, Carlo; Ciofini, Ilaria

    2018-01-01

    The computationally assisted, accelerated design of inorganic functional materials often relies on the ability of a given electronic structure method to return the correct electronic ground state of the material in question. Outlining difficulties with current density functionals and wave function-based approaches, we highlight why double hybrid density functionals represent promising candidates for this purpose. In turn, we show that PBE0-DH (and PBE-QIDH) offers a significant improvement over its hybrid parent functional PBE0 [as well as B3LYP* and coupled cluster singles and doubles with perturbative triples (CCSD(T))] when computing spin-state splitting energies, using high-level diffusion Monte Carlo calculations as a reference. We refer to the opposing influence of Hartree-Fock (HF) exchange and MP2, which permits higher levels of HF exchange and a concomitant reduction in electronic density error, as the reason for the improved performance of double-hybrid functionals relative to hybrid functionals. Additionally, using 16 transition metal (Fe and Co) complexes, we show that low-spin states are stabilised by increasing contributions from MP2 within the double hybrid formulation. Furthermore, this stabilisation effect is more prominent for high field strength ligands than low field strength ligands.

  20. Men's Sheds function and philosophy: towards a framework for future research and men's health promotion.

    Science.gov (United States)

    Wilson, Nathan J; Cordier, Reinie; Doma, Kenji; Misan, Gary; Vaz, Sharmila

    2015-08-01

    The Men's Shed movement supports a range of men's health promotion initiatives. This paper examines whether a Men's Shed typology could inform future research and enable more efficient and targeted health promotion activities through Men's Sheds. The International Men's Shed Survey consisted of a cross-sectional exploration of sheds, their members, and health and social activities. Survey data about shed 'function' and 'philosophy' were analysed using descriptive and inferential statistics. A framework of Men's Sheds based on function and philosophy demonstrated that most sheds serve a primary utility function, a secondary social function, but most importantly a primary social opportunity philosophy. Sheds with a primary health philosophy participated in fewer health promotion activities when compared with sheds without a primary health philosophy. In addition to the uniform health promotion resources distributed by the Men's Shed associations, specific health promotion activities, such as prostate education, are being initiated from an individual shed level. This framework can potentially be used to enable future research and health promotion activities to be more efficiently and effectively targeted. SO WHAT? Men experience poorer health and well being outcomes than women. This framework offers a novel approach to providing targeted health promotion activities to men in an environment where it is okay to talk about men's health.

  1. Transcranial brain stimulation to promote functional recovery after stroke

    DEFF Research Database (Denmark)

    Raffin, Estelle; Siebner, Hartwig R

    2014-01-01

    as a therapeutic tool. RECENT FINDINGS: Recent meta-analyses showed that the treatment effects of NIBS in patients with stroke are rather inconsistent across studies and the evidence for therapeutic efficacy is still uncertain. This raises the question of how NIBS can be developed further to improve its...... therapeutic efficacy. SUMMARY: This review addressed six questions: How does NIBS facilitate the recovery of function after stroke? Which brain regions should be targeted by NIBS? Is there a particularly effective NIBS modality that should be used? Does the location of the stroke influence the therapeutic...... will be critical to fully unfold the therapeutic effects of NIBS and will pave the way towards adaptive NIBS protocols, in which NIBS is tailored to the individual patient....

  2. [The value of double contrast arthrotomography combined with cinematography in the diagnosis of functional and structural TMJ alterations].

    Science.gov (United States)

    Engelke, W; Grossniklaus, B; Sailer, H F

    1991-01-01

    Double contrast arthrotomography combined with cinematography as a diagnostic instrument establishing functional and structural TMJ alterations is evaluated for its diagnostic value and reliability within the chain of diagnostic measures applied. In 131 patients double-contrast arthrotomography was followed by a comprehensive history of joint problems, and verification of the clinical findings as well as the arthrographic diagnosis and the post-arthrographic TMJ alterations. Our interest was focussed, among others, on the question whether arthrography alone would have any therapeutic effect or produce an alteration in TMJ function.

  3. Disruption of Aneuploidy and Senescence Induced by Aurora Inhibition Promotes Intrinsic Apoptosis in Double Hit or Double Expressor Diffuse Large B-cell Lymphomas.

    Science.gov (United States)

    Islam, Shariful; Qi, Wenqing; Morales, Carla; Cooke, Laurence; Spier, Catherine; Weterings, Eric; Mahadevan, Daruka

    2017-10-01

    Double hit (DH) or double expressor (DE) diffuse large B-cell lymphomas (DLBCL) are aggressive non-Hodgkin's lymphomas (NHL) with translocations and/or overexpressions of MYC and BCL-2 , which are difficult to treat. Aurora kinase (AK) inhibition with alisertib in DH/DE-DLBCL induces cell death in ∼30%, while ∼70% are aneuploid and senescent cells (AASC), a mitotic escape mechanism contributing to drug resistance. These AASCs elaborated a high metabolic rate by increased AKT/mTOR and ERK/MAPK activity via BTK signaling through the chronic active B-cell receptor (BCR) pathway. Combinations of alisertib + ibrutinib or alisertib + ibrutinib + rituximab significantly reduced AASCs with enhanced intrinsic cell death. Inhibition of AK + BTK reduced phosphorylation of AKT/mTOR and ERK-1/2, upregulated phospho-H2A-X and Chk-2 (DNA damage), reduced Bcl-6, and decreased Bcl-2 and Bcl-xL and induced apoptosis by PARP cleavage. In a DE-DLBCL SCID mouse xenograft model, ibrutinib alone was inactive, while alisertib + ibrutinib was additive with a tumor growth inhibition (TGI) rate of ∼25%. However, TGI for ibrutinib + rituximab was ∼50% to 60%. In contrast, triple therapy showed a TGI rate of >90%. Kaplan-Meier survival analysis showed that 67% of mice were alive at day 89 with triple therapy versus 20% with ibrutinib + rituximab. All treatments were well tolerated with no changes in body weights. A novel triple therapy consisting of alisertib + ibrutinib + rituximab inhibits AASCs induced by AK inhibition in DH/DE-DLBCL leading to a significant antiproliferative signal, enhanced intrinsic apoptosis and may be of therapeutic potential in these lymphomas. Mol Cancer Ther; 16(10); 2083-93. ©2017 AACR . ©2017 American Association for Cancer Research.

  4. The structural and electronic properties of monovalent sidewall functionalized double-walled carbon nanotubes

    International Nuclear Information System (INIS)

    Jalili, Seifollah; Jamali, Maryam

    2012-01-01

    Highlights: ► (6,0)-(13,0) DWCNT, built from (6,0) and (13,0) SWCNTs, is a metallic nanotubes. ► NH 2 /(6,0)-(13,0) and COOH/(6,0)-(13,0) is semimetal and semiconductor, respectively. ► In NH 2 /(6,0)-(13,0) electrons transferred mainly from inner tube to NH 2 group. - Abstract: The structural and electronic properties of (6,0)-(13,0) double-walled carbon nanotubes (DWCNTs) and monovalent sidewall functionalized DWCNTs with –NH 2 and –COOH groups were studied using density functional theory. The results show that pure (6,0)-(13,0) DWCNTs are metallic. However, by functionalizing a DWCNT, local distortions are induced in the outer tube sidewall along the radial direction. The resulting structures, NH 2 /(6,0)-(13,0) and COOH/(6,0)-(13,0) DWCNTs, exhibit significant structural changes, and are semimetal with no energy gap and semiconducting with a small energy gap, respectively. In NH 2 /(6,0)-(13,0) DWCNTs, new electronic states are created and distributed on the outer wall and NH 2 group by electron transfer from the inner tube to the NH 2 group. In COOH/(6,0)-(13,0) DWCNTs, new states are created and distributed on the inner wall, but there is insignificant charge transfer between the inner tube and the COOH group. These results confirm that local atomic structural distortion on DWCNTs caused by sidewall functionalization can modify the electronic structures of DWCNTs.

  5. Double-hydrophobic elastin-like polypeptides with added functional motifs: Self-assembly and cytocompatibility.

    Science.gov (United States)

    Le, Duc H T; Tsutsui, Yoko; Sugawara-Narutaki, Ayae; Yukawa, Hiroshi; Baba, Yoshinobu; Ohtsuki, Chikara

    2017-09-01

    We have recently developed a novel double-hydrophobic elastin-like triblock polypeptide called GPG, designed after the uneven distribution of two different hydrophobic domains found in elastin, an extracellular matrix protein providing elasticity and resilience to tissues. Upon temperature trigger, GPG undergoes a sequential self-assembling process to form flexible beaded nanofibers with high homogeneity and excellent dispersibility in water. Given that GPG might be a potential elastin-mimetic material, we sought to explore the biological activities of this block polypeptide. Besides GPG, several functionalized derivatives were also constructed by fusing functional motifs such as KAAK or KAAKGRGDS at the C-terminal of GPG. Although the added motifs affected the kinetics of fiber formation and β-sheet contents, all three GPGs assembled into beaded nanofibers at the physiological temperature. The resulting GPG nanofibers preserved their beaded structures in cell culture medium; therefore, they were coated on polystyrene substrates to study their cytocompatibility toward mouse embryonic fibroblasts, NIH-3T3. Among the three polypeptides, GPG having the cell-binding motif GRGDS derived from fibronectin showed excellent cell adhesion and cell proliferation properties compared to other conventional materials, suggesting its promising applications as extracellular matrices for mammalian cells. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2475-2484, 2017. © 2017 Wiley Periodicals, Inc.

  6. Photo double ionization of He: C3-like wave function for the two electron continuum

    Energy Technology Data Exchange (ETDEWEB)

    Otranto, S.; Garibotti, C.R. [Conicet and Centro Atomico Bariloche (Argentina); Otranto, S. [Universidad Nacional del Sur, Dept. de Fisica, Bahia Blanca (Argentina)

    2002-12-01

    We evaluate the triply differential cross-section (TDCS) for photo double ionization (PDI) of helium. A first approximation to the final state can be obtained by neglecting the e-e interaction and the non-orthogonal kinetic energy. This leads to the C2 model which proposes as solution a product of 2 independent Coulomb wave plane waves. A better approximation is the C3 model where the C3 wave describes the e-e motion as independent of the presence of the nucleus and represents it by a Coulomb continuum wave. The C3 wave function mainly consists in the product of 3 Coulomb waves, each one representing the interaction between a pair of particles. We use a C3 final continuum wave function with an inter-electronic effective coordinate to express the nuclear screening. Comparison with the standard C3 model shows that the TDCS is enhanced in the threshold region by effect of the reduced inter-electronic repulsion introduced by the present model. A more accurate description of the intermediate energy region is also obtained. Comparison with recent experimental data shows a good overall agreement of the angular distributions. The theoretical PDI total cross-section shows a relevant improvement in the intermediate energy region relative to the C3 model, which converges to data for photon energies larger than 1 keV.

  7. Photo double ionization of He: C3-like wave function for the two electron continuum

    International Nuclear Information System (INIS)

    Otranto, S.; Garibotti, C.R.; Otranto, S.

    2002-01-01

    We evaluate the triply differential cross-section (TDCS) for photo double ionization (PDI) of helium. A first approximation to the final state can be obtained by neglecting the e-e interaction and the non-orthogonal kinetic energy. This leads to the C2 model which proposes as solution a product of 2 independent Coulomb wave plane waves. A better approximation is the C3 model where the C3 wave describes the e-e motion as independent of the presence of the nucleus and represents it by a Coulomb continuum wave. The C3 wave function mainly consists in the product of 3 Coulomb waves, each one representing the interaction between a pair of particles. We use a C3 final continuum wave function with an inter-electronic effective coordinate to express the nuclear screening. Comparison with the standard C3 model shows that the TDCS is enhanced in the threshold region by effect of the reduced inter-electronic repulsion introduced by the present model. A more accurate description of the intermediate energy region is also obtained. Comparison with recent experimental data shows a good overall agreement of the angular distributions. The theoretical PDI total cross-section shows a relevant improvement in the intermediate energy region relative to the C3 model, which converges to data for photon energies larger than 1 keV

  8. Double Wigner distribution function of a first-order optical system with a hard-edge aperture.

    Science.gov (United States)

    Pan, Weiqing

    2008-01-01

    The effect of an apertured optical system on Wigner distribution can be expressed as a superposition integral of the input Wigner distribution function and the double Wigner distribution function of the apertured optical system. By introducing a hard aperture function into a finite sum of complex Gaussian functions, the double Wigner distribution functions of a first-order optical system with a hard aperture outside and inside it are derived. As an example of application, the analytical expressions of the Wigner distribution for a Gaussian beam passing through a spatial filtering optical system with an internal hard aperture are obtained. The analytical results are also compared with the numerical integral results, and they show that the analytical results are proper and ascendant.

  9. Ubiquitin-like protein UBL5 promotes the functional integrity of the Fanconi anemia pathway

    DEFF Research Database (Denmark)

    Oka, Yasuyoshi; Bekker-Jensen, Simon; Mailand, Niels

    2015-01-01

    in promoting the function of the Fanconi anemia (FA) pathway for repair of DNA interstrand crosslinks (ICLs), mediated by a specific interaction with the central FA pathway component FANCI. UBL5-deficient cells display spliceosome-independent reduction of FANCI protein stability, defective FANCI function...

  10. Functional characteristics of a double positive feedback loop coupled with autorepression

    International Nuclear Information System (INIS)

    Banerjee, Subhasis; Bose, Indrani

    2008-01-01

    We study the functional characteristics of a two-gene motif consisting of a double positive feedback loop and an autoregulatory negative feedback loop. The motif appears in the gene regulatory network controlling the functional activity of pancreatic β-cells. The model exhibits bistability and hysteresis in appropriate parameter regions. The two stable steady states correspond to low (OFF state) and high (ON state) protein levels, respectively. Using a deterministic approach, we show that the region of bistability increases in extent when the copy number of one of the genes is reduced from 2 to 1. The negative feedback loop has the effect of reducing the size of the bistable region. Loss of a gene copy, brought about by mutations, hampers the normal functioning of the β-cells giving rise to the genetic disorder, maturity-onset diabetes of the young (MODY). The diabetic phenotype makes its appearance when a sizable fraction of the β-cells is in the OFF state. Using stochastic simulation techniques we show that, on reduction of the gene copy number, there is a transition from the monostable ON to the ON state in the bistable region of the parameter space. Fluctuations in the protein levels, arising due to the stochastic nature of gene expression, can give rise to transitions between the ON and OFF states. We show that as the strength of autorepression increases, the ON → OFF state transitions become less probable whereas the reverse transitions are more probable. The implications of the results in the context of the occurrence of MODY are pointed out

  11. Functional characteristics of a double positive feedback loop coupled with autorepression

    Science.gov (United States)

    Banerjee, Subhasis; Bose, Indrani

    2008-12-01

    We study the functional characteristics of a two-gene motif consisting of a double positive feedback loop and an autoregulatory negative feedback loop. The motif appears in the gene regulatory network controlling the functional activity of pancreatic β-cells. The model exhibits bistability and hysteresis in appropriate parameter regions. The two stable steady states correspond to low (OFF state) and high (ON state) protein levels, respectively. Using a deterministic approach, we show that the region of bistability increases in extent when the copy number of one of the genes is reduced from 2 to 1. The negative feedback loop has the effect of reducing the size of the bistable region. Loss of a gene copy, brought about by mutations, hampers the normal functioning of the β-cells giving rise to the genetic disorder, maturity-onset diabetes of the young (MODY). The diabetic phenotype makes its appearance when a sizable fraction of the β-cells is in the OFF state. Using stochastic simulation techniques we show that, on reduction of the gene copy number, there is a transition from the monostable ON to the ON state in the bistable region of the parameter space. Fluctuations in the protein levels, arising due to the stochastic nature of gene expression, can give rise to transitions between the ON and OFF states. We show that as the strength of autorepression increases, the ON → OFF state transitions become less probable whereas the reverse transitions are more probable. The implications of the results in the context of the occurrence of MODY are pointed out.

  12. An analytical expression for the non-singlet structure functions at small χ in the double logarithmic approximation

    International Nuclear Information System (INIS)

    Lublinsky, M.

    2004-01-01

    A simple analytic expression for the non-singlet structure function fns is given. The expression is derived from the result of B. I. Ermolaev et al. (1996) obtained by low x resummation of the quark ladder diagrams in the double logarithmic approximation of perturbative QCD. (orig.)

  13. Functions and Requirements for Automated Liquid Level Gauge Instruments in Single-Shell and Double-Shell Tank Farms

    International Nuclear Information System (INIS)

    CARPENTER, K.E.

    1999-01-01

    This functions and requirements document defines the baseline requirements and criteria for the design, purchase, fabrication, construction, installation, and operation of automated liquid level gauge instruments in the Tank Farms. This document is intended to become the technical baseline for current and future installation, operation and maintenance of automated liquid level gauges in single-shell and double-shell tank farms

  14. Spermatogenesis-related ring finger gene ZNF230 promoter: identification and functional analysis

    DEFF Research Database (Denmark)

    Xu, Wenming; Zhang, Sizhong; Qiu, Weimin

    2009-01-01

    reporter Plasmids. Overexpression and site-directed mutation test were used to characterize the cis-element. The results showed ZNF230 gene promoter to be GC rich and not contain a TATA box. Deletion analysis of the 5'-flanking region of ZNF230 in HEK293 cells indicated that the sequence encompassing from...... nt -131 to +152 has a basal transcriptional activity. Site-directed mutation test and mithramycin A treatment demonstrated that the ZNF230 promoter contained a functional Sp1 site. Overexpression of the Sox5 protein activated the promoter activity. A 312-bp fragment surrounding the transcription...

  15. Disruption of Lysosome Function Promotes Tumor Growth and Metastasis in Drosophila *

    OpenAIRE

    Chi, Congwu; Zhu, Huanhu; Han, Min; Zhuang, Yuan; Wu, Xiaohui; Xu, Tian

    2010-01-01

    Lysosome function is essential to many physiological processes. It has been suggested that deregulation of lysosome function could contribute to cancer. Through a genetic screen in Drosophila, we have discovered that mutations disrupting lysosomal degradation pathway components contribute to tumor development and progression. Loss-of-function mutations in the Class C vacuolar protein sorting (VPS) gene, deep orange (dor), dramatically promote tumor overgrowth and invasion of the RasV12 cells....

  16. Phosphor Dysprosium-Doped Layered Double Hydroxides Exchanged with Different Organic Functional Groups

    Directory of Open Access Journals (Sweden)

    David Ricardo Martínez Vargas

    2013-01-01

    Full Text Available The layers of a Zn/Al layered double hydroxide (LDH were doped with Dy3+ cations. Among some compositions, the Zn2+ : Al3+ : Dy3+ molar ratio equal to 30 : 9 : 1 presented a single crystalline phase. Organic anions with carboxylic, amino, sulfate, or phosphate functional groups were intercalated as single layers between LDH layers as confirmed by X-ray diffraction and infrared spectroscopy. Photoluminescence spectra of the nitrate intercalated LDH showed a wide emission band with strong intensity in the yellow region (around 574 nm, originated due to symmetry distortion of the octahedral coordination in dysprosium centers. Moreover, a broad red band emission was also detected apparently due to the presence of zinc oxide. The distorted symmetry of the dysprosium coordination environment, also confirmed by X-ray photoelectron spectroscopy analysis, was modified after the intercalation with phenyl phosphonate (PP, aspartate (Asp, adipate (Adip, and serinate (Ser anions; the emission as measured from PL spectra of these LDH was more intense in the blue region (ca. 486 nm, thus indicating an increase in symmetry of dysprosium octahedrons. The red emission band from zinc oxide kept the same intensity after intercalation of dodecyl sulfate (DDS. An additional emission of unknown origin at λ = 767 nm was present in all LDHs.

  17. An Access Control Protocol for Wireless Sensor Network Using Double Trapdoor Chameleon Hash Function

    Directory of Open Access Journals (Sweden)

    Tejeshwari Thakur

    2016-01-01

    Full Text Available Wireless sensor network (WSN, a type of communication system, is normally deployed into the unattended environment where the intended user can get access to the network. The sensor nodes collect data from this environment. If the data are valuable and confidential, then security measures are needed to protect them from the unauthorized access. This situation requires an access control protocol (ACP in the design of sensor network because of sensor nodes which are vulnerable to various malicious attacks during the authentication and key establishment and the new node addition phase. In this paper, we propose a secured ACP for such WSN. This protocol is based on Elliptic Curve Discrete Log Problem (ECDLP and double trapdoor chameleon hash function which secures the WSN from malicious attacks such as node masquerading attack, replay attack, man-in-the-middle attack, and forgery attacks. Proposed ACP has a special feature known as session key security. Also, the proposed ACP is more efficient as it requires only one modular multiplication during the initialization phase.

  18. On function classes related pertaining to strong approximation of double Fourier series

    Science.gov (United States)

    Baituyakova, Zhuldyz

    2015-09-01

    The investigation of embedding of function classes began a long time ago. After Alexits [1], Leindler [2], and Gogoladze[3] investigated estimates of strong approximation by Fourier series in 1965, G. Freud[4] raised the corresponding saturation problem in 1969. The list of the authors dealing with embedding problems partly is also very long. It suffices to mention some names: V. G. Krotov, W. Lenski, S. M. Mazhar, J. Nemeth, E. M. Nikisin, K. I. Oskolkov, G. Sunouchi, J. Szabados, R. Taberski and V. Totik. Study on this topic has since been carried on over a decade, but it seems that most of the results obtained are limited to the case of one dimension. In this paper, embedding results are considered which arise in the strong approximation by double Fourier series. We prove theorem on the interrelation between the classes Wr1,r2HS,M ω and H(λ, p, r1, r2, ω(δ1, δ2)), in the one-dimensional case proved by L. Leindler.

  19. Further results on periods and period doubling for iterates of the trapezoic function

    International Nuclear Information System (INIS)

    Beyer, W.A.; Stein, P.R.

    1982-01-01

    The trapezoidal function lambda f/sub e/(x), is defined for fixed e element of (0,1] and for lambda element of [1,2] by lambda f/sub e/ (x) = lambda for /x-1/< 1-e and lambda f/sub e/(x) = lambda(1-/x-1/)/(1-e) for 1 greater than or equal to /x-1/greater than or equal to 1-e. For a fixed e, this is a one parameter family of endomorphisms of the interval [0,2]. The structure of the periods (or cycles) of these mappings is studied. In addition, the metric properties of the corresponding bifurcation diagrams are considered; in particular, the rate of convergence of a sequence of bifurcation points in the (x,lambda) plane is studied. It is shown to be different from that found by Feigenbaum and others for mappings which are not flat at the top. The limiting case e = 1 is of special interest. For cycles and containing a point x element of[e,2-e], the period quadruplicates instead of doubling as it does in the usual case

  20. Construction and functional characterization of double and triple mutants of parallel beta-bulge of ubiquitin.

    Science.gov (United States)

    Sharma, Mrinal; Prabha, C Ratna

    2011-12-01

    Ubiquitin, a small eukaryotic protein serving as a post-translational modification on many important proteins, plays central role in cellular homeostasis and cell cycle regulation. Ubiquitin features two beta-bulges, the second beta-bulge, located at the C-terminal region of the protein along with type II turn, holds 3 residues Glu64(1), Ser65(2) and Gln2(X). Percent frequency of occurrence of such a sequence in parallel beta-bulge is very low. However, the sequence and structure have been conserved in ubiquitin through out the evolution. Present study involves replacement of residues in unusual beta-bulge of ubiquitin by introducing mutations in combination through site directed mutagenesis, generating double and triple mutants and their functional characterization. Mutant ubiquitins cloned in yeast expression vector YEp96 tested for growth profile, viability assay and heat stress complementation study have revealed significant decrease in growth rate, loss of viability and non-complementation of heat sensitive phenotype with UbE64G-S65D and UbQ2N-E64G-S65D mutations. However, UbQ2N-S65D did not show any negative effects in the above assays. Present results show that, replacement of residues in beta-bulge of ubiquitin exerts severe effects on growth and viability in Saccharomyces cerevisiae due to functional failure of the mutant ubiquitins UbE64G-S65D and UbQ2N-E64G-S65D.

  1. Functional characterization of Pol III U6 promoters for gene knockdown and knockout in Plutella xylostella.

    Science.gov (United States)

    Huang, Yuping; Wang, Yajun; Zeng, Baosheng; Liu, Zhaoxia; Xu, Xuejiao; Meng, Qian; Huang, Yongping; Yang, Guang; Vasseur, Liette; Gurr, Geoff M; You, Minsheng

    2017-10-01

    RNA polymerase type III (Pol-III) promoters such as U6 are commonly used to express small RNAs, including short hairpin RNAs (shRNAs) and single guide RNAs (sgRNAs). Functional U6 promoters are widely used in CRISPR systems, and their characterization can facilitate genome editing of non-model organisms. In the present study, six U6 small nuclear RNA (snRNA) promoters containing two conserved elements of a proximal sequence element (PSEA) and a TATA box, were identified and characterized in the diamondback moth (Plutella xylostella) genome. Relative efficiency of the U6 promoters to express shRNA induced EGFP knockdown was tested in a P. xylostella cell line, revealing that the PxU6:3 promoter had the strongest expression effect. Further work with the PxU6:3 promoter showed its efficacy in EGFP knockout using CRISPR/Cas9 system in the cells. The expression plasmids with versatile Pxabd-A gene specific sgRNA driven by the PxU6:3 promoter, combined with Cas9 mRNA, could induce mutagenesis at specific genomic loci in vivo. The phenotypes induced by sgRNA expression plasmids were similar to those done in vitro transcription sgRNAs. A plasmid with two tandem arranged PxU6:3:sgRNA expression cassettes targeting Pxabd-A loci was generated, which caused a 28,856 bp fragment deletion, suggesting that the multi-sgRNA expression plasmid can be used for multi-targeting. Our work indicates that U6 snRNA promoters can be used for functional studies of genes with the approach of reverse genetics in P. xylostella. These essential promoters also provide valuable potential for CRISPR-derived gene drive as a tactic for population control in this globally significant pest. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Tree species diversity promotes aboveground carbon storage through functional diversity and functional dominance.

    Science.gov (United States)

    Mensah, Sylvanus; Veldtman, Ruan; Assogbadjo, Achille E; Glèlè Kakaï, Romain; Seifert, Thomas

    2016-10-01

    The relationship between biodiversity and ecosystem function has increasingly been debated as the cornerstone of the processes behind ecosystem services delivery. Experimental and natural field-based studies have come up with nonconsistent patterns of biodiversity-ecosystem function, supporting either niche complementarity or selection effects hypothesis. Here, we used aboveground carbon (AGC) storage as proxy for ecosystem function in a South African mistbelt forest, and analyzed its relationship with species diversity, through functional diversity and functional dominance. We hypothesized that (1) diversity influences AGC through functional diversity and functional dominance effects; and (2) effects of diversity on AGC would be greater for functional dominance than for functional diversity. Community weight mean (CWM) of functional traits (wood density, specific leaf area, and maximum plant height) were calculated to assess functional dominance (selection effects). As for functional diversity (complementarity effects), multitrait functional diversity indices were computed. The first hypothesis was tested using structural equation modeling. For the second hypothesis, effects of environmental variables such as slope and altitude were tested first, and separate linear mixed-effects models were fitted afterward for functional diversity, functional dominance, and both. Results showed that AGC varied significantly along the slope gradient, with lower values at steeper sites. Species diversity (richness) had positive relationship with AGC, even when slope effects were considered. As predicted, diversity effects on AGC were mediated through functional diversity and functional dominance, suggesting that both the niche complementarity and the selection effects are not exclusively affecting carbon storage. However, the effects were greater for functional diversity than for functional dominance. Furthermore, functional dominance effects were strongly transmitted by CWM of

  3. Isolation and functional characterization of Lycopene β-cyclase (CYC-B promoter from Solanum habrochaites

    Directory of Open Access Journals (Sweden)

    Chinnusamy Viswanathan

    2010-04-01

    to -437 bp 5' to ATG led to significant increase in the activity of GUS in the transgenic plants. Promoter deletion analysis led to the identification of a short promoter region (-436 bp to ATG that exhibited a higher promoter strength but similar developmental expression pattern as compared with the full-length ShCYC-B promoter. Conclusion Functional characterization of the full-length ShCYC-B promoter and its deletion fragments in transient expression system in fruto as well as in stable transgenic tomato revealed that the promoter is developmentally regulated and its expression is upregulated in chromoplast-rich flowers and fruits. Our study identified a short promoter region with functional activity and developmental expression pattern similar to that of the full-length ShCYC-B promoter. This 436 bp promoter region can be used in promoter::reporter fusion molecular genetic screens to identify mutants impaired in CYC-B expression, and thus can be a valuable tool in understanding carotenoid metabolism in tomato. Moreover, this short promoter region of ShCYC-B may be useful in genetic engineering of carotenoid content and other agronomic traits in tomato fruits.

  4. Cholecalciferol, Calcitriol, and Vascular Function in CKD: A Randomized, Double-Blind Trial.

    Science.gov (United States)

    Kendrick, Jessica; Andrews, Emily; You, Zhiying; Moreau, Kerrie; Nowak, Kristen L; Farmer-Bailey, Heather; Seals, Douglas R; Chonchol, Michel

    2017-09-07

    High circulating vitamin D levels are associated with lower cardiovascular mortality in CKD, possibly by modifying endothelial function. We examined the effect of calcitriol versus cholecalciferol supplementation on vascular endothelial function in patients with CKD. We performed a prospective, double-blind, randomized trial of 128 adult patients with eGFR=15-44 ml/min per 1.73 m 2 and serum 25-hydroxyvitamin D level Colorado. Participants were randomly assigned to oral cholecalciferol (2000 IU daily) or calcitriol (0.5 μ g) daily for 6 months. The primary end point was change in brachial artery flow-mediated dilation. Secondary end points included changes in circulating markers of mineral metabolism and circulating and cellular markers of inflammation. One hundred and fifteen patients completed the study. The mean (SD) age and eGFR of participants were 58±12 years old and 33.0±10.2 ml/min per 1.73 m 2 , respectively. There were no significant differences between groups at baseline. After 6 months, neither calcitriol nor cholecalciferol treatment resulted in a significant improvement in flow-mediated dilation (mean±SD percentage flow-mediated dilation; calcitriol: baseline 4.8±3.1%, end of study 5.1±3.6%; cholecalciferol: baseline 5.2±5.2%, end of study 4.7±3.6%); 25-hydroxyvitamin D levels increased significantly in the cholecalciferol group compared with the calcitriol group (cholecalciferol: 11.0±9.5 ng/ml; calcitriol: -0.8±4.8 ng/ml; P <0.001). Parathyroid hormone levels decreased significantly in the calcitriol group compared with the cholecalciferol group (median [interquartile range]; calcitriol: -22.1 [-48.7-3.5] pg/ml; cholecalciferol: -0.3 [-22.6-16.9] pg/ml; P =0.004). Six months of therapy with calcitriol or cholecalciferol did not improve vascular endothelial function or improve inflammation in patients with CKD. Copyright © 2017 by the American Society of Nephrology.

  5. Fanconi anemia group A and C double-mutant mice: functional evidence for a multi-protein Fanconi anemia complex.

    Science.gov (United States)

    Noll, Meenakshi; Battaile, Kevin P; Bateman, Raynard; Lax, Timothy P; Rathbun, Keany; Reifsteck, Carol; Bagby, Grover; Finegold, Milton; Olson, Susan; Grompe, Markus

    2002-07-01

    Fanconi anemia (FA) is a genetically heterogeneous disorder associated with defects in at least eight genes. The biochemical function(s) of the FA proteins are unknown, but together they define the FA pathway, which is involved in cellular responses to DNA damage and in other cellular processes. It is currently unknown whether all FA proteins are involved in controlling a single function or whether some of the FA proteins have additional roles. The aim of this study was 1) to determine whether the FA group A and group C genes have identical or partially distinct functions, and 2) to have a better model for human FA. We generated mice with a targeted mutation in fanca and crossed them with fancc disrupted animals. Several phenotypes including sensitivity to DNA cross linkers and ionizing radiation, hematopoietic colony growth, and germ cell loss were analyzed in fanca-/-, fancc-/-, fanca/fancc double -/-, and controls. Fibroblast cells and hematopoietic precursors from fanca/fancc double-mutant mice were not more sensitive to MMC than those of either single mutant. fanca/fancc double mutants had no evidence for an additive phenotype at the cellular or organismal level. These results support a model where both FANCA and FANCC are part of a multi-protein nuclear FA complex with identical function in cellular responses to DNA damage and germ cell survival.

  6. The promoter of the glucoamylase-encoding gene of Aspergillus niger functions in Ustilago maydis

    Energy Technology Data Exchange (ETDEWEB)

    Smith, T.L. (Dept. of Agriculture, Madison, WI (United States) Univ. of Wisconsin, Madison (United States)); Gaskell, J.; Cullen, D. (Dept. of Agriculture, Madison, WI (United States)); Berka, R.M.; Yang, M.; Henner, D.J. (Genentech Inc., San Francisco, CA (United States))

    1990-01-01

    Promoter sequences from the Aspergillus niger glucoamylase-encoding gene (glaA) were linked to the bacterial hygromycin (Hy) phosphotransferase-encoding gene (hph) and this chimeric marker was used to select Hy-resistant (Hy[sup R]) Ustilago maydis transformants. This is an example of an Ascomycete promoter functioning in a Basidiomycete. Hy[sup R] transformants varied with respect to copy number of integrated vector, mitotic stability, and tolerance to Hy. Only 216 bp of glaA promoter sequence is required for expression in U. maydis but this promoter is not induced by starch as it is in Aspergillus spp. The transcription start points are the same in U. maydis and A. niger.

  7. Cloning and Functional Analysis of the Promoter of an Ascorbate Oxidase Gene from Gossypium hirsutum.

    Directory of Open Access Journals (Sweden)

    Shan Xin

    Full Text Available Apoplastic ascorbate oxidase (AO plays significant roles in plant cell growth. However, the mechanism of underlying the transcriptional regulation of AO in Gossypium hirsutum remains unclear. Here, we obtained a 1,920-bp promoter sequence from the Gossypium hirsutum ascorbate oxidase (GhAO1 gene, and this GhAO1 promoter included a number of known cis-elements. Promoter activity analysis in overexpressing pGhAO1::GFP-GUS tobacco (Nicotiana benthamiana showed that the GhAO1 promoter exhibited high activity, driving strong reporter gene expression in tobacco trichomes, leaves and roots. Promoter 5'-deletion analysis demonstrated that truncated GhAO1 promoters with serial 5'-end deletions had different GUS activities. A 360-bp fragment was sufficient to activate GUS expression. The P-1040 region had less GUS activity than the P-720 region, suggesting that the 320-bp region from nucleotide -720 to -1040 might include a cis-element acting as a silencer. Interestingly, an auxin-responsive cis-acting element (TGA-element was uncovered in the promoter. To analyze the function of the TGA-element, tobacco leaves transformed with promoters with different 5' truncations were treated with indole-3-acetic acid (IAA. Tobacco leaves transformed with the promoter regions containing the TGA-element showed significantly increased GUS activity after IAA treatment, implying that the fragment spanning nucleotides -1760 to -1600 (which includes the TGA-element might be a key component for IAA responsiveness. Analyses of the AO promoter region and AO expression pattern in Gossypium arboreum (Ga, diploid cotton with an AA genome, Gossypium raimondii (Gr, diploid cotton with a DD genome and Gossypium hirsutum (Gh, tetraploid cotton with an AADD genome indicated that AO promoter activation and AO transcription were detected together only in D genome/sub-genome (Gr and Gh cotton. Taken together, these results suggest that the 1,920-bp GhAO1 promoter is a functional sequence

  8. Cloning and Functional Analysis of the Promoter of an Ascorbate Oxidase Gene from Gossypium hirsutum.

    Science.gov (United States)

    Xin, Shan; Tao, Chengcheng; Li, Hongbin

    2016-01-01

    Apoplastic ascorbate oxidase (AO) plays significant roles in plant cell growth. However, the mechanism of underlying the transcriptional regulation of AO in Gossypium hirsutum remains unclear. Here, we obtained a 1,920-bp promoter sequence from the Gossypium hirsutum ascorbate oxidase (GhAO1) gene, and this GhAO1 promoter included a number of known cis-elements. Promoter activity analysis in overexpressing pGhAO1::GFP-GUS tobacco (Nicotiana benthamiana) showed that the GhAO1 promoter exhibited high activity, driving strong reporter gene expression in tobacco trichomes, leaves and roots. Promoter 5'-deletion analysis demonstrated that truncated GhAO1 promoters with serial 5'-end deletions had different GUS activities. A 360-bp fragment was sufficient to activate GUS expression. The P-1040 region had less GUS activity than the P-720 region, suggesting that the 320-bp region from nucleotide -720 to -1040 might include a cis-element acting as a silencer. Interestingly, an auxin-responsive cis-acting element (TGA-element) was uncovered in the promoter. To analyze the function of the TGA-element, tobacco leaves transformed with promoters with different 5' truncations were treated with indole-3-acetic acid (IAA). Tobacco leaves transformed with the promoter regions containing the TGA-element showed significantly increased GUS activity after IAA treatment, implying that the fragment spanning nucleotides -1760 to -1600 (which includes the TGA-element) might be a key component for IAA responsiveness. Analyses of the AO promoter region and AO expression pattern in Gossypium arboreum (Ga, diploid cotton with an AA genome), Gossypium raimondii (Gr, diploid cotton with a DD genome) and Gossypium hirsutum (Gh, tetraploid cotton with an AADD genome) indicated that AO promoter activation and AO transcription were detected together only in D genome/sub-genome (Gr and Gh) cotton. Taken together, these results suggest that the 1,920-bp GhAO1 promoter is a functional sequence with a

  9. Pimpinella anisum in the treatment of functional dyspepsia: A double-blind, randomized clinical trial

    Directory of Open Access Journals (Sweden)

    S Ashraffodin Ghoshegir

    2015-01-01

    Full Text Available Background: We aimed to evaluate the effects of Pimpinella anisum (anise from Apiaceae family on relieving the symptoms of postprandial distress syndrome (PDS in this double-blind randomized clinical trial. Materials and Methods: Totally, 107 patients attending the gastroenterology clinic, aged 18-65 years, diagnosed with PDS according to ROME III criteria and signed a written consent form were enrolled. They were randomized to receive either anise or placebo, blindly, for 4 weeks. Anise group included 47 patients and received anise powders, 3 g after each meal (3 times/day. Control group involved 60 patients and received placebo powders (corn starch, 3 gafter each meal (3 times/day. The severity of Functional dyspepsia (FD symptoms was assessed by FD severity scale. Assessments were done at baseline and by the end of weeks 2, 4 and 12. Mean scores of severity of FD symptoms and the frequency distribution of patients across the study period were compared. Results: The age, sex, body mass index, smoking history, and coffee drinking pattern of the intervention and control groups were not significantly different. Mean (standard deviation total scores of FD severity scale before intervention in the anise and control groups were 10.6 (4.1 and 10.96 (4.1, respectively (P = 0.6. They were 7.04 (4.1 and 12.30 (4.3 by week 2, respectively (P = 0.0001, 2.44 (4.2 and 13.05 (5.2 by week 4, respectively (P = 0.0001, and 1.08 (3.8 and 13.30 (6.2 by week 12, respectively (P = 0.0001. Conclusion: This study showed the effectiveness of anise in relieving the symptoms of postpartum depression. The findings were consistent across the study period at weeks 2, 4 and 12.

  10. Thermogravimetric pyrolysis kinetics of bamboo waste via Asymmetric Double Sigmoidal (Asym2sig) function deconvolution.

    Science.gov (United States)

    Chen, Chuihan; Miao, Wei; Zhou, Cheng; Wu, Hongjuan

    2017-02-01

    Thermogravimetric kinetic of bamboo waste (BW) pyrolysis has been studied using Asymmetric Double Sigmoidal (Asym2sig) function deconvolution. Through deconvolution, BW pyrolytic profiles could be separated into three reactions well, each of which corresponded to pseudo hemicelluloses (P-HC), pseudo cellulose (P-CL), and pseudo lignin (P-LG) decomposition. Based on Friedman method, apparent activation energy of P-HC, P-CL, P-LG was found to be 175.6kJ/mol, 199.7kJ/mol, and 158.4kJ/mol, respectively. Energy compensation effects (lnk 0, z vs. E z ) of pseudo components were in well linearity, from which pre-exponential factors (k 0 ) were determined as 6.22E+11s -1 (P-HC), 4.50E+14s -1 (P-CL) and 1.3E+10s -1 (P-LG). Integral master-plots results showed pyrolytic mechanism of P-HC, P-CL, and P-LG was reaction order of f(α)=(1-α) 2 , f(α)=1-α and f(α)=(1-α) n (n=6-8), respectively. Mechanism of P-HC and P-CL could be further reconstructed to n-th order Avrami-Erofeyev model of f(α)=0.62(1-α)[-ln(1-α)] -0.61 (n=0.62) and f(α)=1.08(1-α)[-ln(1-α)] 0.074 (n=1.08). Two-steps reaction was more suitable for P-LG pyrolysis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. High-Frequency Promoter Firing Links THO Complex Function to Heavy Chromatin Formation

    DEFF Research Database (Denmark)

    Mouaikel, John; Causse, Sébastien Z; Rougemaille, Mathieu

    2013-01-01

    The THO complex is involved in transcription, genome stability, and messenger ribonucleoprotein (mRNP) formation, but its precise molecular function remains enigmatic. Under heat shock conditions, THO mutants accumulate large protein-DNA complexes that alter the chromatin density of target genes...... (heavy chromatin), defining a specific biochemical facet of THO function and a powerful tool of analysis. Here, we show that heavy chromatin distribution is dictated by gene boundaries and that the gene promoter is necessary and sufficient to convey THO sensitivity in these conditions. Single......-molecule fluorescence insitu hybridization measurements show that heavy chromatin formation correlates with an unusually high firing pace of the promoter with more than 20 transcription events per minute. Heavy chromatin formation closely follows the modulation of promoter firing and strongly correlates with polymerase...

  12. Exploring strain-promoted 1,3-dipolar cycloadditions of end functionalized polymers

    NARCIS (Netherlands)

    Ledin, Petr A; Kolishetti, Nagesh; Hudlikar, Manish S; Boons, Geert-Jan

    2014-01-01

    Strain-promoted 1,3-dipolar cycloaddition of cyclooctynes with 1,3-dipoles such as azides, nitrones, and nitrile oxides, are of interest for the functionalization of polymers. In this study, we have explored the use of a 4-dibenzocyclooctynol (DIBO)-containing chain transfer agent in reversible

  13. Study of the Wigner function at the device boundaries in one-dimensional single- and double-barrier structures

    International Nuclear Information System (INIS)

    Savio, Andrea; Poncet, Alain

    2011-01-01

    In this work, we compute the Wigner distribution function on one-dimensional devices from wave functions generated by solving the Schroedinger equation. Our goal is to investigate certain issues that we encountered in implementing Wigner transport equation solvers, such as the large discrepancies observed between the boundary conditions and the solution in the neighborhood of the boundaries. By evaluating the Wigner function without solving the Wigner transport equation, we intend to ensure that the actual boundary conditions are consistent with those commonly applied in literature. We study both single- and double-barrier unbiased structures. We use simple potential profiles, so that we can compute the wave functions analytically for better accuracy. We vary a number of structure geometry, material, meshing, and numerical parameters, among which are the contact length, the barrier height, the number of incident wave functions, and the numerical precision used for the computations, and we observe how the Wigner function at the device boundaries is affected. For the double-barrier structures, we look at the density matrix function and we study a model for the device transmission spectrum which helps explain the lobelike artifacts that we observe on the Wigner function.

  14. Human RECQ5 helicase promotes repair of DNA double-strand breaks by synthesis-dependent strand annealing

    Czech Academy of Sciences Publication Activity Database

    Paliwal, S.; Kanagaraj, R.; Sturzenegger, A.; Burdová, Kamila; Janščák, Pavel

    2014-01-01

    Roč. 42, č. 4 (2014), s. 2380-2390 ISSN 0305-1048 R&D Projects: GA ČR GA204/09/0565; GA ČR GAP305/10/0281 Grant - others:Swiss National Science Foundation(CH) 31003A-129747; Swiss National Science Foundation(CH) 31003A_146206 Institutional support: RVO:68378050 Keywords : Human RECQ5 helicase * DNA double-strand breaks * mitotic homologous recombination Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 9.112, year: 2014

  15. Type 1 plaminogen activator inhibitor gene: Functional analysis and glucocorticoid regulation of its promoter

    International Nuclear Information System (INIS)

    Van Zonneveld, A.J.; Curriden, S.A.; Loskutoff, D.J.

    1988-01-01

    Plasminogen activator inhibitor type 1 is an important component of the fibrinolytic system and its biosynthesis is subject to complex regulation. To study this regulation at the level of transcription, the authors have identified and sequenced the promoter of the human plasminogen activator inhibitor type 1 gene. Nuclease protection experiments were performed by using endothelial cell mRNA and the transcription initiation (cap) site was established. Sequence analysis of the 5' flanking region of the gene revealed a perfect TATA box at position -28 to position -23, the conserved distance from the cap site. Comparative functional studies with the firefly luciferase gene as a reporter gene showed that fragments derived from this 5' flanking region exhibited high promoter activity when transfected into bovine aortic endothelial cells and mouse Ltk - fibroblasts but were inactive when introduced into HeLa cells. These studies indicate that the fragments contain the plasminogen activator inhibitor type 1 promoter and that it is expressed in a tissue-specific manner. Although the fragments were also silent in rat FTO2B hepatoma cells, their promoter activity could be induced up to 40-fold with the synthetic glucocorticoid dexamethasone. Promoter deletion mapping experiments and studies involving the fusion of promoter fragments to a heterologous gene indicated that dexamethasone induction is mediated by a glucocorticoid responsive element with enhancer-like properties located within the region between nucleotides -305 and +75 of the plasminogen activator inhibitor type 1 gene

  16. 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.

  17. On the contact values of the density profiles in an electric double layer using density functional theory

    Directory of Open Access Journals (Sweden)

    L.B. Bhuiyan

    2012-06-01

    Full Text Available A recently proposed, local second contact value theorem [Henderson D., Boda D., J. Electroanal. Chem., 2005, Vol. 582, 16] for the charge profile of an electric double layer is used in conjunction with existing Monte Carlo data from the literature to assess the contact behavior of the electrode-ion distributions predicted by the density functional theory. The results for the contact values of the co- and counterion distributions and their product are obtained for the symmetric valency, restricted primitive model planar double layer for a range of electrolyte concentrations and temperatures. Overall the theoretical results satisfy the second contact value theorem reasonably well the agreement with the simulations being semi-quantitative or better. The product of the co- and counterion contact values as a function of the electrode surface charge density is qualitative with the simulations with increasing deviations at higher concentrations.

  18. Herbicide and fertilizers promote analogous phylogenetic responses but opposite functional responses in plant communities

    DEFF Research Database (Denmark)

    Pellissier, Loïc; Wisz, Mary S.; Strandberg, Beate

    2014-01-01

    on long-term experiment we show that fertilizer and herbicides (glyphosate) have contrasting effects on functional structure, but can increase phylogenetic diversity in semi-natural plant communities. We found that an increase in nitrogen promoted an increase in the average specific leaf area and canopy...... height at the community level, but an increase in glyphosate promoted a decrease in those traits. Phylogenetic diversity of plant communities increased when herbicide and fertilizer were applied together, likely because functional traits facilitating plant success in those conditions were......Throughout the world, herbicides and fertilizers change species composition in agricultural communities, but how do the cumulative effects of these chemicals impact the functional and phylogenetic structure of non-targeted communities when they drift into adjacent semi-natural habitats? Based...

  19. Practical measures of cognitive function and promotion of their performance in the context of research

    Directory of Open Access Journals (Sweden)

    Mariusz Gujski

    2016-07-01

    Full Text Available The aging of the population generates a number of very interesting research questions in the fields of medicine, psychology, sociology, demography, and many others. One of the issues subject to both intensive research by scientists and exploration by practitioners is associated with cognitive functions. The article presents current knowledge regarding practical actions in the field of promoting cognitive function using diagnostic programmes and training using modern technologies. An important aspect presented in this study is also related to the welfare of the maintenance or improvement of cognitive function. Information and communication technologies will contribute to the dissemination of computerized cognitive training, also personalized.

  20. HDAC4 and HDAC6 sustain DNA double strand break repair and stem-like phenotype by promoting radioresistance in glioblastoma cells.

    Science.gov (United States)

    Marampon, Francesco; Megiorni, Francesca; Camero, Simona; Crescioli, Clara; McDowell, Heather P; Sferra, Roberta; Vetuschi, Antonella; Pompili, Simona; Ventura, Luca; De Felice, Francesca; Tombolini, Vincenzo; Dominici, Carlo; Maggio, Roberto; Festuccia, Claudio; Gravina, Giovanni Luca

    2017-07-01

    The role of histone deacetylase (HDAC) 4 and 6 in glioblastoma (GBM) radioresistance was investigated. We found that tumor samples from 31 GBM patients, who underwent temozolomide and radiotherapy combined treatment, showed HDAC4 and HDAC6 expression in 93.5% and 96.7% of cases, respectively. Retrospective clinical data analysis demonstrated that high-intensity HDAC4 and/or HDAC6 immunostaining was predictive of poor clinical outcome. In vitro experiments revealed that short hairpin RNA-mediated silencing of HDAC4 or HDAC6 radiosensitized U87MG and U251MG GBM cell lines by promoting DNA double-strand break (DSBs) accumulation and by affecting DSBs repair molecular machinery. We found that HDAC6 knock-down predisposes to radiation therapy-induced U251MG apoptosis- and U87MG autophagy-mediated cell death. HDAC4 silencing promoted radiation therapy-induced senescence, independently by the cellular context. Finally, we showed that p53 WT expression contributed to the radiotherapy lethal effects and that HDAC4 or HDAC6 sustained GBM stem-like radioresistant phenotype. Altogether, these observations suggest that HDAC4 and HDAC6 are guardians of irradiation-induced DNA damages and stemness, thus promoting radioresistance, and may represent potential prognostic markers and therapeutic targets in GBM. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Finite-time generalized function matrix projective lag synchronization of coupled dynamical networks with different dimensions via the double power function nonlinear feedback control method

    International Nuclear Information System (INIS)

    Dai, Hao; Si, Gangquan; Jia, Lixin; Zhang, Yanbin

    2014-01-01

    This paper investigates the problem of finite-time generalized function matrix projective lag synchronization between two different coupled dynamical networks with different dimensions of network nodes. The double power function nonlinear feedback control method is proposed in this paper to guarantee that the state trajectories of the response network converge to the state trajectories of the drive network according to a function matrix in a given finite time. Furthermore, in comparison with the traditional nonlinear feedback control method, the new method improves the synchronization efficiency, and shortens the finite synchronization time. Numerical simulation results are presented to illustrate the effectiveness of this method. (papers)

  2. Acetyl salicylic acid–ZnAl layered double hydroxide functional nanohybrid for skin care application

    CSIR Research Space (South Africa)

    Mosangi, Damodar

    2016-10-01

    Full Text Available In this study, a pharmaceutically active ingredient, acetyl salicylic acid (ASA), was intercalated into ZnAl layered double hydroxide (LDH). The LDH–ASA nanohybrid material was characterized by XRD, FTIR, SEM, ICP-MS, TEM and TGA. Successful...

  3. Low x Double ln2(1/x) Resummation Effects at the Sum Rules for Nucleon Structure Function g1

    International Nuclear Information System (INIS)

    Ziaja, B.

    2001-01-01

    We have estimated the contributions to the moments of polarized nucleon structure function g 1 (x,Q 2 ) coming from the region of the very low x (10 -5 2 (1/x) resummation. The Q 2 evolution of g 1 was described by the unified evolution equations incorporating both the leading order Altarelli-Parisi evolution at large and moderate x, and the double ln 2 (1/x) resummation at small x. The moments were obtained by integrating out the extrapolated nucleon structure function in the region 10 -5 < x<1. (author)

  4. Characterization and functional analyses of the human G protein-coupled receptor kinase 4 gene promoter.

    Science.gov (United States)

    Hasenkamp, Sandra; Telgmann, Ralph; Staessen, Jan A; Hagedorn, Claudia; Dördelmann, Corinna; Bek, Martin; Brand-Herrmann, Stefan-Martin; Brand, Eva

    2008-10-01

    The G protein-coupled receptor kinase 4 is involved in renal sodium handling and blood pressure regulation. Missense variants have already been tested functionally and are associated with hypertension, but no data on promoter analyses are yet available. We scanned 94 hypertensive white subjects for genetic variation and performed promoter reporter gene analyses in HEK293T, COS7, and SaOs-2 cells. Transient transfections with various full lengths and wild-type deletion constructs revealed that 1851 bp of the flanking region and 275 bp of the 5'-untranslated region were sufficient for transcriptional activities and composed a powerful cis-active element in the distal 293 bp. The -1702T and +2T alleles resulted in drastic general reductions of promoter function, whereas an activity increasing effect of +268C was cell type specific. Electrophoretic mobility-shift assay, supershift, and cotransfection analyses of transcription factor binding sites predicted in silico (Alibaba2.1/Transfac7) resulted in allele-specific binding patterns of nuclear proteins and identified the participation of CCAAT/enhancer-binding protein transcription factor family members. The G protein-coupled receptor kinase 4 core promoter resides in the first 1851 bp upstream of its transcription start site. The 4 identified genetic variants within this region exert allele-specific impact on both cell type- and stimulation-dependent transcription and may affect the expression balance of renal G protein-coupled receptor kinase 4.

  5. Genome-wide function of H2B ubiquitylation in promoter and genic regions.

    Science.gov (United States)

    Batta, Kiran; Zhang, Zhenhai; Yen, Kuangyu; Goffman, David B; Pugh, B Franklin

    2011-11-01

    Nucleosomal organization in and around genes may contribute substantially to transcriptional regulation. The contribution of histone modifications to genome-wide nucleosomal organization has not been systematically evaluated. In the present study, we examine the role of H2BK123 ubiquitylation, a key regulator of several histone modifications, on nucleosomal organization at promoter, genic, and transcription termination regions in Saccharomyces cerevisiae. Using high-resolution MNase chromatin immunoprecipitation and sequencing (ChIP-seq), we map nucleosome positioning and occupancy in mutants of the H2BK123 ubiquitylation pathway. We found that H2B ubiquitylation-mediated nucleosome formation and/or stability inhibits the assembly of the transcription machinery at normally quiescent promoters, whereas ubiquitylation within highly active gene bodies promotes transcription elongation. This regulation does not proceed through ubiquitylation-regulated histone marks at H3K4, K36, and K79. Our findings suggest that mechanistically similar functions of H2B ubiquitylation (nucleosome assembly) elicit different functional outcomes on genes depending on its positional context in promoters (repressive) versus transcribed regions (activating).

  6. Constraint-induced movement therapy promotes brain functional reorganization in stroke patients with hemiplegia

    Science.gov (United States)

    Wang, Wenqing; Wang, Aihui; Yu, Limin; Han, Xuesong; Jiang, Guiyun; Weng, Changshui; Zhang, Hongwei; Zhou, Zhiqiang

    2012-01-01

    Stroke patients with hemiplegia exhibit flexor spasms in the upper limb and extensor spasms in the lower limb, and their movement patterns vary greatly. Constraint-induced movement therapy is an upper limb rehabilitation technique used in stroke patients with hemiplegia; however, studies of lower extremity rehabilitation are scarce. In this study, stroke patients with lower limb hemiplegia underwent conventional Bobath therapy for 4 weeks as baseline treatment, followed by constraint-induced movement therapy for an additional 4 weeks. The 10-m maximum walking speed and Berg balance scale scores significantly improved following treatment, and lower extremity motor function also improved. The results of functional MRI showed that constraint-induced movement therapy alleviates the reduction in cerebral functional activation in patients, which indicates activation of functional brain regions and a significant increase in cerebral blood perfusion. These results demonstrate that constraint-induced movement therapy promotes brain functional reorganization in stroke patients with lower limb hemiplegia. PMID:25337108

  7. Steady state conductance in a double quantum dot array: the nonequilibrium equation-of-motion Green function approach.

    Science.gov (United States)

    Levy, Tal J; Rabani, Eran

    2013-04-28

    We study steady state transport through a double quantum dot array using the equation-of-motion approach to the nonequilibrium Green functions formalism. This popular technique relies on uncontrolled approximations to obtain a closure for a hierarchy of equations; however, its accuracy is questioned. We focus on 4 different closures, 2 of which were previously proposed in the context of the single quantum dot system (Anderson impurity model) and were extended to the double quantum dot array, and develop 2 new closures. Results for the differential conductance are compared to those attained by a master equation approach known to be accurate for weak system-leads couplings and high temperatures. While all 4 closures provide an accurate description of the Coulomb blockade and other transport properties in the single quantum dot case, they differ in the case of the double quantum dot array, where only one of the developed closures provides satisfactory results. This is rationalized by comparing the poles of the Green functions to the exact many-particle energy differences for the isolate system. Our analysis provides means to extend the equation-of-motion technique to more elaborate models of large bridge systems with strong electronic interactions.

  8. Ubiquitin-like protein UBL5 promotes the functional integrity of the Fanconi anemia pathway.

    Science.gov (United States)

    Oka, Yasuyoshi; Bekker-Jensen, Simon; Mailand, Niels

    2015-05-12

    Ubiquitin and ubiquitin-like proteins (UBLs) function in a wide array of cellular processes. UBL5 is an atypical UBL that does not form covalent conjugates with cellular proteins and which has a known role in modulating pre-mRNA splicing. Here, we report an unexpected involvement of human UBL5 in promoting the function of the Fanconi anemia (FA) pathway for repair of DNA interstrand crosslinks (ICLs), mediated by a specific interaction with the central FA pathway component FANCI. UBL5-deficient cells display spliceosome-independent reduction of FANCI protein stability, defective FANCI function in response to DNA damage and hypersensitivity to ICLs. By mapping the sequence determinants underlying UBL5-FANCI binding, we generated separation-of-function mutants to demonstrate that key aspects of FA pathway function, including FANCI-FANCD2 heterodimerization, FANCD2 and FANCI monoubiquitylation and maintenance of chromosome stability after ICLs, are compromised when the UBL5-FANCI interaction is selectively inhibited by mutations in either protein. Together, our findings establish UBL5 as a factor that promotes the functionality of the FA DNA repair pathway. © 2015 The Authors.

  9. Acid-functionalized polyolefin materials and their use in acid-promoted chemical reactions

    Science.gov (United States)

    Oyola, Yatsandra; Tian, Chengcheng; Bauer, John Christopher; Dai, Sheng

    2016-06-07

    An acid-functionalized polyolefin material that can be used as an acid catalyst in a wide range of acid-promoted chemical reactions, wherein the acid-functionalized polyolefin material includes a polyolefin backbone on which acid groups are appended. Also described is a method for the preparation of the acid catalyst in which a precursor polyolefin is subjected to ionizing radiation (e.g., electron beam irradiation) of sufficient power and the irradiated precursor polyolefin reacted with at least one vinyl monomer having an acid group thereon. Further described is a method for conducting an acid-promoted chemical reaction, wherein an acid-reactive organic precursor is contacted in liquid form with a solid heterogeneous acid catalyst comprising a polyolefin backbone of at least 1 micron in one dimension and having carboxylic acid groups and either sulfonic acid or phosphoric acid groups appended thereto.

  10. Fumarase is involved in DNA double-strand break resection through a functional interaction with Sae2

    DEFF Research Database (Denmark)

    Leshets, Michael; Ramamurthy, Dharanidharan; Lisby, Michael

    2018-01-01

    One of the most severe forms of DNA damage is the double-strand break (DSB). Failure to properly repair the damage can cause mutation, gross chromosomal rearrangements and lead to the development of cancer. In eukaryotes, homologous recombination (HR) and non-homologous end joining (NHEJ) are the......One of the most severe forms of DNA damage is the double-strand break (DSB). Failure to properly repair the damage can cause mutation, gross chromosomal rearrangements and lead to the development of cancer. In eukaryotes, homologous recombination (HR) and non-homologous end joining (NHEJ......) are the main DSB repair pathways. Fumarase is a mitochondrial enzyme which functions in the tricarboxylic acid cycle. Intriguingly, the enzyme can be readily detected in the cytosolic compartment of all organisms examined, and we have shown that cytosolic fumarase participates in the DNA damage response...

  11. Structure of cylindrical electric double layers: Comparison of density functional and modified Poisson-Boltzmann theories with Monte Carlo simulations

    Directory of Open Access Journals (Sweden)

    V.Dorvilien

    2013-01-01

    Full Text Available The structure of cylindrical double layers is studied using a modified Poisson Boltzmann theory and the density functional approach. In the model double layer the electrode is a cylindrical polyion that is infinitely long, impenetrable, and uniformly charged. The polyion is immersed in a sea of equi-sized rigid ions embedded in a dielectric continuum. An in-depth comparison of the theoretically predicted zeta potentials, the mean electrostatic potentials, and the electrode-ion singlet density distributions is made with the corresponding Monte Carlo simulation data. The theories are seen to be consistent in their predictions that include variations in ionic diameters, electrolyte concentrations, and electrode surface charge densities, and are also able to reproduce well some new and existing Monte Carlo results.

  12. Promoting social behavior with oxytocin in high-functioning autism spectrum disorders

    OpenAIRE

    Andari, Elissar; Duhamel, Jean-René; Zalla, Tiziana; Herbrecht, Evelyn; Leboyer, Marion; Sirigu, Angela

    2010-01-01

    Social adaptation requires specific cognitive and emotional competences. Individuals with high-functioning autism or with Asperger syndrome cannot understand or engage in social situations despite preserved intellectual abilities. Recently, it has been suggested that oxytocin, a hormone known to promote mother-infant bonds, may be implicated in the social deficit of autism. We investigated the behavioral effects of oxytocin in 13 subjects with autism. In a simulated ball game where participan...

  13. Structure and Function of a Novel ATPase that Interacts with Holliday Junction Resolvase Hjc and Promotes Branch Migration.

    Science.gov (United States)

    Zhai, Binyuan; DuPrez, Kevin; Doukov, Tzanko I; Li, Huan; Huang, Mengting; Shang, Guijun; Ni, Jinfeng; Gu, Lichuan; Shen, Yulong; Fan, Li

    2017-04-07

    Holliday junction (HJ) is a hallmark intermediate in DNA recombination and must be processed by dissolution (for double HJ) or resolution to ensure genome stability. Although HJ resolvases have been identified in all domains of life, there is a long-standing effort to search in prokaryotes and eukarya for proteins promoting HJ migration. Here, we report the structural and functional characterization of a novel ATPase, Sulfolobus islandicusPilT N-terminal-domain-containing ATPase (SisPINA), encoded by the gene adjacent to the resolvase Hjc coding gene. PINA is conserved in archaea and vital for S. islandicus viability. Purified SisPINA forms hexameric rings in the crystalline state and in solution, similar to the HJ migration helicase RuvB in Gram-negative bacteria. Structural analysis suggests that ATP binding and hydrolysis cause conformational changes in SisPINA to drive branch migration. Further studies reveal that SisPINA interacts with SisHjc and coordinates HJ migration and cleavage. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Generalized zeta function representation of groups and 2-dimensional topological Yang-Mills theory: The example of GL(2, #Mathematical Double-Struck Capital F#{sub q}) and PGL(2, #Mathematical Double-Struck Capital F#{sub q})

    Energy Technology Data Exchange (ETDEWEB)

    Roche, Ph., E-mail: philippe.roche@univ-montp2.fr [Université Montpellier 2, CNRS, L2C, IMAG, Montpellier (France)

    2016-03-15

    We recall the relation between zeta function representation of groups and two-dimensional topological Yang-Mills theory through Mednikh formula. We prove various generalisations of Mednikh formulas and define generalization of zeta function representations of groups. We compute some of these functions in the case of the finite group GL(2, #Mathematical Double-Struck Capital F#{sub q}) and PGL(2, #Mathematical Double-Struck Capital F#{sub q}). We recall the table characters of these groups for any q, compute the Frobenius-Schur indicator of their irreducible representations, and give the explicit structure of their fusion rings.

  15. Structural and functional reorganization of propriospinal connections promotes functional recovery after spinal cord injury

    Directory of Open Access Journals (Sweden)

    Linard Filli

    2015-01-01

    Full Text Available Axonal regeneration and fiber regrowth is limited in the adult central nervous system, but research over the last decades has revealed a high intrinsic capacity of brain and spinal cord circuits to adapt and reorganize after smaller injuries or denervation. Short-distance fiber growth and synaptic rewiring was found in cortex, brain stem and spinal cord and could be associated with restoration of sensorimotor functions that were impaired by the injury. Such processes of structural plasticity were initially observed in the corticospinal system following spinal cord injury or stroke, but recent studies showed an equally high potential for structural and functional reorganization in reticulospinal, rubrospinal or propriospinal projections. Here we review the lesion-induced plastic changes in the propriospinal pathways, and we argue that they represent a key mechanism triggering sensorimotor recovery upon incomplete spinal cord injury. The formation or strengthening of spinal detour pathways bypassing supraspinal commands around the lesion site to the denervated spinal cord were identified as prominent neural substrate inducing substantial motor recovery in different species from mice to primates. Indications for the existence of propriospinal bypasses were also found in humans after cortical stroke. It is mandatory for current research to dissect the biological mechanisms underlying spinal circuit remodeling and to investigate how these processes can be stimulated in an optimal way by therapeutic interventions (e.g., fiber-growth enhancing interventions, rehabilitation. This knowledge will clear the way for the development of novel strategies targeting the remarkable plastic potential of propriospinal circuits to maximize functional recovery after spinal cord injury.

  16. Structural and Functional Characterization of a New Double Variant Haemoglobin (HbG-Philadelphia/Duarte α(2)β(2)).

    Science.gov (United States)

    Fais, Antonella; Casu, Mariano; Ruggerone, Paolo; Ceccarelli, Matteo; Porcu, Simona; Era, Benedetta; Anedda, Roberto; Sollaino, Maria Carla; Galanello, Renzo; Corda, Marcella

    2011-01-01

    WE REPORT THE FIRST CASE OF COSEGREGATION OF TWO HAEMOGLOBINS (HBS): HbG-Philadelphia [α68(E17)Asn → Lys] and HbDuarte [β62(E6)Ala → Pro]. The proband is a young patient heterozygous also for β°-thalassaemia. We detected exclusively two haemoglobin variants: HbDuarte and HbG-Philadelphia/Duarte. Functional study of the new double variant HbG-Philadelphia/Duarte exhibited an increase in oxygen affinity, with a slight decrease of cooperativity and Bohr effect. This functional behaviour is attributed to β62Ala → Pro instead of α68Asn → Lys substitution. Indeed, HbG-Philadelphia isolated in our laboratory from blood cells donor carrier for this variant is not affected by any functional modification, whereas purified Hb Duarte showed functional properties very similar to the double variant. NMR and MD simulation studies confirmed that the presence of Pro instead of Ala at the β62 position produces displacement of the E helix and modifications of the tertiary structure. The substitution α68(E17)Asn → Lys does not cause significant structural and dynamical modifications of the protein. A possible structure-based rational of substitution effects is suggested.

  17. Recombinational micro-evolution of functionally different metallothionein promoter alleles from Orchesella cincta

    Directory of Open Access Journals (Sweden)

    van Straalen Nico M

    2007-06-01

    Full Text Available Abstract Background Metallothionein (mt transcription is elevated in heavy metal tolerant field populations of Orchesella cincta (Collembola. This suggests that natural selection acts on transcriptional regulation of mt in springtails at sites where cadmium (Cd levels in soil reach toxic values This study investigates the nature and the evolutionary origin of polymorphisms in the metallothionein promoter (pmt and their functional significance for mt expression. Results We sequenced approximately 1600 bp upstream the mt coding region by genome walking. Nine pmt alleles were discovered in NW-European populations. They differ in the number of some indels, consensus transcription factor binding sites and core promoter elements. Extensive recombination events between some of the alleles can be inferred from the alignment. A deviation from neutral expectations was detected in a cadmium tolerant population, pointing towards balancing selection on some promoter stretches. Luciferase constructs were made from the most abundant alleles, and responses to Cd, paraquat (oxidative stress inducer and moulting hormone were studied in cell lines. By using paraquat we were able to dissect the effect of oxidative stress from the Cd specific effect, and extensive differences in mt induction levels between these two stressors were observed. Conclusion The pmt alleles evolved by a number of recombination events, and exhibited differential inducibilities by Cd, paraquat and molting hormone. In a tolerant population from a metal contaminated site, promoter allele frequencies differed significantly from a reference site and nucleotide polymorphisms in some promoter stretches deviated from neutral expectations, revealing a signature of balancing selection. Our results suggest that the structural differences in the Orchesella cincta metallothionein promoter alleles contribute to the metallothionein -over-expresser phenotype in cadmium tolerant populations.

  18. Cloning and Functional Analysis of Phosphoethanolamine Methyltransferase Promoter from Maize (Zea mays L.

    Directory of Open Access Journals (Sweden)

    Gai-Li Niu

    2018-01-01

    Full Text Available Betaine, a non-toxic osmoprotectant, is believed to accumulate considerably in plants under stress conditions to maintain the osmotic pressure and promote a variety of processes involved in growth and development. Phosphoethanolamine N-methyltransferase (PEAMT, a key enzyme for betaine synthesis, is reported to be regulated by its upstream promoter. In the present investigation, by using the transgenic approach, a 1048 bp long promoter region of ZmPEAMT gene from Zea mays was cloned and functionally characterized in tobacco. Computational analysis affirmed the existence of abiotic stress responsive cis-elements like ABRE, MYC, HST, LST etc., as well as pathogen, wound and phytohormone responsive motifs. For transformation in tobacco, four 5′-deletion constructs of 826 bp (P2, 642 bp (P3, 428 bp (P4 and 245 bp (P5 were constructed from the 1048 bp (P1 promoter fragment. The transgenic plants generated through a single event exhibited a promising expression of GUS reporter protein in the leaf tissues of treated with salt, drought, oxidative and cold stress as well as control plants. The GUS expression level progressively reduced from P1 to P5 in the leaf tissues, whereas a maximal expression was observed with the P3 construct in the leaves of control plants. The expression of GUS was noted to be higher in the leaves of osmotically- or salt-treated transgenic plants than that in the untreated (control plants. An effective expression of GUS in the transgenic plants manifests that this promoter can be employed for both stress-inducible and constitutive expression of gene(s. Due to this characteristic, this potential promoter can be effectively used for genetic engineering of several crops.

  19. Clinical evaluation of immune-promoting functions of the developed product (HemoHIM)

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kyoung Soo; Lee, Ill Kyoo; Kwon, Soon Gil [The Catholic University of Korea, Seoul (Korea, Republic of)

    2007-07-15

    We performed a clinical study to evaluate the immune promotion and antioxidant effects of the developed product (HemoHIM) in healthy or subhealthy people. Volunteers with white blood cell numbers between 5000 and 10000/ul were recruited and the subjects were selected by appropriate inclusion and exclusion rules. The subjects were randomly assigned to 3 groups (HemoHIM 6g/day, HemoHIM 12g/day, Placebo). HemoHIM or placebo were adminstered for 2 months and the blood were collected and analyzed at 1 month and 2 month after the intake. The collected blood was analyzed for blood cell number, serum biochemical values (liver and kidney function), immunological activity of blood cells, antioxidant activity of blood plasma, and stress hormone level in the saliva. Finally the data of 88 subjects were analyzed for the immune promoting and antioxidant effects of HemoHIM. In results, no significant changes in blood cell numbers (white blood cell, lymphocyte, red blood cell) were observed in HemoHIM intake groups. However, NK cell activity were increased in HemoHIM intake groups and also IFN-gamma and IL-12, the biomarkers of immune cell functions, were increased in proportion to the dose and intake periode of HemoHIM. The antioxidant biomarker (TAS) was not significantly changed by HemoHIM intake. Besides, the serum biochemical analysis for liver and kidney functions, and the general medical examination showed the HemoHIM showed no side-effects, thus reconfirming its safety in humans. In conclusion, this study showed HemoHIM has a significant effects on the promotion of immune functions, while it has neither side-effects nor toxicity in humans. The results of this study may be utilized for the scientific data to acquire the Health Functional Food Certification of HemoHIM from Korea FDA

  20. Human hepatocyte growth factor promotes functional recovery in primates after spinal cord injury.

    Science.gov (United States)

    Kitamura, Kazuya; Fujiyoshi, Kanehiro; Yamane, Jun-Ichi; Toyota, Fumika; Hikishima, Keigo; Nomura, Tatsuji; Funakoshi, Hiroshi; Nakamura, Toshikazu; Aoki, Masashi; Toyama, Yoshiaki; Okano, Hideyuki; Nakamura, Masaya

    2011-01-01

    Many therapeutic interventions for spinal cord injury (SCI) using neurotrophic factors have focused on reducing the area damaged by secondary, post-injury degeneration, to promote functional recovery. Hepatocyte growth factor (HGF), which is a potent mitogen for mature hepatocytes and a mediator of the inflammatory responses to tissue injury, was recently highlighted as a potent neurotrophic factor in the central nervous system. We previously reported that introducing exogenous HGF into the injured rodent spinal cord using a herpes simplex virus-1 vector significantly reduces the area of damaged tissue and promotes functional recovery. However, that study did not examine the therapeutic effects of administering HGF after injury, which is the most critical issue for clinical application. To translate this strategy to human treatment, we induced a contusive cervical SCI in the common marmoset, a primate, and then administered recombinant human HGF (rhHGF) intrathecally. Motor function was assessed using an original open field scoring system focusing on manual function, including reach-and-grasp performance and hand placement in walking. The intrathecal rhHGF preserved the corticospinal fibers and myelinated areas, thereby promoting functional recovery. In vivo magnetic resonance imaging showed significant preservation of the intact spinal cord parenchyma. rhHGF-treatment did not give rise to an abnormal outgrowth of calcitonin gene related peptide positive fibers compared to the control group, indicating that this treatment did not induce or exacerbate allodynia. This is the first study to report the efficacy of rhHGF for treating SCI in non-human primates. In addition, this is the first presentation of a novel scale for assessing neurological motor performance in non-human primates after contusive cervical SCI.

  1. Human hepatocyte growth factor promotes functional recovery in primates after spinal cord injury.

    Directory of Open Access Journals (Sweden)

    Kazuya Kitamura

    Full Text Available Many therapeutic interventions for spinal cord injury (SCI using neurotrophic factors have focused on reducing the area damaged by secondary, post-injury degeneration, to promote functional recovery. Hepatocyte growth factor (HGF, which is a potent mitogen for mature hepatocytes and a mediator of the inflammatory responses to tissue injury, was recently highlighted as a potent neurotrophic factor in the central nervous system. We previously reported that introducing exogenous HGF into the injured rodent spinal cord using a herpes simplex virus-1 vector significantly reduces the area of damaged tissue and promotes functional recovery. However, that study did not examine the therapeutic effects of administering HGF after injury, which is the most critical issue for clinical application. To translate this strategy to human treatment, we induced a contusive cervical SCI in the common marmoset, a primate, and then administered recombinant human HGF (rhHGF intrathecally. Motor function was assessed using an original open field scoring system focusing on manual function, including reach-and-grasp performance and hand placement in walking. The intrathecal rhHGF preserved the corticospinal fibers and myelinated areas, thereby promoting functional recovery. In vivo magnetic resonance imaging showed significant preservation of the intact spinal cord parenchyma. rhHGF-treatment did not give rise to an abnormal outgrowth of calcitonin gene related peptide positive fibers compared to the control group, indicating that this treatment did not induce or exacerbate allodynia. This is the first study to report the efficacy of rhHGF for treating SCI in non-human primates. In addition, this is the first presentation of a novel scale for assessing neurological motor performance in non-human primates after contusive cervical SCI.

  2. Translationally controlled tumor protein supplemented chitosan modified glass ionomer cement promotes osteoblast proliferation and function

    International Nuclear Information System (INIS)

    Sangsuwan, Jiraporn; Wanichpakorn, Supreya; Kedjarune-Leggat, Ureporn

    2015-01-01

    The objective of this study was to evaluate the effect of translationally controlled tumor protein (TCTP) supplemented in a novel glass ionomer cement (BIO-GIC) on normal human osteoblasts (NHost cells). BIO-GIC was a glass ionomer cement (GIC) modified by adding chitosan and albumin to promote the release of TCTP. NHost cells were seeded on specimens of GIC, GIC + TCTP, BIO-GIC and BIO-GIC + TCTP. Cell proliferation was determined by BrdU assay. It was found that BIO-GIC + TCTP had significantly higher proliferation of cells than other specimens. Bone morphogenetic protein-2 (BMP-2) and osteopontin (OPN) gene expressions assessed by quantitative real time PCR and alkaline phosphatase (ALP) activity were used to determine cell differentiation. Bone cell function was investigated by calcium deposition using alizarin assay. Both BMP-2 and OPN gene expressions of cells cultured on specimens with added TCTP increased gradually up-regulation after day 1 and reached the highest on day 3 then down-regulation on day 7. The ALP activity of cells cultured on BIO-GIC + TCTP for 7 days and calcium content after 14 days were significantly higher than other groups. BIO-GIC + TCTP can promote osteoblast cells proliferation, differentiation and function. - Highlights: • Developed a new GIC by supplementing TCTP in BIO-GIC (GIC with chitosan and albumin) • BIO-GIC + TCTP released a higher amount of TCTP than GIC + TCTP. • BIO-GIC + TCTP promoted cell proliferation higher than other specimens and control. • BIO-GIC + TCTP promoted osteoblasts differentiation and function

  3. Translationally controlled tumor protein supplemented chitosan modified glass ionomer cement promotes osteoblast proliferation and function

    Energy Technology Data Exchange (ETDEWEB)

    Sangsuwan, Jiraporn [Department of Molecular Biology and Bioinformatics, Center for Genomics and Bioinformatics Research, Faculty of Science, Prince of Songkla University, Hat Yai, Songkhla 90112 (Thailand); Department of Oral Biology and Occlusion, Faculty of Dentistry, Prince of Songkla University, Hat Yai, Songkhla 90112 (Thailand); Wanichpakorn, Supreya; Kedjarune-Leggat, Ureporn [Department of Oral Biology and Occlusion, Faculty of Dentistry, Prince of Songkla University, Hat Yai, Songkhla 90112 (Thailand)

    2015-09-01

    The objective of this study was to evaluate the effect of translationally controlled tumor protein (TCTP) supplemented in a novel glass ionomer cement (BIO-GIC) on normal human osteoblasts (NHost cells). BIO-GIC was a glass ionomer cement (GIC) modified by adding chitosan and albumin to promote the release of TCTP. NHost cells were seeded on specimens of GIC, GIC + TCTP, BIO-GIC and BIO-GIC + TCTP. Cell proliferation was determined by BrdU assay. It was found that BIO-GIC + TCTP had significantly higher proliferation of cells than other specimens. Bone morphogenetic protein-2 (BMP-2) and osteopontin (OPN) gene expressions assessed by quantitative real time PCR and alkaline phosphatase (ALP) activity were used to determine cell differentiation. Bone cell function was investigated by calcium deposition using alizarin assay. Both BMP-2 and OPN gene expressions of cells cultured on specimens with added TCTP increased gradually up-regulation after day 1 and reached the highest on day 3 then down-regulation on day 7. The ALP activity of cells cultured on BIO-GIC + TCTP for 7 days and calcium content after 14 days were significantly higher than other groups. BIO-GIC + TCTP can promote osteoblast cells proliferation, differentiation and function. - Highlights: • Developed a new GIC by supplementing TCTP in BIO-GIC (GIC with chitosan and albumin) • BIO-GIC + TCTP released a higher amount of TCTP than GIC + TCTP. • BIO-GIC + TCTP promoted cell proliferation higher than other specimens and control. • BIO-GIC + TCTP promoted osteoblasts differentiation and function.

  4. Transplantation of specific human astrocytes promotes functional recovery after spinal cord injury.

    Directory of Open Access Journals (Sweden)

    Stephen J A Davies

    2011-03-01

    Full Text Available Repairing trauma to the central nervous system by replacement of glial support cells is an increasingly attractive therapeutic strategy. We have focused on the less-studied replacement of astrocytes, the major support cell in the central nervous system, by generating astrocytes from embryonic human glial precursor cells using two different astrocyte differentiation inducing factors. The resulting astrocytes differed in expression of multiple proteins thought to either promote or inhibit central nervous system homeostasis and regeneration. When transplanted into acute transection injuries of the adult rat spinal cord, astrocytes generated by exposing human glial precursor cells to bone morphogenetic protein promoted significant recovery of volitional foot placement, axonal growth and notably robust increases in neuronal survival in multiple spinal cord laminae. In marked contrast, human glial precursor cells and astrocytes generated from these cells by exposure to ciliary neurotrophic factor both failed to promote significant behavioral recovery or similarly robust neuronal survival and support of axon growth at sites of injury. Our studies thus demonstrate functional differences between human astrocyte populations and suggest that pre-differentiation of precursor cells into a specific astrocyte subtype is required to optimize astrocyte replacement therapies. To our knowledge, this study is the first to show functional differences in ability to promote repair of the injured adult central nervous system between two distinct subtypes of human astrocytes derived from a common fetal glial precursor population. These findings are consistent with our previous studies of transplanting specific subtypes of rodent glial precursor derived astrocytes into sites of spinal cord injury, and indicate a remarkable conservation from rat to human of functional differences between astrocyte subtypes. In addition, our studies provide a specific population of human

  5. A systematic comparison of different approaches of density functional theory for the study of electrical double layers

    International Nuclear Information System (INIS)

    Yang, Guomin; Liu, Longcheng

    2015-01-01

    Based on the best available knowledge of density functional theory (DFT), the reference-fluid perturbation method is here extended to yield different approaches that well account for the cross correlations between the Columbic interaction and the hard-sphere exclusion in an inhomogeneous ionic hard-sphere fluid. In order to quantitatively evaluate the advantage and disadvantage of different approaches in describing the interfacial properties of electrical double layers, this study makes a systematic comparison against Monte Carlo simulations over a wide range of conditions. The results suggest that the accuracy of the DFT approaches is well correlated to a coupling parameter that describes the coupling strength of electrical double layers by accounting for the steric effect and that can be used to classify the systems into two regimes. In the weak-coupling regime, the approaches based on the bulk-fluid perturbation method are shown to be more accurate than the counterparts based on the reference-fluid perturbation method, whereas they exhibit the opposite behavior in the strong-coupling regime. More importantly, the analysis indicates that, with a suitable choice of the reference fluid, the weighted correlation approximation (WCA) to DFT gives the best account of the coupling effect of the electrostatic-excluded volume correlations. As a result, a piecewise WCA approach can be developed that is robust enough to describe the structural and thermodynamic properties of electrical double layers over both weak- and strong-coupling regimes

  6. Broadening of the x-ray emission line due to the instrumental function of the double-crystal spectrometer

    International Nuclear Information System (INIS)

    Tochio, T.; Ito, Y.; Omote, K.

    2002-01-01

    The influence of the instrumental function on the Cu Kα 1 emission line was investigated for the case of a double-crystal spectrometer. The magnitude of broadening for both Si(220) and Si(440) was calculated for a Lorentzian emission line with the width of 1-5 eV; the broadening for Si(220) is 0.12-0.18 eV while that for Si(440) is only 0.015-0.043 eV. The former is too large to be neglected, so the correction for the instrumental function is important. The spectrum affected by the instrumental function seems to keep the shape of Lorentzian though its width is larger. The fact indicates that the Lorentzian fitting analysis is effective if the appropriate correction for width is done

  7. Characterization and functional analysis of the Paralichthys olivaceus prdm1 gene promoter.

    Science.gov (United States)

    Li, Peizhen; Wang, Bo; Cao, Dandan; Liu, Yuezhong; Zhang, Quanqi; Wang, Xubo

    2017-10-01

    PR domain containing protein 1 (Prdm1) is a transcriptional repressor identified in various species and plays multiple important roles in immune response and embryonic development. However, little is known about the transcriptional regulation of the prdm1 gene. This study aims to characterize the promoter of Paralichthys olivaceus prdm1 (Po-prdm1) gene and determine the regulatory mechanism of Po-prdm1 expression. A 2000bp-long 5'-flanking region (translation initiation site designated as +1) of the Po-prdm1 gene was isolated and characterized. The regulatory elements in this fragment were then investigated and many putative transcription factor (TF) binding sites involved in immunity and multiple tissue development were identified. A 5'-deletion analysis was then conducted, and the ability of the deletion mutants to promote luciferase and green fluorescent protein (GFP) expression in a flounder gill cell line was examined. The results revealed that the minimal promoter is located in the region between -446 and -13bp, and the region between -1415 and -13bp enhanced the promoter activity. Site-directed mutation analysis was subsequently performed on the putative regulatory elements sites, and the results indicated that FOXP1, MSX and BCL6 binding sites play negative functional roles in the regulation of the Po-prdm1 expression in FG cells. In vivo analysis demonstrated that a GFP reporter gene containing 1.4kb-long promoter fragment (-1415/-13) was expressed in the head and trunk muscle fibres of transient transgenic zebrafish embryos. Our study provided the basic information for the exploration of Po-prdm1 regulation and expression. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Promotion of health and human functionality - 10.5020/18061230.2013.p5

    Directory of Open Access Journals (Sweden)

    Ana Cristhina de Oliveira Brasil

    2013-08-01

    Full Text Available For the development of public health policies in Brazil, two aspects should be taken into consideration, namely, the demographic transition and the epidemiological transition. More and more, it is perceivable an increase in the number of elderly people living with numerous disabilities and also an epidemiological profile. National Household Sample Survey (Pesquisa Nacional por Amostra de Domicílios - PNAD 1998-2003 indicates a distribution of chronic diseases that, consequently, has generated an expressive number of disabilities. These people with disabilities need health services, and use them when they manage to access them. However, the current models of healthcare for the elderly or people with disabilities are expensive and, in some aspects, are not efficient, requiring preventive strategies and health equipment for the maintenance or recovery of health of an aged population. Thus, the public policy agenda of Brazil should give priority to the maintenance of the functionality of the aged, with monitoring of health status, specific preventive actions on health and education, and care seeking an integral and multidimensional attention, not necessarily focused on disease(1. The need to develop policies and strategies, particularly on health promotion, with a look detached from the disease is justified because health problems come not only from the disease, but from any other circumstance or health condition, such as, pregnancy , aging, stress, genetic predisposition – all classified by D-10, nevertheless, not being able to measure the status alterations related to health, and much less to sort and describe the context in which these problems occur, which complicates and jeopardizes the planning and solvability of actions and services in health, unlike the data by means of qualifiers that the International Classification of Functioning, Disability and Health (ICF has the potential to generate(2. Brazil is a member country of the World Health

  9. Determination of an effective scoring function for RNA-RNA interactions with a physics-based double-iterative method.

    Science.gov (United States)

    Yan, Yumeng; Wen, Zeyu; Zhang, Di; Huang, Sheng-You

    2018-05-18

    RNA-RNA interactions play fundamental roles in gene and cell regulation. Therefore, accurate prediction of RNA-RNA interactions is critical to determine their complex structures and understand the molecular mechanism of the interactions. Here, we have developed a physics-based double-iterative strategy to determine the effective potentials for RNA-RNA interactions based on a training set of 97 diverse RNA-RNA complexes. The double-iterative strategy circumvented the reference state problem in knowledge-based scoring functions by updating the potentials through iteration and also overcame the decoy-dependent limitation in previous iterative methods by constructing the decoys iteratively. The derived scoring function, which is referred to as DITScoreRR, was evaluated on an RNA-RNA docking benchmark of 60 test cases and compared with three other scoring functions. It was shown that for bound docking, our scoring function DITScoreRR obtained the excellent success rates of 90% and 98.3% in binding mode predictions when the top 1 and 10 predictions were considered, compared to 63.3% and 71.7% for van der Waals interactions, 45.0% and 65.0% for ITScorePP, and 11.7% and 26.7% for ZDOCK 2.1, respectively. For unbound docking, DITScoreRR achieved the good success rates of 53.3% and 71.7% in binding mode predictions when the top 1 and 10 predictions were considered, compared to 13.3% and 28.3% for van der Waals interactions, 11.7% and 26.7% for our ITScorePP, and 3.3% and 6.7% for ZDOCK 2.1, respectively. DITScoreRR also performed significantly better in ranking decoys and obtained significantly higher score-RMSD correlations than the other three scoring functions. DITScoreRR will be of great value for the prediction and design of RNA structures and RNA-RNA complexes.

  10. Electroacupuncture promotes post-stroke functional recovery via enhancing endogenous neurogenesis in mouse focal cerebral ischemia.

    Directory of Open Access Journals (Sweden)

    Yu Ri Kim

    Full Text Available To investigate the question of whether electroacupuncture (EA promotes functional recovery via enhancement of proliferation and differentiation of neuronal stem cells (NSCs in ischemic stroke, EA stimulation with 2 Hz was applied at bilateral acupoints to Baihui (GV20 and Dazhui (GV14 in middle cerebral artery occlusion (MCAO mice. EA stimulation improved neuromotor function and cognitive ability after ischemic stroke. EA stimulation resulted in an increase in the number of proliferated cells, especially in the subventricular zone (SVZ of the ipsilateral hemisphere. Although a very limited number of NSCs survived and differentiated into neurons or astrocytes, EA treatment resulted in a significant increase in the number of proliferative cells and differentiated cells in the hippocampus and SVZ of the ipsilateral hemisphere compared to MCAO mice. EA stimulation resulted in significantly increased mRNA expression of brain-derived neurotrophic factor (BDNF and vascular endothelial growth factor (VEGF. Protein levels of these factors were confirmed in the ipsilateral hippocampus and SVZ by immunohistochemical and Western blotting analyses. Expression of phosphorylated phosphatidylinositol-3-kinase, BDNF, and VEGF-mediated down-stream were enhanced by EA stimulation in newly formed neuroblasts. These results indicate that EA treatment after ischemic stroke may promote post-stroke functional recovery by enhancement of proliferation and differentiation of NSCs via the BDNF and VEGF signaling pathway.

  11. Herbicide and fertilizers promote analogous phylogenetic responses but opposite functional responses in plant communities

    International Nuclear Information System (INIS)

    Pellissier, Loïc; Wisz, Mary S; Strandberg, Beate; Damgaard, Christian

    2014-01-01

    Throughout the world, herbicides and fertilizers change species composition in agricultural communities, but how do the cumulative effects of these chemicals impact the functional and phylogenetic structure of non-targeted communities when they drift into adjacent semi-natural habitats? Based on long-term experiment we show that fertilizer and herbicides (glyphosate) have contrasting effects on functional structure, but can increase phylogenetic diversity in semi-natural plant communities. We found that an increase in nitrogen promoted an increase in the average specific leaf area and canopy height at the community level, but an increase in glyphosate promoted a decrease in those traits. Phylogenetic diversity of plant communities increased when herbicide and fertilizer were applied together, likely because functional traits facilitating plant success in those conditions were not phylogenetically conserved. Species richness also decreased with increasing levels of nitrogen and glyphosate. Our results suggest that predicting the cumulative effects of agrochemicals is more complex than anticipated due to their distinct selection of traits that may or may not be conserved phylogenetically. Precautionary efforts to mitigate drift of agricultural chemicals into semi-natural habitats are warranted to prevent unforeseeable biodiversity shifts. (paper)

  12. Functionalization of CoCr surfaces with cell adhesive peptides to promote HUVECs adhesion and proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Castellanos, Maria Isabel, E-mail: maria.isabel.castellanos@upc.edu [Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Technical University of Catalonia (UPC), ETSEIB, 08028 Barcelona (Spain); Centre for Research in Nanoengineering (CRNE), UPC, 08028 Barcelona (Spain); Mas-Moruno, Carlos, E-mail: carles.mas.moruno@upc.edu [Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Technical University of Catalonia (UPC), ETSEIB, 08028 Barcelona (Spain); Centre for Research in Nanoengineering (CRNE), UPC, 08028 Barcelona (Spain); Grau, Anna, E-mail: agraugar@gmail.com [Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Technical University of Catalonia (UPC), ETSEIB, 08028 Barcelona (Spain); Centre for Research in Nanoengineering (CRNE), UPC, 08028 Barcelona (Spain); Serra-Picamal, Xavier, E-mail: xserrapicamal@gmail.com [Institute for Bioengineering of Catalonia (IBEC), 08028 Barcelona (Spain); University of Barcelona and CIBER-BBN, 08036 Barcelona (Spain); Institució Catalana de Recerca i Estudis Avançats (ICREA), 08010 Barcelona (Spain); Trepat, Xavier, E-mail: xtrepat@ub.edu [Institute for Bioengineering of Catalonia (IBEC), 08028 Barcelona (Spain); University of Barcelona and CIBER-BBN, 08036 Barcelona (Spain); Institució Catalana de Recerca i Estudis Avançats (ICREA), 08010 Barcelona (Spain); Albericio, Fernando, E-mail: fernando.albericio@irbbarcelona.org [Department of Chemistry, University of Barcelona, CIBER-BBN, 08028 Barcelona (Spain); Joner, Michael, E-mail: michaeljoner@me.com [Department of Cardiology, Deutsches Herzzentrum München, 80636 Munich (Germany); CVPath Institute, Gaithersburg, MD 20878 (United States); and others

    2017-01-30

    Highlights: • We immobilized peptides on CoCr alloy through physisorption and covalent bonding. • Surface activation is an essential step prior to silanization to enhance peptide attachment. • Biofunctionalized surface characteristics were discussed. • RGDS, YIGSR and combination peptides display an improved HUVECs adhesion and proliferation. - Abstract: Biomimetic surface modification with peptides that have specific cell-binding moieties is a promising approach to improve endothelialization of metal-based stents. In this study, we functionalized CoCr surfaces with RGDS, REDV, YIGSR peptides and their combinations to promote endothelial cells (ECs) adhesion and proliferation. An extensive characterization of the functionalized surfaces was performed by XPS analysis, surface charge and quartz crystal microbalance with dissipation monitoring (QCM-D), which demonstrated the successful immobilization of the peptides to the surface. Cell studies demonstrated that the covalent functionalization of CoCr surfaces with an equimolar combination of RGDS and YIGSR represents the most powerful strategy to enhance the early stages of ECs adhesion and proliferation, indicating a positive synergistic effect between the two peptide motifs. Although these peptide sequences slightly increased smooth muscle cells (SMCs) adhesion, these values were ten times lower than those observed for ECs. The combination of RGDS with the REDV sequence did not show synergistic effects in promoting the adhesion or proliferation of ECs. The strategy presented in this study holds great potential to overcome clinical limitations of current metal stents by enhancing their capacity to support surface endothelialization.

  13. Curcumin promotes nerve regeneration and functional recovery after sciatic nerve crush injury in diabetic rats.

    Science.gov (United States)

    Ma, Junxiong; Yu, Hailong; Liu, Jun; Chen, Yu; Wang, Qi; Xiang, Liangbi

    2016-01-01

    Curcumin is capable of promoting peripheral nerve regeneration in normal condition. However, it is unclear whether its beneficial effect on nerve regeneration still exists under diabetic mellitus. The present study was designed to investigate such a possibility. Diabetes in rats was developed by a single dose of streptozotocin at 50 mg/kg. Immediately after nerve crush injury, the diabetic rats were intraperitoneally administrated daily for 4 weeks with curcumin (50 mg/kg, 100 mg/kg and 300 mg/kg), or normal saline, respectively. The axonal regeneration was investigated by morphometric analysis and retrograde labeling. The functional recovery was evaluated by electrophysiological studies and behavioral analysis. Axonal regeneration and functional recovery was significantly enhanced by curcumin, which were significantly better than those in vehicle saline group. In addition, high doses of curcumin (100 mg/kg and 300 mg/kg) achieved better axonal regeneration and functional recovery than low dose (50 mg/kg). In conclusion, curcumin is capable of promoting nerve regeneration after sciatic nerve crush injury in diabetes mellitus, highlighting its therapeutic values as a neuroprotective agent for peripheral nerve injury repair in diabetes mellitus. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  14. Combined motor cortex and spinal cord neuromodulation promotes corticospinal system functional and structural plasticity and motor function after injury.

    Science.gov (United States)

    Song, Weiguo; Amer, Alzahraa; Ryan, Daniel; Martin, John H

    2016-03-01

    An important strategy for promoting voluntary movements after motor system injury is to harness activity-dependent corticospinal tract (CST) plasticity. We combine forelimb motor cortex (M1) activation with co-activation of its cervical spinal targets in rats to promote CST sprouting and skilled limb movement after pyramidal tract lesion (PTX). We used a two-step experimental design in which we first established the optimal combined stimulation protocol in intact rats and then used the optimal protocol in injured animals to promote CST repair and motor recovery. M1 was activated epidurally using an electrical analog of intermittent theta burst stimulation (iTBS). The cervical spinal cord was co-activated by trans-spinal direct current stimulation (tsDCS) that was targeted to the cervical enlargement, simulated from finite element method. In intact rats, forelimb motor evoked potentials (MEPs) were strongly facilitated during iTBS and for 10 min after cessation of stimulation. Cathodal, not anodal, tsDCS alone facilitated MEPs and also produced a facilitatory aftereffect that peaked at 10 min. Combined iTBS and cathodal tsDCS (c-tsDCS) produced further MEP enhancement during stimulation, but without further aftereffect enhancement. Correlations between forelimb M1 local field potentials and forelimb electromyogram (EMG) during locomotion increased after electrical iTBS alone and further increased with combined stimulation (iTBS+c-tsDCS). This optimized combined stimulation was then used to promote function after PTX because it enhanced functional connections between M1 and spinal circuits and greater M1 engagement in muscle contraction than either stimulation alone. Daily application of combined M1 iTBS on the intact side and c-tsDCS after PTX (10 days, 27 min/day) significantly restored skilled movements during horizontal ladder walking. Stimulation produced a 5.4-fold increase in spared ipsilateral CST terminations. Combined neuromodulation achieves optimal motor

  15. Functional evolution in the plant SQUAMOSA-PROMOTER BINDING PROTEIN-LIKE (SPL gene family

    Directory of Open Access Journals (Sweden)

    Jill Christine Preston

    2013-04-01

    Full Text Available The SQUAMOSA-PROMOTER BINDING PROTEIN-LIKE (SPL family of transcription factors is functionally diverse, controlling a number of fundamental aspects of plant growth and development, including vegetative phase change, flowering time, branching, and leaf initiation rate. In natural plant populations, variation in flowering time and shoot architecture have major consequences for fitness. Likewise, in crop species, variation in branching and developmental rate impact biomass and yield. Thus, studies aimed at dissecting how the various functions are partitioned among different SPL genes in diverse plant lineages are key to providing insight into the genetic basis of local adaptation and have already garnered attention by crop breeders. Here we use phylogenetic reconstruction to reveal nine major SPL gene lineages, each of which is described in terms of function and diversification. To assess evidence for ancestral and derived functions within each SPL gene lineage, we use ancestral character state reconstructions. Our analyses suggest an emerging pattern of sub-functionalization, neo-functionalization, and possible convergent evolution following both ancient and recent gene duplication. Based on these analyses we suggest future avenues of research that may prove fruitful for elucidating the importance of SPL gene evolution in plant growth and development.

  16. Comparing the Functioning of Youth and Adult Partnerships for Health Promotion.

    Science.gov (United States)

    Brown, Louis D; Redelfs, Alisha H; Taylor, Thomas J; Messer, Reanna L

    2015-09-01

    Youth partnerships are a promising but understudied strategy for prevention and health promotion. Specifically, little is known about how the functioning of youth partnerships differs from that of adult partnerships. Accordingly, this study compared the functioning of youth partnerships with that of adult partnerships. Several aspects of partnership functioning, including leadership, task focus, cohesion, participation costs and benefits, and community support, were examined. Standardized partnership functioning surveys were administered to participants in three smoke-free youth coalitions (n = 44; 45 % female; 43 % non-Hispanic white; mean age = 13) and in 53 Communities That Care adult coalitions (n = 673; 69 % female; 88 % non-Hispanic white; mean age = 49). Multilevel regression analyses showed that most aspects of partnership functioning did not differ significantly between youth and adult partnerships. These findings are encouraging given the success of the adult partnerships in reducing community-level rates of substance use and delinquency. Although youth partnership functioning appears to be strong enough to support effective prevention strategies, youth partnerships faced substantially more participation difficulties than adult partnerships. Strategies that youth partnerships can use to manage these challenges, such as creative scheduling and increasing opportunities for youth to help others directly, are discussed.

  17. Optimization of pentacene double floating gate memories based on charge injection regulated by SAM functionalization

    Directory of Open Access Journals (Sweden)

    S. Li

    2018-02-01

    Full Text Available Pentacene based double nano-floating gate memories (NFGM by using gold nanoparticles (Au NPs and reduced graphene oxide (rGO sheets as charge trapping layers are prepared and demonstrated. Particularly, the NFGM chemically treated by 2,3,4,5,6-pentafluorobenzenethiol (PFBT self-assembled monolayers (SAM exhibits excellent memory performances, including high mobility of 0.23 cm2V-1s-1, the large memory window of 51 V, and the stable retention property more than 108 s. Comparing the performances of NFGM without treating with PFBT SAM, the improving performances of the memory devices by SAM modification are explained by the increase of charge injection, which could be further investigated by XPS and UPS. In particular, the results highlight the utility of SAM modulations and controlling of charge transport in the development of organic transistor memories.

  18. Optimization of pentacene double floating gate memories based on charge injection regulated by SAM functionalization

    Science.gov (United States)

    Li, S.; Guérin, D.; Lenfant, S.; Lmimouni, K.

    2018-02-01

    Pentacene based double nano-floating gate memories (NFGM) by using gold nanoparticles (Au NPs) and reduced graphene oxide (rGO) sheets as charge trapping layers are prepared and demonstrated. Particularly, the NFGM chemically treated by 2,3,4,5,6-pentafluorobenzenethiol (PFBT) self-assembled monolayers (SAM) exhibits excellent memory performances, including high mobility of 0.23 cm2V-1s-1, the large memory window of 51 V, and the stable retention property more than 108 s. Comparing the performances of NFGM without treating with PFBT SAM, the improving performances of the memory devices by SAM modification are explained by the increase of charge injection, which could be further investigated by XPS and UPS. In particular, the results highlight the utility of SAM modulations and controlling of charge transport in the development of organic transistor memories.

  19. Hydroxy double salts loaded with bioactive ions: Synthesis, intercalation mechanisms, and functional performance

    International Nuclear Information System (INIS)

    Kaassis, Abdessamad Y.A.; Xu, Si-Min; Guan, Shanyue; Evans, David G.; Wei, Min; Williams, Gareth R.

    2016-01-01

    The intercalation of the anions of diclofenac (Dic), naproxen (Nap), and valproic acid (Val) into three hydroxy double salts (HDSs) has been explored in this work. Experiments were performed with [Co 1.2 Zn 3.8 (OH) 8 ](NO 3 ) 2 ·2H 2 O (CoZn-NO 3 ), [Ni 2 Zn 3 (OH) 8 ](NO 3 ) 2 ·2H 2 O (NiZn-NO 3 ) and [Zn 5 (OH) 8 ](NO 3 ) 2 ·2H 2 O (Zn-NO 3 ). It proved possible to intercalate diclofenac and naproxen into all three HDSs. In contrast, Val could be intercalated into CoZn-NO 3 but when it was reacted with Zn-NO 3 the HDS structure was destroyed, and the product comprised ZnO. Successful intercalation was verified by X-ray diffraction, IR spectroscopy, and elemental microanalysis. Molecular dynamics simulations showed the Dic and Nap ions to arrange themselves in an “X” shape in the interlayer space, forming a bilayer. Val was found to adopt a position with its aliphatic groups parallel to the HDS layer, again in a bilayer. In situ time resolved X-ray diffraction experiments revealed that intercalation of Dic and Nap into CoZn-NO 3 and Zn-NO 3 is mechanistically complex, with a number of intermediate phases observed. In contrast, the intercalation of all three guests into NiZn-NO 3 and of Val into CoZn-NO 3 are simple one step reactions proceeding directly from the starting material to the product. The HDS-drug composites were found to have sustained release profiles. - Graphical abstract: Seven new drug intercalates of hydroxy double salts (HDSs) have been prepared and characterised. The intercalation mechanisms have been explored, and the drug release properties of the HDS/drug composites quantified. Display Omitted

  20. [Objective assessment of the functional impact of dry eye severity on the quality of vision by double-pass aberrometry].

    Science.gov (United States)

    Habay, T; Majzoub, S; Perrault, O; Rousseau, C; Pisella, P J

    2014-03-01

    To assess the functional impact of the severity of dry eye on the quality of vision by measuring an Objective Scatter Index (OSI) using double pass aberrometry. Twenty-eight patients (56 eyes) with dry eye syndromes of varying severity participated in this study. A double-pass aberrometer was used to measure the dynamic changes in the OSI for 20 seconds. The mean and standard deviations of the OSI and the number of blinks occurring during the examination were compared as a function of the clinical severity of dry eye disease. The mean OSI increased with the severity of dry eye syndrome with a significant difference for stages 3 (P0.8) or visual acuity (P>0.2). Standard deviation of the OSI also increased with the severity of dry eye disease, with a significant difference for stages 3 (P0.2). The values of the OSI standard deviation represented the dynamic nature of aberrometric changes related to the instability of the tear film. Quality of vision of patients deteriorated in relation to the severity of their dry eye. The analysis of OSI standard deviation appears to be an objective way to assess the intensity of subjective visual disturbances reported by patients with dry eye syndrome. It also provides a new tool to assess the severity of damage to the ocular surface. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  1. On the growth estimates of entire functions of double complex variables

    Directory of Open Access Journals (Sweden)

    Sanjib Datta

    2017-08-01

    Full Text Available Recently Datta et al. (2016 introduced the idea of relative type and relative weak type of entire functions of two complex variables with respect to another entire function of two complex variables and prove some related growth properties of it. In this paper, further we study some growth properties of entire functions of two complex variables on the basis of their relative types and relative weak types as introduced by Datta et al (2016.

  2. First functional polymorphism in CFTR promoter that results in decreased transcriptional activity and Sp1/USF binding

    International Nuclear Information System (INIS)

    Taulan, M.; Lopez, E.; Guittard, C.; Rene, C.; Baux, D.; Altieri, J.P.; DesGeorges, M.; Claustres, M.; Romey, M.C.

    2007-01-01

    Growing evidences show that functionally relevant polymorphisms in various promoters alter both transcriptional activity and affinities of existing protein-DNA interactions, and thus influence disease progression in humans. We previously reported the -94G>T CFTR promoter variant in a female CF patient in whom any known disease-causing mutation has been detected. To investigate whether the -94G>T could be a regulatory variant, we have proceeded to in silico analyses and functional studies including EMSA and reporter gene assays. Our data indicate that the promoter variant decreases basal CFTR transcriptional activity in different epithelial cells and alters binding affinities of both Sp1 and USF nuclear proteins to the CFTR promoter. The present report provides evidence for the first functional polymorphism that negatively affects the CFTR transcriptional activity and demonstrates a cooperative role of Sp1 and USF transcription factors in transactivation of the CFTR gene promoter

  3. Targeting artificial transcription factors to the utrophin A promoter: effects on dystrophic pathology and muscle function.

    Science.gov (United States)

    Lu, Yifan; Tian, Chai; Danialou, Gawiyou; Gilbert, Rénald; Petrof, Basil J; Karpati, George; Nalbantoglu, Josephine

    2008-12-12

    Duchenne muscular dystrophy is caused by a genetic defect in the dystrophin gene. The absence of dystrophin results in muscle fiber necrosis and regeneration, leading to progressive muscle fiber loss. Utrophin is a close analogue of dystrophin. A substantial, ectopic expression of utrophin in the extrasynaptic sarcolemma of dystrophin-deficient muscle fibers can prevent deleterious effects of dystrophin deficiency. An alternative approach for the extrasynaptic up-regulation of utrophin involves the augmentation of utrophin transcription via the endogenous utrophin A promoter using custom-designed transcriptional activator proteins with zinc finger (ZFP) motifs. We tested a panel of custom-designed ZFP for their ability to activate the utrophin A promoter. Expression of one such ZFP efficiently increased, in a time-dependent manner, utrophin transcript and protein levels both in vitro and in vivo. In dystrophic mouse (mdx) muscles, administration of adenoviral vectors expressing this ZFP led to significant enhancement of muscle function with decreased necrosis, restoration of the dystrophin-associated proteins, and improved resistance to eccentric contractions. These studies provide evidence that specifically designed ZFPs can act as strong transcriptional activators of the utrophin A promoter. These may thus serve as attractive therapeutic agents for dystrophin deficiency states such as Duchenne muscular dystrophy.

  4. FoxO3A promotes metabolic adaptation to hypoxia by antagonizing Myc function

    DEFF Research Database (Denmark)

    Jensen, Kim Steen; Binderup, Tina; Jensen, Klaus Thorleif

    2011-01-01

    Exposure of metazoan organisms to hypoxia engages a metabolic switch orchestrated by the hypoxia-inducible factor 1 (HIF-1). HIF-1 mediates induction of glycolysis and active repression of mitochondrial respiration that reduces oxygen consumption and inhibits the production of potentially harmful...... tumour tissue in vivo and that FoxO3A short-hairpin RNA (shRNA)-expressing xenograft tumours are decreased in size and metabolically changed. Our findings define a novel mechanism by which FoxO3A promotes metabolic adaptation and stress resistance in hypoxia....... reactive oxygen species (ROS). Here, we show that FoxO3A is activated in hypoxia downstream of HIF-1 and mediates the hypoxic repression of a set of nuclear-encoded mitochondrial genes. FoxO3A is required for hypoxic suppression of mitochondrial mass, oxygen consumption, and ROS production and promotes...... cell survival in hypoxia. FoxO3A is recruited to the promoters of nuclear-encoded mitochondrial genes where it directly antagonizes c-Myc function via a mechanism that does not require binding to the consensus FoxO recognition element. Furthermore, we show that FoxO3A is activated in human hypoxic...

  5. A Novel Growth-Promoting Pathway Formed by GDNF-Overexpressing Schwann Cells Promotes Propriospinal Axonal Regeneration, Synapse formation, and Partial Recovery of Function after Spinal Cord Injury

    Science.gov (United States)

    Deng, Lingxiao; Deng, Ping; Ruan, Yiwen; Xu, Zao Cheng; Liu, Naikui; Wen, Xuejun; Smith, George M.; Xu, Xiao-Ming

    2013-01-01

    Descending propriospinal neurons (DPSN) are known to establish functional relays for supraspinal signals, and they display a greater growth response after injury than do the long projecting axons. However, their regenerative response is still deficient due to their failure to depart from growth supportive cellular transplants back into the host spinal cord, which contains numerous impediments to axon growth. Here we report the construction of a continuous growth-promoting pathway in adult rats, formed by grafted Schwann cells (SCs) overexpressing glial cell line-derived neurotrophic factor (GDNF). We demonstrate that such a growth-promoting pathway, extending from the axonal cut ends to the site of innervation in the distal spinal cord, promoted regeneration of DPSN axons through and beyond the lesion gap of a spinal cord hemisection. Within the distal host spinal cord, regenerated DPSN axons formed synapses with host neurons leading to the restoration of action potentials and partial recovery of function. PMID:23536080

  6. CRA-1 uncovers a double-strand break-dependent pathway promoting the assembly of central region proteins on chromosome axes during C. elegans meiosis.

    Science.gov (United States)

    Smolikov, Sarit; Schild-Prüfert, Kristina; Colaiácovo, Mónica P

    2008-06-06

    The synaptonemal complex (SC), a tripartite proteinaceous structure that forms between homologous chromosomes during meiosis, is crucial for faithful chromosome segregation. Here we identify CRA-1, a novel and conserved protein that is required for the assembly of the central region of the SC during C. elegans meiosis. In the absence of CRA-1, central region components fail to extensively localize onto chromosomes at early prophase and instead mostly surround the chromatin at this stage. Later in prophase, central region proteins polymerize along chromosome axes, but for the most part fail to connect the axes of paired homologous chromosomes. This defect results in an inability to stabilize homologous pairing interactions, altered double-strand break (DSB) repair progression, and a lack of chiasmata. Surprisingly, DSB formation and repair are required to promote the polymerization of the central region components along meiotic chromosome axes in cra-1 mutants. In the absence of both CRA-1 and any one of the C. elegans homologs of SPO11, MRE11, RAD51, or MSH5, the polymerization observed along chromosome axes is perturbed, resulting in the formation of aggregates of the SC central region proteins. While radiation-induced DSBs rescue this polymerization in cra-1; spo-11 mutants, they fail to do so in cra-1; mre-11, cra-1; rad-51, and cra-1; msh-5 mutants. Taken together, our studies place CRA-1 as a key component in promoting the assembly of a tripartite SC structure. Moreover, they reveal a scenario in which DSB formation and repair can drive the polymerization of SC components along chromosome axes in C. elegans.

  7. Self-assembly and stability of double rosette nanostructures with biological functionalities

    NARCIS (Netherlands)

    ten Cate, M.G.J.; Omerovic, Merdan; Oshovsky, G.; Crego Calama, Mercedes; Reinhoudt, David

    2005-01-01

    The syntheses of calix[4]arene dimelamines that are functionalized with alkyl, aminoalkyl, ureido, pyridyl, carbohydrate, amino acid and peptide functionalities, and their self-assembly with barbituric acid or cyanuric acid derivatives into well-defined hydrogen-bonded nanostructures are described.

  8. Differential Relationships between RAN Performance, Behaviour Ratings, and Executive Function Measures: Searching for a Double Dissociation

    Science.gov (United States)

    Stringer, Ronald W.; Toplak, Maggie E.; Stanovich, Keith E.

    2004-01-01

    In this study, we investigated the relationships between rapid naming of letters, digits and colours, and reading ability and executive function. We gave fifty-six grade three and four children rapid automatised naming tasks using letters and digits as stimuli, executive function measures including the Stroop task, a working memory task and the…

  9. Promoter hypermethylation of KLF4 inactivates its tumor suppressor function in cervical carcinogenesis.

    Directory of Open Access Journals (Sweden)

    Wen-Ting Yang

    Full Text Available OBJECTIVE: The KLF4 gene has been shown to be inactivated in cervical carcinogenesis as a tumor suppressor. However, the mechanism of KLF4 silencing in cervical carcinomas has not yet been identified. DNA methylation plays a key role in stable suppression of gene expression. METHODS: The methylation status of the KLF4 promoter CpG islands was analyzed by bisulfite sequencing (BSQ in tissues of normal cervix and cervical cancer. KLF4 gene expression was detected by RT-PCR, immunohistochemistry and western blot. KLF4 promoter methylation in cervical cancer cell line was determined by BSQ and methylation-specific polymerase chain reaction (MS-PCR. Cell proliferation ability was detected by cell growth curve and MTT assay. RESULTS: The methylated allele was found in 41.90% of 24 cervical cancer tissues but only in 11.11% of 11 normal cervix tissues (P<0.005. KLF4 mRNA levels were significantly reduced in cervical cancer tissues compared with normal cervix tissues (P<0.01 and KLF4 mRNA expression showed a significant negative correlation with the promoter hypermethylation (r = -0.486, P = 0.003. Cervical cancer cell lines also showed a significant negative correlation between KLF4 expression and hypermethylation. After treatment with the demethylating agent 5-Azacytidine (5-Aza, the expression of KLF4 in the cervical cancer cell lines at both mRNA and protein levels was drastically increased, the cell proliferation ability was inhibited and the chemosensitivity for cisplatin was significantly increased. CONCLUSION: KLF4 gene is inactivated by methylation-induced silencing mechanisms in a large subset of cervical carcinomas and KLF4 promoter hypermethylation inactivates the gene's function as a tumor suppressor in cervical carcinogenesis.

  10. Identifying functional transcription factor binding sites in yeast by considering their positional preference in the promoters.

    Directory of Open Access Journals (Sweden)

    Fu-Jou Lai

    Full Text Available Transcription factor binding site (TFBS identification plays an important role in deciphering gene regulatory codes. With comprehensive knowledge of TFBSs, one can understand molecular mechanisms of gene regulation. In the recent decades, various computational approaches have been proposed to predict TFBSs in the genome. The TFBS dataset of a TF generated by each algorithm is a ranked list of predicted TFBSs of that TF, where top ranked TFBSs are statistically significant ones. However, whether these statistically significant TFBSs are functional (i.e. biologically relevant is still unknown. Here we develop a post-processor, called the functional propensity calculator (FPC, to assign a functional propensity to each TFBS in the existing computationally predicted TFBS datasets. It is known that functional TFBSs reveal strong positional preference towards the transcriptional start site (TSS. This motivates us to take TFBS position relative to the TSS as the key idea in building our FPC. Based on our calculated functional propensities, the TFBSs of a TF in the original TFBS dataset could be reordered, where top ranked TFBSs are now the ones with high functional propensities. To validate the biological significance of our results, we perform three published statistical tests to assess the enrichment of Gene Ontology (GO terms, the enrichment of physical protein-protein interactions, and the tendency of being co-expressed. The top ranked TFBSs in our reordered TFBS dataset outperform the top ranked TFBSs in the original TFBS dataset, justifying the effectiveness of our post-processor in extracting functional TFBSs from the original TFBS dataset. More importantly, assigning functional propensities to putative TFBSs enables biologists to easily identify which TFBSs in the promoter of interest are likely to be biologically relevant and are good candidates to do further detailed experimental investigation. The FPC is implemented as a web tool at http://santiago.ee.ncku.edu.tw/FPC/.

  11. Promoting a functional macroinvertebrate approach in the biomonitoring of Italian lotic systems

    Directory of Open Access Journals (Sweden)

    Richard W. Merritt

    2016-06-01

    Full Text Available Over fifty years of research on freshwater macroinvertebrates has been driven largely by the state of the taxonomy of these organisms. Significant advances have been and continue to be made in developing ever more refined keys to macroinvertebrate groups. When advances in macroinvertebrate ecological research are restricted by the level of detail in identifications, then analysis by function is a viable alternative. The focus on function, namely adaptations of macroinvertebrates to habitats and the utilization of food resources, has facilitated ecological evaluation of freshwater ecosystems. This classification is based not on what insects eat, but how they obtain their food. These categories are called 'functional feeding groups', as the name implies, denoting their functional role when describing how and where they feed. This is the basis for the functional feeding group (FFG method that was initially developed in the early 1960s. Taxonomy is applied only to the level of detail that allows assignment to one of five functional feeding group categories: detrital shredders, scrapers, filtering collectors, gatherers, and predators. The aim of this short communication, originating from the presentation of R.W. Merritt at the Biomonitoring Symposium in Rome, 2015, is to promote the use of a functional approach in biomonitoring, especially in Italian and European lotic systems. Here, we present two case studies and we discuss the advantages of the method, especially considering the great availability of quantitative data on macroinvertebrates after the implementation of the WFD 2000/60. We are confident that the increase of functional assessment of ecosystem attributes could have important and direct repercussions in the understanding and management of running waters.

  12. l-Theanine as a Functional Food Additive: Its Role in Disease Prevention and Health Promotion

    Directory of Open Access Journals (Sweden)

    Jackson Williams

    2016-05-01

    Full Text Available Tea has been consumed for thousands of years and is an integral part of people’s daily routine, as an everyday drink and a therapeutic aid for health promotion. Consumption of tea has been linked to a sense of relaxation commonly associated with the content of the non-proteinogenic amino acid theanine, which is found within the tea leaves. The aim of this review article is to outline the current methods for synthesis, extraction and purification of theanine, as well as to examine its potential benefits related to human health. These include improvements in cognitive and immune function, cancer prevention, reduced cardiovascular risk and its potential usefulness as a functional food product.

  13. Functional interplay between Mediator and TFIIB in preinitiation complex assembly in relation to promoter architecture.

    Science.gov (United States)

    Eychenne, Thomas; Novikova, Elizaveta; Barrault, Marie-Bénédicte; Alibert, Olivier; Boschiero, Claire; Peixeiro, Nuno; Cornu, David; Redeker, Virginie; Kuras, Laurent; Nicolas, Pierre; Werner, Michel; Soutourina, Julie

    2016-09-15

    Mediator is a large coregulator complex conserved from yeast to humans and involved in many human diseases, including cancers. Together with general transcription factors, it stimulates preinitiation complex (PIC) formation and activates RNA polymerase II (Pol II) transcription. In this study, we analyzed how Mediator acts in PIC assembly using in vivo, in vitro, and in silico approaches. We revealed an essential function of the Mediator middle module exerted through its Med10 subunit, implicating a key interaction between Mediator and TFIIB. We showed that this Mediator-TFIIB link has a global role on PIC assembly genome-wide. Moreover, the amplitude of Mediator's effect on PIC formation is gene-dependent and is related to the promoter architecture in terms of TATA elements, nucleosome occupancy, and dynamics. This study thus provides mechanistic insights into the coordinated function of Mediator and TFIIB in PIC assembly in different chromatin contexts. © 2016 Eychenne et al.; Published by Cold Spring Harbor Laboratory Press.

  14. Visualizing the complex functions and mechanisms of the anaphase promoting complex/cyclosome (APC/C)

    Science.gov (United States)

    Alfieri, Claudio; Zhang, Suyang

    2017-01-01

    The anaphase promoting complex or cyclosome (APC/C) is a large multi-subunit E3 ubiquitin ligase that orchestrates cell cycle progression by mediating the degradation of important cell cycle regulators. During the two decades since its discovery, much has been learnt concerning its role in recognizing and ubiquitinating specific proteins in a cell-cycle-dependent manner, the mechanisms governing substrate specificity, the catalytic process of assembling polyubiquitin chains on its target proteins, and its regulation by phosphorylation and the spindle assembly checkpoint. The past few years have witnessed significant progress in understanding the quantitative mechanisms underlying these varied APC/C functions. This review integrates the overall functions and properties of the APC/C with mechanistic insights gained from recent cryo-electron microscopy (cryo-EM) studies of reconstituted human APC/C complexes. PMID:29167309

  15. Hydroxy double salts loaded with bioactive ions: Synthesis, intercalation mechanisms, and functional performance

    Energy Technology Data Exchange (ETDEWEB)

    Kaassis, Abdessamad Y.A. [UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX (United Kingdom); Xu, Si-Min; Guan, Shanyue; Evans, David G. [State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing 100029 (China); Wei, Min, E-mail: weimin@mail.buct.edu.cn [State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing 100029 (China); Williams, Gareth R., E-mail: g.williams@ucl.ac.uk [UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX (United Kingdom)

    2016-06-15

    The intercalation of the anions of diclofenac (Dic), naproxen (Nap), and valproic acid (Val) into three hydroxy double salts (HDSs) has been explored in this work. Experiments were performed with [Co{sub 1.2}Zn{sub 3.8}(OH){sub 8}](NO{sub 3}){sub 2}·2H{sub 2}O (CoZn-NO{sub 3}), [Ni{sub 2}Zn{sub 3}(OH){sub 8}](NO{sub 3}){sub 2}·2H{sub 2}O (NiZn-NO{sub 3}) and [Zn{sub 5}(OH){sub 8}](NO{sub 3}){sub 2}·2H{sub 2}O (Zn-NO{sub 3}). It proved possible to intercalate diclofenac and naproxen into all three HDSs. In contrast, Val could be intercalated into CoZn-NO{sub 3} but when it was reacted with Zn-NO{sub 3} the HDS structure was destroyed, and the product comprised ZnO. Successful intercalation was verified by X-ray diffraction, IR spectroscopy, and elemental microanalysis. Molecular dynamics simulations showed the Dic and Nap ions to arrange themselves in an “X” shape in the interlayer space, forming a bilayer. Val was found to adopt a position with its aliphatic groups parallel to the HDS layer, again in a bilayer. In situ time resolved X-ray diffraction experiments revealed that intercalation of Dic and Nap into CoZn-NO{sub 3} and Zn-NO{sub 3} is mechanistically complex, with a number of intermediate phases observed. In contrast, the intercalation of all three guests into NiZn-NO{sub 3} and of Val into CoZn-NO{sub 3} are simple one step reactions proceeding directly from the starting material to the product. The HDS-drug composites were found to have sustained release profiles. - Graphical abstract: Seven new drug intercalates of hydroxy double salts (HDSs) have been prepared and characterised. The intercalation mechanisms have been explored, and the drug release properties of the HDS/drug composites quantified. Display Omitted.

  16. GADD34 Function in Protein Trafficking Promotes Adaptation to Hyperosmotic Stress in Human Corneal Cells

    Directory of Open Access Journals (Sweden)

    Dawid Krokowski

    2017-12-01

    Full Text Available Summary: GADD34, a stress-induced regulatory subunit of the phosphatase PP1, is known to function in hyperosmotic stress through its well-known role in the integrated stress response (ISR pathway. Adaptation to hyperosmotic stress is important for the health of corneal epithelial cells exposed to changes in extracellular osmolarity, with maladaptation leading to dry eye syndrome. This adaptation includes induction of SNAT2, an endoplasmic reticulum (ER-Golgi-processed protein, which helps to reverse the stress-induced loss of cell volume and promote homeostasis through amino acid uptake. Here, we show that GADD34 promotes the processing of proteins synthesized on the ER during hyperosmotic stress independent of its action in the ISR. We show that GADD34/PP1 phosphatase activity reverses hyperosmotic-stress-induced Golgi fragmentation and is important for cis- to trans-Golgi trafficking of SNAT2, thereby promoting SNAT2 plasma membrane localization and function. These results suggest that GADD34 is a protective molecule for ocular diseases such as dry eye syndrome. : Here, Krokowski et al. show that GADD34/PP1 protects the microtubule network, prevents Golgi fragmentation, and preserves protein trafficking independent of its action in the integrated stress response (ISR. In osmoadaptation, GADD34 facilitates trans-Golgi-mediated processing of the endoplasmic reticulum (ER-synthesized amino acid transporter SNAT2, which in turn increases amino acid uptake. Keywords: SNAT2, GADD34, hyperosmotic stress, amino acid transport, Golgi fragmentation, ISR

  17. Motor cortex electrical stimulation augments sprouting of the corticospinal tract and promotes recovery of motor function

    Science.gov (United States)

    Carmel, Jason B.; Martin, John H.

    2014-01-01

    The corticospinal system—with its direct spinal pathway, the corticospinal tract (CST) – is the primary system for controlling voluntary movement. Our approach to CST repair after injury in mature animals was informed by our finding that activity drives establishment of connections with spinal cord circuits during postnatal development. After incomplete injury in maturity, spared CST circuits sprout, and partially restore lost function. Our approach harnesses activity to augment this injury-dependent CST sprouting and to promote function. Lesion of the medullary pyramid unilaterally eliminates all CST axons from one hemisphere and allows examination of CST sprouting from the unaffected hemisphere. We discovered that 10 days of electrical stimulation of either the spared CST or motor cortex induces CST axon sprouting that partially reconstructs the lost CST. Stimulation also leads to sprouting of the cortical projection to the magnocellular red nucleus, where the rubrospinal tract originates. Coordinated outgrowth of the CST and cortical projections to the red nucleus could support partial re-establishment of motor systems connections to the denervated spinal motor circuits. Stimulation restores skilled motor function in our animal model. Lesioned animals have a persistent forelimb deficit contralateral to pyramidotomy in the horizontal ladder task. Rats that received motor cortex stimulation either after acute or chronic injury showed a significant functional improvement that brought error rate to pre-lesion control levels. Reversible inactivation of the stimulated motor cortex reinstated the impairment demonstrating the importance of the stimulated system to recovery. Motor cortex electrical stimulation is an effective approach to promote spouting of spared CST axons. By optimizing activity-dependent sprouting in animals, we could have an approach that can be translated to the human for evaluation with minimal delay. PMID:24994971

  18. Coniferyl aldehyde attenuates radiation enteropathy by inhibiting cell death and promoting endothelial cell function.

    Science.gov (United States)

    Jeong, Ye-Ji; Jung, Myung Gu; Son, Yeonghoon; Jang, Jun-Ho; Lee, Yoon-Jin; Kim, Sung-Ho; Ko, Young-Gyo; Lee, Yun-Sil; Lee, Hae-June

    2015-01-01

    Radiation enteropathy is a common complication in cancer patients. The aim of this study was to investigate whether radiation-induced intestinal injury could be alleviated by coniferyl aldehyde (CA), an HSF1-inducing agent that increases cellular HSP70 expression. We systemically administered CA to mice with radiation enteropathy following abdominal irradiation (IR) to demonstrate the protective effects of CA against radiation-induced gastrointestinal injury. CA clearly alleviated acute radiation-induced intestinal damage, as reflected by the histopathological data and it also attenuated sub-acute enteritis. CA prevented intestinal crypt cell death and protected the microvasculature in the lamina propria during the acute and sub-acute phases of damage. CA induced HSF1 and HSP70 expression in both intestinal epithelial cells and endothelial cells in vitro. Additionally, CA protected against not only the apoptotic cell death of both endothelial and epithelial cells but also the loss of endothelial cell function following IR, indicating that CA has beneficial effects on the intestine. Our results provide novel insight into the effects of CA and suggest its role as a therapeutic candidate for radiation-induced enteropathy due to its ability to promote rapid re-proliferation of the intestinal epithelium by the synergic effects of the inhibition of cell death and the promotion of endothelial cell function.

  19. The endogenous proteoglycan-degrading enzyme ADAMTS-4 promotes functional recovery after spinal cord injury

    Directory of Open Access Journals (Sweden)

    Tauchi Ryoji

    2012-03-01

    Full Text Available Abstract Background Chondroitin sulfate proteoglycans are major inhibitory molecules for neural plasticity under both physiological and pathological conditions. The chondroitin sulfate degrading enzyme chondroitinase ABC promotes functional recovery after spinal cord injury, and restores experience-dependent plasticity, such as ocular dominance plasticity and fear erasure plasticity, in adult rodents. These data suggest that the sugar chain in a proteoglycan moiety is essential for the inhibitory activity of proteoglycans. However, the significance of the core protein has not been studied extensively. Furthermore, considering that chondroitinase ABC is derived from bacteria, a mammalian endogenous enzyme which can inactivate the proteoglycans' activity is desirable for clinical use. Methods The degradation activity of ADAMTS-4 was estimated for the core proteins of chondroitin sulfate proteoglycans, that is, brevican, neurocan and phosphacan. To evaluate the biological significance of ADMATS-4 activity, an in vitro neurite growth assay and an in vivo neuronal injury model, spinal cord contusion injury, were employed. Results ADAMTS-4 digested proteoglycans, and reversed their inhibition of neurite outgrowth. Local administration of ADAMTS-4 significantly promoted motor function recovery after spinal cord injury. Supporting these findings, the ADAMTS-4-treated spinal cord exhibited enhanced axonal regeneration/sprouting after spinal cord injury. Conclusions Our data suggest that the core protein in a proteoglycan moiety is also important for the inhibition of neural plasticity, and provides a potentially safer tool for the treatment of neuronal injuries.

  20. Proton Conductivity of Proton Exchange Membrane Synergistically Promoted by Different Functionalized Metal-Organic Frameworks.

    Science.gov (United States)

    Rao, Zhuang; Tang, Beibei; Wu, Peiyi

    2017-07-12

    In this study, two functionalized metal-organic frameworks (MOFs), UiO-66-SO 3 H and UiO-66-NH 2 , were synthesized. Then, different composite proton exchange membranes (PEMs) were prepared by single doping and codoping of these two MOFs, respectively. It was found that codoping of these two MOFs with suitable sizes was more conducive to the proton conductivity enhancement of the composite PEM. A synergistic effect between these two MOFs led to the the formation of more consecutive hydration channels in the composite PEM. It further greatly promoted the proton conductivity of the composite PEM. The proton conductivity of the codoped PEM reached up to 0.256 S/cm under 90 °C, 95% RH, which was ∼1.17 times higher than that of the recast Nafion (0.118 S/cm). Besides, the methanol permeability of the codoped PEM was prominently decreased owing to the methanol trapping effect of the pores of these two MOFs. Meanwhile, the high water and thermal stabilities of these two MOFs were beneficial to the high proton conductivity stability of the codoped PEM under high humidity and high temperature. The proton conductivity of the codoped PEM was almost unchanged throughout 3000 min of testing under 90 °C, 95% RH. This work provides a valuable reference for designing different functionalized MOFs to synergistically promote the proton conductivities of PEMs.

  1. The Double-Edged Sword: Conserved Functions of Extracellular Hsp90 in Wound Healing and Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hance, Michael W.; Nolan, Krystal D.; Isaacs, Jennifer S., E-mail: isaacsj@musc.edu [Department of Cell and Molecular Pharmacology, Medical University of South Carolina, Hollings Cancer Center, Charleston, SC 29412 (United States)

    2014-05-06

    Heat shock proteins (Hsps) represent a diverse group of chaperones that play a vital role in the protection of cells against numerous environmental stresses. Although our understanding of chaperone biology has deepened over the last decade, the “atypical” extracellular functions of Hsps have remained somewhat enigmatic and comparatively understudied. The heat shock protein 90 (Hsp90) chaperone is a prototypic model for an Hsp family member exhibiting a duality of intracellular and extracellular functions. Intracellular Hsp90 is best known as a master regulator of protein folding. Cancers are particularly adept at exploiting this function of Hsp90, providing the impetus for the robust clinical development of small molecule Hsp90 inhibitors. However, in addition to its maintenance of protein homeostasis, Hsp90 has also been identified as an extracellular protein. Although early reports ascribed immunoregulatory functions to extracellular Hsp90 (eHsp90), recent studies have illuminated expanded functions for eHsp90 in wound healing and cancer. While the intended physiological role of eHsp90 remains enigmatic, its evolutionarily conserved functions in wound healing are easily co-opted during malignancy, a pathology sharing many properties of wounded tissue. This review will highlight the emerging functions of eHsp90 and shed light on its seemingly dichotomous roles as a benevolent facilitator of wound healing and as a sinister effector of tumor progression.

  2. Quantitative evaluation of myocardial perfusion and heart function using a non-invasive double isotope technique

    Energy Technology Data Exchange (ETDEWEB)

    Knapp, W H; Doll, J; Georgi, P [Deutsches Krebsforschungszentrum, Heidelberg (Germany, F.R.). Inst. fuer Nuklearmedizin; Tillmanns, H [Heidelberg Univ. (Germany, F.R.). Innere Medizin 3

    1976-11-01

    This paper describes a non-invasive double nuclide technique for the simultaneous measurement of minimal cardiac transit times (MTT) and regional 'myocardial appearance times' (MAT) using gamma camera and computer. MAT is defined as the time lag between the appearance of an indicator with myocardial affinity in the aortic root and its extraction in the myocardial cells. The extraction can be identified as an increase of the ratio between the count rates of the two nuclides e.g. /sup 201/Tl-chloride and sup(113m)In DTPA. The clinical evaluation of this method allows the following conclusions: 1) MAT, determined over several circumscript myocardial regions permits the qualitative diagnosis of a coronary artery disease with high confidence. 2) Indices of nutritive myocardial blood flow (INF), derived by MAT using several representative areas of myocardium, show a definite correlation to the degree of coronary artery disease. In addition to the localization of infarction and the determination of infarct size, the technique described promises a quantitative evaluation of the regional myocardial perfusion. Simultaneously measured MTT help to assess segmental cardiac performance.

  3. Functional dissection of a napin gene promoter: identification of promoter elements required for embryo and endosperm-specific transcription.

    Science.gov (United States)

    Ellerström, M; Stålberg, K; Ezcurra, I; Rask, L

    1996-12-01

    The promoter region (-309 to +44) of the Brassica napus storage protein gene napA was studied in transgenic tobacco by successive 5' as well as internal deletions fused to the reporter gene GUS (beta-glucuronidase). The expression in the two main tissues of the seed, the endosperm and the embryo, was shown to be differentially regulated. This tissue-specific regulation within the seed was found to affect the developmental expression during seed development. The region between -309 to -152, which has a large effect on quantitative expression, was shown to harbour four elements regulating embryo and one regulating endosperm expression. This region also displayed enhancer activity. Deletion of eight bp from position -152 to position -144 totally abolished the activity of the napA promoter. This deletion disrupted a cis element with similarity to an ABA-responsive element (ABRE) overlapping with an E-box, demonstrating its crucial importance for quantitative expression. An internal deletion of the region -133 to -120, resulted in increased activity in both leaves and endosperm and a decreased activity in the embryo. Within this region, a cis element similar to the (CA)n element, found in other storage protein promoters, was identified. This suggest that the (CA)n element is important for conferring seed specificity by serving both as an activator and a repressor element.

  4. Effect of Strong Acid Functional Groups on Electrode Rise Potential in Capacitive Mixing by Double Layer Expansion

    KAUST Repository

    Hatzell, Marta C.; Raju, Muralikrishna; Watson, Valerie J.; Stack, Andrew G.; van Duin, Adri C. T.; Logan, Bruce E.

    2014-01-01

    © 2014 American Chemical Society. The amount of salinity-gradient energy that can be obtained through capacitive mixing based on double layer expansion depends on the extent the electric double layer (EDL) is altered in a low salt concentration (LC) electrolyte (e.g., river water). We show that the electrode-rise potential, which is a measure of the EDL perturbation process, was significantly (P = 10-5) correlated to the concentration of strong acid surface functional groups using five types of activated carbon. Electrodes with the lowest concentration of strong acids (0.05 mmol g-1) had a positive rise potential of 59 ± 4 mV in the LC solution, whereas the carbon with the highest concentration (0.36 mmol g-1) had a negative rise potential (-31 ± 5 mV). Chemical oxidation of a carbon (YP50) using nitric acid decreased the electrode rise potential from 46 ± 2 mV (unaltered) to -6 ± 0.5 mV (oxidized), producing a whole cell potential (53 ± 1.7 mV) that was 4.4 times larger than that obtained with identical electrode materials (from 12 ± 1 mV). Changes in the EDL were linked to the behavior of specific ions in a LC solution using molecular dynamics and metadynamics simulations. The EDL expanded in the LC solution when a carbon surface (pristine graphene) lacked strong acid functional groups, producing a positive-rise potential at the electrode. In contrast, the EDL was compressed for an oxidized surface (graphene oxide), producing a negative-rise electrode potential. These results established the linkage between rise potentials and specific surface functional groups (strong acids) and demonstrated on a molecular scale changes in the EDL using oxidized or pristine carbons.

  5. Effect of Strong Acid Functional Groups on Electrode Rise Potential in Capacitive Mixing by Double Layer Expansion

    KAUST Repository

    Hatzell, Marta C.

    2014-12-02

    © 2014 American Chemical Society. The amount of salinity-gradient energy that can be obtained through capacitive mixing based on double layer expansion depends on the extent the electric double layer (EDL) is altered in a low salt concentration (LC) electrolyte (e.g., river water). We show that the electrode-rise potential, which is a measure of the EDL perturbation process, was significantly (P = 10-5) correlated to the concentration of strong acid surface functional groups using five types of activated carbon. Electrodes with the lowest concentration of strong acids (0.05 mmol g-1) had a positive rise potential of 59 ± 4 mV in the LC solution, whereas the carbon with the highest concentration (0.36 mmol g-1) had a negative rise potential (-31 ± 5 mV). Chemical oxidation of a carbon (YP50) using nitric acid decreased the electrode rise potential from 46 ± 2 mV (unaltered) to -6 ± 0.5 mV (oxidized), producing a whole cell potential (53 ± 1.7 mV) that was 4.4 times larger than that obtained with identical electrode materials (from 12 ± 1 mV). Changes in the EDL were linked to the behavior of specific ions in a LC solution using molecular dynamics and metadynamics simulations. The EDL expanded in the LC solution when a carbon surface (pristine graphene) lacked strong acid functional groups, producing a positive-rise potential at the electrode. In contrast, the EDL was compressed for an oxidized surface (graphene oxide), producing a negative-rise electrode potential. These results established the linkage between rise potentials and specific surface functional groups (strong acids) and demonstrated on a molecular scale changes in the EDL using oxidized or pristine carbons.

  6. Arthroscopic double row cuff repair with suture-bridging and autologous conditioned plasma injection: Functional and structural results.

    Science.gov (United States)

    Werthel, Jean-David; Pelissier, Alexandre; Massin, Philippe; Boyer, Patrick; Valenti, Philippe

    2014-10-01

    The double row cuff repair with suture bridging is commonly used for arthroscopic rotator cuff repair (RCR). Despite its biomechanical qualities, the rate of iterative tears with this technique is important. The aim of our study was to evaluate the effect of autologous conditioned plasma (ACP) on functional results and on the rate of iterative tears after RCR by suture bridging. A consecutive series of 65 patients who underwent arthroscopic double-row suture bridge (Speed-Bridge, Arthrex) primary cuff repair of symptomatic full-thickness supraspinatus tear (retraction 4 were considered as iterative tears. Mean follow-up was 19 months (+/-42) in the 2 groups. The mean quantity of ACP injected was 6ml. (+/-1.5) and no specific complication of the injection was found. Mean preoperative Constant-Murley scores were 41,2 (±7,7) and 38 (±11)in group B. Mean normalized Constant-Murley score increased from 41 points (±7) pre-operatively to 70 points (±8) post-operatively in group A and from 38 points (±11) to 73 points (±11) in group B. There were no significative differences between the two groups (P > 0.05). In group A, 31 repairs were Sugaya 1-3 (94%), vs. 30 in group B (93%), and 1 was type 4 in group A (5%) vs. 2 in group B (8%). In both groups, RCR with suture bridging gave successful functional outcomes, with a low rate of iterative tear. In this preliminary study, the adjuvant effect of ACP injections could not be showed on both functional and structural results. Longer follow-up is needed to evaluate potential differences.

  7. [Functional meat products; development and evaluation of their health-promoting properties].

    Science.gov (United States)

    Olmedilla-Alonso, Begoña; Jiménez-Colmenero, Francisco

    2014-06-01

    For a number of reasons, meat products are an exceptionally adequate means for introducing different bioactive compounds into the diet without modifying eating habits. In recent years, there has been a notable development of meat products designed as potentially functional foods. Within the framework of the functional food, this article provides a general view of the reasons that motivate and justify their formulation, with special emphasis on: a) aspects to be considered in their design in order to be able to make nutrition claims and statements concerning their health-promoting properties; b) the strategies employed to optimize the presence of functional ingredients, favoring the presence of beneficial bioactive compounds and limiting others with negative consequences for our health, and c) the procedures for demonstrating a relationship between the consumption of potentially functional meat products with beneficial effects on health and the way in which these studies are reflected in the literature. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  8. Hypoxia Enhances Immunosuppression by Inhibiting CD4+ Effector T Cell Function and Promoting Treg Activity

    Directory of Open Access Journals (Sweden)

    Astrid M. Westendorf

    2017-03-01

    Full Text Available Background/Aims: Hypoxia occurs in many pathological conditions, including inflammation and cancer. Within this context, hypoxia was shown to inhibit but also to promote T cell responses. Due to this controversial function, we aimed to explore whether an insufficient anti-tumour response during colitis-associated colon cancer could be ascribed to a hypoxic microenvironment. Methods: Colitis-associated colon cancer was induced in wildtype mice, and hypoxia as well as T cell immunity were analysed in the colonic tumour tissues. In addition, CD4+ effector T cells and regulatory T cells were cultured under normoxic and hypoxic conditions and examined regarding their phenotype and function. Results: We observed severe hypoxia in the colon of mice suffering from colitis-associated colon cancer that was accompanied by a reduced differentiation of CD4+ effector T cells and an enhanced number and suppressive activity of regulatory T cells. Complementary ex vivo and in vitro studies revealed that T cell stimulation under hypoxic conditions inhibited the differentiation, proliferation and IFN-γ production of TH1 cells and enhanced the suppressive capacity of regulatory T cells. Moreover, we identified an active role for HIF-1α in the modulation of CD4+ T cell functions under hypoxic conditions. Conclusion: Our data indicate that oxygen availability can function as a local modulator of CD4+ T cell responses and thus influences tumour immune surveillance in inflammation-associated colon cancer.

  9. Disruption of lysosome function promotes tumor growth and metastasis in Drosophila.

    Science.gov (United States)

    Chi, Congwu; Zhu, Huanhu; Han, Min; Zhuang, Yuan; Wu, Xiaohui; Xu, Tian

    2010-07-09

    Lysosome function is essential to many physiological processes. It has been suggested that deregulation of lysosome function could contribute to cancer. Through a genetic screen in Drosophila, we have discovered that mutations disrupting lysosomal degradation pathway components contribute to tumor development and progression. Loss-of-function mutations in the Class C vacuolar protein sorting (VPS) gene, deep orange (dor), dramatically promote tumor overgrowth and invasion of the Ras(V12) cells. Knocking down either of the two other components of the Class C VPS complex, carnation (car) and vps16A, also renders Ras(V12) cells capable for uncontrolled growth and metastatic behavior. Finally, chemical disruption of the lysosomal function by feeding animals with antimalarial drugs, chloroquine or monensin, leads to malignant tumor growth of the Ras(V12) cells. Taken together, our data provide evidence for a causative role of lysosome dysfunction in tumor growth and invasion and indicate that members of the Class C VPS complex behave as tumor suppressors.

  10. [Comparison of ocular modulation transfer function measurements by ray tracing wavefront technology and double-pass system].

    Science.gov (United States)

    Qiao, Liya; Cai, Xiaogu; Wan, Xiuhua; Guan, Zheng; Xiong, Ying; Lin, Zhong; Zhang, Ye; Tan, Jiaxuan; Wang, Ningli

    2015-01-01

    To compare the agreement of the ocular modulation transfer function (MTF) measured by double-pass system and ray tracing wavefront aberrometry, and to analyze the correlations of two MTFs with the visual acuity and contrast sensitivity function results. Comparative study. Subjects with no ocular diseases were consecutively enrolled in an epidemic study field located at the Dongyangzhuang Health Center, Yongnian County, Handan City, Hebei Province, China. After comprehensive ophthalmic examinations, the mean values of subtracted lower order aberration MTF at 5, 10, 15, 20, 25, and 30 cycle/degree(c/d) spatial frequencies were obtained with a double-pass system (optical quality analysis system II, OQAS II system) and a ray tracing wavefront aberrometer (iTrace visual function analyzer, iTrace system) in the 4.0 mm and 6.0 mm pupil after dilation, respectively. Paired-sample t test and Bland-Altman analysis were used to compare the difference and agreement of MTFs obtained with two instruments. Correlation analysis was preformed between two MTF measurement results and subjective visual quality including visual acuity and contrast sensitivity function. Two hundred and fifty-one healthy eyes of 163 subjects were enrolled, aged 30 to 60, mean (44.1 ± 9.7) years, including 139 eyes of 81 males and 112 eyes of 82 females. The mean value of MTF at 5, 10, 15, 20.25, 30 c/d obtained by iTrace in 4.0 mm pupil were 0.730 ± 0.138, 0.431 ± 0.159, 0.262 ± 0.120, 0.169 ± 0.078, 0.118 ± 0.053, 0.094 ± 0.043. The value obtained by OQASII were 0.347 ± 0.123, 0.162 ± 0.086, 0.072 ± 0.049, 0.042 ± 0.033, 0.026 ± 0.022, 0.017 ± 0.022, The result of iTrace were all significant higher than OQAS in both 4mm(t = 38.72, 28.03, 27.32, 27.59, 29.23, 28.96, P < 0.01) and 6.0 mm(t = 4.60, 3.19, 9.34, 13.41, 16.96, 20.24, P < 0.01)pupil diameter. The iTrace-OQAS II MTF difference was smaller in the 6.0 mm pupil. Bland-Altman analysis indicated that the agreement of two instruments was

  11. Hydroxy double salts loaded with bioactive ions: Synthesis, intercalation mechanisms, and functional performance

    Science.gov (United States)

    Y. A. Kaassis, Abdessamad; Xu, Si-Min; Guan, Shanyue; Evans, David G.; Wei, Min; Williams, Gareth R.

    2016-06-01

    The intercalation of the anions of diclofenac (Dic), naproxen (Nap), and valproic acid (Val) into three hydroxy double salts (HDSs) has been explored in this work. Experiments were performed with [Co1.2Zn3.8(OH)8](NO3)2·2H2O (CoZn-NO3), [Ni2Zn3(OH)8](NO3)2·2H2O (NiZn-NO3) and [Zn5(OH)8](NO3)2·2H2O (Zn-NO3). It proved possible to intercalate diclofenac and naproxen into all three HDSs. In contrast, Val could be intercalated into CoZn-NO3 but when it was reacted with Zn-NO3 the HDS structure was destroyed, and the product comprised ZnO. Successful intercalation was verified by X-ray diffraction, IR spectroscopy, and elemental microanalysis. Molecular dynamics simulations showed the Dic and Nap ions to arrange themselves in an "X" shape in the interlayer space, forming a bilayer. Val was found to adopt a position with its aliphatic groups parallel to the HDS layer, again in a bilayer. In situ time resolved X-ray diffraction experiments revealed that intercalation of Dic and Nap into CoZn-NO3 and Zn-NO3 is mechanistically complex, with a number of intermediate phases observed. In contrast, the intercalation of all three guests into NiZn-NO3 and of Val into CoZn-NO3 are simple one step reactions proceeding directly from the starting material to the product. The HDS-drug composites were found to have sustained release profiles.

  12. Identification and functional characterisation of the promoter of the calcium sensor gene CBL1 from the xerophyte Ammopiptanthus mongolicus

    Directory of Open Access Journals (Sweden)

    Yin Weilun

    2010-01-01

    Full Text Available Abstract Background CBL1 is a calcium sensor that regulates drought, cold and salt signals in Arabidopsis. Overexpression of CBL1 gene in Arabidopsis and in Ammopiptanthus mongolicus showed different tolerant activities. We are interested in understanding the molecular mechanism of the upstream region of the CBL1 gene of A. mongolicus (AmCBL1. We investigated and characterized the promoter of the AmCBL1 gene, for promoters play a very important role in regulating gene expression in eukaryotes. Results A 1683-bp 5' flanking region was isolated from A. mongolicus. The sequence was identified as AmCBL1 promoter. Analysis of the promoter sequence indicated a 690-bp intron and some basic cis-acting elements were related to various environmental stresses and plant hormones. To identify the functional region of the AmCBL1 promoter, five plant expression vectors fused with the GUS (β-glucuronidase gene, driven by series deleted fragments of AmCBL1 promoter at different lengths from -1659, -1414, -1048, -296 to -167 bp relative to the transcriptional start site were constructed and transformed into Nicotiana tabacum L. cv. 89. Functional properties of each promoter segment were examined by GUS staining and fluorescence quantitative analyses using at least three single-copy PCR-positive plants of transgenic tobacco, treated with various environmental stresses and plant hormones for different times. We demonstrated that the AmCBL1 promoter was a vascular-specific and multiple-stress-inducible promoter. Our results further imply that the promoter fragment B1S3 possessed sufficient essential cis-acting elements, accounting for vascular-specific and stress-induced expression patterns. It may also indicate that for response to some stresses certain cis-elements are required in tissues outside the region of the B1S3 construct. Conclusions To help resolve uncertainties about the upstream regulatory mechanism of the CBL1 gene in desert plants, we suggest that

  13. Chopped or Long Roughage: What Do Calves Prefer? Using Cross Point Analysis of Double Demand Functions

    DEFF Research Database (Denmark)

    Webb, Laura E.; Jensen, Margit Bak; Engel, Bas

    2014-01-01

    trained to work for roughage rewards from two simultaneously available panels. The cost (number of muzzle presses) required on the panels varied in each session (left panel/right panel): 7/35, 14/28, 21/21, 28/14, 35/7. Demand functions were estimated from the proportion of rewards achieved on one panel...

  14. The role of oleate-functionalized layered double hydroxide in the melt compounding of polypropylene nanocomposites

    Czech Academy of Sciences Publication Activity Database

    Donato, R. K.; Luza, L.; da Silva, R. F.; Moro, C. C.; Guzatto, R.; Samios, D.; Matějka, Libor; Dimzoski, Bojan; Amico, S. C.; Schrekker, H. S.

    2012-01-01

    Roč. 32, č. 8 (2012), s. 2396-2403 ISSN 0928-4931 Institutional research plan: CEZ:AV0Z40500505 Keywords : renewable feedstock functionalized nanofiller * polymer-matrix nanocomposite * melt compounding Subject RIV: CD - Macromolecular Chemistry Impact factor: 2.404, year: 2012

  15. Functionality of promoter microsatellites of arginine vasopressin receptor 1A (AVPR1A): implications for autism

    LENUS (Irish Health Repository)

    Tansey, Katherine E

    2011-03-31

    Abstract Background Arginine vasopressin (AVP) has been hypothesized to play a role in aetiology of autism based on a demonstrated involvement in the regulation of social behaviours. The arginine vasopressin receptor 1A gene (AVPR1A) is widely expressed in the brain and is considered to be a key receptor for regulation of social behaviour. Moreover, genetic variation at AVPR1A has been reported to be associated with autism. Evidence from non-human mammals implicates variation in the 5\\'-flanking region of AVPR1A in variable gene expression and social behaviour. Methods We examined four tagging single nucleotide polymorphisms (SNPs) (rs3803107, rs1042615, rs3741865, rs11174815) and three microsatellites (RS3, RS1 and AVR) at the AVPR1A gene for association in an autism cohort from Ireland. Two 5\\'-flanking region polymorphisms in the human AVPR1A, RS3 and RS1, were also tested for their effect on relative promoter activity. Results The short alleles of RS1 and the SNP rs11174815 show weak association with autism in the Irish population (P = 0.036 and P = 0.008, respectively). Both RS1 and RS3 showed differences in relative promoter activity by length. Shorter repeat alleles of RS1 and RS3 decreased relative promoter activity in the human neuroblastoma cell line SH-SY5Y. Conclusions These aligning results can be interpreted as a functional route for this association, namely that shorter alleles of RS1 lead to decreased AVPR1A transcription, which may proffer increased susceptibility to the autism phenotype.

  16. Electronic correlation without double counting via a combination of spin projected Hartree-Fock and density functional theories

    Energy Technology Data Exchange (ETDEWEB)

    Garza, Alejandro J.; Jiménez-Hoyos, Carlos A. [Department of Chemistry, Rice University, Houston, Texas 77251-1892 (United States); Scuseria, Gustavo E. [Department of Chemistry and Department of Physics and Astronomy, Rice University, Houston, Texas 77251-1892, USA and Chemistry Department, Faculty of Science, King Abdulaziz University, Jeddah 21589 (Saudi Arabia)

    2014-06-28

    Several schemes to avoid the double counting of correlations in methods that merge multireference wavefunctions with density functional theory (DFT) are studied and here adapted to a combination of spin-projected Hartree-Fock (SUHF) and DFT. The advantages and limitations of the new method, denoted SUHF+f{sub c}DFT, are explored through calculations on benchmark sets in which the accounting of correlations is challenging for pure SUHF or DFT. It is shown that SUHF+f{sub c}DFT can greatly improve the description of certain molecular properties (e.g., singlet-triplet energy gaps) which are not improved by simple addition of DFT dynamical correlation to SUHF. However, SUHF+f{sub c}DFT is also shown to have difficulties dissociating certain types of bonds and describing highly charged ions with static correlation. Possible improvements to the current SUHF+f{sub c}DFT scheme are discussed in light of these results.

  17. Time-dependent density functional theory for the charging kinetics of electric double layer containing room-temperature ionic liquids.

    Science.gov (United States)

    Lian, Cheng; Zhao, Shuangliang; Liu, Honglai; Wu, Jianzhong

    2016-11-28

    Understanding the charging kinetics of electric double layers is of fundamental importance for the design and development of novel electrochemical devices such as supercapacitors and field-effect transistors. In this work, we study the dynamic behavior of room-temperature ionic liquids using a classical time-dependent density functional theory that accounts for the molecular excluded volume effects, the electrostatic correlations, and the dispersion forces. While the conventional models predict a monotonic increase of the surface charge with time upon application of an electrode voltage, our results show that dispersion between ions results in a non-monotonic increase of the surface charge with the duration of charging. Furthermore, we investigate the effects of van der Waals attraction between electrode/ionic-liquid interactions on the charging processes.

  18. Randomised double blind placebo controlled trial on Lactobacillus reuteri DSM 17938: improvement in symptoms and bowel habit in functional constipation.

    Science.gov (United States)

    Riezzo, G; Orlando, A; D'Attoma, B; Linsalata, M; Martulli, M; Russo, F

    2018-01-29

    Dysbiosis may contribute to constipation and its symptoms, therefore probiotic administration could improve significantly gut health and functions. The aim of the study was to investigate the effects of a long-lasting administration of Lactobacillus reuteri DSM 17938 (LR DSM 17938) on symptoms and quality of life (QoL) score in patients with functional constipation (FC). 56 FC patients with normal colonic transit time and without anorectal disorders and pelvic floor dysfunctions completed the study. LR DSM 17938 was administered for 105 days in a randomised double-blind clinical trial (28 patients per arm). Individual and cumulative scores including the Constipaq, a modified Constipation Scoring System (CSS) that considers the patient assessment of constipation-QoL (PAC-QoL), were calculated during the preliminary visit (V0), at day 15 (end of the induction period with a LR DSM 17938 double dosage, 4×10 8 cfu), day 60 (intermediate evaluation) and day 105 (V4) after a standard dosage (2×10 8 cfu). At the end of treatment, the beneficial effect of LR DSM 17938 compared to placebo was significantly evident for symptoms related to gas content and dysbiosis (abdominal discomfort, pain and bloating), incomplete defecation and helps for defecation (PDSM 17938 treatment, a marked and positive effect on both the CSS single and the cumulative items was evident with the exception of unfruitful attempt and Bristol score. Present findings indicate that LR DSM 17938 has an effect on symptoms different from stool consistency, and they suggest that this probiotic can effectively be used in association therapy rather than as single-drug therapy in the management of FC.

  19. An Improved Ensemble of Random Vector Functional Link Networks Based on Particle Swarm Optimization with Double Optimization Strategy.

    Science.gov (United States)

    Ling, Qing-Hua; Song, Yu-Qing; Han, Fei; Yang, Dan; Huang, De-Shuang

    2016-01-01

    For ensemble learning, how to select and combine the candidate classifiers are two key issues which influence the performance of the ensemble system dramatically. Random vector functional link networks (RVFL) without direct input-to-output links is one of suitable base-classifiers for ensemble systems because of its fast learning speed, simple structure and good generalization performance. In this paper, to obtain a more compact ensemble system with improved convergence performance, an improved ensemble of RVFL based on attractive and repulsive particle swarm optimization (ARPSO) with double optimization strategy is proposed. In the proposed method, ARPSO is applied to select and combine the candidate RVFL. As for using ARPSO to select the optimal base RVFL, ARPSO considers both the convergence accuracy on the validation data and the diversity of the candidate ensemble system to build the RVFL ensembles. In the process of combining RVFL, the ensemble weights corresponding to the base RVFL are initialized by the minimum norm least-square method and then further optimized by ARPSO. Finally, a few redundant RVFL is pruned, and thus the more compact ensemble of RVFL is obtained. Moreover, in this paper, theoretical analysis and justification on how to prune the base classifiers on classification problem is presented, and a simple and practically feasible strategy for pruning redundant base classifiers on both classification and regression problems is proposed. Since the double optimization is performed on the basis of the single optimization, the ensemble of RVFL built by the proposed method outperforms that built by some single optimization methods. Experiment results on function approximation and classification problems verify that the proposed method could improve its convergence accuracy as well as reduce the complexity of the ensemble system.

  20. Biomaterials that promote cell-cell interactions enhance the paracrine function of MSCs.

    Science.gov (United States)

    Qazi, Taimoor H; Mooney, David J; Duda, Georg N; Geissler, Sven

    2017-09-01

    Mesenchymal stromal cells (MSCs) secrete paracrine factors that play crucial roles during tissue regeneration. Whether this paracrine function is influenced by the properties of biomaterials in general, and those used for cell delivery in particular, largely remains unexplored. Here, we investigated if three-dimensional culture in distinct microenvironments - nanoporous hydrogels (mean pore size ∼5 nm) and macroporous scaffolds (mean pore size ∼120 μm) - affects the secretion pattern of MSCs, and consequently leads to differential paracrine effects on target progenitor cells such as myoblasts. We report that compared to MSCs encapsulated in hydrogels, scaffold seeded MSCs show an enhanced secretion profile and exert beneficial paracrine effects on various myoblast functions including migration and proliferation. Additionally, we show that the heightened paracrine effects of scaffold seeded cells can in part be attributed to N-cadherin mediated cell-cell interactions during culture. In hydrogels, this physical interaction between cells is prevented by the encapsulating matrix. Functionally blocking N-cadherin negatively affected the secretion profile and paracrine effects of MSCs on myoblasts, with stronger effects observed for scaffold seeded compared to hydrogel encapsulated cells. Together, these findings demonstrate that the therapeutic potency of MSCs can be enhanced by biomaterials that promote cell-cell interactions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Intraspinal Delivery of Polyethylene Glycol-coated Gold Nanoparticles Promotes Functional Recovery After Spinal Cord Injury.

    Science.gov (United States)

    Papastefanaki, Florentia; Jakovcevski, Igor; Poulia, Nafsika; Djogo, Nevena; Schulz, Florian; Martinovic, Tamara; Ciric, Darko; Loers, Gabrielle; Vossmeyer, Tobias; Weller, Horst; Schachner, Melitta; Matsas, Rebecca

    2015-06-01

    Failure of the mammalian central nervous system (CNS) to regenerate effectively after injury leads to mostly irreversible functional impairment. Gold nanoparticles (AuNPs) are promising candidates for drug delivery in combination with tissue-compatible reagents, such as polyethylene glycol (PEG). PEG administration in CNS injury models has received interest for potential therapy, but toxicity and low bioavailability prevents clinical application. Here we show that intraspinal delivery of PEG-functionalized 40-nm-AuNPs at early stages after mouse spinal cord injury is beneficial for recovery. Positive outcome of hind limb motor function was accompanied by attenuated inflammatory response, enhanced motor neuron survival, and increased myelination of spared or regrown/sprouted axons. No adverse effects, such as body weight loss, ill health, or increased mortality were observed. We propose that PEG-AuNPs represent a favorable drug-delivery platform with therapeutic potential that could be further enhanced if PEG-AuNPs are used as carriers of regeneration-promoting molecules.

  2. Shaping Early Reorganization of Neural Networks Promotes Motor Function after Stroke

    Science.gov (United States)

    Volz, L. J.; Rehme, A. K.; Michely, J.; Nettekoven, C.; Eickhoff, S. B.; Fink, G. R.; Grefkes, C.

    2016-01-01

    Neural plasticity is a major factor driving cortical reorganization after stroke. We here tested whether repetitively enhancing motor cortex plasticity by means of intermittent theta-burst stimulation (iTBS) prior to physiotherapy might promote recovery of function early after stroke. Functional magnetic resonance imaging (fMRI) was used to elucidate underlying neural mechanisms. Twenty-six hospitalized, first-ever stroke patients (time since stroke: 1–16 days) with hand motor deficits were enrolled in a sham-controlled design and pseudo-randomized into 2 groups. iTBS was administered prior to physiotherapy on 5 consecutive days either over ipsilesional primary motor cortex (M1-stimulation group) or parieto-occipital vertex (control-stimulation group). Hand motor function, cortical excitability, and resting-state fMRI were assessed 1 day prior to the first stimulation and 1 day after the last stimulation. Recovery of grip strength was significantly stronger in the M1-stimulation compared to the control-stimulation group. Higher levels of motor network connectivity were associated with better motor outcome. Consistently, control-stimulated patients featured a decrease in intra- and interhemispheric connectivity of the motor network, which was absent in the M1-stimulation group. Hence, adding iTBS to prime physiotherapy in recovering stroke patients seems to interfere with motor network degradation, possibly reflecting alleviation of post-stroke diaschisis. PMID:26980614

  3. Trichostatin A Promotes the Generation and Suppressive Functions of Regulatory T Cells

    Directory of Open Access Journals (Sweden)

    Cristian Doñas

    2013-01-01

    Full Text Available Regulatory T cells are a specific subset of lymphocytes that suppress immune responses and play a crucial role in the maintenance of self-tolerance. They can be generated in the thymus as well as in the periphery through differentiation of naïve CD4+ T cells. The forkhead box P3 transcription factor (Foxp3 is a crucial molecule regulating the generation and function of Tregs. Here we show that the foxp3 gene promoter becomes hyperacetylated in in vitro differentiated Tregs compared to naïve CD4+ T cells. We also show that the histone deacetylase inhibitor TSA stimulated the in vitro differentiation of naïve CD4+ T cells into Tregs and that this induction was accompanied by a global increase in histone H3 acetylation. Importantly, we also demonstrated that Tregs generated in the presence of TSA have phenotypical and functional differences from the Tregs generated in the absence of TSA. Thus, TSA-generated Tregs showed increased suppressive activities, which could potentially be explained by a mechanism involving the ectonucleotidases CD39 and CD73. Our data show that TSA could potentially be used to enhance the differentiation and suppressive function of CD4+Foxp3+ Treg cells.

  4. The effect of dispersion status with functionalized graphenes for electric double-layer capacitors

    International Nuclear Information System (INIS)

    Chen, Y.-R.; Chiu, K.-F.; Lin, H.C.; Hsieh, C.-Y.; Tsai, C.B.; Chu, B.T.T.

    2014-01-01

    Highlights: • MrGO/NMP can reduce the IR drops and R ct of the supercapacitors. • M-rGO can provide excellent plane-to-point conducting network. • M-rGO can effectively enhance high rate performance of supercapacitors. • M-rGO additive can deliver high capacity under high rate cycling. - Abstract: Graphene with oxygen (M-rGO and H-rGO) and nitrogen (N-rGO) related functional groups have been fabricated. Reduced graphenes including H-rGO, M-rGO and N-rGO were mixed with activated carbons as the composite electrodes and characterized for supercapacitors. The effects of the functional groups on graphenes as the conductive additive have been investigated. It was found that a suitable content of functional groups can improve the stability of dispersion, and therefore reduce the internal resistance (IR drop) and charge transfer resistance (R ct ) resulting in higher rate capability. The supercapacitor with M-rGO and KS6 as additive at the activated carbon electrode can be operated at a rate as high as 6 A/g and exhibits a capacitance of 208 F/g, whereas the supercapacitor using only KS6 as additive shows a capacitance of only 107 F/g. The graphene contained supercapacitor has been cycled over 2000 times at 4 A/g with almost no capacitance fading

  5. The effect of dispersion status with functionalized graphenes for electric double-layer capacitors

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Y.-R., E-mail: d98527015@ntu.edu.tw [Department of Materials Science and Engineering, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd, Taipei 10617, Taiwan (China); Department of Materials Science and Engineering, Feng Chia University, 100 Wen Hwa Rd, 407 Taichung, Taiwan (China); Chiu, K.-F. [Department of Materials Science and Engineering, Feng Chia University, 100 Wen Hwa Rd, 407 Taichung, Taiwan (China); Lin, H.C. [Department of Materials Science and Engineering, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd, Taipei 10617, Taiwan (China); Hsieh, C.-Y. [Enerage Inc., No. 5, Ligong 3rd Rd, Wujie Township, Yilan County 26841, Taiwan (China); Tsai, C.B. [Taiwan Textile Research Institute, No. 6, Chengtian Rd, Tucheng City, Taipei 23674, Taiwan (China); Chu, B.T.T. [Laboratory for Functional Polymers, Swiss Federal Laboratories for Materials Science and Technology (Empa), Überlandstrasse 129, 8600 Dübendorf (Switzerland)

    2014-12-15

    Highlights: • MrGO/NMP can reduce the IR drops and R{sub ct} of the supercapacitors. • M-rGO can provide excellent plane-to-point conducting network. • M-rGO can effectively enhance high rate performance of supercapacitors. • M-rGO additive can deliver high capacity under high rate cycling. - Abstract: Graphene with oxygen (M-rGO and H-rGO) and nitrogen (N-rGO) related functional groups have been fabricated. Reduced graphenes including H-rGO, M-rGO and N-rGO were mixed with activated carbons as the composite electrodes and characterized for supercapacitors. The effects of the functional groups on graphenes as the conductive additive have been investigated. It was found that a suitable content of functional groups can improve the stability of dispersion, and therefore reduce the internal resistance (IR drop) and charge transfer resistance (R{sub ct}) resulting in higher rate capability. The supercapacitor with M-rGO and KS6 as additive at the activated carbon electrode can be operated at a rate as high as 6 A/g and exhibits a capacitance of 208 F/g, whereas the supercapacitor using only KS6 as additive shows a capacitance of only 107 F/g. The graphene contained supercapacitor has been cycled over 2000 times at 4 A/g with almost no capacitance fading.

  6. CD163 promotes hematoma absorption and improves neurological functions in patients with intracerebral hemorrhage

    Directory of Open Access Journals (Sweden)

    Wen-jing Xie

    2016-01-01

    Full Text Available Clinical outcomes are positively associated with hematoma absorption. The monocyte-macrophage scavenger receptor, CD163, plays an important role in the metabolism of hemoglobin, and a soluble form of CD163 is present in plasma and other tissue fluids; therefore, we speculated that serum CD163 affects hematoma absorption after intracerebral hemorrhage. Patients with intracerebral hemorrhage were divided into high- and low-level groups according to the average CD163 level (1,977.79 ± 832.91 ng/mL. Compared with the high-level group, the low-level group had a significantly slower hematoma absorption rate, and significantly increased National Institutes of Health Stroke Scale scores and modified Rankin Scale scores. These results suggest that CD163 promotes hematoma absorption and the recovery of neurological function in patients with intracerebral hemorrhage.

  7. Promoting social behavior with oxytocin in high-functioning autism spectrum disorders.

    Science.gov (United States)

    Andari, Elissar; Duhamel, Jean-René; Zalla, Tiziana; Herbrecht, Evelyn; Leboyer, Marion; Sirigu, Angela

    2010-03-02

    Social adaptation requires specific cognitive and emotional competences. Individuals with high-functioning autism or with Asperger syndrome cannot understand or engage in social situations despite preserved intellectual abilities. Recently, it has been suggested that oxytocin, a hormone known to promote mother-infant bonds, may be implicated in the social deficit of autism. We investigated the behavioral effects of oxytocin in 13 subjects with autism. In a simulated ball game where participants interacted with fictitious partners, we found that after oxytocin inhalation, patients exhibited stronger interactions with the most socially cooperative partner and reported enhanced feelings of trust and preference. Also, during free viewing of pictures of faces, oxytocin selectively increased patients' gazing time on the socially informative region of the face, namely the eyes. Thus, under oxytocin, patients respond more strongly to others and exhibit more appropriate social behavior and affect, suggesting a therapeutic potential of oxytocin through its action on a core dimension of autism.

  8. Silk-based biomaterials functionalized with fibronectin type II promotes cell adhesion.

    Science.gov (United States)

    Pereira, Ana Margarida; Machado, Raul; da Costa, André; Ribeiro, Artur; Collins, Tony; Gomes, Andreia C; Leonor, Isabel B; Kaplan, David L; Reis, Rui L; Casal, Margarida

    2017-01-01

    The objective of this work was to exploit the fibronectin type II (FNII) module from human matrix metalloproteinase-2 as a functional domain for the development of silk-based biopolymer blends that display enhanced cell adhesion properties. The DNA sequence of spider dragline silk protein (6mer) was genetically fused with the FNII coding sequence and expressed in Escherichia coli. The chimeric protein 6mer+FNII was purified by non-chromatographic methods. Films prepared from 6mer+FNII by solvent casting promoted only limited cell adhesion of human skin fibroblasts. However, the performance of the material in terms of cell adhesion was significantly improved when 6mer+FNII was combined with a silk-elastin-like protein in a concentration-dependent behavior. With this work we describe a novel class of biopolymer that promote cell adhesion and potentially useful as biomaterials for tissue engineering and regenerative medicine. This work reports the development of biocompatible silk-based composites with enhanced cell adhesion properties suitable for biomedical applications in regenerative medicine. The biocomposites were produced by combining a genetically engineered silk-elastin-like protein with a genetically engineered spider-silk-based polypeptide carrying the three domains of the fibronectin type II module from human metalloproteinase-2. These composites were processed into free-standing films by solvent casting and characterized for their biological behavior. To our knowledge this is the first report of the exploitation of all three FNII domains as a functional domain for the development of bioinspired materials with improved biological performance. The present study highlights the potential of using genetically engineered protein-based composites as a platform for the development of new bioinspired biomaterials. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  9. PDGF-metronidazole-encapsulated nanofibrous functional layers on collagen membrane promote alveolar ridge regeneration

    Directory of Open Access Journals (Sweden)

    Ho MH

    2017-08-01

    Full Text Available Ming-Hua Ho,1 Hao-Chieh Chang,2,3 Yu-Chia Chang,3 Jeiannete Claudia,1 Tzu-Chiao Lin,2 Po-Chun Chang2,3 1Department of Chemical Engineering, College of Engineering, National Taiwan University of Science and Technology, Taipei, Taiwan; 2Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan; 3Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan Abstract: This study aimed to develop a functionally graded membrane (FGM to prevent infection and promote tissue regeneration. Poly(L-lactide-co-D,L-lactide encapsulating platelet-derived growth factor (PDLLA-PDGF or metronidazole (PDLLA-MTZ was electrospun to form a nanofibrous layer on the inner or outer surface of a clinically available collagen membrane, respectively. The membrane was characterized for the morphology, molecule release profile, in vitro and in vivo biocompatibility, and preclinical efficiency for alveolar ridge regeneration. The PDLLA-MTZ and PDLLA-PDGF nanofibers were 800–900 nm in diameter, and the thicknesses of the functional layers were 20–30 µm, with sustained molecule release over 28 days. All of the membranes tested were compatible with cell survival in vitro and showed good tissue integration with minimal fibrous capsule formation or inflammation. Cell proliferation was especially prominent on the PDLLA-PDGF layer in vivo. On the alveolar ridge, all FGMs reduced wound dehiscence compared with the control collagen membrane, and the FGM with PDLLA-PDGF promoted osteogenesis significantly. In conclusion, the FGMs with PDLLA-PDGF and PDLLA-MTZ showed high biocompatibility and facilitated wound healing compared with conventional membrane, and the FGM with PDLLA-PDGF enhanced alveolar ridge regeneration in vivo. The design represents a beneficial modification, which may be easily adapted for future clinical use. Keywords: tissue engineering, platelet-derived growth factor, metronidazole, alveolar process

  10. [Pharmacological analysis of the effect of natural double-helical nucleic acids on the detoxifying function of the liver].

    Science.gov (United States)

    Masycheva, V I; Morozova, E N; Nadolinnaia, I G

    1988-10-01

    The effect of interferon inductors i.e. double stranded RNAs from S. cerevisiae and phage F6 on the liver detoxicating function was studied on noninbred albino mice. The liver detoxicating function was tested by duration of hexenal sleep. It was shown that intraperitoneal administration of the yeast and phage RNAs in doses of 1/5 LD50 for three times led to increasing of the narcotic sleep duration in the animals by 65 and 207 per cent, respectively. The effect was of the dose-dependent nature. The doses not inducing reliable inhibition of hexenal metabolism were equal to 1/10 LD50 for the yeast dsRNA and 1/27 LD50 for the phage dsRNA. The inhibitory effect of the dsRNAs was retained for 2-3 days after discontinuation of the drug use. When the dsRNAs were administered simultaneously with nembutal, an inductor of the liver microsomal enzymes, the dsRNAs eliminated its inducing effect. Simultaneous administration of alpha-tocopherol lowered the dsRNA effect on hexenal metabolism. The findings suggested that the dsRNA inhibitory effect on the liver detoxicating function was grounded on the mechanisms associated with inhibition of syntheses and activation of lipid peroxidation specific of the monooxygenase system under the action of the dsRNAs.

  11. Effect of levodopa in combination with physiotherapy on functional motor recovery after stroke: a prospective, randomised, double-blind study.

    Science.gov (United States)

    Scheidtmann, K; Fries, W; Müller, F; Koenig, E

    2001-09-08

    Functional disability is generally caused by hemiplegia after stroke. Physiotherapy used to be the only way of improving motor function in such patients. However, administration of amphetamines in addition to exercise improves motor recovery in animals, probably by increasing the concentration of norepinephrine in the central nervous system. Our aim was to ascertain whether levodopa could enhance the efficacy of physiotherapy after hemiplegia. We did a prospective, randomised, placebo-controlled, double-blind study in which we enrolled 53 primary stroke patients. For the first 3 weeks patients received single doses of levodopa 100 mg or placebo daily in combination with physiotherapy. For the second 3 weeks patients had only physiotherapy. We quantitatively assessed motor function every week with Rivermead motor assessment (RMA). Six patients were excluded from analyses because of non-neurological complications. Motor recovery was significantly improved after 3 weeks of drug intervention in those on levodopa (RMA improved by 6.4 points) compared with placebo (4.1), and the result was independent of initial degree of impairment (pstroke rehabilitation.

  12. Properties of a planar electric double layer under extreme conditions investigated by classical density functional theory and Monte Carlo simulations.

    Science.gov (United States)

    Zhou, Shiqi; Lamperski, Stanisław; Zydorczak, Maria

    2014-08-14

    Monte Carlo (MC) simulation and classical density functional theory (DFT) results are reported for the structural and electrostatic properties of a planar electric double layer containing ions having highly asymmetric diameters or valencies under extreme concentration condition. In the applied DFT, for the excess free energy contribution due to the hard sphere repulsion, a recently elaborated extended form of the fundamental measure functional is used, and coupling of Coulombic and short range hard-sphere repulsion is described by a traditional second-order functional perturbation expansion approximation. Comparison between the MC and DFT results indicates that validity interval of the traditional DFT approximation expands to high ion valences running up to 3 and size asymmetry high up to diameter ratio of 4 whether the high valence ions or the large size ion are co- or counter-ions; and to a high bulk electrolyte concentration being close to the upper limit of the electrolyte mole concentration the MC simulation can deal with well. The DFT accuracy dependence on the ion parameters can be self-consistently explained using arguments of liquid state theory, and new EDL phenomena such as overscreening effect due to monovalent counter-ions, extreme layering effect of counter-ions, and appearance of a depletion layer with almost no counter- and co-ions are observed.

  13. DOUBLE-EXPONENTIAL FITTING FUNCTION FOR EVALUATION OF COSMIC-RAY-INDUCED NEUTRON FLUENCE RATE IN ARBITRARY LOCATIONS.

    Science.gov (United States)

    Li, Huailiang; Yang, Yigang; Wang, Qibiao; Tuo, Xianguo; Julian Henderson, Mark; Courtois, Jérémie

    2017-12-01

    The fluence rate of cosmic-ray-induced neutrons (CRINs) varies with many environmental factors. While many current simulation and experimental studies have focused mainly on the altitude variation, the specific rule that the CRINs vary with geomagnetic cutoff rigidity (which is related to latitude and longitude) was not well considered. In this article, a double-exponential fitting function F=(A1e-A2CR+A3)eB1Al, is proposed to evaluate the CRINs' fluence rate varying with geomagnetic cutoff rigidity and altitude. The fitting R2 can have a value up to 0.9954, and, moreover, the CRINs' fluence rate in an arbitrary location (latitude, longitude and altitude) can be easily evaluated by the proposed function. The field measurements of the CRINs' fluence rate and H*(10) rate in Mt. Emei and Mt. Bowa were carried out using a FHT-762 and LB 6411 neutron prober, respectively, and the evaluation results show that the fitting function agrees well with the measurement results. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  14. Gain-of-function mutant p53 but not p53 deletion promotes head and neck cancer progression in response to oncogenic K-ras

    Science.gov (United States)

    Acin, Sergio; Li, Zhongyou; Mejia, Olga; Roop, Dennis R; El-Naggar, Adel K; Caulin, Carlos

    2015-01-01

    Mutations in p53 occur in over 50% of the human head and neck squamous cell carcinomas (SCCHN). The majority of these mutations result in the expression of mutant forms of p53, rather than deletions in the p53 gene. Some p53 mutants are associated with poor prognosis in SCCHN patients. However, the molecular mechanisms that determine the poor outcome of cancers carrying p53 mutations are unknown. Here, we generated a mouse model for SCCHN and found that activation of the endogenous p53 gain-of-function mutation p53R172H, but not deletion of p53, cooperates with oncogenic K-ras during SCCHN initiation, accelerates oral tumour growth, and promotes progression to carcinoma. Mechanistically, expression profiling of the tumours that developed in these mice and studies using cell lines derived from these tumours determined that mutant p53 induces the expression of genes involved in mitosis, including cyclin B1 and cyclin A, and accelerates entry in mitosis. Additionally, we discovered that this oncogenic function of mutant p53 was dependent on K-ras because the expression of cyclin B1 and cyclin A decreased, and entry in mitosis was delayed, after suppressing K-ras expression in oral tumour cells that express p53R172H. The presence of double-strand breaks in the tumours suggests that oncogene-dependent DNA damage resulting from K-ras activation promotes the oncogenic function of mutant p53. Accordingly, DNA damage induced by doxorubicin also induced increased expression of cyclin B1 and cyclin A in cells that express p53R172H. These findings represent strong in vivo evidence for an oncogenic function of endogenous p53 gain-of-function mutations in SCCHN and provide a mechanistic explanation for the genetic interaction between oncogenic K-ras and mutant p53. PMID:21952947

  15. Repair of exogenous DNA double-strand breaks promotes chromosome synapsis in SPO11-mutant mouse meiocytes, and is altered in the absence of HORMAD1.

    Science.gov (United States)

    Carofiglio, Fabrizia; Sleddens-Linkels, Esther; Wassenaar, Evelyne; Inagaki, Akiko; van Cappellen, Wiggert A; Grootegoed, J Anton; Toth, Attila; Baarends, Willy M

    2018-03-01

    Repair of SPO11-dependent DNA double-strand breaks (DSBs) via homologous recombination (HR) is essential for stable homologous chromosome pairing and synapsis during meiotic prophase. Here, we induced radiation-induced DSBs to study meiotic recombination and homologous chromosome pairing in mouse meiocytes in the absence of SPO11 activity (Spo11 YF/YF model), and in the absence of both SPO11 and HORMAD1 (Spo11/Hormad1 dko). Within 30 min after 5 Gy irradiation of Spo11 YF/YF mice, 140-160 DSB repair foci were detected, which specifically localized to the synaptonemal complex axes. Repair of radiation-induced DSBs was incomplete in Spo11 YF/YF compared to Spo11 +/YF meiocytes. Still, repair of exogenous DSBs promoted partial recovery of chromosome pairing and synapsis in Spo11 YF/YF meiocytes. This indicates that at least part of the exogenous DSBs can be processed in an interhomolog recombination repair pathway. Interestingly, in a seperate experiment, using 3 Gy of irradiation, we observed that Spo11/Hormad1 dko spermatocytes contained fewer remaining DSB repair foci at 48 h after irradiation compared to irradiated Spo11 knockout spermatocytes. Together, these results show that recruitment of exogenous DSBs to the synaptonemal complex, in conjunction with repair of exogenous DSBs via the homologous chromosome, contributes to homology recognition. In addition, the data suggest a role for HORMAD1 in DNA repair pathway choice in mouse meiocytes. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  16. Caries-preventive effectiveness of fluoride varnish as adjunct to oral health promotion and supervised tooth brushing in preschool children: a double-blind randomized controlled trial.

    Science.gov (United States)

    Agouropoulos, A; Twetman, S; Pandis, N; Kavvadia, K; Papagiannoulis, L

    2014-10-01

    To evaluate the effect of biannual fluoride varnish applications in preschool children as an adjunct to school-based oral health promotion and supervised tooth brushing with 1000ppm fluoride toothpaste. 424 preschool children, 2-5 year of age, from 10 different pre schools in Athens were invited to this double-blind randomized controlled trial and 328 children completed the 2-year programme. All children received oral health education with hygiene instructions twice yearly and attended supervised tooth brushing once daily. The test group was treated with fluoride varnish (0.9% diflurosilane) biannually while the control group had placebo applications. The primary endpoints were caries prevalence and increment; secondary outcomes were gingival health, mutans streptococci growth and salivary buffer capacity. The groups were balanced at baseline and no significant differences in caries prevalence or increment were displayed between the groups after 1 and 2 years, respectively. There was a reduced number of new pre-cavitated enamel lesions during the second year of the study (p=0.05) but the decrease was not statistically significant. The secondary endpoints were unaffected by the varnish treatments. Under the present conditions, biannual fluoride varnish applications in preschool children did not show significant caries-preventive benefits when provided as an adjunct to school-based supervised tooth brushing with 1000ppm fluoride toothpaste. In community based, caries prevention programmes, for high caries risk preschool children, a fluoride varnish may add little to caries prevention, when 1000ppm fluoride toothpaste is used daily. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. A 6-month, randomized, double-blind, placebo-controlled study evaluating the ability of a marine complex supplement to promote hair growth in men with thinning hair.

    Science.gov (United States)

    Ablon, Glynis

    2016-12-01

    Male pattern baldness, or androgenetic alopecia, affects approximately 50% of the adult population and can cause poor self-image, low self-esteem and have a significant negative impact on the quality of life. An oral nutraceutical supplement based on a marine complex formulation has previously been reported to significantly increase the number of terminal hairs in women with thinning hair. The objective of this double-blind, placebo-controlled study was to confirm the beneficial effects of a similar marine complex supplement in adult male subjects with thinning hair (Viviscal ® Man; Lifes2good, Inc., Chicago, IL, USA). Healthy adult male subjects with thinning hair associated with clinically diagnosed male pattern hair loss were enrolled and randomized to receive study drug or placebo twice daily. At Day 90, subjects indicated a significant improvement in three of six quality of life measures as well as a significant overall improvement in quality of life. After 180 days, significant increases were observed for total hair count, total hair density, and terminal hair density (for each, P = 0.001). The investigator assessments revealed significant improvements in terminal and vellus hair count and terminal hair density. Hair pull test results were significantly lower (fewer hairs removed) for study drug vs. placebo at Days 90 (P < 0.05) and 180 (P < 0.01). There were no reports of treatment-emergent adverse events. The results of this study showed for the first time that a dietary supplement containing a marine complex and other ingredients can decrease hair shedding and promote hair growth in men with thinning hair. © 2016 Wiley Periodicals, Inc.

  18. Sequential double excitations from linear-response time-dependent density functional theory

    Energy Technology Data Exchange (ETDEWEB)

    Mosquera, Martín A.; Ratner, Mark A.; Schatz, George C., E-mail: g-schatz@northwestern.edu [Department of Chemistry, Northwestern University, 2145 Sheridan Rd., Evanston, Illinois 60208 (United States); Chen, Lin X. [Department of Chemistry, Northwestern University, 2145 Sheridan Rd., Evanston, Illinois 60208 (United States); Chemical Sciences and Engineering Division, Argonne National Laboratory, 9700 South Cass Ave., Lemont, Illinois 60439 (United States)

    2016-05-28

    Traditional UV/vis and X-ray spectroscopies focus mainly on the study of excitations starting exclusively from electronic ground states. However there are many experiments where transitions from excited states, both absorption and emission, are probed. In this work we develop a formalism based on linear-response time-dependent density functional theory to investigate spectroscopic properties of excited states. We apply our model to study the excited-state absorption of a diplatinum(II) complex under X-rays, and transient vis/UV absorption of pyrene and azobenzene.

  19. Formation of double-strand breaks in DNA of γ-irradiated bacteria depending on the function of fast repair processes of DNA single-strand breaks

    International Nuclear Information System (INIS)

    Petrov, S.I.; Gaziev, A.I.

    1980-01-01

    The formation of double-strand breaks in DNA of γ-irradiated ( 60 Co)Ex coli bacteria depending on the function of fast repair processes of DNA single-strand breaks, is investigated. The profiles of sedimentation of DNA Ex coli cells, irradiated at 0-2 deg C in the salt medium and in EDTA-borate buffer, are presented. It is shown that when irradiating cells in EDTA-borate buffer, the output of single- and double strand breaks in DNA is much higher than in the case of their irradiation in the minimum salt medium. The dependence of output of single-strand and double-strand breaks depending on the radiatier doze of E coli cells in the salt medium and EDTA-borate buffer, is studied. The supposition is made on the presence of a regulative interaction between the accumulation of DNA single-breaks and their repair with the formation of double-strand breaks. The functionating of fast and superfast repair processes considerably affects the formation of double-strand breaks in DNA of a bacterium cell. A considerable amount of double-breaks registered immediately after irradiation forms due to a close position of single-strand breaks on the opposite DNA strands

  20. Application of double-hybrid density functionals to charge transfer in N-substituted pentacenequinones.

    Science.gov (United States)

    Sancho-García, J C

    2012-05-07

    A set of N-heteroquinones, deriving from oligoacenes, have been recently proposed as n-type organic semiconductors with high electron mobilities in thin-film transistors. Generally speaking, this class of compounds self-assembles in neighboring π-stacks linked by weak hydrogen bonds. We aim at theoretically characterizing here the sequential charge transport (hopping) process expected to take place across these arrays of molecules. To do so, we need to accurately address the preferred packing of these materials simultaneously to single-molecule properties related to charge-transfer events, carefully employing dispersion-corrected density functional theory methods to accurately extract the key molecular parameters governing this phenomenon at the nanoscale. This study confirms the great deal of interest around these compounds, since controlled functionalization of model molecules (i.e., pentacene) allows to efficiently tune the corresponding charge mobilities, and the capacity of modern quantum-chemical methods to predict it after rationalizing the underlying structure-property relationships.

  1. VEGF induces sensory and motor peripheral plasticity, alters bladder function, and promotes visceral sensitivity.

    Science.gov (United States)

    Malykhina, Anna P; Lei, Qi; Erickson, Chris S; Epstein, Miles L; Saban, Marcia R; Davis, Carole A; Saban, Ricardo

    2012-12-19

    This work tests the hypothesis that bladder instillation with vascular endothelial growth factor (VEGF) modulates sensory and motor nerve plasticity, and, consequently, bladder function and visceral sensitivity.In addition to C57BL/6J, ChAT-cre mice were used for visualization of bladder cholinergic nerves. The direct effect of VEGF on the density of sensory nerves expressing the transient receptor potential vanilloid subfamily 1 (TRPV1) and cholinergic nerves (ChAT) was studied one week after one or two intravesical instillations of the growth factor.To study the effects of VEGF on bladder function, mice were intravesically instilled with VEGF and urodynamic evaluation was assessed. VEGF-induced alteration in bladder dorsal root ganglion (DRG) neurons was performed on retrogradly labeled urinary bladder afferents by patch-clamp recording of voltage gated Na+ currents. Determination of VEGF-induced changes in sensitivity to abdominal mechanostimulation was performed by application of von Frey filaments. In addition to an overwhelming increase in TRPV1 immunoreactivity, VEGF instillation resulted in an increase in ChAT-directed expression of a fluorescent protein in several layers of the urinary bladder. Intravesical VEGF caused a profound change in the function of the urinary bladder: acute VEGF (1 week post VEGF treatment) reduced micturition pressure and longer treatment (2 weeks post-VEGF instillation) caused a substantial reduction in inter-micturition interval. In addition, intravesical VEGF resulted in an up-regulation of voltage gated Na(+) channels (VGSC) in bladder DRG neurons and enhanced abdominal sensitivity to mechanical stimulation. For the first time, evidence is presented indicating that VEGF instillation into the mouse bladder promotes a significant increase in peripheral nerve density together with alterations in bladder function and visceral sensitivity. The VEGF pathway is being proposed as a key modulator of neural plasticity in the pelvis and

  2. VEGF induces sensory and motor peripheral plasticity, alters bladder function, and promotes visceral sensitivity

    Directory of Open Access Journals (Sweden)

    Malykhina Anna P

    2012-12-01

    Full Text Available Abstract Background This work tests the hypothesis that bladder instillation with vascular endothelial growth factor (VEGF modulates sensory and motor nerve plasticity, and, consequently, bladder function and visceral sensitivity. In addition to C57BL/6J, ChAT-cre mice were used for visualization of bladder cholinergic nerves. The direct effect of VEGF on the density of sensory nerves expressing the transient receptor potential vanilloid subfamily 1 (TRPV1 and cholinergic nerves (ChAT was studied one week after one or two intravesical instillations of the growth factor. To study the effects of VEGF on bladder function, mice were intravesically instilled with VEGF and urodynamic evaluation was assessed. VEGF-induced alteration in bladder dorsal root ganglion (DRG neurons was performed on retrogradly labeled urinary bladder afferents by patch-clamp recording of voltage gated Na+ currents. Determination of VEGF-induced changes in sensitivity to abdominal mechanostimulation was performed by application of von Frey filaments. Results In addition to an overwhelming increase in TRPV1 immunoreactivity, VEGF instillation resulted in an increase in ChAT-directed expression of a fluorescent protein in several layers of the urinary bladder. Intravesical VEGF caused a profound change in the function of the urinary bladder: acute VEGF (1 week post VEGF treatment reduced micturition pressure and longer treatment (2 weeks post-VEGF instillation caused a substantial reduction in inter-micturition interval. In addition, intravesical VEGF resulted in an up-regulation of voltage gated Na+ channels (VGSC in bladder DRG neurons and enhanced abdominal sensitivity to mechanical stimulation. Conclusions For the first time, evidence is presented indicating that VEGF instillation into the mouse bladder promotes a significant increase in peripheral nerve density together with alterations in bladder function and visceral sensitivity. The VEGF pathway is being proposed as a

  3. Enhanced Heme Function and Mitochondrial Respiration Promote the Progression of Lung Cancer Cells

    Science.gov (United States)

    Alam, Md Maksudul; Shah, Ajit; Cao, Thai M.; Sullivan, Laura A.; Brekken, Rolf; Zhang, Li

    2013-01-01

    Lung cancer is the leading cause of cancer-related mortality, and about 85% of the cases are non-small-cell lung cancer (NSCLC). Importantly, recent advance in cancer research suggests that altering cancer cell bioenergetics can provide an effective way to target such advanced cancer cells that have acquired mutations in multiple cellular regulators. This study aims to identify bioenergetic alterations in lung cancer cells by directly measuring and comparing key metabolic activities in a pair of cell lines representing normal and NSCLC cells developed from the same patient. We found that the rates of oxygen consumption and heme biosynthesis were intensified in NSCLC cells. Additionally, the NSCLC cells exhibited substantially increased levels in an array of proteins promoting heme synthesis, uptake and function. These proteins include the rate-limiting heme biosynthetic enzyme ALAS, transporter proteins HRG1 and HCP1 that are involved in heme uptake, and various types of oxygen-utilizing hemoproteins such as cytoglobin and cytochromes. Several types of human tumor xenografts also displayed increased levels of such proteins. Furthermore, we found that lowering heme biosynthesis and uptake, like lowering mitochondrial respiration, effectively reduced oxygen consumption, cancer cell proliferation, migration and colony formation. In contrast, lowering heme degradation does not have an effect on lung cancer cells. These results show that increased heme flux and function are a key feature of NSCLC cells. Further, increased generation and supply of heme and oxygen-utilizing hemoproteins in cancer cells will lead to intensified oxygen consumption and cellular energy production by mitochondrial respiration, which would fuel cancer cell proliferation and progression. The results show that inhibiting heme and respiratory function can effectively arrest the progression of lung cancer cells. Hence, understanding heme function can positively impact on research in lung cancer

  4. Double N-arylation reaction of polyhalogenated 4,4’-bipyridines. Expedious synthesis of functionalized 2,7-diazacarbazoles

    Directory of Open Access Journals (Sweden)

    Mohamed Abboud

    2012-02-01

    Full Text Available Unusual 2,7-diazacarbazoles were prepared in one step from readily available tetra-halogenated 4,4’-bipyridines by using a double N-arylation reaction in the presence of the Pd–XPhos catalyst system. Moderate to good yields were obtained in this site-selective Buchwald–Hartwig double amination. The functionalization of these tricyclic derivatives was performed by using Pd-catalyzed cross-coupling reactions such as the Stille and Suzuki couplings. Two compounds were analyzed by X-ray diffraction and show π–π stacking involving the diazacarbazole moieties and the phenyl rings of functionalized groups.

  5. Double hollow MoS{sub 2} nano-spheres: Synthesis, tribological properties, and functional conversion from lubrication to photocatalysis

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Yueru [Department of Chemical and Materials Engineering, Hefei University, Hefei 230601 (China); Hu, Kunhong, E-mail: hukunhong@163.com [Department of Chemical and Materials Engineering, Hefei University, Hefei 230601 (China); Hu, Enzhu; Guo, Jianhua; Han, Chengliang [Department of Chemical and Materials Engineering, Hefei University, Hefei 230601 (China); Hu, Xianguo [Institute of Tribology, Hefei University of Technology, Hefei 230009 (China)

    2017-01-15

    Highlights: • Novel double-hollow-sphere MoS{sub 2} nanoparticles were synthesized on sericite. • Friction and wear decreased by 22.4 and 63.5% by the novel MoS{sub 2}/sericite. • Friction induced conversion of MoS{sub 2}/sericite from lubricant to catalyst. • MoS{sub 2}/sericite can be used as a photocatalyst after lubricating service life. • A possible approach was proposed for designing a novel green lubricant. - Abstract: Molybdenum disulfide (MoS{sub 2}) has extensive applications in industries as solid lubricants and catalysts. To improve the lubricating performance of MoS{sub 2}, novel double-hollow-sphere MoS{sub 2} (DHSM) nanoparticles with an average diameter of approximately 90 nm were synthesized on sericite mica (SM). When the DHSM/SM composite was used as an additive in polyalphaolefin oil, friction and wear decreased by 22.4% and 63.5% respectively. The low friction and wear were attributed to the easy exfoliation of DHSM. The DHSM/SM composite was then rubbed under 40 MPa for 1 h to investigate the exfoliation and functional conversion behaviors of DHSM. Results showed that DHSM (lubricating structure) on SM could be completely exfoliated into nanosheets (catalytic structure) by rubbing. The nanosheets exfoliated from DHSM presented good photocatalytic activity for the removal of organic compounds from waste water. This work provided both a novel solid lubricant for industrial applications and a possible approach to designing a novel green lubricant for use as a photocatalyst in organic-waste treatment after lubricating service life.

  6. Construction of a fucoidan/laminin functional multilayer to direction vascular cell fate and promotion hemocompatibility

    International Nuclear Information System (INIS)

    Ye, Changrong; Wang, Yan; Su, Hong; Yang, Ping; Huang, Nan; Maitz, Manfred F.; Zhao, Anshan

    2016-01-01

    Surface biofunctional modification of cardiovascular stents is a versatile approach to reduce the adverse effects after implantation. In this work, a novel multifunctional coating was fabricated by coimmobilization of the sulfated polysaccharide of brown algae fucoidan and laminin to biomimic the vascular intimal conditions in order to support rapid endothelialization, prevent restenosis and improve hemocompatibility. The surface properties of the coating such as hydrophilicity, bonding density of biomolecules and stability were evaluated and optimized. According to the biocompatibility tests, the fucoidan/laminin multilayer coated surface displayed less platelet adhesion with favorable anticoagulant property. In addition, the fucoidan/laminin complex showed function to selectively regulate vascular cells growth behavior. The proliferation of endothelial cells (ECs) on the fucoidan/laminin biofunctional coating was significantly promoted. For the smooth muscle cells (SMCs), inhibitory effects on cell adhesion and proliferation were observed. In conclusion, the fucoidan/laminin biofunctional coating was successfully fabricated with desirable anticoagulant and endothelialization properties which show a promising application in the vascular devices such as vascular stents or grafts surface modification. - Highlights: • Construction of fucoidan/laminin functional multilayer to biomimic the basement membrane of vascular • The fucoidan/laminin complex demonstrates anti-coagulation property. • The fucoidan/laminin complex can selectively regulate EC and SMC growth behavior to prevent restenosis.

  7. Functional characterization of the vitellogenin promoter in the silkworm, Bombyx mori.

    Science.gov (United States)

    Xu, J; Wang, Y Q; Li, Z Q; Ling, L; Zeng, B S; You, L; Chen, Y Z; Aslam, A F M; Huang, Y P; Tan, A J

    2014-10-01

    Genetic transformation and genome editing technologies have been successfully established in the lepidopteran insect model, the domesticated silkworm, Bombyx mori, providing great potential for functional genomics and practical applications. However, the current lack of cis-regulatory elements in B. mori gene manipulation research limits further exploitation in functional gene analysis. In the present study, we characterized a B. mori endogenous promoter, Bmvgp, which is a 798-bp DNA sequence adjacent to the 5'-end of the vitellogenin gene (Bmvg). PiggyBac-based transgenic analysis shows that Bmvgp precisely directs expression of a reporter gene, enhanced green fluorescent protein (EGFP), in a sex-, tissue- and stage-specific manner. In transgenic animals, EGFP expression can be detected in the female fat body from larval-pupal ecdysis to the following pupal and adult stage. Furthermore, in vitro and in vivo experiments revealed that EGFP expression can be activated by 20-hydroxyecdysone, which is consistent with endogenous Bmvg expression. These data indicate that Bmvgp is an effective endogenous cis-regulatory element in B. mori. © 2014 The Royal Entomological Society.

  8. Construction of a fucoidan/laminin functional multilayer to direction vascular cell fate and promotion hemocompatibility

    Energy Technology Data Exchange (ETDEWEB)

    Ye, Changrong; Wang, Yan; Su, Hong; Yang, Ping; Huang, Nan [Key Laboratory of Advanced Materials Technology of Ministry of Education, Department of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031 (China); Maitz, Manfred F. [Leibniz Institute of Polymer Research Dresden, Max Bergmann Center of Biomaterials Dresden, Dresden 01069 (Germany); Zhao, Anshan [Key Laboratory of Advanced Materials Technology of Ministry of Education, Department of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031 (China)

    2016-07-01

    Surface biofunctional modification of cardiovascular stents is a versatile approach to reduce the adverse effects after implantation. In this work, a novel multifunctional coating was fabricated by coimmobilization of the sulfated polysaccharide of brown algae fucoidan and laminin to biomimic the vascular intimal conditions in order to support rapid endothelialization, prevent restenosis and improve hemocompatibility. The surface properties of the coating such as hydrophilicity, bonding density of biomolecules and stability were evaluated and optimized. According to the biocompatibility tests, the fucoidan/laminin multilayer coated surface displayed less platelet adhesion with favorable anticoagulant property. In addition, the fucoidan/laminin complex showed function to selectively regulate vascular cells growth behavior. The proliferation of endothelial cells (ECs) on the fucoidan/laminin biofunctional coating was significantly promoted. For the smooth muscle cells (SMCs), inhibitory effects on cell adhesion and proliferation were observed. In conclusion, the fucoidan/laminin biofunctional coating was successfully fabricated with desirable anticoagulant and endothelialization properties which show a promising application in the vascular devices such as vascular stents or grafts surface modification. - Highlights: • Construction of fucoidan/laminin functional multilayer to biomimic the basement membrane of vascular • The fucoidan/laminin complex demonstrates anti-coagulation property. • The fucoidan/laminin complex can selectively regulate EC and SMC growth behavior to prevent restenosis.

  9. Lambert W-function based exact representation for double diode model of solar cells: Comparison on fitness and parameter extraction

    International Nuclear Information System (INIS)

    Gao, Xiankun; Cui, Yan; Hu, Jianjun; Xu, Guangyin; Yu, Yongchang

    2016-01-01

    Highlights: • Lambert W-function based exact representation (LBER) is presented for double diode model (DDM). • Fitness difference between LBER and DDM is verified by reported parameter values. • The proposed LBER can better represent the I–V and P–V characteristics of solar cells. • Parameter extraction difference between LBER and DDM is validated by two algorithms. • The parameter values extracted from LBER are more accurate than those from DDM. - Abstract: Accurate modeling and parameter extraction of solar cells play an important role in the simulation and optimization of PV systems. This paper presents a Lambert W-function based exact representation (LBER) for traditional double diode model (DDM) of solar cells, and then compares their fitness and parameter extraction performance. Unlike existing works, the proposed LBER is rigorously derived from DDM, and in LBER the coefficients of Lambert W-function are not extra parameters to be extracted or arbitrary scalars but the vectors of terminal voltage and current of solar cells. The fitness difference between LBER and DDM is objectively validated by the reported parameter values and experimental I–V data of a solar cell and four solar modules from different technologies. The comparison results indicate that under the same parameter values, the proposed LBER can better represent the I–V and P–V characteristics of solar cells and provide a closer representation to actual maximum power points of all module types. Two different algorithms are used to compare the parameter extraction performance of LBER and DDM. One is our restart-based bound constrained Nelder-Mead (rbcNM) algorithm implemented in Matlab, and the other is the reported R_c_r-IJADE algorithm executed in Visual Studio. The comparison results reveal that, the parameter values extracted from LBER using two algorithms are always more accurate and robust than those from DDM despite more time consuming. As an improved version of DDM, the

  10. Influence of ion pairing in ionic liquids on electrical double layer structures and surface force using classical density functional approach.

    Science.gov (United States)

    Ma, Ke; Forsman, Jan; Woodward, Clifford E

    2015-05-07

    We explore the influence of ion pairing in room temperature ionic liquids confined by planar electrode surfaces. Using a coarse-grained model for the aromatic ionic liquid [C4MIM(+)][BF4 (-)], we account for an ion pairing component as an equilibrium associating species within a classical density functional theory. We investigated the resulting structure of the electrical double layer as well as the ensuing surface forces and differential capacitance, as a function of the degree of ion association. We found that the short-range structure adjacent to surfaces was remarkably unaffected by the degree of ion pairing, up to several molecular diameters. This was even the case for 100% of ions being paired. The physical implications of ion pairing only become apparent in equilibrium properties that depend upon the long-range screening of charges, such as the asymptotic behaviour of surface forces and the differential capacitance, especially at low surface potential. The effect of ion pairing on capacitance is consistent with their invocation as a source of the anomalous temperature dependence of the latter. This work shows that ion pairing effects on equilibrium properties are subtle and may be difficult to extract directly from simulations.

  11. Does double-row rotator cuff repair improve functional outcome of patients compared with single-row technique? A systematic review.

    Science.gov (United States)

    DeHaan, Alexander M; Axelrad, Thomas W; Kaye, Elizabeth; Silvestri, Lorenzo; Puskas, Brian; Foster, Timothy E

    2012-05-01

    The advantage of single-row versus double-row arthroscopic rotator cuff repair techniques has been a controversial issue in sports medicine and shoulder surgery. There is biomechanical evidence that double-row techniques are superior to single-row techniques; however, there is no clinical evidence that the double-row technique provides an improved functional outcome. When compared with single-row rotator cuff repair, double-row fixation, although biomechanically superior, has no clinical benefit with respect to retear rate or improved functional outcome. Systematic review. The authors reviewed prospective studies of level I or II clinical evidence that compared the efficacy of single- and double-row rotator cuff repairs. Functional outcome scores included the American Shoulder and Elbow Surgeons (ASES) shoulder scale, the Constant shoulder score, and the University of California, Los Angeles (UCLA) shoulder rating scale. Radiographic failures and complications were also analyzed. A test of heterogeneity for patient demographics was also performed to determine if there were differences in the patient profiles across the included studies. Seven studies fulfilled our inclusion criteria. The test of heterogeneity across these studies showed no differences. The functional ASES, Constant, and UCLA outcome scores revealed no difference between single- and double-row rotator cuff repairs. The total retear rate, which included both complete and partial retears, was 43.1% for the single-row repair and 27.2% for the double-row repair (P = .057), representing a trend toward higher failures in the single-row group. Through a comprehensive literature search and meta-analysis of current arthroscopic rotator cuff repairs, we found that the single-row repairs did not differ from the double-row repairs in functional outcome scores. The double-row repairs revealed a trend toward a lower radiographic proven retear rate, although the data did not reach statistical significance. There

  12. Self concepts, health locus of control and cognitive functioning associated with health-promoting lifestyles in schizophrenia.

    Science.gov (United States)

    Chuang, Shu Ping; Wu, Jo Yung Wei; Wang, Chien Shu; Liu, Chia Hsuan; Pan, Li Hsiang

    2016-10-01

    The study aimed to investigate the relationship among self concepts, health locus of control, cognitive functioning and health-promoting lifestyles in patients diagnosed with schizophrenia. We examined health-promoting lifestyles through self-efficacy, self-esteem, health locus of control and neurocognitive factors. Fifty-six people with schizophrenia were enrolled in the study group. All subjects participated in the self-esteem (Rosenberg Self-Esteem Scale), self-efficacy (General Self-Efficacy Scale), health locus of control (The Multidimensional Health Locus of Control Scales), health-promoting lifestyles (Health Promotion Life-style Profile-II) and a series of neurocognitive measures. Stepwise regression analysis revealed that self-efficacy, internal health locus of control and attentional set-shifting accounted for 42% of the variance in total health-promoting lifestyles scores. Self-efficacy, self-esteem, internal and powerful others health locus of control and attentional set-shifting were significant predictors for domains of health-promoting lifestyles, respectively. Study findings can help mental health professionals maintain and improve health-promoting behaviors through a better understanding of self-esteem, self-efficacy, health locus of control and neurocognitive functioning among people with schizophrenia. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Promoting functional foods as acceptable alternatives to doping: potential for information-based social marketing approach.

    Science.gov (United States)

    James, Ricky; Naughton, Declan P; Petróczi, Andrea

    2010-11-10

    Substances with performance enhancing properties appear on a continuum, ranging from prohibited performance enhancing drugs (PED) through dietary supplements to functional foods (FF). Anti-doping messages designed to dissuade athletes from using PEDs have been typically based on moralising sport competition and/or employing scare campaigns with focus on the negative consequences. Campaigns offering comparable and acceptable alternatives are nonexistent, nor are athletes helped in finding these for themselves. It is timely that social marketing strategies for anti-doping prevention and intervention incorporate media messages that complement the existing approaches by promoting comparable and acceptable alternatives to doping. To facilitate this process, the aim of this study was to ascertain whether a single exposure knowledge-based information intervention led to increased knowledge and subsequently result in changes in beliefs and automatic associations regarding performance enhancements. In a repeated measure design, 115 male recreational gym users were recruited and provided with a brief information pamphlet on nitrite/nitrate and erythropoietin as a comparison. Measures of knowledge, beliefs and automatic associations were taken before and after the intervention with at least 24 hours between the two assessments. The psychological tests included explicit measures of beliefs and cognitive attitudes toward FF and PED using a self-reported questionnaire and computerised assessments of automatic associations using the modified and shortened version of the Implicit Association Test. The information based intervention significantly increased knowledge (p social marketing campaigns for drug free sport should follow appropriate market segmentation and use targeted messages via promoting the natural form as opposed to the purified form of the main active ingredient.

  14. Promoting functional foods as acceptable alternatives to doping: potential for information-based social marketing approach

    Directory of Open Access Journals (Sweden)

    Petróczi Andrea

    2010-11-01

    Full Text Available Abstract Background Substances with performance enhancing properties appear on a continuum, ranging from prohibited performance enhancing drugs (PED through dietary supplements to functional foods (FF. Anti-doping messages designed to dissuade athletes from using PEDs have been typically based on moralising sport competition and/or employing scare campaigns with focus on the negative consequences. Campaigns offering comparable and acceptable alternatives are nonexistent, nor are athletes helped in finding these for themselves. It is timely that social marketing strategies for anti-doping prevention and intervention incorporate media messages that complement the existing approaches by promoting comparable and acceptable alternatives to doping. To facilitate this process, the aim of this study was to ascertain whether a single exposure knowledge-based information intervention led to increased knowledge and subsequently result in changes in beliefs and automatic associations regarding performance enhancements. Methods In a repeated measure design, 115 male recreational gym users were recruited and provided with a brief information pamphlet on nitrite/nitrate and erythropoietin as a comparison. Measures of knowledge, beliefs and automatic associations were taken before and after the intervention with at least 24 hours between the two assessments. The psychological tests included explicit measures of beliefs and cognitive attitudes toward FF and PED using a self-reported questionnaire and computerised assessments of automatic associations using the modified and shortened version of the Implicit Association Test. Results The information based intervention significantly increased knowledge (p p p Conclusion Evidence was found that even a single exposure to a persuasive positive message can lead to belief change and can create new or alter existing associations - but only in the specific domain. Interventions to change outcome expectations in a positive

  15. Optically-Induced Neuronal Activity Is Sufficient to Promote Functional Motor Axon Regeneration In Vivo.

    Directory of Open Access Journals (Sweden)

    Patricia J Ward

    Full Text Available Peripheral nerve injuries are common, and functional recovery is very poor. Beyond surgical repair of the nerve, there are currently no treatment options for these patients. In experimental models of nerve injury, interventions (such as exercise and electrical stimulation that increase neuronal activity of the injured neurons effectively enhance axon regeneration. Here, we utilized optogenetics to determine whether increased activity alone is sufficient to promote motor axon regeneration. In thy-1-ChR2/YFP transgenic mice in which a subset of motoneurons express the light-sensitive cation channel, channelrhodopsin (ChR2, we activated axons in the sciatic nerve using blue light immediately prior to transection and surgical repair of the sciatic nerve. At four weeks post-injury, direct muscle EMG responses evoked with both optical and electrical stimuli as well as the ratio of these optical/electrical evoked EMG responses were significantly greater in mice that received optical treatment. Thus, significantly more ChR2+ axons successfully re-innervated the gastrocnemius muscle in mice that received optical treatment. Sections of the gastrocnemius muscles were reacted with antibodies to Synaptic Vesicle Protein 2 (SV2 to quantify the number of re-occupied motor endplates. The number of SV2+ endplates was greater in mice that received optical treatment. The number of retrogradely-labeled motoneurons following intramuscular injection of cholera toxin subunit B (conjugated to Alexa Fluor 555 was greater in mice that received optical treatment. Thus, the acute (1 hour, one-time optical treatment resulted in robust, long-lasting effects compared to untreated animals as well as untreated axons (ChR2-. We conclude that neuronal activation is sufficient to promote motor axon regeneration, and this regenerative effect is specific to the activated neurons.

  16. Folate deficiency facilitates recruitment of upstream binding factor to hot spots of DNA double-strand breaks of rRNA genes and promotes its transcription.

    Science.gov (United States)

    Xie, Qiu; Li, Caihua; Song, Xiaozhen; Wu, Lihua; Jiang, Qian; Qiu, Zhiyong; Cao, Haiyan; Yu, Kaihui; Wan, Chunlei; Li, Jianting; Yang, Feng; Huang, Zebing; Niu, Bo; Jiang, Zhengwen; Zhang, Ting

    2017-03-17

    The biogenesis of ribosomes in vivo is an essential process for cellular functions. Transcription of ribosomal RNA (rRNA) genes is the rate-limiting step in ribosome biogenesis controlled by environmental conditions. Here, we investigated the role of folate antagonist on changes of DNA double-strand breaks (DSBs) landscape in mouse embryonic stem cells. A significant DSB enhancement was detected in the genome of these cells and a large majority of these DSBs were found in rRNA genes. Furthermore, spontaneous DSBs in cells under folate deficiency conditions were located exclusively within the rRNA gene units, representing a H3K4me1 hallmark. Enrichment H3K4me1 at the hot spots of DSB regions enhanced the recruitment of upstream binding factor (UBF) to rRNA genes, resulting in the increment of rRNA genes transcription. Supplement of folate resulted in a restored UBF binding across DNA breakage sites of rRNA genes, and normal rRNA gene transcription. In samples from neural tube defects (NTDs) with low folate level, up-regulation of rRNA gene transcription was observed, along with aberrant UBF level. Our results present a new view by which alterations in folate levels affects DNA breakage through epigenetic control leading to the regulation of rRNA gene transcription during the early stage of development. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  17. Cyclic-glycine-proline accelerates mammary involution by promoting apoptosis and inhibiting IGF-1 function.

    Science.gov (United States)

    Singh-Mallah, Gagandeep; McMahon, Christopher D; Guan, Jian; Singh, Kuljeet

    2017-12-01

    In rodents, post-lactational involution of mammary glands is characterized by the loss of mammary epithelial cells via apoptosis, which is associated with a decline in the expression of insulin-like growth factor-1 (IGF-1). Overexpression of IGF-1 delays involution by inhibiting apoptosis of epithelial cells and preserving the remaining secretory alveoli. Cyclic-glycine-proline (cGP), a metabolite of IGF-1, normalizes IGF-1 function under pathological conditions by regulating the bioavailability of IGF-1. The present study investigated the effect of cGP on the physiological decline in IGF-1 function during post-lactational mammary involution. Rat dams were gavaged with either cGP (3 mg/kg) or saline once per day from post-natal d8-22. Before collecting tissue on post-natal d23, a pair of mammary glands were sealed on d20 (72 hr-engorgement, thus representative of late-involution) and d22 (24 hr-engorgement, thus representative of mid-involution), while the remaining glands were allowed to involute naturally (early-involution). During early-involution, cGP accelerated the loss of mammary cells through apoptosis, resulting in an earlier clearance of intact secretory alveoli compared with the control group. This coincided with an earlier up-regulation of the cell survival factors, Bcl-xl and IGF-1R, in the early-involution cGP glands compared with the control glands. During late-involution, cGP reduced the bioactivity of IGF-1, which was evident through decreased phosphorylation of IGF-1R in the regressed alveoli. Maternal administration of cGP did not alter milk production and composition during early-, peak-, or late-stage of lactation. These data show that cGP accelerates post-lactational involution by promoting apoptosis and the physiological decline in IGF-1 function. © 2017 Wiley Periodicals, Inc.

  18. EGF Functionalized Polymer-Coated Gold Nanoparticles Promote EGF Photostability and EGFR Internalization for Photothermal Therapy.

    Directory of Open Access Journals (Sweden)

    Catarina Oliveira Silva

    Full Text Available The application of functionalized nanocarriers on photothermal therapy for cancer ablation has wide interest. The success of this application depends on the therapeutic efficiency and biocompatibility of the system, but also on the stability and biorecognition of the conjugated protein. This study aims at investigating the hypothesis that EGF functionalized polymer-coated gold nanoparticles promote EGF photostability and EGFR internalization, making these conjugated particles suitable for photothermal therapy. The conjugated gold nanoparticles (100-200 nm showed a plasmon absorption band located within the near-infrared range (650-900 nm, optimal for photothermal therapy applications. The effects of temperature, of polymer-coated gold nanoparticles and of UVB light (295nm on the fluorescence properties of EGF have been investigated with steady-state and time-resolved fluorescence spectroscopy. The fluorescence properties of EGF, including the formation of Trp and Tyr photoproducts, is modulated by temperature and by the intensity of the excitation light. The presence of polymeric-coated gold nanoparticles reduced or even avoided the formation of Trp and Tyr photoproducts when EGF is exposed to UVB light, protecting this way the structure and function of EGF. Cytotoxicity studies of conjugated nanoparticles carried out in normal-like human keratinocytes showed small, concentration dependent decreases in cell viability (0-25%. Moreover, conjugated nanoparticles could activate and induce the internalization of overexpressed Epidermal Growth Factor Receptor in human lung carcinoma cells. In conclusion, the gold nanoparticles conjugated with Epidermal Growth Factor and coated with biopolymers developed in this work, show a potential application for near infrared photothermal therapy, which may efficiently destroy solid tumours, reducing the damage of the healthy tissue.

  19. EGF Functionalized Polymer-Coated Gold Nanoparticles Promote EGF Photostability and EGFR Internalization for Photothermal Therapy

    Science.gov (United States)

    Silva, Catarina Oliveira; Petersen, Steffen B.; Reis, Catarina Pinto; Rijo, Patrícia; Molpeceres, Jesús; Fernandes, Ana Sofia; Gonçalves, Odete; Gomes, Andreia C.; Correia, Isabel; Vorum, Henrik; Neves-Petersen, Maria Teresa

    2016-01-01

    The application of functionalized nanocarriers on photothermal therapy for cancer ablation has wide interest. The success of this application depends on the therapeutic efficiency and biocompatibility of the system, but also on the stability and biorecognition of the conjugated protein. This study aims at investigating the hypothesis that EGF functionalized polymer-coated gold nanoparticles promote EGF photostability and EGFR internalization, making these conjugated particles suitable for photothermal therapy. The conjugated gold nanoparticles (100–200 nm) showed a plasmon absorption band located within the near-infrared range (650–900 nm), optimal for photothermal therapy applications. The effects of temperature, of polymer-coated gold nanoparticles and of UVB light (295nm) on the fluorescence properties of EGF have been investigated with steady-state and time-resolved fluorescence spectroscopy. The fluorescence properties of EGF, including the formation of Trp and Tyr photoproducts, is modulated by temperature and by the intensity of the excitation light. The presence of polymeric-coated gold nanoparticles reduced or even avoided the formation of Trp and Tyr photoproducts when EGF is exposed to UVB light, protecting this way the structure and function of EGF. Cytotoxicity studies of conjugated nanoparticles carried out in normal-like human keratinocytes showed small, concentration dependent decreases in cell viability (0–25%). Moreover, conjugated nanoparticles could activate and induce the internalization of overexpressed Epidermal Growth Factor Receptor in human lung carcinoma cells. In conclusion, the gold nanoparticles conjugated with Epidermal Growth Factor and coated with biopolymers developed in this work, show a potential application for near infrared photothermal therapy, which may efficiently destroy solid tumours, reducing the damage of the healthy tissue. PMID:27788212

  20. The Pacific White Shrimp β-actin Promoter: Functional Properties and the Potential Application for Transduction System Using Recombinant Baculovirus.

    Science.gov (United States)

    Shi, Yingli; Xiang, Jianhai; Zhou, Guangzhou; Ron, Tetsuzan Benny; Tong, Hsin-I; Kang, Wen; Sun, Si; Lu, Yuanan

    2016-06-01

    A newly isolated Pacific white shrimp (Litopenaeus vannamei) beta-actin promoter SbaP and its derivative compact construct SbaP (ENX) have recently been demonstrated to promote ectopic gene expression in vitro and in vivo. To further explore the potential transduction application, this newly isolated shrimp promoter SbaP was comparatively tested with cytomegalovirus (CMV), simian virus 40 (SV40), polyhedrin (Polh), and white spot syndrome virus immediate early gene 1 (WSSV ie1) four constitutive promoters and a beta-actin promoter (TbaP) from tilapia fish to characterize its promoting function in eight different cell lines. Luciferase quantitation assays revealed that SbaP can drive luciferase gene expression in all eight cell lines including sf21 (insect), PAC2 (zebrafish), EPC (carp), CHSE-214 (chinook salmon), GSTEF (green sea turtle), MS-1 (monk seal), 293T (human), and HeLa (human), but at different levels. Comparative analysis revealed that the promoting activity of SbaP was lower (≤10-fold) than CMV but higher (2-20 folds) than Polh in most of these cell lines tested. Whereas, SbaP mediated luciferase expression in sf21 cells was over 20-fold higher than CMV, SV40, Polh, and TbaP promoter. Compared to the SbaP, SbaP (ENX), which was constructed on the basis of SbaP by deletion of two "negative" regulatory elements, exhibited no significant change of promoting activity in EPC and PAC2 cells, but a 5 and 16 % lower promoting effect in 293T and HeLa cells, respectively. Additionally, a recombinant baculovirus was constructed under the control of SbaP (ENX), and efficient promoter activity of newly generated baculoviral vector was detected both in vitro of infected sf21 cells and in vivo of injected indicator shrimp. These results warrant the potential application of SbaP, particularly SbaP (ENX) in ectopic gene expression in future.

  1. Dietary nitrate improves vascular function in patients with hypercholesterolemia: a randomized, double-blind, placebo-controlled study123

    Science.gov (United States)

    Velmurugan, Shanti; Gan, Jasmine Ming; Rathod, Krishnaraj S; Khambata, Rayomand S; Ghosh, Suborno M; Hartley, Amy; Van Eijl, Sven; Sagi-Kiss, Virag; Chowdhury, Tahseen A; Curtis, Mike; Kuhnle, Gunter GC; Wade, William G; Ahluwalia, Amrita

    2016-01-01

    Background: The beneficial cardiovascular effects of vegetables may be underpinned by their high inorganic nitrate content. Objective: We sought to examine the effects of a 6-wk once-daily intake of dietary nitrate (nitrate-rich beetroot juice) compared with placebo intake (nitrate-depleted beetroot juice) on vascular and platelet function in untreated hypercholesterolemics. Design: A total of 69 subjects were recruited in this randomized, double-blind, placebo-controlled parallel study. The primary endpoint was the change in vascular function determined with the use of ultrasound flow-mediated dilatation (FMD). Results: Baseline characteristics were similar between the groups, with primary outcome data available for 67 patients. Dietary nitrate resulted in an absolute increase in the FMD response of 1.1% (an ∼24% improvement from baseline) with a worsening of 0.3% in the placebo group (P nitrate group, showing a trend (P = 0.06) to improvement in comparison with the placebo group. Dietary nitrate also caused a small but significant reduction (7.6%) in platelet-monocyte aggregates compared with an increase of 10.1% in the placebo group (P = 0.004), with statistically significant reductions in stimulated (ex vivo) P-selectin expression compared with the placebo group (P nitrate were detected. The composition of the salivary microbiome was altered after the nitrate treatment but not after the placebo treatment (P nitrate treatment; of those taxa present, 2 taxa were responsible for >1% of this change, with the proportions of Rothia mucilaginosa trending to increase and Neisseria flavescens (P nitrate treatment relative to after placebo treatment. Conclusions: Sustained dietary nitrate ingestion improves vascular function in hypercholesterolemic patients. These changes are associated with alterations in the oral microbiome and, in particular, nitrate-reducing genera. Our findings provide additional support for the assessment of the potential of dietary nitrate as a

  2. Correction: General optimization procedure towards the design of a new family of minimal parameter spin-component-scaled double-hybrid density functional theory.

    Science.gov (United States)

    Roch, Loïc M; Baldridge, Kim K

    2018-02-07

    Correction for 'General optimization procedure towards the design of a new family of minimal parameter spin-component-scaled double-hybrid density functional theory' by Loïc M. Roch and Kim K. Baldridge, Phys. Chem. Chem. Phys., 2017, 19, 26191-26200.

  3. Does interscalene catheter placement with stimulating catheters improve postoperative pain or functional outcome after shoulder surgery? A prospective, randomized and double-blinded trial

    NARCIS (Netherlands)

    Stevens, Markus F.; Werdehausen, Robert; Golla, Elisabeth; Braun, Sebastian; Hermanns, Henning; Ilg, Ansgar; Willers, Reinhardt; Lipfert, Peter

    2007-01-01

    BACKGROUND: In this prospective, randomized, double-blind trial we investigated the use of stimulating catheters in patients during and after shoulder surgery; functional improvement being the primary outcome measurement. METHODS: After eliciting an adequate muscular twitch at

  4. Mechanisms underlying the promotion of functional recovery by deferoxamine after spinal cord injury in rats

    Directory of Open Access Journals (Sweden)

    Jian Hao

    2017-01-01

    Full Text Available Deferoxamine, a clinically safe drug used for treating iron overload, also repairs spinal cord injury although the mechanism for this action remains unknown. Here, we determined whether deferoxamine was therapeutic in a rat model of spinal cord injury and explored potential mechanisms for this effect. Spinal cord injury was induced by impacting the spinal cord at the thoracic T10 vertebra level. One group of injured rats received deferoxamine, a second injured group received saline, and a third group was sham operated. Both 2 days and 2 weeks after spinal cord injury, total iron ion levels and protein expression levels of the proinflammatory cytokines tumor necrosis factor-α and interleukin-1β and the pro-apoptotic protein caspase-3 in the spinal cords of the injured deferoxamine-treated rats were significantly lower than those in the injured saline-treated group. The percentage of the area positive for glial fibrillary acidic protein immunoreactivity and the number of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells were also significantly decreased both 2 days and 2 weeks post injury, while the number of NeuN-positive cells and the percentage of the area positive for the oligodendrocyte marker CNPase were increased in the injured deferoxamine-treated rats. At 14–56 days post injury, hind limb motor function in the deferoxamine-treated rats was superior to that in the saline-treated rats. These results suggest that deferoxamine decreases total iron ion, tumor necrosis factor-α, interleukin-1β, and caspase-3 expression levels after spinal cord injury and inhibits apoptosis and glial scar formation to promote motor function recovery.

  5. Italian ICF training programs: describing and promoting human functioning and research.

    Science.gov (United States)

    Francescutti, Carlo; Fusaro, Guido; Leonardi, Matilde; Martinuzzi, Andrea; Sala, Marina; Russo, Emanuela; Frare, Mara; Pradal, Monica; Zampogna, Daniela; Cosentino, Alessandro; Raggi, Alberto

    2009-01-01

    Purpose of the article is to report on 5 years of ICF training experiences in Italy aimed at promoting a consistent approach to ICF's field application. More than 7000 persons participated in around 150 training events: almost half were organised by political bodies, at national, regional or local level, directly linked to implementation experiences. Few training events were organised by the school sector, while training commissioned by NGOs represent a relevant area and, in our opinion, constitute the first step towards a full inclusion of persons with disabilities. Central pillars of our training modules are: the inclusion of all ICF components in the description of functional profiles, the need of providing brief theoretical background information before moving to practical aspects and the importance of providing personalised face to face training modules, in contrast to self-administered learning modules, or web-based protocols. On the basis of our experience, we can conclude that training's objectives are generally reached: trainees improved their knowledge of the ICF and its related tools, and are able to begin practical applications in their contexts.

  6. NF45/ILF2 tissue expression, promoter analysis, and interleukin-2 transactivating function

    International Nuclear Information System (INIS)

    Zhao Guohua; Shi Lingfang; Qiu Daoming; Hu Hong; Kao, Peter N.

    2005-01-01

    NF45/ILF2 associates with NF90/ILF3 in the nucleus and regulates IL-2 gene transcription at the antigen receptor response element (ARRE)/NF-AT DNA target sequence (P.N. Kao, L. Chen, G. Brock, J. Ng, A.J. Smith, B. Corthesy, J. Biol. Chem. 269 (1994) 20691-20699). NF45 is widely expressed in normal tissues, especially testis, brain, and kidney, with a predominantly nuclear distribution. NF45 mRNA expression is increased in lymphoma and leukemia cell lines. The human and murine NF45 proteins differ only by substitution of valine by isoleucine at amino acid 142. Fluorescence in situ hybridization localized the human NF45 gene to chromosome 1q21.3, and mouse NF45 gene to chromosome 3F1. Promoter analysis of 2.5 kB of the murine NF45 gene reveals that significant activation is conferred by factors, possible including NF-Y, that bind to the CCAAT-box sequence. The function of human NF45 in regulating IL-2 gene expression was characterized in Jurkat T-cells stably transfected with plasmids directing expression of NF45 cDNA in sense or antisense orientations. NF45 sense expression increased IL-2 luciferase reporter gene activity 120-fold, and IL-2 protein expression 2-fold compared to control cells. NF45 is a highly conserved, regulated transcriptional activator, and one target gene is IL-2

  7. Synthesis of a Novel Allyl-Functionalized Deep Eutectic Solvent to Promote Dissolution of Cellulose

    Directory of Open Access Journals (Sweden)

    Hongwei Ren

    2016-08-01

    Full Text Available Deep eutectic solvents (DESs offer attractive options for the “green” dissolution of cellulose. However, the protic hydroxyl group causes weak dissolving ability of DESs, requiring the substitution of hydroxyl groups in the cation. In this study, a novel allyl-functionalized DES was synthesized and characterized, and its possible effect on improved dissolution of cellulose was investigated. The DES was synthesized by a eutectic mixture of allyl triethyl ammonium chloride ([ATEAm]Cl and oxalic acid (Oxa at a molar ratio of 1:1 and a freezing point of 49 °C. The [ATEAm]Cl-Oxa exhibited high polarity (56.40 kcal/mol, dipolarity/polarizability effects (1.10, hydrogen-bond donating acidity (0.41, hydrogen-bond basicity (0.89, and low viscosity (76 cP at 120 °C owing to the π-π conjugative effect induced by the allyl group. The correlation between temperature and viscosity on the [ATEAm]Cl-Oxa fit the Arrhenius equation well. The [ATEAm]Cl-Oxa showed low pseudo activation energy for viscous flow (44.56 kJ/mol. The improved properties of the [ATEAm]Cl-Oxa noticeably promoted the solubility (6.48 wt.% of cellulose.

  8. CIITA promoter I CARD-deficient mice express functional MHC class II genes in myeloid and lymphoid compartments.

    Science.gov (United States)

    Zinzow-Kramer, W M; Long, A B; Youngblood, B A; Rosenthal, K M; Butler, R; Mohammed, A-U-R; Skountzou, I; Ahmed, R; Evavold, B D; Boss, J M

    2012-06-01

    Three distinct promoters control the master regulator of major histocompatibility complex (MHC) class II expression, class II transactivator (CIITA), in a cell type-specific manner. Promoter I (pI) CIITA, expressed primarily by dendritic cells (DCs) and macrophages, expresses a unique isoform that contains a caspase-recruitment domain (CARD). The activity and function of this isoform are not understood, but are believed to enhance the function of CIITA in antigen-presenting cells. To determine whether isoform I of CIITA has specific functions, CIITA mutant mice were created in which isoform I was replaced with isoform III sequences. Mice in which pI and the CARD-encoding exon were deleted were also created. No defect in the formation of CD4 T cells, the ability to respond to a model antigen or bacterial or viral challenge was observed in mice lacking CIITA isoform I. Although CIITA and MHC-II expression was decreased in splenic DCs, pI knockout animals expressed CIITA from downstream promoters, suggesting that control of pI activity is mediated by unknown distal elements that could act at pIII, the B-cell promoter. Thus, no critical function is linked to the CARD domain of CIITA isoform I with respect to basic immune system development, function and challenge.

  9. From harmful Microcystis blooms to multi-functional core-double-shell microsphere bio-hydrochar materials.

    Science.gov (United States)

    Bi, Lei; Pan, Gang

    2017-11-13

    Harmful algal blooms (HABs) induced by eutrophication is becoming a serious global environmental problem affecting public health and aquatic ecological sustainability. A novel strategy for the utilization of biomass from HABs was developed by converting the algae cells into hollow mesoporous bio-hydrochar microspheres via hydrothermal carbonization method. The hollow microspheres were used as microreactors and carriers for constructing CaO 2 core-mesoporous shell-CaO 2 shell microspheres (OCRMs). The CaO 2 shells could quickly increase dissolved oxygen to extremely anaerobic water in the initial 40 min until the CaO 2 shells were consumed. The mesoporous shells continued to act as regulators restricting the release of oxygen from CaO 2 cores. The oxygen-release time using OCRMs was 7 times longer than when directly using CaO 2 . More interestingly, OCRMs presented a high phosphate removal efficiency (95.6%) and prevented the pH of the solution from rising to high levels in comparison with directly adding CaO 2 due to the OH - controlled-release effect of OCRMs. The distinct core-double-shell micro/nanostructure endowed the OCRMs with triple functions for oxygen controlled-release, phosphorus removal and less impact on water pH. The study is to explore the possibility to prepare smarter bio-hydrochar materials by utilizing algal blooms.

  10. Cloning and Functional Analysis of the Promoter of an Ascorbate Oxidase Gene from Gossypium hirsutum

    OpenAIRE

    Xin, Shan; Tao, Chengcheng; Li, Hongbin

    2016-01-01

    Apoplastic ascorbate oxidase (AO) plays significant roles in plant cell growth. However, the mechanism of underlying the transcriptional regulation of AO in Gossypium hirsutum remains unclear. Here, we obtained a 1,920-bp promoter sequence from the Gossypium hirsutum ascorbate oxidase (GhAO1) gene, and this GhAO1 promoter included a number of known cis-elements. Promoter activity analysis in overexpressing pGhAO1::GFP-GUS tobacco (Nicotiana benthamiana) showed that the GhAO1 promoter exhibite...

  11. EphA4 blockers promote axonal regeneration and functional recovery following spinal cord injury in mice.

    Directory of Open Access Journals (Sweden)

    Yona Goldshmit

    Full Text Available Upregulation and activation of developmental axon guidance molecules, such as semaphorins and members of the Eph receptor tyrosine kinase family and their ligands, the ephrins, play a role in the inhibition of axonal regeneration following injury to the central nervous system. Previously we have demonstrated in a knockout model that axonal regeneration following spinal cord injury is promoted in the absence of the axon guidance protein EphA4. Antagonism of EphA4 was therefore proposed as a potential therapy to promote recovery from spinal cord injury. To further assess this potential, two soluble recombinant blockers of EphA4, unclustered ephrin-A5-Fc and EphA4-Fc, were examined for their ability to promote axonal regeneration and to improve functional outcome following spinal cord hemisection in wildtype mice. A 2-week administration of either of these blockers following spinal cord injury was sufficient to promote substantial axonal regeneration and functional recovery by 5 weeks following injury. Both inhibitors produced a moderate reduction in astrocytic gliosis, indicating that much of the effect of the blockers may be due to promotion of axon growth. These studies provide definitive evidence that soluble inhibitors of EphA4 function offer considerable therapeutic potential for the treatment of spinal cord injury and may have broader potential for the treatment of other central nervous system injuries.

  12. Effect of short-term estrogen therapy on endothelial function: a double-blinded, randomized, controlled trial.

    Science.gov (United States)

    Hurtado, R; Celani, M; Geber, S

    2016-10-01

    To evaluate the effect of short-term hormone replacement therapy with 0.625 mg conjugated estrogens daily on endothelial function of healthy postmenopausal women, using flow-mediated dilation (FMD) of the brachial artery. We performed a double-blinded, randomized, controlled trial over 3 years. Randomization was performed using computer-generated sorting. All participants were blinded to the use of conjugated equine estrogens (CEE) or placebo and FMD was assessed by a blinded examiner, before and after 28 days of medication. A total of 64 healthy postmenopausal women were selected and randomly assigned into two groups of treatment: 0.625 mg of CEE or placebo. FMD values were statistically different between the groups (p = 0.025): the group receiving CEE showed a FMD value of 0.011 compared to the placebo group (FMD = -0.082). The two groups were additionally evaluated for homogeneity through the Shapiro-Wilk test in respect to variables that could interfere with endothelial function such as age (p = 0.729), body mass index (p = 0.891), and time since menopause (p = 0.724). Other variables were excluded during selection of the participants such as chronic vascular conditions, smoking, and sedentary lifestyle. Our results demonstrate that the administration of 0.625 mg CEE for 28 days is effective in improving vascular nitric oxide-dependent dilation assessed by FMD of the brachial artery in postmenopausal women. NCT01482416.

  13. Taurine Supplementation Lowers Blood Pressure and Improves Vascular Function in Prehypertension: Randomized, Double-Blind, Placebo-Controlled Study.

    Science.gov (United States)

    Sun, Qianqian; Wang, Bin; Li, Yingsha; Sun, Fang; Li, Peng; Xia, Weijie; Zhou, Xunmei; Li, Qiang; Wang, Xiaojing; Chen, Jing; Zeng, Xiangru; Zhao, Zhigang; He, Hongbo; Liu, Daoyan; Zhu, Zhiming

    2016-03-01

    Taurine, the most abundant, semiessential, sulfur-containing amino acid, is well known to lower blood pressure (BP) in hypertensive animal models. However, no rigorous clinical trial has validated whether this beneficial effect of taurine occurs in human hypertension or prehypertension, a key stage in the development of hypertension. In this randomized, double-blind, placebo-controlled study, we assessed the effects of taurine intervention on BP and vascular function in prehypertension. We randomly assigned 120 eligible prehypertensive individuals to receive either taurine supplementation (1.6 g per day) or a placebo for 12 weeks. Taurine supplementation significantly decreased the clinic and 24-hour ambulatory BPs, especially in those with high-normal BP. Mean clinic systolic BP reduction for taurine/placebo was 7.2/2.6 mm Hg, and diastolic BP was 4.7/1.3 mm Hg. Mean ambulatory systolic BP reduction for taurine/placebo was 3.8/0.3 mm Hg, and diastolic BP was 3.5/0.6 mm Hg. In addition, taurine supplementation significantly improved endothelium-dependent and endothelium-independent vasodilation and increased plasma H2S and taurine concentrations. Furthermore, changes in BP were negatively correlated with both the plasma H2S and taurine levels in taurine-treated prehypertensive individuals. To further elucidate the hypotensive mechanism, experimental studies were performed both in vivo and in vitro. The results showed that taurine treatment upregulated the expression of hydrogen sulfide-synthesizing enzymes and reduced agonist-induced vascular reactivity through the inhibition of transient receptor potential channel subtype 3-mediated calcium influx in human and mouse mesenteric arteries. In conclusion, the antihypertensive effect of chronic taurine supplementation shows promise in the treatment of prehypertension through improvement of vascular function. © 2016 American Heart Association, Inc.

  14. Effect of Uric Acid-Lowering Agents on Endothelial Function: A Randomized, Double-Blind, Placebo-Controlled Trial.

    Science.gov (United States)

    Borgi, Lea; McMullan, Ciaran; Wohlhueter, Ann; Curhan, Gary C; Fisher, Naomi D; Forman, John P

    2017-02-01

    Higher levels of serum uric acid are independently associated with endothelial dysfunction, a mechanism for incident hypertension. Overweight/obese individuals are more prone to endothelial dysfunction than their lean counterparts. However, the effect of lowering serum uric acid on endothelial dysfunction in these individuals has not been examined thoroughly. In this randomized, double-blind, placebo-controlled trial of nonhypertensive, overweight, or obese individuals with higher serum uric acid (body mass index ≥25 kg/m 2 and serum uric acid ≥5.0 mg/dL), we assigned subjects to probenecid (500-1000 mg/d), allopurinol (300-600 mg/d), or matching placebo. The primary outcome was endothelium-dependent vasodilation measured by brachial artery ultrasound at baseline and 8 weeks. By the end of the trial, 47, 49, and 53 participants had been allocated to receive probenecid, allopurinol, and placebo, respectively. Mean serum uric acid levels significantly decreased in the probenecid (from 6.1 to 3.5 mg/dL) and allopurinol groups (from 6.1 to 2.9 mg/dL) but not in the placebo group (6.1 to 5.6 mg/dL). None of the interventions produced any significant change in endothelium-dependent vasodilation (probenecid, 7.4±5.1% at baseline and 8.3±5.1% at 8 weeks; allopurinol, 7.6±6.0% at baseline and 6.2±4.8% at 8 weeks; and placebo, 6.5±3.8% at baseline and 7.1±4.9% at 8 weeks). In this randomized, double-blind, placebo-controlled trial, uric acid lowering did not affect endothelial function in overweight or obese nonhypertensive individuals. These data do not support the hypothesis that uric acid is causally related to endothelial dysfunction, a potential mechanism for development of hypertension. © 2016 American Heart Association, Inc.

  15. Valsartan improves adipose tissue function in humans with impaired glucose metabolism: a randomized placebo-controlled double-blind trial.

    Directory of Open Access Journals (Sweden)

    Gijs H Goossens

    Full Text Available BACKGROUND: Blockade of the renin-angiotensin system (RAS reduces the incidence of type 2 diabetes mellitus. In rodents, it has been demonstrated that RAS blockade improved adipose tissue (AT function and glucose homeostasis. However, the effects of long-term RAS blockade on AT function have not been investigated in humans. Therefore, we examined whether 26-wks treatment with the angiotensin II type 1 receptor blocker valsartan affects AT function in humans with impaired glucose metabolism (IGM. METHODOLOGY/PRINCIPAL FINDINGS: We performed a randomized, double-blind, placebo-controlled parallel-group study, in which 38 subjects with IGM were treated with valsartan (VAL, 320 mg/d or placebo (PLB for 26 weeks. Before and after treatment, an abdominal subcutaneous AT biopsy was collected for measurement of adipocyte size and AT gene/protein expression of angiogenesis/capillarization, adipogenesis, lipolytic and inflammatory cell markers. Furthermore, we evaluated fasting and postprandial AT blood flow (ATBF ((133Xe wash-out, systemic inflammation and insulin sensitivity (hyperinsulinemic-euglycemic clamp. VAL treatment markedly reduced adipocyte size (P<0.001, with a shift toward a higher proportion of small adipocytes. In addition, fasting (P = 0.043 and postprandial ATBF (P = 0.049 were increased, whereas gene expression of angiogenesis/capillarization, adipogenesis and macrophage infiltration markers in AT was significantly decreased after VAL compared with PLB treatment. Interestingly, the change in adipocyte size was associated with alterations in insulin sensitivity and reduced AT gene expression of macrophage infiltration markers. VAL did not alter plasma monocyte-chemoattractant protein (MCP-1, TNF-α, adiponectin and leptin concentrations. CONCLUSIONS/SIGNIFICANCE: 26-wks VAL treatment markedly reduced abdominal subcutaneous adipocyte size and AT macrophage infiltration markers, and increased ATBF in IGM subjects. The VAL

  16. Promoting Appropriate Behavior in Daily Life Contexts Using Functional Analytic Psychotherapy in Early-Adolescent Children

    Science.gov (United States)

    Cattivelli, Roberto; Tirelli, Valentina; Berardo, Federica; Perini, Silvia

    2012-01-01

    The topics of social skills development in adolescents and ways to promote this process have been amply investigated in both the clinical and educational literature. Yet, although this line of research has led to the development of many different approaches for this population, most have shown little effectiveness in promoting further social…

  17. Porcine synapsin 1: SYN1 gene analysis and functional characterization of the promoter

    DEFF Research Database (Denmark)

    Hedegaard, Claus; Kjaer-Sorensen, Kasper; Madsen, Lone Bruhn

    2013-01-01

    of elements responsible for neuron-specific expression. Expression analysis of SYN1 demonstrated presence of transcript during embryonic development. Analysis of GFP expression in transgenic zebrafish embryos suggests that the pig SYN1 promoter directs expression in neuronal cells. Thus, the SYN1 promoter...

  18. Functional analysis of a novel human serotonin transporter gene promoter in immortalized raphe cells

    DEFF Research Database (Denmark)

    Mortensen, O V; Thomassen, M; Larsen, M B

    1999-01-01

    were found to possess the additional 379 bp fragment. The integrity of the promoter was furthermore confirmed by genomic Southern blotting. The promoter activity was analyzed by reporter gene assays in neuronal and non-neuronal serotonergic cell lines. In immortalized serotonergic raphe neurons, RN46A...

  19. Apolipoprotein E Mimetic Promotes Functional and Histological Recovery in Lysolecithin-Induced Spinal Cord Demyelination in Mice

    OpenAIRE

    Gu, Zhen; Li, Fengqiao; Zhang, Yi Ping; Shields, Lisa B.E.; Hu, Xiaoling; Zheng, Yiyan; Yu, Panpan; Zhang, Yongjie; Cai, Jun; Vitek, Michael P.; Shields, Christopher B.

    2014-01-01

    Objective Considering demyelination is the pathological hallmark of multiple sclerosis (MS), reducing demyelination and/or promoting remyelination is a practical therapeutic strategy to improve functional recovery for MS. An apolipoprotein E (apoE)-mimetic peptide COG112 has previously demonstrated therapeutic efficacy on functional and histological recovery in a mouse experimental autoimmune encephalomyelitis (EAE) model of human MS. In the current study, we further investigated whether COG1...

  20. How does health-promoting lifestyle relate to sexual function among women of reproductive age in Iran?

    Science.gov (United States)

    Abedi, Parvin; Jorfi, Maryam; Afshari, Poorandokht; Fakhri, Ahmad

    2017-08-01

    This study aimed to evaluate the relation between health-promoting lifestyle and sexual function among women of reproductive age. In this cross-sectional study, 1200 women were recruited randomly from 10 public health centers in Ahvaz, Iran. A demographic questionnaire, Health Promoting Lifestyle Profile 2 (HPLP2), and Female Sexual Function Index (FSFI) were used for data collection. The inclusion criteria were as follows: women aged 15-45 years, married, monogamous, and having basic literacy. Data were analyzed using Kruskal-Wallis test, chi-square test, Spearman correlation coefficient, and logistic regression. All aspects of sexual function showed a significant relationship with different dimensions of HPLP2, except for pain and physical activity ( p function than other women (OR = 1.10, 95% CI: 1.06-1.14, p relations and stress management also showed a significant correlation with sexual function. Results of this study showed that health-promoting lifestyle dimensions are significantly related to all aspects of sexual function in women of reproductive age. Health policy makers should take lifestyle-related factors of reproductive-aged women into account when seeking to improve the sexual wellbeing of this population. Further attention should also be given to assessing the direction of causality.

  1. Functional Analysis of Maize Silk-Specific ZmbZIP25 Promoter

    Directory of Open Access Journals (Sweden)

    Wanying Li

    2018-03-01

    Full Text Available ZmbZIP25 (Zea mays bZIP (basic leucine zipper transcription factor 25 is a function-unknown protein that belongs to the D group of the bZIP transcription factor family. RNA-seq data showed that the expression of ZmbZIP25 was tissue-specific in maize silks, and this specificity was confirmed by RT-PCR (reverse transcription-polymerase chain reaction. In situ RNA hybridization showed that ZmbZIP25 was expressed exclusively in the xylem of maize silks. A 5′ RACE (rapid amplification of cDNA ends assay identified an adenine residue as the transcription start site of the ZmbZIP25 gene. To characterize this silk-specific promoter, we isolated and analyzed a 2450 bp (from −2083 to +367 and a 2600 bp sequence of ZmbZIP25 (from −2083 to +517, the transcription start site was denoted +1. Stable expression assays in Arabidopsis showed that the expression of the reporter gene GUS driven by the 2450 bp ZmbZIP25 5′-flanking fragment occurred exclusively in the papillae of Arabidopsis stigmas. Furthermore, transient expression assays in maize indicated that GUS and GFP expression driven by the 2450 bp ZmbZIP25 5′-flanking sequences occurred only in maize silks and not in other tissues. However, no GUS or GFP expression was driven by the 2600 bp ZmbZIP25 5′-flanking sequences in either stable or transient expression assays. A series of deletion analyses of the 2450 bp ZmbZIP25 5′-flanking sequence was performed in transgenic Arabidopsis plants, and probable elements prediction analysis revealed the possible presence of negative regulatory elements within the 161 bp region from −1117 to −957 that were responsible for the specificity of the ZmbZIP25 5′-flanking sequence.

  2. Low-energy extracorporeal shock wave therapy for promotion of vascular endothelial growth factor expression and angiogenesis and improvement of locomotor and sensory functions after spinal cord injury.

    Science.gov (United States)

    Yahata, Kenichiro; Kanno, Haruo; Ozawa, Hiroshi; Yamaya, Seiji; Tateda, Satoshi; Ito, Kenta; Shimokawa, Hiroaki; Itoi, Eiji

    2016-12-01

    OBJECTIVE Extracorporeal shock wave therapy (ESWT) is widely used to treat various human diseases. Low-energy ESWT increases expression of vascular endothelial growth factor (VEGF) in cultured endothelial cells. The VEGF stimulates not only endothelial cells to promote angiogenesis but also neural cells to induce neuroprotective effects. A previous study by these authors demonstrated that low-energy ESWT promoted expression of VEGF in damaged neural tissue and improved locomotor function after spinal cord injury (SCI). However, the neuroprotective mechanisms in the injured spinal cord produced by low-energy ESWT are still unknown. In the present study, the authors investigated the cell specificity of VEGF expression in injured spinal cords and angiogenesis induced by low-energy ESWT. They also examined the neuroprotective effects of low-energy ESWT on cell death, axonal damage, and white matter sparing as well as the therapeutic effect for improvement of sensory function following SCI. METHODS Adult female Sprague-Dawley rats were divided into the SCI group (SCI only) and SCI-SW group (low-energy ESWT applied after SCI). Thoracic SCI was produced using a New York University Impactor. Low-energy ESWT was applied to the injured spinal cord 3 times a week for 3 weeks after SCI. Locomotor function was evaluated using the Basso, Beattie, and Bresnahan open-field locomotor score for 42 days after SCI. Mechanical and thermal allodynia in the hindpaw were evaluated for 42 days. Double staining for VEGF and various cell-type markers (NeuN, GFAP, and Olig2) was performed at Day 7; TUNEL staining was also performed at Day 7. Immunohistochemical staining for CD31, α-SMA, and 5-HT was performed on spinal cord sections taken 42 days after SCI. Luxol fast blue staining was performed at Day 42. RESULTS Low-energy ESWT significantly improved not only locomotion but also mechanical and thermal allodynia following SCI. In the double staining, expression of VEGF was observed in Neu

  3. Double-Layer Surface Modification of Polyamide Denture Base Material by Functionalized Sol-Gel Based Silica for Adhesion Improvement.

    Science.gov (United States)

    Hafezeqoran, Ali; Koodaryan, Roodabeh

    2017-09-21

    Limited surface treatments have been proposed to improve the bond strength between autopolymerizing resin and polyamide denture base materials. Still, the bond strength of autopolymerizing resins to nylon polymer is not strong enough to repair the fractured denture effectively. This study aimed to introduce a novel method to improve the adhesion of autopolymerizing resin to polyamide polymer by a double layer deposition of sol-gel silica and N-2-(aminoethyl)-3-aminopropyltrimethoxysilane (AE-APTMS). The silica sol was synthesized by acid-catalyzed hydrolysis of tetraethylorthosilicate (TEOS) as silica precursors. Polyamide specimens were dipped in TEOS-derived sol (TS group, n = 28), and exposed to ultraviolet (UV) light under O 2 flow for 30 minutes. UV-treated specimens were immersed in AE-APTMS solution and left for 24 hours at room temperature. The other specimens were either immersed in AE-APTMS solution (AP group, n = 28) or left untreated (NT group, n = 28). Surface characterization was investigated by fourier transform infrared spectroscopy (FTIR) and atomic force microscopy (AFM). Two autopolymerizing resins (subgroups G and T, n = 14) were bonded to the specimens, thermocycled, and then tested for shear bond strength with a universal testing machine. Data were analyzed with one-way ANOVA followed by Tukey's HSD (α = 0.05). FTIR spectra of treated surfaces confirmed the chemical modification and appearance of functional groups on the polymer. One-way ANOVA revealed significant differences in shear bond strength among the study groups. Tukey's HSD showed that TS T and TS G groups had significantly higher shear bond strength than control groups (p = 0.001 and p < 0.001, respectively). Moreover, bond strength values of AP T were statistically significant compared to controls (p = 0.017). Amino functionalized TEOS-derived silica coating is a simple and cost-effective method for improving the bond strength between the autopolymerizing resin and polyamide

  4. Effect of the double-counting functional on the electronic and magnetic properties of half-metallic magnets using the GGA+U method

    International Nuclear Information System (INIS)

    Tsirogiannis, Christos; Galanakis, Iosif

    2015-01-01

    Methods based on the combination of the usual density functional theory (DFT) codes with the Hubbard models are widely used to investigate the properties of strongly correlated materials. Using first-principle calculations we study the electronic and magnetic properties of 20 half-metallic magnets performing self-consistent GGA+U calculations using both the atomic-limit (AL) and around-mean-field (AMF) functionals for the double counting term, used to subtract the correlation part from the DFT total energy, and compare these results to the usual generalized-gradient-approximation (GGA) calculations. Overall the use of AMF produces results similar to the GGA calculations. On the other hand the effect of AL is diversified depending on the studied material. In general the AL functional produces a stronger tendency towards magnetism leading in some cases to unphysical electronic and magnetic properties. Thus the choice of the adequate double-counting functional is crucial for the results obtained using the GGA+U method. - Highlights: • Ab initio study of half-metallic magnets. • Role of electronic correlations. • Double-counting term. • Atomic-limit vs around-mean-field functionals

  5. Functional promoter upstream p53 regulatory sequence of IGFBP3 that is silenced by tumor specific methylation

    International Nuclear Information System (INIS)

    Hanafusa, Tadashi; Shinji, Toshiyuki; Shiraha, Hidenori; Nouso, Kazuhiro; Iwasaki, Yoshiaki; Yumoto, Eichiro; Ono, Toshiro; Koide, Norio

    2005-01-01

    Insulin-like growth factor binding protein (IGFBP)-3 functions as a carrier of insulin-like growth factors (IGFs) in circulation and a mediator of the growth suppression signal in cells. There are two reported p53 regulatory regions in the IGFBP3 gene; one upstream of the promoter and one intronic. We previously reported a hot spot of promoter hypermethylation of IGFBP-3 in human hepatocellular carcinomas and derivative cell lines. As the hot spot locates at the putative upstream p53 consensus sequences, these p53 consensus sequences are really functional is a question to be answered. In this study, we examined the p53 consensus sequences upstream of the IGFBP-3 promoter for the p53 induced expression of IGFBP-3. Deletion, mutagenesis, and methylation constructs of IGFBP-3 promoter were assessed in the human hepatoblastoma cell line HepG2 for promoter activity. Deletions and mutations of these sequences completely abolished the expression of IGFBP-3 in the presence of p53 overexpression. In vitro methylation of these p53 consensus sequences also suppressed IGFBP-3 expression. In contrast, the expression of IGFBP-3 was not affected in the absence of p53 overexpression. Further, we observed by electrophoresis mobility shift assay that p53 binding to the promoter region was diminished when methylated. From these observations, we conclude that four out of eleven p53 consensus sequences upstream of the IGFBP-3 promoter are essential for the p53 induced expression of IGFBP-3, and hypermethylation of these sequences selectively suppresses p53 induced IGFBP-3 expression in HepG2 cells

  6. Classical density functional theory and Monte Carlo simulation study of electric double layer in the vicinity of a cylindrical electrode

    Science.gov (United States)

    Zhou, Shiqi; Lamperski, Stanisław; Sokołowska, Marta

    2017-07-01

    We have performed extensive Monte-Carlo simulations and classical density functional theory (DFT) calculations of the electrical double layer (EDL) near a cylindrical electrode in a primitive model (PM) modified by incorporating interionic dispersion interactions. It is concluded that (i) in general, an unsophisticated use of the mean field (MF) approximation for the interionic dispersion interactions does not distinctly worsen the classical DFT performance, even if the salt ions considered are highly asymmetrical in size (3:1) and charge (5:1), the bulk molar concentration considered is high up to a total bulk ion packing fraction of 0.314, and the surface charge density of up to 0.5 C m-2. (ii) More specifically, considering the possible noises in the simulation, the local volume charge density profiles are the most accurately predicted by the classical DFT in all situations, and the co- and counter-ion singlet distributions are also rather accurately predicted; whereas the mean electrostatic potential profile is relatively less accurately predicted due to an integral amplification of minor inaccuracy of the singlet distributions. (iii) It is found that the layered structure of the co-ion distribution is abnormally possible only if the surface charge density is high enough (for example 0.5 C m-2) moreover, the co-ion valence abnormally influences the peak height of the first counter-ion layer, which decreases with the former. (iv) Even if both the simulation and DFT indicate an insignificant contribution of the interionic dispersion interaction to the above three ‘local’ quantities, it is clearly shown by the classical DFT that the interionic dispersion interaction does significantly influence a ‘global’ quantity like the cylinder surface-aqueous electrolyte interfacial tension, and this may imply the role of the interionic dispersion interaction in explaining the specific Hofmeister effects. We elucidate all of the above observations based on the

  7. Protection of Salivary Function by Concomitant Pilocarpine During Radiotherapy: A Double-Blind, Randomized, Placebo-Controlled Study

    International Nuclear Information System (INIS)

    Burlage, Fred R.; Roesink, Judith M.; Kampinga, Harm H.; Coppes, Rob P.; Terhaard, Chris; Langendijk, Johannes A.; Luijk, Peter van; Stokman, Monique A.; Vissink, Arjan

    2008-01-01

    Purpose: To investigate the effect of concomitant administration of pilocarpine during radiotherapy for head-and-neck squamous cell carcinoma (HNSCC) on postradiotherapy xerostomia. Methods and Materials: A prospective, double blind, placebo-controlled randomized trial including 170 patients with HNSCC was executed to study the protective effect of pilocarpine on radiotherapy-induced parotid gland dysfunction. The primary objective endpoint was parotid flow rate complication probability (PFCP) scored 6 weeks, 6 months, and 12 months after radiotherapy. Secondary endpoints included Late Effects of Normal Tissue/Somatic Objective Management Analytic scale (LENT SOMA) and patient-rated xerostomia scores. For all parotid glands, dose-volume histograms were assessed because the dose distribution in the parotid glands is considered the most important prognostic factor with regard to radiation-induced salivary dysfunction. Results: Although no significant differences in PFCP were found for the two treatments arms, a significant (p = 0.03) reduced loss of parotid flow 1 year after radiotherapy was observed in those patients who received pilocarpine and a mean parotid dose above 40 Gy. The LENT SOMA and patient-rated xerostomia scores showed similar trends toward less dryness-related complaints for the pilocarpine group. Conclusions: Concomitant administration of pilocarpine during radiotherapy did not improve the PFCP or LENT SOMA and patient-rated xerostomia scores. In a subgroup of patients with a mean dose above 40 Gy, pilocarpine administration resulted in sparing of parotid gland function. Therefore, pilocarpine could be provided to patients in whom sufficient sparing of the parotid is not achievable

  8. Functional, genetic and chemical characterization of biosurfactants produced by plant growth-promoting Pseudomonas putida 267

    NARCIS (Netherlands)

    Kruijt, M.; Tran, H.; Raaijmakers, J.M.

    2009-01-01

    Aims: Plant growth-promoting Pseudomonas putida strain 267, originally isolated from the rhizosphere of black pepper, produces biosurfactants that cause lysis of zoospores of the oomycete pathogen Phytophthora capsici. The biosurfactants were characterized, the biosynthesis gene(s) partially

  9. The frequent evolutionary birth and death of functional promoters in mouse and human

    DEFF Research Database (Denmark)

    Young, Robert S.; Hayashizaki, Yosihide; Andersson, Robin

    2015-01-01

    Promoters are central to the regulation of gene expression. Changes in gene regulation are thought to underlie much of the adaptive diversification between species and phenotypic variation within populations. In contrast to earlier work emphasizing the importance of enhancer evolution and subtle...... diverged. Tissue-restricted promoters are the most evolutionarily volatile where retrotransposition is an important, but not the sole source of innovation. There is considerable heterogeneity of turnover rates between promoters in different tissues, but the consistency of these in both lineages suggests...... decaying with weak transcriptional output and relaxed selective constraint. Our results suggest that promoter gain and loss is an important process in the evolutionary rewiring of gene regulation and may be a significant source of phenotypic diversification....

  10. Development and Provision of Functional Foods to Promote Health on Long-Duration Space Missions

    Science.gov (United States)

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

    2016-01-01

    During long-duration NASA space missions, such as proposed missions to Mars, astronauts may experience negative physiological effects such as bone loss. Functional foods such as high-lycopene, high-flavonoids and high-omega-3 products and fruits and vegetables may mitigate the negative effects of spaceflight on physiological factors including the bone health of crewmembers. Previous studies showed that current ISS provisions provide high-lycopene and high-omega-3 food items but the variety is limited, which could promote menu fatigue. Bioactive compounds can degrade like other chemical compounds and lose functionality. The native concentrations and stability of bioactive compounds have never been determined in spaceflight foods, and adequate information is not available for commercial products for the storage durations required for space exploration (5 years). The purpose of this task is to develop new spaceflight foods that are high in omega-3 fatty acids, lycopene, or flavonoids, identify commercial products with these bioactive compounds that meet spaceflight requirements, and define the stability of these nutrients in storage to enable purposeful functional food incorporation into the space food system. The impact of storage temperature on the stability of lutein, lycopene, beta-carotene, omega-3 fatty acids, phenolics, anthocyanins and sterols is being studied in 12 ISS menu items stored at three different temperatures (4, 21, 35 degree C) over 2 years. Additionally, nutrient and quality stability are being assessed on a larger food set stored at 21 degree C over 2 years that contains twelve newly developed foods, 10 commercial products repackaged to spaceflight requirements, and another 5 current ISS menu items expected to be good sources of omega-3 fatty acids, lycopene, or flavonoids. All items were shipped overnight to the Linus Pauling Institute at Oregon State University (Corvalis, OR) after processing and 1-year of storage and analyzed for bioactive

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

    Science.gov (United States)

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

    2017-05-03

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

  12. Function of Corynebacterium glutamicum promoters in Eschrichia coli, Streptomyces lividans, and Baccillus subtilis

    Czech Academy of Sciences Publication Activity Database

    Pátek, Miroslav; Muth, G.; Wohlleben, W.

    2003-01-01

    Roč. 104, - (2003), s. 325-334 ISSN 0168-1656 R&D Projects: GA AV ČR IPP1050128; GA ČR GA525/01/0916 Institutional research plan: CEZ:AV0Z5020903 Keywords : corynebacterium glutamicum * escherichia coli * promoters Subject RIV: EE - Microbiology, Virology Impact factor: 2.543, year: 2003

  13. FoxO3A promotes metabolic adaptation to hypoxia by antagonizing Myc function

    OpenAIRE

    Jensen, Kim Steen; Binderup, Tina; Jensen, Klaus Thorleif; Therkelsen, Ib; Borup, Rehannah; Nilsson, Elise; Multhaupt, Hinke; Bouchard, Caroline; Quistorff, Bjørn; Kjær, Andreas; Landberg, Göran; Staller, Peter

    2011-01-01

    This paper characterizes FoxO3A as required for hypoxic suppression of mitochondrial mass, oxygen consumption, and ROS production. Mechanistically, FoxO3A is shown to promote hypoxic cell survival by directly antagonizing c-Myc at nuclear encoded mitochondrial genes.

  14. Extra Virgin Olive Oil Polyphenols Promote Cholesterol Efflux and Improve HDL Functionality

    Directory of Open Access Journals (Sweden)

    Hicham Berrougui

    2015-01-01

    Full Text Available Results of the present work give evidence from the beneficial role of extra virgin olive of oil (EVOO consumption towards oxidative stress and cardiovascular diseases. Polyphenols contained in EVOO are responsible for inhibiting lipoproteins oxidative damages and promoting reverse cholesterol transport process via ABCA1 pathway.

  15. Apolipoprotein E Mimetic Promotes Functional and Histological Recovery in Lysolecithin-Induced Spinal Cord Demyelination in Mice.

    Science.gov (United States)

    Gu, Zhen; Li, Fengqiao; Zhang, Yi Ping; Shields, Lisa B E; Hu, Xiaoling; Zheng, Yiyan; Yu, Panpan; Zhang, Yongjie; Cai, Jun; Vitek, Michael P; Shields, Christopher B

    2013-04-01

    Considering demyelination is the pathological hallmark of multiple sclerosis (MS), reducing demyelination and/or promoting remyelination is a practical therapeutic strategy to improve functional recovery for MS. An apolipoprotein E (apoE)-mimetic peptide COG112 has previously demonstrated therapeutic efficacy on functional and histological recovery in a mouse experimental autoimmune encephalomyelitis (EAE) model of human MS. In the current study, we further investigated whether COG112 promotes remyelination and improves functional recovery in lysolecithin induced focal demyelination in the white matter of spinal cord in mice. A focal demyelination model was created by stereotaxically injecting lysolecithin into the bilateral ventrolateral funiculus (VLF) of T8 and T9 mouse spinal cords. Immediately after lysolecithin injection mice were treated with COG112, prefix peptide control or vehicle control for 21 days. The locomotor function of the mice was measured by the beam walking test and Basso Mouse Scale (BMS) assessment. The nerve transmission of the VLF of mice was assessed in vivo by transcranial magnetic motor evoked potentials (tcMMEPs). The histological changes were also examined by by eriochrome cyanine staining, immunohistochemistry staining and electron microscopy (EM) method. The area of demyelination in the spinal cord was significantly reduced in the COG112 group. EM examination showed that treatment with COG112 increased the thickness of myelin sheaths and the numbers of surviving axons in the lesion epicenter. Locomotor function was improved in COG112 treated animals when measured by the beam walking test and BMS assessment compared to controls. TcMMEPs also demonstrated the COG112-mediated enhancement of amplitude of evoked responses. The apoE-mimetic COG112 demonstrates a favorable combination of activities in suppressing inflammatory response, mitigating demyelination and in promoting remyelination and associated functional recovery in animal model

  16. Effect of valsartan on systemic right ventricular function: a double-blind, randomized, placebo-controlled pilot trial

    NARCIS (Netherlands)

    Bom, T. van der; Winter, M.M.; Bouma, B.J.; Groenink, M.; Vliegen, H.W.; Pieper, P.G.; Dijk, A.P.J. van; Sieswerda, G.T.; Roos-Hesselink, J.W.; Zwinderman, A.H.; Mulder, B.J.

    2013-01-01

    BACKGROUND: The role of angiotensin II receptor blockers in patients with a systemic right ventricle has not been elucidated. METHODS AND RESULTS: We conducted a multicenter, double-blind, parallel, randomized controlled trial of angiotensin II receptor blocker valsartan 160 mg twice daily compared

  17. Effect of valsartan on systemic right ventricular function: a double-blind, randomized, placebo-controlled pilot trial

    NARCIS (Netherlands)

    van der Bom, Teun; Winter, Michiel M.; Bouma, Berto J.; Groenink, Maarten; Vliegen, Hubert W.; Pieper, Petronella G.; van Dijk, Arie P. J.; Sieswerda, Gertjan T.; Roos-Hesselink, Jolien W.; Zwinderman, Aeilko H.; Mulder, Barbara J. M.

    2013-01-01

    The role of angiotensin II receptor blockers in patients with a systemic right ventricle has not been elucidated. We conducted a multicenter, double-blind, parallel, randomized controlled trial of angiotensin II receptor blocker valsartan 160 mg twice daily compared with placebo in patients with a

  18. Effect of Valsartan on Systemic Right Ventricular Function A Double-Blind, Randomized, Placebo-Controlled Pilot Trial

    NARCIS (Netherlands)

    van der Bom, Teun; Winter, Michiel M.; Bouma, Berto J.; Groenink, Maarten; Vliegen, Hubert W.; Pieper, Petronella G.; van Dijk, Arie P. J.; Sieswerda, Gertjan T.; Roos-Hesselink, Jolien W.; Zwinderman, Aeilko H.; Mulder, Barbara J. M.

    2013-01-01

    Background-The role of angiotensin II receptor blockers in patients with a systemic right ventricle has not been elucidated. Methods and Results-We conducted a multicenter, double-blind, parallel, randomized controlled trial of angiotensin II receptor blocker valsartan 160 mg twice daily compared

  19. Double-Layer Structured CO2 Adsorbent Functionalized with Modified Polyethyleneimine for High Physical and Chemical Stability.

    Science.gov (United States)

    Jeon, Sunbin; Jung, Hyunchul; Kim, Sung Hyun; Lee, Ki Bong

    2018-06-18

    CO 2 capture using polyethyleneimine (PEI)-impregnated silica adsorbents has been receiving a lot of attention. However, the absence of physical stability (evaporation and leaching of amine) and chemical stability (urea formation) of the PEI-impregnated silica adsorbent has been generally established. Therefore, in this study, a double-layer impregnated structure, developed using modified PEI, is newly proposed to enhance the physical and chemical stabilities of the adsorbent. Epoxy-modified PEI and diepoxide-cross-linked PEI were impregnated via a dry impregnation method in the first and second layers, respectively. The physical stability of the double-layer structured adsorbent was noticeably enhanced when compared to the conventional adsorbents with a single layer. In addition to the enhanced physical stability, the result of simulated temperature swing adsorption cycles revealed that the double-layer structured adsorbent presented a high potential working capacity (3.5 mmol/g) and less urea formation under CO 2 -rich regeneration conditions. The enhanced physical and chemical stabilities as well as the high CO 2 working capacity of the double-layer structured adsorbent were mainly attributed to the second layer consisting of diepoxide-cross-linked PEI.

  20. Diversity of Dominant Bacterial Taxa in Activated Sludge Promotes Functional Resistance following Toxic Shock Loading

    KAUST Repository

    Saikaly, Pascal; Oerther, Daniel B. Barton

    2010-01-01

    and functional resistance. In this system, activated sludge bacterial communities with higher biodiversity are functionally more resistant to disturbance caused by toxic shock loading. © 2010 Springer Science+Business Media, LLC.

  1. Si-Jun-Zi Decoction Treatment Promotes the Restoration of Intestinal Function after Obstruction by Regulating Intestinal Homeostasis

    Directory of Open Access Journals (Sweden)

    Xiangyang Yu

    2014-01-01

    Full Text Available Intestinal obstruction is a common disease requiring abdominal surgery with significant morbidity and mortality. Currently, an effective medical treatment for obstruction, other than surgical resection or decompression, does not exist. Si-Jun-Zi Decoction is a famous Chinese medicine used to replenish qi and invigorate the functions of the spleen. Modern pharmacological studies show that this prescription can improve gastrointestinal function and strengthen immune function. In this study, we investigated the effects of a famous Chinese herbal formula, Si-Jun-Zi Decoction, on the restoration of intestinal function after the relief of obstruction in a rabbit model. We found that Si-Jun-Zi Decoction could reduce intestinal mucosal injury while promoting the recovery of the small intestine. Further, Si-Jun-Zi Decoction could regulate the intestinal immune system. Our results suggest that Si-Jun-Zi Decoction promotes the restoration of intestinal function after obstruction by regulating intestinal homeostasis. Our observations indicate that Si-Jun-Zi Decoction is potentially a therapeutic drug for intestinal obstruction.

  2. Function of the EGR-1/TIS8 radiation inducible promoter in a minimal HSV-1 amplicon system

    International Nuclear Information System (INIS)

    Spear, M.A.; Sakamoto, K.M.; Herrlinger, U.; Pechan, P.; Breakefield, X.O.

    1997-01-01

    Purpose: To evaluate function of the EGR-1/TIS8 promoter region in minimal HSV-1 amplicon system in order to determine the feasibility of using the system to regulate vector replication with radiation. Materials and Methods: A 600-base pair 5' upstream region of the EGR-1 promoter linked to chloramphenicol acetyltransferase (CAT) was recombined into a minimal HSV-1 amplicon vector system (pONEC). pONEC or a control plasmid was transfected into U87 glioma cells using the Lipofectamine method. Thirty-six hours later one aliquot of cells from each transfection was irradiated to a dose of 20 Gy and another identical aliquot served as a control. CAT activity was assayed 8 hours after irradiation. Results: pONEC transfected cells irradiated with 20 Gy demonstrated 2.0 fold increase in CAT activity compared to non-irradiated cells. Cells transfected with control plasmid showed no change in CAT activity. Unirradiated pONEC cells had CAT activity 1.3 times those transfected with control plasmid. Conclusion: We have previously created HSV-1 gene therapy amplicon vector systems which allow virus-amplicon interdependent replication, with the intent of regulating replication. The above data demonstrates that a minimal amplicon system will allow radiation dependent regulation by the EGR-1 promoter, thus indicating the possibility of using this system to regulate onsite, spatially and temporally regulated vector production. Baseline CAT activity was higher and relative induction lower than other reported expression constructs, which raises concern for the ability of the system to produce a differential in transcription levels sufficient for this purpose. This is possibly the result of residual promoter/enhancer elements remaining in the HSV-1 sequences. We are attempting to create constructs lacking these elements. Addition of secondary promoter sequences may also be of use. We are also currently evaluating the efficacy of the putative IEX-1 radiation inducible promoter region in

  3. Functional promoter variant in zinc finger protein 202 predicts severe atherosclerosis and ischemic heart disease

    DEFF Research Database (Denmark)

    Frikke-Schmidt, R.; Nordestgaard, Børge; Grande, Peer

    2008-01-01

    Objectives This study was designed to test the hypotheses that single nucleotide polymorphisms ( SNPs), in zinc finger protein 202 ( ZNF202), predict severe atherosclerosis and ischemic heart disease ( IHD). Background ZNF202 is a transcriptional repressor controlling promoter elements in genes...... involved in vascular maintenance and lipid metabolism. Methods We first determined genotype association for 9 ZNF202 SNPs with severe atherosclerosis ( ankle brachial index >0.7 vs. ...,998 controls. Finally, we determined whether g. -660A>G altered transcriptional activity of the ZNF202 promoter in vitro. Results Cross-sectionally, ZNF202 g. -660 GG versus AA homozygosity predicted an odds ratio for severe atherosclerosis of 2.01 ( 95% confidence interval [CI]: 1.34 to 3.01). Prospectively...

  4. Developmental Functions of miR156-Regulated SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) Genes in Arabidopsis thaliana.

    Science.gov (United States)

    Xu, Mingli; Hu, Tieqiang; Zhao, Jianfei; Park, Mee-Yeon; Earley, Keith W; Wu, Gang; Yang, Li; Poethig, R Scott

    2016-08-01

    Correct developmental timing is essential for plant fitness and reproductive success. Two important transitions in shoot development-the juvenile-to-adult vegetative transition and the vegetative-to-reproductive transition-are mediated by a group of genes targeted by miR156, SQUAMOSA PROMOTER BINDING PROTEIN (SBP) genes. To determine the developmental functions of these genes in Arabidopsis thaliana, we characterized their expression patterns, and their gain-of-function and loss-of-function phenotypes. Our results reveal that SBP-LIKE (SPL) genes in Arabidopsis can be divided into three functionally distinct groups: 1) SPL2, SPL9, SPL10, SPL11, SPL13 and SPL15 contribute to both the juvenile-to-adult vegetative transition and the vegetative-to-reproductive transition, with SPL9, SP13 and SPL15 being more important for these processes than SPL2, SPL10 and SPL11; 2) SPL3, SPL4 and SPL5 do not play a major role in vegetative phase change or floral induction, but promote the floral meristem identity transition; 3) SPL6 does not have a major function in shoot morphogenesis, but may be important for certain physiological processes. We also found that miR156-regulated SPL genes repress adventitious root development, providing an explanation for the observation that the capacity for adventitious root production declines as the shoot ages. miR156 is expressed at very high levels in young seedlings, and declines in abundance as the shoot develops. It completely blocks the expression of its SPL targets in the first two leaves of the rosette, and represses these genes to different degrees at later stages of development, primarily by promoting their translational repression. These results provide a framework for future studies of this multifunctional family of transcription factors, and offer new insights into the role of miR156 in Arabidopsis development.

  5. Functional role of bacteria from invasive Phragmites australis in promotion of host growth

    Science.gov (United States)

    Soares, M. A.; Li, H-Y; Kowalski, Kurt P.; Bergen, M.; Torres, M. S.; White, J. F.

    2016-01-01

    We hypothesize that bacterial endophytes may enhance the competitiveness and invasiveness of Phragmites australis. To evaluate this hypothesis, endophytic bacteria were isolated from P. australis. The majority of the shoot meristem isolates represent species from phyla Firmicutes, Proteobacteria, and Actinobacteria. We chose one species from each phylum to characterize further and to conduct growth promotion experiments in Phragmites. Bacteria tested include Bacillus amyloliquefaciens A9a, Achromobacter spanius B1, and Microbacterium oxydans B2. Isolates were characterized for known growth promotional traits, including indole acetic acid (IAA) production, secretion of hydrolytic enzymes, phosphate solubilization, and antibiosis activity. Potentially defensive antimicrobial lipopeptides were assayed for through application of co-culturing experiments and mass spectrometer analysis. B. amyloliquefaciens A9a and M. oxydans B2 produced IAA. B. amyloliquefaciens A9a secreted antifungal lipopeptides. Capability to promote growth of P. australis under low nitrogen conditions was evaluated in greenhouse experiments. All three isolates were found to increase the growth of P. australis under low soil nitrogen conditions and showed increased absorption of isotopic nitrogen into plants. This suggests that the Phragmites microbes we evaluated most likely promote growth of Phragmites by enhanced scavenging of nitrogenous compounds from the rhizosphere and transfer to host roots. Collectively, our results support the hypothesis that endophytic bacteria play a role in enhancing growth of P. australis in natural populations. Gaining a better understanding of the precise contributions and mechanisms of endophytes in enabling P. australis to develop high densities rapidly could lead to new symbiosis-based strategies for management and control of the host.

  6. Increased sales and thefts of candy as a function of sales promotion activities: Preliminary findings.

    Science.gov (United States)

    Carter, N; Kindstedt, A; Melin, L

    1995-01-01

    We used an A-B-A design to evaluate the effects of two commonly used promotional activities-price reduction and increased exposure, in combination and separately-on sales and thefts of candy at a grocery store. The combination of activities and the increased exposure condition produced the greatest increases in sales. The combination of activities was also associated with the greatest increase in thefts.

  7. Functional analysis of the rice rubisco activase promoter in transgenic Arabidopsis

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Zhipan; Lu, Qingtao; Wen, Xiaogang [Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences, Beijing 100093 (China); Chen, Fan [Key Laboratory of Molecular and Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100080 (China); Lu, Congming, E-mail: lucm@ibcas.ac.cn [Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences, Beijing 100093 (China)

    2012-02-17

    Highlights: Black-Right-Pointing-Pointer Rice rubisco activase promoter was analyzed in transgenic Arabidopsis system. Black-Right-Pointing-Pointer Region conferring tissue specific and light inducible expression of Rca was identified. Black-Right-Pointing-Pointer -58 to +43 bp region mediates tissue-specific expression of rice Rca. Black-Right-Pointing-Pointer Light inducible expression of rice Rca is mediated by -297 to -58 bp region. Black-Right-Pointing-Pointer Rice nuclear proteins bind specifically with the light inducible region. -- Abstract: To gain a better understanding of the regulatory mechanism of the rice rubisco activase (Rca) gene, variants of the Rca gene promoter (one full-length and four deletion mutants) fused to the coding region of the bacterial reporter gene {beta}-glucuronidase (GUS) were introduced into Arabidopsis via Agrobacterium-mediated transformation. Our results show that a 340 bp fragment spanning from -297 to +43 bp relative to the transcription initiation site is enough to promote tissue-specific and light-inducible expression of the rice Rca gene as done by the full-length promoter (-1428 to +43 bp). Further deletion analysis indicated that the region conferring tissue-specificity of Rca expression is localized within a 105 bp fragment from -58 to +43 bp, while light-inducible expression of Rca is mediated by the region from -297 to -58 bp. Gel shift assays and competition experiments demonstrated that rice nuclear proteins bind specifically with the fragment conferring light responsiveness at more than one binding site. This implies that multiple cis-elements may be involved in light-induced expression of the rice Rca gene. These works provide a useful reference for understanding transcriptional regulation mechanism of the rice Rca gene, and lay a strong foundation for further detection of related cis-elements and trans-factors.

  8. Functional model of the system promotion affiliate program in partner networks

    OpenAIRE

    Дмитро Сергійович Міроненко

    2017-01-01

    Structural analysis of business processes in promoting affiliate programs in the advertisement network has been done. Processes are considered according to the IDEF0 methodology. The viewpoints of advertisers, webmasters and marketers greatly experienced in affiliate marketing have been taken into account. A virtual company and the business process in it (affiliate program publication and selection, comparative analysis of the affiliate program, advertisement program start, summing up and eff...

  9. Functional analysis of the rice rubisco activase promoter in transgenic Arabidopsis

    International Nuclear Information System (INIS)

    Yang, Zhipan; Lu, Qingtao; Wen, Xiaogang; Chen, Fan; Lu, Congming

    2012-01-01

    Highlights: ► Rice rubisco activase promoter was analyzed in transgenic Arabidopsis system. ► Region conferring tissue specific and light inducible expression of Rca was identified. ► −58 to +43 bp region mediates tissue-specific expression of rice Rca. ► Light inducible expression of rice Rca is mediated by −297 to −58 bp region. ► Rice nuclear proteins bind specifically with the light inducible region. -- Abstract: To gain a better understanding of the regulatory mechanism of the rice rubisco activase (Rca) gene, variants of the Rca gene promoter (one full-length and four deletion mutants) fused to the coding region of the bacterial reporter gene β-glucuronidase (GUS) were introduced into Arabidopsis via Agrobacterium-mediated transformation. Our results show that a 340 bp fragment spanning from −297 to +43 bp relative to the transcription initiation site is enough to promote tissue-specific and light-inducible expression of the rice Rca gene as done by the full-length promoter (−1428 to +43 bp). Further deletion analysis indicated that the region conferring tissue-specificity of Rca expression is localized within a 105 bp fragment from −58 to +43 bp, while light-inducible expression of Rca is mediated by the region from −297 to −58 bp. Gel shift assays and competition experiments demonstrated that rice nuclear proteins bind specifically with the fragment conferring light responsiveness at more than one binding site. This implies that multiple cis-elements may be involved in light-induced expression of the rice Rca gene. These works provide a useful reference for understanding transcriptional regulation mechanism of the rice Rca gene, and lay a strong foundation for further detection of related cis-elements and trans-factors.

  10. Ligand-Promoted C(sp(3) )-H Olefination en Route to Multi-functionalized Pyrazoles.

    Science.gov (United States)

    Yang, Weibo; Ye, Shengqing; Schmidt, Yvonne; Stamos, Dean; Yu, Jin-Quan

    2016-05-17

    A Pd-catalyzed/N-heterocycle-directed C(sp(3) )-H olefination has been developed. The monoprotected amino acid ligand (MPAA) is found to significantly promote Pd-catalyzed C(sp(3) )-H olefination for the first time. Cu(OAc)2 instead of Ag(+) salts are used as the terminal oxidant. This reaction provides a useful method for the synthesis of alkylated pyrazoles. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Functional molecular analysis of a circadian clock gene timeless promoter from the drosophilid fly Chymomyza costata

    Czech Academy of Sciences Publication Activity Database

    Kobelková, Alena; Bajgar, Adam; Doležel, David

    2010-01-01

    Roč. 25, č. 6 (2010), s. 399-409 ISSN 0748-7304 R&D Projects: GA ČR GP204/08/P579; GA ČR(CZ) GA204/07/1032; GA AV ČR IAA500960802 Institutional research plan: CEZ:AV0Z50070508 Keywords : timeless promoter * E-box * Chymomyza costata Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.309, year: 2010

  12. General optimization procedure towards the design of a new family of minimal parameter spin-component-scaled double-hybrid density functional theory.

    Science.gov (United States)

    Roch, Loïc M; Baldridge, Kim K

    2017-10-04

    A general optimization procedure towards the development and implementation of a new family of minimal parameter spin-component-scaled double-hybrid (mSD) density functional theory (DFT) is presented. The nature of the proposed exchange-correlation functional establishes a methodology with minimal empiricism. This new family of double-hybrid (DH) density functionals is demonstrated using the PBEPBE functional, illustrating the optimization procedure to the mSD-PBEPBE method, and the performance characteristics shown for a set of non-covalent complexes covering a broad regime of weak interactions. With only two parameters, mSD-PBEPBE and its cost-effective counterpart, RI-mSD-PBEPBE, show a mean absolute error of ca. 0.4 kcal mol -1 averaged over 66 weak interacting systems. Following a successive 2D-grid refinement for a CBS extrapolation of the coefficients, the optimization procedure can be recommended for the design and implementation of a variety of additional DH methods using any of the plethora of currently available functionals.

  13. Frequency and zero-point vibrational energy scale factors for double-hybrid density functionals (and other selected methods): can anharmonic force fields be avoided?

    Science.gov (United States)

    Kesharwani, Manoj K; Brauer, Brina; Martin, Jan M L

    2015-03-05

    We have obtained uniform frequency scaling factors λ(harm) (for harmonic frequencies), λ(fund) (for fundamentals), and λ(ZPVE) (for zero-point vibrational energies (ZPVEs)) for the Weigend-Ahlrichs and other selected basis sets for MP2, SCS-MP2, and a variety of DFT functionals including double hybrids. For selected levels of theory, we have also obtained scaling factors for true anharmonic fundamentals and ZPVEs obtained from quartic force fields. For harmonic frequencies, the double hybrids B2PLYP, B2GP-PLYP, and DSD-PBEP86 clearly yield the best performance at RMSD = 10-12 cm(-1) for def2-TZVP and larger basis sets, compared to 5 cm(-1) at the CCSD(T) basis set limit. For ZPVEs, again, the double hybrids are the best performers, reaching root-mean-square deviations (RMSDs) as low as 0.05 kcal/mol, but even mainstream functionals like B3LYP can get down to 0.10 kcal/mol. Explicitly anharmonic ZPVEs only are marginally more accurate. For fundamentals, however, simple uniform scaling is clearly inadequate.

  14. Promotion of selective pathways in isomerizing functionalization of plant oils by rigid framework substituents

    KAUST Repository

    Christl, Josefine T.

    2014-10-14

    The 1,2-(CH2P(1-adamantyl)2)2C6H4 (dadpx) coordinated palladium complex [(dadpx)Pd(OTf)2] (1) is a catalyst precursor for the isomerizing methoxycarbonylation of the internal double bond of methyl oleate, with an unprecedented selectivity (96%) for the linear diester 1,19-dimethyl nonadecanedioate. Rapid formation of the catalytically active solvent-coordinated hydride species [(dadpx)PdH(MeOH)]+ (3-MeOH) is evidenced by NMR spectroscopy, and further isolation and X-ray crystal structure analysis of [(dadpx)PdH(PPh3)]+ (3-PPh3). DFT calculations of key steps of the catalytic cycle unravel methanolysis as the decisive step for enhanced selectivity and the influence of the rigid adamantyl framework on this step by destabilization of transition states of unselective pathways.

  15. Elucidation and functional characterization of CsPSY and CsUGT promoters in Crocus sativus L.

    Science.gov (United States)

    Bhat, Archana; Mishra, Sonal; Kaul, Sanjana; Dhar, Manoj K

    2018-01-01

    The dried stigmas of Crocus sativus constitute the saffron, which is considered to be the costliest spice of the world. Saffron is valuable for its constituents, which are mainly apocarotenoids. In order to enhance the production of apocarotenoids, it is imperative to understand the regulation of apocarotenoid biosynthetic pathway. In C. sativus, although the pathway has been elucidated, the information regarding the regulation of the pathwaygenes is scanty. During the present investigation, the characterization of promoters regulating the expression of two important genes i.e. CsPSY and CsUGT was performed. We successfully cloned the promoters of both the genes, which were functionally characterized in Crocus sativus and Nicotiana tabaccum. In silico analysis of the promoters demonstrated the presence of several important cis regulatory elements responding tolight, hormonesand interaction with transcription factors (TFs). Further analysis suggested the regulation of CsPSY promoter by Abscisic acid (ABA) and that of CsUGT by Gibberellic acid (GA). In addition, we also observed ABA and GA mediated modulation in the expression of significant TFs and CsPSY and CsUGT transcripts. Overall, the study addresses issues related to regulation of key genes of apocarotenoid pathway in C.sativus.

  16. Far infra-red therapy promotes ischemia-induced angiogenesis in diabetic mice and restores high glucose-suppressed endothelial progenitor cell functions

    Directory of Open Access Journals (Sweden)

    Huang Po-Hsun

    2012-08-01

    Full Text Available Abstract Background Far infra-red (IFR therapy was shown to exert beneficial effects in cardiovascular system, but effects of IFR on endothelial progenitor cell (EPC and EPC-related vasculogenesis remain unclear. We hypothesized that IFR radiation can restore blood flow recovery in ischemic hindlimb in diabetic mice by enhancement of EPCs functions and homing process. Materials and methods Starting at 4 weeks after the onset of diabetes, unilateral hindlimb ischemia was induced in streptozotocine (STZ-induced diabetic mice, which were divided into control and IFR therapy groups (n = 6 per group. The latter mice were placed in an IFR dry sauna at 34°C for 30 min once per day for 5 weeks. Results Doppler perfusion imaging demonstrated that the ischemic limb/normal side blood perfusion ratio in the thermal therapy group was significantly increased beyond that in controls, and significantly greater capillary density was seen in the IFR therapy group. Flow cytometry analysis showed impaired EPCs (Sca-1+/Flk-1+ mobilization after ischemia surgery in diabetic mice with or without IFR therapy (n = 6 per group. However, as compared to those in the control group, bone marrow-derived EPCs differentiated into endothelial cells defined as GFP+/CD31+ double-positive cells were significantly increased in ischemic tissue around the vessels in diabetic mice that received IFR radiation. In in-vitro studies, cultured EPCs treated with IFR radiation markedly augmented high glucose-impaired EPC functions, inhibited high glucose-induced EPC senescence and reduced H2O2 production. Nude mice received human EPCs treated with IFR in high glucose medium showed a significant improvement in blood flow recovery in ischemic limb compared to those without IFR therapy. IFR therapy promoted blood flow recovery and new vessel formation in STZ-induced diabetic mice. Conclusions Administration of IFR therapy promoted collateral flow recovery and new vessel formation in STZ

  17. Comprehensive genetic assessment of a functional TLR9 promoter polymorphism: no replicable association with asthma or asthma-related phenotypes

    Directory of Open Access Journals (Sweden)

    Celedón Juan C

    2011-02-01

    Full Text Available Abstract Background Prior studies suggest a role for a variant (rs5743836 in the promoter of toll-like receptor 9 (TLR9 in asthma and other inflammatory diseases. We performed detailed genetic association studies of the functional variant rs5743836 with asthma susceptibility and asthma-related phenotypes in three independent cohorts. Methods rs5743836 was genotyped in two family-based cohorts of children with asthma and a case-control study of adult asthmatics. Association analyses were performed using chi square, family-based and population-based testing. A luciferase assay was performed to investigate whether rs5743836 genotype influences TLR9 promoter activity. Results Contrary to prior reports, rs5743836 was not associated with asthma in any of the three cohorts. Marginally significant associations were found with FEV1 and FVC (p = 0.003 and p = 0.008, respectively in one of the family-based cohorts, but these associations were not significant after correcting for multiple comparisons. Higher promoter activity of the CC genotype was demonstrated by luciferase assay, confirming the functional importance of this variant. Conclusion Although rs5743836 confers regulatory effects on TLR9 transcription, this variant does not appear to be an important asthma-susceptibility locus.

  18. ATF3 expression improves motor function in the ALS mouse model by promoting motor neuron survival and retaining muscle innervation.

    Science.gov (United States)

    Seijffers, Rhona; Zhang, Jiangwen; Matthews, Jonathan C; Chen, Adam; Tamrazian, Eric; Babaniyi, Olusegun; Selig, Martin; Hynynen, Meri; Woolf, Clifford J; Brown, Robert H

    2014-01-28

    ALS is a fatal neurodegenerative disease characterized by a progressive loss of motor neurons and atrophy of distal axon terminals in muscle, resulting in loss of motor function. Motor end plates denervated by axonal retraction of dying motor neurons are partially reinnervated by remaining viable motor neurons; however, this axonal sprouting is insufficient to compensate for motor neuron loss. Activating transcription factor 3 (ATF3) promotes neuronal survival and axonal growth. Here, we reveal that forced expression of ATF3 in motor neurons of transgenic SOD1(G93A) ALS mice delays neuromuscular junction denervation by inducing axonal sprouting and enhancing motor neuron viability. Maintenance of neuromuscular junction innervation during the course of the disease in ATF3/SOD1(G93A) mice is associated with a substantial delay in muscle atrophy and improved motor performance. Although disease onset and mortality are delayed, disease duration is not affected. This study shows that adaptive axonal growth-promoting mechanisms can substantially improve motor function in ALS and importantly, that augmenting viability of the motor neuron soma and maintaining functional neuromuscular junction connections are both essential elements in therapy for motor neuron disease in the SOD1(G93A) mice. Accordingly, effective protection of optimal motor neuron function requires restitution of multiple dysregulated cellular pathways.

  19. Effect of an educational intervention to promote intradialysis aerobic exercises on the functional state of hemodialysis patients from Mexico

    Directory of Open Access Journals (Sweden)

    Carlos Enrique Cabrera-Pivaral

    2016-11-01

    Full Text Available Introduction: Health education search to influence on persons’ attitude for to improve your health by mean of healthy habits promotion. In patients with hemodialysis your functional capacity usually is diminished for physical inactivity. Objective: To evaluate the effect of a health education intervention for aerobic exercise’s promotion on the functional capacity in hemodialysis patients from Mexico. Methods: Quasi-experimental study beforeafter with control group in Hospital Medical Care Units of the Mexican Institute of Social Security, Jalisco’s Delegation, with a universe of 26 patients with hemodialysis purposively sampled, 14 in Group “A” (experimental and 12 in Group “B” (control. It included variables: age, gender and functional capacity. The intervention consisted of directed dialogue on biopsychosocial factors of renal disease, functional capacity and nutrition, with accompaniment in aerobic exercises of 30 minutes/week for 20 weeks. It evaluated functional capacity with Delta Test and it compared means before and after with Student’s T (p ≤ 0,05. Results: There were no statistically significant differences between age and gender of patients in the “A” and “B” Groups. Mean functional capacity before and after: Group “A” 14 ± 5 vs 8 ± 4 (p < 0,001, Group “B” 16 ± 4 vs 17 ± 5 (p = 0,405. Conclusions: The health education influenced favorably on the physical activity of patients with hemodialysis and improved your functional capacity. To implement aerobic exercise programs during hemodialysis sessions it advisable.

  20. Visual Restoration after Cataract Surgery Promotes Functional and Structural Brain Recovery

    Directory of Open Access Journals (Sweden)

    Haotian Lin

    2018-04-01

    Full Text Available Background: Visual function and brain function decline concurrently with aging. Notably, cataract patients often present with accelerated age-related decreases in brain function, but the underlying mechanisms are still unclear. Optical structures of the anterior segment of the eyes, such as the lens and cornea, can be readily reconstructed to improve refraction and vision quality. However, the effects of visual restoration on human brain function and structure remain largely unexplored. Methods: A prospective, controlled clinical trial was conducted. Twenty-six patients with bilateral age-related cataracts (ARCs who underwent phacoemulsification and intraocular lens implantation and 26 healthy controls without ARC, matched for age, sex, and education, were recruited. Visual functions (including visual acuity, visual evoke potential, and contrast sensitivity, the Mini-Mental State Examination and functional magnetic resonance imaging (including the fractional amplitude of low-frequency fluctuations and grey matter volume variation were assessed for all the participants and reexamined for ARC patients after cataract surgery. This trial was registered with ClinicalTrials.gov (NCT02644720. Findings: Compared with the healthy controls, the ARC patients presented decreased brain functionality as well as structural alterations in visual and cognitive-related brain areas preoperatively. Three months postoperatively, significant functional improvements were observed in the visual and cognitive-related brain areas of the patients. Six months postoperatively, the patients' grey matter volumes in these areas were significantly increased. Notably, both the function and structure in the visual and cognitive-related brain areas of the patients improved significantly and became comparable to those of the healthy controls 6 months postoperatively. Interpretation: We demonstrated that ocular reconstruction can functionally and structurally reverse cataract

  1. Surgery as a Double-Edged Sword: A Clinically Feasible Approach to Overcome the Metastasis-Promoting Effects of Surgery by Blunting Stress and Prostaglandin Responses

    International Nuclear Information System (INIS)

    Benish, Marganit; Ben-Eliyahu, Shamgar

    2010-01-01

    Surgery remains an essential therapeutic approach for most solid malignancies, including breast cancer. However, surgery also constitutes a risk factor for promotion of pre-existing micrometastases and the initiation of new metastases through several mechanisms, including the release of prostaglandins and stress hormones (e.g., catecholamines and glucocorticoids). However, the perioperative period also presents an opportunity for cell mediated immunity (CMI) and other mechanisms to eradicate or control minimal residual disease, provided that the deleterious effects of surgery are minimized. Here, we discuss the key role of endogenous stress hormones and prostaglandins in promoting the metastatic process through their direct impact on malignant cells, and through their deleterious impact on anti-cancer CMI. We further discuss the effects of anesthetic techniques, the extent of surgery, pain alleviation, and timing within the menstrual cycle with respect to their impact on tumor recurrence and physiological stress responses. Last, we suggest an attractive perioperative drug regimen, based on a combination of a cyclooxygenase (COX)-2 inhibitor and a β-adrenergic blocker, which we found effective in attenuating immune suppression and the metastasis-promoting effects of surgery in several tumor models. This regimen is clinically applicable, and could potentially promote disease free survival in patients operated for breast and other types of cancer

  2. Surgery as a Double-Edged Sword: A Clinically Feasible Approach to Overcome the Metastasis-Promoting Effects of Surgery by Blunting Stress and Prostaglandin Responses

    Energy Technology Data Exchange (ETDEWEB)

    Benish, Marganit; Ben-Eliyahu, Shamgar, E-mail: shamgar@post.tau.ac.il [Neuroimmunology Research Unit, Department of Psychology, Tel Aviv University, Tel Aviv 69978 (Israel)

    2010-11-24

    Surgery remains an essential therapeutic approach for most solid malignancies, including breast cancer. However, surgery also constitutes a risk factor for promotion of pre-existing micrometastases and the initiation of new metastases through several mechanisms, including the release of prostaglandins and stress hormones (e.g., catecholamines and glucocorticoids). However, the perioperative period also presents an opportunity for cell mediated immunity (CMI) and other mechanisms to eradicate or control minimal residual disease, provided that the deleterious effects of surgery are minimized. Here, we discuss the key role of endogenous stress hormones and prostaglandins in promoting the metastatic process through their direct impact on malignant cells, and through their deleterious impact on anti-cancer CMI. We further discuss the effects of anesthetic techniques, the extent of surgery, pain alleviation, and timing within the menstrual cycle with respect to their impact on tumor recurrence and physiological stress responses. Last, we suggest an attractive perioperative drug regimen, based on a combination of a cyclooxygenase (COX)-2 inhibitor and a β-adrenergic blocker, which we found effective in attenuating immune suppression and the metastasis-promoting effects of surgery in several tumor models. This regimen is clinically applicable, and could potentially promote disease free survival in patients operated for breast and other types of cancer.

  3. Melatonin successfully rescues hippocampal bioenergetics and improves cognitive function following drug intoxication by promoting Nrf2-ARE signaling activity.

    Science.gov (United States)

    Chen, Li-You; Renn, Ting-Yi; Liao, Wen-Chieh; Mai, Fu-Der; Ho, Ying-Jui; Hsiao, George; Lee, Ai-Wei; Chang, Hung-Ming

    2017-09-01

    Prolonged exposure to gamma-hydroxybutyric acid (GHB) would cause drug intoxication in which impaired cognitive function results from enhanced hippocampal oxidative stress may serve as a major symptom in this deficiency. Considering melatonin possesses significant anti-oxidative efficacy, this study aimed to determine whether melatonin would successfully promote the nuclear factor erythroid 2-related factor 2 and antioxidant responsive element (Nrf2-ARE) signaling, depress oxidative stress, and rescue hippocampal bioenergetics and cognitive function following drug intoxication injury. Adolescent rats subjected to 10 days of GHB were received melatonin at doses of either 10 or 100 mg/kg. Time-of-flight secondary ion mass spectrometry, biochemical assay, quantitative histochemistry, [ 14 C]-2-deoxyglucose analysis, together with Morris water maze were employed to detect the molecular signaling, oxidative status, bioenergetic level, as well as the cognitive performances, respectively. Results indicated that in GHB-intoxicated rats, enhanced oxidative stress, increased cholesterol level, and decreased anti-oxidative enzymes activities were detected in hippocampal regions. Intense oxidative stress paralleled well with reduced bioenergetics and poor performance in behavioral testing. However, in rats treated with melatonin following GHB intoxication, all above parameters and cognitive function were gradually returned to nearly normal levels. Melatonin also remarkably promoted the translocation of Nrf2 from cytoplasm to nucleus in a dose-dependent manner, thereby increased the Nrf2-ARE signaling-related downstream anti-oxidative enzymes activities. As melatonin effectively rescues hippocampal bioenergetics through depressing the oxidative stress by promoting Nrf2-ARE molecular machinery, this study thus highlights for the first time that clinical use of melatonin may serve as a therapeutic strategy to improve the cognitive function in unsuspecting victims suffered from

  4. Survival of the most transferable at the top of Jacob's ladder: Defining and testing the ωB97M(2) double hybrid density functional

    Science.gov (United States)

    Mardirossian, Narbe; Head-Gordon, Martin

    2018-06-01

    A meta-generalized gradient approximation, range-separated double hybrid (DH) density functional with VV10 non-local correlation is presented. The final 14-parameter functional form is determined by screening trillions of candidate fits through a combination of best subset selection, forward stepwise selection, and random sample consensus (RANSAC) outlier detection. The MGCDB84 database of 4986 data points is employed in this work, containing a training set of 870 data points, a validation set of 2964 data points, and a test set of 1152 data points. Following an xDH approach, orbitals from the ωB97M-V density functional are used to compute the second-order perturbation theory correction. The resulting functional, ωB97M(2), is benchmarked against a variety of leading double hybrid density functionals, including B2PLYP-D3(BJ), B2GPPLYP-D3(BJ), ωB97X-2(TQZ), XYG3, PTPSS-D3(0), XYGJ-OS, DSD-PBEP86-D3(BJ), and DSD-PBEPBE-D3(BJ). Encouragingly, the overall performance of ωB97M(2) on nearly 5000 data points clearly surpasses that of all of the tested density functionals. As a Rung 5 density functional, ωB97M(2) completes our family of combinatorially optimized functionals, complementing B97M-V on Rung 3, and ωB97X-V and ωB97M-V on Rung 4. The results suggest that ωB97M(2) has the potential to serve as a powerful predictive tool for accurate and efficient electronic structure calculations of main-group chemistry.

  5. Functional outcome and quality of life after traumatic total brachial plexus injury treated by nerve transfer or single/double free muscle transfers: a comparative study.

    Science.gov (United States)

    Satbhai, N G; Doi, K; Hattori, Y; Sakamoto, S

    2016-02-01

    Between 2002 and 2011, 81 patients with a traumatic total brachial plexus injury underwent reconstruction by double free muscle transfer (DFMT, 47 cases), single muscle transfer (SMT, 16 cases) or nerve transfers (NT, 18 cases). They were evaluated for functional outcome and quality of life (QoL) using the Disability of Arm, Shoulder and Hand questionnaire, both pre- and post-operatively. The three groups were compared and followed-up for at least 24 months. The mean shoulder abduction and flexion were comparable in all groups, but external rotation was significantly better in the DFMT group as were range and quantitative power of elbow flexion. Patients who had undergone DFMT had reasonable total active finger movement and hook grip strength. All groups showed improvement in function at a level greater than a minimum clinically important difference. The DFMT group showed the greatest improvement. Patients in the DFMT group had a better functional outcome and QoL recovery than those in the NT and SMT groups. Double free muscle transfer procedure is capable of restoring maximum function in patients of total brachial plexus palsy. ©2016 The British Editorial Society of Bone & Joint Surgery.

  6. Anyalysis of Msx1 and Msx2 Transactivation Function in the Context of the Heat Shock 70 (Hspa1b) Gene Promoter

    OpenAIRE

    Zhuang, Fengfeng; Nguyen, Manuel P.; Shuler, Charles; Liu, Yi-Hsin

    2009-01-01

    Previous studies have shown that Msx proteins control gene transcription predominantly through repression mechanisms. However, gene expression studies using either the gain-of-function or the loss-of-function mutants revealed many gene targets whose expression require functional Msx proteins. To date, investigations into the mechanisms of Msx-dependent trans-activation have been hindered by the lack of a responsive promoter. Here, we demonstrated the usefulness of the mouse Hspa1b promoter in...

  7. Functional Foods and Nutraceuticals as Dietary Intervention in Chronic Diseases; Novel Perspectives for Health Promotion and Disease Prevention.

    Science.gov (United States)

    Adefegha, Stephen Adeniyi

    2017-12-27

    Functional foods describe the importance of foods in promoting health and preventing diseases aside their primary role of providing the body with the required amount of essential nutrients such as proteins, carbohydrates, vitamins, fats, and oils needed for its healthy survival. This review explains the interaction of functional food bioactive compounds including polyphenols (phenolic acids [hydroxybenzoic acids and hydroxycinnamic acids], flavonoids [flavonols, flavones, flavanols, flavanones, isoflavones, proanthocyanidins], stilbenes, and lignans), terpenoids, carotenoids, alkaloids, omega-3 and polyunsaturated fatty acids, among others with critical enzymes (α- amylase, α- glucosidase, angiotensin-I converting enzyme [ACE], acetylcholinesterase [AChE], and arginase) linked to some degenerative diseases (type-2 diabetes, cardiovascular diseases [hypertension], neurodegenerative diseases [Alzheimer's disease] and erectile dysfunction). Different functional food bioactive compounds may synergistically/additively confer an overwhelming protection against these degenerative diseases by modulating/altering the activities of these critical enzymes of physiological importance.

  8. Functional characterization of the Gentiana lutea zeaxanthin epoxidase (GlZEP) promoter in transgenic tomato plants.

    Science.gov (United States)

    Yang, Qingjie; Yuan, Dawei; Shi, Lianxuan; Capell, Teresa; Bai, Chao; Wen, Nuan; Lu, Xiaodan; Sandmann, Gerhard; Christou, Paul; Zhu, Changfu

    2012-10-01

    The accumulation of carotenoids in plants depends critically on the spatiotemporal expression profiles of the genes encoding enzymes in the carotenogenic pathway. We cloned and characterized the Gentiana lutea zeaxanthin epoxidase (GlZEP) promoter to determine its role in the regulation of carotenogenesis, because the native gene is expressed at high levels in petals, which contain abundant chromoplasts. We transformed tomato (Solanum lycopersicum cv. Micro-Tom) plants with the gusA gene encoding the reporter enzyme β-glucuronidase (GUS) under the control of the GlZEP promoter, and investigated the reporter expression profile at the mRNA and protein levels. We detected high levels of gusA expression and GUS activity in chromoplast-containing flowers and fruits, but minimal levels in immature fruits containing green chloroplasts, in sepals, leaves, stems and roots. GlZEP-gusA expression was strictly associated with fruit development and chromoplast differentiation, suggesting an evolutionarily-conserved link between ZEP and the differentiation of organelles that store carotenoid pigments. The impact of our results on current models for the regulation of carotenogenesis in plants is discussed.

  9. Cloning and functional analysis of promoters of three GnRH genes in a cichlid

    International Nuclear Information System (INIS)

    Kitahashi, Takashi; Sato, Hideki; Sakuma, Yasuo; Parhar, Ishwar S.

    2005-01-01

    Mechanisms regulating gonadotropin-releasing hormone (GnRH) types, a key molecule for reproductive physiology, remain unclear. In the present study, we cloned the promoters of GnRH1, GnRH2, and GnRH3 genes in the tilapia, Oreochromis niloticus; and found putative binding sites for glucocorticoid receptors, Sp1, C/EBP, GATA, and Oct-1, but not for androgen receptors in all three GnRH promoters using computer analysis. The presence of binding sites for progesterone receptors in GnRH1, estrogen receptors in GnRH1 and GnRH2, and thyroid hormone receptors in GnRH1 and GnRH3 suggests direct action of steroid hormones on GnRH types. Our observation of SOX and LINE-like sequences exclusively in GnRH1, COUP in GnRH2, and retinoid X receptors in GnRH3 suggests their role in sexual differentiation, midbrain segmentation, and visual cue integration, respectively. Thus, the characteristic binding sites for nuclear receptors and transcription factors support the notion that each GnRH type is regulated differently and has distinct physiological roles

  10. Non-invasive brain stimulation to promote motor and functional recovery following spinal cord injury

    Directory of Open Access Journals (Sweden)

    Aysegul Gunduz

    2017-01-01

    Full Text Available We conducted a systematic review of studies using non-invasive brain stimulation (NIBS: repetitive transcranial magnetic stimulation (rTMS and transcranial direct current stimulation (tDCS as a research and clinical tool aimed at improving motor and functional recovery or spasticity in patients following spinal cord injury (SCI under the assumption that if the residual corticospinal circuits could be stimulated appropriately, the changes might be accompanied by functional recovery or an improvement in spasticity. This review summarizes the literature on the changes induced by NIBS in the motor and functional recovery and spasticity control of the upper and lower extremities following SCI.

  11. Structural and functional analysis of mouse Msx1 gene promoter: sequence conservation with human MSX1 promoter points at potential regulatory elements.

    Science.gov (United States)

    Gonzalez, S M; Ferland, L H; Robert, B; Abdelhay, E

    1998-06-01

    Vertebrate Msx genes are related to one of the most divergent homeobox genes of Drosophila, the muscle segment homeobox (msh) gene, and are expressed in a well-defined pattern at sites of tissue interactions. This pattern of expression is conserved in vertebrates as diverse as quail, zebrafish, and mouse in a range of sites including neural crest, appendages, and craniofacial structures. In the present work, we performed structural and functional analyses in order to identify potential cis-acting elements that may be regulating Msx1 gene expression. To this end, a 4.9-kb segment of the 5'-flanking region was sequenced and analyzed for transcription-factor binding sites. Four regions showing a high concentration of these sites were identified. Transfection assays with fragments of regulatory sequences driving the expression of the bacterial lacZ reporter gene showed that a region of 4 kb upstream of the transcription start site contains positive and negative elements responsible for controlling gene expression. Interestingly, a fragment of 130 bp seems to contain the minimal elements necessary for gene expression, as its removal completely abolishes gene expression in cultured cells. These results are reinforced by comparison of this region with the human Msx1 gene promoter, which shows extensive conservation, including many consensus binding sites, suggesting a regulatory role for them.

  12. Conjugation-promoted reaction of open-cage fullerene: A density functional theory study

    KAUST Repository

    Guo, Yong; Yan, Jingjing; Khashab, Niveen M.

    2012-01-01

    Density functional theory calculations are performed to study the addition mechanism of e-rich moieties such as triethyl phosphite to a carbonyl group on the rim of a fullerene orifice. Three possible reaction channels have been investigated

  13. Spin-polarization and spin-dependent logic gates in a double quantum ring based on Rashba spin-orbit effect: Non-equilibrium Green's function approach

    International Nuclear Information System (INIS)

    Eslami, Leila; Esmaeilzadeh, Mahdi

    2014-01-01

    Spin-dependent electron transport in an open double quantum ring, when each ring is made up of four quantum dots and threaded by a magnetic flux, is studied. Two independent and tunable gate voltages are applied to induce Rashba spin-orbit effect in the quantum rings. Using non-equilibrium Green's function formalism, we study the effects of electron-electron interaction on spin-dependent electron transport and show that although the electron-electron interaction induces an energy gap, it has no considerable effect when the bias voltage is sufficiently high. We also show that the double quantum ring can operate as a spin-filter for both spin up and spin down electrons. The spin-polarization of transmitted electrons can be tuned from −1 (pure spin-down current) to +1 (pure spin-up current) by changing the magnetic flux and/or the gates voltage. Also, the double quantum ring can act as AND and NOR gates when the system parameters such as Rashba coefficient are properly adjusted

  14. Disruption of ATP-sensitive potassium channel function in skeletal muscles promotes production and secretion of musclin

    Energy Technology Data Exchange (ETDEWEB)

    Sierra, Ana, E-mail: ana-sierra@uiowa.edu [Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, IA 52242 (United States); Subbotina, Ekaterina, E-mail: ekaterina-subbotina@uiowa.edu [Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, IA 52242 (United States); Zhu, Zhiyong, E-mail: zhiyong-zhu@uiowa.edu [Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, IA 52242 (United States); Gao, Zhan, E-mail: zhan-gao@uiowa.edu [Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, IA 52242 (United States); Koganti, Siva Rama Krishna, E-mail: sivaramakrishna.koganti@ttuhc.edu [Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, IA 52242 (United States); Coetzee, William A., E-mail: william.coetzee@nyumc.org [Department of Pediatrics, NYU School of Medicine, New York, NY 10016 (United States); Goldhamer, David J., E-mail: david.goldhamer@uconn.edu [Center for Regenerative Biology, Department of Molecular and Cell Biology, Advanced Technology Laboratory, University of Connecticut, 1392 Storrs Road Unit 4243, Storrs, Connecticut 06269 (United States); Hodgson-Zingman, Denice M., E-mail: denice-zingman@uiowa.edu [Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, IA 52242 (United States); Fraternal Order of Eagles Diabetes Research Center, Carver College of Medicine, Iowa City, IA 52242 (United States); Zingman, Leonid V., E-mail: leonid-zingman@uiowa.edu [Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, IA 52242 (United States); Fraternal Order of Eagles Diabetes Research Center, Carver College of Medicine, Iowa City, IA 52242 (United States); Department of Veterans Affairs, Medical Center, Iowa City, IA 52242 (United States)

    2016-02-26

    Sarcolemmal ATP-sensitive potassium (K{sub ATP}) channels control skeletal muscle energy use through their ability to adjust membrane excitability and related cell functions in accordance with cellular metabolic status. Mice with disrupted skeletal muscle K{sub ATP} channels exhibit reduced adipocyte size and increased fatty acid release into the circulation. As yet, the molecular mechanisms underlying this link between skeletal muscle K{sub ATP} channel function and adipose mobilization have not been established. Here, we demonstrate that skeletal muscle-specific disruption of K{sub ATP} channel function in transgenic (TG) mice promotes production and secretion of musclin. Musclin is a myokine with high homology to atrial natriuretic peptide (ANP) that enhances ANP signaling by competing for elimination. Augmented musclin production in TG mice is driven by a molecular cascade resulting in enhanced acetylation and nuclear exclusion of the transcription factor forkhead box O1 (FOXO1) – an inhibitor of transcription of the musclin encoding gene. Musclin production/secretion in TG is paired with increased mobilization of fatty acids and a clear trend toward increased circulating ANP, an activator of lipolysis. These data establish K{sub ATP} channel-dependent musclin production as a potential mechanistic link coupling “local” skeletal muscle energy consumption with mobilization of bodily resources from fat. Understanding such mechanisms is an important step toward designing interventions to manage metabolic disorders including those related to excess body fat and associated co-morbidities. - Highlights: • ATP-sensitive K{sup +} channels regulate musclin production by skeletal muscles. • Lipolytic ANP signaling is promoted by augmented skeletal muscle musclin production. • Skeletal muscle musclin transcription is promoted by a CaMKII/HDAC/FOXO1 pathway. • Musclin links adipose mobilization to energy use in K{sub ATP} channel deficient skeletal muscle.

  15. Disruption of ATP-sensitive potassium channel function in skeletal muscles promotes production and secretion of musclin

    International Nuclear Information System (INIS)

    Sierra, Ana; Subbotina, Ekaterina; Zhu, Zhiyong; Gao, Zhan; Koganti, Siva Rama Krishna; Coetzee, William A.; Goldhamer, David J.; Hodgson-Zingman, Denice M.; Zingman, Leonid V.

    2016-01-01

    Sarcolemmal ATP-sensitive potassium (K_A_T_P) channels control skeletal muscle energy use through their ability to adjust membrane excitability and related cell functions in accordance with cellular metabolic status. Mice with disrupted skeletal muscle K_A_T_P channels exhibit reduced adipocyte size and increased fatty acid release into the circulation. As yet, the molecular mechanisms underlying this link between skeletal muscle K_A_T_P channel function and adipose mobilization have not been established. Here, we demonstrate that skeletal muscle-specific disruption of K_A_T_P channel function in transgenic (TG) mice promotes production and secretion of musclin. Musclin is a myokine with high homology to atrial natriuretic peptide (ANP) that enhances ANP signaling by competing for elimination. Augmented musclin production in TG mice is driven by a molecular cascade resulting in enhanced acetylation and nuclear exclusion of the transcription factor forkhead box O1 (FOXO1) – an inhibitor of transcription of the musclin encoding gene. Musclin production/secretion in TG is paired with increased mobilization of fatty acids and a clear trend toward increased circulating ANP, an activator of lipolysis. These data establish K_A_T_P channel-dependent musclin production as a potential mechanistic link coupling “local” skeletal muscle energy consumption with mobilization of bodily resources from fat. Understanding such mechanisms is an important step toward designing interventions to manage metabolic disorders including those related to excess body fat and associated co-morbidities. - Highlights: • ATP-sensitive K"+ channels regulate musclin production by skeletal muscles. • Lipolytic ANP signaling is promoted by augmented skeletal muscle musclin production. • Skeletal muscle musclin transcription is promoted by a CaMKII/HDAC/FOXO1 pathway. • Musclin links adipose mobilization to energy use in K_A_T_P channel deficient skeletal muscle.

  16. Diversity of Dominant Bacterial Taxa in Activated Sludge Promotes Functional Resistance following Toxic Shock Loading

    KAUST Repository

    Saikaly, Pascal

    2010-12-14

    Examining the relationship between biodiversity and functional stability (resistance and resilience) of activated sludge bacterial communities following disturbance is an important first step towards developing strategies for the design of robust biological wastewater treatment systems. This study investigates the relationship between functional resistance and biodiversity of dominant bacterial taxa by subjecting activated sludge samples, with different levels of biodiversity, to toxic shock loading with cupric sulfate (Cu[II]), 3,5-dichlorophenol (3,5-DCP), or 4-nitrophenol (4-NP). Respirometric batch experiments were performed to determine the functional resistance of activated sludge bacterial community to the three toxicants. Functional resistance was estimated as the 30 min IC50 or the concentration of toxicant that results in a 50% reduction in oxygen utilization rate compared to a referential state represented by a control receiving no toxicant. Biodiversity of dominant bacterial taxa was assessed using polymerase chain reaction-terminal restriction fragment length polymorphism (PCR-T-RFLP) targeting the 16S ribosomal RNA (16S rRNA) gene. Statistical analysis of 30 min IC50 values and PCR-T-RFLP data showed a significant positive correlation (P<0.05) between functional resistance and microbial diversity for each of the three toxicants tested. To our knowledge, this is the first study showing a positive correlation between biodiversity of dominant bacterial taxa in activated sludge and functional resistance. In this system, activated sludge bacterial communities with higher biodiversity are functionally more resistant to disturbance caused by toxic shock loading. © 2010 Springer Science+Business Media, LLC.

  17. Development Model Sustainable Promoted by the Family Agriculture in Function of Environmental Preservation

    Directory of Open Access Journals (Sweden)

    Sônia Maria Agra Zamith

    2016-10-01

    Full Text Available The objective of the research is to indicate directions of alternatives to self-sustainable development outlined at the principle of a family socioeconomic context, and sustainability, environmental  protection  promoted  by  family  agriculture.  The  inclusion  of  Family agriculture model in the discussion, of the preliminary verification of the agricultural production methods used by family units at the time ensuring the livelihood and allows the marketing  of  surplus  production  levels.  The  method  employed  was  the  hypothetical- deductive, with explanatory purpose, which means corresponded to the selection of authors who have the necessary support to the understanding of the precautionary principle in environmental law.

  18. Effects of a Lutein and Zeaxanthin Intervention on Cognitive Function: A Randomized, Double-Masked, Placebo-Controlled Trial of Younger Healthy Adults.

    Science.gov (United States)

    Renzi-Hammond, Lisa M; Bovier, Emily R; Fletcher, Laura M; Miller, L Stephen; Mewborn, Catherine M; Lindbergh, Cutter A; Baxter, Jeffrey H; Hammond, Billy R

    2017-11-14

    Background: Past studies have suggested that higher lutein (L) and zeaxanthin (Z) levels in serum and in the central nervous system (as quantified by measuring macular pigment optical density, MPOD) are related to improved cognitive function in older adults. Very few studies have addressed the issue of xanthophylls and cognitive function in younger adults, and no controlled trials have been conducted to date to determine whether or not supplementation with L + Z can change cognitive function in this population. Objective: The purpose of this study was to determine whether or not supplementation with L + Z could improve cognitive function in young (age 18-30), healthy adults. Design: A randomized, double-masked, placebo-controlled trial design was used. Fifty-one young, healthy subjects were recruited as part of a larger study on xanthophylls and cognitive function. Subjects were randomized into active supplement ( n = 37) and placebo groups ( n = 14). MPOD was measured psychophysically using customized heterochromatic flicker photometry. Cognitive function was measured using the CNS Vital Signs testing platform. MPOD and cognitive function were measured every four months for a full year of supplementation. Results: Supplementation increased MPOD significantly over the course of the year, vs. placebo ( p cognitive function in young, healthy adults. Magnitudes of effects are similar to previous work reporting correlations between MPOD and cognition in other populations.

  19. Functional model of the system promotion affiliate program in partner networks

    Directory of Open Access Journals (Sweden)

    Дмитро Сергійович Міроненко

    2017-07-01

    Full Text Available Structural analysis of business processes in promoting affiliate programs in the advertisement network has been done. Processes are considered according to the IDEF0 methodology. The viewpoints of advertisers, webmasters and marketers greatly experienced in affiliate marketing have been taken into account. A virtual company and the business process in it (affiliate program publication and selection, comparative analysis of the affiliate program, advertisement program start, summing up and effectiveness analysis of the affiliate programis the subject of the research. The basic and additional characteristics of the affiliate program must be considered for its effective promotion. The basic characteristics are: description, the main goal, advertiser’s commission for successful operations, test period duration, type of traffic, advertisement materials, targeting. The additional characteristics are: rated online resource, which provides goods or services as compared to the analogues, ranking by country, ranking by category, time spent on making up the internet website, number of the online resource pages, the percentage of visitors who leave the website directly at the entrance page or look through not more than one site, the visitors country of residence, the source of the traffic used by the visitors, the keywords, from which the social networking resources visitors come, interests of the visitors, Internet resources analogues, relating to Internet resource Mobile Apps. The criteria of evaluation the effectiveness of affiliate programs and advertising in general have been introduced: effective number of visitors (visitor becomes effective after the goal, an action, target number of the visitors, costs of advertising, conversion, profit and return on investment

  20. Double logarithmic term Ln2(1/x) in the polarized non singlet structure function at small x in valon model

    International Nuclear Information System (INIS)

    Taghavi Shahri Fatemeh; Arash, F.

    2009-01-01

    We study the low x behavior of non-singlet spin structure Function, of the nucleon in the so-called the valon representation. We find the double logarithmic term Ln 2 (1/x) in the polarized non singlet structure function at small x with using the valon model .The Structure of the valon itself develops through the perturbative dressing of a valence quark in QCD, which is independent of the hosting hadron. The results of non-singlet spin structure Function is in excellent agreement with the experimental data from HERMES collaborations for the entire measured range of x. It also provides an acceptable agreement with the older data from SMC, E143 and E155 experiments. We have further compared our results with those from AA, BB, GRSV, and DNS global fits. (authors)

  1. Generalized localization for the double trigonometric Fourier series and the Walsh-Fourier series of functions in L log +L log + log +L

    International Nuclear Information System (INIS)

    Bloshanskaya, S K; Bloshanskii, I L; Roslova, T Y

    1998-01-01

    For an arbitrary open set Ω subset of I 2 =[0,1) 2 and an arbitrary function f element of L log + L log + log + L(I 2 ) such that f=0 on Ω the double Fourier series of f with respect to the trigonometric system Ψ=E and the Walsh-Paley system Ψ=W is shown to converge to zero (over rectangles) almost everywhere on Ω. Thus, it is proved that generalized localization almost everywhere holds on arbitrary open subsets of the square I 2 for the double trigonometric Fourier series and the Walsh-Fourier series of functions in the class L log + L log + log + L (in the case of summation over rectangles). It is also established that such localization breaks down on arbitrary sets that are not dense in I 2 , in the classes Φ Ψ (L)(I 2 ) for the orthonormal system Ψ=E and an arbitrary function such that Φ E (u)=o(u log + log + u) as u→∞ or for Φ W (u)=u( log + log + u) 1-ε , 0<ε<1

  2. Early enteral immune nutrition support after radical operation for gastric cancer on promoting the recovery of gastrointestinal function and immune function

    Directory of Open Access Journals (Sweden)

    Zhi-Gang Li

    2016-05-01

    Full Text Available Objective: To analyze the effect of early enteral immune nutrition support after radical operation for gastric cancer on the recovery of gastrointestinal function and immune function. Methods: A total of 106 cases of patients received radical operation for gastric cancer in our hospital were selected as research subjects, and according to different ways of postoperative nutrition intervention, all patients were divided into observation group (n=50 and control group (n=56. Control group received conventional enteral nutrition intervention, observation group received postoperative early enteral immune nutrition support, and then differences in postoperative intestinal mucosa barrier function, gastrointestinal hormone levels, immune function levels and nutrition-related indicator values were compared between two groups. Results: After observation group received enteral immune nutrition intervention, serum DAO, PS and D-lactate levels as well as urine L/M ratio were lower than those of control group; serum GAS, CCK, MTL and SP values of observation group after intervention were higher than those of control group, and GLU, VIP, GIP and SS values were lower than those of control group; CD4, IgG, NK cell, C3, C4, CH50 and S-IgA levels of observation group after intervention were higher than those of control group; serum ALB, PRE, TRF and RBP levels of observation group after intervention were higher than those of control group. Conclusion: Early enteral immune nutrition support after radical operation for gastric cancer is conducive to the recovery of gastrointestinal function and the promotion of immune state, eventually promotes patients’ postoperative overall recovery and has active clinical significance.

  3. Mental exercising through simple socializing: social interaction promotes general cognitive functioning.

    Science.gov (United States)

    Ybarra, Oscar; Burnstein, Eugene; Winkielman, Piotr; Keller, Matthew C; Manis, Melvin; Chan, Emily; Rodriguez, Joel

    2008-02-01

    Social interaction is a central feature of people's life and engages a variety of cognitive resources. Thus, social interaction should facilitate general cognitive functioning. Previous studies suggest such a link, but they used special populations (e.g., elderly with cognitive impairment), measured social interaction indirectly (e.g., via marital status), and only assessed effects of extended interaction in correlational designs. Here the relation between mental functioning and direct indicators of social interaction was examined in a younger and healthier population. Study 1 using survey methodology found a positive relationship between social interaction, assessed via amount of actual social contact, and cognitive functioning in people from three age groups including younger adults. Study 2 using an experimental design found that a small amount of social interaction (10 min) can facilitate cognitive performance. The findings are discussed in the context of the benefits social relationships have for so many aspects of people's lives.

  4. Gain-of-function mutant p53 activates small GTPase Rac1 through SUMOylation to promote tumor progression.

    Science.gov (United States)

    Yue, Xuetian; Zhang, Cen; Zhao, Yuhan; Liu, Juan; Lin, Alan W; Tan, Victor M; Drake, Justin M; Liu, Lianxin; Boateng, Michael N; Li, Jun; Feng, Zhaohui; Hu, Wenwei

    2017-08-15

    Tumor suppressor p53 is frequently mutated in human cancer. Mutant p53 often promotes tumor progression through gain-of-function (GOF) mechanisms. However, the mechanisms underlying mutant p53 GOF are not well understood. In this study, we found that mutant p53 activates small GTPase Rac1 as a critical mechanism for mutant p53 GOF to promote tumor progression. Mechanistically, mutant p53 interacts with Rac1 and inhibits its interaction with SUMO-specific protease 1 (SENP1), which in turn inhibits SENP1-mediated de-SUMOylation of Rac1 to activate Rac1. Targeting Rac1 signaling by RNAi, expression of the dominant-negative Rac1 (Rac1 DN), or the specific Rac1 inhibitor NSC23766 greatly inhibits mutant p53 GOF in promoting tumor growth and metastasis. Furthermore, mutant p53 expression is associated with enhanced Rac1 activity in clinical tumor samples. These results uncover a new mechanism for Rac1 activation in tumors and, most importantly, reveal that activation of Rac1 is an unidentified and critical mechanism for mutant p53 GOF in tumorigenesis, which could be targeted for therapy in tumors containing mutant p53. © 2017 Yue et al.; Published by Cold Spring Harbor Laboratory Press.

  5. Identification of a functional element in the promoter of the silkworm (Bombyx mori) fat body-specific gene Bmlp3.

    Science.gov (United States)

    Xu, Hanfu; Deng, Dangjun; Yuan, Lin; Wang, Yuancheng; Wang, Feng; Xia, Qingyou

    2014-08-01

    30K proteins are a group of structurally related proteins that play important roles in the life cycle of the silkworm Bombyx mori and are largely synthesized and regulated in a time-dependent manner in the fat body. Little is known about the upstream regulatory elements associated with the genes encoding these proteins. In the present study, the promoter of Bmlp3, a fat body-specific gene encoding a 30K protein family member, was characterized by joining sequences containing the Bmlp3 promoter with various amounts of 5' upstream sequences to a luciferase reporter gene. The results indicated that the sequences from -150 to -250bp and -597 to -675bp upstream of the Bmlp3 transcription start site were necessary for high levels of luciferase activity. Further analysis showed that a 21-bp sequence located between -230 and -250 was specifically recognized by nuclear factors from silkworm fat bodies and BmE cells, and could enhance luciferase reporter-gene expression 2.8-fold in BmE cells. This study provides new insights into the Bmlp3 promoter and contributes to the further clarification of the function and developmental regulation of Bmlp3. Copyright © 2014. Published by Elsevier B.V.

  6. Trajectories of recovery of social and physical functioning in major depression, dysthymic disorder and double depression: a 3-year follow-up.

    Science.gov (United States)

    Rhebergen, Didi; Beekman, Aartjan T F; de Graaf, Ron; Nolen, Willem A; Spijker, Jan; Hoogendijk, Witte J; Penninx, Brenda W J H

    2010-07-01

    Depressive disorders have a large impact on psychosocial functioning. Since lower functioning predicts recurrence of a depressive episode, insight into the post-morbid course of psychosocial functioning of persons with different depressive disorders may facilitate recurrence prevention. Data were derived from NEMESIS, an epidemiologic survey in the adult population in the Netherlands. Respondents, who met the CIDI criteria of major depression (MDD; n=102), dysthymic disorder (Dysth; n=66) or double depression (DD; n=73) at baseline, and recovered during three year follow-up, were included; as was a control group without any diagnosis (NoDiag, n=4140). Functioning was assessed using the Groningen Social Disability Schedule (GSDS) and the SF-36 physical health summary-scale. Linear Mixed Models were conducted to compare 3-year trajectories of functioning across depressive groups and with NoDiag group. Compared to NoDiag, all depressed groups were significantly impaired on social and physical functioning. Dysth and DD had a lower level of post-morbid physical functioning compared to MDD (after 1 and 3 years respectively: Dysth: B=-13.8, p=.002 and B=-8.11, p=.09; DD: B=-8.9, p=.03 and B=-9.1, p=.05). Determinants for impaired social functioning (neuroticism) and for impaired physical functioning (age, comorbid somatic disorders and neuroticism) were identified. Attrition was higher among persons with a depression. Inclusion of the drop-outs would most likely have resulted in stronger associations, since we expect lower functioning among the drop-outs. This study indicates the long-term debilitating effects of psychopathology, even after recovery of depressive disorders. Duration of the index symptoms appears to be associated with impaired functioning, since especially those with Dysthymia (either with or without a MDD) showed slower and less recovery of functioning.

  7. Memory function and serotonin transporter promoter gene polymorphism in ecstasy (MDMA) users

    NARCIS (Netherlands)

    Reneman, Liesbeth; Schilt, T.; de Win, Maartje M.; Booij, Jan; Schmand, Ben; van den Brink, Wim; Bakker, Onno

    2006-01-01

    Although 3,4-methylenedioxymethamphetamine (MDMA or ecstasy) has been shown to damage brain serotonin (5-HT) neurons in animals and possibly humans, little is known about the long-term consequences of MDMA-induced 5-HT neurotoxic lesions on functions in which 5-HT is involved, such as cognitive

  8. Using Multiple Schedules during Functional Communication Training to Promote Rapid Transfer of Treatment Effects

    Science.gov (United States)

    Fisher, Wayne W.; Greer, Brian D.; Fuhrman, Ashley M.; Querim, Angie C.

    2015-01-01

    Multiple schedules with signaled periods of reinforcement and extinction have been used to thin reinforcement schedules during functional communication training (FCT) to make the intervention more practical for parents and teachers. We evaluated whether these signals would also facilitate rapid transfer of treatment effects across settings and…

  9. S,O-Ligand-Promoted Palladium-Catalyzed C-H Functionalization Reactions of Nondirected Arenes

    NARCIS (Netherlands)

    Naksomboon, K.; Valderas, C.; Gomez-Martinez, M.; Alvarez-Casao, Y.; Fernández Ibáñez, M.A.

    Pd(II)-catalyzed C-H functionalization of non directed arenes has been realized using an inexpensive and easily accessible type of bidentate S,O-ligand. The catalytic system shows high efficiency in the C-H olefination reaction of electron-rich and electron-poor arenes. This methodology is

  10. Protein arginine methyltransferase 5 functions as an epigenetic activator of the androgen receptor to promote prostate cancer cell growth.

    Science.gov (United States)

    Deng, X; Shao, G; Zhang, H-T; Li, C; Zhang, D; Cheng, L; Elzey, B D; Pili, R; Ratliff, T L; Huang, J; Hu, C-D

    2017-03-02

    Protein arginine methyltransferase 5 (PRMT5) is an emerging epigenetic enzyme that mainly represses transcription of target genes via symmetric dimethylation of arginine residues on histones H4R3, H3R8 and H2AR3. Accumulating evidence suggests that PRMT5 may function as an oncogene to drive cancer cell growth by epigenetic inactivation of several tumor suppressors. Here, we provide evidence that PRMT5 promotes prostate cancer cell growth by epigenetically activating transcription of the androgen receptor (AR) in prostate cancer cells. Knockdown of PRMT5 or inhibition of PRMT5 by a specific inhibitor reduces the expression of AR and suppresses the growth of multiple AR-positive, but not AR-negative, prostate cancer cells. Significantly, knockdown of PRMT5 in AR-positive LNCaP cells completely suppresses the growth of xenograft tumors in mice. Molecular analysis reveals that PRMT5 binds to the proximal promoter region of the AR gene and contributes mainly to the enriched symmetric dimethylation of H4R3 in the same region. Mechanistically, PRMT5 is recruited to the AR promoter by its interaction with Sp1, the major transcription factor responsible for AR transcription, and forms a complex with Brg1, an ATP-dependent chromatin remodeler, on the proximal promoter region of the AR gene. Furthermore, PRMT5 expression in prostate cancer tissues is significantly higher than that in benign prostatic hyperplasia tissues, and PRMT5 expression correlates positively with AR expression at both the protein and mRNA levels. Taken together, our results identify PRMT5 as a novel epigenetic activator of AR in prostate cancer. Given that inhibiting AR transcriptional activity or androgen synthesis remains the major mechanism of action for most existing anti-androgen agents, our findings also raise an interesting possibility that targeting PRMT5 may represent a novel approach for prostate cancer treatment by eliminating AR expression.

  11. Muscle type-specific responses to NAD+ salvage biosynthesis promote muscle function in Caenorhabditis elegans.

    Science.gov (United States)

    Vrablik, Tracy L; Wang, Wenqing; Upadhyay, Awani; Hanna-Rose, Wendy

    2011-01-15

    Salvage biosynthesis of nicotinamide adenine dinucleotide (NAD(+)) from nicotinamide (NAM) lowers NAM levels and replenishes the critical molecule NAD(+) after it is hydrolyzed. This pathway is emerging as a regulator of multiple biological processes. Here we probe the contribution of the NAM-NAD(+) salvage pathway to muscle development and function using Caenorhabditis elegans. C. elegans males with mutations in the nicotinamidase pnc-1, which catalyzes the first step of this NAD(+) salvage pathway, cannot mate due to a spicule muscle defect. Multiple muscle types are impaired in the hermaphrodites, including body wall muscles, pharyngeal muscles and vulval muscles. An active NAD(+) salvage pathway is required for optimal function of each muscle cell type. However, we found surprising muscle-cell-type specificity in terms of both the timing and relative sensitivity to perturbation of NAD(+) production or NAM levels. Active NAD(+) biosynthesis during development is critical for function of the male spicule protractor muscles during adulthood, but these muscles can surprisingly do without salvage biosynthesis in adulthood under the conditions examined. The body wall muscles require ongoing NAD(+) salvage biosynthesis both during development and adulthood for maximum function. The vulval muscles do not function in the presence of elevated NAM concentrations, but NAM supplementation is only slightly deleterious to body wall muscles during development or upon acute application in adults. Thus, the pathway plays distinct roles in different tissues. As NAM-NAD(+) biosynthesis also impacts muscle differentiation in vertebrates, we propose that similar complexities may be found among vertebrate muscle cell types. Copyright © 2010 Elsevier Inc. All rights reserved.

  12. Mapping the functional landscape of frequent phenylalanine hydroxylase (PAH) genotypes promotes personalised medicine in phenylketonuria.

    Science.gov (United States)

    Danecka, Marta K; Woidy, Mathias; Zschocke, Johannes; Feillet, François; Muntau, Ania C; Gersting, Søren W

    2015-03-01

    In phenylketonuria, genetic heterogeneity, frequent compound heterozygosity, and the lack of functional data for phenylalanine hydroxylase genotypes hamper reliable phenotype prediction and individualised treatment. A literature search revealed 690 different phenylalanine hydroxylase genotypes in 3066 phenylketonuria patients from Europe and the Middle East. We determined phenylalanine hydroxylase function of 30 frequent homozygous and compound heterozygous genotypes covering 55% of the study population, generated activity landscapes, and assessed the phenylalanine hydroxylase working range in the metabolic (phenylalanine) and therapeutic (tetrahydrobiopterin) space. Shared patterns in genotype-specific functional landscapes were linked to biochemical and pharmacological phenotypes, where (1) residual activity below 3.5% was associated with classical phenylketonuria unresponsive to pharmacological treatment; (2) lack of defined peak activity induced loss of response to tetrahydrobiopterin; (3) a higher cofactor need was linked to inconsistent clinical phenotypes and low rates of tetrahydrobiopterin response; and (4) residual activity above 5%, a defined peak of activity, and a normal cofactor need were associated with pharmacologically treatable mild phenotypes. In addition, we provide a web application for retrieving country-specific information on genotypes and genotype-specific phenylalanine hydroxylase function that warrants continuous extension, updates, and research on demand. The combination of genotype-specific functional analyses with biochemical, clinical, and therapeutic data of individual patients may serve as a powerful tool to enable phenotype prediction and to establish personalised medicine strategies for dietary regimens and pharmacological treatment in phenylketonuria. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  13. Programmed cell death promotes male sterility in the functional dioecious Opuntia stenopetala (Cactaceae).

    Science.gov (United States)

    Flores-Rentería, Lluvia; Orozco-Arroyo, Gregorio; Cruz-García, Felipe; García-Campusano, Florencia; Alfaro, Isabel; Vázquez-Santana, Sonia

    2013-09-01

    The sexual separation in dioecious species has interested biologists for decades; however, the cellular mechanism leading to unisexuality has been poorly understood. In this study, the cellular changes that lead to male sterility in the functionally dioecious cactus, Opuntia stenopetala, are described. The spatial and temporal patterns of programmed cell death (PCD) were determined in the anthers of male and female flowers using scanning electron microscopy analysis and histological observations, focusing attention on the transition from bisexual to unisexual development. In addition, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling assays were used as an indicator of DNA fragmentation to corroborate PCD. PCD was detected in anthers of both female and male flowers, but their patterns differed in time and space. Functionally male individuals developed viable pollen, and normal development involved PCD on each layer of the anther wall, which occurred progressively from the inner (tapetum) to the outer layer (epidermis). Conversely, functional female individuals aborted anthers by premature and displaced PCD. In anthers of female flowers, the first signs of PCD, such as a nucleus with irregular shape, fragmented and condensed chromatin, high vacuolization and condensed cytoplasm, occurred at the microspore mother cell stage. Later these features were observed simultaneously in all anther wall layers, connective tissue and filament. Neither pollen formation nor anther dehiscence was detected in female flowers of O. stenopetala due to total anther disruption. Temporal and spatial changes in the patterns of PCD are responsible for male sterility of female flowers in O. stenopetala. Male fertility requires the co-ordination of different events, which, when altered, can lead to male sterility and to functionally unisexual individuals. PCD could be a widespread mechanism in the determination of functionally dioecious species.

  14. Using Virtual Technology to Promote Functional Communication in Aphasia: Preliminary Evidence From Interactive Dialogues With Human and Virtual Clinicians.

    Science.gov (United States)

    Kalinyak-Fliszar, Michelene; Martin, Nadine; Keshner, Emily; Rudnicky, Alex; Shi, Justin; Teodoro, Gregory

    2015-11-01

    We investigated the feasibility of using a virtual clinician (VC) to promote functional communication abilities of persons with aphasia (PWAs). We aimed to determine whether the quantity and quality of verbal output in dialogues with a VC would be the same or greater than those with a human clinician (HC). Four PWAs practiced dialogues for 2 sessions each with a HC and VC. Dialogues from before and after practice were transcribed and analyzed for content. We compared measures taken before and after practice in the VC and HC conditions. Results were mixed. Participants either produced more verbal output with the VC or showed no difference on this measure between the VC and HC conditions. Participants also showed some improvement in postpractice narratives. Results provide support for the feasibility and applicability of virtual technology to real-life communication contexts to improve functional communication in PWAs.

  15. Distinguishing the Transcription Regulation Patterns in Promoters of Human Genes with Different Function or Evolutionary Age

    KAUST Repository

    Alam, Tanvir

    2012-07-01

    Distinguishing transcription regulatory patterns of different gene groups is a common problem in various bioinformatics studies. In this work we developed a methodology to deal with such a problem based on machine learning techniques. We applied our method to two biologically important problems related to detecting a difference in transcription regulation of: a/ protein-coding and long non-coding RNAs (lncRNAs) in human, as well as b/ a difference between primate-specific and non-primate-specific long non-coding RNAs. Our method is capable to classify RNAs using various regulatory features of genes that transcribe into these RNAs, such as nucleotide frequencies, transcription factor binding sites, de novo sequence motifs, CpG islands, repetitive elements, histone modification marks, and others. Ten-fold cross-validation tests suggest that our model can distinguish protein-coding and non-coding RNAs with accuracy above 80%. Twenty-fold cross-validation tests suggest that our model can distinguish primate-specific from non-primate-specific promoters of lncRNAs with accuracy above 80%. Consequently, we can hypothesize that transcription of the groups of genes mentioned above are regulated by different mechanisms. Feature selection techniques allowed us to reduce the number of features significantly while keeping the accuracy around 80%. Consequently, we can conclude that selected features play significant role in transcription regulation of coding and non-coding genes, as well as primate-specific and non-primate-specific lncRNA genes.

  16. Identification and functional analysis of a second RBF-2 binding site within the HIV-1 promoter

    International Nuclear Information System (INIS)

    Dahabieh, Matthew S.; Ooms, Marcel; Malcolm, Tom; Simon, Viviana; Sadowski, Ivan

    2011-01-01

    Transcription from the HIV-1 long terminal repeat (LTR) is mediated by numerous host transcription factors. In this study we characterized an E-box motif (RBE1) within the core promoter that was previously implicated in both transcriptional activation and repression. We show that RBE1 is a binding site for the RBF-2 transcription factor complex (USF1, USF2, and TFII-I), previously shown to bind an upstream viral element, RBE3. The RBE1 and RBE3 elements formed complexes of identical mobility and protein constituents in gel shift assays, both with Jurkat T-cell nuclear extracts and recombinant USF/TFII-I. Furthermore, both elements are regulators of HIV-1 expression; mutations in LTR-luciferase reporters and in HIV-1 molecular clones resulted in decreased transcription, virion production, and proviral expression in infected cells. Collectively, our data indicate that RBE1 is a bona fide RBF-2 binding site and that the RBE1 and RBE3 elements are necessary for mediating proper transcription from the HIV-1 LTR.

  17. α7 Nicotinic Receptor Promotes the Neuroprotective Functions of Astrocytes against Oxaliplatin Neurotoxicity

    Directory of Open Access Journals (Sweden)

    Lorenzo Di Cesare Mannelli

    2015-01-01

    Full Text Available Neuropathies are characterized by a complex response of the central nervous system to injuries. Glial cells are recruited to maintain neuronal homeostasis but dysregulated activation leads to pain signaling amplification and reduces the glial neuroprotective power. Recently, we highlighted the property of α7 nicotinic-acetylcholine-receptor (nAChR agonists to relieve pain and induce neuroprotection simultaneously with a strong increase in astrocyte density. Aimed to study the role of α7 nAChR in the neuron-glia cross-talk, we treated primary rat neurons and astrocytes with the neurotoxic anticancer drug oxaliplatin evaluating the effect of the α7 nAChR agonist PNU-282987 (PNU. Oxaliplatin (1 μM, 48 h reduced cell viability and increased caspase-3 activity of neuron monocultures without damaging astrocytes. In cocultures, astrocytes were not able to protect neurons by oxaliplatin even if glial cell metabolism was stimulated (pyruvate increase. On the contrary, the coculture incubation with 10 μM PNU improved neuron viability and inhibited apoptosis. In the absence of astrocytes, the protection disappeared. Furthermore, PNU promoted the release of the anti-inflammatory cytokine TGF-β1 and the expression of the glutamate-detoxifying enzyme glutamine synthetase. The α7 nAChR stimulation protects neurons from oxaliplatin toxicity through an astrocyte-mediated mechanism. α7 nAChR is suggested for recovering the homeostatic role of astrocytes.

  18. Ubiquitination of MBNL1 Is Required for Its Cytoplasmic Localization and Function in Promoting Neurite Outgrowth

    Directory of Open Access Journals (Sweden)

    Pei-Ying Wang

    2018-02-01

    Full Text Available The Muscleblind-like protein family (MBNL plays an important role in regulating the transition between differentiation and pluripotency and in the pathogenesis of myotonic dystrophy type 1 (DM1, a CTG expansion disorder. How different MBNL isoforms contribute to the differentiation and are affected in DM1 has not been investigated. Here, we show that the MBNL1 cytoplasmic, but not nuclear, isoform promotes neurite morphogenesis and reverses the morphological defects caused by expanded CUG RNA. Cytoplasmic MBNL1 is polyubiquitinated by lysine 63 (K63. Reduced cytoplasmic MBNL1 in the DM1 mouse brain is consistent with the reduced extent of K63 ubiquitination. Expanded CUG RNA induced the deubiqutination of cytoplasmic MBNL1, which resulted in nuclear translocation and morphological impairment that could be ameliorated by inhibiting K63-linked polyubiquitin chain degradation. Our results suggest that K63-linked ubiquitination of MBNL1 is required for its cytoplasmic localization and that deubiquitination of cytoplasmic MBNL1 is pathogenic in the DM1 brain.

  19. A novel functional polymorphism in the Cdc6 promoter is associated with the risk for hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Xiong Xingdong; Fang Jianhong; Qiu Fuen; Zhao Jing; Cheng Jiasen; Yuan Yunfei; Li Shengping; Zhuang Shimei

    2008-01-01

    Cdc6 is essential for DNA replication and its deregulation is involved in carcinogenesis. To date, the biological significance of the polymorphism in Cdc6 promoter is still unknown. In this study, we aimed to evaluate the influence of the Cdc6 -515A>G polymorphism (rs4134994) on the individual's susceptibility to cancer and on the function of Cdc6. The Cdc6 -515A>G polymorphism was genotyped in 387 hepatocellular carcinoma (HCC) and 389 age- and sex-matched healthy subjects. The association between the genotypes and the risk for HCC was then estimated by unconditional logistic regression analysis with adjustment for age, sex and HBV status. Compared with the AA homozygotes, the homozygous GG genotype (adjusted OR = 0.36, 95% confidence interval (CI) = 0.18-0.72, P = 0.004) or the combined AG/GG genotypes (adjusted OR = 0.56, 95% CI = 0.36-0.86, P = 0.008) were statistically significantly associated with the reduced risk for HCC. Moreover, the analysis using luciferase reporter system showed that the G-allelic Cdc6 promoter displayed a decreased transcriptional activity compared with the A-allelic one. These results indicate that the individuals with G allele may have reduced Cdc6 expression and are therefore in reduced risk for HCC. Further investigation using electrophoretic mobility shift assay (EMSA) revealed that the G allele had a stronger binding strength to nuclear protein(s) which might function as negative regulator(s) for Cdc6 transcription. Our findings suggest that the -515A>G polymorphism may affect the Cdc6 promoter binding affinity with nuclear protein(s) and in turn the Cdc6 expression, which consequently modulates the individual's susceptibility to HCC

  20. Functional collagen conduits combined with human mesenchymal stem cells promote regeneration after sciatic nerve transection in dogs.

    Science.gov (United States)

    Cui, Yi; Yao, Yao; Zhao, Yannan; Xiao, Zhifeng; Cao, Zongfu; Han, Sufang; Li, Xing; Huan, Yong; Pan, Juli; Dai, Jianwu

    2018-05-01

    Numerous studies have focused on the development of novel and innovative approaches for the treatment of peripheral nerve injury using artificial nerve guide conduits. In this study, we attempted to bridge 3.5-cm defects of the sciatic nerve with a longitudinally oriented collagen conduit (LOCC) loaded with human umbilical cord mesenchymal stem cells (hUC-MSCs). The LOCC contains a bundle of longitudinally aligned collagenous fibres enclosed in a hollow collagen tube. Our previous studies showed that an LOCC combined with neurotrophic factors enhances peripheral nerve regeneration. However, it remained unknown whether an LOCC seeded with hUC-MSCs could also promote regeneration. In this study, using various histological and electrophysiological analyses, we found that an LOCC provides mechanical support to newly growing nerves and functions as a structural scaffold for cells, thereby stimulating sciatic nerve regeneration. The LOCC and hUC-MSCs synergistically promoted regeneration and improved the functional recovery in a dog model of sciatic nerve injury. Therefore, the combined use of an LOCC and hUC-MSCs might have therapeutic potential for the treatment of peripheral nerve injury. Copyright © 2018 John Wiley & Sons, Ltd.

  1. Tula and Puumala hantavirus NSs ORFs are functional and the products inhibit activation of the interferon-beta promoter.

    Science.gov (United States)

    Jääskeläinen, Kirsi M; Kaukinen, Pasi; Minskaya, Ekaterina S; Plyusnina, Angelina; Vapalahti, Olli; Elliott, Richard M; Weber, Friedemann; Vaheri, Antti; Plyusnin, Alexander

    2007-10-01

    The S RNA genome segment of hantaviruses carried by Arvicolinae and Sigmodontinae rodents encodes the nucleocapsid (N) protein and has an overlapping (+1) open reading frame (ORF) for a putative nonstructural protein (NSs). The aim of this study was to determine whether the ORF is functional. A protein corresponding to the predicted size of Tula virus (TULV) NSs was detected using coupled in vitro transcription and translation from a cloned S segment cDNA, and a protein corresponding to the predicted size of Puumala virus (PUUV) NSs was detected in infected cells by Western blotting with an anti-peptide serum. The activities of the interferon beta (IFN-beta) promoter, and nuclear factor kappa B (NF-kappaB)- and interferon regulatory factor-3 (IRF-3) responsive promoters, were inhibited in COS-7 cells transiently expressing TULV or PUUV NSs. Also IFN-beta mRNA levels in IFN-competent MRC5 cells either infected with TULV or transiently expressing NSs were decreased. These data demonstrate that Tula and Puumala hantaviruses have a functional NSs ORF. The findings may explain why the NSs ORF has been preserved in the genome of most hantaviruses during their long evolution and why hantavirus-infected cells secrete relatively low levels of IFNs. (c) 2007 Wiley-Liss, Inc.

  2. Using multiple schedules during functional communication training to promote rapid transfer of treatment effects.

    Science.gov (United States)

    Fisher, Wayne W; Greer, Brian D; Fuhrman, Ashley M; Querim, Angie C

    2015-12-01

    Multiple schedules with signaled periods of reinforcement and extinction have been used to thin reinforcement schedules during functional communication training (FCT) to make the intervention more practical for parents and teachers. We evaluated whether these signals would also facilitate rapid transfer of treatment effects across settings and therapists. With 2 children, we conducted FCT in the context of mixed (baseline) and multiple (treatment) schedules introduced across settings or therapists using a multiple baseline design. Results indicated that when the multiple schedules were introduced, the functional communication response came under rapid discriminative control, and problem behavior remained at near-zero rates. We extended these findings with another individual by using a more traditional baseline in which problem behavior produced reinforcement. Results replicated those of the previous participants and showed rapid reductions in problem behavior when multiple schedules were implemented across settings. © Society for the Experimental Analysis of Behavior.

  3. Microsoft Technology as an Optimization Tool in Promoting Security and Functionality of the Educational System

    Directory of Open Access Journals (Sweden)

    Jelena Jardas Antonic

    2008-10-01

    Full Text Available Abstract - In the cooperation with the City of Rijeka, the project of analysis of the functional and security situation of information infrastructure has been initiated in 24 schools in the authority of the city. Having completed the multicriteria analysis of the collected data, we have built a model of implementing Microsoft service technologies. The implementation should satisfy the elementary security principles that are required by the security standards today, maximizing functionality of infrastructure and minimizing network administration tasks. Server technology that has been used in this solution is Microsoft Widows 2003 Server R2 and Internet Security and Acceleration Server 2006, as well as the GFI WebMonitor and antivirus.

  4. Functionalized isothianaphthene monomers that promote quinoidal character in donor-acceptor copolymers for organic photovoltaics

    KAUST Repository

    Douglas, Jessica D.

    2012-05-22

    A series of low band gap isothianaphthene-based (ITN) polymers with various electron-withdrawing substituents and intrinsic quinoidal character were synthesized, characterized, and tested in organic photovoltaic (OPV) devices. The three investigated ITN cores contained either ester, imide, or nitrile functionalities and were each synthesized in only four linear steps. The relative electron-withdrawing strength of the three substituents on the ITN moiety was evaluated and correlated to the optical and electronic properties of ITN-based copolymers. The ester- and imide-containing p-type polymers reached device efficiencies as high as 3% in bulk heterojunction blends with phenyl C 61-butyric acid methyl ester (PC 61BM), while the significantly electron-deficient nitrile-functionalized polymer behaved as an n-type material with an efficiency of 0.3% in bilayer devices with poly(3-(4-n-octyl)phenylthiophene) (POPT). © 2012 American Chemical Society.

  5. Functional and structural comparisons of the arthroscopic knotless double-row suture bridge and single-row repair for anterosuperior rotator cuff tears.

    Science.gov (United States)

    Ide, Junji; Karasugi, Tatsuki; Okamoto, Nobukazu; Taniwaki, Takuya; Oka, Kiyoshi; Mizuta, Hiroshi

    2015-10-01

    We compared the outcomes of knotless double-row suture bridge and single-row repairs in patients undergoing arthroscopic repair for anterosuperior rotator cuff tears. We included 61 full-thickness anterosuperior rotator cuff tears treated by arthroscopic repair, namely, single-row repair (group 1: 25 shoulders; mean patient age, 64 years) and the knotless double-row suture bridge repair (group 2: 36 shoulders; mean patient age, 62 years). Preoperative and postoperative magnetic resonance imaging was performed for all shoulders. Clinical outcomes were evaluated for mean follow-up periods of 81 months (range, 72-96 months) in group 1 and 34 months (range, 24-42 months) in group 2, using the University of California, Los Angeles and Japanese Orthopaedic Association assessments. At the final follow-up, both groups showed improvement in the average University of California, Los Angeles and Japanese Orthopaedic Association scores and range of motion, although no intergroup differences were observed. Both groups showed improved abduction strength, and the average score was higher in group 2 (P = .0112). The lift-off and belly-press test results were improved in both groups. Postoperatively, the incidence of positive lift-off tests tended to be lower (P = .075) and that of positive belly-press tests was lower in group 2, P = .049). The repair failure rate tended to be lower in group 2 (14% [5 of 36]) than in group 1 (32% [8 of 25]; P = .0839). Arthroscopic knotless double-row suture bridge repair of anterosuperior rotator cuff tears yielded functional outcomes equivalent to those of single-row repair and may be useful for improving subscapularis function, abduction strength, and tendon healing. Copyright © 2015 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

  6. Stereoselective synthesis of diazaspiro[5.5]undecane derivatives via base promoted [5+1] double Michael addition of N,N-dimethylbarbituric acid to diaryliedene acetones

    Directory of Open Access Journals (Sweden)

    Mohammad Shahidul Islam

    2017-01-01

    Full Text Available The nitrogen containing spiro-heterocycle is one of the privileged synthetic motif that constitutes various naturally occurring molecules and displays a broad range of pharmaceutical and biological activities. A new methodology was developed for the synthesis of 2,4-diazaspiro[5.5]undecane-1,3,5,9-tetraones spiro-heterocyclic derivatives via cascade cyclization of [5+1] double Michael addition reaction of N,N-dimethylbarbituric acid with the derivatives of diaryldivinylketones in the presence of diethylamine at ambient temperature. The developed protocol is highly capable of furnishing diazaspiro[5.5]undecane derivatives 3a–m in excellent yields (up to 98%, from easily accessible symmetric and non-symmetric divinylketones 2a–m, containing aryl and heteroaryl substituents. The diazaspiro-heterocyclic structure was mainly elucidated by NMR and X-ray crystallographic techniques. The single-crystal X-ray studies revealed that, the cyclohexanone unit of spirocycles often prefers a chair conformation rather than twisted conformation. The intermolecular hydrogen bonding and CArH⋯π, π–π stacking interactions driving forces are mainly responsible for the crystal packing.

  7. Biomimetic hydrogels direct spinal progenitor cell differentiation and promote functional recovery after spinal cord injury

    Science.gov (United States)

    Geissler, Sydney A.; Sabin, Alexandra L.; Besser, Rachel R.; Gooden, Olivia M.; Shirk, Bryce D.; Nguyen, Quan M.; Khaing, Zin Z.; Schmidt, Christine E.

    2018-04-01

    Objective. Demyelination that results from disease or traumatic injury, such as spinal cord injury (SCI), can have a devastating effect on neural function and recovery. Many researchers are examining treatments to minimize demyelination by improving oligodendrocyte availability in vivo. Transplantation of stem and oligodendrocyte progenitor cells is a promising option, however, trials are plagued by undirected differentiation. Here we introduce a biomaterial that has been optimized to direct the differentiation of neural progenitor cells (NPCs) toward oligodendrocytes as a cell delivery vehicle after SCI. Approach. A collagen-based hydrogel was modified to mimic the mechanical properties of the neonatal spinal cord, and components present in the developing extracellular matrix were included to provide appropriate chemical cues to the NPCs to direct their differentiation toward oligodendrocytes. The hydrogel with cells was then transplanted into a unilateral cervical contusion model of SCI to examine the functional recovery with this treatment. Six behavioral tests and histological assessment were performed to examine the in vivo response to this treatment. Main results. Our results demonstrate that we can achieve a significant increase in oligodendrocyte differentiation of NPCs compared to standard culture conditions using a three-component biomaterial composed of collagen, hyaluronic acid, and laminin that has mechanical properties matched to those of neonatal neural tissue. Additionally, SCI rats with hydrogel transplants, with and without NPCs, showed functional recovery. Animals transplanted with hydrogels with NPCs showed significantly increased functional recovery over six weeks compared to the media control group. Significance. The three-component hydrogel presented here has the potential to provide cues to direct differentiation in vivo to encourage regeneration of the central nervous system.

  8. CRISPR/Cas9 Promotes Functional Study of Testis Specific X-Linked Gene In Vivo.

    Directory of Open Access Journals (Sweden)

    Minyan Li

    Full Text Available Mammalian spermatogenesis is a highly regulated multistage process of sperm generation. It is hard to uncover the real function of a testis specific gene in vitro since the in vitro model is not yet mature. With the development of the CRISPR/Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated 9 system, we can now rapidly generate knockout mouse models of testis specific genes to study the process of spermatogenesis in vivo. SYCP3-like X-linked 2 (SLX2 is a germ cell specific component, which contains a Cor1 domain and belongs to the XLR (X-linked, lymphocyte regulated family. Previous studies suggested that SLX2 might play an important role in mouse spermatogenesis based on its subcellular localization and interacting proteins. However, the function of SLX2 in vivo is still elusive. Here, to investigate the functions of SLX2 in spermatogenesis, we disrupted the Slx2 gene by using the CRISPR/Cas9 system. Since Slx2 is a testis specific X-linked gene, we obtained knockout male mice in the first generation and accelerated the study process. Compared with wild-type mice, Slx2 knockout mice have normal testis and epididymis. Histological observation of testes sections showed that Slx2 knockout affected none of the three main stages of spermatogenesis: mitosis, meiosis and spermiogenesis. In addition, we further confirmed that disruption of Slx2 did not affect the number of spermatogonial stem cells, meiosis progression or XY body formation by immunofluorescence analysis. As spermatogenesis was normal in Slx2 knockout mice, these mice were fertile. Taken together, we showed that Slx2 itself is not an essential gene for mouse spermatogenesis and CRISPR/Cas9 technique could speed up the functional study of testis specific X-linked gene in vivo.

  9. Promoting functional foods as acceptable alternatives to doping: potential for information-based social marketing approach

    OpenAIRE

    Petróczi Andrea; Naughton Declan P; James Ricky

    2010-01-01

    Abstract Background Substances with performance enhancing properties appear on a continuum, ranging from prohibited performance enhancing drugs (PED) through dietary supplements to functional foods (FF). Anti-doping messages designed to dissuade athletes from using PEDs have been typically based on moralising sport competition and/or employing scare campaigns with focus on the negative consequences. Campaigns offering comparable and acceptable alternatives are nonexistent, nor are athletes he...

  10. Congenital maxillary double lip

    Directory of Open Access Journals (Sweden)

    Dinesh Singh Chauhan

    2012-01-01

    Full Text Available Double lip, also referred to as "macrocheilia," is a rare anomaly which affects the upper lip more commonly than the lower lip. It consists of a fold of excess or redundant hypertrophic tissue on the mucosal side of the lip. The congenital double lip is believed to be present at birth and becomes more prominent after eruption of teeth. It affects esthetics and also interferes with speech and mastication. Simple surgical excision produces good functional and cosmetic results. We report a case of a non-syndromic congenital maxillary double lip in a 21-year-old male patient.

  11. Impaired atrial electromechanical function and atrial fibrillation promotion in alloxan-induced diabetic rabbits.

    Science.gov (United States)

    Fu, Huaying; Liu, Changle; Li, Jian; Zhou, Changyu; Cheng, Lijun; Liu, Tong; Li, Guangping

    2013-01-01

    Diabetes mellitus (DM) is an independent risk factor for atrial fibrillation (AF). However, the underlying mechanisms are still not clearly elucidated. The aim of this study was to evaluate the atrial electromechanical function, atrial electrophysiological changes and AF inducibility in alloxan-induced diabetic rabbits. In 8 alloxan-induced diabetic rabbits and 8 controls, we evaluated atrial electromechanical function by tissue Doppler imaging. Isolated Langendorff-perfused rabbit hearts were prepared to measure atrial refractory effective period (AERP) and its dispersion (AERPD), interatrial conduction time (IACT) and vulnerability to AF. Atrial interstitial fibrosis was evaluated by Sirius-Red staining. Compared with controls, left atrial lateral wall Pa'-start interval (Pastart) and right atrial wall Pastart were increased in diabetic rabbits. AERPD was increased and IACT was prolonged in diabetic rabbits. Inducibility of AF in diabetic group was significant higher than controls (6/8 vs. 1/8, p TEMA); left atrial lateral wall Papeak and TEMA, left atrial posterior wall TEMA, and IACT were correlated with atrial areas of fibrosis. Atrial electromechanical function is impaired in diabetic rabbits, and is associated with atrial fibrosis and interatrial electrical conduction delay.

  12. Exercise promotes motor functional recovery in rats with corticospinal tract injury: anti-apoptosis mechanism

    Directory of Open Access Journals (Sweden)

    Ting-ting Hou

    2015-01-01

    Full Text Available Studies have shown that exercise interventions can improve functional recovery after spinal cord injury, but the mechanism of action remains unclear. To investigate the mechanism, we established a unilateral corticospinal tract injury model in rats by pyramidotomy, and used a single pellet reaching task and horizontal ladder walking task as exercise interventions postoperatively. Functional recovery of forelimbs and forepaws in the rat models was noticeably enhanced after the exercises. Furthermore, TUNEL staining revealed significantly fewer apoptotic cells in the spinal cord of exercised rats, and western blot analysis showed that spinal cord expression of the apoptosis-related protein caspase-3 was significantly lower, and the expression of Bcl-2 was significantly higher, while the expression of Bax was not signifiantly changed after exercise, compared with the non-exercised group. Expression of these proteins decreased with time after injury, towards the levels observed in sham-operated rats, however at 4 weeks postoperatively, caspase-3 expression remained significantly greater than in sham-operated rats. The present findings indicate that a reduction in apoptosis is one of the mechanisms underlying the improvement of functional recovery by exercise interventions after corticospinal tract injury.

  13. Thioetherification of chloroheteroarenes: a binuclear catalyst promotes wide scope and high functional-group tolerance.

    Science.gov (United States)

    Platon, Mélanie; Wijaya, Novi; Rampazzi, Vincent; Cui, Luchao; Rousselin, Yoann; Saeys, Mark; Hierso, Jean-Cyrille

    2014-09-22

    A constrained binuclear palladium catalyst system affords selective thioetherification of a wide range of functionalized arenethiols with chloroheteroaromatic partners with the highest turnover numbers (TONs) reported to date and tolerates a large variety of reactive functions. The scope of this system includes the coupling of thiophenols with six- and five-membered 2-chloroheteroarenes (i.e., functionalized pyridine, pyrazine, quinoline, pyrimidine, furane, and thiazole) and 3-bromoheteroarenes (i.e., pyridine and furane). Electron-rich congested thiophenols and fluorinated thiophenols are also suitable partners. The coupling of unprotected amino-2-chloropyridines with thiophenol and the successful employment of synthetically valuable chlorothiophenols are described with the same catalyst system. DFT studies attribute the high performance of this binuclear palladium catalyst to the decreased stability of thiolate-containing resting states. Palladium loading was as low as 0.2 mol %, which is important for industrial application and is a step forward in solving catalyst activation/deactivation problems. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Exposure of Monocytes to Lipoarabinomannan Promotes Their Differentiation into Functionally and Phenotypically Immature Macrophages

    Directory of Open Access Journals (Sweden)

    Leslie Chávez-Galán

    2015-01-01

    Full Text Available Lipoarabinomannan (LAM is a lipid virulence factor secreted by Mycobacterium tuberculosis (Mtb, the etiologic agent of tuberculosis. LAM can be measured in the urine or serum of tuberculosis patients (TB-patients. Circulating monocytes are the precursor cells of alveolar macrophages and might be exposed to LAM in patients with active TB. We speculated that exposing monocytes to LAM could produce phenotypically and functionally immature macrophages. To test our hypothesis, human monocytes were stimulated with LAM (24–120 hours and various readouts were measured. The study showed that when monocytes were exposed to LAM, the frequency of CD68+, CD33+, and CD86+ macrophages decreased, suggesting that monocyte differentiation into mature macrophages was affected. Regarding functionality markers, TLR2+ and TLR4+ macrophages also decreased, but the percentage of MMR+ expression did not change. LAM-exposed monocytes generated macrophages that were less efficient in producing proinflammatory cytokines such as TNF-α and IFN-γ; however, their phagocytic capacity was not modified. Taken together, these data indicate that LAM exposure influenced monocyte differentiation and produced poorly functional macrophages with a different phenotype. These results may help us understand how mycobacteria can limit the quality of the innate and adaptive immune responses.

  15. Functional, genetic and chemical characterization of biosurfactants produced by plant growth-promoting Pseudomonas putida 267.

    Science.gov (United States)

    Kruijt, Marco; Tran, Ha; Raaijmakers, Jos M

    2009-08-01

    Plant growth-promoting Pseudomonas putida strain 267, originally isolated from the rhizosphere of black pepper, produces biosurfactants that cause lysis of zoospores of the oomycete pathogen Phytophthora capsici. The biosurfactants were characterized, the biosynthesis gene(s) partially identified, and their role in control of Phytophthora damping-off of cucumber evaluated. The biosurfactants were shown to lyse zoospores of Phy. capsici and inhibit growth of the fungal pathogens Botrytis cinerea and Rhizoctonia solani. In vitro assays further showed that the biosurfactants of strain 267 are essential in swarming motility and biofilm formation. In spite of the zoosporicidal activity, the biosurfactants did not play a significant role in control of Phytophthora damping-off of cucumber, since both wild type strain 267 and its biosurfactant-deficient mutant were equally effective, and addition of the biosurfactants did not provide control. Genetic characterization revealed that surfactant biosynthesis in strain 267 is governed by homologues of PsoA and PsoB, two nonribosomal peptide synthetases involved in production of the cyclic lipopeptides (CLPs) putisolvin I and II. The structural relatedness of the biosurfactants of strain 267 to putisolvins I and II was supported by LC-MS and MS-MS analyses. The biosurfactants produced by Ps. putida 267 were identified as putisolvin-like CLPs; they are essential in swarming motility and biofilm formation, and have zoosporicidal and antifungal activities. Strain 267 provides excellent biocontrol activity against Phytophthora damping-off of cucumber, but the lipopeptide surfactants are not involved in disease suppression. Pseudomonas putida 267 suppresses Phy. capsici damping-off of cucumber and provides a potential supplementary strategy to control this economically important oomycete pathogen. The putisolvin-like biosurfactants exhibit zoosporicidal and antifungal activities, yet they do not contribute to biocontrol of Phy

  16. Galactosylated poly(ε-caprolactone) membrane promoted liver-specific functions of HepG2 cells in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yan, E-mail: zhang_yan@ecust.edu.cn [The Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237 (China); Zhang, Yi [The Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237 (China); Chen, Min; Zhou, Yan [The State Key Laboratory of Bioreactor Engineering, School of Bioengineering, East China University of Science and Technology, Shanghai, 200237 (China); Lang, Meidong, E-mail: mdlang@ecust.edu.cn [The Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237 (China)

    2014-08-01

    The lack of pendant functional groups on the PCL backbone has been a great challenge for surface bioactivation of poly(ε-caprolactone) (PCL). In the present study, covalently galactosylated PCL (GPCL) was developed through coupling between the amino-functionalized PCL (NPCL) and the lactobionic acid (LA) and its potential application in maintenance of physiological functions of HepG2 cells was further evaluated. The structure and properties of GPCL were explored by {sup 1}H NMR, FT-IR, GPC and DSC. Moreover, the incorporation of galactose ligands onto GPCL membranes not only promoted higher wettability, but also radically changed surface morphology in comparison with PCL and NPCL according to the contact angle measurement and atomic force microscopy. When HepG2 cells were seeded onto these membranes, the cells on GPCL membranes showed more pronounced cell adhesion and tended to form aggregates during the initial adhesion stage and then progressively grew into multi-layer structures compared to those without galactose ligands by the observation with fluorescence microscope and scanning electron microscopy. Furthermore, live–dead assay and functional tests demonstrated that HepG2 cells on GPCL membranes had superior viability and maintained better liver-specific functions. Collectively, GPCL has great potential for hepatic tissue engineering scaffolds. - Graphical abstract: The specific recognition between the galactose ligands on the galactosylated poly(ε-caprolactone) membrane and the ASGPR on the HepG2 cell surface. The galactosylated poly(ε-caprolactone) membranes improved the cell-matrix interaction. The galactosylated functionalized PCL scaffold is a potential candidate for liver tissue engineering. - Highlights: • The specific recognition between the galactose ligands on the galactosylated poly(ε-caprolactone) membrane and the ASGPR on the HepG2 cell surface. • The galactosylated poly(ε-caprolactone) membranes improved the cell-matrix interaction.

  17. Exercise Training and Recreational Activities to Promote Executive Functions in Chronic Stroke: A Proof-of-Concept Study

    Science.gov (United States)

    Liu-Ambrose, Teresa; Eng, Janice J

    2015-01-01

    Background Stroke survivors represent a target population in need of intervention strategies to promote cognitive function and prevent dementia. Both exercise and recreational activities are promising strategies. We assessed the effect of a six-month exercise and recreation program on executive functions in adults with chronic stroke. Methods A six-month ancillary study within a multi-centre randomized trial. Twenty-eight chronic stroke survivors (i.e., ≥ 12 months since an index stroke) were randomized to one of two experimental groups: intervention (INT; n=12) or delayed intervention (D-INT; n=16). Participants of the INT group received a six-month community-based structured program that included two sessions of exercise training and one session of recreation and leisure activities per week. Participants of the D-INT group received usual care. The primary outcome measure was the Stroop Test, a cognitive test of selective attention and conflict resolution. Secondary cognitive measures included set shifting and working memory. Mood, functional capacity, and general balance and mobility were additional secondary outcome measures. Results Compared with the D-INT group, the INT group significantly improved selective attention and conflict resolution (p=0.02), working memory (p=0.04), and functional capacity (p=0.02) at the end of the six-month intervention period. Improved selective attention and conflict resolution was significantly associated with functional capacity at six months (r=0.39; p=0.04). Conclusions This is the first randomized study to demonstrate that an exercise and recreation program can significantly benefit executive functions in community-dwelling chronic stroke survivors who are mildly cognitively impaired – a population at high-risk for dementia and functional decline. Thus, clinicians should consider prescribing exercise and recreational activities in the cognitive rehabilitation of chronic stroke survivors. Clinical Trial Registration http

  18. Double Trouble

    NARCIS (Netherlands)

    Elsaesser, Thomas; Kievit, Robert; Simons, Jan

    1994-01-01

    Double Trouble highlights the career of Dutch scriptwriter and television producer Chiem van Houweninge, well-known for his long-running TV comedy series and as author of episodes for TV detective series. Double Trouble gives Van Houweninge's own views on writing and filming in television prime

  19. [Therapeutic effect of double fill nine tastes soup in treating recurrent respiratory infection (RRI) and change of immune function in children].

    Science.gov (United States)

    Wang, Youcheng; Zhang, Lijuan; Hu, Guohua; Wang, Menghe; Tang, Xiaoyuan; Guo, Hui; Shi, Yimei; Chen, Shufang; Shi, Changchun

    2012-04-01

    To investigate the therapeutic effect of double fill nine tastes soup in treating children recurrent respiratory infection (RRTI) and the change of immune function. 77 RRTI patients were randomly selected into observation and control groups. The observation group was treated with Chinese medicine- double fill nine tastes soup,water frying points 2 times oral. The control was treated with transfer factor oral liquid,every 10 mL,2 times daily oral. Treatment periods were both two months. IgA, IgG, IgM and IL-12, TNF-alpha, INF-gamma were detected before and after treatment to assess the clinical effects and the changes of immune factors, meanwhile, a health group was established. Before treatment, compared with the health group, the serum IgA, IgG, IgM, IgE, IL-12, TNF-alpha, IFN-gamma in both groups were significantly different (P soup has significant effects in treating recurrent respiratory infection (RRI) and enhance the immune function in children.

  20. Designing an artificial neural network using radial basis function to model exergetic efficiency of nanofluids in mini double pipe heat exchanger

    Science.gov (United States)

    Ghasemi, Nahid; Aghayari, Reza; Maddah, Heydar

    2018-06-01

    The present study aims at predicting and optimizing exergetic efficiency of TiO2-Al2O3/water nanofluid at different Reynolds numbers, volume fractions and twisted ratios using Artificial Neural Networks (ANN) and experimental data. Central Composite Design (CCD) and cascade Radial Basis Function (RBF) were used to display the significant levels of the analyzed factors on the exergetic efficiency. The size of TiO2-Al2O3/water nanocomposite was 20-70 nm. The parameters of ANN model were adapted by a training algorithm of radial basis function (RBF) with a wide range of experimental data set. Total mean square error and correlation coefficient were used to evaluate the results which the best result was obtained from double layer perceptron neural network with 30 neurons in which total Mean Square Error(MSE) and correlation coefficient (R2) were equal to 0.002 and 0.999, respectively. This indicated successful prediction of the network. Moreover, the proposed equation for predicting exergetic efficiency was extremely successful. According to the optimal curves, the optimum designing parameters of double pipe heat exchanger with inner twisted tape and nanofluid under the constrains of exergetic efficiency 0.937 are found to be Reynolds number 2500, twisted ratio 2.5 and volume fraction( v/v%) 0.05.

  1. Blueberries improve endothelial function, but not blood pressure, in adults with metabolic syndrome: a randomized, double-blind, placebo-controlled clinical trial.

    Science.gov (United States)

    Stull, April J; Cash, Katherine C; Champagne, Catherine M; Gupta, Alok K; Boston, Raymond; Beyl, Robbie A; Johnson, William D; Cefalu, William T

    2015-05-27

    Blueberry consumption has been shown to have various health benefits in humans. However, little is known about the effect of blueberry consumption on blood pressure, endothelial function and insulin sensitivity in humans. The present study investigated the role of blueberry consumption on modifying blood pressure in subjects with metabolic syndrome. In addition, endothelial function and insulin sensitivity (secondary measurements) were also assessed. A double-blind and placebo-controlled study was conducted in 44 adults (blueberry, n = 23; and placebo, n = 21). They were randomized to receive a blueberry or placebo smoothie twice daily for six weeks. Twenty-four-hour ambulatory blood pressure, endothelial function and insulin sensitivity were assessed pre- and post-intervention. The blood pressure and insulin sensitivity did not differ between the blueberry and placebo groups. However, the mean change in resting endothelial function, expressed as reactive hyperemia index (RHI), was improved significantly more in the group consuming the blueberries versus the placebo group (p = 0.024). Even after adjusting for confounding factors, i.e., the percent body fat and gender, the blueberry group still had a greater improvement in endothelial function when compared to their counterpart (RHI; 0.32 ± 0.13 versus -0.33 ± 0.14; p = 0.0023). In conclusion, daily dietary consumption of blueberries did not improve blood pressure, but improved (i.e., increased) endothelial function over six weeks in subjects with metabolic syndrome.

  2. Restoring the consistency with the contact density theorem of a classical density functional theory of ions at a planar electrical double layer.

    Science.gov (United States)

    Gillespie, Dirk

    2014-11-01

    Classical density functional theory (DFT) of fluids is a fast and efficient theory to compute the structure of the electrical double layer in the primitive model of ions where ions are modeled as charged, hard spheres in a background dielectric. While the hard-core repulsive component of this ion-ion interaction can be accurately computed using well-established DFTs, the electrostatic component is less accurate. Moreover, many electrostatic functionals fail to satisfy a basic theorem, the contact density theorem, that relates the bulk pressure, surface charge, and ion densities at their distances of closest approach for ions in equilibrium at a smooth, hard, planar wall. One popular electrostatic functional that fails to satisfy the contact density theorem is a perturbation approach developed by Kierlik and Rosinberg [Phys. Rev. A 44, 5025 (1991)PLRAAN1050-294710.1103/PhysRevA.44.5025] and Rosenfeld [J. Chem. Phys. 98, 8126 (1993)JCPSA60021-960610.1063/1.464569], where the full free-energy functional is Taylor-expanded around a bulk (homogeneous) reference fluid. Here, it is shown that this functional fails to satisfy the contact density theorem because it also fails to satisfy the known low-density limit. When the functional is corrected to satisfy this limit, a corrected bulk pressure is derived and it is shown that with this pressure both the contact density theorem and the Gibbs adsorption theorem are satisfied.

  3. Fibrin matrices with affinity-based delivery systems and neurotrophic factors promote functional nerve regeneration.

    Science.gov (United States)

    Wood, Matthew D; MacEwan, Matthew R; French, Alexander R; Moore, Amy M; Hunter, Daniel A; Mackinnon, Susan E; Moran, Daniel W; Borschel, Gregory H; Sakiyama-Elbert, Shelly E

    2010-08-15

    Glial-derived neurotrophic factor (GDNF) and nerve growth factor (NGF) have both been shown to enhance peripheral nerve regeneration following injury and target different neuronal populations. The delivery of either growth factor at the site of injury may, therefore, result in quantitative differences in motor nerve regeneration and functional recovery. In this study we evaluated the effect of affinity-based delivery of GDNF or NGF from fibrin-filled nerve guidance conduits (NGCs) on motor nerve regeneration and functional recovery in a 13 mm rat sciatic nerve defect. Seven experimental groups were evaluated consisting of GDNF or NGF and the affinity-based delivery system (DS) within NGCs, control groups excluding the DS and/or growth factor, and nerve isografts. Groups with growth factor in the conduit demonstrated equivalent or superior performance in behavioral tests and relative muscle mass measurements compared to isografts at 12 weeks. Additionally, groups with GDNF demonstrated greater specific twitch and tetanic force production in extensor digitorum longus (EDL) muscle than the isograft control, while groups with NGF produced demonstrated similar force production compared to the isograft control. Assessment of motor axon regeneration by retrograde labeling further revealed that the number of ventral horn neurons regenerating across NGCs containing GDNF and NGF DS was similar to the isograft group and these counts were greater than the groups without growth factor. Overall, the GDNF DS group demonstrated superior functional recovery and equivalent motor nerve regeneration compared to the isograft control, suggesting it has potential as a treatment for motor nerve injury.

  4. Lateralized kappa opioid receptor signaling from the amygdala central nucleus promotes stress-induced functional pain.

    Science.gov (United States)

    Nation, Kelsey M; De Felice, Milena; Hernandez, Pablo I; Dodick, David W; Neugebauer, Volker; Navratilova, Edita; Porreca, Frank

    2018-05-01

    The response of diffuse noxious inhibitory controls (DNIC) is often decreased, or lost, in stress-related functional pain syndromes. Because the dynorphin/kappa opioid receptor (KOR) pathway is activated by stress, we determined its role in DNIC using a model of stress-induced functional pain. Male, Sprague-Dawley rats were primed for 7 days with systemic morphine resulting in opioid-induced hyperalgesia. Fourteen days after priming, when hyperalgesia was resolved, rats were exposed to environmental stress and DNIC was evaluated by measuring hind paw response threshold to noxious pressure (test stimulus) after capsaicin injection in the forepaw (conditioning stimulus). Morphine priming without stress did not alter DNIC. However, stress produced a loss of DNIC in morphine-primed rats in both hind paws that was abolished by systemic administration of the KOR antagonist, nor-binaltorphimine (nor-BNI). Microinjection of nor-BNI into the right, but not left, central nucleus of the amygdala (CeA) prevented the loss of DNIC in morphine-primed rats. Diffuse noxious inhibitory controls were not modulated by bilateral nor-BNI in the rostral ventromedial medulla. Stress increased dynorphin content in both the left and right CeA of primed rats, reaching significance only in the right CeA; no change was observed in the rostral ventromedial medulla or hypothalamus. Although morphine priming alone is not sufficient to influence DNIC, it establishes a state of latent sensitization that amplifies the consequences of stress. After priming, stress-induced dynorphin/KOR signaling from the right CeA inhibits DNIC in both hind paws, likely reflecting enhanced descending facilitation that masks descending inhibition. Kappa opioid receptor antagonists may provide a new therapeutic strategy for stress-related functional pain disorders.

  5. ATM/ATR-mediated phosphorylation of PALB2 promotes RAD51 function

    DEFF Research Database (Denmark)

    Ahlskog, Johanna K; Larsen, Brian D; Achanta, Kavya

    2016-01-01

    DNA damage activates the ATM and ATR kinases that coordinate checkpoint and DNA repair pathways. An essential step in homology-directed repair (HDR) of DNA breaks is the formation of RAD51 nucleofilaments mediated by PALB2-BRCA2; however, roles of ATM and ATR in this critical step of HDR are poor...... function, as the PALB2-dependent checkpoint response is normal in cells expressing the phospho-deficient PALB2 mutant. Collectively, our findings highlight a critical importance of PALB2 phosphorylation as a novel regulatory step in genome maintenance after genotoxic stress....

  6. Effect of the laxative magnesium oxide on gastrointestinal functional recovery in fast-track colonic resection: a double-blind, placebo-controlled randomized study

    DEFF Research Database (Denmark)

    Andersen, J; Christensen, H; Pachler, J H

    2012-01-01

    Aim: A double-blind randomised controlled study was conducted to compare the effect of magnesium oxide (1 g 12-hourly) with placebo given within an evidence-based multimodal rehabilitation programme on gastrointestinal recovery, pain, mobilisation and hospital stay after open colonic resection....... Method: Of sixty two potentially eligible patients, thirteen were excluded leaving 22 in the magnesium oxide group and 27 in the placebo group. The main outcome measure was time to normalization of bowel function. Secondary outcome measures included post operative nausea, vomiting, pain, fatigue...... were similar in the groups (p>0.3). The median postoperative hospital stay was three days in both groups (p>0.65). Conclusion: Magnesium oxide does not enhance the recovery of gastrointestinal function within the context of an evidence-based multimodal rehabilitation programme after open colonic...

  7. Episodic feeling-of-knowing accuracy and cued recall in the elderly: evidence for double dissociation involving executive functioning and processing speed.

    Science.gov (United States)

    Perrotin, Audrey; Isingrini, Michel; Souchay, Céline; Clarys, David; Taconnat, Laurence

    2006-05-01

    This research investigated adult age differences in a metamemory monitoring task-episodic feeling-of-knowing (FOK) and in an episodic memory task-cued recall. Executive functioning and processing speed were examined as mediators of these age differences. Young and elderly adults were administered an episodic FOK task, a cued recall task, executive tests and speed tests. Age-related decline was observed on all the measures. Correlation analyses revealed a pattern of double dissociation which indicates a specific relationship between executive score and FOK accuracy, and between speed score and cued recall. When executive functioning and processing speed were evaluated concurrently on FOK and cued recall variables, hierarchical regression analyses showed that executive score was a better mediator of age-related variance in FOK, and that speed score was the better mediator of age-related variance in cued recall.

  8. Double-stranded RNA promotes CTL-independent tumor cytolysis mediated by CD11b+Ly6G+ intratumor myeloid cells through the TICAM-1 signaling pathway

    Science.gov (United States)

    Shime, Hiroaki; Matsumoto, Misako; Seya, Tsukasa

    2017-01-01

    PolyI:C, a synthetic double-stranded RNA analog, acts as an immune-enhancing adjuvant that regresses tumors in cytotoxic T lymphocyte (CTL)-dependent and CTL-independent manner, the latter of which remains largely unknown. Tumors contain CD11b+Ly6G+ cells, known as granulocytic myeloid-derived suppressor cells (G-MDSCs) or tumor-associated neutrophils (TANs) that play a critical role in tumor progression and development. Here, we demonstrate that CD11b+Ly6G+ cells respond to polyI:C and exhibit tumoricidal activity in an EL4 tumor implant model. PolyI:C-induced inhibition of tumor growth was attributed to caspase-8/3 cascade activation in tumor cells that occurred independently of CD8α+/CD103+ dendritic cells (DCs) and CTLs. CD11b+Ly6G+ cells was essential for the antitumor effect because depletion of CD11b+Ly6G+ cells totally abrogated tumor regression and caspase activation after polyI:C treatment. CD11b+Ly6G+ cells that had been activated with polyI:C showed cytotoxicity and inhibited tumor growth through the production of reactive oxygen species (ROS)/reactive nitrogen species (RNS). These responses were abolished in either Toll/interleukin-1 receptor domain-containing adaptor molecule-1 (TICAM-1)−/− or interferon (IFN)-αβ receptor 1 (IFNAR1)−/− mice. Thus, our results suggest that polyI:C activates the TLR3/TICAM-1 and IFNAR signaling pathways in CD11b+Ly6G+ cells in tumors, thereby eliciting their antitumor activity, independent of those in CD8α+/CD103+ DCs that prime CTLs. PMID:27834952

  9. CD147 promotes the formation of functional osteoclasts through NFATc1 signalling

    International Nuclear Information System (INIS)

    Nishioku, Tsuyoshi; Terasawa, Mariko; Baba, Misaki; Yamauchi, Atsushi; Kataoka, Yasufumi

    2016-01-01

    CD147, a membrane glycoprotein of the immunoglobulin superfamily, is highly upregulated during dynamic cellular events including tissue remodelling. Elevated CD147 expression is present in the joint of rheumatoid arthritis patients. However, the role of CD147 in bone destruction remains unclear. To determine whether CD147 is involved in osteoclastogenesis, we studied its expression in mouse osteoclasts and its role in osteoclast differentiation and function. CD147 expression was markedly upregulated during osteoclast differentiation. To investigate the role of CD147 in receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclastogenesis and bone resorption activity, osteoclast precursor cells were transfected with CD147 siRNA. Decreased CD147 expression inhibited osteoclast formation and bone resorption, inhibited RANKL-induced nuclear translocation of the nuclear factor of activated T cells (NFAT) c1 and decreased the expression of the d2 isoform of vacuolar ATPase Vo domain and cathepsin K. Therefore, CD147 plays a critical role in the differentiation and function of osteoclasts by upregulating NFATc1 through the autoamplification of its expression in osteoclastogenesis. - Highlights: • CD147 expression was markedly upregulated during osteoclast differentiation. • Downregulation of CD147 expression inhibited osteoclastgenesis and bone resorption. • Decreased CD147 expression inhibited RANKL-induced nuclear translocation of NFATc1.

  10. CD147 promotes the formation of functional osteoclasts through NFATc1 signalling.

    Science.gov (United States)

    Nishioku, Tsuyoshi; Terasawa, Mariko; Baba, Misaki; Yamauchi, Atsushi; Kataoka, Yasufumi

    2016-04-29

    CD147, a membrane glycoprotein of the immunoglobulin superfamily, is highly upregulated during dynamic cellular events including tissue remodelling. Elevated CD147 expression is present in the joint of rheumatoid arthritis patients. However, the role of CD147 in bone destruction remains unclear. To determine whether CD147 is involved in osteoclastogenesis, we studied its expression in mouse osteoclasts and its role in osteoclast differentiation and function. CD147 expression was markedly upregulated during osteoclast differentiation. To investigate the role of CD147 in receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclastogenesis and bone resorption activity, osteoclast precursor cells were transfected with CD147 siRNA. Decreased CD147 expression inhibited osteoclast formation and bone resorption, inhibited RANKL-induced nuclear translocation of the nuclear factor of activated T cells (NFAT) c1 and decreased the expression of the d2 isoform of vacuolar ATPase Vo domain and cathepsin K. Therefore, CD147 plays a critical role in the differentiation and function of osteoclasts by upregulating NFATc1 through the autoamplification of its expression in osteoclastogenesis. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Bacterial genotoxin functions as immune-modulator and promotes host survival

    Directory of Open Access Journals (Sweden)

    Riccardo Guidi

    2016-07-01

    Full Text Available Bacterial genotoxins are effectors that cause DNA damage in target cells. Many aspects of the biology of these toxins have been characterised in vitro, such as structure, cellular internalisation pathways and effects on the target cells. However, little is known about their function in vivo. Salmonella enterica serovar Typhi (S. Typhi is a Gram-negative, intracellular bacterium that causes typhoid fever, a debilitating disease infecting more than 20 million people every year. S. Typhi produce a genotoxin named typhoid toxin (TT, but its role in the contest of host infection is poorly characterized. The major obstacle in addressing this issue is that S. Typhi is exclusively a human pathogen. To overcome this limitation, we have used as model bacterium S. Typhimurium, and engineered it to produce endogenous levels of an active and inactive typhoid toxin, hereby named as TT (or genotoxic and cdtB (or control, respectively. To our surprise, infection with the genotoxin strain strongly suppressed intestinal inflammation, leading to a better survival of the host during the acute phase of infection, suggesting typhoid toxin may exert a protective role. The presence of a functional genotoxin was also associated with an increased frequency of asymptomatic carriers.

  12. Assessing and Promoting Functional Resilience in Flight Crews During Exploration Missions

    Science.gov (United States)

    Shelhamer, M.

    2015-01-01

    The NASA Human Research Program works to mitigate risks to health and performance on extended missions. However, research should be directed not only to mitigating known risks, but also to providing crews with tools to assess and enhance resilience, as a group and individually. We can draw on ideas from complexity theory to assess resilience. The entire crew or the individual crewmember can be viewed as a complex system composed of subsystems; the interactions between subsystems are of crucial importance. Understanding the interactions can provide important information even in the absence of complete information on the component subsystems. Enabled by advances in noninvasive measurement of physiological and behavioral parameters, subsystem monitoring can be implemented within a mission and during training to establish baselines. Coupled with mathematical modeling, this can provide assessment of health and function. Since the web of physiological systems (and crewmembers) can be interpreted as a network in mathematical terms, we can draw on recent work that relates the structure of such networks to their resilience (ability to self-organize in the face of perturbation). Some of the many parameters and interactions to choose from include: sleep cycles, coordination of work and meal times, cardiorespiratory rhythms, circadian rhythms and body temperature, stress markers and cognition, sleep and performance, immune function and nutritional status. Tools for resilience are then the means to measure and analyze these parameters, incorporate them into models of normal variability and interconnectedness, and recognize when parameters or their couplings are outside of normal limits.

  13. CD147 promotes the formation of functional osteoclasts through NFATc1 signalling

    Energy Technology Data Exchange (ETDEWEB)

    Nishioku, Tsuyoshi, E-mail: nishiokut@niu.ac.jp [Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Nagasaki International University, 2825-7 Huis Ten Bosch, Sasebo, Nagasaki 859-3298 (Japan); Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180 (Japan); Terasawa, Mariko; Baba, Misaki; Yamauchi, Atsushi; Kataoka, Yasufumi [Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180 (Japan)

    2016-04-29

    CD147, a membrane glycoprotein of the immunoglobulin superfamily, is highly upregulated during dynamic cellular events including tissue remodelling. Elevated CD147 expression is present in the joint of rheumatoid arthritis patients. However, the role of CD147 in bone destruction remains unclear. To determine whether CD147 is involved in osteoclastogenesis, we studied its expression in mouse osteoclasts and its role in osteoclast differentiation and function. CD147 expression was markedly upregulated during osteoclast differentiation. To investigate the role of CD147 in receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclastogenesis and bone resorption activity, osteoclast precursor cells were transfected with CD147 siRNA. Decreased CD147 expression inhibited osteoclast formation and bone resorption, inhibited RANKL-induced nuclear translocation of the nuclear factor of activated T cells (NFAT) c1 and decreased the expression of the d2 isoform of vacuolar ATPase Vo domain and cathepsin K. Therefore, CD147 plays a critical role in the differentiation and function of osteoclasts by upregulating NFATc1 through the autoamplification of its expression in osteoclastogenesis. - Highlights: • CD147 expression was markedly upregulated during osteoclast differentiation. • Downregulation of CD147 expression inhibited osteoclastgenesis and bone resorption. • Decreased CD147 expression inhibited RANKL-induced nuclear translocation of NFATc1.

  14. MCUR1 Is a Scaffold Factor for the MCU Complex Function and Promotes Mitochondrial Bioenergetics

    Directory of Open Access Journals (Sweden)

    Dhanendra Tomar

    2016-05-01

    Full Text Available Mitochondrial Ca2+ Uniporter (MCU-dependent mitochondrial Ca2+ uptake is the primary mechanism for increasing matrix Ca2+ in most cell types. However, a limited understanding of the MCU complex assembly impedes the comprehension of the precise mechanisms underlying MCU activity. Here, we report that mouse cardiomyocytes and endothelial cells lacking MCU regulator 1 (MCUR1 have severely impaired [Ca2+]m uptake and IMCU current. MCUR1 binds to MCU and EMRE and function as a scaffold factor. Our protein binding analyses identified the minimal, highly conserved regions of coiled-coil domain of both MCU and MCUR1 that are necessary for heterooligomeric complex formation. Loss of MCUR1 perturbed MCU heterooligomeric complex and functions as a scaffold factor for the assembly of MCU complex. Vascular endothelial deletion of MCU and MCUR1 impaired mitochondrial bioenergetics, cell proliferation, and migration but elicited autophagy. These studies establish the existence of a MCU complex that assembles at the mitochondrial integral membrane and regulates Ca2+-dependent mitochondrial metabolism.

  15. Inhibition of Murine Pulmonary Microvascular Endothelial Cell Apoptosis Promotes Recovery of Barrier Function under Septic Conditions

    Directory of Open Access Journals (Sweden)

    Lefeng Wang

    2017-01-01

    Full Text Available Sepsis is characterized by injury of the pulmonary microvasculature and the pulmonary microvascular endothelial cells (PMVEC, leading to barrier dysfunction and acute respiratory distress syndrome (ARDS. Our recent work identified a strong correlation between PMVEC apoptosis and microvascular leak in septic mice in vivo, but the specific role of apoptosis in septic PMVEC barrier dysfunction remains unclear. Thus, we hypothesize that PMVEC apoptosis is likely required for PMVEC barrier dysfunction under septic conditions in vitro. Septic stimulation (mixture of tumour necrosis factor α, interleukin 1β, and interferon γ [cytomix] of isolated murine PMVEC resulted in a significant loss of barrier function as early as 4 h after stimulation, which persisted until 24 h. PMVEC apoptosis, as reflected by caspase activation, DNA fragmentation, and loss of membrane polarity, was first apparent at 8 h after cytomix. Pretreatment of PMVEC with the pan-caspase inhibitor Q-VD significantly decreased septic PMVEC apoptosis and was associated with reestablishment of PMVEC barrier function at 16 and 24 h after stimulation but had no effect on septic PMVEC barrier dysfunction over the first 8 h. Collectively, our data suggest that early septic murine PMVEC barrier dysfunction driven by proinflammatory cytokines is not mediated through apoptosis, but PMVEC apoptosis contributes to late septic PMVEC barrier dysfunction.

  16. Double-dissociation between the mechanism leading to impulsivity and inattention in Attention Deficit Hyperactivity Disorder: A resting-state functional connectivity study.

    Science.gov (United States)

    Sanefuji, Masafumi; Craig, Michael; Parlatini, Valeria; Mehta, Mitul A; Murphy, Declan G; Catani, Marco; Cerliani, Leonardo; Thiebaut de Schotten, Michel

    2017-01-01

    Two core symptoms characterize Attention Deficit Hyperactivity Disorder (ADHD) subtypes: inattentiveness and hyperactivity-impulsivity. While previous brain imaging research investigated ADHD as if it was a homogenous condition, its two core symptoms may originate from different brain mechanisms. We, therefore, hypothesized that the functional connectivity of cortico-striatal and attentional networks would be different between ADHD subtypes. We studied 165 children (mean age 10.93 years; age range, 7-17 year old) diagnosed as having ADHD based on their revised Conner's rating scale score and 170 typical developing individuals (mean age 11.46 years; age range, 7-17 year old) using resting state functional fMRI. Groups were matched for age, IQ and head motion during the MRI acquisition. We fractionated the ADHD group into predominantly inattentive, hyperactive-impulsive and combined subtypes based on their revised Conner's rating scale score. We then analyzed differences in resting state functional connectivity of the cortico-striatal and attentional networks between these subtypes. We found a double dissociation of functional connectivity in the cortico-striatal and ventral attentional networks, reflecting the subtypes of the ADHD participants. Particularly, the hyperactive-impulsive subtype was associated with increased connectivity in cortico-striatal network, whereas the inattentive subtype was associated with increased connectivity in the right ventral attention network. Our study demonstrated for the first time a right lateralized, double dissociation between specific networks associated with hyperactivity-impulsivity and inattentiveness in ADHD children, providing a biological basis for exploring symptom dimensions and revealing potential targets for more personalized treatments. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Genomic structure and promoter functional analysis of GnRH3 gene in large yellow croaker (Larimichthys crocea).

    Science.gov (United States)

    Huang, Wei; Zhang, Jianshe; Liao, Zhi; Lv, Zhenming; Wu, Huifei; Zhu, Aiyi; Wu, Changwen

    2016-01-15

    Gonadotropin-releasing hormone III (GnRH3) is considered to be a key neurohormone in fish reproduction control. In the present study, the cDNA and genomic sequences of GnRH3 were cloned and characterized from large yellow croaker Larimichthys crocea. The cDNA encoded a protein of 99 amino acids with four functional motifs. The full-length genome sequence was composed of 3797 nucleotides, including four exons and three introns. Higher identities of amino acid sequences and conserved exon-intron organizations were found between LcGnRH3 and other GnRH3 genes. In addition, some special features of the sequences were detected in partial species. For example, two specific residues (V and A) were found in the family Sciaenidae, and the unique 75-72 bp type of the open reading frame 2 and 3 existed in the family Cyprinidae. Analysis of the 2576 bp promoter fragment of LcGnRH3 showed a number of transcription factor binding sites, such as AP1, CREB, GATA-1, HSF, FOXA2, and FOXL1. Promoter functional analysis using an EGFP reporter fusion in zebrafish larvae presented positive signals in the brain, including the olfactory region, the terminal nerve ganglion, the telencephalon, and the hypothalamus. The expression pattern was generally consistent with the endogenous GnRH3 GFP-expressing transgenic zebrafish lines, but the details were different. These results indicate that the structure and function of LcGnRH3 are generally similar to the other teleost GnRH3 genes, but there exist some distinctions among them. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Conjugation-promoted reaction of open-cage fullerene: a density functional theory study.

    Science.gov (United States)

    Guo, Yong; Yan, Jingjing; Khashab, Niveen M

    2012-02-01

    Density functional theory calculations are performed to study the addition mechanism of e-rich moieties such as triethyl phosphite to a carbonyl group on the rim of a fullerene orifice. Three possible reaction channels have been investigated. The obtained results show that the reaction of a carbonyl group on a fullerene orifice with triethyl phosphite most likely proceeds along the classical Abramov reaction; however, the classical product is not stable and is converted into the experimental product. An attack on a fullerene carbonyl carbon will trigger a rearrangement of the phosphate group to the carbonyl oxygen as the conversion transition state is stabilized by fullerene conjugation. This work provides a new insight on the reactivity of open-cage fullerenes, which may prove helpful in designing new switchable fullerene systems. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Migrate small, sound big: functional constraints on body size promote tracheal elongation in cranes.

    Science.gov (United States)

    Jones, M R; Witt, C C

    2014-06-01

    Organismal traits often represent the outcome of opposing selection pressures. Although social or sexual selection can cause the evolution of traits that constrain function or survival (e.g. ornamental feathers), it is unclear how the strength and direction of selection respond to ecological shifts that increase the severity of the constraint. For example, reduced body size might evolve by natural selection to enhance flight performance in migratory birds, but social or sexual selection favouring large body size may provide a countervailing force. Tracheal elongation is a potential outcome of these opposing pressures because it allows birds to convey an auditory signal of exaggerated body size. We predicted that the evolution of migration in cranes has coincided with a reduction in body size and a concomitant intensification of social or sexual selection for apparent large body size via tracheal elongation. We used a phylogenetic comparative approach to examine the relationships among migration distance, body mass and trachea length in cranes. As predicted, we found that migration distance correlated negatively with body size and positively with proportional trachea length. This result was consistent with our hypothesis that evolutionary reductions in body size led to intensified selection for trachea length. The most likely ultimate causes of intensified positive selection on trachea length are the direct benefits of conveying a large body size in intraspecific contests for mates and territories. We conclude that the strength of social or sexual selection on crane body size is linked to the degree of functional constraint. © 2014 The Authors. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

  20. Toll like Receptor 2 engagement on CD4+ T cells promotes TH9 differentiation and function.

    Science.gov (United States)

    Karim, Ahmad Faisal; Reba, Scott M; Li, Qing; Boom, W Henry; Rojas, Roxana E

    2017-09-01

    We have recently demonstrated that mycobacterial ligands engage Toll like receptor 2 (TLR2) on CD4 + T cells and up-regulate T-cell receptor (TCR) triggered Th1 responses in vitro and in vivo. To better understand the role of T-cell expressed TLR2 on CD4 + T-cell differentiation and function, we conducted a gene expression analysis of murine naïve CD4 + T-cells stimulated in the presence or absence of TLR2 co-stimulation. Unexpectedly, naïve CD4 + T-cells co-stimulated via TLR2 showed a significant up-regulation of Il9 mRNA compared to cells co-stimulated via CD28. Under TH9 differentiation, we observed up-regulation of TH9 differentiation, evidenced by increases in both percent of IL-9 secreting cells and IL-9 in culture supernatants in the presence of TLR2 agonist both in polyclonal and Ag85B cognate peptide specific stimulations. Under non-polarizing conditions, TLR2 engagement on CD4 + T-cells had minimal effect on IL-9 secretion and TH9 differentiation, likely due to a prominent effect of TLR2 signaling on IFN-γ secretion and TH1 differentiation. We also report that, TLR2 signaling in CD4 + T cells increased expression of transcription factors BATF and PU.1, known to positively regulate TH9 differentiation. These results reveal a novel role of T-cell expressed TLR2 in enhancing the differentiation and function of TH9 T cells. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Adjunctive sarcosine plus benzoate improved cognitive function in chronic schizophrenia patients with constant clinical symptoms: A randomised, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Lin, Chun-Yuan; Liang, Sun-Yuan; Chang, Yue-Cune; Ting, Shuo-Yen; Kao, Ching-Ling; Wu, Yu-Hsin; Tsai, Guochuan E; Lane, Hsien-Yuan

    2017-08-01

    Objectives Hypofunction of NMDA receptor is implicated in the pathophysiology, particularly cognitive impairment, of schizophrenia. Sarcosine, a glycine transporter I (GlyT-1) inhibitor, and sodium benzoate, a d-amino acid oxidase (DAAO) inhibitor, can both enhance NMDA receptor-mediated neurotransmission. We proposed simultaneously inhibiting DAAO and GlyT-1 may be more effective than inhibition of either in improving the cognitive and global functioning of schizophrenia patients. Methods This study compared add-on sarcosine (2 g/day) plus benzoate (1 g/day) vs. sarcosine (2 g/day) for the clinical symptoms, as well as the cognitive and global functioning, of chronic schizophrenia patients in a 12-week, double-blind, randomised, placebo-controlled trial. Participants were measured with the Positive and Negative Syndrome Scale and the Global Assessment of Functioning Scale every 3 weeks. Seven cognitive domains, recommended by the Measurement and Treatment Research to Improve Cognition in Schizophrenia Committee, were measured at weeks 0 and 12. Results Adjunctive sarcosine plus benzoate, but not sarcosine alone, improved the cognitive and global functioning of patients with schizophrenia, even when their clinical symptoms had not improved. Conclusions This finding suggests N-methyl-d-aspartate receptor-enhancement therapy can improve the cognitive function of patients with schizophrenia, further indicating this pro-cognitive effect can be primary without improvement in clinical symptoms.

  2. Effects of Lutein/Zeaxanthin Supplementation on the Cognitive Function of Community Dwelling Older Adults: A Randomized, Double-Masked, Placebo-Controlled Trial

    Directory of Open Access Journals (Sweden)

    Billy R. Hammond

    2017-08-01

    Full Text Available Background: High levels of xanthophyll carotenoids lutein (L and zeaxanthin (Z in the central nervous system have been previously correlated with improved cognitive function in community-dwelling older adults. In this study, we tested the effects of supplementing L and Z on older men and women with a range of baseline cognitive abilities.Objective: The purpose of this study was to determine whether or not supplementation with L+Z could improve cognitive function in community-dwelling, older adults.Design: Double-masked, randomized, placebo-controlled trial. A total of 62 older adults were randomized into groups receiving either 12 mg L+Z or a visually identical placebo. Data from 51 participants (M = 73.7 years were available for analysis. Retinal L+Z levels (macular pigment optical density, MPOD were measured psychophysically using heterochromatic flicker photometry as a biomarker of cortical L+Z levels. Cognitive function was measured using the CNS Vital Signs computerized test platform.Results: Participants receiving the active L+Z supplement had statistically significant increases in MPOD (p < 0.03 and improvements in complex attention (p < 0.02 and cognitive flexibility domains (p < 0.04, relative to participants taking the placebo. A trend was also seen for the executive function domain (p = 0.073. In male participants only, supplementation yielded improved composite memory (p = 0.04.Conclusions: Supplementation with L+Z improved cognitive function in community-dwelling, older men and women.

  3. Identification, Functional Study, and Promoter Analysis of HbMFT1, a Homolog of MFT from Rubber Tree (Hevea brasiliensis

    Directory of Open Access Journals (Sweden)

    Zhenghong Bi

    2016-03-01

    Full Text Available A homolog of MOTHER OF FT AND TFL1 (MFT was isolated from Hevea brasiliensis and its biological function was investigated. Protein multiple sequence alignment and phylogenetic analysis revealed that HbMFT1 conserved critical amino acid residues to distinguish MFT, FLOWERING LOCUS T (FT and TERMINAL FLOWER1 (TFL1-like proteins and showed a closer genetic relationship to the MFT-like group. The accumulation of HbMFT1 was generally detected in various tissues except pericarps, with the highest expression in embryos and relatively higher expression in roots and stems of seedlings, flowering inflorescences, and male and female flowers. HbMFT1 putative promoter analysis showed that tissue-specific, environmental change responsive and hormone-signaling responsive elements were generally present. HbMFT1 was strongly induced under a short-day condition at 28 °C, with the highest expression after the onset of a day. Overexpression of HbMFT1 inhibited seed germination, seedling growth, and flowering in transgenic Arabidopsis. The qRT-PCR further confirmed that APETALA1 (AP1 and FRUITFULL (FUL were drastically down-regulated in 35S::HbMFT1 plants. A histochemical β-glucuronidase (GUS assay showed that HbMFT1::GUS activity was mainly detected in stamens and mature seeds coinciding with its original expression and notably induced in rosette leaves and seedlings of transgenic Arabidopsis by exogenous abscisic acid (ABA due to the presence of ABA cis-elements in HbMFT1 promoter. These results suggested that HbMFT1 was mainly involved in maintenance of seed maturation and stamen development, but negatively controlled germination, growth and development of seedlings and flowering. In addition, the HbMFT1 promoter can be utilized in controlling transgene expression in stamens and seeds of rubber tree or other plant species.

  4. Maresin 1 Promotes Inflammatory Resolution, Neuroprotection, and Functional Neurological Recovery After Spinal Cord Injury.

    Science.gov (United States)

    Francos-Quijorna, Isaac; Santos-Nogueira, Eva; Gronert, Karsten; Sullivan, Aaron B; Kopp, Marcel A; Brommer, Benedikt; David, Samuel; Schwab, Jan M; López-Vales, Ruben

    2017-11-29

    Resolution of inflammation is defective after spinal cord injury (SCI), which impairs tissue integrity and remodeling and leads to functional deficits. Effective pharmacological treatments for SCI are not currently available. Maresin 1 (MaR1) is a highly conserved specialized proresolving mediator (SPM) hosting potent anti-inflammatory and proresolving properties with potent tissue regenerative actions. Here, we provide evidence that the inappropriate biosynthesis of SPM in the lesioned spinal cord hampers the resolution of inflammation and leads to deleterious consequences on neurological outcome in adult female mice. We report that, after spinal cord contusion injury in adult female mice, the biosynthesis of SPM is not induced in the lesion site up to 2 weeks after injury. Exogenous administration of MaR1, a highly conserved SPM, propagated inflammatory resolution after SCI, as revealed by accelerated clearance of neutrophils and a reduction in macrophage accumulation at the lesion site. In the search of mechanisms underlying the proresolving actions of MaR1 in SCI, we found that this SPM facilitated several hallmarks of resolution of inflammation, including reduction of proinflammatory cytokines (CXCL1, CXCL2, CCL3, CCL4, IL6, and CSF3), silencing of major inflammatory intracellular signaling cascades (STAT1, STAT3, STAT5, p38, and ERK1/2), redirection of macrophage activation toward a prorepair phenotype, and increase of the phagocytic engulfment of neutrophils by macrophages. Interestingly, MaR1 administration improved locomotor recovery significantly and mitigated secondary injury progression in a clinical relevant model of SCI. These findings suggest that proresolution, immunoresolvent therapies constitute a novel approach to improving neurological recovery after acute SCI. SIGNIFICANCE STATEMENT Inflammation is a protective response to injury or infection. To result in tissue homeostasis, inflammation has to resolve over time. Incomplete or delayed

  5. Anxiolytics may promote locomotor function recovery in spinal cord injury patients

    Directory of Open Access Journals (Sweden)

    Pierre A Guertin

    2008-09-01

    Full Text Available Pierre A GuertinNeuroscience Unit, Laval University Medical Center (CHUL, Quebec City, CanadaAbstract: Recent findings in animal models of paraplegia suggest that specific nonbenzodiazepine anxiolytics may temporarily restore locomotor functions after spinal cord injury (SCI. Experiments using in vitro models have revealed, indeed, that selective serotonin receptor (5-HTR ligands such as 5-HTR1A agonists, known as relatively safe anxiolytics, can acutely elicit episodes of rhythmic neuronal activity refered to as fictive locomotion in isolated spinal cord preparations. Along the same line, in vivo studies have recently shown that this subclass of anxiolytics can induce, shortly after systemic administration (eg, orally or subcutaneously, some locomotor-like hindlimb movements during 45–60 minutes in completely spinal cord-transected (Tx rodents. Using ‘knock-out’ mice (eg, 5-HTR7-/- and selective antagonists, it has been clearly established that both 5-HTR1A and 5-HTR7 were critically involved in mediating the pro-locomotor effects induced by 8-OH-DPAT (typically referred to as a 5-HTR1A agonist in Tx animals. Taken together, these in vitro and in vivo data strongly support the idea that 5-HTR1A agonists may eventually become constitutive elements of a novel first-in-class combinatorial treatment aimed at periodically inducing short episodes of treadmill stepping in SCI patients.Keywords: 5-HT agonists, anxiolytics, locomotion, SCI

  6. Ihh/Gli2 signaling promotes osteoblast differentiation by regulating Runx2 expression and function.

    Science.gov (United States)

    Shimoyama, Atsuko; Wada, Masahiro; Ikeda, Fumiyo; Hata, Kenji; Matsubara, Takuma; Nifuji, Akira; Noda, Masaki; Amano, Katsuhiko; Yamaguchi, Akira; Nishimura, Riko; Yoneda, Toshiyuki

    2007-07-01

    Genetic and cell biological studies have indicated that Indian hedgehog (Ihh) plays an important role in bone development and osteoblast differentiation. However, the molecular mechanism by which Ihh regulates osteoblast differentiation is complex and remains to be fully elucidated. In this study, we investigated the role of Ihh signaling in osteoblast differentiation using mesenchymal cells and primary osteoblasts. We observed that Ihh stimulated alkaline phosphatase (ALP) activity, osteocalcin expression, and calcification. Overexpression of Gli2- but not Gli3-induced ALP, osteocalcin expression, and calcification of these cells. In contrast, dominant-negative Gli2 markedly inhibited Ihh-dependent osteoblast differentiation. Ihh treatment or Gli2 overexpression also up-regulated the expression of Runx2, an essential transcription factor for osteoblastogenesis, and enhanced the transcriptional activity and osteogenic action of Runx2. Coimmunoprecipitation analysis demonstrated a physical interaction between Gli2 and Runx2. Moreover, Ihh or Gli2 overexpression failed to increase ALP activity in Runx2-deficient mesenchymal cells. Collectively, these results suggest that Ihh regulates osteoblast differentiation of mesenchymal cells through up-regulation of the expression and function of Runx2 by Gli2.

  7. Conjugation-promoted reaction of open-cage fullerene: A density functional theory study

    KAUST Repository

    Guo, Yong

    2012-01-20

    Density functional theory calculations are performed to study the addition mechanism of e-rich moieties such as triethyl phosphite to a carbonyl group on the rim of a fullerene orifice. Three possible reaction channels have been investigated. The obtained results show that the reaction of a carbonyl group on a fullerene orifice with triethyl phosphite most likely proceeds along the classical Abramov reaction; however, the classical product is not stable and is converted into the experimental product. An attack on a fullerene carbonyl carbon will trigger a rearrangement of the phosphate group to the carbonyl oxygen as the conversion transition state is stabilized by fullerene conjugation. This work provides a new insight on the reactivity of open-cage fullerenes, which may prove helpful in designing new switchable fullerene systems. Not that classical: The reaction of a carbonyl group on the fullerene orifice with triethyl phosphite most likely proceeds following the Abramov reaction to firstly form a classical product. However, this product is not stable and turns into an experimental product as the conversion transition state is stabilized by fullerene conjugation (see picture). Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Scaffoldless tissue-engineered nerve conduit promotes peripheral nerve regeneration and functional recovery after tibial nerve injury in rats

    Institute of Scientific and Technical Information of China (English)

    Aaron M. Adams; Keith W. VanDusen; Tatiana Y. Kostrominova; Jacob P. Mertens; Lisa M. Larkin

    2017-01-01

    Damage to peripheral nerve tissue may cause loss of function in both the nerve and the targeted muscles it innervates. This study compared the repair capability of engineered nerve conduit (ENC), engineered fibroblast conduit (EFC), and autograft in a 10-mm tibial nerve gap. ENCs were fabricated utilizing primary fibroblasts and the nerve cells of rats on embryonic day 15 (E15). EFCs were fabricated utilizing primary fi-broblasts only. Following a 12-week recovery, nerve repair was assessed by measuring contractile properties in the medial gastrocnemius muscle, distal motor nerve conduction velocity in the lateral gastrocnemius, and histology of muscle and nerve. The autografts, ENCs and EFCs reestablished 96%, 87% and 84% of native distal motor nerve conduction velocity in the lateral gastrocnemius, 100%, 44% and 44% of native specific force of medical gastrocnemius, and 63%, 61% and 67% of native medial gastrocnemius mass, re-spectively. Histology of the repaired nerve revealed large axons in the autograft, larger but fewer axons in the ENC repair, and many smaller axons in the EFC repair. Muscle histology revealed similar muscle fiber cross-sectional areas among autograft, ENC and EFC repairs. In conclusion, both ENCs and EFCs promot-ed nerve regeneration in a 10-mm tibial nerve gap repair, suggesting that the E15 rat nerve cells may not be necessary for nerve regeneration, and EFC alone can suffice for peripheral nerve injury repair.

  9. Dual therapeutic functions of F-5 fragment in burn wounds: preventing wound progression and promoting wound healing in pigs

    Directory of Open Access Journals (Sweden)

    Ayesha Bhatia

    2016-01-01

    Full Text Available Burn injuries are a leading cause of morbidity including prolonged hospitalization, disfigurement, and disability. Currently there is no Food and Drug Administration-approved burn therapeutics. A clinical distinction of burn injuries from other acute wounds is the event of the so-called secondary burn wound progression within the first week of the injury, in which a burn expands horizontally and vertically from its initial boundary to a larger area. Therefore, an effective therapeutics for burns should show dual abilities to prevent the burn wound progression and thereafter promote burn wound healing. Herein we report that topically applied F-5 fragment of heat shock protein-90α is a dual functional agent to promote burn wound healing in pigs. First, F-5 prevents burn wound progression by protecting the surrounding cells from undergoing heat-induced caspase 3 activation and apoptosis with increased Akt activation. Accordingly, F-5–treated burn and excision wounds show a marked decline in inflammation. Thereafter, F-5 accelerates burn wound healing by stimulating the keratinocyte migration-led reepithelialization, leading to wound closure. This study addresses a topical agent that is capable of preventing burn wound progression and accelerating burn wound healing.

  10. Dual therapeutic functions of F-5 fragment in burn wounds: preventing wound progression and promoting wound healing in pigs.

    Science.gov (United States)

    Bhatia, Ayesha; O'Brien, Kathryn; Chen, Mei; Wong, Alex; Garner, Warren; Woodley, David T; Li, Wei

    2016-01-01

    Burn injuries are a leading cause of morbidity including prolonged hospitalization, disfigurement, and disability. Currently there is no Food and Drug Administration-approved burn therapeutics. A clinical distinction of burn injuries from other acute wounds is the event of the so-called secondary burn wound progression within the first week of the injury, in which a burn expands horizontally and vertically from its initial boundary to a larger area. Therefore, an effective therapeutics for burns should show dual abilities to prevent the burn wound progression and thereafter promote burn wound healing. Herein we report that topically applied F-5 fragment of heat shock protein-90α is a dual functional agent to promote burn wound healing in pigs. First, F-5 prevents burn wound progression by protecting the surrounding cells from undergoing heat-induced caspase 3 activation and apoptosis with increased Akt activation. Accordingly, F-5-treated burn and excision wounds show a marked decline in inflammation. Thereafter, F-5 accelerates burn wound healing by stimulating the keratinocyte migration-led reepithelialization, leading to wound closure. This study addresses a topical agent that is capable of preventing burn wound progression and accelerating burn wound healing.

  11. A Bayesian Double Fusion Model for Resting-State Brain Connectivity Using Joint Functional and Structural Data

    KAUST Repository

    Kang, Hakmook; Ombao, Hernando; Fonnesbeck, Christopher; Ding, Zhaohua; Morgan, Victoria L.

    2017-01-01

    DTI that could potentially enhance estimation of resting-state functional connectivity (FC) between brain regions. To overcome this limitation, we develop a Bayesian hierarchical spatiotemporal model that incorporates structural connectivity (SC

  12. Prehabilitation with Whey Protein Supplementation on Perioperative Functional Exercise Capacity in Patients Undergoing Colorectal Resection for Cancer: A Pilot Double-Blinded Randomized Placebo-Controlled Trial.

    Science.gov (United States)

    Gillis, Chelsia; Loiselle, Sarah-Eve; Fiore, Julio F; Awasthi, Rashami; Wykes, Linda; Liberman, A Sender; Stein, Barry; Charlebois, Patrick; Carli, Francesco

    2016-05-01

    A previous comprehensive prehabilitation program, providing nutrition counseling with whey protein supplementation, exercise, and psychological care, initiated 4 weeks before colorectal surgery for cancer, improved functional capacity before surgery and accelerated functional recovery. Those receiving standard of care deteriorated. The specific role of nutritional prehabilitation alone on functional recovery is unknown. This study was undertaken to estimate the impact of nutrition counseling with whey protein on preoperative functional walking capacity and recovery in patients undergoing colorectal resection for cancer. We conducted a double-blinded randomized controlled trial at a single university-affiliated tertiary center located in Montreal, Quebec, Canada. Colon cancer patients (n=48) awaiting elective surgery for nonmetastatic disease were randomized to receive either individualized nutrition counseling with whey protein supplementation to meet protein needs or individualized nutrition counseling with a nonnutritive placebo. Counseling and supplementation began 4 weeks before surgery and continued for 4 weeks after surgery. The primary outcome was change in functional walking capacity as measured with the 6-minute walk test. The distance was recorded at baseline, the day of surgery, and 4 weeks after surgery. A change of 20 m was considered clinically meaningful. The whey group experienced a mean improvement in functional walking capacity before surgery of +20.8 m, with a standard deviation of 42.6 m, and the placebo group improved by +1.2 (65.5) m (P=0.27). Four weeks after surgery, recovery rates were similar between groups (P=0.81). Clinically meaningful improvements in functional walking capacity were achieved before surgery with whey protein supplementation. These pilot results are encouraging and justify larger-scale trials to define the specific role of nutrition prehabilitation on functional recovery after surgery. Copyright © 2016 Academy of

  13. Effects of a Lutein and Zeaxanthin Intervention on Cognitive Function: A Randomized, Double-Masked, Placebo-Controlled Trial of Younger Healthy Adults

    Directory of Open Access Journals (Sweden)

    Lisa M. Renzi-Hammond

    2017-11-01

    Full Text Available Background: Past studies have suggested that higher lutein (L and zeaxanthin (Z levels in serum and in the central nervous system (as quantified by measuring macular pigment optical density, MPOD are related to improved cognitive function in older adults. Very few studies have addressed the issue of xanthophylls and cognitive function in younger adults, and no controlled trials have been conducted to date to determine whether or not supplementation with L + Z can change cognitive function in this population. Objective: The purpose of this study was to determine whether or not supplementation with L + Z could improve cognitive function in young (age 18–30, healthy adults. Design: A randomized, double-masked, placebo-controlled trial design was used. Fifty-one young, healthy subjects were recruited as part of a larger study on xanthophylls and cognitive function. Subjects were randomized into active supplement (n = 37 and placebo groups (n = 14. MPOD was measured psychophysically using customized heterochromatic flicker photometry. Cognitive function was measured using the CNS Vital Signs testing platform. MPOD and cognitive function were measured every four months for a full year of supplementation. Results: Supplementation increased MPOD significantly over the course of the year, vs. placebo (p < 0.001. Daily supplementation with L + Z and increases in MPOD resulted in significant improvements in spatial memory (p < 0.04, reasoning ability (p < 0.05 and complex attention (p < 0.04, above and beyond improvements due to practice effects. Conclusions: Supplementation with L + Z improves CNS xanthophyll levels and cognitive function in young, healthy adults. Magnitudes of effects are similar to previous work reporting correlations between MPOD and cognition in other populations.

  14. Catalysis mechanism of Pd-promoted γ-alumina in the thermal decomposition of methane to hydrogen: A density functional theory study

    International Nuclear Information System (INIS)

    Salam, M. Abdus; Abdullah, Bawadi

    2017-01-01

    Thermo-catalytic methane decomposition to elemental hydrogen mechanism in transitional metals (Pd, Ni & Mo) promoted Al_2O_3 (001) catalyst have been studied using the density functional theory (DFT). Decomposition reactions are spontaneous and favourable above 775 K for all promoter. Pd-promoted Al_2O_3 (001) catalyst demonstrates a breakthrough decomposition activity in hydrogen production as compared to Ni− and Mo-promoted Al_2O_3 (001) catalysts. The activation energy (E_a) range of the catalysis for Pd promoted Al_2O_3 (001) catalysts is 0.003–0.34 eV. Whereas, Ni and Mo promoted Al_2O_3 (001) catalysts display activation energy E_a in the range of 0.63–1.15 eV and 0.04–5.98 eV, respectively. Pd-promoted catalyst also shows a higher adsorption energy (−0.68 eV) and reactivity than that of Ni and Mo promoted Al_2O_3 (001) catalysts. The rates of successive decomposition of methane are found to be 16.15 × 10"1"2, 15.95 × 10"1"2 and 16.09 × 10"1"2 s"−"1 for the promoter of Pd, Ni and Mo, respectively. Pd promoted Al_2O_3 (001) catalyst reduces the methane decomposition temperature (775 K) and deactivation rate significantly. The catalytic conditions and catalyst is promising in producing hydrogen to support hydrogen economy. - Highlights: • Transition metals (Pd, Ni & Mo) promoted γ-alumina catalysts are designed successfully. • Pd-promoted catalyst showed breakthrough activity in methane decomposition to hydrogen. • DFT study explored the catalysis mechanism of methane decomposition at atomic level. • Pd-promoted catalyst reduced temperature and activation barrier of methane decomposition reaction significantly.

  15. Endothelial cell-derived matrix promotes the metabolic functional maturation of hepatocyte via integrin-Src signalling.

    Science.gov (United States)

    Guo, Xinyue; Li, Weihong; Ma, Minghui; Lu, Xin; Zhang, Haiyan

    2017-11-01

    The extracellular matrix (ECM) microenvironment is involved in the regulation of hepatocyte phenotype and function. Recently, the cell-derived extracellular matrix has been proposed to represent the bioactive and biocompatible materials of the native ECM. Here, we show that the endothelial cell-derived matrix (EC matrix) promotes the metabolic maturation of human adipose stem cell-derived hepatocyte-like cells (hASC-HLCs) through the activation of the transcription factor forkhead box protein A2 (FOXA2) and the nuclear receptors hepatocyte nuclear factor 4 alpha (HNF4α) and pregnane X receptor (PXR). Reducing the fibronectin content in the EC matrix or silencing the expression of α5 integrin in the hASC-HLCs inhibited the effect of the EC matrix on Src phosphorylation and hepatocyte maturation. The inhibition of Src phosphorylation using the inhibitor PP2 or silencing the expression of Src in hASC-HLCs also attenuated the up-regulation of the metabolic function of hASC-HLCs in a nuclear receptor-dependent manner. These data elucidate integrin-Src signalling linking the extrinsic EC matrix signals and metabolic functional maturation of hepatocyte. This study provides a model for studying the interaction between hepatocytes and non-parenchymal cell-derived matrix. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  16. Chemical chaperones exceed the chaperone effects of RIC-3 in promoting assembly of functional α7 AChRs.

    Directory of Open Access Journals (Sweden)

    Alexander Kuryatov

    Full Text Available Functional α7 nicotinic acetylcholine receptors (AChRs do not assemble efficiently in cells transfected with α7 subunits unless the cells are also transfected with the chaperone protein RIC-3. Despite the presence of RIC-3, large amounts of these subunits remain improperly assembled. Thus, additional chaperone proteins are probably required for efficient assembly of α7 AChRs. Cholinergic ligands can act as pharmacological chaperones to promote assembly of mature AChRs and upregulate the amount of functional AChRs. In addition, we have found that the chemical chaperones 4-phenylbutyric acid (PBA and valproic acid (VPA greatly increase the amount of functional α7 AChRs produced in a cell line expressing both α7 and RIC-3. Increased α7 AChR expression allows assay of drug action using a membrane potential-sensitive fluorescent indicator. Both PBA and VPA also increase α7 expression in the SH-SY5Y neuroblastoma cell line that endogenously expresses α7 AChRs. VPA increases expression of endogenous α7 AChRs in hippocampal neurons but PBA does not. RIC-3 is insufficient for optimal assembly of α7 AChRs, but provides assay conditions for detecting additional chaperones. Chemical chaperones are a useful pragmatic approach to express high levels of human α7 AChRs for drug selection and characterization and possibly to increase α7 expression in vivo.

  17. Efficacy of walking exercise in promoting cognitive-psychosocial functions in men with prostate cancer receiving androgen deprivation therapy

    Directory of Open Access Journals (Sweden)

    Lee C

    2012-07-01

    Full Text Available Abstract Background Prostate cancer is the most commonly diagnosed non-melanoma cancer among men. Androgen deprivation therapy (ADT has been the core therapy for men with advanced prostate cancer. It is only in recent years that clinicians began to recognize the cognitive-psychosocial side effects from ADT, which significantly compromise the quality of life of prostate cancer survivors. The objectives of the study are to determine the efficacy of a simple and accessible home-based, walking exercise program in promoting cognitive and psychosocial functions of men with prostate cancer receiving ADT. Methods A 6-month prospective, single-blinded, randomized controlled trial will be conducted to compare the Exercise Group with the Control Group. Twenty men with prostate cancer starting ADT will be recruited and randomly assigned to one of the two groups: the Exercise Group will receive instructions in setting up an individualized 6-month home-based, walking exercise program, while the Control Group will receive standard medical advice from the attending physician. The primary outcomes will be psychosocial and cognitive functions. Cognitive functions including memory, attention, working memory, and executive function will be assessed using a battery of neurocognitive tests at baseline and 6 months. Psychosocial functions including depression, anxiety and self-esteem will be assessed at baseline, 3 and 6 months using the Center for Epidemiological Studies Depression Scale, Spielberger State-Trait Anxiety Inventory, and Rosenberg Self-Esteem Scale. Discussion The significance of the cognitive-psychosocial side effects of ADT in men with prostate cancer has only been recently recognized, and the management remains unclear. This study addresses this issue by designing a simple and accessible home-based, exercise program that may potentially have significant impact on reducing the cognitive and psychosocial side effects of ADT, and ultimately

  18. Assessing and Promoting Functional Resilience in Flight Crews During Exploration Missions

    Science.gov (United States)

    Shelhamer, Mark

    2015-01-01

    NASA plans to send humans to Mars in about 20 years. The NASA Human Research Program supports research to mitigate the major risks to human health and performance on extended missions. However, there will undoubtedly be unforeseen events on any mission of this nature - thus mitigation of known risks alone is not sufficient to ensure optimal crew health and performance. Research should be directed not only to mitigating known risks, but also to providing crews with the tools to assess and enhance resilience, as a group and individually. We can draw on ideas from complexity theory and network theory to assess crew and individual resilience. The entire crew or the individual crewmember can be viewed as a complex system that is composed of subsystems (individual crewmembers or physiological subsystems), and the interactions between subsystems are of crucial importance for overall health and performance. An understanding of the structure of the interactions can provide important information even in the absence of complete information on the component subsystems. This is critical in human spaceflight, since insufficient flight opportunities exist to elucidate the details of each subsystem. Enabled by recent advances in noninvasive measurement of physiological and behavioral parameters, subsystem monitoring can be implemented within a mission and also during preflight training to establish baseline values and ranges. Coupled with appropriate mathematical modeling, this can provide real-time assessment of health and function, and detect early indications of imminent breakdown. Since the interconnected web of physiological systems (and crewmembers) can be interpreted as a network in mathematical terms, we can draw on recent work that relates the structure of such networks to their resilience (ability to self-organize in the face of perturbation). There are many parameters and interactions to choose from. Normal variability is an established characteristic of a healthy

  19. Functional promoter haplotypes of the human FAS gene are associated with the phenotype of SLE characterized by thrombocytopenia

    DEFF Research Database (Denmark)

    Nolsøe, R L; Kelly, J A; Pociot, F

    2005-01-01

    Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by production of autoantibodies against intracellular antigens and tissue injury. Defective apoptosis of activated immune cells leads to the development of autoantibodies in SLE. FasL initiated apoptosis is central...... for peripheral tolerance. Fas deficiencies in humans and mice predispose toward systemic autoimmunity. SLE is conferred by many genes. The genetic effects may be concentrated by familial clustering or by stratifying of subphenotypes. We have tested polymorphisms and haplotypes in FAS and FASL for association...... to SLE or subphenotypes in 126 multiplex American SLE pedigrees and found association of the FAS codon214 AC(C/T) as well as the FAS-670G>A'-codon214 AC(C/T)' haplotype to thrombocytopenia in SLE. Furthermore we have functionally characterized the FAS/FASL promoter polymorphisms associated with SLE...

  20. Pea proteins oral supplementation promotes muscle thickness gains during resistance training: a double-blind, randomized, Placebo-controlled clinical trial vs. Whey protein.

    Science.gov (United States)

    Babault, Nicolas; Païzis, Christos; Deley, Gaëlle; Guérin-Deremaux, Laetitia; Saniez, Marie-Hélène; Lefranc-Millot, Catherine; Allaert, François A

    2015-01-01

    The effects of protein supplementation on muscle thickness and strength seem largely dependent on its composition. The current study aimed at comparing the impact of an oral supplementation with vegetable Pea protein (NUTRALYS®) vs. Whey protein and Placebo on biceps brachii muscle thickness and strength after a 12-week resistance training program. One hundred and sixty one males, aged 18 to 35 years were enrolled in the study and underwent 12 weeks of resistance training on upper limb muscles. According to randomization, they were included in the Pea protein (n = 53), Whey protein (n = 54) or Placebo (n = 54) group. All had to take 25 g of the proteins or placebo twice a day during the 12-week training period. Tests were performed on biceps muscles at inclusion (D0), mid (D42) and post training (D84). Muscle thickness was evaluated using ultrasonography, and strength was measured on an isokinetic dynamometer. Results showed a significant time effect for biceps brachii muscle thickness (P Pea, Whey and Placebo, respectively; P Pea group as compared to Placebo whereas there was no difference between Whey and the two other conditions. Muscle strength also increased with time with no statistical difference between groups. In addition to an appropriate training, the supplementation with pea protein promoted a greater increase of muscle thickness as compared to Placebo and especially for people starting or returning to a muscular strengthening. Since no difference was obtained between the two protein groups, vegetable pea proteins could be used as an alternative to Whey-based dietary products. The present trial has been registered at ClinicalTrials.gov (NCT02128516).

  1. Transplantation of mononuclear cells from human umbilical cord blood promotes functional recovery after traumatic spinal cord injury in Wistar rats

    International Nuclear Information System (INIS)

    Rodrigues, L.P.; Iglesias, D.; Nicola, F.C.; Steffens, D.; Valentim, L.; Witczak, A.; Zanatta, G.; Achaval, M.; Pranke, P.; Netto, C.A.

    2011-01-01

    Cell transplantation is a promising experimental treatment for spinal cord injury. The aim of the present study was to evaluate the efficacy of mononuclear cells from human umbilical cord blood in promoting functional recovery when transplanted after a contusion spinal cord injury. Female Wistar rats (12 weeks old) were submitted to spinal injury with a MASCIS impactor and divided into 4 groups: control, surgical control, spinal cord injury, and one cell-treated lesion group. Mononuclear cells from umbilical cord blood of human male neonates were transplanted in two experiments: a) 1 h after surgery, into the injury site at a concentration of 5 x 10 6 cells diluted in 10 µL 0.9% NaCl (N = 8-10 per group); b) into the cisterna magna, 9 days after lesion at a concentration of 5 x 10 6 cells diluted in 150 µL 0.9% NaCl (N = 12-14 per group). The transplanted animals were immunosuppressed with cyclosporin-A (10 mg/kg per day). The BBB scale was used to evaluate motor behavior and the injury site was analyzed with immunofluorescent markers to label human transplanted cells, oligodendrocytes, neurons, and astrocytes. Spinal cord injury rats had 25% loss of cord tissue and cell treatment did not affect lesion extension. Transplanted cells survived in the injured area for 6 weeks after the procedure and both transplanted groups showed better motor recovery than the untreated ones (P < 0.05). The transplantation of mononuclear cells from human umbilical cord blood promoted functional recovery with no evidence of cell differentiation

  2. Small molecule kaempferol modulates PDX-1 protein expression and subsequently promotes pancreatic β-cell survival and function via CREB

    Science.gov (United States)

    Zhang, Yanling.; Zhen, Wei.; Maechler, Pierre; Liu, Dongmin

    2013-01-01

    Chronic hyperlipidemia causes β-cell apoptosis and dysfunction, thereby contributing to the pathogenesis of T2D. Thus, searching for agents to promote pancreatic β-cell survival and improve its function could be a promising strategy to prevent and treat T2D. We investigated the effects of kaempferol, a small molecule isolated from ginkgo biloba, on apoptosis and function of β-cells and further determined the mechanism underlying its actions. Kaempferol treatment promoted viability, inhibited apoptosis, and reduced caspase-3 activity in INS-1E cells and human islets chronically exposed to palmitate. In addition, kaempferol prevented the lipotoxicity-induced down-regulation of anti-apoptotic proteins Akt and Bcl-2. The cytoprotective effects of kaempferol were associated with improved insulin secretion, synthesis, and PDX-1 expression. Chronic hyperlipidemia significantly diminished cAMP production, PKA activation, and CREB phosphorylation and its regulated transcriptional activity in β-cells, all of which were restored by kaempferol treatment. Disruption of CREB expression by transfection of CREB siRNA in INS-1E cells or adenoviral transfer of dominant-negative forms of CREB in human islets ablated kaempferol protection of β-cell apoptosis and dysfunction caused by palmitate. Incubation of INS-1E cells or human islets with kaempferol for 48 h induced PDX-1 expression. This effect of kaempferol on PDX-1 expression was not shared by a host of structurally related flavonoid compounds. PDX-1 gene knockdown reduced kaempferol–stimulated cAMP generation and CREB activation in INS-1E cells. These findings demonstrate that kaempferol is a novel survivor factor for pancreatic β-cells via up-regulating the PDX-1/cAMP/PKA/CREB signaling cascade. PMID:22819546

  3. EPO-independent functional EPO receptor in breast cancer enhances estrogen receptor activity and promotes cell proliferation

    International Nuclear Information System (INIS)

    Reinbothe, Susann; Larsson, Anna-Maria; Vaapil, Marica; Wigerup, Caroline; Sun, Jianmin; Jögi, Annika; Neumann, Drorit; Rönnstrand, Lars; Påhlman, Sven

    2014-01-01

    Highlights: • New anti-human EPOR antibody confirms full-length EPOR expression in breast cancer cells. • Proliferation of breast cancer cells is not affected by rhEPO treatment in vitro. • EPOR knockdown impairs proliferation of ERa positive breast cancer cells. • EPOR knockdown reduces AKT phosphorylation and ERa activity. - Abstract: The main function of Erythropoietin (EPO) and its receptor (EPOR) is the stimulation of erythropoiesis. Recombinant human EPO (rhEPO) is therefore used to treat anemia in cancer patients. However, clinical trials have indicated that rhEPO treatment might promote tumor progression and has a negative effect on patient survival. In addition, EPOR expression has been detected in several cancer forms. Using a newly produced anti-EPOR antibody that reliably detects the full-length isoform of the EPOR we show that breast cancer tissue and cells express the EPOR protein. rhEPO stimulation of cultured EPOR expressing breast cancer cells did not result in increased proliferation, overt activation of EPOR (receptor phosphorylation) or a consistent activation of canonical EPOR signaling pathway mediators such as JAK2, STAT3, STAT5, or AKT. However, EPOR knockdown experiments suggested functional EPO receptors in estrogen receptor positive (ERα + ) breast cancer cells, as reduced EPOR expression resulted in decreased proliferation. This effect on proliferation was not seen in ERα negative cells. EPOR knockdown decreased ERα activity further supports a mechanism by which EPOR affects proliferation via ERα-mediated mechanisms. We show that EPOR protein is expressed in breast cancer cells, where it appears to promote proliferation by an EPO-independent mechanism in ERα expressing breast cancer cells

  4. EPO-independent functional EPO receptor in breast cancer enhances estrogen receptor activity and promotes cell proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Reinbothe, Susann; Larsson, Anna-Maria; Vaapil, Marica; Wigerup, Caroline [Department of Laboratory Medicine, Translational Cancer Research, Medicon Village, Lund University, SE-223 81 Lund (Sweden); CREATE Health, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv (Israel); Sun, Jianmin [Department of Laboratory Medicine, Translational Cancer Research, Medicon Village, Lund University, SE-223 81 Lund (Sweden); Jögi, Annika [Department of Laboratory Medicine, Translational Cancer Research, Medicon Village, Lund University, SE-223 81 Lund (Sweden); CREATE Health, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv (Israel); Neumann, Drorit [Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv (Israel); Rönnstrand, Lars [Department of Laboratory Medicine, Translational Cancer Research, Medicon Village, Lund University, SE-223 81 Lund (Sweden); Påhlman, Sven, E-mail: sven.pahlman@med.lu.se [Department of Laboratory Medicine, Translational Cancer Research, Medicon Village, Lund University, SE-223 81 Lund (Sweden); CREATE Health, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv (Israel)

    2014-02-28

    Highlights: • New anti-human EPOR antibody confirms full-length EPOR expression in breast cancer cells. • Proliferation of breast cancer cells is not affected by rhEPO treatment in vitro. • EPOR knockdown impairs proliferation of ERa positive breast cancer cells. • EPOR knockdown reduces AKT phosphorylation and ERa activity. - Abstract: The main function of Erythropoietin (EPO) and its receptor (EPOR) is the stimulation of erythropoiesis. Recombinant human EPO (rhEPO) is therefore used to treat anemia in cancer patients. However, clinical trials have indicated that rhEPO treatment might promote tumor progression and has a negative effect on patient survival. In addition, EPOR expression has been detected in several cancer forms. Using a newly produced anti-EPOR antibody that reliably detects the full-length isoform of the EPOR we show that breast cancer tissue and cells express the EPOR protein. rhEPO stimulation of cultured EPOR expressing breast cancer cells did not result in increased proliferation, overt activation of EPOR (receptor phosphorylation) or a consistent activation of canonical EPOR signaling pathway mediators such as JAK2, STAT3, STAT5, or AKT. However, EPOR knockdown experiments suggested functional EPO receptors in estrogen receptor positive (ERα{sup +}) breast cancer cells, as reduced EPOR expression resulted in decreased proliferation. This effect on proliferation was not seen in ERα negative cells. EPOR knockdown decreased ERα activity further supports a mechanism by which EPOR affects proliferation via ERα-mediated mechanisms. We show that EPOR protein is expressed in breast cancer cells, where it appears to promote proliferation by an EPO-independent mechanism in ERα expressing breast cancer cells.

  5. Transplantation of mononuclear cells from human umbilical cord blood promotes functional recovery after traumatic spinal cord injury in Wistar rats

    Energy Technology Data Exchange (ETDEWEB)

    Rodrigues, L.P. [Programa de Pós-Graduação em Neurociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Iglesias, D. [Laboratório de Hematologia e Células-Tronco, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Nicola, F.C. [Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Steffens, D. [Laboratório de Hematologia e Células-Tronco, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Valentim, L.; Witczak, A.; Zanatta, G. [Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Achaval, M. [Departamento de Ciências Morfológicas, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Pranke, P. [Laboratório de Hematologia e Células-Tronco, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Netto, C.A. [Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil)

    2011-12-23

    Cell transplantation is a promising experimental treatment for spinal cord injury. The aim of the present study was to evaluate the efficacy of mononuclear cells from human umbilical cord blood in promoting functional recovery when transplanted after a contusion spinal cord injury. Female Wistar rats (12 weeks old) were submitted to spinal injury with a MASCIS impactor and divided into 4 groups: control, surgical control, spinal cord injury, and one cell-treated lesion group. Mononuclear cells from umbilical cord blood of human male neonates were transplanted in two experiments: a) 1 h after surgery, into the injury site at a concentration of 5 x 10{sup 6} cells diluted in 10 µL 0.9% NaCl (N = 8-10 per group); b) into the cisterna magna, 9 days after lesion at a concentration of 5 x 10{sup 6} cells diluted in 150 µL 0.9% NaCl (N = 12-14 per group). The transplanted animals were immunosuppressed with cyclosporin-A (10 mg/kg per day). The BBB scale was used to evaluate motor behavior and the injury site was analyzed with immunofluorescent markers to label human transplanted cells, oligodendrocytes, neurons, and astrocytes. Spinal cord injury rats had 25% loss of cord tissue and cell treatment did not affect lesion extension. Transplanted cells survived in the injured area for 6 weeks after the procedure and both transplanted groups showed better motor recovery than the untreated ones (P < 0.05). The transplantation of mononuclear cells from human umbilical cord blood promoted functional recovery with no evidence of cell differentiation.

  6. Development and validation of double and single Wiebe function for multi-injection mode Diesel engine combustion modelling for hardware-in-the-loop applications

    International Nuclear Information System (INIS)

    Maroteaux, Fadila; Saad, Charbel; Aubertin, Fabrice

    2015-01-01

    Highlights: • Modelling of Diesel engine combustion with multi-injection mode was conducted. • Double and single Wiebe correlations for pilot, main and post combustion processes were calibrated. • Ignition delay time correlations have been developed and calibrated using experimental data for each injection. • The complete in-cylinder model has been applied successfully to real time simulations on HiL test bed. - Abstract: The improvement of Diesel engine performances in terms of fuel consumption and pollutant emissions has a huge impact on management system and diagnostic procedure. Validation and testing of engine performances can benefit from the use of theoretical models, for the reduction of development time and costs. Hardware in the Loop (HiL) test bench is a suitable way to achieve these objectives. However, the increasing complexity of management systems rises challenges for the development of very reduced physical models able to run in real time applications. This paper presents an extension of a previously developed phenomenological Diesel combustion model suitable for real time applications on a HiL test bench. In the earlier study, the modelling efforts have been targeted at high engine speeds with a very short computational time window, and where the engine operates with single injection. In the present work, a modelling of in-cylinder processes at low and medium engine speeds with multi-injection is performed. In order to reach an adequate computational time, the combustion progress during the pilot and main injection periods has been treated through a double Wiebe function, while the post combustion period has required a single Wiebe function. This paper describes the basic system models and their calibration and validation against experimental data. The use of the developed correlations of Wiebe coefficients and ignition delay times for each combustion phase, included in the in-cylinder crank angle global model, is applied for the prediction

  7. Functional intercalated nanocomposites with chitosan-glutathione-glycylsarcosine and layered double hydroxides for topical ocular drug delivery.

    Science.gov (United States)

    Xu, Tingting; Xu, Xiaoyue; Gu, Yan; Fang, Lei; Cao, Feng

    2018-01-01

    To enhance ocular bioavailability, the traditional strategies have focused on prolonging precorneal retention and improving corneal permeability by nano-carriers with positive charge, thiolated polymer, absorption enhancer and so on. Glycylsarcosine (GS) as an active target ligand of the peptide tranpsporter-1 (PepT-1), could specific interact with the PepT-1 on the cornea and guide the nanoparticles to the treating site. The objective of the study was to explore the active targeting intercalated nanocomposites based on chitosan-glutathione-glycylsarcosine (CG-GS) and layered double hydroxides (LDH) as novel carriers for the treatment of mid-posterior diseases. CG-GS-LDH intercalated nanocomposites were prepared by the coprecipitation hydrothermal method. In vivo precorneal retention study, ex vivo fluorescence images, in vivo experiment for distribution and irritation were studied in rabbits. The cytotoxicity and cellular uptake were studied in human corneal epithelial primary cells (HCEpiC). CG-GS-LDH nanocomposites were prepared successfully and characterized by FTIR and XRD. Experiments with rabbits showed longer precorneal retention and higher distribution of fluorescence probe/model drug. In vitro cytological study, CG-GS-LDH nanocomposites exhibited enhanced cellular uptake compared to pure drug solution. Furthermore, the investigation of cellular uptake mechanisms demonstrated that both the active transport by PepT-1 and clathrin-mediated endocytosis were involved in the internalization of CG-GS-LDH intercalated nanocomposites. An ocular irritation study and a cytotoxicity test indicated that these nanocomposites produced no significant irritant effects. The active targeting intercalated nanocomposites could have great potential for topical ocular drug delivery due to the capacity for prolonging the retention on the ocular surface, enhancing the drug permeability through the cornea, and efficiently delivering the drug to the targeted site.

  8. PEG 3350 (Transipeg) versus lactulose in the treatment of childhood functional constipation: a double blind, randomised, controlled, multicentre trial.

    Science.gov (United States)

    Voskuijl, W; de Lorijn, F; Verwijs, W; Hogeman, P; Heijmans, J; Mäkel, W; Taminiau, J; Benninga, M

    2004-11-01

    Recently, polyethylene glycol (PEG 3350) has been suggested as a good alternative laxative to lactulose as a treatment option in paediatric constipation. However, no large randomised controlled trials exist evaluating the efficacy of either laxative. To compare PEG 3350 (Transipeg: polyethylene glycol with electrolytes) with lactulose in paediatric constipation and evaluate clinical efficacy/side effects. One hundred patients (aged 6 months-15 years) with paediatric constipation were included in an eight week double blinded, randomised, controlled trial. After faecal disimpaction, patients PEG 3350 (2.95 g/sachet) or lactulose (6 g/sachet) while children > or =6 years started with 2 sachets/day. Primary outcome measures were: defecation and encopresis frequency/week and successful treatment after eight weeks. Success was defined as a defecation frequency > or =3/week and encopresis PEG 3350: 3 pre v 7 post treatment/week; lactulose: 3 pre v 6 post/week) and a significant decrease in encopresis frequency (PEG 3350: 10 pre v 3 post/week; lactulose: 8 pre v 3 post/week) was found in both groups (NS). However, success was significantly higher in the PEG group (56%) compared with the lactulose group (29%). PEG 3350 patients reported less abdominal pain, straining, and pain at defecation than children using lactulose. However, bad taste was reported significantly more often in the PEG group. PEG 3350 (0.26 (0.11) g/kg), compared with lactulose (0.66 (0.32) g/kg), provided a higher success rate with fewer side effects. PEG 3350 should be the laxative of first choice in childhood constipation.

  9. PEG 3350 (Transipeg) versus lactulose in the treatment of childhood functional constipation: a double blind, randomised, controlled, multicentre trial

    Science.gov (United States)

    Voskuijl, W; de Lorijn, F; Verwijs, W; Hogeman, P; Heijmans, J; Mäkel, W; Taminiau, J; Benninga, M

    2004-01-01

    Background: Recently, polyethylene glycol (PEG 3350) has been suggested as a good alternative laxative to lactulose as a treatment option in paediatric constipation. However, no large randomised controlled trials exist evaluating the efficacy of either laxative. Aims: To compare PEG 3350 (Transipeg: polyethylene glycol with electrolytes) with lactulose in paediatric constipation and evaluate clinical efficacy/side effects. Patients: One hundred patients (aged 6 months–15 years) with paediatric constipation were included in an eight week double blinded, randomised, controlled trial. Methods: After faecal disimpaction, patients encopresis frequency/week and successful treatment after eight weeks. Success was defined as a defecation frequency ⩾3/week and encopresis ⩽1 every two weeks. Secondary outcome measures were side effects after eight weeks of treatment. Results: A total of 91 patients (49 male) completed the study. A significant increase in defecation frequency (PEG 3350: 3 pre v 7 post treatment/week; lactulose: 3 pre v 6 post/week) and a significant decrease in encopresis frequency (PEG 3350: 10 pre v 3 post/week; lactulose: 8 pre v 3 post/week) was found in both groups (NS). However, success was significantly higher in the PEG group (56%) compared with the lactulose group (29%). PEG 3350 patients reported less abdominal pain, straining, and pain at defecation than children using lactulose. However, bad taste was reported significantly more often in the PEG group. Conclusions: PEG 3350 (0.26 (0.11) g/kg), compared with lactulose (0.66 (0.32) g/kg), provided a higher success rate with fewer side effects. PEG 3350 should be the laxative of first choice in childhood constipation. PMID:15479678

  10. Tailoring surface properties and structure of layered double hydroxides using silanes with different number of functional groups

    International Nuclear Information System (INIS)

    Tao, Qi; He, Hongping; Li, Tian; Frost, Ray L.; Zhang, Dan; He, Zisen

    2014-01-01

    Four silanes, trimethylchlorosilane (TMCS), dimethyldiethoxylsilane (DMDES), 3-aminopropyltriethoxysilane (APTES) and tetraethoxysilane (TEOS), were adopted to graft layered double hydroxides (LDH) via an induced hydrolysis silylation method (IHS). Fourier transform infrared spectra (FTIR) and 29 Si MAS nuclear magnetic resonance spectra ( 29 Si MAS NMR) indicated that APTES and TEOS can be grafted onto LDH surfaces via condensation with hydroxyl groups of LDH, while TMCS and DMDES could only be adsorbed on the LDH surface with a small quantity. A combination of X-ray diffraction patterns (XRD) and 29 Si MAS NMR spectra showed that silanes were exclusively present in the external surface and had little influence on the long range order of LDH. The surfactant intercalation experiment indicated that the adsorbed and/or grafted silane could not fix the interlamellar spacing of the LDH. However, they will form crosslink between the particles and affect the further surfactant intercalation in the silylated samples. The replacement of water by ethanol in the tactoids and/or aggregations and the polysiloxane oligomers formed during silylation procedure can dramatically increase the value of BET surface area (S BET ) and total pore volumes (V p ) of the products. - Graphical abstract: The replacement of water by ethanol in the tactoids and aggregations of LDHs, and the polysiloxane oligomers formed during silylation process can dramatically increase the BET surface area (S BET ) and the total pore volume (V p ) of the silylated products. - Highlights: • Silanes with multifunctional groups were grafted onto LDH surface in C 2 H 5 OH medium. • The number of hydrolysable groups in silanes affects the structure of grafted LDH. • Replacement of H 2 O by C 2 H 5 OH in aggregations increases S BET and V p of grafted LDH. • Polysiloxane oligomers contribute to the increase of S BET and V p of grafted LDH

  11. Functionalization of layered double hydroxides by intumescent flame retardant: Preparation, characterization, and application in ethylene vinyl acetate copolymer

    International Nuclear Information System (INIS)

    Huang Guobo; Fei Zhengdong; Chen Xiaoying; Qiu Fangli; Wang Xu; Gao Jianrong

    2012-01-01

    Highlights: ► LDHs were modified with compound PAHPA. ► EVA/PAHPA-LDHs nanocomposites were prepared by melt blending. ► PAHPA-LDHs improved the flame retardancy of the nanocomposites. - Abstract: A phosphorus-nitrogen containing compound, N-(2-(5,5-dimethyl-1,3,2-dioxaphosphinyl-2-ylamino)-hexylacetamide-2-propyl acid (PAHPA), is synthesized and characterized. A novel flame retardant, namely layered double hydroxides (LDHs) modified with PAHPA (PAHPA-LDHs), is prepared by ion-exchange of LDHs with PAHPA. The results from Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy and energy dispersive X-ray analysis with a high-angle annular dark-field scanning transmission electron microscope show that PAHPA intercalated LDHs. The X-ray diffraction and transmission electron microscopy (TEM) results show that PAHPA-LDHs achieve well dispersion in ethylene vinyl acetate copolymer (EVA) matrix and the EVA/PAHPA-LDHs nanocomposites (i.e. EVA filled with 5 wt% PAHPA-LDHs) are formed by polymer melt intercalation. Thermal stability and flammability properties are investigated by thermogravimetric analysis and cone calorimeter tests. The results show that the addition of PAHPA-LDHs improves thermal stability and reduces obviously the flammability of EVA resin. Compared with pure EVA resin, the peak heat release rate of the EVA/PAHPA-LDHs nanocomposites is reduced by about 43%. The results of scanning electron microscopy and TEM indicate that a compact and dense intumescent char is formed for the EVA/PAHPA-LDHs nanocomposites after combustion.

  12. Knockdown of SCF(Skp2 function causes double-parked accumulation in the nucleus and DNA re-replication in Drosophila plasmatocytes.

    Directory of Open Access Journals (Sweden)

    Paul T Kroeger

    Full Text Available In Drosophila, circulating hemocytes are derived from the cephalic mesoderm during the embryonic wave of hematopoiesis. These cells are contributed to the larva and persist through metamorphosis into the adult. To analyze this population of hemocytes, we considered data from a previously published RNAi screen in the hematopoietic niche, which suggested several members of the SCF complex play a role in lymph gland development. eater-Gal4;UAS-GFP flies were crossed to UAS-RNAi lines to knockdown the function of all known SCF complex members in a plasmatocyte-specific fashion, in order to identify which members are novel regulators of plasmatocytes. This specific SCF complex contains five core members: Lin-19-like, SkpA, Skp2, Roc1a and complex activator Nedd8. The complex was identified by its very distinctive large cell phenotype. Furthermore, these large cells stained for anti-P1, a plasmatocyte-specific antibody. It was also noted that the DNA in these cells appeared to be over-replicated. Gamma-tubulin and DAPI staining suggest the cells are undergoing re-replication as they had multiple centrioles and excessive DNA content. Further experimentation determined enlarged cells were BrdU-positive indicating they have progressed through S-phase. To determine how these cells become enlarged and undergo re-replication, cell cycle proteins were analyzed by immunofluorescence. This analysis identified three proteins that had altered subcellular localization in these enlarged cells: Cyclin E, Geminin and Double-parked. Previous research has shown that Double-parked must be degraded to exit S-phase, otherwise the DNA will undergo re-replication. When Double-parked was titrated from the nucleus by an excess of its inhibitor, geminin, the enlarged cells and aberrant protein localization phenotypes were partially rescued. The data in this report suggests that the SCF(Skp2 complex is necessary to ubiquitinate Double-parked during plasmatocyte cell division

  13. Functional variant in complement C3 gene promoter and genetic susceptibility to temporal lobe epilepsy and febrile seizures.

    Directory of Open Access Journals (Sweden)

    Sarah Jamali

    Full Text Available BACKGROUND: Human mesial temporal lobe epilepsies (MTLE represent the most frequent form of partial epilepsies and are frequently preceded by febrile seizures (FS in infancy and early childhood. Genetic associations of several complement genes including its central component C3 with disorders of the central nervous system, and the existence of C3 dysregulation in the epilepsies and in the MTLE particularly, make it the C3 gene a good candidate for human MTLE. METHODOLOGY/PRINCIPAL FINDINGS: A case-control association study of the C3 gene was performed in a first series of 122 patients with MTLE and 196 controls. Four haplotypes (HAP1 to 4 comprising GF100472, a newly discovered dinucleotide repeat polymorphism [(CA8 to (CA15] in the C3 promoter region showed significant association after Bonferroni correction, in the subgroup of MTLE patients having a personal history of FS (MTLE-FS+. Replication analysis in independent patients and controls confirmed that the rare HAP4 haplotype comprising the minimal length allele of GF100472 [(CA8], protected against MTLE-FS+. A fifth haplotype (HAP5 with medium-size (CA11 allele of GF100472 displayed four times higher frequency in controls than in the first cohort of MTLE-FS+ and showed a protective effect against FS through a high statistical significance in an independent population of 97 pure FS. Consistently, (CA11 allele by its own protected against pure FS in a second group of 148 FS patients. Reporter gene assays showed that GF100472 significantly influenced C3 promoter activity (the higher the number of repeats, the lower the transcriptional activity. Taken together, the consistent genetic data and the functional analysis presented here indicate that a newly-identified and functional polymorphism in the promoter of the complement C3 gene might participate in the genetic susceptibility to human MTLE with a history of FS, and to pure FS. CONCLUSIONS/SIGNIFICANCE: The present study provides important

  14. Zinc deficiency promotes cystitis-related bladder pain by enhancing function and expression of Cav3.2 in mice.

    Science.gov (United States)

    Ozaki, Tomoka; Matsuoka, Junki; Tsubota, Maho; Tomita, Shiori; Sekiguchi, Fumiko; Minami, Takeshi; Kawabata, Atsufumi

    2018-01-15

    Ca v 3.2 T-type Ca 2+ channel activity is suppressed by zinc that binds to the extracellular histidine-191 of Ca v 3.2, and enhanced by H 2 S that interacts with zinc. Ca v 3.2 in nociceptors is upregulated in an activity-dependent manner. The enhanced Ca v 3.2 activity by H 2 S formed by the upregulated cystathionine-γ-lyase (CSE) is involved in the cyclophosphamide (CPA)-induced cystitis-related bladder pain in mice. We thus asked if zinc deficiency affects the cystitis-related bladder pain in mice by altering Ca v 3.2 function and/or expression. Dietary zinc deficiency for 2 weeks greatly decreased zinc concentrations in the plasma but not bladder tissue, and enhanced the bladder pain/referred hyperalgesia (BP/RH) following CPA at 200mg/kg, a subeffective dose, but not 400mg/kg, a maximal dose, an effect abolished by pharmacological blockade or gene silencing of Ca v 3.2. Acute zinc deficiency caused by systemic N,N,N',N'-tetrakis-(2-pyridylmethyl)-ethylendiamine (TPEN), a zinc chelator, mimicked the dietary zinc deficiency-induced Ca v 3.2-dependent promotion of BP/RH following CPA at 200mg/kg. CPA at 400mg/kg alone or TPEN plus CPA at 200mg/kg caused Ca v 3.2 overexpression accompanied by upregulation of Egr-1 and USP5, known to promote transcriptional expression and reduce proteasomal degradation of Ca v 3.2, respectively, in the dorsal root ganglia (DRG). The CSE inhibitor, β-cyano-l-alanine, prevented the BP/RH and upregulation of Ca v 3.2, Egr-1 and USP5 in DRG following TPEN plus CPA at 200mg/kg. Together, zinc deficiency promotes bladder pain accompanying CPA-induced cystitis by enhancing function and expression of Ca v 3.2 in nociceptors, suggesting a novel therapeutic avenue for treatment of bladder pain, such as zinc supplementation. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Neurofeedback to improve neurocognitive functioning of children treated for a brain tumor: design of a randomized controlled double-blind trial

    Directory of Open Access Journals (Sweden)

    de Ruiter Marieke A

    2012-12-01

    Full Text Available Abstract Background Neurotoxicity caused by treatment for a brain tumor is a major cause of neurocognitive decline in survivors. Studies have shown that neurofeedback may enhance neurocognitive functioning. This paper describes the protocol of the PRISMA study, a randomized controlled trial to investigate the efficacy of neurofeedback to improve neurocognitive functioning in children treated for a brain tumor. Methods/Design Efficacy of neurofeedback will be compared to placebo training in a randomized controlled double-blind trial. A total of 70 brain tumor survivors in the age range of 8 to 18 years will be recruited. Inclusion also requires caregiver-reported neurocognitive problems and being off treatment for more than two years. A group of 35 healthy siblings will be included as the control group. On the basis of a qEEG patients will be assigned to one of three treatment protocols. Thereafter patients will be randomized to receive either neurofeedback training (n=35 or placebo training (n=35. Neurocognitive tests, and questionnaires administered to the patient, caregivers, and teacher, will be used to evaluate pre- and post-intervention functioning, as well as at 6-month follow-up. Siblings will be administered the same tests and questionnaires once. Discussion If neurofeedback proves to be effective for pediatric brain tumor survivors, this can be a valuable addition to the scarce interventions available to improve neurocognitive and psychosocial functioning. Trial registration ClinicalTrials.gov NCT00961922.

  16. Neurofeedback to improve neurocognitive functioning of children treated for a brain tumor: design of a randomized controlled double-blind trial

    International Nuclear Information System (INIS)

    Ruiter, Marieke A de; Meeteren, Antoinette YN Schouten-Van; Mourik, Rosa van; Janssen, Tieme WP; Greidanus, Juliette EM; Oosterlaan, Jaap; Grootenhuis, Martha A

    2012-01-01

    Neurotoxicity caused by treatment for a brain tumor is a major cause of neurocognitive decline in survivors. Studies have shown that neurofeedback may enhance neurocognitive functioning. This paper describes the protocol of the PRISMA study, a randomized controlled trial to investigate the efficacy of neurofeedback to improve neurocognitive functioning in children treated for a brain tumor. Efficacy of neurofeedback will be compared to placebo training in a randomized controlled double-blind trial. A total of 70 brain tumor survivors in the age range of 8 to 18 years will be recruited. Inclusion also requires caregiver-reported neurocognitive problems and being off treatment for more than two years. A group of 35 healthy siblings will be included as the control group. On the basis of a qEEG patients will be assigned to one of three treatment protocols. Thereafter patients will be randomized to receive either neurofeedback training (n=35) or placebo training (n=35). Neurocognitive tests, and questionnaires administered to the patient, caregivers, and teacher, will be used to evaluate pre- and post-intervention functioning, as well as at 6-month follow-up. Siblings will be administered the same tests and questionnaires once. If neurofeedback proves to be effective for pediatric brain tumor survivors, this can be a valuable addition to the scarce interventions available to improve neurocognitive and psychosocial functioning. ClinicalTrials.gov NCT00961922

  17. A Comparative Evaluation of the Effect of Double Casting Technique Using Functionally Generated Path and Conventional Single Casting with Respect to Functional Articulation, Patient Satisfaction and Chair Side Time, in Single Unit Molar Teeth: An In Vivo Study.

    Science.gov (United States)

    Memon, Sarfaraz

    2014-12-01

    A stable centric occlusal position that shows no evidence of occlusal disease should not be altered. Confirmative restorative dentistry deals with making restorations that are in harmony with existing jaw relations. Conventional techniques for construction have been unsuccessful in producing a prosthesis that can be inserted without minor intraoral occlusal adjustment. This study was conducted to evaluate the benefits of the double casting technique with FGP over the conventional casting technique. Ten patients with root canal treated maxillary molar were selected for the fabrication of metal crown. Two techniques, one involving the conventional fabrication and other using functionally generated path with double casting were used to fabricate the prosthesis. A comparison based on various parameters which was done between the two techniques. The change in the height of castings for the double casting group was less compared to the conventional group and was highly statistically significant (P casting group than the conventional group (P casting group compared to conventional (P casting technique resulted in castings which had better dimensional accuracy, less occlusal correction and better patient satisfaction compared to the conventional castings.

  18. Dielectric function and double absorption onset of monoclinic Cu2SnS3

    DEFF Research Database (Denmark)

    Crovetto, Andrea; Chen, Rongzhen; Ettlinger, Rebecca Bolt

    2016-01-01

    In this work, we determine experimentally the dielectric function of monoclinic Cu2SnS3 (CTS) by spectroscopic ellipsometry from 0.7 to 5.9 eV. An experimental approach is proposed to overcome the challenges of extracting the dielectric function of Cu2SnS3 when grown on a glass/Mo substrate...... secondary phases, is not needed to explain such an absorption spectrum. Finally, we show that the absorption coefficient of CTS is particularly large in the near-band gap spectral region when compared to similar photovoltaic materials....

  19. Carbohydrates Alone or Mixing With Beef or Whey Protein Promote Similar Training Outcomes in Resistance Training Males: A Double-Blind, Randomized Controlled Clinical Trial.

    Science.gov (United States)

    Naclerio, Fernando; Seijo-Bujia, Marco; Larumbe-Zabala, Eneko; Earnest, Conrad P

    2017-10-01

    Beef powder is a new high-quality protein source scarcely researched relative to exercise performance. The present study examined the impact of ingesting hydrolyzed beef protein, whey protein, and carbohydrate on strength performance (1RM), body composition (via plethysmography), limb circumferences and muscular thickness (via ultrasonography), following an 8-week resistance-training program. After being randomly assigned to one of the following groups: Beef, Whey, or Carbohydrate, twenty four recreationally physically active males (n = 8 per treatment) ingested 20 g of supplement, mixed with orange juice, once a day (immediately after workout or before breakfast). Post intervention changes were examined as percent change and 95% CIs. Beef (2.0%, CI, 0.2-2.38%) and Whey (1.4%, CI, 0.2-2.6%) but not Carbohydrate (0.0%, CI, -1.2-1.2%) increased fat-free mass. All groups increased vastus medialis thickness: Beef (11.1%, CI, 6.3-15.9%), Whey (12.1%, CI, 4.0, -20.2%), Carbohydrate (6.3%, CI, 1.9-10.6%). Beef (11.2%, CI, 5.9-16.5%) and Carbohydrate (4.5%, CI, 1.6-7.4%), but not Whey (1.1%, CI, -1.7-4.0%), increased biceps brachialis thickness, while only Beef increased arm (4.8%, CI, 2.3-7.3%) and thigh (11.2%, 95%CI 0.4-5.9%) circumferences. Although the three groups significantly improved 1RM Squat (Beef 21.6%, CI 5.5-37.7%; Whey 14.6%, CI, 5.9-23.3%; Carbohydrate 19.6%, CI, 2.2-37.1%), for the 1RM bench press the improvements were significant for Beef (15.8% CI 7.0-24.7%) and Whey (5.8%, CI, 1.7-9.8%) but not for carbohydrate (11.4%, CI, -0.9-23.6%). Protein-carbohydrate supplementation supports fat-free mass accretion and lower body hypertrophy. Hydrolyzed beef promotes upper body hypertrophy along with similar performance outcomes as observed when supplementing with whey isolate or maltodextrin.

  20. Self-care essential extras: an integration of holistic nursing, functional medicine, and health coaching to promote therapeutic lifestyle change and decrease chronic disease.

    Science.gov (United States)

    Scattergood, Donna M

    2010-01-01

    The Essential Vitality Program blends holistic nursing, functional medicine, and health coaching to promote lifestyle changes that modify risk factors of costly chronic disease. Karl is a client who experienced enhanced vitality, decreased chronic pain and medications use, and improved meaningful functioning, by partnering with a holistic nurse coach.

  1. The zinc finger E-box-binding homeobox 1 (Zeb1) promotes the conversion of mouse fibroblasts into functional neurons.

    Science.gov (United States)

    Yan, Long; Li, Yue; Shi, Zixiao; Lu, Xiaoyin; Ma, Jiao; Hu, Baoyang; Jiao, Jianwei; Wang, Hongmei

    2017-08-04

    The zinc finger E-box-binding transcription factor Zeb1 plays a pivotal role in the epithelial-mesenchymal transition. Numerous studies have focused on the molecular mechanisms by which Zeb1 contributes to this process. However, the functions of Zeb1 beyond the epithelial-mesenchymal transition remain largely elusive. Using a transdifferentiation system to convert mouse embryonic fibroblasts (MEFs) into functional neurons via the neuronal transcription factors achaete-scute family bHLH (basic helix-loop-helix) transcription factor1 ( Ascl1 ), POU class 3 homeobox 2 (POU3F2/ Brn2 ), and neurogenin 2 (Neurog2, Ngn2 ) (ABN), we found that Zeb1 was up-regulated during the early stages of transdifferentiation. Knocking down Zeb1 dramatically attenuated the transdifferentiation efficiency, whereas Zeb1 overexpression obviously increased the efficiency of transdifferentiation from MEFs to neurons. Interestingly, Zeb1 improved the transdifferentiation efficiency induced by even a single transcription factor ( e.g. Asc1 or Ngn2 ). Zeb1 also rapidly promoted the maturation of induced neuron cells to functional neurons and improved the formation of neuronal patterns and electrophysiological characteristics. Induced neuron cells could form functional synapse in vivo after transplantation. Genome-wide RNA arrays showed that Zeb1 overexpression up-regulated the expression of neuron-specific genes and down-regulated the expression of epithelial-specific genes during conversion. Taken together, our results reveal a new role for Zeb1 in the transdifferentiation of MEFs into neurons. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  2. Efficacy of the natural antioxidant astaxanthin in the treatment of functional dyspepsia in patients with or without Helicobacter pylori infection: a prospective, randomized, double blind, and placebo-controlled study5

    DEFF Research Database (Denmark)

    Kupcinskas, L.; Lafolie, P.; Lignell, A.

    2008-01-01

    OBJECTIVES: The aim of this study was to evaluate the efficacy of the natural antioxidant astaxanthin in functional dyspepsia in different doses and compared with placebo. DESIGN: The study was a controlled, prospective, randomized, and double blind trial. PARTICIPANTS: Patients with functional d...

  3. Green function of the double-fractional Fokker-Planck equation: Path integral and stochastic differential equations

    Science.gov (United States)

    Kleinert, H.; Zatloukal, V.

    2013-11-01

    The statistics of rare events, the so-called black-swan events, is governed by non-Gaussian distributions with heavy power-like tails. We calculate the Green functions of the associated Fokker-Planck equations and solve the related stochastic differential equations. We also discuss the subject in the framework of path integration.

  4. Clinical efficacy and safety of cisapride and clebopride in the management of chronic functional dyspepsia: a double-blind, randomized study.

    Science.gov (United States)

    Sabbatini, F; Minieri, M; Manzi, G; Piai, G; D'Angelo, V; Mazzacca, G

    1991-01-01

    The clinical efficacy and the safety of chronic oral administration of cisapride, a new gastrointestinal prokinetic agent, (10 mg tid) and clebopride (0.5 mg tid) was assayed in 48 outpatients affected with functional dyspepsia, in a randomized double-blind study. Each of the drugs induced a significant reduction in dyspeptic symptoms after 2 and 4 weeks (p less than 0.001). Two patients, given clebopride, dropped out of the study because of severe side effects during the first week of treatment. Mild adverse reactions were reported in 6 out of 23 cisapride-treated patients and in 10 out of 20 clebopride-treated patients who completed the study. The most common side effect of cisapride was diarrhoea and that of clebopride was drowsiness. Cisapride appears to be as effective as clebopride in reducing dyspeptic symptoms and seems to induce less severe side effects.

  5. An efficient formulation and implementation of the analytic energy gradient method to the single and double excitation coupled-cluster wave function - Application to Cl2O2

    Science.gov (United States)

    Rendell, Alistair P.; Lee, Timothy J.

    1991-01-01

    The analytic energy gradient for the single and double excitation coupled-cluster (CCSD) wave function has been reformulated and implemented in a new set of programs. The reformulated set of gradient equations have a smaller computational cost than any previously published. The iterative solution of the linear equations and the construction of the effective density matrices are fully vectorized, being based on matrix multiplications. The new method has been used to investigate the Cl2O2 molecule, which has recently been postulated as an important intermediate in the destruction of ozone in the stratosphere. In addition to reporting computational timings, the CCSD equilibrium geometries, harmonic vibrational frequencies, infrared intensities, and relative energetics of three isomers of Cl2O2 are presented.

  6. Functional characterization of a strong bi-directional constitutive plant promoter isolated from cotton leaf curl Burewala virus.

    Directory of Open Access Journals (Sweden)

    Zainul A Khan

    Full Text Available Cotton leaf curl Burewala virus (CLCuBuV, belonging to the genus Begomovirus, possesses single-stranded monopartite DNA genome. The bidirectional promoters representing Rep and coat protein (CP genes of CLCuBuV were characterized and their efficacy was assayed. Rep and CP promoters of CLCuBuV and 35S promoter of Cauliflower mosaic virus (CaMV were fused with β-glucuronidase (GUS and green fluorescent protein (GFP reporter genes. GUS activity in individual plant cells driven by Rep, CP and 35S promoters was estimated using real-time PCR and fluorometric GUS assay. Histochemical staining of GUS in transformed tobacco (Nicotiana tabacum cv. Xanthi leaves showed highest expression driven by Rep promoter followed by 35S promoter and CP promoter. The expression level of GUS driven by Rep promoter in transformed tobacco plants was shown to be two to four-fold higher than that of 35S promoter, while the expression by CP promoter was slightly lower. Further, the expression of GFP was monitored in agroinfiltrated leaves of N. benthamiana, N. tabacum and cotton (Gossypium hirsutum plants using confocal laser scanning microscopy. Rep promoter showed strong consistent transient expression in tobacco and cotton leaves as compared to 35S promoter. The strong constitutive CLCuBuV Rep promoter developed in this study could be very useful for high level expression of transgenes in a wide variety of plant cells.

  7. Tailoring surface properties and structure of layered double hydroxides using silanes with different number of functional groups

    Energy Technology Data Exchange (ETDEWEB)

    Tao, Qi [Key Laboratory of Mineralogy and Metallogeny, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou 510640 (China); Chemistry Discipline, Faculty of Science and Technology, Queensland University of Technology, Brisbane, Queensland 4001 (Australia); He, Hongping, E-mail: hehp@gig.ac.cn [Key Laboratory of Mineralogy and Metallogeny, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou 510640 (China); Chemistry Discipline, Faculty of Science and Technology, Queensland University of Technology, Brisbane, Queensland 4001 (Australia); Li, Tian [Key Laboratory of Mineralogy and Metallogeny, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou 510640 (China); University of Chinese, Academy of Sciences, Beijing 100039 (China); Frost, Ray L. [Chemistry Discipline, Faculty of Science and Technology, Queensland University of Technology, Brisbane, Queensland 4001 (Australia); Zhang, Dan; He, Zisen [Key Laboratory of Mineralogy and Metallogeny, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou 510640 (China); University of Chinese, Academy of Sciences, Beijing 100039 (China)

    2014-05-01

    Four silanes, trimethylchlorosilane (TMCS), dimethyldiethoxylsilane (DMDES), 3-aminopropyltriethoxysilane (APTES) and tetraethoxysilane (TEOS), were adopted to graft layered double hydroxides (LDH) via an induced hydrolysis silylation method (IHS). Fourier transform infrared spectra (FTIR) and {sup 29}Si MAS nuclear magnetic resonance spectra ({sup 29}Si MAS NMR) indicated that APTES and TEOS can be grafted onto LDH surfaces via condensation with hydroxyl groups of LDH, while TMCS and DMDES could only be adsorbed on the LDH surface with a small quantity. A combination of X-ray diffraction patterns (XRD) and {sup 29}Si MAS NMR spectra showed that silanes were exclusively present in the external surface and had little influence on the long range order of LDH. The surfactant intercalation experiment indicated that the adsorbed and/or grafted silane could not fix the interlamellar spacing of the LDH. However, they will form crosslink between the particles and affect the further surfactant intercalation in the silylated samples. The replacement of water by ethanol in the tactoids and/or aggregations and the polysiloxane oligomers formed during silylation procedure can dramatically increase the value of BET surface area (S{sub BET}) and total pore volumes (V{sub p}) of the products. - Graphical abstract: The replacement of water by ethanol in the tactoids and aggregations of LDHs, and the polysiloxane oligomers formed during silylation process can dramatically increase the BET surface area (S{sub BET}) and the total pore volume (V{sub p}) of the silylated products. - Highlights: • Silanes with multifunctional groups were grafted onto LDH surface in C{sub 2}H{sub 5}OH medium. • The number of hydrolysable groups in silanes affects the structure of grafted LDH. • Replacement of H{sub 2}O by C{sub 2}H{sub 5}OH in aggregations increases S{sub BET} and V{sub p} of grafted LDH. • Polysiloxane oligomers contribute to the increase of S{sub BET} and V{sub p} of grafted LDH.

  8. Hsp90α regulates ATM and NBN functions in sensing and repair of DNA double-strand breaks.

    Science.gov (United States)

    Pennisi, Rosa; Antoccia, Antonio; Leone, Stefano; Ascenzi, Paolo; di Masi, Alessandra

    2017-08-01

    The molecular chaperone heat shock protein 90 (Hsp90α) regulates cell proteostasis and mitigates the harmful effects of endogenous and exogenous stressors on the proteome. Indeed, the inhibition of Hsp90α ATPase activity affects the cellular response to ionizing radiation (IR). Although the interplay between Hsp90α and several DNA damage response (DDR) proteins has been reported, its role in the DDR is still unclear. Here, we show that ataxia-telangiectasia-mutated kinase (ATM) and nibrin (NBN), but not 53BP1, RAD50, and MRE11, are Hsp90α clients as the Hsp90α inhibitor 17-(allylamino)-17-demethoxygeldanamycin (17-AAG) induces ATM and NBN polyubiquitination and proteosomal degradation in normal fibroblasts and lymphoblastoid cell lines. Hsp90α-ATM and Hsp90α-NBN complexes are present in unstressed and irradiated cells, allowing the maintenance of ATM and NBN stability that is required for the MRE11/RAD50/NBN complex-dependent ATM activation and the ATM-dependent phosphorylation of both NBN and Hsp90α in response to IR-induced DNA double-strand breaks (DSBs). Hsp90α forms a complex also with ph-Ser1981-ATM following IR. Upon phosphorylation, NBN dissociates from Hsp90α and translocates at the DSBs, while phThr5/7-Hsp90α is not recruited at the damaged sites. The inhibition of Hsp90α affects nuclear localization of MRE11 and RAD50, impairs DDR signaling (e.g., BRCA1 and CHK2 phosphorylation), and slows down DSBs repair. Hsp90α inhibition does not affect DNA-dependent protein kinase (DNA-PK) activity, which possibly phosphorylates Hsp90α and H2AX after IR. Notably, Hsp90α inhibition causes H2AX phosphorylation in proliferating cells, this possibly indicating replication stress events. Overall, present data shed light on the regulatory role of Hsp90α on the DDR, controlling ATM and NBN stability and influencing the DSBs signaling and repair. © 2017 Federation of European Biochemical Societies.

  9. Effect of transcutaneous electrical nerve stimulation on pain, function, and quality of life in fibromyalgia: a double-blind randomized clinical trial.

    Science.gov (United States)

    Noehren, Brian; Dailey, Dana L; Rakel, Barbara A; Vance, Carol G T; Zimmerman, Miriam B; Crofford, Leslie J; Sluka, Kathleen A

    2015-01-01

    Fibromyalgia is a common chronic pain condition that has a significant impact on quality of life and often leads to disability. To date, there have been few well-controlled trials assessing the utility of nonpharmacological treatment modalities such as transcutaneous electrical nerve stimulation (TENS) in the management of pain and improvement in function in individuals with fibromyalgia. The purpose of this study will be to complete a long-term, multicenter study to assess the effects of TENS in women with fibromyalgia. This will be a phase II randomized, double-blind, placebo-controlled, multicenter clinical trial. Three hundred forty-three participants with fibromyalgia will be recruited for this study. Participants will be randomly assigned to 1 of 3 groups: the intervention (TENS), placebo, or no treatment. After completing the randomized period, all participants will receive the intervention for 1 month. The participants will be asked to use TENS at the highest tolerable level for at least 2 hours daily during physical activity. The primary outcome will be pain with movement, with secondary outcomes assessing functional abilities, patient-reported outcomes, and quantitative sensory testing. Because having participants refrain from their typical medications is not practical, their usage and any change in medication use will be recorded. The results of this study will provide some of the first evidence from a large-scale, double-blind, placebo-controlled trial on the effectiveness of TENS on pain control and quality-of-life changes in patients with fibromyalgia. © 2015 American Physical Therapy Association.

  10. TROPICS 1: a phase III, randomized, double-blind, placebo-controlled study of tenecteplase for restoration of function in dysfunctional central venous catheters.

    Science.gov (United States)

    Gabrail, Nashat; Sandler, Eric; Charu, Veena; Anas, Nick; Lim, Eduardo; Blaney, Martha; Ashby, Mark; Gillespie, Barbara S; Begelman, Susan M

    2010-12-01

    To evaluate the efficacy and safety of the thrombolytic tenecteplase, a fibrin-specific recombinant tissue plasminogen activator, for restoring function to dysfunctional central venous catheters (CVCs). In this double-blind, placebo-controlled study, eligible patients with dysfunctional nonhemodialysis CVCs were randomly assigned to two treatment arms. In the first arm (TNK-TNK-PBO), patients received an initial dose of intraluminal tenecteplase (TNK) (up to 2 mg), a second dose of tenecteplase if indicated, and a third placebo (PBO) dose. In the PBO-TNK-TNK arm, placebo was instilled first followed by up to two doses of tenecteplase, if needed, for restoration of catheter function. After administration of each dose, CVC function was assessed at 15, 30, and 120 minutes. There were 97 patients who received either TNK-TNK-PBO (n = 50) or PBO-TNK-TNK (n = 47). Within 120 minutes of initial study drug instillation, catheter function was restored to 30 patients (60%) in the TNK-TNK-PBO arm and 11 patients (23%) in the PBO-TNK-TNK arm, for a treatment difference of 37 percentage points (95% confidence interval 18-55; P = .0002). Cumulative restoration rates for CVC function increased to 87% after the second dose of tenecteplase in both study arms combined. Two patients developed a deep vein thrombosis (DVT) after exposure to tenecteplase; one DVT was considered to be drug related. No cases of intracranial hemorrhage, major bleeding, embolic events, catheter-related bloodstream infections, or catheter-related complications were reported. Tenecteplase was efficacious for restoration of catheter function in these study patients with dysfunctional CVCs. Copyright © 2010 SIR. Published by Elsevier Inc. All rights reserved.

  11. The potential of electrical stimulation to promote functional recovery after peripheral nerve injury--comparisons between rats and humans.

    Science.gov (United States)

    Gordon, T; Brushart, T M; Amirjani, N; Chan, K M

    2007-01-01

    The declining capacity for injured peripheral nerves to regenerate their axons with time and distance is accounted for, at least in part, by the chronic axotomy of the neurons and Schwann cell denervation prior to target reinnervation. A largely unrecognized site of delay is the surgical suture site where, in rats, 4 weeks is required for all neurons to regenerate their axons across the site. Low frequency stimulation for just 1 h after surgery accelerates this axon crossing in association with upregulation of neurotrophic factors in the neurons. We translated these findings to human patients by examining the number of reinnervated motor units in the median nerve-innervated thenar muscles before and after carpel tunnel release surgery in a randomized controlled trial. Motor unit number estimates (MUNE) in patients with moderate and severe carpal tunnel syndrome were significantly lower than normal. This number increased significantly by 6-8 months after surgery and reached normal values by 12 months in contrast to a non-significant increase in the control unstimulated group. Tests including the Purdue Pegboard Test verified the more rapid functional recovery after stimulation. The data indicate a feasible strategy to promote axonal regeneration in humans that has the potential to improve functional outcomes, especially in combination with strategies to sustain the regenerative capacity of neurons and the support of Schwann cells over distance and time.

  12. Black Tea High-Molecular-Weight Polyphenol-Rich Fraction Promotes Hypertrophy during Functional Overload in Mice

    Directory of Open Access Journals (Sweden)

    Yuki Aoki

    2017-03-01

    Full Text Available Mitochondria activation factor (MAF is a high-molecular-weight polyphenol extracted from black tea that stimulates training-induced 5′ adenosine monophosphate-activated protein kinase (AMPK activation and improves endurance capacity. Originally, MAF was purified from black tea using butanol and acetone, making it unsuitable for food preparation. Hence, we extracted a MAF-rich sample “E80” from black tea, using ethanol and water only. Here, we examined the effects of E80 on resistance training. Eight-week old C57BL/6 mice were fed with a normal diet or a diet containing 0.5% E80 for 4, 7 and 14 days under conditions of functional overload. It was found that E80 administration promoted overload-induced hypertrophy and induced phosphorylation of the Akt/mammalian target of rapamycin (mTOR pathway proteins, such as Akt, P70 ribosomal protein S6 kinase (p70S6K, and S6 in the plantaris muscle. Therefore, functional overload and E80 administration accelerated mTOR signaling and increased protein synthesis in the muscle, thereby inducing hypertrophy.

  13. WNT10B functional dualism: beta-catenin/Tcf-dependent growth promotion or independent suppression with deregulated expression in cancer.

    Science.gov (United States)

    Yoshikawa, Hirohide; Matsubara, Kenichi; Zhou, Xiaoling; Okamura, Shu; Kubo, Takahiko; Murase, Yaeko; Shikauchi, Yuko; Esteller, Manel; Herman, James G; Wei Wang, Xin; Harris, Curtis C

    2007-11-01

    We found aberrant DNA methylation of the WNT10B promoter region in 46% of primary hepatocellular carcinoma (HCC) and 15% of colon cancer samples. Three of 10 HCC and one of two colon cancer cell lines demonstrated low or no expression, and 5-aza-2'deoxycytidine reactivated WNT10B expression with the induction of demethylation, indicating that WNT10B is silenced by DNA methylation in some cancers, whereas WNT10B expression is up-regulated in seven of the 10 HCC cell lines and a colon cancer cell line. These results indicate that WNT10B can be deregulated by either overexpression or silencing in cancer. We found that WNT10B up-regulated beta-catenin/Tcf activity. However, WNT10B-overexpressing cells demonstrated a reduced growth rate and anchorage-independent growth that is independent of the beta-catenin/Tcf activation, because mutant beta-catenin-transduced cells did not suppress growth, and dominant-negative hTcf-4 failed to alleviate the growth suppression by WNT10B. Although WNT10B expression alone inhibits cell growth, it acts synergistically with the fibroblast growth factor (FGF) to stimulate cell growth. WNT10B is bifunctional, one function of which is involved in beta-catenin/Tcf activation, and the other function is related to the down-regulation of cell growth through a different mechanism. We suggest that FGF switches WNT10B from a negative to a positive cell growth regulator.

  14. Creative music therapy to promote brain structure, function, and neurobehavioral outcomes in preterm infants: a randomized controlled pilot trial protocol.

    Science.gov (United States)

    Haslbeck, Friederike Barbara; Bucher, Hans-Ulrich; Bassler, Dirk; Hagmann, Cornelia

    2017-01-01

    Preterm birth is associated with increased risk of neurological impairment and deficits in cognition, motor function, and behavioral problems. Limited studies indicate that multi-sensory experiences support brain development in preterm infants. Music appears to promote neurobiological processes and neuronal learning in the human brain. Creative music therapy (CMT) is an individualized, interactive therapeutic approach based on the theory and methods of Nordoff and Robbins. CMT may promote brain development in preterm infants via concurrent interaction and meaningful auditory stimulation. We hypothesize that preterm infants who receive creative music therapy during neonatal intensive care admission will have developmental benefits short- and long-term brain function. A prospective, randomized controlled single-center pilot trial involving 60 clinically stable preterm infants under 32 weeks of gestational age is conducted in preparation for a multi-center trial. Thirty infants each are randomized to either standard neonatal intensive care or standard care with CMT. Music therapy intervention is approximately 20 min in duration three times per week. A trained music therapist sings for the infants in lullaby style, individually entrained and adjusted to the infant's rhythm and affect. Primary objectives of this study are feasibility of protocol implementation and investigating the potential mechanism of efficacy for this new intervention. To examine the effect of this new intervention, non-invasive, quantitative magnetic resonance imaging (MRI) methods at corrected age and standardized neurodevelopmental assessments using the Bayley Scales of Infant and Toddler Development third edition at a corrected age of 24 months and Kaufman Assessment Battery for Children at 5 years will be performed. All assessments will be performed and analyzed by blinded experts. To our knowledge, this is the first randomized controlled clinical trial to systematically examine possible

  15. Emerging Importance of Helicases in Plant Stress Tolerance: Characterization of Oryza sativa Repair Helicase XPB2 Promoter and Its Functional Validation in Tobacco under Multiple Stresses.

    Science.gov (United States)

    Raikwar, Shailendra; Srivastava, Vineet K; Gill, Sarvajeet S; Tuteja, Renu; Tuteja, Narendra

    2015-01-01

    Genetic material always remains at the risk of spontaneous or induced damage which challenges the normal functioning of DNA molecule, thus, DNA repair is vital to protect the organisms against genetic damage. Helicases, the unique molecular motors, are emerged as prospective molecules to engineer stress tolerance in plants and are involved in nucleic acid metabolism including DNA repair. The repair helicase, XPB is an evolutionary conserved protein present in different organisms, including plants. Availability of few efficient promoters for gene expression in plants provoked us to study the promoter of XPB for better understanding of gene regulation under stress conditions. Here, we report the in silico analysis of novel stress inducible promoter of Oryza sativa XPB2 (OsXPB2). The in vivo validation of functionality/activity of OsXPB2 promoter under abiotic and hormonal stress conditions was performed by Agrobacterium-mediated transient assay in tobacco leaves using OsXPB2::GUS chimeric construct. The present research revealed that OsXPB2 promoter contains cis-elements accounting for various abiotic stresses (salt, dehydration, or cold) and hormone (Auxin, ABA, or MeJA) induced GUS expression/activity in the promoter-reporter assay. The promoter region of OsXPB2 contains CACG, GTAACG, CACGTG, CGTCA CCGCCGCGCT cis acting-elements which are reported to be salt, dehydration, cold, MeJA, or ABA responsive, respectively. Functional analysis was done by Agrobacterium-mediated transient assay using agroinfiltration in tobacco leaves, followed by GUS staining and fluorescence quantitative analyses. The results revealed high induction of GUS activity under multiple abiotic stresses as compared to mock treated control. The present findings suggest that OsXPB2 promoter is a multi-stress inducible promoter and has potential applications in sustainable crop production under abiotic stresses by regulating desirable pattern of gene expression.

  16. A 1-kb bacteriophage lambda fragment functions as an insulator to effectively block enhancer-promoter interactions in Arabidopsis thaliana

    Science.gov (United States)

    The 35S cauliflower mosaic virus (CaMV) promoter contains an enhancer element that is able to override the tissue-, organ- and developmental-stage specificity of nearby promoters. Consequently, the precise control of transgene expression in transgenic plants, which often contain the 35S CaMV promot...

  17. Principles of brain plasticity in improving sensorimotor function of the knee and leg in patients with anterior cruciate ligament injury: a double-blind randomized exploratory trial

    Directory of Open Access Journals (Sweden)

    Ageberg Eva

    2012-05-01

    Full Text Available Abstract Background Severe traumatic knee injury, including injury to the anterior cruciate ligament (ACL, leads to impaired sensorimotor function. Although improvements are achieved by training, impairment often persists. Because good sensorimotor function is associated with better patient-reported function and a potential lower risk of future joint problems, more effective treatment is warranted. Temporary cutaneous anesthesia of adjacent body parts was successfully used on the hand and foot to improve sensorimotor function. The aim of this study was to test whether this principle of brain plasticity could be used on the knee. The hypothesis was that temporary anesthesia of the skin area above and below the knee would improve sensorimotor function of the ipsilateral knee and leg in subjects with ACL injury. Methods In this double-blind exploratory study, 39 subjects with ACL injury (mean age 24 years, SD 5.2, 49% women, mean 52 weeks after injury or reconstruction and self-reported functional limitations and lack of trust in the knee were randomized to temporary local cutaneous application of anesthetic (EMLA® (n = 20 or placebo cream (n = 19. Fifty grams of EMLA®, or placebo, was applied on the leg 10 cm above and 10 cm below the center of patella, leaving the area around the knee without cream. Measures of sensory function (perception of touch, vibration sense, knee kinesthesia and motor function (knee muscle strength, hop test were assessed before and after 90 minutes of treatment with EMLA® or placebo. The paired t-test was used for comparisons within groups and analysis of variance between groups, except for ordinal data where the Wilcoxon signed rank test, or Mann–Whitney test, was used. The number of subjects needed was determined by an a priori sample size calculation. Results No statistically significant or clinically relevant differences were seen over time (before vs. after in the measures of sensory or motor

  18. The Effect of Korean Red Ginseng on Sexual Function in Premenopausal Women: Placebo-Controlled, Double-Blind, Crossover Clinical Trial

    Directory of Open Access Journals (Sweden)

    Ho Seok Chung

    2015-01-01

    Full Text Available This study investigated whether Korean red ginseng (KRG extracts could improve sexual function in premenopausal women. Forty-one premenopausal women participated in this placebo-controlled, double-blind, and crossover clinical study with administration of either three ginseng capsules (1 g per capsule or placebo daily. After 8 weeks of medication of KRG or placebo, medication was changed for the subjects to placebo or KRG after 2 weeks of washout period. The efficacy of KRG extracts was measured by using Female Sexual Function Index (FSFI. Results. Twenty-three women completed the study. Total FSFI scores increased after KRG treatment (from 20.13±2.87 to 23.98±4.10, p=0.015 and placebo treatment (from 20.06±2.64 to 23.78±3.28, p=0.003. However, this change was not significantly different between the two groups (p=0.702. KRG treatment significantly improved sexual desire, arousal, orgasm, and satisfaction domains; however, there was no treatment effect compared with placebo. There was a case of gastric discomfort after taking KRG extracts. Oral administration of KRG extracts improved sexual function in premenopausal women; however, there were no statistical significant changes compared to placebo. It implies that KRG extracts have a substantial placebo effect in premenopausal women with sexual dysfunction.

  19. Aural stimulation with capsaicin ointment improved swallowing function in elderly patients with dysphagia: a randomized, placebo-controlled, double-blind, comparative study.

    Science.gov (United States)

    Kondo, Eiji; Jinnouchi, Osamu; Nakano, Seiichi; Ohnishi, Hiroki; Kawata, Ikuji; Okamoto, Hidehiko; Takeda, Noriaki

    2017-01-01

    The aim of this study was to assess whether aural stimulation with ointment containing capsaicin improves swallowing function in elderly patients with dysphagia. A randomized, placebo-controlled, double-blind, comparative study. Secondary hospital. Twenty elderly dysphagic patients with a history of cerebrovascular disorder or Parkinson's disease were randomly divided into two groups: 10 receiving aural stimulation with 0.025% capsaicin ointment and 10 stimulated with placebo. The ointments were applied to the external auditory canal with a cotton swab. Then, swallowing of a bolus of blue-dyed water was recorded using transnasal videoendoscopy, and the swallowing function was evaluated according to both endoscopic swallowing scoring and Sensory-Motor-Reflex-Clearance (SMRC) scale. The sum of endoscopic swallowing scores was significantly decreased 30 and 60 min after a single administration in patients treated with capsaicin, but not with placebo. Reflex score, but not Sensory, Motion and Clearance scores, of the SMRC scale was significantly increased 5, 30 and 60 min after single administration in patients treated with capsaicin, but not with placebo. No patient showed signs of adverse effects. As capsaicin is an agonist of the transient receptor potential vanilloid 1 (TRPV1), these findings suggest that improvement of the swallowing function, especially glottal closure and cough reflexes, in elderly dysphagic patients was due to TRPV1-mediated aural stimulation of vagal Arnold's nerve with capsaicin, but not with a nonspecific mechanical stimulation with a cotton swab.

  20. Atomoxetine Effects on Executive Function as Measured by the BRIEF-A in Young Adults with ADHD: A Randomized, Double-Blind, Placebo-Controlled Study

    Science.gov (United States)

    Adler, Lenard A.; Clemow, David B.; Williams, David W.; Durell, Todd M.

    2014-01-01

    Objective To evaluate the effect of atomoxetine treatment on executive functions in young adults with attention-deficit/hyperactivity disorder (ADHD). Methods In this Phase 4, multi-center, double-blind, placebo-controlled trial, young adults (18–30 years) with ADHD were randomized to receive atomoxetine (20–50 mg BID, N = 220) or placebo (N = 225) for 12 weeks. The Behavior Rating Inventory of Executive Function-Adult (BRIEF-A) consists of 75 self-report items within 9 nonoverlapping clinical scales measuring various aspects of executive functioning. Mean changes from baseline to 12-week endpoint on the BRIEF-A were analyzed using an ANCOVA model (terms: baseline score, treatment, and investigator). Results At baseline, there were no significant treatment group differences in the percentage of patients with BRIEF-A composite or index T-scores ≥60 (p>.5), with over 92% of patients having composite scores ≥60 (≥60 deemed clinically meaningful for these analyses). At endpoint, statistically significantly greater mean reductions were seen in the atomoxetine versus placebo group for the BRIEF-A Global Executive Composite (GEC), Behavioral Regulation Index (BRI), and Metacognitive Index (MI) scores, as well as the Inhibit, Self-Monitor, Working Memory, Plan/Organize and Task Monitor subscale scores (patomoxetine versus placebo group as measured by changes in the BRIEF-A scales. Trial Registration ClinicalTrials.gov NCT00510276 PMID:25148243

  1. A double-blind, randomized, placebo-controlled trial of itopride (100 and 200 mg three times daily) on gastric motor and sensory function in healthy volunteers.

    Science.gov (United States)

    Choung, R S; Talley, N J; Peterson, J; Camilleri, M; Burton, D; Harmsen, W S; Zinsmeister, A R

    2007-03-01

    Itopride, a dopamine D2 antagonist and acetylcholinesterase inhibitor, significantly improved symptoms in patients with functional dyspepsia in one phase II randomized trial. However, the mechanisms by which itopride may improve symptoms are unknown. We aimed to compare the effects of two doses of itopride and placebo on gastric volumes, gastric emptying, small bowel transit and satiation in female and male healthy volunteers. Randomized, double-blind, placebo-controlled study evaluated gastric function before and after 7 days of itopride 100 mg (n = 16) or 200 mg (n = 15) or placebo (n = 15) t.i.d. Validated methods were used to study gastric accommodation (single photon emission computed tomography), gastric emptying and orocecal transit and satiation postnutrient challenge. The three arms were comparable with regard to age, gender and body mass index. There were no statistically significant effects of itopride on gastric emptying, orocecal transit, fasting gastric volume, maximum tolerated volume or aggregate symptom score with nutrient drink challenge. Postprandial (PP) change in gastric volume differed in the three groups (P = 0.019): 625[+/-28 (SEM)], 555(+/-26) and 512(+/-33) in placebo, itopride 100 and 200 mg groups, respectively. In healthy subjects, itopride reduced total PP gastric volume without accelerating gastric emptying or significantly altering gastric motor and sensory function in healthy individuals.

  2. A Randomized, Double-Blind Study Assessing Changes in Cognitive Function in Indian School Children Receiving a Combination of Bacopa monnieri and Micronutrient Supplementation vs. Placebo

    Directory of Open Access Journals (Sweden)

    Tora Mitra-Ganguli

    2017-11-01

    Full Text Available Several studies have indicated a chronic cognitive enhancing effect of Bacopa monnieri across different ages and cognitive impairment associated with vitamin and mineral deficiencies in children. Therefore, we investigated the effects of 4-month supplementation with a combination of B. monnieri extract and multiple micronutrients on cognitive functions in Indian school children aged 7–12 years. This was a randomized, double-blind, parallel design, single-center study in which 300 children were randomized to receive a beverage either fortified with B. monnieri and multiple micronutrients (“fortified” or a non-fortified isocaloric equivalent (“control” twice-daily for 4 months. Cognitive function was assessed by the Cambridge Neuropsychological Automated Test Battery (CANTAB administered at baseline, Day 60 and Day 121. The primary endpoint was change in short-term memory (working memory from baseline in subjects receiving “fortified” vs. “control” beverages after 4 months. Secondary endpoints included sustained attention, episodic memory, and executive function. The “fortified” beverage did not significantly improve short-term memory or any of the secondary outcomes tested relative to the “control” beverage. However, the spatial working memory “strategy” score showed significant improvement on Day 60 (difference between groups in change from baseline: −0.55; p < 0.05, but not on Day 121 due to the active intervention. Study products were well-tolerated. Reasons for these unexpected findings are discussed.

  3. A functional variant in the stearoyl-CoA desaturase gene promoter enhances fatty acid desaturation in pork.

    Directory of Open Access Journals (Sweden)

    Joan Estany

    Full Text Available There is growing public concern about reducing saturated fat intake. Stearoyl-CoA desaturase (SCD is the lipogenic enzyme responsible for the biosynthesis of oleic acid (18 ∶ 1 by desaturating stearic acid (18 ∶ 0. Here we describe a total of 18 mutations in the promoter and 3' non-coding region of the pig SCD gene and provide evidence that allele T at AY487830:g.2228T>C in the promoter region enhances fat desaturation (the ratio 18 ∶ 1/18 ∶ 0 in muscle increases from 3.78 to 4.43 in opposite homozygotes without affecting fat content (18 ∶ 0+18 ∶ 1, intramuscular fat content, and backfat thickness. No mutations that could affect the functionality of the protein were found in the coding region. First, we proved in a purebred Duroc line that the C-T-A haplotype of the 3 single nucleotide polymorphisms (SNPs (g.2108C>T; g.2228T>C; g.2281A>G of the promoter region was additively associated to enhanced 18 ∶ 1/18 ∶ 0 both in muscle and subcutaneous fat, but not in liver. We show that this association was consistent over a 10-year period of overlapping generations and, in line with these results, that the C-T-A haplotype displayed greater SCD mRNA expression in muscle. The effect of this haplotype was validated both internally, by comparing opposite homozygote siblings, and externally, by using experimental Duroc-based crossbreds. Second, the g.2281A>G and the g.2108C>T SNPs were excluded as causative mutations using new and previously published data, restricting the causality to g.2228T>C SNP, the last source of genetic variation within the haplotype. This mutation is positioned in the core sequence of several putative transcription factor binding sites, so that there are several plausible mechanisms by which allele T enhances 18 ∶ 1/18 ∶ 0 and, consequently, the proportion of monounsaturated to saturated fat.

  4. Design Of the Approximation Function of a Pedometer based on Artificial Neural Network for the Healthy Life Style Promotion in Diabetic Patients

    OpenAIRE

    Vega Corona, Antonio; Zárate Banda, Magdalena; Barron Adame, Jose Miguel; Martínez Celorio, René Alfredo; Andina de la Fuente, Diego

    2008-01-01

    The present study describes the design of an Artificial Neural Network to synthesize the Approximation Function of a Pedometer for the Healthy Life Style Promotion. Experimentally, the approximation function is synthesized using three basic digital pedometers of low cost, these pedometers were calibrated with an advanced pedometer that calculates calories consumed and computes distance travelled with personal stride input. The synthesized approximation function by means of the designed neural...

  5. Adenovirus vector expressing keratinocyte growth factor using CAG promoter impairs pulmonary function of mice with elastase-induced emphysema.

    Science.gov (United States)

    Oki, Hiroshi; Yazawa, Takuya; Baba, Yasuko; Kanegae, Yumi; Sato, Hanako; Sakamoto, Seiko; Goto, Takahisa; Saito, Izumu; Kurahashi, Kiyoyasu

    2017-07-01

    Pulmonary emphysema impairs quality of life and increases mortality. It has previously been shown that administration of adenovirus vector expressing murine keratinocyte growth factor (KGF) before elastase instillation prevents pulmonary emphysema in mice. We therefore hypothesized that therapeutic administration of KGF would restore damage to lungs caused by elastase instillation and thus improve pulmonary function in an animal model. KGF expressing adenovirus vector, which prevented bleomycin-induced pulmonary fibrosis in a previous study, was constructed. Adenovirus vector (1.0 × 10 9 plaque-forming units) was administered intratracheally one week after administration of elastase into mouse lungs. One week after administration of KGF-vector, exercise tolerance testing and blood gas analysis were performed, after which the lungs were removed under deep anesthesia. KGF-positive pneumocytes were more numerous, surfactant protein secretion in the airspace greater and mean linear intercept of lungs shorter in animals that had received KGF than in control animals. Unexpectedly, however, arterial blood oxygenation was worse in the KGF group and maximum running speed, an indicator of exercise capacity, had not improved after KGF in mice with elastase-induced emphysema, indicating that KGF-expressing adenovirus vector impaired pulmonary function in these mice. Notably, vector lacking KGF-expression unit did not induce such impairment, implying that the KGF expression unit itself may cause the damage to alveolar cells. Possible involvement of the CAG promoter used for KGF expression in impairing pulmonary function is discussed. © 2017 The Societies and John Wiley & Sons Australia, Ltd.

  6. Combining neurotrophin-transduced schwann cells and rolipram to promote functional recovery from subacute spinal cord injury.

    Science.gov (United States)

    Flora, Govinder; Joseph, Gravil; Patel, Samik; Singh, Amanpreet; Bleicher, Drew; Barakat, David J; Louro, Jack; Fenton, Stephanie; Garg, Maneesh; Bunge, Mary Bartlett; Pearse, Damien D

    2013-01-01

    Following spinal cord injury (SCI), both an inhibitory environment and lack of intrinsic growth capacity impede axonal regeneration. In a previous study, prevention of cyclic adenosine monophosphate (AMP) hydrolysis by the phosphodiesterase-4 inhibitor rolipram, in combination with Schwann cell (SC) grafts, promoted significant supraspinal and proprioceptive fiber growth and/or sparing and improved locomotion. In another study, transplanted SCs transduced to generate a bifunctional neurotrophin (D15A) led to significant increases in graft SCs and axons, including supraspinal and myelinated axons. Here we studied the growth and myelination of local and supraspinal axons and functional outcome following the combination of rolipram administration and neurotrophin-transduced SC implantation after SCI. Rolipram was administer