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Sample records for agonist-induced functional differentiation

  1. Effects of inhibitors of protein synthesis and intracellular transport on the gamma-aminobutyric acid agonist-induced functional differentiation of cultured cerebellar granule cells

    DEFF Research Database (Denmark)

    Belhage, B; Hansen, G H; Meier, E;

    1990-01-01

    differentiation and GABA receptor expression was investigated in cultured cerebellar granule cells. After 4 days in culture the neurons were exposed to the inhibitors for 6 h in the simultaneous presence of THIP. Subsequently, cultures were either fixed for electron microscopic examination or used for preparation...... of membranes for [3H]GABA binding assays. In some experiments the functional activity of the newly induced low-affinity GABA receptors was assessed by investigation of the ability of GABA to inhibit neurotransmitter release from the neurons. These experiments were performed to differentiate between...... an intracellular and a plasma membrane localization of the receptors. In all experiments cultures treated with THIP alone served as controls. The inhibitors of protein synthesis totally abolished the ability of THIP to induce low-affinity GABA receptors. In contrast, the inhibitors of intracellular transport...

  2. Differential β-arrestin2 requirements for constitutive and agonist-induced internalization of the CB1 cannabinoid receptor.

    Science.gov (United States)

    Gyombolai, Pál; Boros, Eszter; Hunyady, László; Turu, Gábor

    2013-06-15

    CB1 cannabinoid receptor (CB1R) undergoes both constitutive and agonist-induced internalization, but the underlying mechanisms of these processes and the role of β-arrestins in the regulation of CB1R function are not completely understood. In this study, we followed CB1R internalization using confocal microscopy and bioluminescence resonance energy transfer measurements in HeLa and Neuro-2a cells. We found that upon activation CB1R binds β-arrestin2 (β-arr2), but not β-arrestin1. Furthermore, both the expression of dominant-negative β-arr2 (β-arr2-V54D) and siRNA-mediated knock-down of β-arr2 impaired the agonist-induced internalization of CB1R. In contrast, neither β-arr2-V54D nor β-arr2-specific siRNA had a significant effect on the constitutive internalization of CB1R. However, both constitutive and agonist-induced internalization of CB1R were impaired by siRNA-mediated depletion of clathrin heavy chain. We conclude that although clathrin is required for both constitutive and agonist-stimulated internalization of CB1R, β-arr2 binding is only required for agonist-induced internalization of the receptor suggesting that the molecular mechanisms underlying constitutive and agonist-induced internalization of CB1R are different.

  3. Type I and II positive allosteric modulators differentially modulate agonist-induced up-regulation of α7 nicotinic acetylcholine receptors

    DEFF Research Database (Denmark)

    Thomsen, Morten Skøtt; Mikkelsen, Jens D

    2012-01-01

    and II α7 nAChR positive allosteric modulators (PAMs) on agonist-induced α7 nAChR up-regulation. We show that the type II PAMs, PNU-120596 (10 μM) or TQS (1 and 10 μM), inhibit up-regulation, as measured by protein levels, induced by the α7 nAChR agonist A-582941 (10 nM or 10 μM), in SH-EP1 cells stably...... and A-582941 induce up-regulation through different mechanisms, and that this confers differential sensitivity to the effects of α7 nAChR PAMs. These results may have implications for the clinical development of α7 nAChR PAMs....

  4. Type I and II positive allosteric modulators differentially modulate agonist-induced up-regulation of α7 nicotinic acetylcholine receptors.

    Science.gov (United States)

    Thomsen, Morten S; Mikkelsen, Jens D

    2012-10-01

    Long-term treatment with nicotine or selective α7 nicotinic acetylcholine receptor (nAChR) agonists increases the number of α7 nAChRs and this up-regulation may be involved in the mechanism underlying the sustained procognitive effect of these compounds. Here, we investigate the influence of type I and II α7 nAChR positive allosteric modulators (PAMs) on agonist-induced α7 nAChR up-regulation. We show that the type II PAMs, PNU-120596 (10 μM) or TQS (1 and 10 μM), inhibit up-regulation, as measured by protein levels, induced by the α7 nAChR agonist A-582941 (10 nM or 10 μM), in SH-EP1 cells stably expressing human α7 nAChR, whereas the type I PAMs AVL-3288 or NS1738 do not. Contrarily, neither type I nor II PAMs affect 10 μM nicotine-induced receptor up-regulation, suggesting that nicotine and A-582941 induce up-regulation through different mechanisms. We further show in vivo that 3 mg/kg PNU-120596 inhibits up-regulation of the α7 nAChR induced by 10 mg/kg A-582941, as measured by [(125)I]-bungarotoxin autoradiography, whereas 1 mg/kg AVL-3288 does not. Given that type II PAMs decrease desensitization of the receptor, whereas type I PAMs do not, these results suggest that receptor desensitization is involved in A-582941-induced up-regulation. Our results are the first to show an in vivo difference between type I and II α7 nAChR PAMs, and demonstrate an agonist-dependent effect of type II PAMs occurring on a much longer time scale than previously appreciated. Furthermore, our data suggest that nicotine and A-582941 induce up-regulation through different mechanisms, and that this confers differential sensitivity to the effects of α7 nAChR PAMs. These results may have implications for the clinical development of α7 nAChR PAMs.

  5. GLYX-13, a NMDA Receptor Glycine-Site Functional Partial Agonist, Induces Antidepressant-Like Effects Without Ketamine-Like Side Effects

    Science.gov (United States)

    Burgdorf, Jeffrey; Zhang, Xiao-lei; Nicholson, Katherine L; Balster, Robert L; David Leander, J; Stanton, Patric K; Gross, Amanda L; Kroes, Roger A; Moskal, Joseph R

    2013-01-01

    Recent human clinical studies with the NMDA receptor (NMDAR) antagonist ketamine have revealed profound and long-lasting antidepressant effects with rapid onset in several clinical trials, but antidepressant effects were preceded by dissociative side effects. Here we show that GLYX-13, a novel NMDAR glycine-site functional partial agonist, produces an antidepressant-like effect in the Porsolt, novelty induced hypophagia, and learned helplessness tests in rats without exhibiting substance abuse-related, gating, and sedative side effects of ketamine in the drug discrimination, conditioned place preference, pre-pulse inhibition and open-field tests. Like ketamine, the GLYX-13-induced antidepressant-like effects required AMPA/kainate receptor activation, as evidenced by the ability of NBQX to abolish the antidepressant-like effect. Both GLYX-13 and ketamine persistently (24 h) enhanced the induction of long-term potentiation of synaptic transmission and the magnitude of NMDAR-NR2B conductance at rat Schaffer collateral-CA1 synapses in vitro. Cell surface biotinylation studies showed that both GLYX-13 and ketamine led to increases in both NR2B and GluR1 protein levels, as measured by Western analysis, whereas no changes were seen in mRNA expression (microarray and qRT-PCR). GLYX-13, unlike ketamine, produced its antidepressant-like effect when injected directly into the medial prefrontal cortex (MPFC). These results suggest that GLYX-13 produces an antidepressant-like effect without the side effects seen with ketamine at least in part by directly modulating NR2B-containing NMDARs in the MPFC. Furthermore, the enhancement of ‘metaplasticity' by both GLYX-13 and ketamine may help explain the long-lasting antidepressant effects of these NMDAR modulators. GLYX-13 is currently in a Phase II clinical development program for treatment-resistant depression. PMID:23303054

  6. functional-differential inequalities

    Directory of Open Access Journals (Sweden)

    Ludwik Byszewski

    1995-01-01

    Full Text Available A theorem about a system of strong impulsive degenerate nonlinear parabolic functional-differential inequalities in an arbitrary parabolic set is proved. As a consequence of the theorem, some theorems about impulsive degenerate nonlinear parabolic differential inequalities and the uniqueness of a classical solution of an impulsive degenerate nonlinear parabolic differential problem are established.

  7. Differentiation of real functions

    CERN Document Server

    Bruckner, Andrew

    1994-01-01

    Topics related to the differentiation of real functions have received considerable attention during the last few decades. This book provides an efficient account of the present state of the subject. Bruckner addresses in detail the problems that arise when dealing with the class \\Delta ' of derivatives, a class that is difficult to handle for a number of reasons. Several generalized forms of differentiation have assumed importance in the solution of various problems. Some generalized derivatives are excellent substitutes for the ordinary derivative when the latter is not known to exist; others are not. Bruckner studies generalized derivatives and indicates "geometric" conditions that determine whether or not a generalized derivative will be a good substitute for the ordinary derivative. There are a number of classes of functions closely linked to differentiation theory, and these are examined in some detail. The book unifies many important results from the literature as well as some results not previously pub...

  8. Effects of inhibitors of protein synthesis and intracellular transport on the gamma-aminobutyric acid agonist-induced functional differentiation of cultured cerebellar granule cells

    DEFF Research Database (Denmark)

    Belhage, B; Hansen, Gert Helge; Meier, E

    1990-01-01

    preparations. This indicates that the low-affinity receptors were not located in the plasma membrane. This is in good agreement with the corresponding morphological findings, that monensin treatment led to an intense vacuolization of the Golgi apparatus, thereby preventing intracellular transport of the newly...

  9. Using Differentials to Differentiate Trigonometric and Exponential Functions

    Science.gov (United States)

    Dray, Tevian

    2013-01-01

    Starting from geometric definitions, we show how differentials can be used to differentiate trigonometric and exponential functions without limits, numerical estimates, solutions of differential equations, or integration.

  10. Using Differentials to Differentiate Trigonometric and Exponential Functions

    Science.gov (United States)

    Dray, Tevian

    2013-01-01

    Starting from geometric definitions, we show how differentials can be used to differentiate trigonometric and exponential functions without limits, numerical estimates, solutions of differential equations, or integration.

  11. Studies on the adrenomedullary dependence of kappa-opioid agonist-induced diuresis in conscious rats.

    Science.gov (United States)

    Borkowski, K. R.

    1989-01-01

    1. The dependence of kappa-opioid agonist-induced diuresis, upon an intact and functional adrenal medulla in conscious rats, was investigated in order to test the hypothesis that the diuresis is mediated by a blood-borne 'diuretic factor', of adrenomedullary origin, released by kappa-opioid receptor stimulation. 2. Confirming previous observations, adrenal demedullation significantly attenuated diuretic responses to the kappa-opioid agonists U50488H, ethylketocyclazocine (EKC) and tifluadom, but did not affect basal urine output, furosemide-induced diuresis or the antidiuretic response to the mu-opioid agonist, buprenorphine. Naloxone abolished U50488H-induced diuresis, confirming an involvement of opioid receptors. 3. Transfusion studies established that blood, from intact rats treated with U50488H, induced diuresis in intact and demedullated recipient rats, whether or not the recipients had been pretreated with naloxone. However, blood from demedullated rats treated with U50448H was unable to induce diuresis when administered to intact or demedullated recipients. 4. It is concluded that kappa-opioid agonist-induced diuresis is dependent upon an intact and functional adrenal medulla and appears to be mediated by a blood-borne 'diuretic factor' of adrenomedullary origin. PMID:2558758

  12. Endothelium-Independent Effect of Fisetin on the Agonist-Induced Regulation of Vascular Contractility.

    Science.gov (United States)

    Je, Hyun Dong; Sohn, Uy Dong; La, Hyen-Oh

    2016-01-01

    Fisetin, a natural flavonoid found in a variety of vegetables and fruits, has been shown to possess many biological functions. The present study was undertaken to investigate the influence of fisetin on vascular smooth muscle contractility and to determine the mechanism involved. Denuded aortic rings from male rats were used and isometric contractions were recorded and combined with molecular experiments. Fisetin significantly relaxed fluoride-, thromboxane A2- or phorbol ester-induced vascular contraction suggesting as a possible anti-hypertensive on the agonist-induced vascular contraction regardless of endothelial nitric oxide synthesis. Furthermore, fisetin significantly inhibited fluoride-induced increases in pMYPT1 levels and phorbol ester-induced increases in pERK1/2 levels suggesting the mechanism involving the inhibition of Rho-kinase activity and the subsequent phosphorylation of MYPT1 and MEK activity and the subsequent phosphorylation of ERK1/2. This study provides evidence regarding the mechanism underlying the relaxation effect of fisetin on agonist-induced vascular contraction regardless of endothelial function.

  13. Cold suppresses agonist-induced activation of TRPV1.

    Science.gov (United States)

    Chung, M-K; Wang, S

    2011-09-01

    Cold therapy is frequently used to reduce pain and edema following acute injury or surgery such as tooth extraction. However, the neurobiological mechanisms of cold therapy are not completely understood. Transient receptor potential vanilloid 1 (TRPV1) is a capsaicin- and heat-gated nociceptive ion channel implicated in thermosensation and pathological pain under conditions of inflammation or injury. Although capsaicin-induced nociception, neuropeptide release, and ionic currents are suppressed by cold, it is not known if cold suppresses agonist-induced activation of recombinant TRPV1. We demonstrate that cold strongly suppressed the activation of recombinant TRPV1 by multiple agonists and capsaicin-evoked currents in trigeminal ganglia neurons under normal and phosphorylated conditions. Cold-induced suppression was partially impaired in a TRPV1 mutant that lacked heat-mediated activation and potentiation. These results suggest that cold-induced suppression of TRPV1 may share a common molecular basis with heat-induced potentiation, and that allosteric inhibition may contribute, in part, to the cold-induced suppression. We also show that combination of cold and a specific antagonist of TRPV1 can produce an additive suppression. Our results provide a mechanistic basis for cold therapy and may enhance anti-nociceptive approaches that target TRPV1 for managing pain under inflammation and tissue injury, including that from tooth extraction.

  14. Functional methods in differential equations

    CERN Document Server

    Hokkanen, Veli-Matti

    2002-01-01

    In recent years, functional methods have become central to the study of theoretical and applied mathematical problems. As demonstrated in this Research Note, functional methods can not only provide more generality, but they can also unify results and techniques and lead to better results than those obtained by classical methods. Presenting entirely original results, the authors use functional methods to explore a broad range of elliptic, parabolic, and hyperbolic boundary value problems and various classes of abstract differential and integral equations. They show that while it is crucial to choose an appropriate functional framework, this approach can lead to mathematical models that better describe concrete physical phenomena. In particular, they reach a concordance between the physical sense and the mathematical sense for the solutions of some special models. Beyond its importance as a survey of the primary techniques used in the area, the results illuminated in this volume will prove valuable in a wealth ...

  15. Approximation of continuously differentiable functions

    CERN Document Server

    Llavona, JG

    1986-01-01

    This self-contained book brings together the important results of a rapidly growing area.As a starting point it presents the classic results of the theory. The book covers such results as: the extension of Wells'' theorem and Aron''s theorem for the fine topology of order m; extension of Bernstein''s and Weierstrass'' theorems for infinite dimensional Banach spaces; extension of Nachbin''s and Whitney''s theorem for infinite dimensional Banach spaces; automatic continuity of homomorphisms in algebras of continuously differentiable functions, etc.

  16. Functional differential equations of third order

    Directory of Open Access Journals (Sweden)

    Tuncay Candan

    2005-04-01

    Full Text Available In this paper, we consider the third-order neutral functional differential equation with distributed deviating arguments. We give sufficient conditions for the oscillatory behavior of this functional differential equation.

  17. Lead exposure impairs NMDA agonist-induced no production in pyramidal hippocampal cells

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    Seyed Nasser Ostad

    2006-03-01

    Full Text Available Chronic exposure to Lead (Pb affects neural functions in central nervous system (CNS particularly the learning and memory. On the other hand, alteration of calcium level in the CNS results in activation of NOS where it is expected to increase nitric oxide level in hippocampus. In this study the role of Lead exposure in NMDA induced NO production in pyramidal hippocampal cells (CA1HP was investigated. The NO level was determined by measurement of concentration of nitrite and nitrate as NO products using the metHb production at 401 nm. The ACBD (NMDA agonist-induced NO level was almost reduced to the control level (2.5 nM in the presence of 10 and 100 nM of Lead acetate. Lead acetate at concentrations which normally results in chronic toxicity did not increase the nitric oxide (NO production by CA1HP. One reason for this finding could be the interaction of Lead with NMDA receptors due to similarity of Pb2+ to Zn2+ ion. Another reason may be related to direct interaction of Lead with NMDA receptors that inhibit the stimulated NO production.

  18. A DIFFERENTIABLE CANTOR-LIKE FUNCTION

    Institute of Scientific and Technical Information of China (English)

    DingChuansong

    1994-01-01

    the Cantor function is one of the most important and useful exaraples in real function theory. Recently there are a lot of research on differentiable Cantor-like functions, but the methods involved are not elementary. In this note a differentiable Cantor-like function was given by an elementary method.

  19. Differential dopamine function in fibromyalgia.

    Science.gov (United States)

    Albrecht, Daniel S; MacKie, Palmer J; Kareken, David A; Hutchins, Gary D; Chumin, Evgeny J; Christian, Bradley T; Yoder, Karmen K

    2016-09-01

    Approximately 30 % of Americans suffer from chronic pain disorders, such as fibromyalgia (FM), which can cause debilitating pain. Many pain-killing drugs prescribed for chronic pain disorders are highly addictive, have limited clinical efficacy, and do not treat the cognitive symptoms reported by many patients. The neurobiological substrates of chronic pain are largely unknown, but evidence points to altered dopaminergic transmission in aberrant pain perception. We sought to characterize the dopamine (DA) system in individuals with FM. Positron emission tomography (PET) with [(18)F]fallypride (FAL) was used to assess changes in DA during a working memory challenge relative to a baseline task, and to test for associations between baseline D2/D3 availability and experimental pain measures. Twelve female subjects with FM and 11 female controls completed study procedures. Subjects received one FAL PET scan while performing a "2-back" task, and one while performing a "0-back" (attentional control, "baseline") task. FM subjects had lower baseline FAL binding potential (BP) in several cortical regions relative to controls, including anterior cingulate cortex. In FM subjects, self-reported spontaneous pain negatively correlated with FAL BP in the left orbitofrontal cortex and parahippocampal gyrus. Baseline BP was significantly negatively correlated with experimental pain sensitivity and tolerance in both FM and CON subjects, although spatial patterns of these associations differed between groups. The data suggest that abnormal DA function may be associated with differential processing of pain perception in FM. Further studies are needed to explore the functional significance of DA in nociception and cognitive processing in chronic pain.

  20. The effect of gonadotropin-releasing hormone agonist-induced down-regulation on pituitary and ovarian function%促性腺激素释放激素激动剂降调对垂体内外的影响

    Institute of Scientific and Technical Information of China (English)

    朱桂金; 徐蓓; 聂睿

    2011-01-01

    catalytic subunit.40%-60% of follicle-stimulating hormone (FSH) secretion is repressed by the immediate action of downregulation,while 90% luteinizing hormone (LH) could be repressed, so downregulation is used to prevent the premature LH surges. Regulation of paracrine secretion by downregulation requires the involvement of FSH and LH and regulatory factors of paracrine secretion have no effect on the promotion of follicular development. The negative feedback of steroid hormone is through the level of hypothalamus and pituitary, while downregulation functions at the level of the gonadotropin-releasing hormone (GnRH) receptors, so the normal positive and negative feedbacks are cancelled by downregulation.There exist GnRH receptors in granulosa cells, theca cells and luteal cells, so it could be presumed theoretically that GnRH may have direct effects on ovary. Both animal experiments and in vitro studiessuggest that GnRH may have a direct action on ovarian granulosa cells through interfering steroid synthesis and follicular development. So except for preventing the premature LH surges and decreasing the detrimental effect of high LH, the effect of GnRH agonist-induced down-regulation increasing pregnancy rate may be also through the immediate action on follicular development, oocyte maturation and endometrial receptivity, but no confirmation has been made by the existing evidence.

  1. Topologies for neutral functional differential equations.

    Science.gov (United States)

    Melvin, W. R.

    1973-01-01

    Bounded topologies are considered for functional differential equations of the neutral type in which present dynamics of the system are influenced by its past behavior. A special bounded topology is generated on a collection of absolutely continuous functions with essentially bounded derivatives, and an application to a class of nonlinear neutral functional differential equations due to Driver (1965) is presented.

  2. On Theories of Superalgebras of Differentiable Functions

    NARCIS (Netherlands)

    Carchedi, D.J.; Roytenberg, D.

    2013-01-01

    This is the first in a series of papers laying the foundations for a differential graded approach to derived differential geometry (and other geometries in characteristic zero). In this paper, we study theories of supercommutative algebras for which infinitely differentiable functions can be

  3. On Theories of Superalgebras of Differentiable Functions

    NARCIS (Netherlands)

    Carchedi, D.J.; Roytenberg, D.

    2013-01-01

    This is the first in a series of papers laying the foundations for a differential graded approach to derived differential geometry (and other geometries in characteristic zero). In this paper, we study theories of supercommutative algebras for which infinitely differentiable functions can be evaluat

  4. Functional differential equations—a reciprocity principle

    Directory of Open Access Journals (Sweden)

    Lloyd K. Williams

    1986-01-01

    Full Text Available The functional differential equations proposed for solution here are mainly ordinary differential equations with fairly general argument deviations. Included among them are equations with involutions and some with reflections of the argument. Solutions will be obtained by quadratures in terms of implicitly defined functions. They have a wide range of applicability from the stability theory of differential-difference equations to electrodynamics and biological models.

  5. Differential analysis of matrix convex functions II

    DEFF Research Database (Denmark)

    Hansen, Frank; Tomiyama, Jun

    2009-01-01

    We continue the analysis in [F. Hansen, and J. Tomiyama, Differential analysis of matrix convex functions. Linear Algebra Appl., 420:102--116, 2007] of matrix convex functions of a fixed order defined in a real interval by differential methods as opposed to the characterization in terms of divide...

  6. Fractional Differentiability of Nowhere Differentiable Functions and Dimensions

    CERN Document Server

    Kolwankar, K M; Kolwankar, Kiran M.; Gangal, Anil D.

    1996-01-01

    Weierstrass's everywhere continuous but nowhere differentiable function is shown to be locally continuously fractionally differentiable everywhere for all orders below the `critical order' 2-s and not so for orders between 2-s and 1, where s, 1function. This observation is consolidated in the general result showing a direct connection between local fractional differentiability and the box dimension/ local Hölder exponent. Lévy index for one dimensional Lévy flights is shown to be the critical order of its characteristic function. Local fractional derivatives of multifractal signals (non-random functions) are shown to provide the local Hölder exponent. It is argued that Local fractional derivatives provide a powerful tool to analyze pointwise behavior of irregular signals.

  7. Lyapunov functionals and stability of stochastic functional differential equations

    CERN Document Server

    Shaikhet, Leonid

    2013-01-01

    Stability conditions for functional differential equations can be obtained using Lyapunov functionals. Lyapunov Functionals and Stability of Stochastic Functional Differential Equations describes the general method of construction of Lyapunov functionals to investigate the stability of differential equations with delays. This work continues and complements the author’s previous book Lyapunov Functionals and Stability of Stochastic Difference Equations, where this method is described for discrete- and continuous-time difference equations. The text begins with a description of the peculiarities of deterministic and stochastic functional differential equations. There follow basic definitions for stability theory of stochastic hereditary systems, and a formal procedure of Lyapunov functionals construction is presented. Stability investigation is conducted for stochastic linear and nonlinear differential equations with constant and distributed delays. The proposed method is used for stability investigation of di...

  8. Intracerebroventricular administration of kappa-agonists induces convulsions in mice.

    Science.gov (United States)

    Bansinath, M; Ramabadran, K; Turndorf, H; Shukla, V K

    1991-07-01

    Intracerebroventricular (ICV) administration of kappa-agonists (PD 117302, U-50488H and U-69593) induced convulsions in a dose-related manner in mice. The dose at which 50% of animals convulsed (CD50) was in nmol ranges for all opioids. Among the opioids used, PD 117302 was the most potent convulsant. ICV administration of either vehicle alone or U-53445E, a non-kappa-opioid (+) enantiomer of U-50488H did not induce convulsions. The convulsive response of kappa-agonists was differentially susceptible for antagonism by naloxone and/or MR 2266. Collectively, these findings support the view that convulsions induced by kappa-agonists in mice involve stereospecific opioid receptor mechanisms. Furthermore, the convulsant effect of kappa-agonists could not be modified by pretreatment with MK-801, ketamine, muscimol or baclofen. It is concluded that kappa-opioid but not NMDA or GABA receptor mechanisms are involved in convulsions induced by kappa-agonists. These results are the first experimental evidence implicating stereospecific kappa-receptor mechanisms in opioid-induced convulsions in mice.

  9. Uniqueness of meromorphic functions concerning differential polynomials

    Institute of Scientific and Technical Information of China (English)

    QIAO Lei

    2007-01-01

    Based on a unicity theorem for entire funcitions concerning differential polynomials proposed by M. L. Fang and W. Hong, we studied the uniqueness problem of two meromorphic functions whose differential polynomials share the same 1-point by proving two theorems and their related lemmas. The results extend and improve given by Fang and Hong's theorem.

  10. The Numerical Approximation of Functional Differential Equations

    CERN Document Server

    Venturi, Daniele

    2016-01-01

    The fundamental importance of functional differential equations has been recognized in many areas of mathematical physics, such as fluid dynamics (Hopf characteristic functional equations), quantum field theory (Schwinger-Dyson equations) and statistical physics (equations for generating functionals and effective action methods). However, no effective numerical method has yet been developed to compute their solution. The purpose of this manuscript is to fill this gap, and provide a new perspective on the problem of numerical approximation of nonlinear functionals and functional differential equations. The proposed methods will be described and demonstrated in various examples.

  11. Screening Test Items for Differential Item Functioning

    Science.gov (United States)

    Longford, Nicholas T.

    2014-01-01

    A method for medical screening is adapted to differential item functioning (DIF). Its essential elements are explicit declarations of the level of DIF that is acceptable and of the loss function that quantifies the consequences of the two kinds of inappropriate classification of an item. Instead of a single level and a single function, sets of…

  12. Stability analysis of impulsive functional differential equations

    CERN Document Server

    Stamova, Ivanka

    2009-01-01

    This book is devoted to impulsive functional differential equations which are a natural generalization of impulsive ordinary differential equations (without delay) and of functional differential equations (without impulses). At the present time the qualitative theory of such equationsis under rapid development. After a presentation of the fundamental theory of existence, uniqueness and continuability of solutions, a systematic development of stability theory for that class of problems is given which makes the book unique. It addresses to a wide audience such as mathematicians, applied research

  13. Function of caspase-14 in trophoblast differentiation

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    Charles Adrian K

    2009-09-01

    Full Text Available Abstract Background Within the human placenta, the cytotrophoblast consists of a proliferative pool of progenitor cells which differentiate to replenish the overlying continuous, multi-nucleated syncytiotrophoblast, which forms the barrier between the maternal and fetal tissues. Disruption to trophoblast differentiation and function may result in impaired fetal development and preeclampsia. Caspase-14 expression is limited to barrier forming tissues. It promotes keratinocyte differentiation by cleaving profilaggrin to stabilise keratin intermediate filaments, and indirectly providing hydration and UV protection. However its role in the trophoblast remains unexplored. Methods Using RNA Interference the reaction of control and differentiating trophoblastic BeWo cells to suppressed caspase-14 was examined for genes pertaining to hormonal, cell cycle and cytoskeletal pathways. Results Transcription of hCG, KLF4 and cytokeratin-18 were increased following caspase-14 suppression suggesting a role for caspase-14 in inhibiting their pathways. Furthermore, hCG, KLF4 and cytokeratin-18 protein levels were disrupted. Conclusion Since expression of these molecules is normally increased with trophoblast differentiation, our results imply that caspase-14 inhibits trophoblast differentiation. This is the first functional study of this unusual member of the caspase family in the trophoblast, where it has a different function than in the epidermis. This knowledge of the molecular underpinnings of trophoblast differentiation may instruct future therapies of trophoblast disease.

  14. Some Aspects of Production Functions Differential Geometry

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    Cătălin Angelo Ioan

    2017-04-01

    Full Text Available The article deals with some aspects of differential production functions with examples for Cobb-Douglas function in two or three variables. There are studied in each case, the conditions of the parameters in order that the sectional curvature be constant.

  15. Numerical methods for hyperbolic differential functional problems

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    Roman Ciarski

    2008-01-01

    Full Text Available The paper deals with the initial boundary value problem for quasilinear first order partial differential functional systems. A general class of difference methods for the problem is constructed. Theorems on the error estimate of approximate solutions for difference functional systems are presented. The convergence results are proved by means of consistency and stability arguments. A numerical example is given.

  16. Functional differentiation of normal human neutrophils.

    Science.gov (United States)

    Glasser, L; Fiederlein, R L

    1987-03-01

    In the past differentiation of human neutrophils has been defined by morphology, cytochemistry, or surface markers. In our experiments we have sequenced the various events that occur during the functional differentiation of the normal human neutrophil and have also examined some of the functional properties in relationship to surface markers and biochemical events. Granulocytes were obtained from the bone marrow and blood of hematologically normal individuals. Cells were separated into different stages of maturation by their physical properties using counterflow centrifugal elutriation and density gradient separation. Three cell fractions were obtained that were enriched for either immature myeloid cells, band neutrophils, or segmented neutrophils. Since the enriched fractions were not entirely pure, methodologies for functional assays were chosen that allowed cytologic evaluation of the functional capacity of each cell type. The criteria used to classify the stages of differentiation included both morphology by light microscopy and DNA labeling with tritiated thymidine. Various neutrophilic properties were studied: Fc receptors, complement receptors (CR1, CR3), phagocytosis of both live and dead opsonized Staphylococcus aureus, microbial killing of S aureus, NBT dye reduction after cellular stimulation with endotoxin, and chemotaxis. Our results indicate that the functional properties of the neutrophil appear in a distinct order. The sequence for the functional differentiation of the human neutrophil appears to be the following: Fc receptors----immune phagocytosis----complement receptors----oxygen-independent microbial killing----oxygen-dependent microbial killing----chemotaxis.

  17. Modelling with twice continuously differentiable functions

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    Sanjo Zlobec

    2014-03-01

    Full Text Available Many real life situations can be described using twice continuously differentiable functions over convex sets with interior points. Such functions have an interesting separation property: At every interior point of the set they separate particular classes of quadratic convex functions from classes of quadratic concave functions. Using this property we introduce new characterizations of the derivative and its zero points. The results are applied to the study of sensitivity of the Cobb-Douglas production function. They are also used to describe the least squares solutions in linear and nonlinear regression.

  18. Asymptotic analysis for functional stochastic differential equations

    CERN Document Server

    Bao, Jianhai; Yuan, Chenggui

    2016-01-01

    This brief treats dynamical systems that involve delays and random disturbances. The study is motivated by a wide variety of systems in real life in which random noise has to be taken into consideration and the effect of delays cannot be ignored. Concentrating on such systems that are described by functional stochastic differential equations, this work focuses on the study of large time behavior, in particular, ergodicity. This brief is written for probabilists, applied mathematicians, engineers, and scientists who need to use delay systems and functional stochastic differential equations in their work. Selected topics from the brief can also be used in a graduate level topics course in probability and stochastic processes.

  19. Pseudo-differential operators and generalized functions

    CERN Document Server

    Toft, Joachim

    2015-01-01

    This book gathers peer-reviewed contributions representing modern trends in the theory of generalized functions and pseudo-differential operators. It is dedicated to Professor Michael Oberguggenberger (Innsbruck University, Austria) in honour of his 60th birthday. The topics covered were suggested by the ISAAC Group in Generalized Functions (GF) and the ISAAC Group in Pseudo-Differential Operators (IGPDO), which met at the 9th ISAAC congress in Krakow, Poland in August 2013. Topics include Columbeau algebras, ultra-distributions, partial differential equations, micro-local analysis, harmonic analysis, global analysis, geometry, quantization, mathematical physics, and time-frequency analysis. Featuring both essays and research articles, the book will be of great interest to graduate students and researchers working in analysis, PDE and mathematical physics, while also offering a valuable complement to the volumes on this topic previously published in the OT series.

  20. Convex functions, monotone operators and differentiability

    CERN Document Server

    Phelps, Robert R

    1993-01-01

    The improved and expanded second edition contains expositions of some major results which have been obtained in the years since the 1st edition. Theaffirmative answer by Preiss of the decades old question of whether a Banachspace with an equivalent Gateaux differentiable norm is a weak Asplund space. The startlingly simple proof by Simons of Rockafellar's fundamental maximal monotonicity theorem for subdifferentials of convex functions. The exciting new version of the useful Borwein-Preiss smooth variational principle due to Godefroy, Deville and Zizler. The material is accessible to students who have had a course in Functional Analysis; indeed, the first edition has been used in numerous graduate seminars. Starting with convex functions on the line, it leads to interconnected topics in convexity, differentiability and subdifferentiability of convex functions in Banach spaces, generic continuity of monotone operators, geometry of Banach spaces and the Radon-Nikodym property, convex analysis, variational princ...

  1. Efficient Estimating Functions for Stochastic Differential Equations

    DEFF Research Database (Denmark)

    Jakobsen, Nina Munkholt

    The overall topic of this thesis is approximate martingale estimating function-based estimationfor solutions of stochastic differential equations, sampled at high frequency. Focuslies on the asymptotic properties of the estimators. The first part of the thesis deals with diffusions observed over...

  2. Differential Testlet Functioning: Definitions and Detection.

    Science.gov (United States)

    Wainer, Howard; And Others

    1991-01-01

    A testlet is an integrated group of test items presented as a unit. The concept of testlet differential item functioning (testlet DIF) is defined, and a statistical method is presented to detect testlet DIF. Data from a testlet-based experimental version of the Scholastic Aptitude Test illustrate the methodology. (SLD)

  3. Estimating the Importance of Differential Item Functioning.

    Science.gov (United States)

    Rudas, Tamas; Zwick, Rebecca

    1997-01-01

    The mixture index of fit (T. Rudas et al, 1994) is used to estimate the fraction of a population for which differential item functioning (DIF) occurs, and this approach is compared to the Mantel Haenszel test of DIF. The proposed noniterative procedure provides information about data portions contributing to DIF. (SLD)

  4. Differential analysis of matrix convex functions

    DEFF Research Database (Denmark)

    Hansen, Frank; Tomiyama, Jun

    2007-01-01

    We analyze matrix convex functions of a fixed order defined in a real interval by differential methods as opposed to the characterization in terms of divided differences given by Kraus [F. Kraus, Über konvekse Matrixfunktionen, Math. Z. 41 (1936) 18-42]. We obtain for each order conditions for ma...

  5. Real and Artificial Differential Item Functioning

    Science.gov (United States)

    Andrich, David; Hagquist, Curt

    2012-01-01

    The literature in modern test theory on procedures for identifying items with differential item functioning (DIF) among two groups of persons includes the Mantel-Haenszel (MH) procedure. Generally, it is not recognized explicitly that if there is real DIF in some items which favor one group, then as an artifact of this procedure, artificial DIF…

  6. Estimating the Importance of Differential Item Functioning.

    Science.gov (United States)

    Rudas, Tamas; Zwick, Rebecca

    1997-01-01

    The mixture index of fit (T. Rudas et al, 1994) is used to estimate the fraction of a population for which differential item functioning (DIF) occurs, and this approach is compared to the Mantel Haenszel test of DIF. The proposed noniterative procedure provides information about data portions contributing to DIF. (SLD)

  7. Agonist-induced hump current production in heterologously-expressed human α4β2-nicotinic acetylcholine receptors

    Institute of Scientific and Technical Information of China (English)

    Qiang LIE; Ke-wei YU; Yong-chang CHANG; Ronald J LUKAS; Jie WU

    2008-01-01

    Aim:To characterize the functional and pharmacological features of agonist-induced hump currents in human α4β2-nicotinic acetylcholine receptors (nAChR).Methods:Whole-cell and outside-out patch recordings were performed using human α4β2-nAChR heterologously expressed in stably-transfected,native nAChR-null subclonal human epithelial 1 (SH-EP1) cells.RT-PCR was used to test the mRNA expression of transfected nAChR.Homology modeling and ace-tylcholine (Ach) docking were applied to show the possible Ach-binding site in the channel pore.Results:The rapid exposure of 10 mmol/L Ach induced an inward current with a decline from peak to steady-state.However,after the re-moval of Ach,an additional inward current,called "hump" current,reoccurred.The ability of agonists to produce these hump currents cannot be easily explained based on drug size,charge,acute potency,or actions as full or partial agonists.Hump currents were associated with a rebound increase in whole-cell conductance,and they had voltage dependence-like peak currents induced by agonist action.Hump currents blocked by the α4β2-nAChR antagonist dihydro-β-erythroidine were reduced when α4β2-nAChR were desensitized,and were more pronounced in the absence of external Ca2+.Outside-out single-channel recordings demon-strated that compared to 1 μmol/L nicotine,100 μmol/L nicotine reduced channel current amplitude,shortened the channel mean open time,and prolonged the channel mean closed time,supporting an agonist-induced open-channel block before hump current production.A docking model also simulated the agonist-binding site in the channel pore.Conclusion:These results support the hypoth-esis that hump currents reflect a rapid release of agonists from the α4β2-nAChR channel pore and a rapid recovery from desensitized α4β2-nAChR.

  8. Mildly oxidized HDL decrease agonist-induced platelet aggregation and release of pro-coagulant platelet extracellular vesicles.

    Science.gov (United States)

    Tafelmeier, M; Fischer, A; Orsó, E; Konovalova, T; Böttcher, A; Liebisch, G; Matysik, S; Schmitz, G

    2017-05-01

    Stored platelet concentrates (PLCs) for therapeutic purpose, develop a platelet storage lesion (PSL), characterized by impaired platelet (PLT) viability and function, platelet extracellular vesicle (PL-EV) release and profound lipidomic changes. Whereas oxidized low-density lipoprotein (oxLDL) activates PLTs and promotes atherosclerosis, effects linked to oxidized high-density lipoprotein (oxHDL) are poorly characterized. PLCs from blood donors were treated with native (nHDL) or mildly oxidized HDL (moxHDL) for 5days under blood banking conditions. Flow cytometry, nanoparticle tracking analysis (NTA), aggregometry, immunoblot analysis and mass spectrometry were carried out to analyze PL-EV and platelet exosomes (PL-EX) release, PLT aggregation, protein expression, and PLT and plasma lipid composition. In comparison to total nHDL, moxHDL significantly decreased PL-EV release by -36% after 5days of PLT storage and partially reversed agonist-induced PLT aggregation. PL-EV release positively correlated with PLT aggregation. MoxHDL improved PLT membrane lipid homeostasis through enhanced uptake of lysophospholipids and their remodeling to corresponding phospholipid species. This also appeared for sphingomyelin (SM) and d18:0/d18:1 sphingosine-1-phosphate (S1P) at the expense of ceramide (Cer) and hexosylceramide (HexCer) leading to reduced Cer/S1P ratio as PLT-viability indicator. This membrane remodeling was associated with increased content of CD36 and maturation of scavenger receptor-B1 (SR-B1) protein in secreted PL-EVs. MoxHDL, more potently than nHDL, improves PLT-membrane lipid homeostasis, partially antagonizes PL-EV release and agonist-induced PLT aggregation. Altogether, this may be the result of more efficient phospho- and sphingolipid remodeling mediated by CD36 and SR-B1 in the absence of ABCA1 on PLTs. As in vitro supplement in PLCs, moxHDL has the potential to improve PLC quality and to prolong storage. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Monotone viable trajectories for functional differential inclusions

    Science.gov (United States)

    Haddad, Georges

    This paper is a study on functional differential inclusions with memory which represent the multivalued version of retarded functional differential equations. The main result gives a necessary and sufficient equations. The main result gives a necessary and sufficient condition ensuring the existence of viable trajectories; that means trajectories remaining in a given nonempty closed convex set defined by given constraints the system must satisfy to be viable. Some motivations for this paper can be found in control theory where F( t, φ) = { f( t, φ, u)} uɛU is the set of possible velocities of the system at time t, depending on the past history represented by the function φ and on a control u ranging over a set U of controls. Other motivations can be found in planning procedures in microeconomics and in biological evolutions where problems with memory do effectively appear in a multivalued version. All these models require viability constraints represented by a closed convex set.

  10. ASYMPTOTIC STABILITIES OF STOCHASTIC FUNCTIONAL DIFFERENTIAL EQUATIONS

    Institute of Scientific and Technical Information of China (English)

    SHEN Yi; JIANG Ming-hui; LIAO Xiao-xin

    2006-01-01

    Asymptotic characteristic of solution of the stochastic functional differential equation was discussed and sufficient condition was established by multiple Lyapunov functions for locating the limit set of t he solution. Moreover, from them many effective criteria on stochastic asymptotic stability, which enable us to construct the Lyapunov functions much more easily in application, were obtained. The results show that the wellknown classical theorem on stochastic asymptotic stability is a special case of our more general results. In the end, application in stochastic Hopfield neural networks is given to verify our results.

  11. Detecting Differential Item Functioning and Differential Test Functioning on Math School Final-exam

    Directory of Open Access Journals (Sweden)

    - Mansyur

    2016-08-01

    Full Text Available This study aims at finding out the characteristics of Differential Item Functioning (DIF and Differential Test Functioning (DTF on school final-exam for Math subject based on Item Response Theory (ITR. The subjects of this study were questions and all of the students’ answer sheets chosen by using convenience sampling method and obtained 286 responses consisted of 147 male and 149 female students’ responses. The data of this study collected using documentation technique by quoting the response of Math school final-exam participants. The data analysis of this study was Item Response Theory approach with model 2P of Lord’s chi-square DIF method. This study showed that from 40 question items analysed theoretically using Item Response Theory (ITR, affected Differential Item Functioning (DIF gender was ten items and affected DIF location (area was 13 items. Meanwhile, Differential Test Functioning (DTF was benefitted for female and least profitable to citizen.

  12. Tau function and moduli of differentials

    CERN Document Server

    Korotkin, Dmitry

    2010-01-01

    The tau function on the moduli space of generic holomorphic 1-differentials on complex algebraic curves is interpreted as a section of a line bundle on the projectivized Hodge bundle over the moduli space of stable curves. The asymptotics of the tau function near the boundary of the moduli space of 1-differentials is computed, and an explicit expression for the pullback of the Hodge class on the projectivized Hodge bundle in terms of the tautological class and the classes of boundary divisors is derived. This expression is used to clarify the geometric meaning of the Kontsevich-Zorich formula for the sum of the Lyapunov exponents associated with the Teichm\\"uller flow on the Hodge bundle.

  13. Detecting Differential Item Functioning and Differential Test Functioning on Math School Final-exam

    OpenAIRE

    - Mansyur; - Muliana

    2016-01-01

    This study aims at finding out the characteristics of Differential Item Functioning (DIF) and Differential Test Functioning (DTF) on school final-exam for Math subject based on Item Response Theory (ITR). The subjects of this study were questions and all of the students’ answer sheets chosen by using convenience sampling method and obtained 286 responses consisted of 147 male and 149 female students’ responses. The data of this study collected using documentation technique by quoting the resp...

  14. Stochastic Functional Differential Equation under Regime Switching

    Directory of Open Access Journals (Sweden)

    Ling Bai

    2012-01-01

    Full Text Available We discuss stochastic functional differential equation under regime switching dx(t=f(xt,r(t,tdt+q(r(tx(tdW1(t+σ(r(t|x(t|βx(tdW2(t. We obtain unique global solution of this system without the linear growth condition; furthermore, we prove its asymptotic ultimate boundedness. Using the ergodic property of the Markov chain, we give the sufficient condition of almost surely exponentially stable of this system.

  15. Real meromorphic functions and linear differential polynomials

    Institute of Scientific and Technical Information of China (English)

    LANGLEY; J.; K.

    2010-01-01

    We determine all real meromorphic functions f in the plane such that f has finitely many zeros, the poles of f have bounded multiplicities, and f and F have finitely many non-real zeros, where F is a linear differential polynomial given by F = f (k) +Σk-1j=0ajf(j) , in which k≥2 and the coefficients aj are real numbers with a0≠0.

  16. Synchronization with propagation - The functional differential equations

    Science.gov (United States)

    Rǎsvan, Vladimir

    2016-06-01

    The structure represented by one or several oscillators couple to a one-dimensional transmission environment (e.g. a vibrating string in the mechanical case or a lossless transmission line in the electrical case) turned to be attractive for the research in the field of complex structures and/or complex behavior. This is due to the fact that such a structure represents some generalization of various interconnection modes with lumped parameters for the oscillators. On the other hand the lossless and distortionless propagation along transmission lines has generated several research in electrical, thermal, hydro and control engineering leading to the association of some functional differential equations to the basic initial boundary value problems. The present research is performed at the crossroad of the aforementioned directions. We shall associate to the starting models some functional differential equations - in most cases of neutral type - and make use of the general theorems for existence and stability of forced oscillations for functional differential equations. The challenges introduced by the analyzed problems for the general theory are emphasized, together with the implication of the results for various applications.

  17. Agonist-induced internalisation of the glucagon-like peptide-1 receptor is mediated by the Gαq pathway.

    Science.gov (United States)

    Thompson, Aiysha; Kanamarlapudi, Venkateswarlu

    2015-01-01

    The glucagon-like peptide-1 receptor (GLP-1R) is a G-protein-coupled receptor (GPCR) and an important target in the treatment of type 2 diabetes mellitus (T2DM). Upon stimulation with agonist, the GLP-1R signals through both Gαs and Gαq coupled pathways to stimulate insulin secretion. The agonist-induced GLP-1R internalisation has recently been shown to be important for insulin secretion. However, the molecular mechanisms underlying GLP-1R internalisation remain unknown. The aim of this study was to determine the role of GLP-1R downstream signalling pathways in its internalisation. Agonist-induced human GLP-1R (hGLP-1R) internalisation and activity were examined using a number of techniques including immunoblotting, ELISA, immunofluorescence and luciferase assays to determine cAMP production, intracellular Ca(2+) accumulation and ERK phosphorylation. Agonist-induced hGLP-1R internalisation is dependent on caveolin-1 and dynamin. Inhibition of the Gαq pathway but not the Gαs pathway affected hGLP-1R internalisation. Consistent with this, hGLP-1R mutant T149M and small-molecule agonists (compound 2 and compound B), which activate only the Gαs pathway, failed to induce internalisation of the receptor. Chemical inhibitors of the Gαq pathway, PKC and ERK phosphorylation significantly reduced agonist-induced hGLP-1R internalisation. These inhibitors also suppressed agonist-induced ERK1/2 phosphorylation demonstrating that the phosphorylated ERK acts downstream of the Gαq pathway in the hGLP-1R internalisation. In summary, agonist-induced hGLP-1R internalisation is mediated by the Gαq pathway. The internalised hGLP-1R stimulates insulin secretion from pancreatic β-cells, indicating the importance of GLP-1 internalisation for insulin secretion.

  18. Generalized functions and partial differential equations

    CERN Document Server

    Friedman, Avner

    2005-01-01

    This self-contained treatment develops the theory of generalized functions and the theory of distributions, and it systematically applies them to solving a variety of problems in partial differential equations. A major portion of the text is based on material included in the books of L. Schwartz, who developed the theory of distributions, and in the books of Gelfand and Shilov, who deal with generalized functions of any class and their use in solving the Cauchy problem. In addition, the author provides applications developed through his own research.Geared toward upper-level undergraduates and

  19. DIFFERENTIAL SUBORDINATIONS AND α-CONVEX FUNCTIONS

    Institute of Scientific and Technical Information of China (English)

    Jacek DZIOK; Ravinder Krishna RAINA; Janusz SOK(O)L

    2013-01-01

    This article presents some new results on the class SLMα of functions that are analytic in the open unit discu ={z:[z[< 1} satisfying the conditions that f(0)=0,f'(0)=1,and α (1+ zf"(z)/f'(z)) + (1-α)zf'(z)/f(x) ∈(p)(u)for all z ∈ u,where α is a real number and (p)(z) =1 + τ2z2/ 1-τz-τ2z2 (z ∈ u).The number τ =(1-√5)/2 is such that τ2 =1 + T.The class SLMα introduced by J.Dziok,R.K.Raina,and J.Sokól [3,Appl.Math.Comput.218 (2011),996-1002] is closely related to the classes of starlike and convex functions.The article deals with several ideas and techniques used in geometric function theory and differential subordinations theory.

  20. Functional myelographic differentiation of lumbar bulging annulus

    Energy Technology Data Exchange (ETDEWEB)

    Park, Choong Ki; Kim, Hong Kil; Park, Sang Gyu; Lee, Young Jung; Yoon, Jong Sup [Hallym University College of Medicine, Seoul (Korea, Republic of)

    1988-08-15

    Herniated disk and bulging annulus are the major causes of lower back pain. It is necessary to differentiate bulging annulus from herniated disk because of their different methods of treatment. Myelography is one of the useful diagnostic methods for disk diseases even though advanced diagnostic modalities such as CT and MRI are more accurate. Functional myelography is not a new technology expect for two additional views, flexion and extension, are obtained with conventional myelography. Differentiation between bulging annulus and herniated disk by conventional myelography is based on the extent and multiplicity of extradural deformity of the contrast filled dural sac and neural sleeve as well as the changes of nerve root. There is no previous report about differential points between bulging annulus and herniated disk according to functional myelography. It is the purpose of this study to find any additional differential points on functional myelography between bulging annulus and herniated disk over convectional myelography. Authors analysed functional myelographic findings of 152 cases from July 1986 to July 1987. Among them, 22 cases who had been suffered from cervical abnormality or vague lower back pain were diagnosed as normal by myelography, and 30 cases of L4-5 herniated disk and 21 cases of L4-5 bulging annulus which had been finally diagnosed by operation were studied. The results were as follows. 1. In normal group, anterior epidural space was gradually widened from the upper lumbar vertebra downward. And anterior epidural space was more sidened at the disk level in extension view than in flexion except for L5-S1 lever. 2. In bulging annulus group, the shape of anterior epidural space in flexion state was as similar as normal. Anoterior epidural space in extension state was more sidened at the buldging annulus than normal, but lesser than herniated disk. 3. In herniated disk group, widening of anterior epidural space at the herniated disk level was

  1. β2-Agonist induced cAMP is decreased in asthmatic airway smooth muscle due to increased PDE4D

    NARCIS (Netherlands)

    Trian, Thomas; Burgess, Janette K; Niimi, Kyoko; Moir, Lyn M; Ge, Qi; Berger, Patrick; Liggett, Stephen B; Black, Judith L; Oliver, Brian G

    2011-01-01

    BACKGROUND AND OBJECTIVE: Asthma is associated with airway narrowing in response to bronchoconstricting stimuli and increased airway smooth muscle (ASM) mass. In addition, some studies have suggested impaired β-agonist induced ASM relaxation in asthmatics, but the mechanism is not known. OBJECTIVE:

  2. Convex functions, monotone operators and differentiability

    CERN Document Server

    Phelps, Robert R

    1989-01-01

    These notes start with an introduction to the differentiability of convex functions on Banach spaces, leading to the study of Asplund spaces and their intriguing relationship to monotone operators (and more general set-values maps) and Banach spaces with the Radon-Nikodym property. While much of this is classical, some of it is presented using streamlined proofs which were not available until recently. Considerable attention is paid to contemporary results on variational principles and perturbed optimization in Banach spaces, exhibiting their close connections with Asplund spaces. An introductory course in functional analysis is adequate background for reading these notes which can serve as the basis for a seminar of a one-term graduate course. There are numerous excercises, many of which form an integral part of the exposition.

  3. Generalized Solutions of Functional Differential Inclusions

    Directory of Open Access Journals (Sweden)

    Anna Machina

    2008-01-01

    Full Text Available We consider the initial value problem for a functional differential inclusion with a Volterra multivalued mapping that is not necessarily decomposable in L1n[a,b]. The concept of the decomposable hull of a set is introduced. Using this concept, we define a generalized solution of such a problem and study its properties. We have proven that standard results on local existence and continuation of a generalized solution remain true. The question on the estimation of a generalized solution with respect to a given absolutely continuous function is studied. The density principle is proven for the generalized solutions. Asymptotic properties of the set of generalized approximate solutions are studied.

  4. Effects of deoxycholylglycine, a conjugated secondary bile acid, on myogenic tone and agonist-induced contraction in rat resistance arteries.

    Directory of Open Access Journals (Sweden)

    Sandeep Khurana

    Full Text Available BACKGROUND: Bile acids (BAs regulate cardiovascular function via diverse mechanisms. Although in both health and disease serum glycine-conjugated BAs are more abundant than taurine-conjugated BAs, their effects on myogenic tone (MT, a key determinant of systemic vascular resistance (SVR, have not been examined. METHODOLOGY/PRINCIPAL FINDINGS: Fourth-order mesenteric arteries (170-250 µm isolated from Sprague-Dawley rats were pressurized at 70 mmHg and allowed to develop spontaneous constriction, i.e., MT. Deoxycholylglycine (DCG; 0.1-100 µM, a glycine-conjugated major secondary BA, induced reversible, concentration-dependent reduction of MT that was similar in endothelium-intact and -denuded arteries. DCG reduced the myogenic response to stepwise increase in pressure (20 to 100 mmHg. Neither atropine nor the combination of L-NAME (a NOS inhibitor plus indomethacin altered DCG-mediated reduction of MT. K(+ channel blockade with glibenclamide (K(ATP, 4-aminopyradine (K(V, BaCl(2 (K(IR or tetraethylammonium (TEA, K(Ca were also ineffective. In Fluo-2-loaded arteries, DCG markedly reduced vascular smooth muscle cell (VSM Ca(2+ fluorescence (∼50%. In arteries incubated with DCG, physiological salt solution (PSS with high Ca(2+ (4 mM restored myogenic response. DCG reduced vascular tone and VSM cytoplasmic Ca(2+ responses (∼50% of phenylephrine (PE- and Ang II-treated arteries, but did not affect KCl-induced vasoconstriction. CONCLUSION: In rat mesenteric resistance arteries DCG reduces pressure- and agonist-induced vasoconstriction and VSM cytoplasmic Ca(2+ responses, independent of muscarinic receptor, NO or K(+ channel activation. We conclude that BAs alter vasomotor responses, an effect favoring reduced SVR. These findings are likely pertinent to vascular dysfunction in cirrhosis and other conditions associated with elevated serum BAs.

  5. Distinguishing Differential Testlet Functioning from Differential Bundle Functioning Using the Multilevel Measurement Model

    Science.gov (United States)

    Beretvas, S. Natasha; Walker, Cindy M.

    2012-01-01

    This study extends the multilevel measurement model to handle testlet-based dependencies. A flexible two-level testlet response model (the MMMT-2 model) for dichotomous items is introduced that permits assessment of differential testlet functioning (DTLF). A distinction is made between this study's conceptualization of DTLF and that of…

  6. Stability and Control of Functional Differential Equations

    CERN Document Server

    Peet, M M

    2006-01-01

    This thesis addresses the question of stability of systems defined by differential equations which contain nonlinearity and delay. In particular, we analyze the stability of a well-known delayed nonlinear implementation of a certain Internet congestion control protocol. We also describe a generalized methodology for proving stability of time-delay systems through the use of semidefinite programming. In Chapters 4 and 5, we consider an Internet congestion control protocol based on the decentralized gradient projection algorithm. For a certain class of utility function, this algorithm was shown to be globally convergent for some sufficiently small value of a gain parameter. Later work gave an explicit bound on this gain for a linearized version of the system. This thesis proves that this bound also implies stability of the original system. In Chapter 7, we describe a general methodology for proving stability of linear time-delay systems by computing solutions to an operator-theoretic version of the Lyapunov ine...

  7. Linear measure functional differential equations with infinite delay

    OpenAIRE

    Monteiro, G.; Slavík, A.

    2014-01-01

    We use the theory of generalized linear ordinary differential equations in Banach spaces to study linear measure functional differential equations with infinite delay. We obtain new results concerning the existence, uniqueness, and continuous dependence of solutions. Even for equations with a finite delay, our results are stronger than the existing ones. Finally, we present an application to functional differential equations with impulses.

  8. Dose-dependent effects of celecoxib on CB-1 agonist-induced antinociception in the mice

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Zarrindast

    2009-04-01

    Full Text Available "nObjective: Endocannabinoid produce analgesia that is comparable which of opioids. The mechanism of antinociceptive effects of (∆ - 9 tetrahydrocannabinol (THC is suggested to be through cyclooxygenase (COX pathway. In the present work, the effect of two extreme dose ranges of celecoxib (mg/kg and ng/kg, a cyclooxygenase-2 (COX-2 antagonist, on arachidonylcyclopropylamide (ACPA, a selective CB1 agonist induced antinociception in mice was examined. "nMethods: We have investigated the interaction between celecoxib, at the doses of mg/kg (50, 100, 200 and 400 i.p.  and ultra low dose (ULD (25 and 50 ng/kg, i.p., on the antinociceptive effect of intracerebroventricular (i.c.v. administration of ACPA (0.004, 0.0625 and 1 μg/mice, using formalin test in mice. "nResults: I.C.V. administration of ACPA induced antinociception. Intraperitoneal administration of celecoxib (mg/kg and its ULD (ng/kg attenuated and potentiated, ACPA antinociceptive effects, respectively. "nConclusion: It is concluded that the mg/kg doses of COX-2 antagonist showed opposite effects compare to the ultra-low dose of the drug.

  9. C-terminal of human histamine H1 receptors regulates their agonist-induced clathrin-mediated internalization and G-protein signaling.

    Science.gov (United States)

    Hishinuma, Shigeru; Nozawa, Hiroki; Akatsu, Chizuru; Shoji, Masaru

    2016-11-01

    It has been suggested that the agonist-induced internalization of G-protein-coupled receptors from the cell surface into intracellular compartments regulates cellular responsiveness. We previously reported that Gq/11 -protein-coupled human histamine H1 receptors internalized via clathrin-dependent mechanisms upon stimulation with histamine. However, the molecular determinants of H1 receptors responsible for agonist-induced internalization remain unclear. In this study, we evaluated the roles of the intracellular C-terminal of human histamine H1 receptors tagged with hemagglutinin (HA) at the N-terminal in histamine-induced internalization in Chinese hamster ovary cells. The histamine-induced internalization was evaluated by the receptor binding assay with [(3) H]mepyramine and confocal immunofluorescence microscopy with an anti-HA antibody. We found that histamine-induced internalization was inhibited under hypertonic conditions or by pitstop, a clathrin terminal domain inhibitor, but not by filipin or nystatin, disruptors of the caveolar structure and function. The histamine-induced internalization was also inhibited by truncation of a single amino acid, Ser487, located at the end of the intracellular C-terminal of H1 receptors, but not by its mutation to alanine. In contrast, the receptor-G-protein coupling, which was evaluated by histamine-induced accumulation of [(3) H]inositol phosphates, was potentiated by truncation of Ser487, but was lost by its mutation to alanine. These results suggest that the intracellular C-terminal of human H1 receptors, which only comprises 17 amino acids (Cys471-Ser487), plays crucial roles in both clathrin-dependent internalization of H1 receptors and G-protein signaling, in which truncation of Ser487 and its mutation to alanine are revealed to result in biased signaling toward activation of G-proteins and clathrin-mediated internalization, respectively.

  10. Oscillation of third order functional differential equations with delay

    Directory of Open Access Journals (Sweden)

    Tuncay Candan

    2003-02-01

    Full Text Available We consider third order functional differential equations with discrete and continuous delay. We then develop several theorems related to the oscillatory behavior of these differential equations.

  11. RAZUMIKHIN-TYPE THEOREMS OF NEUTRAL STOCHASTIC FUNCTIONAL DIFFERENTIAL EQUATIONS

    Institute of Scientific and Technical Information of China (English)

    Zhou Shaobo; Hu Shigeng

    2009-01-01

    The stability of stochastic functional differential equation with Markovian switching was studied by several authors, but there was almost no work on the stability of the neutral stochastic functional differential equations with Markovian switching. The aim of this article is to close this gap. The authors establish Razumikhin-type theorem of the neutral stochastic functional differential equations with Markovian switching, and those without Markovian switching.

  12. nor-BNI Antagonism of Kappa Opioid Agonist-Induced Reinstatement of Ethanol-Seeking Behavior

    Directory of Open Access Journals (Sweden)

    Erin Harshberger

    2016-01-01

    Full Text Available Recent work suggests that the dynorphin (DYN/kappa opioid receptor (KOR system may be a key mediator in the behavioral effects of alcohol. The objective of the present study was to examine the ability of the KOR antagonist norbinaltorphimine (nor-BNI to attenuate relapse to ethanol seeking due to priming injections of the KOR agonist U50,488 at time points consistent with KOR selectivity. Male Wistar rats were trained to self-administer a 10% ethanol solution, and then responding was extinguished. Following extinction, rats were injected with U50,488 (0.1–10 mg/kg, i.p. or saline and were tested for the reinstatement of ethanol seeking. Next, the ability of the nonselective opioid receptor antagonist naltrexone (0 or 3.0 mg/kg, s.c. and nor-BNI (0 or 20.0 mg/kg, i.p. to block U50,488-induced reinstatement was examined. Priming injections U50,488 reinstated responding on the previously ethanol-associated lever. Pretreatment with naltrexone reduced the reinstatement of ethanol-seeking behavior. nor-BNI also attenuated KOR agonist-induced reinstatement, but to a lesser extent than naltrexone, when injected 24 hours prior to injections of U50,488, a time point that is consistent with KOR selectivity. While these results suggest that activation of KORs is a key mechanism in the regulation of ethanol-seeking behavior, U50,488-induced reinstatement may not be fully selective for KORs.

  13. Effects of intracellular alkalinization on resting and agonist-induced vascular tone.

    Science.gov (United States)

    Danthuluri, N R; Deth, R C

    1989-03-01

    To evaluate the influence of intracellular alkalinization on basal and agonist-induced vascular tone, we studied the effect of NH4Cl on rat aorta. NH4Cl induced a gradually developing contraction in a dose-dependent manner. Although the contractile response to 20 mM NH4Cl was associated with a latent period (LP) of 23.4 +/- 2.8 min, intracellular pH (pHi) measurements in cultured rat aortic smooth muscle cells showed that NH4Cl-induced intracellular alkalinization was immediate and transient, returning to basal pHi levels in about 30-35 min. Agents that elevate Ca2+, such as A23187 and high KCl, significantly reduced the LP associated with 20 mM NH4Cl-induced contraction. NH4Cl-induced contractions were sensitive to extracellular Ca2+ removal and to the addition of forskolin (1 microM); however, NH4Cl by itself did not cause Ca2+-influx as shown by 45Ca-uptake studies. Addition of 20 mM NH4Cl to precontracted tissues resulted in a transient relaxation, which was complete in approximately 10 min, followed by a contraction above the original level of tone. NH4Cl pretreatment caused time-dependent alterations in both the rapid and slow phases of phenylephrine and angiotensin II contractions. Rapid-phase of phenylephrine and angiotensin II contractions. Rapid-phase responses were diminished at shorter NH4Cl incubation times (10 min), whereas slow-phase response was augmented after a longer incubation (20 min). Overall, the vasorelaxant and vasoconstrictor effects induced by NH4Cl suggest a complex relationship between intracellular alkalinization and arterial contractility.

  14. Adenosine-A1 receptor agonist induced hyperalgesic priming type II.

    Science.gov (United States)

    Araldi, Dioneia; Ferrari, Luiz F; Levine, Jon D

    2016-03-01

    We have recently shown that repeated exposure of the peripheral terminal of the primary afferent nociceptor to the mu-opioid receptor (MOR) agonist DAMGO ([D-Ala, N-Me-Phe, Gly-ol]-enkephalin acetate salt) induces a model of transition to chronic pain that we have termed type II hyperalgesic priming. Similar to type I hyperalgesic priming, there is a markedly prolonged response to subsequent administration of proalgesic cytokines, prototypically prostaglandin E2 (PGE2). However, type II hyperalgesic priming differs from type I in being rapidly induced, protein kinase A (PKA), rather than PKCε dependent, not reversed by a protein translation inhibitor, occurring in female as well as in male rats, and isolectin B4-negative neuron dependent. We report that, as with the repeated injection of a MOR agonist, the repeated administration of an agonist at the A1-adenosine receptor, also a Gi-protein coupled receptor, N-cyclopentyladenosine (CPA), also produces priming similar to DAMGO-induced type II hyperalgesic priming. In this study, we demonstrate that priming induced by repeated exposure to this A1-adenosine receptor agonist shares the same mechanisms, as MOR-agonist induced priming. However, the prolongation of PGE2 hyperalgesia induced by repeated administration of CPA depends on G-protein αi subunit activation, differently from DAMGO-induced type II priming, in which it depends on the β/γ subunit. These data implicate a novel form of Gi-protein signaling pathway in the type II hyperalgesic priming induced by repeated administration of an agonist at A1-adenosine receptor to the peripheral terminal of the nociceptor.

  15. STING agonists induce an innate antiviral immune response against hepatitis B virus.

    Science.gov (United States)

    Guo, Fang; Han, Yanxing; Zhao, Xuesen; Wang, Jianghua; Liu, Fei; Xu, Chunxiao; Wei, Lai; Jiang, Jian-Dong; Block, Timothy M; Guo, Ju-Tao; Chang, Jinhong

    2015-02-01

    Chronicity of hepatitis B virus (HBV) infection is due to the failure of a host to mount a sufficient immune response to clear the virus. The aim of this study was to identify small-molecular agonists of the pattern recognition receptor (PRR)-mediated innate immune response to control HBV infection. To achieve this goal, a coupled mouse macrophage and hepatocyte culture system mimicking the intrahepatic environment was established and used to screen small-molecular compounds that activate macrophages to produce cytokines, which in turn suppress HBV replication in a hepatocyte-derived stable cell line supporting HBV replication in a tetracycline-inducible manner. An agonist of the mouse stimulator of interferon (IFN) genes (STING), 5,6-dimethylxanthenone-4-acetic acid (DMXAA), was found to induce a robust cytokine response in macrophages that efficiently suppressed HBV replication in mouse hepatocytes by reducing the amount of cytoplasmic viral nucleocapsids. Profiling of cytokines induced by DMXAA and agonists of representative Toll-like receptors (TLRs) in mouse macrophages revealed that, unlike TLR agonists that induced a predominant inflammatory cytokine/chemokine response, the STING agonist induced a cytokine response dominated by type I IFNs. Moreover, as demonstrated in an HBV hydrodynamic mouse model, intraperitoneal administration of DMXAA significantly induced the expression of IFN-stimulated genes and reduced HBV DNA replication intermediates in the livers of mice. This study thus proves the concept that activation of the STING pathway induces an antiviral cytokine response against HBV and that the development of small-molecular human STING agonists as immunotherapeutic agents for treatment of chronic hepatitis B is warranted.

  16. Monotone Semiflows Generated by Functional Differential Equations,

    Science.gov (United States)

    1986-02-01

    These results have been applied to ordinary differential equations in Rn (see e.g. [10,23]) where the well-known Kamke theorem applies and to nonlinear...sufficient condition (H) Whenever 0 - 0 and ,i(0) = i( 0) it follows that fi(0) ( fi(O). For those familiar with the Kamke (quasimonotone) condition for...ordinary differential equations, (H) will seem quite natural, it reduces to the Kamke condition. The order preserving property of a semiflow is not

  17. Continuous nowhere differentiable functions the monsters of analysis

    CERN Document Server

    Jarnicki, Marek

    2015-01-01

    This book covers the construction, analysis, and theory of continuous nowhere differentiable functions, comprehensively and accessibly. After illuminating the significance of the subject through an overview of its history, the reader is introduced to the sophisticated toolkit of ideas and tricks used to study the explicit continuous nowhere differentiable functions of Weierstrass, Takagi–van der Waerden, Bolzano, and others. Modern tools of functional analysis, measure theory, and Fourier analysis are applied to examine the generic nature of continuous nowhere differentiable functions, as well as linear structures within the (nonlinear) space of continuous nowhere differentiable functions. To round out the presentation, advanced techniques from several areas of mathematics are brought together to give a state-of-the-art analysis of Riemann’s continuous, and purportedly nowhere differentiable, function. For the reader’s benefit, claims requiring elaboration, and open problems, are clearly indicated. An a...

  18. DIF Trees: Using Classification Trees to Detect Differential Item Functioning

    Science.gov (United States)

    Vaughn, Brandon K.; Wang, Qiu

    2010-01-01

    A nonparametric tree classification procedure is used to detect differential item functioning for items that are dichotomously scored. Classification trees are shown to be an alternative procedure to detect differential item functioning other than the use of traditional Mantel-Haenszel and logistic regression analysis. A nonparametric…

  19. Strict Stability Criteria for Impulsive Functional Differential Systems

    Directory of Open Access Journals (Sweden)

    Kaien Liu

    2008-02-01

    Full Text Available By using Lyapunov functions and Razumikhin techniques, the strict stability of impulsive functional differential systems is investigated. Some comparison theorems are given by virtue of differential inequalities. The corresponding theorems in the literature can be deduced from our results.

  20. Nonlinear differentiation equation and analytic function spaces

    OpenAIRE

    Li, Hao; Li, Songxiao

    2015-01-01

    In this paper we consider the nonlinear complex differential equation $$(f^{(k)})^{n_{k}}+A_{k-1}(z)(f^{(k-1)})^{n_{k-1}}+\\cdot\\cdot\\cdot+A_{1}(z)(f')^{n_{1}}+A_{0}(z)f^{n_{0}}=0, $$where $ A_{j}(z)$, $ j=0, \\cdots, k-1 $, are analytic in the unit disk $ \\mathbb{D} $, $ n_{j}\\in R^{+} $ for all $ j=0, \\cdots, k $. We investigate this nonlinear differential equation from two aspects. On one hand, we provide some sufficient conditions on coefficients such that all solutions of this equation bel...

  1. "Detecting Differential Item Functioning and Differential Step Functioning due to Differences that ""Should"" Matter"

    Directory of Open Access Journals (Sweden)

    Tess Miller

    2010-07-01

    Full Text Available This study illustrates the use of differential item functioning (DIF and differential step functioning (DSF analyses to detect differences in item difficulty that are related to experiences of examinees, such as their teachers' instructional practices, that are relevant to the knowledge, skill, or ability the test is intended to measure. This analysis is in contrast to the typical use of DIF or DSF to detect differences related to characteristics of examinees, such as gender, language, or cultural knowledge, that should be irrelevant. Using data from two forms of Ontario's Grade 9 Assessment of Mathematics, analyses were performed comparing groups of students defined by their teachers' instructional practices. All constructed-response items were tested for DIF using the Mantel Chi-Square, standardized Liu Agresti cumulative common log-odds ratio, and standardized Cox's noncentrality parameter. Items exhibiting moderate to large DIF were subsequently tested for DSF. In contrast to typical DIF or DSF analyses, which inform item development, these analyses have the potential to inform instructional practice.

  2. Select G-Protein-Coupled Receptors Modulate Agonist-Induced Signaling via a ROCK, LIMK, and β-Arrestin 1 Pathway

    Directory of Open Access Journals (Sweden)

    Nitish Mittal

    2013-11-01

    Full Text Available G-protein-coupled receptors (GPCRs are typically present in a basal, inactive state but, when bound to an agonist, activate downstream signaling cascades. In studying arrestin regulation of opioid receptors in dorsal root ganglia (DRG neurons, we find that agonists of delta opioid receptors (δORs activate cofilin through Rho-associated coiled-coil-containing protein kinase (ROCK, LIM domain kinase (LIMK, and β-arrestin 1 (β-arr1 to regulate actin polymerization. This controls receptor function, as assessed by agonist-induced inhibition of voltage-dependent Ca2+ channels in DRGs. Agonists of opioid-receptor-like receptors (ORL1 similarly influence the function of this receptor through ROCK, LIMK, and β-arr1. Functional evidence of this cascade was demonstrated in vivo, where the behavioral effects of δOR or ORL1 agonists were enhanced in the absence of β-arr1 or prevented by inhibiting ROCK. This pathway allows δOR and ORL1 agonists to rapidly regulate receptor function.

  3. Select G-protein-coupled receptors modulate agonist-induced signaling via a ROCK, LIMK, and β-arrestin 1 pathway.

    Science.gov (United States)

    Mittal, Nitish; Roberts, Kristofer; Pal, Katsuri; Bentolila, Laurent A; Fultz, Elissa; Minasyan, Ani; Cahill, Catherine; Pradhan, Amynah; Conner, David; DeFea, Kathryn; Evans, Christopher; Walwyn, Wendy

    2013-11-27

    G-protein-coupled receptors (GPCRs) are typically present in a basal, inactive state but, when bound to an agonist, activate downstream signaling cascades. In studying arrestin regulation of opioid receptors in dorsal root ganglia (DRG) neurons, we find that agonists of delta opioid receptors (δORs) activate cofilin through Rho-associated coiled-coil-containing protein kinase (ROCK), LIM domain kinase (LIMK), and β-arrestin 1 (β-arr1) to regulate actin polymerization. This controls receptor function, as assessed by agonist-induced inhibition of voltage-dependent Ca(2+) channels in DRGs. Agonists of opioid-receptor-like receptors (ORL1) similarly influence the function of this receptor through ROCK, LIMK, and β-arr1. Functional evidence of this cascade was demonstrated in vivo, where the behavioral effects of δOR or ORL1 agonists were enhanced in the absence of β-arr1 or prevented by inhibiting ROCK. This pathway allows δOR and ORL1 agonists to rapidly regulate receptor function. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Select G-protein coupled receptors modulate agonist-induced signaling via a ROCK, LIMK and β-arrestin 1 pathway

    Science.gov (United States)

    Mittal, Nitish; Roberts, Kristofer; Pal, Katsuri; Bentolila, Laurent A.; Fultz, Elissa; Minasyan, Ani; Cahill, Catherine; Pradhan, Amynah; Conner, David; DeFea, Kathryn; Evans, Christopher; Walwyn, Wendy

    2013-01-01

    G-protein coupled receptors (GPCRs) are typically present in a basal, inactive state, but when bound to agonist they activate downstream signaling cascades. In studying arrestin regulation of opioid receptors in dorsal root ganglia (DRG) neurons, we find that agonists of delta opioid receptors (δORs) activate cofilin through Rho-associated coiled-coiled containing protein kinase (ROCK), LIM domain kinase (LIMK) and β- arrestin 1 (β-arr1), to regulate actin polymerization. This controls receptor function, as assessed by agonist-induced inhibition of voltage-dependent Ca2+ channels in DRGs. Agonists of opioid-receptor like receptors (ORL1) similarly influence the function of this receptor through ROCK, LIMK and β-arr1. Functional evidence of this cascade was demonstrated in vivo where the behavioral effects of δOR or ORL1 agonists were enhanced in the absence of β-arr1 or prevented by inhibiting ROCK. This pathway allows δOR and ORL1 agonists to rapidly regulate receptor function. PMID:24239352

  5. Net and Global Differential Item Functioning in PISA Polytomously Scored Science Items: Application of the Differential Step Functioning Framework

    Science.gov (United States)

    Akour, Mutasem; Sabah, Saed; Hammouri, Hind

    2015-01-01

    The purpose of this study was to apply two types of Differential Item Functioning (DIF), net and global DIF, as well as the framework of Differential Step Functioning (DSF) to real testing data to investigate measurement invariance related to test language. Data from the Program for International Student Assessment (PISA)-2006 polytomously scored…

  6. Differential functioning of Bender Visual-Motor Gestalt Test items.

    Science.gov (United States)

    Sisto, Fermino Fernandes; Dos Santos, Acácia Aparecida Angeli; Noronha, Ana Paula Porto

    2010-02-01

    Differential Item Functioning (DIF) refers to items that do not function the same way for comparable members of different groups. The present study focuses on analyzing and classifying sex-related differential item functioning in the Bender Visual-Motor Gestalt Test. Subjects were 1,052 children attending public schools (513 boys, 539 girls, ages 6-10 years). The protocols were scored using the Bender Graduated Scoring System, which evaluates only the distortion criterion using the Rasch logistic response model. The scoring system fit the Rasch model, although two items were found to be biased by sex. When analyzing differential functioning of items for boys and girls separately, the number of differentially functioning items was equal.

  7. Controllability of Impulsive Neutral Functional Differential Inclusions in Banach Spaces

    Directory of Open Access Journals (Sweden)

    X. J. Wan

    2013-01-01

    Full Text Available We investigate the controllability of impulsive neutral functional differential inclusions in Banach spaces. Our main aim is to find an effective method to solve the controllability problem of impulsive neutral functional differential inclusions with multivalued jump sizes in Banach spaces. Based on a fixed point theorem with regard to condensing map, sufficient conditions for the controllability of the impulsive neutral functional differential inclusions in Banach spaces are derived. Moreover, a remark is given to explain less conservative criteria for special cases, and work is improved in the previous literature.

  8. Functional Implications of Neuroendocrine Differentiated Cells in Prostate Cancer

    NARCIS (Netherlands)

    J. Jongsma (Johan)

    2000-01-01

    textabstractThis thesis focuses on NE differentiation in prostate cancer, especially in prostate cancer models. We studied the effects of androgen depletion on the NE differentiated status of in vivo and in vitro prostatic tumor models. Knowledge concerning the function of NE cells in the normal hum

  9. Curriculum, Translation, and Differential Functioning of Measurement and Geometry Items

    Science.gov (United States)

    Emenogu, Barnabas C.; Childs, Ruth A.

    2005-01-01

    A test item exhibits differential item functioning (DIF) if students with the same ability find it differentially difficult. When the item is administered in French and English, differences in language difficulty and meaning are the most likely explanations. However, curriculum differences may also contribute to DIF. The responses of Ontario…

  10. Functional Implications of Neuroendocrine Differentiated Cells in Prostate Cancer

    NARCIS (Netherlands)

    J. Jongsma (Johan)

    2000-01-01

    textabstractThis thesis focuses on NE differentiation in prostate cancer, especially in prostate cancer models. We studied the effects of androgen depletion on the NE differentiated status of in vivo and in vitro prostatic tumor models. Knowledge concerning the function of NE cells in the normal

  11. Differential and Functional Identities for the Elliptic Trilogarithm

    Directory of Open Access Journals (Sweden)

    Ian A.B. Strachan

    2009-03-01

    Full Text Available When written in terms of $vartheta$-functions, the classical Frobenius-Stickelberger pseudo-addition formula takes a very simple form. Generalizations of this functional identity are studied, where the functions involved are derivatives (including derivatives with respect to the modular parameter of the elliptic trilogarithm function introduced by Beilinson and Levin. A differential identity satisfied by this function is also derived. These generalized Frobenius-Stickelberger identities play a fundamental role in the development of elliptic solutions of the Witten-Dijkgraaf-Verlinde-Verlinde equations of associativity, with the simplest case reducing to the above mentioned differential identity.

  12. Differential subordination for meromorphic multivalent quasi-convex functions

    OpenAIRE

    R. W. Ibrahim; M. Darus

    2010-01-01

    We introduce new classes of meromorphic multivalent quasi-convex functions and find some sufficient differential subordination theorems for such classes in punctured unit disk with applications in fractional calculus.

  13. Differential subordination for meromorphic multivalent quasi-convex functions

    Directory of Open Access Journals (Sweden)

    R. W. Ibrahim

    2010-02-01

    Full Text Available We introduce new classes of meromorphic multivalent quasi-convex functions and find some sufficient differential subordination theorems for such classes in punctured unit disk with applications in fractional calculus.

  14. Comparison theorems for neutral stochastic functional differential equations

    Science.gov (United States)

    Bai, Xiaoming; Jiang, Jifa

    2016-05-01

    The comparison theorems under Wu and Freedman's order are proved for neutral stochastic functional differential equations with finite or infinite delay whose drift terms satisfy the quasimonotone condition and diffusion term is the same.

  15. Controllability of impulsive functional differential systems with nonlocal conditions

    Directory of Open Access Journals (Sweden)

    Yansheng Liu

    2013-08-01

    Full Text Available In this article, we study the controllability of impulsive functional differential equations with nonlocal conditions. We establish sufficient conditions for controllability, via the measure of noncompactness and Monch fixed point theorem.

  16. Approximate controllability of neutral functional differential system with unbounded delay

    Directory of Open Access Journals (Sweden)

    Jong Yeoul Park

    2001-01-01

    Full Text Available We consider a class of control systems governed by the neutral functional differential equation with unbounded delay and study the approximate controllability of the system. An example is given to illustrate the result.

  17. On Certain Subclasses of Analytic Functions Defined by Differential Subordination

    Directory of Open Access Journals (Sweden)

    Hesam Mahzoon

    2011-01-01

    Full Text Available We introduce and study certain subclasses of analytic functions which are defined by differential subordination. Coefficient inequalities, some properties of neighborhoods, distortion and covering theorems, radius of starlikeness, and convexity for these subclasses are given.

  18. Involvement of phosphodiesterase 4 in beta-adrenoceptor agonist-induced amylase release in parotid acinar cells.

    Science.gov (United States)

    Satoh, Keitaro; Guo, Ming-Yu; Sairenji, Nakayasu

    2009-06-01

    beta-Adrenoceptor activation increases intracellular cAMP levels and consequently induces exocytotic amylase release in parotid acinar cells. Phosphodiesterase (PDE) catalyses the hydrolysis of cAMP, which terminates the downstream signaling of this second messenger. We investigated the involvement of PDE4, a cAMP-PDE, in beta-adrenoceptor agonist-induced amylase release in mouse, rat and rabbit parotid acinar cells by using the specific PDE4 inhibitor rolipram. cAMP-PDE activity was detected in mouse, rat and rabbit parotid acinar cells. In the presence of rolipram, cAMP-PDE activity was reduced by about 31%, 38% and 33% in mouse, rat and rabbit parotid acinar cells, respectively. The increase in cAMP levels induced by the beta-adrenoceptor agonist isoproterenol was enhanced in the presence of rolipram in mouse, rat and rabbit parotid acinar cells. Isoproterenol-induced amylase release, but not constitutive amylase release, was also enhanced in the presence of rolipram in mouse, rat and rabbit parotid acinar cells. These results suggest that the rolipram-sensitive cAMP-PDE, PDE4, is involved in beta-adrenoceptor agonist-induced amylase release in parotid acinar cells.

  19. Generating functionals and Lagrangian partial differential equations

    Energy Technology Data Exchange (ETDEWEB)

    Vankerschaver, Joris; Liao, Cuicui; Leok, Melvin [Department of Mathematics, University of California, San Diego, 9500 Gilman Drive, Dept. 0112, La Jolla, California 92093-0112 (United States)

    2013-08-15

    The main goal of this paper is to derive an alternative characterization of the multisymplectic form formula for classical field theories using the geometry of the space of boundary values. We review the concept of Type-I/II generating functionals defined on the space of boundary data of a Lagrangian field theory. On the Lagrangian side, we define an analogue of Jacobi's solution to the Hamilton–Jacobi equation for field theories, and we show that by taking variational derivatives of this functional, we obtain an isotropic submanifold of the space of Cauchy data, described by the so-called multisymplectic form formula. As an example of the latter, we show that Lorentz's reciprocity principle in electromagnetism is a particular instance of the multisymplectic form formula. We also define a Hamiltonian analogue of Jacobi's solution, and we show that this functional is a Type-II generating functional. We finish the paper by defining a similar framework of generating functions for discrete field theories, and we show that for the linear wave equation, we recover the multisymplectic conservation law of Bridges.

  20. The Fractional Differential Polynomial Neural Network for Approximation of Functions

    Directory of Open Access Journals (Sweden)

    Rabha W. Ibrahim

    2013-09-01

    Full Text Available In this work, we introduce a generalization of the differential polynomial neural network utilizing fractional calculus. Fractional calculus is taken in the sense of the Caputo differential operator. It approximates a multi-parametric function with particular polynomials characterizing its functional output as a generalization of input patterns. This method can be employed on data to describe modelling of complex systems. Furthermore, the total information is calculated by using the fractional Poisson process.

  1. Local behavior of autonomous neutral functional differential equations.

    Science.gov (United States)

    Hale, J. K.

    1972-01-01

    Basic problems for a special class of neutral functional differential equations (NFDE) are formulated, and some contributions to a general qualitative theory in the neighborhood of an equilibrium point are indicated. The properties of a NFDE (G,f) are examined to determine in what sense these properties are insensitive to small changes in (G,f) in the topology G x F. The special class of equations that is introduced includes retarded functional differential equations and difference equations.

  2. On Homogeneous Differential Polynomials of Meromorphic Functions

    Institute of Scientific and Technical Information of China (English)

    Wei Chuan LIN; Hong Xun YI

    2005-01-01

    In this paper, we study one conjecture proposed by W. Bergweiler and show that any transcendental meromorphic functions f(z) have the form exp(αz +β) if f(z)f″(z) - a(f′(z))2 ≠ 0,where a ≠ 1, n+1/n, n ∈ N. Moreover, an analogous normality criterion is obtained.

  3. Deterministic Differential Properties of the Compression Function of BMW

    DEFF Research Database (Denmark)

    Guo, Jian; Thomsen, Søren Steffen

    2011-01-01

    In this paper, we give some determinstic differential properties for the compression function of SHA-3 candidate Blue Midnight Wish (tweaked version for round 2). The computational complexity is about 20 compression function calls. This applies to security parameters 0/16, 1/15, and 2/14. The eff....../14. The efficient differentials can be used to find pseudo-preimages of the compression function with marginal gain over brute force. However, none of these attacks threaten the security of the BMW hash functions....

  4. Early maternal deprivation and neonatal single administration with a cannabinoid agonist induce long-term sex-dependent psychoimmunoendocrine effects in adolescent rats.

    Science.gov (United States)

    Llorente, Ricardo; Arranz, Lorena; Marco, Eva-María; Moreno, Enrique; Puerto, Marta; Guaza, Carmen; De la Fuente, Mónica; Viveros, Maria-Paz

    2007-07-01

    Maternal deprivation [24h on postnatal day 9] might represent an animal model of schizophrenia and behavioural and neurochemical alterations observed in adulthood may be mediated by hippocampal impairments induced by abnormally increased glucocorticoids due to neonatal stress. We aimed to provide new data for psychoimmunoendocrine characterization of this animal model by evaluating its effects in adolescent rats of both genders. In previous studies we found that cannabinoid compounds counteracted the enhanced impulsivity of maternally deprived animals and that the cannabinoid receptor agonist WIN 55,212-2 showed neuroprotective properties in neonatal rats. So, we hypothesised that this compound could counteract at least some of the detrimental effects that we expected to find in maternally deprived animals. Accordingly, the drug was administered immediately after the maternal deprivation period. Maternally deprived males showed significantly decreased motor activity in the holeboard and the plus-maze. The cannabinoid agonist induced, exclusively in males, a significant anxiogenic-like effect, which was reversed by maternal deprivation. In the forced swimming test, both treatments independently induced depressive-like responses. Maternal deprivation reduced immunological function whereas the drug exerted tissue-dependent effects on the immune parameters analysed. Maternally deprived females showed reduced corticosterone levels whereas the cannabinoid agonist increased hormone concentration in all groups. In general, the results show detrimental effects of both treatments as well as intriguing interactions, notably in relation to emotional behaviour and certain immunological responses.

  5. ALMOST PERIODIC SOLUTIONS TO STOCHASTIC FUNCTIONAL DIFFERENTIAL EQUATIONS

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    By applying the properties of almost periodic function and exponential dichotomy of linear system as well as Banach fixed point theorem,we establish the conditions for the existence and uniqueness of square-mean almost periodic solution to some stochastic functional differential equations.

  6. The Fully-Differential Quark Beam Function at NNLO

    CERN Document Server

    Gaunt, Jonathan R

    2014-01-01

    We present the first calculation of a fully-unintegrated parton distribution (beam function) at next-to-next-to-leading order (NNLO). We obtain the fully-differential beam function for quark-initiated processes by matching it onto standard parton distribution functions (PDFs) at two loops. The fully-differential beam function is a universal ingredient in resummed predictions of observables probing both the virtuality as well as the transverse momentum of the incoming quark in addition to its usual longitudinal momentum fraction. For such double-differential observables our result is an important contribution to the resummation of large logarithms related to collinear initial-state radiation (ISR) through N3LL.

  7. Convergence to equilibria in scalar nonquasimonotone functional differential equations

    Science.gov (United States)

    Pituk, Mihály

    We consider a class of scalar functional differential equations generating a strongly order preserving semiflow with respect to the exponential ordering introduced by Smith and Thieme. It is shown that the boundedness of all solutions and the stability properties of an equilibrium are exactly the same as for the ordinary differential equation which is obtained by "ignoring the delays". The result on the boundedness of the solutions, combined with a convergence theorem due to Smith and Thieme, leads to explicit necessary and sufficient conditions for the convergence of all solutions starting from a dense subset of initial data. Under stronger conditions, guaranteeing that the functional differential equation is asymptotically equivalent to a scalar ordinary differential equation, a similar result is proved for the convergence of all solutions.

  8. Robust fractional order differentiators using generalized modulating functions method

    KAUST Repository

    Liu, Dayan

    2015-02-01

    This paper aims at designing a fractional order differentiator for a class of signals satisfying a linear differential equation with unknown parameters. A generalized modulating functions method is proposed first to estimate the unknown parameters, then to derive accurate integral formulae for the left-sided Riemann-Liouville fractional derivatives of the studied signal. Unlike the improper integral in the definition of the left-sided Riemann-Liouville fractional derivative, the integrals in the proposed formulae can be proper and be considered as a low-pass filter by choosing appropriate modulating functions. Hence, digital fractional order differentiators applicable for on-line applications are deduced using a numerical integration method in discrete noisy case. Moreover, some error analysis are given for noise error contributions due to a class of stochastic processes. Finally, numerical examples are given to show the accuracy and robustness of the proposed fractional order differentiators.

  9. Stability of a Neutral Stochastic Functional Differential Equations

    Institute of Scientific and Technical Information of China (English)

    LI Bi-wen

    2005-01-01

    Sufficient condition for stochastic unifrom stability of a neutral stochastic functional differential equation is given, especially, new techniques are developed to cope with the neutral delay case, we obtained the sufficient condition for asymptotic stabillty of neutral stochastic differential delay equations. Due to the new techniques developed in this paper, the results obtained are very general and useful. The theory developed here gives a unified treatment for various asymptotic estimates e.g. exponential and polynomial bounds.

  10. Active components of ginger potentiate β-agonist-induced relaxation of airway smooth muscle by modulating cytoskeletal regulatory proteins.

    Science.gov (United States)

    Townsend, Elizabeth A; Zhang, Yi; Xu, Carrie; Wakita, Ryo; Emala, Charles W

    2014-01-01

    β-Agonists are the first-line therapy to alleviate asthma symptoms by acutely relaxing the airway. Purified components of ginger relax airway smooth muscle (ASM), but the mechanisms are unclear. By elucidating these mechanisms, we can explore the use of phytotherapeutics in combination with traditional asthma therapies. The objectives of this study were to: (1) determine if 6-gingerol, 8-gingerol, or 6-shogaol potentiate β-agonist-induced ASM relaxation; and (2) define the mechanism(s) of action responsible for this potentiation. Human ASM was contracted in organ baths. Tissues were relaxed dose dependently with β-agonist, isoproterenol, in the presence of vehicle, 6-gingerol, 8-gingerol, or 6-shogaol (100 μM). Primary human ASM cells were used for cellular experiments. Purified phosphodiesterase (PDE) 4D or phospholipase C β enzyme was used to assess inhibitory activity of ginger components using fluorescent assays. A G-LISA assay was used to determine the effects of ginger constituents on Ras homolog gene family member A activation. Significant potentiation of isoproterenol-induced relaxation was observed with each of the ginger constituents. 6-Shogaol showed the largest shift in isoproterenol half-maximal effective concentration. 6-Gingerol, 8-gingerol, or 6-shogaol significantly inhibited PDE4D, whereas 8-gingerol and 6-shogaol also inhibited phospholipase C β activity. 6-Shogaol alone inhibited Ras homolog gene family member A activation. In human ASM cells, these constituents decreased phosphorylation of 17-kD protein kinase C-potentiated inhibitory protein of type 1 protein phosphatase and 8-gingerol decreased myosin light chain phosphorylation. Isolated components of ginger potentiate β-agonist-induced relaxation in human ASM. This potentiation involves PDE4D inhibition and cytoskeletal regulatory proteins. Together with β-agonists, 6-gingerol, 8-gingerol, or 6-shogaol may augment existing asthma therapy, resulting in relief of symptoms through

  11. On Entire and Meromorphic Functions That Share One Small Function with Their Differential Polynomial

    Directory of Open Access Journals (Sweden)

    Subhas S. Bhoosnurmath

    2013-01-01

    Full Text Available We study the uniqueness of meromorphic functions that share one small function with more general differential polynomial P[f]. As corollaries, we obtain results which answer open questions posed by Yu (2003.

  12. Early development of executive functions: a differential study

    Directory of Open Access Journals (Sweden)

    Sylvia Sastre-Riba

    2015-05-01

    Full Text Available The ontogeny of executive functions is essential in explaining differential and normative developmental trends. Executive functions must be studied from an early age given their consequential effects on mental flexibility, monitoring information, planning, and cognitive control. We propose a differential study in alternative developmental courses through observing typical babies, Down syndrome babies, and babies with risk-factors at birth (due to low weight or to congenital hypothyroidism. Applymg Systematic Observational Methodology, spontaneous babies' activity was registered. The results indicated that: a Typical babies showed better shifting and action flexibility in order to obtain a goal, thus better results; b Among the higher risk-babies, the lower efficacy in executive functioning was observed in underweight babies. Those with hypothyroidism were more in line with the typical babies; c Underweight babies showed a good level of combining actions but they obtained inferior results; d Down syndrome babies displayed more executive functioning difficulty, lower flexibility, high perseveration and less error detection.

  13. On Parameter Differentiation for Integral Representations of Associated Legendre Functions

    Science.gov (United States)

    Cohl, Howard S.

    2011-05-01

    For integral representations of associated Legendre functions in terms of modified Bessel functions, we establish justification for differentiation under the integral sign with respect to parameters. With this justification, derivatives for associated Legendre functions of the first and second kind with respect to the degree are evaluated at odd-half-integer degrees, for general complex-orders, and derivatives with respect to the order are evaluated at integer-orders, for general complex-degrees. We also discuss the properties of the complex function f: C\\{-1,1}→C given by f(z)=z/((z+1)1/2(z-1)1/2).

  14. On parameter differentiation for integral representations of associated Legendre functions

    CERN Document Server

    Cohl, Howard S

    2011-01-01

    For integral representations of associated Legendre functions in terms of modified Bessel functions, we establish justification for differentiation under the integral sign with respect to parameters. With this justification, derivatives for associated Legendre functions of the first and second kind with respect to the degree are evaluated at odd-half-integer degrees, for general complex-orders, and derivatives with respect to the order are evaluated at integer-orders, for general complex-degrees. We also discuss the properties of the complex function $f:\\C\\setminus\\{-1,1\\}\\to\\C$ given by $f(z)=z/\\sqrt{(z+1)(z-1)}$.

  15. Hyperbolic function method for solving nonlinear differential-different equations

    Institute of Scientific and Technical Information of China (English)

    Zhu Jia-Min

    2005-01-01

    An algorithm is devised to obtained exact travelling wave solutions of differential-different equations by means of hyperbolic function. For illustration, we apply the method to solve the discrete nonlinear (2+1)-dimensional Toda lattice equation and the discretized nonlinear mKdV lattice equation, and successfully constructed some explicit and exact travelling wave solutions.

  16. Positivity and storage functions for quadratic differential forms

    NARCIS (Netherlands)

    Trentelman, Hendrikus; Willems, Jan C.

    1996-01-01

    Differential equations and one-variable polynomial matrices play an essential role in describing dynamics of systems. When studying functions of the dynamical variables or specifying performance criteria in optimal control, we invariably encounter quadratic expressions in the variables and their der

  17. Disentangling Sources of Differential Item Functioning in Multilanguage Assessments.

    Science.gov (United States)

    Ercikan, Kadriye

    2002-01-01

    Disentangled sources of differential item functioning (DIF) in a multilanguage assessment for which multiple factors were expected to be causing DIF. Data for the Third International Mathematics and Science study for four countries and two languages (3,000 to 11,000 cases in each comparison group) reveal amounts and sources of DIF. (SLD)

  18. Using Mixed Methods to Interpret Differential Item Functioning

    Science.gov (United States)

    Benítez, Isabel; Padilla, José-Luis; Hidalgo Montesinos, María Dolores; Sireci, Stephen G.

    2016-01-01

    Analysis of differential item functioning (DIF) is often used to determine if cross-lingual assessments are equivalent across languages. However, evidence on the causes of cross-lingual DIF is still evasive. Expert appraisal is a qualitative method useful for obtaining detailed information about problematic elements in the different linguistic…

  19. Periodic Solutions for Functional Differential Inclusions With Infinite Delay

    Institute of Scientific and Technical Information of China (English)

    李勇; 周钦德; 吕显瑞

    1994-01-01

    By means of asymptotic fixed point theory,it is established that every dissipative functional differential inclusion (probably with infinite delay) has a periodic solution.This provides a theoretical basis for the applications of Liapunov’s second method to multivalued systems.As a result,a positive answer to Hutson’s open problem is given for more general multivalued systems.

  20. Effect of Multiple Testing Adjustment in Differential Item Functioning Detection

    Science.gov (United States)

    Kim, Jihye; Oshima, T. C.

    2013-01-01

    In a typical differential item functioning (DIF) analysis, a significance test is conducted for each item. As a test consists of multiple items, such multiple testing may increase the possibility of making a Type I error at least once. The goal of this study was to investigate how to control a Type I error rate and power using adjustment…

  1. Exploring Crossing Differential Item Functioning by Gender in Mathematics Assessment

    Science.gov (United States)

    Ong, Yoke Mooi; Williams, Julian; Lamprianou, Iasonas

    2015-01-01

    The purpose of this article is to explore crossing differential item functioning (DIF) in a test drawn from a national examination of mathematics for 11-year-old pupils in England. An empirical dataset was analyzed to explore DIF by gender in a mathematics assessment. A two-step process involving the logistic regression (LR) procedure for…

  2. Mild Solutions of Neutral Stochastic Partial Functional Differential Equations

    Directory of Open Access Journals (Sweden)

    T. E. Govindan

    2011-01-01

    Full Text Available This paper studies the existence and uniqueness of a mild solution for a neutral stochastic partial functional differential equation using a local Lipschitz condition. When the neutral term is zero and even in the deterministic special case, the result obtained here appears to be new. An example is included to illustrate the theory.

  3. Detecting Differential Item Functioning Using Logistic Regression Procedures.

    Science.gov (United States)

    Swaminathan, Hariharan; Rogers, H. Jane

    1990-01-01

    A logistic regression model for characterizing differential item functioning (DIF) between two groups is presented. A distinction is drawn between uniform and nonuniform DIF in terms of model parameters. A statistic for testing the hypotheses of no DIF is developed, and simulation studies compare it with the Mantel-Haenszel procedure. (Author/TJH)

  4. Differential Item Functioning on Two Tests of EFL Proficiency.

    Science.gov (United States)

    Ryan, Katherine E.; Bachman, Lyle F.

    1992-01-01

    The extent to which items from the Test of English as a Foreign Language and the First Certificate in English function differently for test-takers of equal ability from different native language and curricular backgrounds was investigated. Results suggest a need for methods like logistic regression to examine nonuniform differential item…

  5. Detection of Differential Item Functioning Using the Lasso Approach

    Science.gov (United States)

    Magis, David; Tuerlinckx, Francis; De Boeck, Paul

    2015-01-01

    This article proposes a novel approach to detect differential item functioning (DIF) among dichotomously scored items. Unlike standard DIF methods that perform an item-by-item analysis, we propose the "LR lasso DIF method": logistic regression (LR) model is formulated for all item responses. The model contains item-specific intercepts,…

  6. Analysis of Differential Item Functioning in the NAEP History Assessment.

    Science.gov (United States)

    Zwick, Rebecca; Ercikan, Kadriye

    The Mantel-Haenszel approach for investigating differential item functioning (DIF) was applied to U.S. history items that were administered as part of the National Assessment of Educational Progress (NAEP). DIF analyses were based on the responses of 7,743 students in grade 11. On some items, Blacks, Hispanics, and females performed more poorly…

  7. Initial and boundary value problems for partial functional differential equations

    OpenAIRE

    Ntouyas , S. K.; P. Ch Tsamatos

    1997-01-01

    In this paper we study the existence of solutions to initial and boundary value problems of partial functional differential equations via a fixed-point analysis approach. Using the topological transversality theorem we derive conditions under which an initial or a boundary value problem has a solution.

  8. Differential Item Functioning on the Graduate Management Admission Test.

    Science.gov (United States)

    O'Neill, Kathleen A.; And Others

    The purpose of this study was to identify differentially functioning items on operational administrations of the Graduate Management Admission Test (GMAT) through the use of the Mantel-Haenszel statistic. Retrospective analyses of data collected over 3 years are reported for black/white and female/male comparisons for the Verbal and Quantitative…

  9. Existence Results for Functional Differential Inclusions with Infinite Delay

    Institute of Scientific and Technical Information of China (English)

    Shi Huang HONG

    2006-01-01

    The aim of the present paper is to investigate the existence of solutions to functional differential inclusions with infinite delay in Banach spaces. A relevant set of phase space axioms is proposed. The main tools used in this paper are certain fixed point theorems based on the set-contraction theory.

  10. PSEUDO-ALMOST PERIODIC SOLUTIONS TO SOME FUNCTIONAL DIFFERENTIAL EQUATIONS

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    This paper is concerned with the pseudo-almost periodic solutions to some functional differential equations. By the exponential dichotomy theory and Schauder’s fixed-point theorem, some results on the existence and uniqueness of pseudo-almost periodic solutions to the system are obtained.

  11. Stability of a Certain Retard Functional Differential Equation

    Institute of Scientific and Technical Information of China (English)

    谷淑会; 高国柱

    2003-01-01

    The authors obtain some sufficient conditions for the stability of zero solutions to some types of the functional equation. (x)(t)+ p(t)-x(t)+q(t)x(t)+f (t, xt)=0 by transformations and the Liapunov's Second method. The obtained conclusions generalize some results of Stability of Equation (x)(t)+p(t)(x)(t)+q(t)x(t)=0 and Jack Hale in his paper of Theory of Functional Differential Equations.

  12. Propofol Modulates Agonist-induced Transient Receptor Potential Vanilloid Subtype-1 Receptor Desensitization via a Protein Kinase Cε-dependent Pathway in Mouse Dorsal Root Ganglion Sensory Neurons

    Science.gov (United States)

    Wickley, Peter J.; Yuge, Ryo; Russell, Mary S.; Zhang, Hongyu; Sulak, Michael A.; Damron, Derek S.

    2011-01-01

    Background The activity of transient receptor potential vanilloid subtype-1 (TRPV1) receptors, key nociceptive transducers in dorsal root ganglion sensory neurons, is enhanced by protein kinase C ε (PKCε) activation. The intravenous anesthetic propofol has been shown to activate PKCε. Our objectives were to examine whether propofol modulates TRPV1 function in dorsal root ganglion neurons via activation of PKCε. Methods Lumbar dorsal root ganglion neurons from wild-type and PKCε-null mice were isolated and cultured for 24 h. Intracellular free Ca2+ concentration was measured in neurons by using fura-2 acetoxymethyl ester. The duration of pain-associated behaviors was also assessed. Phosphorylation of PKCε and TRPV1 and the cellular translocation of PKCε from cytosol to membrane compartments were assessed by immunoblot analysis. Results In wild-type neurons, repeated stimulation with capsaicin (100 nM) progressively decreased the transient rise in intracellular free Ca2+ concentration. After desensitization, exposure to propofol rescued the Ca2+ response. The resensitizing effect of propofol was absent in neurons obtained from PKCε-null mice. Moreover, the capsaicin-induced desensitization of TRPV1 was markedly attenuated in the presence of propofol in neurons from wild-type mice but not in neurons from PKCε-null mice. Propofol also prolonged the duration of agonist-induced pain associated behaviors in wild-type mice. In addition, propofol increased phosphorylation of PKCε as well as TRPV1 and stimulated translocation of PKCε from cytosolic to membrane fraction. Discussion Our results indicate that propofol modulates TRPV1 sensitivity to capsaicin and that this most likely occurs through a PKCε-mediated phosphorylation of TRPV1. PMID:20808213

  13. Analysis III analytic and differential functions, manifolds and Riemann surfaces

    CERN Document Server

    Godement, Roger

    2015-01-01

    Volume III sets out classical Cauchy theory. It is much more geared towards its innumerable applications than towards a more or less complete theory of analytic functions. Cauchy-type curvilinear integrals are then shown to generalize to any number of real variables (differential forms, Stokes-type formulas). The fundamentals of the theory of manifolds are then presented, mainly to provide the reader with a "canonical'' language and with some important theorems (change of variables in integration, differential equations). A final chapter shows how these theorems can be used to construct the compact Riemann surface of an algebraic function, a subject that is rarely addressed in the general literature though it only requires elementary techniques. Besides the Lebesgue integral, Volume IV will set out a piece of specialized mathematics towards which the entire content of the previous volumes will converge: Jacobi, Riemann, Dedekind series and infinite products, elliptic functions, classical theory of modular fun...

  14. Estimation and Inference of Directionally Differentiable Functions: Theory and Applications

    Science.gov (United States)

    Fang, Zheng

    This dissertation addresses a large class of irregular models in economics and statistics -- settings in which the parameters of interest take the form φ(theta 0), where φ is a known directionally differentiable function and theta 0 is estimated by thetan. Chapter 1 provides a tractable framework for conducting inference, Chapter 2 focuses on optimality of estimation, and Chapter 3 applies the developed theory to construct a test whether a Hilbert space valued parameter belongs to a convex set and to derive the uniform weak convergence of the Grenander distribution function -- i.e. the least concave majorant of the empirical distribution function -- under minimal assumptions.

  15. Functional differential equations with unbounded delay in extrapolation spaces

    Directory of Open Access Journals (Sweden)

    Mostafa Adimy

    2014-08-01

    Full Text Available We study the existence, regularity and stability of solutions for nonlinear partial neutral functional differential equations with unbounded delay and a Hille-Yosida operator on a Banach space X. We consider two nonlinear perturbations: the first one is a function taking its values in X and the second one is a function belonging to a space larger than X, an extrapolated space. We use the extrapolation techniques to prove the existence and regularity of solutions and we establish a linearization principle for the stability of the equilibria of our equation.

  16. [High ability children and their differential cognitive functioning].

    Science.gov (United States)

    Sastre-Riba, S

    2008-01-01

    From the neuroconstructivist point of view, cognitive development is understood as a process of successive and continuous reorganization whose changing mechanisms and differential outcomes (typical and atypical) must be studied. High intellectual abilities are one of their differential manifestations but its concept and nature is confused conditioning the validity of its identification and the efficacy of the interventional programs. To propose a clarifying definition of the nature of high intellectual abilities and their manifestations: giftedness, talent and genious, as well as their cognitive functioning and neurological correlates. A qualitative task analysis is applied to 41 participants with intellectual profiles corresponding to: giftedness, talent and typical intelligence, previously obtained. Results show differences on the cognitive results, not only referred to the quantity of informations produced but in the data organization more complex and hard interrelated among the gifted participants. It must be a differential process of resolution adjusted to each one of the profiles studied.

  17. Differentiable but exact formulation of density-functional theory.

    Science.gov (United States)

    Kvaal, Simen; Ekström, Ulf; Teale, Andrew M; Helgaker, Trygve

    2014-05-14

    The universal density functional F of density-functional theory is a complicated and ill-behaved function of the density-in particular, F is not differentiable, making many formal manipulations more complicated. While F has been well characterized in terms of convex analysis as forming a conjugate pair (E, F) with the ground-state energy E via the Hohenberg-Kohn and Lieb variation principles, F is nondifferentiable and subdifferentiable only on a small (but dense) subset of its domain. In this article, we apply a tool from convex analysis, Moreau-Yosida regularization, to construct, for any ε > 0, pairs of conjugate functionals ((ε)E, (ε)F) that converge to (E, F) pointwise everywhere as ε → 0(+), and such that (ε)F is (Fréchet) differentiable. For technical reasons, we limit our attention to molecular electronic systems in a finite but large box. It is noteworthy that no information is lost in the Moreau-Yosida regularization: the physical ground-state energy E(v) is exactly recoverable from the regularized ground-state energy (ε)E(v) in a simple way. All concepts and results pertaining to the original (E, F) pair have direct counterparts in results for ((ε)E, (ε)F). The Moreau-Yosida regularization therefore allows for an exact, differentiable formulation of density-functional theory. In particular, taking advantage of the differentiability of (ε)F, a rigorous formulation of Kohn-Sham theory is presented that does not suffer from the noninteracting representability problem in standard Kohn-Sham theory.

  18. Differentiable but exact formulation of density-functional theory

    Energy Technology Data Exchange (ETDEWEB)

    Kvaal, Simen, E-mail: simen.kvaal@kjemi.uio.no; Ekström, Ulf; Helgaker, Trygve [Centre for Theoretical and Computational Chemistry, Department of Chemistry, University of Oslo, P.O. Box 1033 Blindern, N-0315 Oslo (Norway); Teale, Andrew M. [Centre for Theoretical and Computational Chemistry, Department of Chemistry, University of Oslo, P.O. Box 1033 Blindern, N-0315 Oslo (Norway); School of Chemistry, University of Nottingham, University Park, Nottingham NG7 2RD (United Kingdom)

    2014-05-14

    The universal density functional F of density-functional theory is a complicated and ill-behaved function of the density—in particular, F is not differentiable, making many formal manipulations more complicated. While F has been well characterized in terms of convex analysis as forming a conjugate pair (E, F) with the ground-state energy E via the Hohenberg–Kohn and Lieb variation principles, F is nondifferentiable and subdifferentiable only on a small (but dense) subset of its domain. In this article, we apply a tool from convex analysis, Moreau–Yosida regularization, to construct, for any ε > 0, pairs of conjugate functionals ({sup ε}E, {sup ε}F) that converge to (E, F) pointwise everywhere as ε → 0{sup +}, and such that {sup ε}F is (Fréchet) differentiable. For technical reasons, we limit our attention to molecular electronic systems in a finite but large box. It is noteworthy that no information is lost in the Moreau–Yosida regularization: the physical ground-state energy E(v) is exactly recoverable from the regularized ground-state energy {sup ε}E(v) in a simple way. All concepts and results pertaining to the original (E, F) pair have direct counterparts in results for ({sup ε}E, {sup ε}F). The Moreau–Yosida regularization therefore allows for an exact, differentiable formulation of density-functional theory. In particular, taking advantage of the differentiability of {sup ε}F, a rigorous formulation of Kohn–Sham theory is presented that does not suffer from the noninteracting representability problem in standard Kohn–Sham theory.

  19. Sodium-dependent phosphate transporters in osteoclast differentiation and function.

    Directory of Open Access Journals (Sweden)

    Giuseppe Albano

    Full Text Available Osteoclasts are multinucleated bone degrading cells. Phosphate is an important constituent of mineralized bone and released in significant quantities during bone resorption. Molecular contributors to phosphate transport during the resorptive activity of osteoclasts have been controversially discussed. This study aimed at deciphering the role of sodium-dependent phosphate transporters during osteoclast differentiation and bone resorption. Our studies reveal RANKL-induced differential expression of sodium-dependent phosphate transport protein IIa (NaPi-IIa transcript and protein during osteoclast development, but no expression of the closely related NaPi-IIb and NaPi-IIc SLC34 family isoforms. In vitro studies employing NaPi-IIa-deficient osteoclast precursors and mature osteoclasts reveal that NaPi-IIa is dispensable for bone resorption and osteoclast differentiation. These results are supported by the analysis of structural bone parameters by high-resolution microcomputed tomography that yielded no differences between adult NaPi-IIa WT and KO mice. By contrast, both type III sodium-dependent phosphate transporters Pit-1 and Pit-2 were abundantly expressed throughout osteoclast differentiation, indicating that they are the relevant sodium-dependent phosphate transporters in osteoclasts and osteoclast precursors. We conclude that phosphate transporters of the SLC34 family have no role in osteoclast differentiation and function and propose that Pit-dependent phosphate transport could be pivotal for bone resorption and should be addressed in further studies.

  20. Gene function in early mouse embryonic stem cell differentiation

    Directory of Open Access Journals (Sweden)

    Campbell Pearl A

    2007-03-01

    Full Text Available Abstract Background Little is known about the genes that drive embryonic stem cell differentiation. However, such knowledge is necessary if we are to exploit the therapeutic potential of stem cells. To uncover the genetic determinants of mouse embryonic stem cell (mESC differentiation, we have generated and analyzed 11-point time-series of DNA microarray data for three biologically equivalent but genetically distinct mESC lines (R1, J1, and V6.5 undergoing undirected differentiation into embryoid bodies (EBs over a period of two weeks. Results We identified the initial 12 hour period as reflecting the early stages of mESC differentiation and studied probe sets showing consistent changes of gene expression in that period. Gene function analysis indicated significant up-regulation of genes related to regulation of transcription and mRNA splicing, and down-regulation of genes related to intracellular signaling. Phylogenetic analysis indicated that the genes showing the largest expression changes were more likely to have originated in metazoans. The probe sets with the most consistent gene changes in the three cell lines represented 24 down-regulated and 12 up-regulated genes, all with closely related human homologues. Whereas some of these genes are known to be involved in embryonic developmental processes (e.g. Klf4, Otx2, Smn1, Socs3, Tagln, Tdgf1, our analysis points to others (such as transcription factor Phf21a, extracellular matrix related Lama1 and Cyr61, or endoplasmic reticulum related Sc4mol and Scd2 that have not been previously related to mESC function. The majority of identified functions were related to transcriptional regulation, intracellular signaling, and cytoskeleton. Genes involved in other cellular functions important in ESC differentiation such as chromatin remodeling and transmembrane receptors were not observed in this set. Conclusion Our analysis profiles for the first time gene expression at a very early stage of m

  1. Regulation of adipocyte differentiation and function by polyunsaturated fatty acids

    DEFF Research Database (Denmark)

    Madsen, Lise; Petersen, Rasmus Koefoed; Kristiansen, Karsten

    2005-01-01

    A diet enriched in PUFAs, in particular of the n-3 family, decreases adipose tissue mass and suppresses development of obesity in rodents. Although several nuclear hormone receptors are identified as PUFA targets, the precise molecular mechanisms underlying the effects of PUFAs still remain...... to be elucidated. Here we review research aimed at elucidating molecular mechanisms governing the effects of PUFAs on the differentiation and function of white fat cells. This review focuses on dietary PUFAs as signaling molecules, with special emphasis on agonistic and antagonistic effects on transcription...... factors currently implicated as key players in adipocyte differentiation and function, including peroxisome proliferator activated receptors (PPARs) (alpha, beta and gamma), sterol regulatory element binding proteins (SREBPs) and liver X receptors (LXRs). We review evidence that dietary n-3 PUFAs decrease...

  2. Inorganic arsenic impairs differentiation and functions of human dendritic cells

    Energy Technology Data Exchange (ETDEWEB)

    Macoch, Mélinda; Morzadec, Claudie [UMR INSERM U1085, Institut de Recherche sur la Santé, l' Environnement et le Travail (IRSET), Université de Rennes 1, 2 avenue du Professeur Léon Bernard, 35043 Rennes (France); Fardel, Olivier [UMR INSERM U1085, Institut de Recherche sur la Santé, l' Environnement et le Travail (IRSET), Université de Rennes 1, 2 avenue du Professeur Léon Bernard, 35043 Rennes (France); Pôle Biologie, Centre Hospitalier Universitaire (CHU) Rennes, 2 rue Henri Le Guilloux, 35033 Rennes (France); Vernhet, Laurent, E-mail: laurent.vernhet@univ-rennes1.fr [UMR INSERM U1085, Institut de Recherche sur la Santé, l' Environnement et le Travail (IRSET), Université de Rennes 1, 2 avenue du Professeur Léon Bernard, 35043 Rennes (France)

    2013-01-15

    Experimental studies have demonstrated that the antileukemic trivalent inorganic arsenic prevents the development of severe pro-inflammatory diseases mediated by excessive Th1 and Th17 cell responses. Differentiation of Th1 and Th17 subsets is mainly regulated by interleukins (ILs) secreted from dendritic cells (DCs) and the ability of inorganic arsenic to impair interferon-γ and IL-17 secretion by interfering with the physiology of DCs is unknown. In the present study, we demonstrate that high concentrations of sodium arsenite (As(III), 1–2 μM) clinically achievable in plasma of arsenic-treated patients, block differentiation of human peripheral blood monocytes into immature DCs (iDCs) by inducing their necrosis. Differentiation of monocytes in the presence of non-cytotoxic concentrations of As(III) (0.1 to 0.5 μM) only slightly impacts endocytotic activity of iDCs or expression of co-stimulatory molecules in cells activated with lipopolysaccharide. However, this differentiation in the presence of As(III) strongly represses secretion of IL-12p70 and IL-23, two major regulators of Th1 and Th17 activities, from iDCs stimulated with different toll-like receptor (TLR) agonists in metalloid-free medium. Such As(III)-exposed DCs also exhibit reduced mRNA levels of IL12A and/or IL12B genes when activated with TLR agonists. Finally, differentiation of monocytes with non-cytotoxic concentrations of As(III) subsequently reduces the ability of activated DCs to stimulate the release of interferon-γ and IL-17 from Th cells. In conclusion, our results demonstrate that clinically relevant concentrations of inorganic arsenic markedly impair in vitro differentiation and functions of DCs, which may contribute to the putative beneficial effects of the metalloid towards inflammatory autoimmune diseases. Highlights: ► Inorganic arsenic impairs differentiation and functions of human dendritic cells (DCs) ► Arsenite (> 1 μM) blocks differentiation of dendritic cells by

  3. Targeting malignant B cells as antigen-presenting cells: TLR-9 agonist induces systemic regression of lymphoma.

    Science.gov (United States)

    Klein-González, Nela; Holtick, Udo; Fairfax, Kirsten; Weihrauch, Martin R; von Bergwelt-Baildon, Michael S

    2011-03-01

    Evaluation of: Brody JD, Ai WZ, Czerwinski DK et al. In situ vaccination with a TLR9 agonist induces systemic lymphoma regression: a Phase I/II study. J. Clin. Oncol. 28(28), 4324-4332 (2010). Despite high response rates of the follicular B-cell lymphoma to monoclonal antibodies, the clinical course of lymphoma is still characterized by a continuous pattern of relapse. Brody and colleagues treated 15 patients with relapsed, low-grade lymphoma using low-dose radiotherapy applied to one of the tumor sites with combined injection of a TLR-9 agonist at the same site. This strategy induced specific immunity and tumor regression in several patients with an objective response rate of 27%. The results indicate an involvement of the tumor TLR-9-expressing B cells acting as antigen-presenting cells. TLR-9 in situ vaccination combined with local radiotherapy clearly warrants further in-depth analysis and investigation in a Phase III randomized trial, and may provide a new opportunity for the treatment of B-cell malignancies.

  4. CtBP1/BARS is an activator of phospholipase D1 necessary for agonist-induced macropinocytosis.

    Science.gov (United States)

    Haga, Yuki; Miwa, Noriko; Jahangeer, Saleem; Okada, Taro; Nakamura, Shun-ichi

    2009-05-06

    Vesicular trafficking such as macropinocytosis is a dynamic process that requires coordinated interactions between specialized proteins and lipids. A recent report suggests the involvement of CtBP1/BARS in epidermal growth factor (EGF)-induced macropinocytosis. Detailed mechanisms as to how lipid remodelling is regulated during macropinocytosis are still undefined. Here, we show that CtBP1/BARS is a physiological activator of PLD1 required in agonist-induced macropinocytosis. EGF-induced macropinocytosis was specifically blocked by 1-butanol but not by 2-butanol. In addition, stimulation of cells by serum or EGF resulted in the association of CtBP1/BARS with PLD1. Finally, CtBP1/BARS activated PLD1 in a synergistic manner with other PLD activators, including ADP-ribosylation factors as demonstrated by in vitro and intact cell systems. The present results shed light on the molecular basis of how the 'fission protein' CtBP1/BARS controls vesicular trafficking events including macropinocytosis.

  5. Exp-function method for solving fractional partial differential equations.

    Science.gov (United States)

    Zheng, Bin

    2013-01-01

    We extend the Exp-function method to fractional partial differential equations in the sense of modified Riemann-Liouville derivative based on nonlinear fractional complex transformation. For illustrating the validity of this method, we apply it to the space-time fractional Fokas equation and the nonlinear fractional Sharma-Tasso-Olver (STO) equation. As a result, some new exact solutions for them are successfully established.

  6. Optimal Differentiation Pricing Policy with Linear Demand Function

    Institute of Scientific and Technical Information of China (English)

    唐小我; 张明善

    2003-01-01

    The main objective in any marketing effort is to consider the optimal conditions to maximize revenue and profit. The optimal market segmentation pricing strategy is investigated under the assumption of an aggregate linear demand function. The optimal conditions to maximize revenue and profit, two closely correlative problems, are obtained respectively. The differentiation pricing policy described here can be easily applied in practice. A numerical example is provided which vividly illustrates the advantage of applying optimal policies.

  7. On Parameter Differentiation for Integral Representations of Associated Legendre Functions

    Directory of Open Access Journals (Sweden)

    Howard S. Cohl

    2011-05-01

    Full Text Available For integral representations of associated Legendre functions in terms of modified Bessel functions, we establish justification for differentiation under the integral sign with respect to parameters. With this justification, derivatives for associated Legendre functions of the first and second kind with respect to the degree are evaluated at odd-half-integer degrees, for general complex-orders, and derivatives with respect to the order are evaluated at integer-orders, for general complex-degrees. We also discuss the properties of the complex function f: C{−1,1}→C given by f(z=z/((z+1^{1/2}(z−1^{1/2}.

  8. Differentiable but exact formulation of density-functional theory

    CERN Document Server

    Kvaal, Simen; Teale, Andrew M; Helgaker, Trygve

    2013-01-01

    The universal density functional $F$ of density-functional theory is a complicated and ill-behaved function of the density--in particular, $F$ is not differentiable, making many formal manipulations more complicated. Whilst $F$ has been well characterized in terms of convex analysis as forming a conjugate pair $(F,E)$ with the ground-state energy $E$ via the Hohenberg-Kohn and Lieb variation principles, $F$ is only subdifferentiable on a small (but dense) set of its domain. In this article, we apply a tool from convex analysis, Moreau-Yosida regularization, to construct, for any $\\epsilon>0$, pairs of conjugate functionals $({}^\\epsilon\\!E,{}^\\epsilon\\! F)$ that converge to $(E,F)$ pointwise everywhere as $\\epsilon\\rightarrow 0^+$, and such that ${}^\\epsilon\\!F$ is (Fr\\'echet) differentiable. For technical reasons, we limit our attention to molecular electronic systems in a finite but large box, which does not change the physics. It is noteworthy that no information is lost in the Moreau-Yosida regularization...

  9. Building the blocks of executive functioning: differentiating early developing processes contributing to executive functioning skills

    NARCIS (Netherlands)

    Mandell, D.J.; Ward, S.E.

    2011-01-01

    The neural processes that underlie executive function begin to develop in infancy. However, it is unclear how the behavior manifested by these processes are related or if they can be differentiated early in development. This study seeks to examine early emerging executive functioning skills in

  10. Building the blocks of executive functioning: differentiating early developing processes contributing to executive functioning skills

    NARCIS (Netherlands)

    Mandell, D.J.; Ward, S.E.

    2011-01-01

    The neural processes that underlie executive function begin to develop in infancy. However, it is unclear how the behavior manifested by these processes are related or if they can be differentiated early in development. This study seeks to examine early emerging executive functioning skills in monke

  11. Systems analysis of a RIG-I agonist inducing broad spectrum inhibition of virus infectivity.

    Directory of Open Access Journals (Sweden)

    Marie-Line Goulet

    Full Text Available The RIG-I like receptor pathway is stimulated during RNA virus infection by interaction between cytosolic RIG-I and viral RNA structures that contain short hairpin dsRNA and 5' triphosphate (5'ppp terminal structure. In the present study, an RNA agonist of RIG-I was synthesized in vitro and shown to stimulate RIG-I-dependent antiviral responses at concentrations in the picomolar range. In human lung epithelial A549 cells, 5'pppRNA specifically stimulated multiple parameters of the innate antiviral response, including IRF3, IRF7 and STAT1 activation, and induction of inflammatory and interferon stimulated genes - hallmarks of a fully functional antiviral response. Evaluation of the magnitude and duration of gene expression by transcriptional profiling identified a robust, sustained and diversified antiviral and inflammatory response characterized by enhanced pathogen recognition and interferon (IFN signaling. Bioinformatics analysis further identified a transcriptional signature uniquely induced by 5'pppRNA, and not by IFNα-2b, that included a constellation of IRF7 and NF-kB target genes capable of mobilizing multiple arms of the innate and adaptive immune response. Treatment of primary PBMCs or lung epithelial A549 cells with 5'pppRNA provided significant protection against a spectrum of RNA and DNA viruses. In C57Bl/6 mice, intravenous administration of 5'pppRNA protected animals from a lethal challenge with H1N1 Influenza, reduced virus titers in mouse lungs and protected animals from virus-induced pneumonia. Strikingly, the RIG-I-specific transcriptional response afforded partial protection from influenza challenge, even in the absence of type I interferon signaling. This systems approach provides transcriptional, biochemical, and in vivo analysis of the antiviral efficacy of 5'pppRNA and highlights the therapeutic potential associated with the use of RIG-I agonists as broad spectrum antiviral agents.

  12. Numerical Analysis for Functional Differential and Integral Equations

    Institute of Scientific and Technical Information of China (English)

    Hermann BRUNNER; Tao TANG; Stefan VANDEWALLE

    2009-01-01

    @@ From December 3-6,2007,the Department of Mathematics at Hong Kong Baptist University hosted the International Workshop on Numerical Analysis and Computational Methods for Functional Differential and Integral Equations. This workshop,organized by Hermann Brunner of Memorial University of Newfoundland (Canada) & Hong Kong Baptist University,Leevan Ling and Tao Tang of Hong Kong Baptist University,and Chengjian Zhang of Huazhong University of Science and Technology (China) brought together some 40 members of research groups in Hong Kong,Taiwan and the mainland of China,Belgium,Canada,Japan,and Portugal.

  13. Stability by fixed point theory for functional differential equations

    CERN Document Server

    Burton, T A

    2006-01-01

    This book is the first general introduction to stability of ordinary and functional differential equations by means of fixed point techniques. It contains an extensive collection of new and classical examples worked in detail and presented in an elementary manner. Most of this text relies on three principles: a complete metric space, the contraction mapping principle, and an elementary variation of parameters formula. The material is highly accessible to upper-level undergraduate students in the mathematical sciences, as well as working biologists, chemists, economists, engineers, mathematicia

  14. The improper infinite derivatives of Takagi's nowhere-differentiable function

    CERN Document Server

    Allaart, Pieter C

    2010-01-01

    Let T be Takagi's continuous but nowhere-differentiable function. Using a representation in terms of Rademacher series due to N. Kono, we give a complete characterization of those points where T has a left-sided, right-sided, or two-sided infinite derivative. This characterization is illustrated by several examples. A consequence of the main result is that the sets of points where T'(x) is infinite have Hausdorff dimension one. As a byproduct of the method of proof, some exact results concerning the modulus of continuity of T are also obtained.

  15. Functional role of Rho-kinase in ameloblast differentiation.

    Science.gov (United States)

    Otsu, Keishi; Kishigami, Ryota; Fujiwara, Naoki; Ishizeki, Kiyoto; Harada, Hidemitsu

    2011-10-01

    During tooth development, inner enamel epithelial (IEE) cells differentiate into enamel-secreting ameloblasts, a polarized and elongated cellular population. The molecular underpinnings of this morphogenesis and cytodifferentiation, however, are not well understood. Here, we show that Rho-associated coiled-coil-containing protein kinase (ROCK) regulates ameloblast differentiation and enamel formation. In mouse incisor organ cultures, inhibition of ROCK, hindered IEE cell elongation and disrupted polarization of differentiated ameloblasts. Expression of enamel matrix proteins, such as amelogenin and ameloblastin, and formation of the terminal band structure of actin and E-cadherin were also perturbed. Cultures of dental epithelial cells revealed that ROCK regulates cell morphology and cell adhesion through localization of actin bundles, E-cadherin, and β-catenin to cell membranes. Moreover, inhibition of ROCK promoted cell proliferation. Small interfering RNA specific for ROCK1 and ROCK2 demonstrated that the ROCK isoforms performed complementary functions in the regulation of actin organization and E-cadherin-mediated cell-cell adhesion. Thus, our results have uncovered a novel role for ROCK in amelogenesis.

  16. Silibinin regulates lipid metabolism and differentiation in functional human adipocytes

    Directory of Open Access Journals (Sweden)

    Ignazio eBarbagallo

    2016-01-01

    Full Text Available Silibinin, a natural plant flavonoid, is the main active constituent found in milk thistle (Silybum marianum. It is known to have hepatoprotective, anti-neoplastic effect and suppresses lipid accumulation in adipocytes. Objective of this study was to investigate the effect of silibinin on adipogenic differentiation and thermogenic capacity of human adipose tissue derived mesenchymal stem cells. Silibinin (10 μM treatment, either at the beginning or at the end of adipogenic differentiation, resulted in an increase of SIRT-1, PPARα, Pgc-1α and UCPs gene expression. Moreover, silibinin administration resulted in a decrease of PPARγ, FABP4, FAS and MEST/PEG1 gene expression during the differentiation, confirming that this compound is able to reduce fatty acid accumulation and adipocyte size. Our data showed that silibinin regulated adipocyte lipid metabolism, inducing thermogenesis and promoting a brown remodelling in adipocyte. Taken together, our findings suggest that silibinin increases UCPs expression by stimulation of SIRT1, PPARα and Pgc-1α, improved metabolic parameters, decreased lipid mass leading to the formation of functional adipocytes.

  17. Differential Density Statistics of Galaxy Distribution and the Luminosity Function

    CERN Document Server

    Albani, V V L; Ribeiro, M B; Stöger, W R; Albani, Vinicius V. L.; Iribarrem, Alvaro S.; Ribeiro, Marcelo B.; Stoeger, William R.

    2006-01-01

    This paper uses data obtained from the galaxy luminosity function (LF) to calculate two types of radial number densities statistics of the galaxy distribution as discussed in Ribeiro (2005), namely the differential density $\\gamma$ and the integral differential density $\\gamma^\\ast$. By applying the theory advanced by Ribeiro and Stoeger (2003), which connects the relativistic cosmology number counts with the astronomically derived LF, the differential number counts $dN/dz$ are extracted from the LF and used to calculate both $\\gamma$ and $\\gamma^\\ast$ with various cosmological distance definitions, namely the area distance, luminosity distance, galaxy area distance and redshift distance. LF data are taken from the CNOC2 galaxy redshift survey and $\\gamma$ and $\\gamma^\\ast$ are calculated for two cosmological models: Einstein-de Sitter and an $\\Omega_{m_0}=0.3$, $\\Omega_{\\Lambda_0}=0.7$ standard cosmology. The results confirm the strong dependency of both statistics on the distance definition, as predicted in...

  18. ß2-adrenoceptor agonist-induced upregulation of tachykinin NK2 receptor expression and function in airway smooth muscle

    NARCIS (Netherlands)

    Katsunuma, T; Roffel, A.F; Elzinga, C.R S; Zaagsma, Hans; Barnes, P.J; Mak, J.CW

    Neurokinin A (NKA) induces bronchoconstriction mediated by tachykinin NK2 receptors in animals and humans, and may be increased in asthma. Because beta(2)-adrenoceptor agonists are the most widely used bronchodilators in asthma, we investigated the effects of the beta(2)-adrenoceptor agonist

  19. Differential Effects of Brain Disorders on Structural and Functional Connectivity

    Science.gov (United States)

    Vega-Pons, Sandro; Olivetti, Emanuele; Avesani, Paolo; Dodero, Luca; Gozzi, Alessandro; Bifone, Angelo

    2017-01-01

    Different measures of brain connectivity can be defined based on neuroimaging read-outs, including structural and functional connectivity. Neurological and psychiatric conditions are often associated with abnormal connectivity, but comparing the effects of the disease on different types of connectivity remains a challenge. In this paper, we address the problem of quantifying the relative effects of brain disease on structural and functional connectivity at a group level. Within the framework of a graph representation of connectivity, we introduce a kernel two-sample test as an effective method to assess the difference between the patients and control group. Moreover, we propose a common representation space for structural and functional connectivity networks, and a novel test statistics to quantitatively assess differential effects of the disease on different types of connectivity. We apply this approach to a dataset from BTBR mice, a murine model of Agenesis of the Corpus Callosum (ACC), a congenital disorder characterized by the absence of the main bundle of fibers connecting the two hemispheres. We used normo-callosal mice (B6) as a comparator. The application of the proposed methods to this data-set shows that the two types of connectivity can be successfully used to discriminate between BTBR and B6, meaning that both types of connectivity are affected by ACC. However, our novel test statistics shows that structural connectivity is significantly more affected than functional connectivity, consistent with the idea that functional connectivity has a robust topology that can tolerate substantial alterations in its structural connectivity substrate. PMID:28119556

  20. Nodal centrality of functional network in the differentiation of schizophrenia.

    Science.gov (United States)

    Cheng, Hu; Newman, Sharlene; Goñi, Joaquín; Kent, Jerillyn S; Howell, Josselyn; Bolbecker, Amanda; Puce, Aina; O'Donnell, Brian F; Hetrick, William P

    2015-10-01

    A disturbance in the integration of information during mental processing has been implicated in schizophrenia, possibly due to faulty communication within and between brain regions. Graph theoretic measures allow quantification of functional brain networks. Functional networks are derived from correlations between time courses of brain regions. Group differences between SZ and control groups have been reported for functional network properties, but the potential of such measures to classify individual cases has been little explored. We tested whether the network measure of betweenness centrality could classify persons with schizophrenia and normal controls. Functional networks were constructed for 19 schizophrenic patients and 29 non-psychiatric controls based on resting state functional MRI scans. The betweenness centrality of each node, or fraction of shortest-paths that pass through it, was calculated in order to characterize the centrality of the different regions. The nodes with high betweenness centrality agreed well with hub nodes reported in previous studies of structural and functional networks. Using a linear support vector machine algorithm, the schizophrenia group was differentiated from non-psychiatric controls using the ten nodes with the highest betweenness centrality. The classification accuracy was around 80%, and stable against connectivity thresholding. Better performance was achieved when using the ranks as feature space as opposed to the actual values of betweenness centrality. Overall, our findings suggest that changes in functional hubs are associated with schizophrenia, reflecting a variation of the underlying functional network and neuronal communications. In addition, a specific network property, betweenness centrality, can classify persons with SZ with a high level of accuracy.

  1. Lie Symmetry Analysis of the Hopf Functional-Differential Equation

    Directory of Open Access Journals (Sweden)

    Daniel D. Janocha

    2015-08-01

    Full Text Available In this paper, we extend the classical Lie symmetry analysis from partial differential equations to integro-differential equations with functional derivatives. We continue the work of Oberlack and Wacławczyk (2006, Arch. Mech. 58, 597, (2013, J. Math. Phys. 54, 072901, where the extended Lie symmetry analysis is performed in the Fourier space. Here, we introduce a method to perform the extended Lie symmetry analysis in the physical space where we have to deal with the transformation of the integration variable in the appearing integral terms. The method is based on the transformation of the product y(xdx appearing in the integral terms and applied to the functional formulation of the viscous Burgers equation. The extended Lie symmetry analysis furnishes all known symmetries of the viscous Burgers equation and is able to provide new symmetries associated with the Hopf formulation of the viscous Burgers equation. Hence, it can be employed as an important tool for applications in continuum mechanics.

  2. DMPD: Macrophage differentiation and function in health and disease. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18251777 Macrophage differentiation and function in health and disease. Naito M. Pa...thol Int. 2008 Mar;58(3):143-55. (.png) (.svg) (.html) (.csml) Show Macrophage differentiation and function in health... and disease. PubmedID 18251777 Title Macrophage differentiation and function in health and disease

  3. An Effect Size Measure for Raju's Differential Functioning for Items and Tests

    Science.gov (United States)

    Wright, Keith D.; Oshima, T. C.

    2015-01-01

    This study established an effect size measure for differential functioning for items and tests' noncompensatory differential item functioning (NCDIF). The Mantel-Haenszel parameter served as the benchmark for developing NCDIF's effect size measure for reporting moderate and large differential item functioning in test items. The effect size of…

  4. Function Substitution in Partial Differential Equations: Nonhomogeneous Boundary Conditions

    Directory of Open Access Journals (Sweden)

    T. V. Oblakova

    2017-01-01

    Full Text Available In this paper we consider a mixed initial-boundary value problem for a parabolic equation with nonhomogeneous boundary conditions. The classical methods of  searching for an analytical solution of such problems in the first stage involve variable substitution  , leading to a problem with homogeneous boundary conditions. In the reference literature ([1], as a rule, the simplest types of variable substitutions are given, under which the new and old unknown functions differ by a term linear in the spatial variable. The form of this additional term depends on the type of the boundary conditions, but is in no way connected with the equation under consideration. Moreover, in the case of the second boundary-value problem, it is necessary to use quadratic additives, since a linear replacement for this type of conditions may not exist. In the educational literature ([2] - [4], it is usually limited to considering only the first boundary-value problem in the general formulation.In this paper, we consider a substitution that takes into account in principle the form of a linear differential operator. Namely, as an additive term, it is proposed to use the parametrically time-dependent solution of the boundary value problem for an ordinary differential equation obtained from the original partial differential equation by the method of separation of the Fourier variables.The existence of the proposed replacement for boundary conditions of any type is proved on the example of a nonstationary heat equation in the presence of heat exchange with the surrounding medium. In this case, the additional term is a linear combination of hyperbolic functions. It is shown that in addition to the "insensitivity" to the type of boundary conditions, the advantages of a new replacement in comparison with the traditional linear (or quadratic substitution include a much simpler structure of the resulting solution. Namely, the described approach allows one to obtain a solution

  5. Non-monotonicity of Lyapunov functions for functional differential equations with enlightenments for related research methods

    Science.gov (United States)

    Zhao, Xueyan; Deng, Feiqi

    2016-07-01

    In this paper, a particular property of Lyapunov functions for functional differential equations (FDEs) is developed, that is the direct dependence of the signs of the derivatives of the Lyapunov functions on the initial data. This property implies that the derivatives of the Lyapunov functions for FDEs cannot be guaranteed to be negative definite generally, and then makes the FDEs differ from the ordinary differential equations constitutionally. With this property, we give some enlightenments for the research methods for establishing stability theorems or criteria for FDEs, which may help us to form a common view about the choice of the investigation methods on the stability of FDEs. The conclusion is stated in both the deterministic and stochastic versions. Two illustrative examples are given to show and verify our conclusion through the paper.

  6. Differential item functioning analysis by applying multiple comparison procedures.

    Science.gov (United States)

    Eusebi, Paolo; Kreiner, Svend

    2015-01-01

    Analysis within a Rasch measurement framework aims at development of valid and objective test score. One requirement of both validity and objectivity is that items do not show evidence of differential item functioning (DIF). A number of procedures exist for the assessment of DIF including those based on analysis of contingency tables by Mantel-Haenszel tests and partial gamma coefficients. The aim of this paper is to illustrate Multiple Comparison Procedures (MCP) for analysis of DIF relative to a variable defining a very large number of groups, with an unclear ordering with respect to the DIF effect. We propose a single step procedure controlling the false discovery rate for DIF detection. The procedure applies for both dichotomous and polytomous items. In addition to providing evidence against a hypothesis of no DIF, the procedure also provides information on subset of groups that are homogeneous with respect to the DIF effect. A stepwise MCP procedure for this purpose is also introduced.

  7. Differential assemblage of functional units in paddy soil microbiomes.

    Directory of Open Access Journals (Sweden)

    Yongkyu Kim

    Full Text Available Flooded rice fields are not only a global food source but also a major biogenic source of atmospheric methane. Using metatranscriptomics, we comparatively explored structural and functional succession of paddy soil microbiomes in the oxic surface layer and anoxic bulk soil. Cyanobacteria, Fungi, Xanthomonadales, Myxococcales, and Methylococcales were the most abundant and metabolically active groups in the oxic zone, while Clostridia, Actinobacteria, Geobacter, Anaeromyxobacter, Anaerolineae, and methanogenic archaea dominated the anoxic zone. The protein synthesis potential of these groups was about 75% and 50% of the entire community capacity, respectively. Their structure-function relationships in microbiome succession were revealed by classifying the protein-coding transcripts into core, non-core, and taxon-specific transcripts based on homologous gene distribution. The differential expression of core transcripts between the two microbiomes indicated that structural succession is primarily governed by the cellular ability to adapt to the given oxygen condition, involving oxidative stress, nitrogen/phosphorus metabolism, and fermentation. By contrast, the non-core transcripts were expressed from genes involved in the metabolism of various carbon sources. Among those, taxon-specific transcripts revealed highly specialized roles of the dominant groups in community-wide functioning. For instance, taxon-specific transcripts involved in photosynthesis and methane oxidation were a characteristic of the oxic zone, while those related to methane production and aromatic compound degradation were specific to the anoxic zone. Degradation of organic matters, antibiotics resistance, and secondary metabolite production were detected to be expressed in both the oxic and anoxic zones, but by different taxonomic groups. Cross-feeding of methanol between members of the Methylococcales and Xanthomonadales was suggested by the observation that in the oxic zone

  8. Contractivity and Exponential Stability of Solutions to Nonlinear Neutral Functional Differential Equations in Banach Spaces

    Institute of Scientific and Technical Information of China (English)

    Wan-sheng WANG; Shou-fu LI; Run-sheng YANG

    2012-01-01

    A series of contractivity and exponential stability results for the solutions to nonlinear neutral functional differential equations (NFDEs) in Banach spaces are obtained,which provide unified theoretical foundation for the contractivity analysis of solutions to nonlinear problems in functional differential equations (FDEs),neutral delay differential equations (NDDEs) and NFDEs of other types which appear in practice.

  9. Wavefront sensing with the differential optical transfer function

    Science.gov (United States)

    Hart, Michael; Codona, Johanan L.

    2012-10-01

    Recently a new technique for estimating the complex field in the pupil of a telescope from image-plane intensity measurements has been introduced by Codona.1, 2 The simplest form of the method uses two images of a point source, one with a small modification introduced in the pupil. The algorithm to recover the pupil field uses a functional derivative of the optical transfer function (OTF), and is simple and non-iterative. The derivative is approximated empirically by the difference between the Fourier transforms of the two PSFs: the differential OTF or dOTF. In keeping with the Hermitian symmetry of the OTF, the dOTF includes two conjugate copies of the pupil field overlapping at the point of modification. By placing the modification near the edge of the pupil, the overlap region can be kept small. It can be eliminated altogether by using a second modification and a third image. The technique can be used in broadband light, at the cost of blurring in the recovered phase that is proportional to the fractional bandwidth. Although the dOTF is unlikely to find application in high frame rate astronomical adaptive optics, it has many potential uses such as optical shop testing, non-common-path wavefront error estimation, segmented telescope phasing and general imaging system diagnostics. In this paper, we review the dOTF concept, theory, and initial experiments to demonstrate the technique.

  10. Multiscale functions, scale dynamics, and applications to partial differential equations

    Science.gov (United States)

    Cresson, Jacky; Pierret, Frédéric

    2016-05-01

    Modeling phenomena from experimental data always begins with a choice of hypothesis on the observed dynamics such as determinism, randomness, and differentiability. Depending on these choices, different behaviors can be observed. The natural question associated to the modeling problem is the following: "With a finite set of data concerning a phenomenon, can we recover its underlying nature? From this problem, we introduce in this paper the definition of multi-scale functions, scale calculus, and scale dynamics based on the time scale calculus [see Bohner, M. and Peterson, A., Dynamic Equations on Time Scales: An Introduction with Applications (Springer Science & Business Media, 2001)] which is used to introduce the notion of scale equations. These definitions will be illustrated on the multi-scale Okamoto's functions. Scale equations are analysed using scale regimes and the notion of asymptotic model for a scale equation under a particular scale regime. The introduced formalism explains why a single scale equation can produce distinct continuous models even if the equation is scale invariant. Typical examples of such equations are given by the scale Euler-Lagrange equation. We illustrate our results using the scale Newton's equation which gives rise to a non-linear diffusion equation or a non-linear Schrödinger equation as asymptotic continuous models depending on the particular fractional scale regime which is considered.

  11. DIFFERENTIABILITY OF CONVEX FUNCTIONS ON SUBLINEAR TOPOLOGICAL SPACES AND VARIATIONAL PRINCIPLES IN LOCALLY CONVEX SPACES

    Institute of Scientific and Technical Information of China (English)

    CHENG LIXIN; TENG YANMEI

    2005-01-01

    This paper presents a type of variational principles for real valued w* lower semicon tinuous functions on certain subsets in duals of locally convex spaces, and resolve a problem concerning differentiability of convex functions on general Banach spaces. They are done through discussing differentiability of convex functions on nonlinear topological spaces and convexification of nonconvex functions on topological linear spaces.

  12. Dystroglycan depletion inhibits the functions of differentiated HL-60 cells.

    Science.gov (United States)

    Martínez-Zárate, Alma Delia; Martínez-Vieyra, Ivette; Alonso-Rangel, Lea; Cisneros, Bulmaro; Winder, Steve J; Cerecedo, Doris

    2014-06-01

    Dystroglycan has recently been characterized in blood tissue cells, as part of the dystrophin glycoprotein complex but to date nothing is known of its role in the differentiation process of neutrophils. We have investigated the role of dystroglycan in the human promyelocytic leukemic cell line HL-60 differentiated to neutrophils. Depletion of dystroglycan by RNAi resulted in altered morphology and reduced properties of differentiated HL-60 cells, including chemotaxis, respiratory burst, phagocytic activities and expression of markers of differentiation. These findings strongly implicate dystroglycan as a key membrane adhesion protein involved in the differentiation process in HL-60 cells.

  13. A linear functional differential equation with distributions in the input

    Directory of Open Access Journals (Sweden)

    Vadim Z. Tsalyuk

    2003-10-01

    Full Text Available This paper studies the functional differential equation $$ dot x(t = int_a^t {d_s R(t,s, x(s} + F'(t, quad t in [a,b], $$ where $F'$ is a generalized derivative, and $R(t,cdot$ and $F$ are functions of bounded variation. A solution is defined by the difference $x - F$ being absolutely continuous and satisfying the inclusion $$ frac{d}{dt} (x(t - F(t in int_a^t {d_s R(t,s,x(s}. $$ Here, the integral in the right is the multivalued Stieltjes integral presented in cite{VTs1} (in this article we review and extend the results in cite{VTs1}. We show that the solution set for the initial-value problem is nonempty, compact, and convex. A solution $x$ is said to have memory if there exists the function $x$ such that $x(a = x(a$, $x(b = x(b$, $ x(t in [x(t-0,x(t+0]$ for $t in (a,b$, and $frac{d}{dt} (x(t - F(t = int_a^t {d_s R(t,s,{x}(s}$, where Lebesgue-Stieltjes integral is used. We show that such solutions form a nonempty, compact, and convex set. It is shown that solutions with memory obey the Cauchy-type formula $$ x(t in C(t,ax(a + int_a^t C(t,s, dF(s. $$

  14. General Large Deviations and Functional Iterated Logarithm Law for Multivalued Stochastic Differential Equations

    OpenAIRE

    Ren, Jiagang; Wu, Jing; Zhang, Hua

    2015-01-01

    In this paper, we prove a large deviation principle of Freidlin-Wentzell's type for the multivalued stochastic differential equations. As an application, we derive a functional iterated logarithm law for the solutions of multivalued stochastic differential equations.

  15. Construction of a Smooth Lyapunov Function for the Robust and Exact Second-Order Differentiator

    OpenAIRE

    2016-01-01

    Differentiators play an important role in (continuous) feedback control systems. In particular, the robust and exact second-order differentiator has shown some very interesting properties and it has been used successfully in sliding mode control, in spite of the lack of a Lyapunov based procedure to design its gains. As contribution of this paper, we provide a constructive method to determine a differentiable Lyapunov function for such a differentiator. Moreover, the Lyapunov function is used...

  16. Functional differentiation of cytotoxic cancer drugs and targeted cancer therapeutics.

    Science.gov (United States)

    Winkler, Gian C; Barle, Ester Lovsin; Galati, Giuseppe; Kluwe, William M

    2014-10-01

    There is no nationally or internationally binding definition of the term "cytotoxic drug" although this term is used in a variety of regulations for pharmaceutical development and manufacturing of drugs as well as in regulations for protecting medical personnel from occupational exposure in pharmacy, hospital, and other healthcare settings. The term "cytotoxic drug" is frequently used as a synonym for any and all oncology or antineoplastic drugs. Pharmaceutical companies generate and receive requests for assessments of the potential hazards of drugs regularly - including cytotoxicity. This publication is intended to provide functional definitions that help to differentiate between generically-cytotoxic cancer drugs of significant risk to normal human tissues, and targeted cancer therapeutics that pose much lesser risks. Together with specific assessments, it provides comprehensible guidance on how to assess the relevant properties of cancer drugs, and how targeted therapeutics discriminate between cancer and normal cells. The position of several regulatory agencies in the long-term is clearly to regulate all drugs regardless of classification, according to scientific risk based data. Despite ongoing discussions on how to replace the term "cytotoxic drugs" in current regulations, it is expected that its use will continue for the near future. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Differential Connexin Function Enhances Self-Renewal in Glioblastoma

    Directory of Open Access Journals (Sweden)

    Masahiro Hitomi

    2015-05-01

    Full Text Available The coordination of complex tumor processes requires cells to rapidly modify their phenotype and is achieved by direct cell-cell communication through gap junction channels composed of connexins. Previous reports have suggested that gap junctions are tumor suppressive based on connexin 43 (Cx43, but this does not take into account differences in connexin-mediated ion selectivity and intercellular communication rate that drive gap junction diversity. We find that glioblastoma cancer stem cells (CSCs possess functional gap junctions that can be targeted using clinically relevant compounds to reduce self-renewal and tumor growth. Our analysis reveals that CSCs express Cx46, while Cx43 is predominantly expressed in non-CSCs. During differentiation, Cx46 is reduced, while Cx43 is increased, and targeting Cx46 compromises CSC maintenance. The difference between Cx46 and Cx43 is reflected in elevated cell-cell communication and reduced resting membrane potential in CSCs. Our data demonstrate a pro-tumorigenic role for gap junctions that is dependent on connexin expression.

  18. Selective oestrogen receptor modulators differentially potentiate brain mitochondrial function.

    Science.gov (United States)

    Irwin, R W; Yao, J; To, J; Hamilton, R T; Cadenas, E; Brinton, R D

    2012-01-01

    The mitochondrial energy-transducing capacity of the brain is important for long-term neurological health and is influenced by endocrine hormone responsiveness. The present study aimed to determine the role of oestrogen receptor (ER) subtypes in regulating mitochondrial function using selective agonists for ERα (propylpyrazoletriol; PPT) and ERβ (diarylpropionitrile; DPN). Ovariectomised female rats were treated with 17β-oestradiol (E(2) ), PPT, DPN or vehicle control. Both ER selective agonists significantly increased the mitochondrial respiratory control ratio and cytochrome oxidase (COX) activity relative to vehicle. Western blots of purified whole brain mitochondria detected ERα and, to a greater extent, ERβ localisation. Pre-treatment with DPN, an ERβ agonist, significantly increased ERβ association with mitochondria. In the hippocampus, DPN activated mitochondrial DNA-encoded COX I expression, whereas PPT was ineffective, indicating that mechanistically ERβ, and not ERα, activated mitochondrial transcriptional machinery. Both selective ER agonists increased protein expression of nuclear DNA-encoded COX IV, suggesting that activation of ERβ or ERα is sufficient. Selective ER agonists up-regulated a panel of bioenergetic enzymes and antioxidant defence proteins. Up-regulated proteins included pyruvate dehydrogenase, ATP synthase, manganese superoxide dismutase and peroxiredoxin V. In vitro, whole cell metabolism was assessed in live primary cultured hippocampal neurones and mixed glia. The results of analyses conducted in vitro were consistent with data obtained in vivo. Furthermore, lipid peroxides, accumulated as a result of hormone deprivation, were significantly reduced by E(2) , PPT and DPN. These findings suggest that the activation of both ERα and ERβ is differentially required to potentiate mitochondrial function in brain. As active components in hormone therapy, synthetically designed oestrogens as well as natural phyto-oestrogen cocktails

  19. Method of the Logistic Function for Finding Analytical Solutions of Nonlinear Differential Equations

    OpenAIRE

    Kudryashov, N. A.

    2015-01-01

    The method of the logistic function is presented for finding exact solutions of nonlinear differential equations. The application of the method is illustrated by using the nonlinear ordinary differential equation of the fourth order. Analytical solutions obtained by this method are presented. These solutions are expressed via exponential functions.logistic function, nonlinear wave, nonlinear ordinary differential equation, Painlev´e test, exact solution

  20. RAZUMIKHIN-TYPE THEOREM FOR NEUTRAL STOCHASTIC FUNCTIONAL DIFFERENTIAL EQUATIONS WITH UNBOUNDED DELAY

    Institute of Scientific and Technical Information of China (English)

    Wu Fuke; Hu Shigeng; Mao Xuerong

    2011-01-01

    This paper establishes the Razumikhin-type theorem on stability for neutral stochastic functional differential equations with unbounded delay.To overcome difficulties from unbounded delay,we develop several different techniques to investigate stability.To show our idea clearly,we examine neutral stochastic delay differential equations with unbounded delay and linear neutral stochastic Volterra unbounded-delay-integro-differential equations.

  1. THIRD-ORDER DIFFERENTIAL SUBORDINATION RESULTS FOR ANALYTIC FUNCTIONS INVOLVING THE GENERALIZED BESSEL FUNCTIONS

    Institute of Scientific and Technical Information of China (English)

    Huo TANG; Erhan DENIZ

    2014-01-01

    In the present paper, we derive some third-order differential subordination results for analytic functions in the open unit disk, using the operator Bcκf by means of normalized form of the generalized Bessel functions of the first kind, which is defined as z(Bcκ+1f(z))′=κBcκf(z)−(κ−1)Bcκ+1f(z), where b, c, p ∈ C and κ = p+(b+1)/2 ∈ C\\Z−0 (Z−0 = {0,−1,−2, · · ·}). The results are obtained by considering suitable classes of admissible functions. Various known or new special cases of our main results are also pointed out.

  2. NONDENSELY DEFINED IMPULSIVE NEUTRAL FUNCTIONAL DIFFERENTIAL INCLUSIONS WITH NONLOCAL CONDITIONS

    Institute of Scientific and Technical Information of China (English)

    Yueju Cao; Xianlong Fu

    2009-01-01

    In this paper, using a fixed point theorem for condensing multi-valued maps, we investigate the existence of integral solutions to a class of nondensely defined neutral evolution impulsive differential inclusions with nonlocal conditions in Banach spaces.

  3. Stability analysis of solutions to nonlinear stiff Volterra functional differential equations in Banach spaces

    Institute of Scientific and Technical Information of China (English)

    LI Shoufu

    2005-01-01

    A series of stability, contractivity and asymptotic stability results of the solutions to nonlinear stiff Volterra functional differential equations (VFDEs) in Banach spaces is obtained, which provides the unified theoretical foundation for the stability analysis of solutions to nonlinear stiff problems in ordinary differential equations(ODEs), delay differential equations(DDEs), integro-differential equations(IDEs) and VFDEs of other type which appear in practice.

  4. A BSDE approach to Nash equilibrium payoffs for stochastic differential games with nonlinear cost functionals

    OpenAIRE

    Lin, Qian

    2011-01-01

    In this paper, we study Nash equilibrium payoffs for nonzero-sum stochastic differential games via the theory of backward stochastic differential equations. We obtain an existence theorem and a characterization theorem of Nash equilibrium payoffs for nonzero-sum stochastic differential games with nonlinear cost functionals defined with the help of a doubly controlled backward stochastic differential equation. Our results extend former ones by Buckdahn, Cardaliaguet and Rainer (2004) and are b...

  5. SINGULARLY PERTURBED NONLINEAR BOUNDARY VALUE PROBLEM FOR A KIND OF VOLTERRA TYPE FUNCTIONAL DIFFERENTIAL EQUATION

    Institute of Scientific and Technical Information of China (English)

    鲁世平

    2003-01-01

    By employing the theory of differential inequality and some analysis methods, a nonlinear boundary value problem subject to a general kind of second-order Volterra functional differential equation was considered first. Then, by constructing the right-side layer function and the outer solution, a nonlinear boundary value problem subject to a kind of second- order Volterra functional differential equation with a small parameter was studied further. By using the differential mean value theorem and the technique of upper and lower solution, a new result on the existence of the solutions to the boundary value problem is obtained, and a uniformly valid asymptotic expansions of the solution is given as well.

  6. Differential item functioning in the figure classification test

    Directory of Open Access Journals (Sweden)

    E. van Zyl

    1998-06-01

    Full Text Available The elimination of unfair discrimination and cultural bias of any kind, is a contentious workplace issue in contemporary South Africa. To ensure fairness in testing, psychometric instruments are subjected to empirical investigations for the detection of possible bias that could lead to selection decisions constituting unfair discrimination. This study was conducted to explore the possible existence of differential item functioning (DIF, or potential bias, in the Figure Classification Test (A121 by means of the Mantel-Haenszel chi-square technique. The sample consisted of 498 men at a production company in the Western Cape. Although statistical analysis revealed significant differences between the mean test scores of three racial groups on the test, very few items were identified as having statistically significant DIF. The possibility is discussed that, despite the presence of some DIF, the differences between the means may not be due to the measuring instrument itself being biased/ but rather to extraneous sources of variation, such as the unequal education and socio-economic backgrounds of the racial groups. It was concluded that there is very little evidence of item bias in the test. Opsomming Die uitskakeling van onregverdige diskriminasie en kultuursydigheid van enige aard, is tans 'n omstrede kwessie in die werkpiek in Suid-Afrika. Ten einde regverdigheid in toetsing te verseker, word psigomefrriese toetse onderwerp aan empiriese ondersoeke na die moontlikheid van sydigheid wat kan lei tot keuringsbesluite wat onregverdige diskriminasie meebring. Hierdie ondersoek is ondemeem om die moontlikheid van differensiele itemfunksionering (DIF, of potensiële sydigheid, in die Figuurindelingtoets (A121, met behulp van die Mantel-Haenszel chikwadraattegniek, te ondersoek. Die steekproef het bestaan uit 498 mans by 'n produksiemaatskappy in die Wes-Kaap. Alhoewel statistiese ontleding beduidende verskille in gemiddelde toetstellings van drie

  7. Second-order complex linear differential equations with special functions or extremal functions as coefficients

    Directory of Open Access Journals (Sweden)

    Xiubi Wu

    2015-05-01

    Full Text Available The classical problem of finding conditions on the entire coefficients A(z and B(z guaranteeing that all nontrivial solutions of $f''+A(zf'+B(zf=0$ are of infinite order is discussed. Two distinct approaches are used. In the first approach the coefficient A(z itself is a solution of a differential equation $w''+P(zw=0$, where P(z is a polynomial. This assumption yields stability on the behavior of A(z via Hille's classical method on asymptotic integration. In this case A(z is a special function of which the Airy integral is one example. The second approach involves extremal functions. It is assumed that either A(z is extremal for Yang's inequality or B(z is extremal for Denjoy's conjecture. A combination of these two approaches is also discussed.

  8. ATTRACTING AND QUASI-INVARIANT SETS OF STOCHASTIC NEUTRAL PARTIAL FUNCTIONAL DIFFERENTIAL EQUATIONS

    Institute of Scientific and Technical Information of China (English)

    Dingshi LI; Daoyi XU

    2013-01-01

    In this article,we investigate a class of stochastic neutral partial functional differential equations.By establishing new integral inequalities,the attracting and quasi-invariant sets of stochastic neutral partial functional differential equations are obtained.The results in [15,16] are generalized and improved.

  9. A Comparison of Function-Based Differential Reinforcement Interventions for Children Engaging in Disruptive Classroom Behavior

    Science.gov (United States)

    LeGray, Matthew W.; Dufrene, Brad A.; Sterling-Turner, Heather; Olmi, D. Joe; Bellone, Katherine

    2010-01-01

    This study provides a direct comparison of differential reinforcement of other behavior (DRO) and differential reinforcement of alternative behavior (DRA). Participants included three children in center-based classrooms referred for functional assessments due to disruptive classroom behavior. Functional assessments included interviews and brief…

  10. The Item Parameter Replication Method for Detecting Differential Functioning in the Polytomous DFIT Framework

    Science.gov (United States)

    Raju, Nambury S.; Fortmann-Johnson, Kristen A.; Kim, Wonsuk; Morris, Scott B.; Nering, Michael L.; Oshima, T. C.

    2009-01-01

    The recent study of Oshima, Raju, and Nanda proposes the item parameter replication (IPR) method for assessing statistical significance of the noncompensatory differential item functioning (NCDIF) index within the differential functioning of items and tests (DFIT) framework. Previous Monte Carlo simulations have found that the appropriate cutoff…

  11. Intergroup differentiation: stereotyping as a function of status hierarchy.

    Science.gov (United States)

    Hopkins, N; Rae, C

    2001-06-01

    The authors explored how negative intergroup comparisons affect intergroup differentiation. More specifically, they tested the prediction that the in-group's negative intergroup comparisons with a high-status group would result in more negative stereotyping of a lower status out-group. The authors elicited stereotypes of a lower status university in 2 conditions. In the 1st, the participants judged only the middle-ranking university in-group and a lower status university. In the 2nd, those judgments followed comparison with a higher status university. In the 2nd condition, there was an increased differentiation between the in-group and the lower status out-group because of the more negative stereotyping of the lower status out-group. This evidence of intergroup differentiation was found only on the dimension judged most important and along which the in-group was negatively compared with the higher status group.

  12. Plasma membrane cholesterol level and agonist-induced internalization of δ-opioid receptors; colocalization study with intracellular membrane markers of Rab family.

    Science.gov (United States)

    Brejchova, Jana; Vosahlikova, Miroslava; Roubalova, Lenka; Parenti, Marco; Mauri, Mario; Chernyavskiy, Oleksandr; Svoboda, Petr

    2016-08-01

    Decrease of cholesterol level in plasma membrane of living HEK293 cells transiently expressing FLAG-δ-OR by β-cyclodextrin (β-CDX) resulted in a slight internalization of δ-OR. Massive internalization of δ-OR induced by specific agonist DADLE was diminished in cholesterol-depleted cells. These results suggest that agonist-induced internalization of δ-OR, which has been traditionally attributed exclusively to clathrin-mediated pathway, proceeds at least partially via membrane domains. Identification of internalized pools of FLAG-δ-OR by colocalization studies with proteins of Rab family indicated the decreased presence of receptors in early endosomes (Rab5), late endosomes and lysosomes (Rab7) and fast recycling vesicles (Rab4). Slow type of recycling (Rab11) was unchanged by cholesterol depletion. As expected, agonist-induced internalization of oxytocin receptors was totally suppressed in β-CDX-treated cells. Determination of average fluorescence lifetime of TMA-DPH, the polar derivative of hydrophobic membrane probe diphenylhexatriene, in live cells by FLIM indicated a significant alteration of the overall PM structure which may be interpreted as an increased "water-accessible space" within PM area. Data obtained by studies of HEK293 cells transiently expressing FLAG-δ-OR by "antibody feeding" method were extended by analysis of the effect of cholesterol depletion on distribution of FLAG-δ-OR in sucrose density gradients prepared from HEK293 cells stably expressing FLAG-δ-OR. Major part of FLAG-δ-OR was co-localized with plasma membrane marker Na,K-ATPase and β-CDX treatment resulted in shift of PM fragments containing both FLAG-δ-OR and Na,K-ATPase to higher density. Thus, the decrease in content of the major lipid constituent of PM resulted in increased density of resulting PM fragments.

  13. Function spaces and partial differential equations volume 2 : contemporary analysis

    CERN Document Server

    Taheri, Ali

    2015-01-01

    This is a book written primarily for graduate students and early researchers in the fields of Analysis and Partial Differential Equations (PDEs). Coverage of the material is essentially self-contained, extensive and novel with great attention to details and rigour.

  14. Function spaces and partial differential equations 2 volume set

    CERN Document Server

    Taheri, Ali

    2015-01-01

    This is a book written primarily for graduate students and early researchers in the fields of Analysis and Partial Differential Equations (PDEs). Coverage of the material is essentially self-contained, extensive and novel with great attention to details and rigour.

  15. Differential expression and function of stamp family proteins in adipocyte differentiation.

    Directory of Open Access Journals (Sweden)

    Jørgen Sikkeland

    Full Text Available Six transmembrane protein of prostate (Stamp proteins play an important role in prostate cancer cell growth. Recently, we found that Stamp2 has a critical role in the integration of inflammatory and metabolic signals in adipose tissue where it is highly expressed and regulated by nutritional and metabolic cues. In this study, we show that all Stamp family members are differentially regulated during adipogenesis: whereas Stamp1 expression is significantly decreased upon differentiation, Stamp2 expression is increased. In contrast, Stamp3 expression is modestly changed in adipocytes compared to preadipocytes, and has a biphasic expression pattern during the course of differentiation. Suppression of Stamp1 or Stamp2 expression both led to inhibition of 3T3-L1 differentiation in concert with diminished expression of the key regulators of adipogenesis - CCAAT/enhancer binding protein alpha (C/ebpα and peroxisome proliferator-activated receptor gamma (Pparγ. Upon Stamp1 knockdown, mitotic clonal expansion was also inhibited. In contrast, Stamp2 knockdown did not affect mitotic clonal expansion, but resulted in a marked decrease in superoxide production that is known to affect adipogenesis. These results suggest that Stamp1 and Stamp2 play critical roles in adipogenesis, but through different mechanisms.

  16. Differentiation mechanism and function of the cereal aleurone cells and hormone effects on them.

    Science.gov (United States)

    Zheng, Yankun; Wang, Zhong

    2014-11-01

    The cereal aleurone cells differentiate from the endosperm epidermis with the exception of endosperm transfer cells. Aleurone cells contain proteins, lipids, and minerals, and are important for digesting the endosperm storage products to nurse the embryo under effects of several hormones during the seed germination. The differentiation of aleurone cells is related to location effect and special gene expression. Moreover, the differentiation of aleurone cells is probably affected by the cues from maternal tissues. In the paper, differentiation mechanism and function of aleurone cells and hormone effects on them are reviewed. Some speculations about the differentiation mechanism of aleurone cells are given here.

  17. New Differential Properties of Sup-type Functions

    Institute of Scientific and Technical Information of China (English)

    Jin-chuan Zhou; Chang-yu Wang

    2009-01-01

    In this paper, we study the directional derivative, subderivative, and subdifferential of sup-type functions without any compactness assumption on the index set. As applications, we provide an estimate of the Lipschitz modulus for sup-type functions.

  18. Construction of a Smooth Lyapunov Function for the Robust and Exact Second-Order Differentiator

    Directory of Open Access Journals (Sweden)

    Tonametl Sanchez

    2016-01-01

    Full Text Available Differentiators play an important role in (continuous feedback control systems. In particular, the robust and exact second-order differentiator has shown some very interesting properties and it has been used successfully in sliding mode control, in spite of the lack of a Lyapunov based procedure to design its gains. As contribution of this paper, we provide a constructive method to determine a differentiable Lyapunov function for such a differentiator. Moreover, the Lyapunov function is used to provide a procedure to design the differentiator’s parameters. Also, some sets of such parameters are provided. The determination of the positive definiteness of the Lyapunov function and negative definiteness of its derivative is converted to the problem of solving a system of inequalities linear in the parameters of the Lyapunov function candidate and also linear in the gains of the differentiator, but bilinear in both.

  19. Spline Approximation for Autonomous Nonlinear Functional Differential Equations.

    Science.gov (United States)

    1980-06-18

    Af(e / a e(-T)/ P(T)dT) + q. An easy calculation using (H2) shows that h has the Lipschitz constant XL(m+l+r1 /2) on In. This proves b) with X0 = i/L...84A(1979), 71-91. [13] R.D. Nussbaum, Uniqueness and nonuniqueness for periodic solutions of x’(t) - -g(x(t-1)), J. Differential Eqs. 34(1979), 25-54

  20. Generalized functions, volume 3 theory of differential equations

    CERN Document Server

    Gel′fand, I M

    2016-01-01

    The first systematic theory of generalized functions (also known as distributions) was created in the early 1950s, although some aspects were developed much earlier, most notably in the definition of the Green's function in mathematics and in the work of Paul Dirac on quantum electrodynamics in physics. The six-volume collection, Generalized Functions, written by I. M. Gel′fand and co-authors and published in Russian between 1958 and 1966, gives an introduction to generalized functions and presents various applications to analysis, PDE, stochastic processes, and representation theory. In Volum

  1. Periodic differential equations an introduction to Mathieu, Lamé, and allied functions

    CERN Document Server

    Arscott, Felix M; Stark, M; Ulam, S

    1964-01-01

    Periodic Differential Equations: An Introduction to Mathieu, Lamé, and Allied Functions covers the fundamental problems and techniques of solution of periodic differential equations. This book is composed of 10 chapters that present important equations and the special functions they generate, ranging from Mathieu's equation to the intractable ellipsoidal wave equation.This book starts with a survey of the main problems related to the formation of periodic differential equations. The subsequent chapters deal with the general theory of Mathieu's equation, Mathieu functions of integral order, and

  2. B-Theory of Runge-Kutta methods for stiff Volterra functional differential equations

    Institute of Scientific and Technical Information of China (English)

    LI; Shoufu(李寿佛)

    2003-01-01

    B-stability and B-convergence theories of Runge-Kutta methods for nonlinear stiff Volterra func-tional differential equations (VFDEs) are established which provide unified theoretical foundation for the studyof Runge-Kutta methods when applied to nonlinear stiff initial value problems (IVPs) in ordinary differentialequations (ODEs), delay differential equations (DDEs), integro-differential equations (IDEs) and VFDEs ofother type which appear in practice.

  3. Comparison of two definitions of lower and upper functions associated to nonlinear second order differential equations

    Directory of Open Access Journals (Sweden)

    Vrkoč Ivo

    2001-01-01

    Full Text Available The notions of lower and upper functions of the second order differential equations take their beginning from the classical work by C. Scorza-Dragoni and have been investigated till now because they play an important role in the theory of nonlinear boundary value problems. Most of them define lower and upper functions as solutions of the corresponding second order differential inequalities. The aim of this paper is to compare two more general approaches. One is due to Rachůnková and Tvrdý (Nonlinear systems of differential inequalities and solvability of certain boundary value problems (J. of Inequal. & Appl. (to appear who defined the lower and upper functions of the given equation as solutions of associated systems of two differential inequalities with solutions possibly not absolutely continuous. The second belongs to Fabry and Habets (Nonlinear Analysis, TMA 10 (1986, 985–1007 and requires the monotonicity of certain integro-differential expressions.

  4. Nonlinear differential equations with exact solutions expressed via the Weierstrass function

    NARCIS (Netherlands)

    Kudryashov, NA

    2004-01-01

    A new problem is studied, that is to find nonlinear differential equations with special solutions expressed via the Weierstrass function. A method is discussed to construct nonlinear ordinary differential equations with exact solutions. The main step of our method is the assumption that nonlinear di

  5. Some Properties of Solutions of a Functional-Differential Equation of Second Order with Delay

    Directory of Open Access Journals (Sweden)

    Veronica Ana Ilea

    2014-01-01

    Full Text Available Existence, uniqueness, data dependence (monotony, continuity, and differentiability with respect to parameter, and Ulam-Hyers stability results for the solutions of a system of functional-differential equations with delays are proved. The techniques used are Perov’s fixed point theorem and weakly Picard operator theory.

  6. Communication abnormalities predict functional outcomes in chronic schizophrenia: differential associations with social and adaptive functions.

    Science.gov (United States)

    Bowie, Christopher R; Harvey, Philip D

    2008-08-01

    Communication abnormalities are hallmark features of schizophrenia. Despite the prevalence and persistence of these symptoms, little is known about their functional implications. In this study, we examined, in a sample of chronically institutionalized schizophrenia patients (N=317), whether two types of communication abnormalities (i.e., verbal underproductivity and disconnected speech) had differential relationships with social and adaptive outcomes. Baseline ratings of verbal underproductivity, disconnected speech, global cognitive performance, and clinical symptoms, were entered into stepwise regression analyses to examine their relationship with 2.5 year social and adaptive outcomes. At baseline, disconnected speech was significantly associated with socially impolite behavior, while verbal underproductivity was associated with social disengagement and impaired friendships. Both types of communication abnormalities were significantly associated with other types of social skills. Verbal underproductivity predicted follow-up social skills, social engagement, and friendships, accounting for more variance than. cognition or symptoms. In contrast to social outcomes, adaptive outcomes were predicted by baseline neurocognition and clinical symptoms, but not communication abnormalities. These findings provide evidence for specific relationships of communication disorder subtypes with diverse impairments in social functions. In this chronically institutionalized sample, communication disorder was a stronger predictor of social, but not adaptive, outcomes than neurocognition or clinical symptoms.

  7. MiRNA-181a regulates Toll-like receptor agonist-induced inflammatory response in human fibroblasts

    OpenAIRE

    Galicia, Johnah C.; Naqvi, Afsar R; Ko, Ching-Chang; Nares, Salvador; Khan, Asma A.

    2014-01-01

    MicroRNAs (miRNA) regulate the synthesis of cytokines in response to Toll-like receptor (TLR) activation. Our recent microarray study comparing normal and inflamed human dental pulps showed that miRNA-181 (miR-181) family is differentially expressed in the presence of inflammation. Prior studies have reported that the dental pulp, which is composed primarily of TLR4/2+ fibroblasts, expresses elevated levels of cytokines including Interleukin-8 (IL-8) when inflamed. In this study, we employed ...

  8. Green's functional for a higher order ordinary integro-differential equation with nonlocal conditions

    Science.gov (United States)

    Özen, Kemal

    2016-12-01

    One of the little-known techniques for ordinary integro-differential equations in literature is Green's functional method, the origin of which dates back to Azerbaijani scientist Seyidali S. Akhiev. According to this method, Green's functional concepts for some simple forms of such equations have been introduced in the several studies. In this study, we extend Green's functional concept to a higher order ordinary integro-differential equation involving generally nonlocal conditions. A novel kind of adjoint problem and Green's functional are constructed for completely nonhomogeneous problem. By means of the obtained Green's functional, the solution to the problem is identified.

  9. Some function spaces and elliptic partial differential equations

    Directory of Open Access Journals (Sweden)

    Pietro Zamboni

    1987-11-01

    Full Text Available In this paper we compare some function spaces which are relevant to an integral inequality.An unique continuation result for nonnegative solution of elliptic P.D.E.'s is also proved.

  10. Multiresolution Analysis by Infinitely Differentiable Compactly Supported Functions

    Science.gov (United States)

    1992-09-01

    Z 2. Wavelet decompositions The up function provides an interesting example of wavelet decompositions via multiresolution. A general discussion of...Math. Surveys 45:1 (1990), 87-120. [I] (;. Strang and G. Fix, A Fourier analysis of the finite element variational method. C.I.M.F. I 1 Ciclo 1971, in Constructi’c Aspects of Functional Analyszs ed. G. Geymonat 1973, 793-840. 10

  11. Evidence for a model of agonist-induced activation of 5-hydroxytryptamine 2A serotonin receptors that involves the disruption of a strong ionic interaction between helices 3 and 6.

    Science.gov (United States)

    Shapiro, David A; Kristiansen, Kurt; Weiner, David M; Kroeze, Wesley K; Roth, Bryan L

    2002-03-29

    5-Hydroxytryptamine 2A (5-HT2A) receptors are essential for the actions of serotonin (5-hydroxytryptamine (5-HT)) on physiological processes as diverse as vascular smooth muscle contraction, platelet aggregation, perception, and emotion. In this study, we investigated the molecular mechanism(s) by which 5-HT activates 5-HT2A receptors using a combination of approaches including site-directed mutagenesis, molecular modeling, and pharmacological analysis using the sensitive, cell-based functional assay R-SAT. Alanine-scanning mutagenesis of residues close to the intracellular end of H6 of the 5-HT2A receptor implicated glutamate Glu-318(6.30) in receptor activation, as also predicted by a newly constructed molecular model of the 5-HT2A receptor, which was based on the x-ray structure of bovine rhodopsin. Close examination of the molecular model suggested that Glu-318(6.30) could form a strong ionic interaction with Arg-173(3.50) of the highly conserved "(D/E)RY motif" located at the interface between the third transmembrane segment and the second intracellular loop (i2). A direct prediction of this hypothesis, that disrupting this ionic interaction by an E318(6.30)R mutation would lead to a highly constitutively active receptor with enhanced affinity for agonist, was confirmed using R-SAT. Taken together, these results predict that the disruption of a strong ionic interaction between transmembrane helices 3 and 6 of 5-HT2A receptors is essential for agonist-induced receptor activation and, as recently predicted by ourselves (B. L. Roth and D. A. Shapiro (2001) Expert Opin. Ther. Targets 5, 685-695) and others, that this may represent a general mechanism of activation for many, but not all, G-protein-coupled receptors.

  12. On Singular Solutions of Linear Functional Differential Equations with Negative Coefficients

    Directory of Open Access Journals (Sweden)

    Rontó András

    2008-01-01

    Full Text Available Abstract The problem on solutions with specified growth for linear functional differential equations with negative coefficients is treated by using two-sided monotone iterations. New theorems on the existence and localisation of such solutions are established.

  13. On Singular Solutions of Linear Functional Differential Equations with Negative Coefficients

    Directory of Open Access Journals (Sweden)

    András Rontó

    2008-10-01

    Full Text Available The problem on solutions with specified growth for linear functional differential equations with negative coefficients is treated by using two-sided monotone iterations. New theorems on the existence and localisation of such solutions are established.

  14. TWIN POSITIVE PERIODIC SOLUTIONS OF FUNCTIONAL DIFFERENTIAL EQUATIONS WITH INFINITE DELAY

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    In this paper, the author studies a class of nonlinear functional differential equation. By using a fixed point theorem in cones, sufficient conditions are established for the existence of twin positive periodic solutions.

  15. EXISTENCE OF PERIODIC SOLUTIONS TO A KIND OF n-ORDER NEUTRAL FUNCTIONAL DIFFERENTIAL EQUATION

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    By means of the continuation theorem of coincidence degree theory, we study a kind of n-order neutral functional differential equation. Some new results on the existence of periodic solutions are obtained.

  16. On the Existence of Periodic Solutions for a Kind of Second Order Neutral Functional Differential Equation

    Institute of Scientific and Technical Information of China (English)

    Shi Ping LU; Wei Gao GE

    2005-01-01

    By means of the continuation theorem of coincidence degree theory, some new results on the non-existence, existence and unique existence of periodic solutions for a kind of second order neutral functional differential equation are obtained.

  17. EXISTENCE OF MILD SOLUTIONS TO SEMILINEAR FRACTIONAL ORDER FUNCTIONAL DIFFERENTIAL EQUATIONS

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    In this paper,we use the analytic semigroup theory of linear operators and fixed point method to prove the existence of mild solutions to a semilinear fractional order functional differential equations in a Banach space.

  18. A Comparison of Mantel-Haenszel Differential Item Functioning Parameters. LSAC Research Report Series.

    Science.gov (United States)

    Schnipke, Deborah L.; Roussos, Louis A.; Pashley, Peter J.

    Differential item functioning (DIF) analyses are conducted to investigate how items function in various subgroups. The Mantel-Haenszel (MH) DIF statistic is used at the Law School Admission Council and other testing companies. When item functioning can be well-described in terms of a one- or two-parameter logistic item response theory (IRT) model…

  19. Uniqueness of solutions of the Cauchy problems for first order partial differential-functional equations

    Directory of Open Access Journals (Sweden)

    Danuta Jaruszewska-Walczak

    1994-05-01

    Full Text Available We formulate a criterion of uniqueness of solutions of a Cauchy problem using the comparison function of the Kamke type. This will be a generalization of classical results concerning first order equations with partial derivatives. We prove that the uniqueness criteria of Perron and Kamke type for differential-function problems are equivalent if given functions are continuous.

  20. Uniqueness of solutions of the Cauchy problems for first order partial differential-functional equations

    OpenAIRE

    Danuta Jaruszewska-Walczak

    1994-01-01

    We formulate a criterion of uniqueness of solutions of a Cauchy problem using the comparison function of the Kamke type. This will be a generalization of classical results concerning first order equations with partial derivatives. We prove that the uniqueness criteria of Perron and Kamke type for differential-function problems are equivalent if given functions are continuous.

  1. Construction of Canonical Polynomial Basis Functions for Solving Special Nth -Order Linear Integro-Differential Equations

    Directory of Open Access Journals (Sweden)

    1 Taiwo O. A

    2013-01-01

    Full Text Available The problem of solving special nth-order linear integro-differential equations has special importance in engineering and sciences that constitutes a good model for many systems in various fields. In this paper, we construct canonical polynomial from the differential parts of special nth-order integro-differential equations and use it as our basis function for the numerical solutions of special nth-order integro-differential equations. The results obtained by this method are compared with those obtained by Adomian Decomposition method. It is also observed that the new method is an effective method with high accuracy. Some examples are given to illustrate the method.

  2. A Holmgren type theorem for partial differential equations whose coefficients are Gevrey functions

    Directory of Open Access Journals (Sweden)

    Masaki Kawagishi

    2010-05-01

    Full Text Available In this article, we consider a uniqueness theorem of Holmgren type for p-th order Kovalevskaja linear partial differential equations whose coefficients are Gevrey functions. We prove that the only $C^p$-solution to the zero initial-valued problem is the identically zero function. To prove this result we use the uniqueness theorem for higher-order ordinary differential equations in Banach scales.

  3. Is the full susceptibility of the square-lattice Ising model a differentially algebraic function?

    Science.gov (United States)

    Guttmann, A. J.; Jensen, I.; Maillard, J.-M.; Pantone, J.

    2016-12-01

    We study the class of non-holonomic power series with integer coefficients that reduce, modulo primes, or powers of primes, to algebraic functions. In particular we try to determine whether the susceptibility of the square-lattice Ising model belongs to this class, and more broadly whether the susceptibility is a solution of a differentially algebraic equation. Initial results on Tutte's nonlinear ordinary differential equation (ODE) and other simple quadratic nonlinear ODEs suggest that a large set of differentially algebraic power series solutions with integer coefficients might reduce to algebraic functions modulo primes, or powers of primes. Since diagonals of rational functions are well-known to reduce, modulo primes, or powers of primes, to algebraic functions, a large subset of differentially algebraic power series with integer coefficients may be viewed as a natural ‘nonlinear’ generalisation of diagonals of rational functions. Here we give several examples of series with integer coefficients and non-zero radius of convergence that reduce to algebraic functions modulo (almost) every prime (or power of a prime). These examples satisfy differentially algebraic equations with the encoding polynomial occasionally possessing quite high degree (and thus difficult to identify even with long series). These examples shed important light on the very nature of such differentially algebraic series. Additionally, we have extended both the high- and low-temperature Ising square-lattice susceptibility series to 5043 coefficients. We find that even this long series is insufficient to determine whether it reduces to algebraic functions modulo 3, 5, etc. This negative result is in contrast to the comparatively easy confirmation that the corresponding series reduce to algebraic functions modulo powers of 2. Finally we show that even with 5043 terms we are unable to identify an underlying differentially algebraic equation for the susceptibility, ruling out a number of

  4. PC02 Beta3-adrenoceptor agonist-induced relaxation of human placental arteries is reduced in pregnancy-induced hypertension

    Institute of Scientific and Technical Information of China (English)

    0BARTHEZ; CROUGET; PGUERARD; MJLEROYZAMIA; MBREUILLER-FOUCHE; EJMORCILLO; TCRPCO; PSAGOT; MDUMAS; MBARDOU

    2004-01-01

    AIM: Preeclampsia is one of the leading causes of neonatal and maternal morbidity and mortality. The purpose of this study is to investigate the functionality of β2- and 133-adrenoreceptors(β-ARs) in human placental arteries and to assess the influence of pregnancy-induced hypertension on β-ARs responsiveness.METHODS: We performed in vitro functional and biochemical studies as well as RT-PCR experiments. RESULTS: SR59119

  5. A COMPREHENSIVE MODEL FOR THE POWER TRANSFORMER DIGITAL DIFFERENTIAL PROTECTION FUNCTIONING RESEARCH

    Directory of Open Access Journals (Sweden)

    Yu. V. Rumiantsev

    2016-01-01

    Full Text Available This article presents a comprehensive model for the two-winding power transformer digital differential protection functioning research. Considered comprehensive model is developed in MatLab-Simulink dynamic simulation environment with the help of SimPowerSystems component library and includes the following elements: power supply, three-phase power transformer, wye-connected current transformers and two-winding power transformer digital differential protection model. Each element of the presented model is described in the degree sufficient for its implementation in the dynamic simulation environment. Particular attention is paid to the digital signal processing principles and to the ways of differential and restraining currents forming of the considered comprehensive model main element – power transformer digital differential protection. With the help of this model the power transformer digital differential protection functioning was researched during internal and external faults: internal short-circuit, external short-circuit with and without current transformers saturation on the power transformer low-voltage side. Each experiment is illustrated with differential and restraining currents waveforms of the digital differential protection under research. Particular attention was paid to the digital protection functioning analysis during power transformer abnormal modes: overexcitation and inrush current condition. Typical current waveforms during these modes were showed and their harmonic content was investigated. The causes of these modes were analyzed in details. Digital differential protection blocking algorithms based on the harmonic content were considered. Drawbacks of theses algorithms were observed and the need of their further technical improvement was marked.

  6. Promoting effect of lactoferrin on barrier function and epithelial differentiation of human keratinocytes.

    Science.gov (United States)

    Uchida, Ryo; Aoki, Reiji; Aoki-Yoshida, Ayako; Tajima, Atsushi; Takayama, Yoshiharu

    2017-02-01

    The purpose of this study was to elucidate the effects of bovine lactoferrin on keratinocyte differentiation and barrier function. Addition of bovine lactoferrin to differentiating HaCaT human keratinocytes led to increased transepithelial electrical resistance (TER), a marker of epithelial barrier function. This elevation was followed by upregulation of two differentiation markers, involucrin and filaggrin. The expression level of sterol regulatory element-binding protein-1 was also enhanced by bovine lactoferrin. The lactoferrin-induced upregulation of involucrin and filaggrin expression were confirmed in normal human epidermal keratinocytes (NHEK). Treatment with SB203580, a p38 mitogen-activated protein kinase (MAPK) α inhibitor, impaired the upregulation of involucrin and filaggrin expression in response to lactoferrin. The elevation of p38 MAPK phosphorylation was further enhanced by lactoferrin in the initial stage of differentiation of HaCaT keratinocytes. The findings suggest that bovine lactoferrin promotes epithelial differentiation by a p38-MAPK-dependent mechanism.

  7. Differentiating High-Functioning Autism and Social Phobia

    Science.gov (United States)

    Tyson, Katherine E.; Cruess, Dean G.

    2012-01-01

    Both high-functioning autism (HFA) and social phobia (SP) involve profound social interaction deficits. Although these disorders share some similar symptoms, they are conceptualized as distinct. Because both HFA and SP are defined behaviorally, the degree of overlap between the two disorders may result in misinterpretation of symptoms. However,…

  8. Relating neuronal firing patterns to functional differentiation of cerebral cortex.

    Directory of Open Access Journals (Sweden)

    Shigeru Shinomoto

    2009-07-01

    Full Text Available It has been empirically established that the cerebral cortical areas defined by Brodmann one hundred years ago solely on the basis of cellular organization are closely correlated to their function, such as sensation, association, and motion. Cytoarchitectonically distinct cortical areas have different densities and types of neurons. Thus, signaling patterns may also vary among cytoarchitectonically unique cortical areas. To examine how neuronal signaling patterns are related to innate cortical functions, we detected intrinsic features of cortical firing by devising a metric that efficiently isolates non-Poisson irregular characteristics, independent of spike rate fluctuations that are caused extrinsically by ever-changing behavioral conditions. Using the new metric, we analyzed spike trains from over 1,000 neurons in 15 cortical areas sampled by eight independent neurophysiological laboratories. Analysis of firing-pattern dissimilarities across cortical areas revealed a gradient of firing regularity that corresponded closely to the functional category of the cortical area; neuronal spiking patterns are regular in motor areas, random in the visual areas, and bursty in the prefrontal area. Thus, signaling patterns may play an important role in function-specific cerebral cortical computation.

  9. ON CERTAIN CLASS OF ANALYTIC FUNCTIONS DEFINED BY DIFFERENTIAL SUBORDINATION

    Institute of Scientific and Technical Information of China (English)

    刘名生

    2002-01-01

    In this paper, the new subclass Bn(λ,α,A,B) of analytic functions is introduced. Its subordination relations, inclusion relations, the inequality properties and convering theorem are discussed. The results obtained in this paper are sharp, which generalize the related works of some authors and some other new results are obtained.

  10. Functional Foods as Differentiated Products: the Italian Yogurt Market

    NARCIS (Netherlands)

    Bonanno, A.

    2013-01-01

    In spite of the growing consumers' interest for functional foods, the knowledge regarding the demand for these products and their profitability is limited. Adapting the LA/AIDS (Linear Approximated–Almost Ideal Demand System) model by means of Pinkse, Slade and Brett's distance metric method (2002),

  11. Optimal Stochastic Control with Recursive Cost Functionals of Stochastic Differential Systems Reflected in a Domain

    CERN Document Server

    Li, Juan

    2012-01-01

    In this paper we study the optimal stochastic control problem for stochastic differential systems reflected in a domain. The cost functional is a recursive one, which is defined via generalized backward stochastic differential equations developed by Pardoux and Zhang [17]. The value function is shown to be the viscosity solution to the associated Hamilton-Jacobi-Bellman equation, which is a fully nonlinear parabolic partial differential equation with a nonlinear Neumann boundary condition. The method of stochastic "backward semigroups" introduced by Peng [18] is adapted to our context.

  12. Differentiating functional brain regions using optical coherence tomography (Conference Presentation)

    Science.gov (United States)

    Gil, Daniel A.; Bow, Hansen C.; Shen, Jin-H.; Joos, Karen M.; Skala, Melissa C.

    2017-02-01

    The human brain is made up of functional regions governing movement, sensation, language, and cognition. Unintentional injury during neurosurgery can result in significant neurological deficits and morbidity. The current standard for localizing function to brain tissue during surgery, intraoperative electrical stimulation or recording, significantly increases the risk, time, and cost of the procedure. There is a need for a fast, cost-effective, and high-resolution intraoperative technique that can avoid damage to functional brain regions. We propose that optical coherence tomography (OCT) can fill this niche by imaging differences in the cellular composition and organization of functional brain areas. We hypothesized this would manifest as differences in the attenuation coefficient measured using OCT. Five functional regions (prefrontal, somatosensory, auditory, visual, and cerebellum) were imaged in ex vivo porcine brains (n=3), a model chosen due to a similar white/gray matter ratio as human brains. The attenuation coefficient was calculated using a depth-resolved model and quantitatively validated with Intralipid phantoms across a physiological range of attenuation coefficients (absolute difference < 0.1cm-1). Image analysis was performed on the attenuation coefficient images to derive quantitative endpoints. We observed a statistically significant difference among the median attenuation coefficients of these five regions (one-way ANOVA, p<0.05). Nissl-stained histology will be used to validate our results and correlate OCT-measured attenuation coefficients to neuronal density. Additional development and validation of OCT algorithms to discriminate brain regions are planned to improve the safety and efficacy of neurosurgical procedures such as biopsy, electrode placement, and tissue resection.

  13. Stochastic partial differential equations a modeling, white noise functional approach

    CERN Document Server

    Holden, Helge; Ubøe, Jan; Zhang, Tusheng

    1996-01-01

    This book is based on research that, to a large extent, started around 1990, when a research project on fluid flow in stochastic reservoirs was initiated by a group including some of us with the support of VISTA, a research coopera­ tion between the Norwegian Academy of Science and Letters and Den norske stats oljeselskap A.S. (Statoil). The purpose of the project was to use stochastic partial differential equations (SPDEs) to describe the flow of fluid in a medium where some of the parameters, e.g., the permeability, were stochastic or "noisy". We soon realized that the theory of SPDEs at the time was insufficient to handle such equations. Therefore it became our aim to develop a new mathematically rigorous theory that satisfied the following conditions. 1) The theory should be physically meaningful and realistic, and the corre­ sponding solutions should make sense physically and should be useful in applications. 2) The theory should be general enough to handle many of the interesting SPDEs that occur in r...

  14. Differentiation and functional regulation of human fetal NK cells.

    Science.gov (United States)

    Ivarsson, Martin A; Loh, Liyen; Marquardt, Nicole; Kekäläinen, Eliisa; Berglin, Lena; Björkström, Niklas K; Westgren, Magnus; Nixon, Douglas F; Michaëlsson, Jakob

    2013-09-01

    The human fetal immune system is naturally exposed to maternal allogeneic cells, maternal antibodies, and pathogens. As such, it is faced with a considerable challenge with respect to the balance between immune reactivity and tolerance. Here, we show that fetal natural killer (NK) cells differentiate early in utero and are highly responsive to cytokines and antibody-mediated stimulation but respond poorly to HLA class I-negative target cells. Strikingly, expression of killer-cell immunoglobulin-like receptors (KIRs) did not educate fetal NK cells but rendered them hyporesponsive to target cells lacking HLA class I. In addition, fetal NK cells were highly susceptible to TGF-β-mediated suppression, and blocking of TGF-β signaling enhanced fetal NK cell responses to target cells. Our data demonstrate that KIR-mediated hyporesponsiveness and TGF-β-mediated suppression are major factors determining human fetal NK cell hyporesponsiveness to HLA class I-negative target cells and provide a potential mechanism for fetal-maternal tolerance in utero. Finally, our results provide a basis for understanding the role of fetal NK cells in pregnancy complications in which NK cells could be involved, for example, during in utero infections and anti-RhD-induced fetal anemia.

  15. The Successor Function and Pareto Optimal Solutions of Cooperative Differential Systems with Concavity. I

    DEFF Research Database (Denmark)

    Andersen, Kurt Munk; Sandqvist, Allan

    1997-01-01

    We investigate the domain of definition and the domain of values for the successor function of a cooperative differential system x'=f(t,x), where the coordinate functions are concave in x for any fixed value of t. Moreover, we give a characterization of a weakly Pareto optimal solution.......We investigate the domain of definition and the domain of values for the successor function of a cooperative differential system x'=f(t,x), where the coordinate functions are concave in x for any fixed value of t. Moreover, we give a characterization of a weakly Pareto optimal solution....

  16. Correspondence between geometrical and differential definitions of the sine and cosine functions and connection with kinematics

    CERN Document Server

    Petrache, Horia I

    2011-01-01

    In classical physics, the familiar sine and cosine functions appear in two forms: (1) geometrical, in the treatment of vectors such as forces and velocities, and (2) differential, as solutions of oscillation and wave equations. These two forms correspond to two different definitions of trigonometric functions, one geometrical using right triangles and unit circles, and the other employing differential equations. Although the two definitions must be equivalent, this equivalence is not demonstrated in textbooks. In this manuscript, the equivalence between the geometrical and the differential definition is presented assuming no a priori knowledge of the properties of sine and cosine functions. We start with the usual length projections on the unit circle and use elementary geometry and elementary calculus to arrive to harmonic differential equations. This more general and abstract treatment not only reveals the equivalence of the two definitions but also provides an instructive perspective on circular and harmon...

  17. Boundary-value problems for elliptic functional-differential equations and their applications

    Science.gov (United States)

    Skubachevskii, A. L.

    2016-10-01

    Boundary-value problems are considered for strongly elliptic functional-differential equations in bounded domains. In contrast to the case of elliptic differential equations, smoothness of generalized solutions of such problems can be violated in the interior of the domain and may be preserved only on some subdomains, and the symbol of a self-adjoint semibounded functional-differential operator can change sign. Both necessary and sufficient conditions are obtained for the validity of a Gårding-type inequality in algebraic form. Spectral properties of strongly elliptic functional-differential operators are studied, and theorems are proved on smoothness of generalized solutions in certain subdomains and on preservation of smoothness on the boundaries of neighbouring subdomains. Applications of these results are found to the theory of non-local elliptic problems, to the Kato square-root problem for an operator, to elasticity theory, and to problems in non-linear optics. Bibliography: 137 titles.

  18. The Dynamic Programming Method of Stochastic Differential Game for Functional Forward-Backward Stochastic System

    Directory of Open Access Journals (Sweden)

    Shaolin Ji

    2013-01-01

    Full Text Available This paper is devoted to a stochastic differential game (SDG of decoupled functional forward-backward stochastic differential equation (FBSDE. For our SDG, the associated upper and lower value functions of the SDG are defined through the solution of controlled functional backward stochastic differential equations (BSDEs. Applying the Girsanov transformation method introduced by Buckdahn and Li (2008, the upper and the lower value functions are shown to be deterministic. We also generalize the Hamilton-Jacobi-Bellman-Isaacs (HJBI equations to the path-dependent ones. By establishing the dynamic programming principal (DPP, we derive that the upper and the lower value functions are the viscosity solutions of the corresponding upper and the lower path-dependent HJBI equations, respectively.

  19. Homogeneous partial differential equations for superpositions of indeterminate functions of several variables

    Energy Technology Data Exchange (ETDEWEB)

    Asai, Kazuto [University of Aizu, Aizu-Wakamatsu (Japan)

    2009-02-28

    We determine essentially all partial differential equations satisfied by superpositions of tree type and of a further special type. These equations represent necessary and sufficient conditions for an analytic function to be locally expressible as an analytic superposition of the type indicated. The representability of a real analytic function by a superposition of this type is independent of whether that superposition involves real-analytic functions or C{sup {rho}}-functions, where the constant {rho} is determined by the structure of the superposition. We also prove that the function u defined by u{sup n}=xu{sup a}+yu{sup b}+zu{sup c}+1 is generally non-representable in any real (resp. complex) domain as f(g(x,y),h(y,z)) with twice differentiable f and differentiable g, h (resp. analytic f, g, h)

  20. Tribbles 3 inhibits brown adipocyte differentiation and function by suppressing insulin signaling

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Ha-Won; Choi, Ran Hee; McClellan, Jamie L. [Division of Applied Physiology, Department of Exercise Science, University of South Carolina, Columbia, SC 29208 (United States); Piroli, Gerardo G.; Frizzell, Norma [Department of Pharmacology, Physiology & Neuroscience, University of South Carolina School of Medicine, Columbia, SC 29208 (United States); Tseng, Yu-Hua; Goodyear, Laurie J. [Research Division, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, MA 02215 (United States); Koh, Ho-Jin, E-mail: kohh@mailbox.sc.edu [Division of Applied Physiology, Department of Exercise Science, University of South Carolina, Columbia, SC 29208 (United States)

    2016-02-19

    Recent studies have demonstrated that adult humans have substantial amounts of functioning brown adipose tissue (BAT). Since BAT has been implicated as an anti-obese and anti-diabetic tissue, it is important to understand the signaling molecules that regulate BAT function. There has been a link between insulin signaling and BAT metabolism as deletion or pharmaceutical inhibition of insulin signaling impairs BAT differentiation and function. Tribbles 3 (TRB3) is a pseudo kinase that has been shown to regulate metabolism and insulin signaling in multiple tissues but the role of TRB3 in BAT has not been studied. In this study, we found that TRB3 expression was present in BAT and overexpression of TRB3 in brown preadipocytes impaired differentiation and decreased expression of BAT markers. Furthermore, TRB3 overexpression resulted in significantly lower oxygen consumption rates for basal and proton leakage, indicating decreased BAT activity. Based on previous studies showing that deletion or pharmaceutical inhibition of insulin signaling impairs BAT differentiation and function, we assessed insulin signaling in brown preadipocytes and BAT in vivo. Overexpression of TRB3 in cells impaired insulin-stimulated IRS1 and Akt phosphorylation, whereas TRB3KO mice displayed improved IRS1 and Akt phosphorylation. Finally, deletion of IRS1 abolished the function of TRB3 to regulate BAT differentiation and metabolism. These data demonstrate that TRB3 inhibits insulin signaling in BAT, resulting in impaired differentiation and function. - Highlights: • TRB3 is expressed in brown adipose tissue and its expression is increased during differentiation. • Overexpression of TRB3 inhibits differentiation and its activity. • Overexpression of TRB3 in brown preadipocytes inhibits insulin signaling. • TRB3KO mice displays improved insulin signaling in brown adipose tissue. • Insulin signaling is required for the effects of TRB3 to regulate brown adipose tissue differentiation and

  1. Differential changes in retina function with normal aging in humans.

    Science.gov (United States)

    Freund, Paul R; Watson, Juliane; Gilmour, Gregory S; Gaillard, Frédéric; Sauvé, Yves

    2011-06-01

    We evaluated the full field electroretinogram (ERG) to assess age-related changes in retina function in humans. ERG recordings were performed on healthy subjects with normal fundus appearance, lack of cataract and 20/20 acuity, aged 20-39 years (n = 27; mean age 25 ± 5, standard deviation), 40-59 years (n = 20; mean 53 ± 5), and 60-82 years (n = 18; mean 69 ± 5). Multiple ERG tests were applied, including light and dark-adapted stimulus-response function, dark adaptation and dynamic of recovery from a single bright flash under dark-adapted conditions. Changes in ERG properties were found in the oldest age group when compared with the two younger age groups. (1) The photopic hill effect was less pronounced. (2) Both photopic a-wave and b-wave amplitudes and implicit times were increased at high stimulus strengths. (3) Dark adaptation time was delayed for pure rod and L/M cone-driven responses, respectively. (4) Dark-adapted a-wave but not b-wave amplitudes were reduced, yielding higher B/A ratios. (5) Dark-adapted a- and b-waves implicit times were prolonged: there was a direct proportional correlation between minimal a-wave implicit times and age. (6) The dynamic of dark current recovery from a bright flash, under dark-adapted conditions, was transiently faster at intervals between 0.9 and 2 s. These results denote that aging of the healthy retina is accompanied by specific functional changes, which must be taken into account to optimally diagnose potential pathologies.

  2. Tables of generalized Airy functions for the asymptotic solution of the differential equation

    CERN Document Server

    Nosova, L N

    1965-01-01

    Tables of Generalized Airy Functions for the Asymptotic Solution of the Differential Equations contains tables of the special functions, namely, the generalized Airy functions, and their first derivatives, for real and pure imaginary values. The tables are useful for calculations on toroidal shells, laminae, rode, and for the solution of certain other problems of mathematical physics. The values of the functions were computed on the ""Strela"" highspeed electronic computer.This book will be of great value to mathematicians, researchers, and students.

  3. Maximum Principles and Boundary Value Problems for First-Order Neutral Functional Differential Equations

    Directory of Open Access Journals (Sweden)

    Domoshnitsky Alexander

    2009-01-01

    Full Text Available We obtain the maximum principles for the first-order neutral functional differential equation where , and are linear continuous operators, and are positive operators, is the space of continuous functions, and is the space of essentially bounded functions defined on . New tests on positivity of the Cauchy function and its derivative are proposed. Results on existence and uniqueness of solutions for various boundary value problems are obtained on the basis of the maximum principles.

  4. Multiscale functions, Scale dynamics and Applications to partial differential equations

    CERN Document Server

    Cresson, Jacky

    2015-01-01

    Modeling phenomena from experimental data, always begin with a \\emph{choice of hypothesis} on the observed dynamics such as \\emph{determinism}, \\emph{randomness}, \\emph{derivability} etc. Depending on these choices, different behaviors can be observed. The natural question associated to the modeling problem is the following : \\emph{"With a finite set of data concerning a phenomenon, can we recover its underlying nature ?} From this problem, we introduce in this paper the definition of \\emph{multi-scale functions}, \\emph{scale calculus} and \\emph{scale dynamics} based on the \\emph{time-scale calculus} (see \\cite{bohn}). These definitions will be illustrated on the \\emph{multi-scale Okamoto's functions}. The introduced formalism explains why there exists different continuous models associated to an equation with different \\emph{scale regimes} whereas the equation is \\emph{scale invariant}. A typical example of such an equation, is the \\emph{Euler-Lagrange equation} and particularly the \\emph{Newton's equation} ...

  5. HYPERDIRE. HYPERgeometric functions DIfferential REduction. MATEMATICA based packages for differential reduction of generalized hypergeometric functions. F{sub D} and F{sub S} Horn-type hypergeometric functions of three variables

    Energy Technology Data Exchange (ETDEWEB)

    Bytev, Vladimir V. [Joint Inst. for Nuclear Research, Dubna (Russian Federation); Kalmykov, Mikhail Yu. [Deutsches Elektronen-Synchrotron (DESY), Zeuthen (Germany); Moch, Sven-Olaf [Deutsches Elektronen-Synchrotron (DESY), Zeuthen (Germany); Hamburg Univ. (Germany). 2. Inst. fuer Theoretische Physik

    2013-12-15

    HYPERDIRE is a project devoted to the creation of a set of Mathematica based programs for the differential reduction of hypergeometric functions. The current version includes two parts: the first one, FdFunction, for manipulations with Appell hypergeometric functions F{sub D} of r variables; and the second one, FsFunction, for manipulations with Lauricella-Saran hypergeometric functions F{sub S} of three variables. Both functions are related with one-loop Feynman diagrams.

  6. Tribbles 3 inhibits brown adipocyte differentiation and function by suppressing insulin signaling.

    Science.gov (United States)

    Jeong, Ha-Won; Choi, Ran Hee; McClellan, Jamie L; Piroli, Gerardo G; Frizzell, Norma; Tseng, Yu-Hua; Goodyear, Laurie J; Koh, Ho-Jin

    2016-02-19

    Recent studies have demonstrated that adult humans have substantial amounts of functioning brown adipose tissue (BAT). Since BAT has been implicated as an anti-obese and anti-diabetic tissue, it is important to understand the signaling molecules that regulate BAT function. There has been a link between insulin signaling and BAT metabolism as deletion or pharmaceutical inhibition of insulin signaling impairs BAT differentiation and function. Tribbles 3 (TRB3) is a pseudo kinase that has been shown to regulate metabolism and insulin signaling in multiple tissues but the role of TRB3 in BAT has not been studied. In this study, we found that TRB3 expression was present in BAT and overexpression of TRB3 in brown preadipocytes impaired differentiation and decreased expression of BAT markers. Furthermore, TRB3 overexpression resulted in significantly lower oxygen consumption rates for basal and proton leakage, indicating decreased BAT activity. Based on previous studies showing that deletion or pharmaceutical inhibition of insulin signaling impairs BAT differentiation and function, we assessed insulin signaling in brown preadipocytes and BAT in vivo. Overexpression of TRB3 in cells impaired insulin-stimulated IRS1 and Akt phosphorylation, whereas TRB3KO mice displayed improved IRS1 and Akt phosphorylation. Finally, deletion of IRS1 abolished the function of TRB3 to regulate BAT differentiation and metabolism. These data demonstrate that TRB3 inhibits insulin signaling in BAT, resulting in impaired differentiation and function.

  7. Imaging Agonist-Induced D2/D3 Receptor Desensitization and Internalization In Vivo with PET/fMRI.

    Science.gov (United States)

    Sander, Christin Y; Hooker, Jacob M; Catana, Ciprian; Rosen, Bruce R; Mandeville, Joseph B

    2016-04-01

    This study investigated the dynamics of dopamine receptor desensitization and internalization, thereby proposing a new technique for non-invasive, in vivo measurements of receptor adaptations. The D2/D3 agonist quinpirole, which induces receptor internalization in vitro, was administered at graded doses in non-human primates while imaging with simultaneous positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). A pronounced temporal divergence between receptor occupancy and fMRI signal was observed: occupancy remained elevated while fMRI responded transiently. Analogous experiments with an antagonist (prochlorperazine) and a lower-affinity agonist (ropinirole) exhibited reduced temporal dissociation between occupancy and function, consistent with a mechanism of desensitization and internalization that depends upon drug efficacy and affinity. We postulated a model that incorporates internalization into a neurovascular-coupling relationship. This model yielded in vivo desensitization/internalization rates (0.2/min for quinpirole) consistent with published in vitro measurements. Overall, these results suggest that simultaneous PET/fMRI enables characterization of dynamic neuroreceptor adaptations in vivo, and may offer a first non-invasive method for assessing receptor desensitization and internalization.

  8. Iteration of Differentiable Functions under m-Modal Maps with Aperiodic Kneading Sequences

    Directory of Open Access Journals (Sweden)

    Maria F. Correia

    2012-01-01

    Full Text Available We consider the dynamical system (, , where is a class of differentiable functions defined on some interval and : → is the operator ∶=∘, where is a differentiable m-modal map. Using an algorithm, we obtained some numerical and symbolic results related to the frequencies of occurrence of critical values of the iterated functions when the kneading sequences of are aperiodic. Moreover, we analyze the evolution as well as the distribution of the aperiodic critical values of the iterated functions.

  9. On positive solutions of functional-differential equations in banach spaces

    Directory of Open Access Journals (Sweden)

    Zima Mirosława

    2001-01-01

    Full Text Available In this paper, we deal with two point boundary value problem (BVP for the functional-differential equation of second order where the function takes values in a cone of a Banach space . For and we obtain the BVP with reflection of the argument. Applying fixed point theorem on strict set-contraction from G. Li, Proc. Amer. Math. Soc. 97 (1986, 277–280, we prove the existence of positive solution in the space . Some inequalities involving and the respective Green's function are used. We also give the application of our existence results to the infinite system of functional–differential equations in the case .

  10. Differential reduction of generalized hypergeometric functions from Feynman diagrams. One-variable case

    Energy Technology Data Exchange (ETDEWEB)

    Bytev, Vladimir V.; Kalmykov, Mikhail Yu.; Kniehl, Bernd A. [Hamburg Univ. (Germany). II. Inst. fuer Theoretische Physik

    2010-03-15

    The differential-reduction algorithm, which allows one to express generalized hypergeometric functions with parameters of arbitrary values in terms of such functions with parameters whose values differ from the original ones by integers, is discussed in the context of evaluating Feynman diagrams. Where this is possible, we compare our results with those obtained using standard techniques. It is shown that the criterion of reducibility of multiloop Feynman integrals can be reformulated in terms of the criterion of reducibility of hypergeometric functions. The relation between the numbers of master integrals obtained by differential reduction and integration by parts is discussed. (orig.)

  11. Formulae and Bounds connected to Optimal Design and Homogenization of Partial Differential Operators and Integral Functionals

    Energy Technology Data Exchange (ETDEWEB)

    Lukkassen, D.

    1996-12-31

    When partial differential equations are set up to model physical processes in strongly heterogeneous materials, effective parameters for heat transfer, electric conductivity etc. are usually required. Averaging methods often lead to convergence problems and in homogenization theory one is therefore led to study how certain integral functionals behave asymptotically. This mathematical doctoral thesis discusses (1) means and bounds connected to homogenization of integral functionals, (2) reiterated homogenization of integral functionals, (3) bounds and homogenization of some particular partial differential operators, (4) applications and further results. 154 refs., 11 figs., 8 tabs.

  12. Children with High-Functioning Autism and Asperger's Syndrome: Can We Differentiate Their Cognitive Profiles?

    Science.gov (United States)

    Planche, Pascale; Lemonnier, Eric

    2012-01-01

    The aim of this study was to investigate whether children with high-functioning autism (HFA) and Asperger's syndrome (AS) can be differentiated from each other and from typically developing children on their cognitive profiles. The present study included a total of 45 participants: children with autism (high-functioning autism or Asperger's…

  13. EXISTENCE OF PERIODIC SOLUTIONS TO A p-LAPLACIAN NEUTRAL FUNCTIONAL DIFFERENTIAL EQUATION WITH VARIABLE PARAMETER

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    By the generalized Borsuk theorem in coincidence degree theory, a p-Laplacian neutral functional differential equation is studied. A new result on the existence of periodic solution is obtained. The interest is that some coeffcient in it is not a constant function and its sign can be changeable, which is different from that in the known literatures.

  14. Building Mathematical Maturity in Calculus: Teaching Implicit Differentiation through a Review of Functions

    Science.gov (United States)

    Hare, Angela; Phillippy, Doug

    2004-01-01

    A program on calculus is conducted, which helps students learn about inherent differentiation through a study of mathematical functions, while simultaneously reinforcing their understanding of functional concepts. This process develops their mathematical experience in the field of calculus and in other advanced quantitative programs.

  15. Children with High-Functioning Autism and Asperger's Syndrome: Can We Differentiate Their Cognitive Profiles?

    Science.gov (United States)

    Planche, Pascale; Lemonnier, Eric

    2012-01-01

    The aim of this study was to investigate whether children with high-functioning autism (HFA) and Asperger's syndrome (AS) can be differentiated from each other and from typically developing children on their cognitive profiles. The present study included a total of 45 participants: children with autism (high-functioning autism or Asperger's…

  16. Hermite-Hadamard and Simpson-Like Type Inequalities for Differentiable Harmonically Convex Functions

    Directory of Open Access Journals (Sweden)

    İmdat İşcan

    2014-01-01

    Full Text Available A new identity for differentiable functions is derived. A consequence of the identity is that the author establishes some new general inequalities containing all of the Hermite-Hadamard and Simpson-like types for functions whose derivatives in absolute value at certain power are harmonically convex. Some applications to special means of real numbers are also given.

  17. On differential subordinations for a class of analytic functions defined by a linear operator

    Directory of Open Access Journals (Sweden)

    V. Ravichandran

    2004-01-01

    Full Text Available We obtain several results concerning the differential subordination between analytic functions and a linear operator defined for a certain family of analytic functions which are introduced here by means of these linear operators. Also, some special cases are considered.

  18. A Generalized Logistic Regression Procedure to Detect Differential Item Functioning among Multiple Groups

    Science.gov (United States)

    Magis, David; Raiche, Gilles; Beland, Sebastien; Gerard, Paul

    2011-01-01

    We present an extension of the logistic regression procedure to identify dichotomous differential item functioning (DIF) in the presence of more than two groups of respondents. Starting from the usual framework of a single focal group, we propose a general approach to estimate the item response functions in each group and to test for the presence…

  19. Differential Item Functioning Analysis of the Mental, Emotional, and Bodily Toughness Inventory

    Science.gov (United States)

    Gao, Yong; Mack, Mick G.; Ragan, Moira A.; Ragan, Brian

    2012-01-01

    In this study the authors used differential item functioning analysis to examine if there were items in the Mental, Emotional, and Bodily Toughness Inventory functioning differently across gender and athletic membership. A total of 444 male (56.3%) and female (43.7%) participants (30.9% athletes and 69.1% non-athletes) responded to the Mental,…

  20. Parental Divorce and Family Functioning: Effects on Differentiation Levels of Young Adults.

    Science.gov (United States)

    Johnson, Patrick; Throngren, Jill M.; Smith, Adina J.

    2001-01-01

    Study examines the effect of parental divorce and various dimensions of functioning in the family of origin on young adult development. Results indicate that parental divorce and family functioning significantly affect differentiation levels of young adults. Implications of the results for counselors and future researchers are provided. (Contains…

  1. Systematically differentiating functions for alternatively spliced isoforms through integrating RNA-seq data.

    Science.gov (United States)

    Eksi, Ridvan; Li, Hong-Dong; Menon, Rajasree; Wen, Yuchen; Omenn, Gilbert S; Kretzler, Matthias; Guan, Yuanfang

    2013-01-01

    Integrating large-scale functional genomic data has significantly accelerated our understanding of gene functions. However, no algorithm has been developed to differentiate functions for isoforms of the same gene using high-throughput genomic data. This is because standard supervised learning requires 'ground-truth' functional annotations, which are lacking at the isoform level. To address this challenge, we developed a generic framework that interrogates public RNA-seq data at the transcript level to differentiate functions for alternatively spliced isoforms. For a specific function, our algorithm identifies the 'responsible' isoform(s) of a gene and generates classifying models at the isoform level instead of at the gene level. Through cross-validation, we demonstrated that our algorithm is effective in assigning functions to genes, especially the ones with multiple isoforms, and robust to gene expression levels and removal of homologous gene pairs. We identified genes in the mouse whose isoforms are predicted to have disparate functionalities and experimentally validated the 'responsible' isoforms using data from mammary tissue. With protein structure modeling and experimental evidence, we further validated the predicted isoform functional differences for the genes Cdkn2a and Anxa6. Our generic framework is the first to predict and differentiate functions for alternatively spliced isoforms, instead of genes, using genomic data. It is extendable to any base machine learner and other species with alternatively spliced isoforms, and shifts the current gene-centered function prediction to isoform-level predictions.

  2. Systematically differentiating functions for alternatively spliced isoforms through integrating RNA-seq data.

    Directory of Open Access Journals (Sweden)

    Ridvan Eksi

    Full Text Available Integrating large-scale functional genomic data has significantly accelerated our understanding of gene functions. However, no algorithm has been developed to differentiate functions for isoforms of the same gene using high-throughput genomic data. This is because standard supervised learning requires 'ground-truth' functional annotations, which are lacking at the isoform level. To address this challenge, we developed a generic framework that interrogates public RNA-seq data at the transcript level to differentiate functions for alternatively spliced isoforms. For a specific function, our algorithm identifies the 'responsible' isoform(s of a gene and generates classifying models at the isoform level instead of at the gene level. Through cross-validation, we demonstrated that our algorithm is effective in assigning functions to genes, especially the ones with multiple isoforms, and robust to gene expression levels and removal of homologous gene pairs. We identified genes in the mouse whose isoforms are predicted to have disparate functionalities and experimentally validated the 'responsible' isoforms using data from mammary tissue. With protein structure modeling and experimental evidence, we further validated the predicted isoform functional differences for the genes Cdkn2a and Anxa6. Our generic framework is the first to predict and differentiate functions for alternatively spliced isoforms, instead of genes, using genomic data. It is extendable to any base machine learner and other species with alternatively spliced isoforms, and shifts the current gene-centered function prediction to isoform-level predictions.

  3. Novel function of the retinoblastoma protein in fat: regulation of white versus brown adipocyte differentiation

    DEFF Research Database (Denmark)

    Hansen, Jacob B; te Riele, Hein; Kristiansen, Karsten

    2004-01-01

    The differentiation of white and brown fat cells is controlled by a similar set of transcription factors, including PPARgamma and C/EBPalpha. However, despite many similarities between the two types of fat cells, they carry out essentially opposite functions in vivo, with white adipocytes being...... the major energy store and brown adipocytes being potent energy-dissipaters through thermogenesis. Yet, little is known about factors differentially regulating the formation of white and brown fat cells. Members of the retinoblastoma protein family (pRB, p107, p130) have been implicated in the regulation...... of adipocyte differentiation, and expression and phosphorylation of the three retinoblastoma family proteins oscillate in a characteristic manner during differentiation of the white preadipocyte cell line 3T3-L1. We have recently demonstrated a surprising function of the retinoblastoma protein...

  4. Differential Light Chain Assembly Influences Outer Arm Dynein Motor Function

    Science.gov (United States)

    DiBella, Linda M.; Gorbatyuk, Oksana; Sakato, Miho; Wakabayashi, Ken-ichi; Patel-King, Ramila S.; Pazour, Gregory J.; Witman, George B.; King, Stephen M.

    2005-01-01

    Tctex1 and Tctex2 were originally described as potential distorters/sterility factors in the non-Mendelian transmission of t-haplotypes in mice. These proteins have since been identified as subunits of cytoplasmic and/or axonemal dyneins. Within the Chlamydomonas flagellum, Tctex1 is a subunit of inner arm I1. We have now identified a second Tctex1-related protein (here termed LC9) in Chlamydomonas. LC9 copurifies with outer arm dynein in sucrose density gradients and is missing only in those strains completely lacking this motor. Zero-length cross-linking of purified outer arm dynein indicates that LC9 interacts directly with both the IC1 and IC2 intermediate chains. Immunoblot analysis revealed that LC2, LC6, and LC9 are missing in an IC2 mutant strain (oda6-r88) that can assemble outer arms but exhibits significantly reduced flagellar beat frequency. This defect is unlikely to be due to lack of LC6, because an LC6 null mutant (oda13) exhibits only a minor swimming abnormality. Using an LC2 null mutant (oda12-1), we find that although some outer arm dynein components assemble in the absence of LC2, they are nonfunctional. In contrast, dyneins from oda6-r88, which also lack LC2, retain some activity. Furthermore, we observed a synthetic assembly defect in an oda6-r88 oda12-1 double mutant. These data suggest that LC2, LC6, and LC9 have different roles in outer arm assembly and are required for wild-type motor function in the Chlamydomonas flagellum. PMID:16195342

  5. Fuchsia and master integrals for splitting functions from differential equations in QCD

    CERN Document Server

    Gituliar, O

    2016-01-01

    We report on the recent progress in reducing differential equations for Feynman master integrals to canonical form with the help of a method proposed by Roman Lee. For the first time, we present Fuchsia --- our open-source implementation of the Lee algorithm written in Python using mathematical routines of a free computer algebra system SageMath. We demonstrate Fuchsia by reducing differential equations for NLO contributions to splitting functions in QCD, which contain both loops and legs integrals.

  6. In vitro differentiation of rat embryonic stem cells into functional cardiomyocytes

    Institute of Scientific and Technical Information of China (English)

    Nan Cao; Jing Liao; Zumei Liu; Wen min Zhu; Jia Wang; Lijun Liu; Lili Yu

    2011-01-01

    The recent breakthrough in the generation of rat embryonic stem cells (rESCs) opens the door to application of gene targeting to create models for the study of human diseases.In addition,the in vitro differentiation system from rESCs into derivatives of three germ layers will serve as a powerful tool and resource for the investigation of mammalian development,cell function,tissue repair,and drug discovery.However,these uses have been limited by the difficulty of in vitro differentiation.The aims of this study were to establish an in vitro differentiation system from rESCs and to investigate whether rESCs are capable of forming terminal-differentiated cardiomyocytes.Using newly established rESCs,we found that embryoid body (EB)-based method used in mouse ESC (mESC) differentiation failed to work for the serum-free cultivated rESCs.We then developed a protocol by combination of three chemical inhibitors and feeder-conditioned medium.Under this condition,rESCs formed EBs,propagated and differentiated into three embryonic germ layers.Moreover,rESC-formed EBs could differentiate into spontaneously beating cardiomyocytes after plating.Analyses of molecular,structural,and functional properties revealed that rESC-derived cardiomyocytes were similar to those derived from fetal rat hearts and mESCs.In conclusion,we successfully developed an in vitro differentiation system for rESCs through which functional myocytes were generated and displayed phenotypes of rat fetal cardiomyocytes.This unique cellular system will provide a new approach to study the early development and cardiac function,and serve as an important tool in pharmacological testing and cell therapy.

  7. Integration Processes of Delay Differential Equation Based on Modified Laguerre Functions

    Directory of Open Access Journals (Sweden)

    Yeguo Sun

    2012-01-01

    Full Text Available We propose long-time convergent numerical integration processes for delay differential equations. We first construct an integration process based on modified Laguerre functions. Then we establish its global convergence in certain weighted Sobolev space. The proposed numerical integration processes can also be used for systems of delay differential equations. We also developed a technique for refinement of modified Laguerre-Radau interpolations. Lastly, numerical results demonstrate the spectral accuracy of the proposed method and coincide well with analysis.

  8. POSITIVE SOLUTIONS TO BOUNDARY VALUE PROBLEM OF FRACTIONAL FUNCTIONAL DIFFERENTIAL EQUATION

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    In this paper,we establish sufficient conditions for the existence of positive solutions to a general class of integral boundary value problem(BVP) of nonlinear fractional functional differential equation.A differential operator is taken in the RiemannLiouville sense.Our analysis relies on the Krasnosel'skii fixed-point theorem in cones.We also give examples to illustrate the applicability of our results.

  9. The Modified Rational Jacobi Elliptic Functions Method for Nonlinear Differential Difference Equations

    Directory of Open Access Journals (Sweden)

    Khaled A. Gepreel

    2012-01-01

    Full Text Available We modified the rational Jacobi elliptic functions method to construct some new exact solutions for nonlinear differential difference equations in mathematical physics via the lattice equation, the discrete nonlinear Schrodinger equation with a saturable nonlinearity, the discrete nonlinear Klein-Gordon equation, and the quintic discrete nonlinear Schrodinger equation. Some new types of the Jacobi elliptic solutions are obtained for some nonlinear differential difference equations in mathematical physics. The proposed method is more effective and powerful to obtain the exact solutions for nonlinear differential difference equations.

  10. Role of Protein Phosphatase 2A in Osteoblast Differentiation and Function.

    Science.gov (United States)

    Okamura, Hirohiko; Yoshida, Kaya; Morimoto, Hiroyuki; Teramachi, Jumpei; Ochiai, Kazuhiko; Haneji, Tatsuji; Yamamoto, Akihito

    2017-02-23

    The reversible phosphorylation of proteins plays hugely important roles in a variety of cellular processes, such as differentiation, proliferation, and apoptosis. These processes are strictly controlled by protein kinases (phosphorylation) and phosphatases (de-phosphorylation). Here we provide a brief history of the study of protein phosphorylation, including a summary of different types of protein kinases and phosphatases. One of the most physiologically important serine/threonine phosphatases is PP2A. This review provides a description of the phenotypes of various PP2A transgenic mice and further focuses on the known functions of PP2A in bone formation, including its role in osteoblast differentiation and function. A reduction in PP2A promotes bone formation and osteoblast differentiation through the regulation of bone-related transcription factors such as Osterix. Interestingly, downregulation of PP2A also stimulates adipocyte differentiation from undifferentiated mesenchymal cells under the appropriate adipogenic differentiation conditions. In osteoblasts, PP2A is also involved in the ability to control osteoclastogenesis as well as in the proliferation and metastasis of osteosarcoma cells. Thus, PP2A is considered to be a comprehensive factor in controlling the differentiation and function of cells derived from mesenchymal cells such as osteoblasts and adipocytes.

  11. Role of Protein Phosphatase 2A in Osteoblast Differentiation and Function

    Directory of Open Access Journals (Sweden)

    Hirohiko Okamura

    2017-02-01

    Full Text Available The reversible phosphorylation of proteins plays hugely important roles in a variety of cellular processes, such as differentiation, proliferation, and apoptosis. These processes are strictly controlled by protein kinases (phosphorylation and phosphatases (de-phosphorylation. Here we provide a brief history of the study of protein phosphorylation, including a summary of different types of protein kinases and phosphatases. One of the most physiologically important serine/threonine phosphatases is PP2A. This review provides a description of the phenotypes of various PP2A transgenic mice and further focuses on the known functions of PP2A in bone formation, including its role in osteoblast differentiation and function. A reduction in PP2A promotes bone formation and osteoblast differentiation through the regulation of bone-related transcription factors such as Osterix. Interestingly, downregulation of PP2A also stimulates adipocyte differentiation from undifferentiated mesenchymal cells under the appropriate adipogenic differentiation conditions. In osteoblasts, PP2A is also involved in the ability to control osteoclastogenesis as well as in the proliferation and metastasis of osteosarcoma cells. Thus, PP2A is considered to be a comprehensive factor in controlling the differentiation and function of cells derived from mesenchymal cells such as osteoblasts and adipocytes.

  12. Targeting MEK1/2 blocks osteoclast differentiation, function and cytokine secretion in multiple myeloma.

    Science.gov (United States)

    Breitkreutz, Iris; Raab, Marc S; Vallet, Sonia; Hideshima, Teru; Raje, Noopur; Chauhan, Dharminder; Munshi, Nikhil C; Richardson, Paul G; Anderson, Kenneth C

    2007-10-01

    Osteolytic bone disease in multiple myeloma (MM) is associated with upregulation of osteoclast (OCL) activity and constitutive inhibition of osteoblast function. The extracellular signal-regulated kinase 1/2 (ERK1/2) pathway mediates OCL differentiation and maturation. We hypothesized that inhibition of ERK1/2 could prevent OCL differentiation and downregulate OCL function. It was found that AZD6244, a mitogen-activated or extracellular signal-regulated protein kinase (MEK) inhibitor, blocked OCL differentiation and formation in a dose-dependent manner, evidenced by decreased alphaVbeta3-integrin expression and tartrate-resistant acid phosphatase positive (TRAP+) cells. Functional dentine disc cultures showed inhibition of OCL-induced bone resorption by AZD6244. Major MM growth and survival factors produced by OCLs including B-cell activation factor (BAFF) and a proliferation-inducing ligand (APRIL), as well as macrophage inflammatory protein (MIP-1alpha), which mediates OCL differentiation and MM, were also significantly inhibited by AZD6244. In addition to ERK inhibition, NFATc1 (nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1) and c-fos were both downregulated, suggesting that AZD6244 targets a later stage of OCL differentiation. These results indicate that AZD6244 inhibits OCL differentiation, formation and bone resorption, thereby abrogating paracrine MM cell survival in the bone marrow microenvironment. The present study therefore provides a preclinical rationale for the evaluation of AZD6244 as a potential new therapy for patients with MM.

  13. Glycine receptor α3 and α2 subunits mediate tonic and exogenous agonist-induced currents in forebrain.

    Science.gov (United States)

    McCracken, Lindsay M; Lowes, Daniel C; Salling, Michael C; Carreau-Vollmer, Cyndel; Odean, Naomi N; Blednov, Yuri A; Betz, Heinrich; Harris, R Adron; Harrison, Neil L

    2017-08-22

    Neuronal inhibition can occur via synaptic mechanisms or through tonic activation of extrasynaptic receptors. In spinal cord, glycine mediates synaptic inhibition through the activation of heteromeric glycine receptors (GlyRs) composed primarily of α1 and β subunits. Inhibitory GlyRs are also found throughout the brain, where GlyR α2 and α3 subunit expression exceeds that of α1, particularly in forebrain structures, and coassembly of these α subunits with the β subunit appears to occur to a lesser extent than in spinal cord. Here, we analyzed GlyR currents in several regions of the adolescent mouse forebrain (striatum, prefrontal cortex, hippocampus, amygdala, and bed nucleus of the stria terminalis). Our results show ubiquitous expression of GlyRs that mediate large-amplitude currents in response to exogenously applied glycine in these forebrain structures. Additionally, tonic inward currents were also detected, but only in the striatum, hippocampus, and prefrontal cortex (PFC). These tonic currents were sensitive to both strychnine and picrotoxin, indicating that they are mediated by extrasynaptic homomeric GlyRs. Recordings from mice deficient in the GlyR α3 subunit (Glra3(-/-)) revealed a lack of tonic GlyR currents in the striatum and the PFC. In Glra2(-/Y) animals, GlyR tonic currents were preserved; however, the amplitudes of current responses to exogenous glycine were significantly reduced. We conclude that functional α2 and α3 GlyRs are present in various regions of the forebrain and that α3 GlyRs specifically participate in tonic inhibition in the striatum and PFC. Our findings suggest roles for glycine in regulating neuronal excitability in the forebrain.

  14. Numerical solution of neutral functional-differential equations with proportional delays

    Directory of Open Access Journals (Sweden)

    Mehmet Giyas Sakar

    2017-07-01

    Full Text Available In this paper, homotopy analysis method is improved with optimal determination of auxiliary parameter by use of residual error function for solving neutral functional-differential equations (NFDEs with proportional delays. Convergence analysis and error estimate of method are given. Some numerical examples are solved and comparisons are made with the existing results. The numerical results show that the homotopy analysis method with residual error function is very effective and simple.

  15. Symbolic Computation of Extended Jacobian Elliptic Function Algorithm for Nonlinear Differential-Different Equations

    Institute of Scientific and Technical Information of China (English)

    DAI Chao-Qing; MENG Jian-Ping; ZHANG Jie-Fang

    2005-01-01

    The Jacobian elliptic function expansion method for nonlinear differential-different equations and its algorithm are presented by using some relations among ten Jacobian elliptic functions and successfully construct more new exact doubly-periodic solutions of the integrable discrete nonlinear Schrodinger equation. When the modulous m → 1or 0, doubly-periodic solutions degenerate to solitonic solutions including bright soliton, dark soliton, new solitons as well as trigonometric function solutions.

  16. Existence of pseudo almost periodic solutions for a class of partial functional differential equations

    Directory of Open Access Journals (Sweden)

    Hui-Sheng Ding

    2013-04-01

    Full Text Available In this paper, we first introduce a new class of pseudo almost periodic type functions and investigate some properties of pseudo almost periodic type functions; and then we discuss the existence of pseudo almost periodic solutions to the class of abstract partial functional differential equations $x'(t=Ax(t+f(t,x_t$ with finite delay in a Banach space X.

  17. Inhibition of NAD(P)H oxidase potentiates AT2 receptor agonist-induced natriuresis in Sprague-Dawley rats.

    Science.gov (United States)

    Sabuhi, Rifat; Asghar, Mohammad; Hussain, Tahir

    2010-10-01

    A positive association between renin-angiotensin system, especially AT1 receptor, and oxidative stress in the pathogenesis of hypertension and cardiovascular/renal diseases has been suggested. However, the role of oxidative stress, especially superoxide radicals in renal sodium handling in response to AT1 and AT2 receptors, is not known. Therefore, the present study was designed to investigate the role of NAD(P)H oxidase (NOX), a major superoxide radical producing enzyme, in AT1 and AT2 receptor function on natriuresis/diuresis in Sprague-Dawley rats. The rats under anesthesia were intravenously infused with NOX inhibitor apocynin (3.5 μg·kg(-1)·min(-1)), the AT1 receptor antagonist candesartan (100 μg/kg; bolus), and the AT2 receptor agonist CGP-42112A (1 μg·kg(-1)·min(-1)) alone and in combinations. Candesartan alone significantly increased urinary flow (UF; μl/30 min) by 53 and urinary Na excretion (U(Na)V; μmol/min) by 0.4 over basal. Preinfusion of apocynin had no effect on the net increase in UF or U(Na)V in response to candesartan. On the other hand, apocynin preinfusion caused profound increases in CGP-42112A-induced UF by 72, U(Na)V by 1.14, and fractional excretion of Na by 7.8. Apocynin and CGP-42112A alone did not cause significant increase in UF or U(Na)V over the basal. CGP-42112A infusion in the presence of apocynin increased urinary nitrite/nitrates and cGMP over basal. The infusion of candesartan, apocynin, and CGP-42112A alone or in combinations had no effect on the blood pressure or the glomerular filtration rate, suggesting tubular effects on natriuresis/diuresis. The data suggest that NOX may have an antagonistic role in AT2 receptor-mediated natriuresis/diuresis possibly via neutralizing nitric oxide and thereby influence fluid-Na homeostasis.

  18. Thymol, a dietary monoterpene phenol abrogates mitochondrial dysfunction in β-adrenergic agonist induced myocardial infarcted rats by inhibiting oxidative stress.

    Science.gov (United States)

    Nagoor Meeran, M F; Jagadeesh, G S; Selvaraj, P

    2016-01-25

    Mitochondrial dysfunction has been suggested to be one of the important pathological events in isoproterenol (ISO), a synthetic catecholamine and β-adrenergic agonist induced myocardial infarction (MI). In this context, we have evaluated the impact of thymol against ISO induced oxidative stress and calcium uniporter malfunction involved in the pathology of mitochondrial dysfunction in rats. Male albino Wistar rats were pre and co-treated with thymol (7.5 mg/kg body weight) daily for 7 days. Isoproterenol (100 mg/kg body weight) was subcutaneously injected into rats on 6th and 7th day to induce MI. To explore the extent of cardiac mitochondrial damage, the activities/levels of cardiac marker enzymes, mitochondrial lipid peroxidation products, antioxidants, lipids, calcium, adenosine triphosphate and multi marker enzymes were evaluated. Isoproterenol induced myocardial infarcted rats showed a significant increase in the activities of cardiac diagnostic markers, heart mitochondrial lipid peroxidation, lipids, calcium, and a significant decrease in the activities/levels of heart mitochondrial superoxide dismutase, catalase, glutathione peroxidase, reduced glutathione, isocitrate, malate, α-ketoglutarate and NADH-dehydrogenases, cytochrome-C-oxidase, and adenosine triphosphate. Thymol pre and co-treatment showed near normalized effects on all the biochemical parameters studied. Transmission electron microscopic findings and mitochondrial swelling studies confirmed our biochemical findings. The in vitro study also revealed the potent free-radical scavenging activity of thymol. Thus, thymol attenuates the involvement of ISO against oxidative stress and calcium uniporter malfunction associated with mitochondrial dysfunction in rats.

  19. New Generalized Hyperbolic Functions to Find New Exact Solutions of the Nonlinear Partial Differential Equations

    Directory of Open Access Journals (Sweden)

    Yusuf Pandir

    2013-01-01

    Full Text Available We firstly give some new functions called generalized hyperbolic functions. By the using of the generalized hyperbolic functions, new kinds of transformations are defined to discover the exact approximate solutions of nonlinear partial differential equations. Based on the generalized hyperbolic function transformation of the generalized KdV equation and the coupled equal width wave equations (CEWE, we find new exact solutions of two equations and analyze the properties of them by taking different parameter values of the generalized hyperbolic functions. We think that these solutions are very important to explain some physical phenomena.

  20. Applications of Jacobi Elliptic Function Expansion Method for Nonlinear Differential-Difference Equations

    Institute of Scientific and Technical Information of China (English)

    XU Gui-Qiong; LI Zhi-Bin

    2005-01-01

    The Jacobi elliptic function expansion method is extended to derive the explicit periodic wave solutions for nonlinear differential-difference equations. Three well-known examples are chosen to illustrate the application of the Jacobi elliptic function expansion method. As a result, three types of periodic wave solutions including Jacobi elliptic sine function, Jacobi elliptic cosine function and the third elliptic function solutions are obtained. It is shown that the shock wave solutions and solitary wave solutions can be obtained at their limit condition.

  1. Computing the numerical solution to functional differential equations: some recent progresses towards E. Hopf's 1952 dream

    Science.gov (United States)

    Venturi, Daniele

    2016-11-01

    The fundamental importance of functional differential equations has been recognized in many areas of mathematical physics, such as fluid dynamics, quantum field theory and statistical physics. For example, in the context of fluid dynamics, the Hopf characteristic functional equation was deemed by Monin and Yaglom to be "the most compact formulation of the turbulence problem", which is the problem of determining the statistical properties of the velocity and pressure fields of Navier-Stokes equations given statistical information on the initial state. However, no effective numerical method has yet been developed to compute the solution to functional differential equations. In this talk I will provide a new perspective on this general problem, and discuss recent progresses in approximation theory for nonlinear functionals and functional equations. The proposed methods will be demonstrated through various examples.

  2. Human embryonic stem cells differentiate into functional renal proximal tubular-like cells.

    Science.gov (United States)

    Narayanan, Karthikeyan; Schumacher, Karl M; Tasnim, Farah; Kandasamy, Karthikeyan; Schumacher, Annegret; Ni, Ming; Gao, Shujun; Gopalan, Began; Zink, Daniele; Ying, Jackie Y

    2013-04-01

    Renal cells are used in basic research, disease models, tissue engineering, drug screening, and in vitro toxicology. In order to provide a reliable source of human renal cells, we developed a protocol for the differentiation of human embryonic stem cells into renal epithelial cells. The differentiated stem cells expressed markers characteristic of renal proximal tubular cells and their precursors, whereas markers of other renal cell types were not expressed or expressed at low levels. Marker expression patterns of these differentiated stem cells and in vitro cultivated primary human renal proximal tubular cells were comparable. The differentiated stem cells showed morphological and functional characteristics of renal proximal tubular cells, and generated tubular structures in vitro and in vivo. In addition, the differentiated stem cells contributed in organ cultures for the formation of simple epithelia in the kidney cortex. Bioreactor experiments showed that these cells retained their functional characteristics under conditions as applied in bioartificial kidneys. Thus, our results show that human embryonic stem cells can differentiate into renal proximal tubular-like cells. Our approach would provide a source for human renal proximal tubular cells that are not affected by problems associated with immortalized cell lines or primary cells.

  3. Convergent functional genomics of oligodendrocyte differentiation identifies multiple autoinhibitory signaling circuits.

    Science.gov (United States)

    Gobert, Rosanna Pescini; Joubert, Lara; Curchod, Marie-Laure; Salvat, Catherine; Foucault, Isabelle; Jorand-Lebrun, Catherine; Lamarine, Marc; Peixoto, Hélène; Vignaud, Chloé; Frémaux, Christèle; Jomotte, Thérèse; Françon, Bernard; Alliod, Chantal; Bernasconi, Lilia; Abderrahim, Hadi; Perrin, Dominique; Bombrun, Agnes; Zanoguera, Francisca; Rommel, Christian; Hooft van Huijsduijnen, Rob

    2009-03-01

    Inadequate remyelination of brain white matter lesions has been associated with a failure of oligodendrocyte precursors to differentiate into mature, myelin-producing cells. In order to better understand which genes play a critical role in oligodendrocyte differentiation, we performed time-dependent, genome-wide gene expression studies of mouse Oli-neu cells as they differentiate into process-forming and myelin basic protein-producing cells, following treatment with three different agents. Our data indicate that different inducers activate distinct pathways that ultimately converge into the completely differentiated state, where regulated gene sets overlap maximally. In order to also gain insight into the functional role of genes that are regulated in this process, we silenced 88 of these genes using small interfering RNA and identified multiple repressors of spontaneous differentiation of Oli-neu, most of which were confirmed in rat primary oligodendrocyte precursors cells. Among these repressors were CNP, a well-known myelin constituent, and three phosphatases, each known to negatively control mitogen-activated protein kinase cascades. We show that a novel inhibitor for one of the identified genes, dual-specificity phosphatase DUSP10/MKP5, was also capable of inducing oligodendrocyte differentiation in primary oligodendrocyte precursors. Oligodendrocytic differentiation feedback loops may therefore yield pharmacological targets to treat disease related to dysfunctional myelin deposition.

  4. Kinetin Improves Barrier Function of the Skin by Modulating Keratinocyte Differentiation Markers

    Science.gov (United States)

    An, Sungkwan; Cha, Hwa Jun; Ko, Jung-Min; Han, Hyunjoo; Kim, Su Young; Kim, Kyung-Suk; Lee, Song Jeong; An, In-Sook; Kim, Sangwon; Youn, Hae Jeong

    2017-01-01

    Background Kinetin is a plant hormone that regulates growth and differentiation. Keratinocytes, the basic building blocks of the epidermis, function in maintaining the skin barrier. Objective We examined whether kinetin induces skin barrier functions in vitro and in vivo. Methods To evaluate the efficacy of kinetin at the cellular level, expression of keratinocyte differentiation markers was assessed. Moreover, we examined the clinical efficacy of kinetin by evaluating skin moisture, transepidermal water loss (TEWL), and skin surface roughness in patients who used kinetin-containing cream. We performed quantitative real-time polymerase chain reaction to measure the expression of keratinocyte differentiation markers in HaCaT cells following treatment. A clinical trial was performed to assess skin moisture, TEWL, and evenness of skin texture in subjects who used kinetin-containing cream for 4 weeks. Results Kinetin increased involucrin, and keratin 1 mRNA in HaCaT cells. Moreover, use of a kinetin-containing cream improved skin moisture and TEWL while decreasing roughness of skin texture. Conclusion Kinetin induced the expression of keratinocyte differentiation markers, suggesting that it may affect differentiation to improve skin moisture content, TEWL, and other signs of skin aging. Therefore, kinetin is a potential new component for use in cosmetics as an anti-aging agent that improves the barrier function of skin. PMID:28223740

  5. Possibility of Undifferentiated Human Thigh Adipose Stem Cells Differentiating into Functional Hepatocytes

    Directory of Open Access Journals (Sweden)

    Jong Hoon Lee

    2012-11-01

    Full Text Available BackgroundThis study aimed to investigate the possibility of isolating mesenchymal stem cells (MSCs from human thigh adipose tissue and the ability of human thigh adipose stem cells (HTASCs to differentiate into hepatocytes.MethodsThe adipose-derived stem cells (ADSCs were isolated from thigh adipose tissue. Growth factors, cytokines, and hormones were added to the collagen coated dishes to induce the undifferentiated HTASCs to differentiate into hepatocyte-like cells. To confirm the experimental results, the expression of hepatocyte-specific markers on undifferentiated and differentiated HTASCs was analyzed using reverse transcription polymerase chain reaction and immunocytochemical staining. Differentiation efficiency was evaluated using functional tests such as periodic acid schiff (PAS staining and detection of the albumin secretion level using enzyme-linked immunosorbent assay (ELISA.ResultsThe majority of the undifferentiated HTASCs were changed into a more polygonal shape showing tight interactions between the cells. The differentiated HTASCs up-regulated mRNA of hepatocyte markers. Immunocytochemical analysis showed that they were intensely stained with anti-albumin antibody compared with undifferentiated HTASCs. PAS staining showed that HTASCs submitted to the hepatocyte differentiation protocol were able to more specifically store glycogen than undifferentiated HTASCs, displaying a purple color in the cytoplasm of the differentiated HTASCs. ELISA analyses showed that differentiated HTASCs could secrete albumin, which is one of the hepatocyte markers.ConclusionsMSCs were islolated from human thigh adipose tissue differentiate to heapatocytes. The source of ADSCs is not only abundant abdominal adipose tissue, but also thigh adipose tissue for cell therapy in liver regeneration and tissue regeneration.

  6. Osteogenic Differentiation of MSC through Calcium Signaling Activation: Transcriptomics and Functional Analysis.

    Science.gov (United States)

    Viti, Federica; Landini, Martina; Mezzelani, Alessandra; Petecchia, Loredana; Milanesi, Luciano; Scaglione, Silvia

    2016-01-01

    The culture of progenitor mesenchymal stem cells (MSC) onto osteoconductive materials to induce a proper osteogenic differentiation and mineralized matrix regeneration represents a promising and widely diffused experimental approach for tissue-engineering (TE) applications in orthopaedics. Among modern biomaterials, calcium phosphates represent the best bone substitutes, due to their chemical features emulating the mineral phase of bone tissue. Although many studies on stem cells differentiation mechanisms have been performed involving calcium-based scaffolds, results often focus on highlighting production of in vitro bone matrix markers and in vivo tissue ingrowth, while information related to the biomolecular mechanisms involved in the early cellular calcium-mediated differentiation is not well elucidated yet. Genetic programs for osteogenesis have been just partially deciphered, and the description of the different molecules and pathways operative in these differentiations is far from complete, as well as the activity of calcium in this process. The present work aims to shed light on the involvement of extracellular calcium in MSC differentiation: a better understanding of the early stage osteogenic differentiation program of MSC seeded on calcium-based biomaterials is required in order to develop optimal strategies to promote osteogenesis through the use of new generation osteoconductive scaffolds. A wide spectrum of analysis has been performed on time-dependent series: gene expression profiles are obtained from samples (MSC seeded on calcium-based scaffolds), together with related microRNAs expression and in vivo functional validation. On this basis, and relying on literature knowledge, hypotheses are made on the biomolecular players activated by the biomaterial calcium-phosphate component. Interestingly, a key role of miR-138 was highlighted, whose inhibition markedly increases osteogenic differentiation in vitro and enhance ectopic bone formation in vivo

  7. Osteogenic Differentiation of MSC through Calcium Signaling Activation: Transcriptomics and Functional Analysis.

    Directory of Open Access Journals (Sweden)

    Federica Viti

    Full Text Available The culture of progenitor mesenchymal stem cells (MSC onto osteoconductive materials to induce a proper osteogenic differentiation and mineralized matrix regeneration represents a promising and widely diffused experimental approach for tissue-engineering (TE applications in orthopaedics. Among modern biomaterials, calcium phosphates represent the best bone substitutes, due to their chemical features emulating the mineral phase of bone tissue. Although many studies on stem cells differentiation mechanisms have been performed involving calcium-based scaffolds, results often focus on highlighting production of in vitro bone matrix markers and in vivo tissue ingrowth, while information related to the biomolecular mechanisms involved in the early cellular calcium-mediated differentiation is not well elucidated yet. Genetic programs for osteogenesis have been just partially deciphered, and the description of the different molecules and pathways operative in these differentiations is far from complete, as well as the activity of calcium in this process. The present work aims to shed light on the involvement of extracellular calcium in MSC differentiation: a better understanding of the early stage osteogenic differentiation program of MSC seeded on calcium-based biomaterials is required in order to develop optimal strategies to promote osteogenesis through the use of new generation osteoconductive scaffolds. A wide spectrum of analysis has been performed on time-dependent series: gene expression profiles are obtained from samples (MSC seeded on calcium-based scaffolds, together with related microRNAs expression and in vivo functional validation. On this basis, and relying on literature knowledge, hypotheses are made on the biomolecular players activated by the biomaterial calcium-phosphate component. Interestingly, a key role of miR-138 was highlighted, whose inhibition markedly increases osteogenic differentiation in vitro and enhance ectopic bone

  8. Periodic solutions of first-order functional differential equations in population dynamics

    CERN Document Server

    Padhi, Seshadev; Srinivasu, P D N

    2014-01-01

    This book provides cutting-edge results on the existence of multiple positive periodic solutions of first-order functional differential equations. It demonstrates how the Leggett-Williams fixed-point theorem can be applied to study the existence of two or three positive periodic solutions of functional differential equations with real-world applications, particularly with regard to the Lasota-Wazewska model, the Hematopoiesis model, the Nicholsons Blowflies model, and some models with Allee effects. Many interesting sufficient conditions are given for the dynamics that include nonlinear characteristics exhibited by population models. The last chapter provides results related to the global appeal of solutions to the models considered in the earlier chapters. The techniques used in this book can be easily understood by anyone with a basic knowledge of analysis. This book offers a valuable reference guide for students and researchers in the field of differential equations with applications to biology, ecology, a...

  9. A Multiagent Transfer Function Neuroapproach to Solve Fuzzy Riccati Differential Equations

    Directory of Open Access Journals (Sweden)

    Mohammad Shazri Shahrir

    2014-01-01

    Full Text Available A numerical solution of fuzzy quadratic Riccati differential equation is estimated using a proposed new approach for neural networks (NN. This proposed new approach provides different degrees of polynomial subspaces for each of the transfer function. This multitude of transfer functions creates unique “agents” in the structure of the NN. Hence it is named as multiagent neuroapproach (multiagent NN. Previous works have shown that results using Runge-Kutta 4th order (RK4 are reliable. The results can be achieved by solving the 1st order nonlinear differential equation (ODE that is found commonly in Riccati differential equation. Multiagent NN shows promising results with the advantage of continuous estimation and improved accuracy that can be produced over Mabood et al. (2013, RK-4, and the existing neuromethod (NM. Numerical examples are discussed to illustrate the proposed method.

  10. Regulator of myeloid differentiation and function:The secret life of Ikaros

    Institute of Scientific and Technical Information of China (English)

    Olivia; L; Francis; Jonathon; L; Payne; Kimberly; J; Payne

    2011-01-01

    Ikaros (also known as Lyf-1) was initially described as a lymphoid-specific transcription factor.Although Ikaros has been shown to regulate hematopoietic stem cell renewal,as well as the development and function of cells from multiple hematopoietic lineages,including the myeloid lineage,Ikaros has primarily been studied in context of lymphoid development and malignancy.This review focuses on the role of Ikaros in myeloid cells.We address the importance of post-transcriptional regulation of Ikaros function;the emerging role of Ikaros in myeloid malignancy;Ikaros as a regulator of myeloid differentiation and function;and the selective expression of Ikaros isoform-x in cells with myeloid potential.We highlight the challenges of dissecting Ikaros function in lineage commitment decisions among lymphoidmyeloid progenitors that have emerged as a major myeloid differentiation pathway in recent studies,which leads to reconstruction of the traditional map of murine and human hematopoiesis.

  11. Computation of Value Functions in Nonlinear Differential Games with State Constraints

    KAUST Repository

    Botkin, Nikolai

    2013-01-01

    Finite-difference schemes for the computation of value functions of nonlinear differential games with non-terminal payoff functional and state constraints are proposed. The solution method is based on the fact that the value function is a generalized viscosity solution of the corresponding Hamilton-Jacobi-Bellman-Isaacs equation. Such a viscosity solution is defined as a function satisfying differential inequalities introduced by M. G. Crandall and P. L. Lions. The difference with the classical case is that these inequalities hold on an unknown in advance subset of the state space. The convergence rate of the numerical schemes is given. Numerical solution to a non-trivial three-dimensional example is presented. © 2013 IFIP International Federation for Information Processing.

  12. Global series solutions of nonlinear differential equations with shocks using Walsh functions

    Science.gov (United States)

    Gnoffo, Peter A.

    2014-02-01

    An orthonormal basis set composed of Walsh functions is used for deriving global solutions (valid over the entire domain) to nonlinear differential equations that include discontinuities. Function gn(x) of the set, a scaled Walsh function in sequency order, is comprised of n piecewise constant values (square waves) across the domain xa⩽x⩽xb. Only two square wave lengths are allowed in any function and a new derivation of the basis functions applies a fractal-like algorithm (infinitely self-similar) focused on the distribution of wave lengths. This distribution is determined by a recursive folding algorithm that propagates fundamental symmetries to successive values of n. Functions, including those with discontinuities, may be represented on the domain as a series in gn(x) with no occurrence of a Gibbs phenomenon (ringing) across the discontinuity. A much more powerful, self-mapping characteristic of the series is closure under multiplication - the product of any two Walsh functions is also a Walsh function. This self-mapping characteristic transforms the solution of nonlinear differential equations to the solution of systems of polynomial equations if the original nonlinearities can be represented as products of the dependent variables and the convergence of the series for n→∞ can be demonstrated. Fundamental operations (reciprocal, integral, derivative) on Walsh function series representations of functions with discontinuities are defined. Examples are presented for solution of the time dependent Burger's equation and for quasi-one-dimensional nozzle flow including a shock.

  13. Does Gender-Specific Differential Item Functioning Affect the Structure in Vocational Interest Inventories?

    Science.gov (United States)

    Beinicke, Andrea; Pässler, Katja; Hell, Benedikt

    2014-01-01

    The study investigates consequences of eliminating items showing gender-specific differential item functioning (DIF) on the psychometric structure of a standard RIASEC interest inventory. Holland's hexagonal model was tested for structural invariance using a confirmatory methodological approach (confirmatory factor analysis and randomization…

  14. Power and Sample Size Calculations for Logistic Regression Tests for Differential Item Functioning

    Science.gov (United States)

    Li, Zhushan

    2014-01-01

    Logistic regression is a popular method for detecting uniform and nonuniform differential item functioning (DIF) effects. Theoretical formulas for the power and sample size calculations are derived for likelihood ratio tests and Wald tests based on the asymptotic distribution of the maximum likelihood estimators for the logistic regression model.…

  15. Examining Type I Error and Power for Detection of Differential Item and Testlet Functioning

    Science.gov (United States)

    Lee, Young-Sun; Cohen, Allan; Toro, Maritsa

    2009-01-01

    In this study, the effectiveness of detection of differential item functioning (DIF) and testlet DIF using SIBTEST and Poly-SIBTEST were examined in tests composed of testlets. An example using data from a reading comprehension test showed that results from SIBTEST and Poly-SIBTEST were not completely consistent in the detection of DIF and testlet…

  16. A Robust Outlier Approach to Prevent Type I Error Inflation in Differential Item Functioning

    Science.gov (United States)

    Magis, David; De Boeck, Paul

    2012-01-01

    The identification of differential item functioning (DIF) is often performed by means of statistical approaches that consider the raw scores as proxies for the ability trait level. One of the most popular approaches, the Mantel-Haenszel (MH) method, belongs to this category. However, replacing the ability level by the simple raw score is a source…

  17. THE UNIT BALL OF C*-ALGEBRA AND DIFFERENTIABILITY OF SUPPORT FUNCTION

    Institute of Scientific and Technical Information of China (English)

    Y. Dehghan; I. Sadeqi

    2005-01-01

    In this paper we show that the unit ball of an infinite dimensional commutative C*-algebra lacks strongly exposed points, so they have no predual. Also in the second part, we use the concept of strongly exposed points in the Frechet differentiability of support convex functions.

  18. Oscillatory and Asymptotic Behavior of a Second-Order Nonlinear Functional Differential Equations

    Institute of Scientific and Technical Information of China (English)

    张全信; 高丽; 王少英

    2012-01-01

    This paper is concerned with oscillatory and asymptotic behavior of solutions of a class of second order nonlinear functional differential equations. By using the generalized Riccati transformation and the integral averaging technique, new oscillation criteria and asymptotic behavior are obtained for all solutions of the equation. Our results generalize and improve some known theorems.

  19. Numerical solutions of a control problem governed by functional differential equations

    Science.gov (United States)

    Banks, H. T.; Thrift, P. R.; Burns, J. A.; Cliff, E. M.

    1978-01-01

    A numerical procedure is proposed for solving optimal control problems governed by linear retarded functional differential equations. The procedure is based on the idea of 'averaging approximations', due to Banks and Burns (1975). For illustration, numerical results generated on an IBM 370/158 computer, which demonstrate the rapid convergence of the method are presented.

  20. A Synthesis of the Peer-Reviewed Differential Bundle Functioning Research

    Science.gov (United States)

    Banks, Kathleen

    2013-01-01

    The purpose of this article was to present a synthesis of the peer-reviewed differential bundle functioning (DBF) research that has been conducted to date. A total of 16 studies were synthesized according to the following characteristics: tests used and learner groups, organizing principles used for developing bundles, DBF detection methods used,…

  1. Stability of Differential Item Functioning over a Single Population in Survey Data

    Science.gov (United States)

    Dodeen, Hamzeh

    2004-01-01

    This study investigates the stability of differential item functioning (DIF) in survey data. Surveys are conducted periodically, and their results are often reported by aggregating responses. Estimating the stability of DIF across subsets of a survey population can be an important indicator in determining the likelihood of DIF stability over…

  2. Controllability of Non-densely Defined Neutral Functional Differential Systems in Abstract Space

    Institute of Scientific and Technical Information of China (English)

    Xianlong FU; Xingbo LIU

    2007-01-01

    In this paper, by means of Sadovskii fixed point theorem, the authors establish a result concerning the controllability for a class of abstract neutral functional differential systems where the linear part is non-densely defined and satisfies the Hille-Yosida condition.As an application, an example is provided to illustrate the obtained result.

  3. Using Multiple-Variable Matching to Identify Cultural Sources of Differential Item Functioning

    Science.gov (United States)

    Wu, Amery D.; Ercikan, Kadriye

    2006-01-01

    Identifying the sources of differential item functioning (DIF) in international assessments is very challenging, because such sources are often nebulous and intertwined. Even though researchers frequently focus on test translation and content area, few actually go beyond these factors to investigate other cultural sources of DIF. This article…

  4. Solvability of Boundary Value Problem at Resonance for Third-Order Functional Differential Equations

    Indian Academy of Sciences (India)

    Pinghua Yang; Zengji Du; Weigao Ge

    2008-05-01

    This paper is devoted to the study of boundary value problem of third-order functional differential equations. We obtain some existence results for the problem at resonance under the condition that the nonlinear terms is bounded or generally unbounded. In this paper we mainly use the topological degree theory.

  5. A robust outlier approach to prevent type I error inflation in Differential Item Functioning

    NARCIS (Netherlands)

    Magis, D.; de Boeck, P.

    2012-01-01

    The identification of differential item functioning (DIF) is often performed by means of statistical approaches that consider the raw scores as proxies for the ability trait level. One of the most popular approaches, the Mantel-Haenszel (MH) method, belongs to this category. However, replacing the a

  6. Multivoxel Patterns Reveal Functionally Differentiated Networks Underlying Auditory Feedback Processing of Speech

    DEFF Research Database (Denmark)

    Zheng, Zane Z.; Vicente-Grabovetsky, Alejandro; MacDonald, Ewen N.

    2013-01-01

    within a multivoxel pattern analysis framework, that this sensorimotor process is supported by functionally differentiated brain networks. During scanning, a real-time speech-tracking system was used to deliver two acoustically different types of distorted auditory feedback or unaltered feedback while...

  7. Existence and exponential stability for impulsive stochastic partial functional differential equations

    Science.gov (United States)

    Xiao, Shuiming; Chen, Huabin

    2017-03-01

    In this paper, the existence and uniqueness, the exponential stability, and the almost sure exponential stability of mild solution for impulsive stochastic partial functional differential equations with finite delay are considered. Some sufficient conditions are established for our concerned problems, and some existing results are generalized and improved. Finally, an illustrative example is provided to show the feasibility and effectiveness of the obtained results.

  8. The functional variable method for finding exact solutions of some nonlinear time-fractional differential equations

    Indian Academy of Sciences (India)

    Wenjun Liu; Kewang Chen

    2013-09-01

    In this paper, we implemented the functional variable method and the modified Riemann–Liouville derivative for the exact solitary wave solutions and periodic wave solutions of the time-fractional Klein–Gordon equation, and the time-fractional Hirota–Satsuma coupled KdV system. This method is extremely simple but effective for handling nonlinear time-fractional differential equations.

  9. Estimating the Importance of Differential Item Functioning. Program Statistics Research Technical Report No. 95-3.

    Science.gov (United States)

    Rudas, Tamas; Zwick, Rebecca

    A method is proposed to assess the importance of differential item functioning (DIF) by estimating the largest possible fraction of the population in which DIF does not occur, or equivalently, the smallest possible portion of the population in which DIF may occur. The approach is based on latent class (C. C. Clogg, 1981) or mixture concepts, and…

  10. Results on the deficiencies of some differential-difference polynomials of meromorphic functions

    Directory of Open Access Journals (Sweden)

    Zheng Xiu-Min

    2016-01-01

    and c be a non-zero complex constant, then δ(∞, f(zm f(z+cf′(z≥δ(∞, f′ and δ(∞,f(z+cnf′(z≥ δ(∞, f′. We also investigate the value distribution of some differential-difference polynomials taking small function a(z with respect to f(z.

  11. Existence of piecewise continuous mild solutions for impulsive functional differential equations with iterated deviating arguments

    Directory of Open Access Journals (Sweden)

    Pradeep Kumar

    2013-10-01

    Full Text Available The objective of this article is to prove the existence of piecewise continuous mild solutions to impulsive functional differential equation with iterated deviating arguments in a Banach space. The results are obtained by using the theory of analytic semigroups and fixed point theorems.

  12. On Some Qualitative Properties of Mild Solutions of Nonlocal Semilinear Functional Differential Equations

    Directory of Open Access Journals (Sweden)

    Jain Rupali S.

    2014-12-01

    Full Text Available In the present paper, we investigate the qualitative properties such as existence, uniqueness and continuous dependence on initial data of mild solutions of first and second order nonlocal semilinear functional differential equations with delay in Banach spaces. Our analysis is based on semigroup theory and modified version of Banach contraction theorem.

  13. Controllability of impulsive functional differential systems with infinite delay in Banach spaces

    Energy Technology Data Exchange (ETDEWEB)

    Chang Yongkui [Department of Mathematics, Lanzhou Jiaotong University, Lanzhou, Gansu 730070 (China)]. E-mail: lzchangyk@163.com

    2007-08-15

    The paper establishes a sufficient condition for the controllability of the first-order impulsive functional differential systems with infinite delay in Banach spaces. We use Schauder's fixed point theorem combined with a strongly continuous operator semigroup. An example is given to illustrate our results.

  14. The Use of Loglinear Models for Assessing Differential Item Functioning Across Manifest and Latent Examinee Groups

    NARCIS (Netherlands)

    Kelderman, Henk; Macready, George B.

    1990-01-01

    Loglinear latent class models are used to detect differential item functioning (DIF). These models are formulated in such a manner that the attribute to be assessed may be continuous, as in a Rasch model, or categorical, as in Latent Class Mastery models. Further, an item may exhibit DIF with respec

  15. EXISTENCE OF POSITIVE PERIODIC SOLUTIONS FOR INFINITE DELAY FUNCTIONAL DIFFERENTIAL EQUATIONS

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    In this paper, the existence of positive periodic solutions for infinite delay functional differential equations(FDEs for short) is discussed by utilizing a fixed point theorem on a cone in Banach space. Some results on the existence of positive periodic solutions are derived.

  16. Controllability of impulsive neutral functional differential inclusions with infinite delay in Banach spaces

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Y.-K. [Department of Mathematics, Lanzhou Jiaotong University, Lanzhou, Gansu 730070 (China)], E-mail: lzchangyk@163.com; Anguraj, A. [Department of Mathematics, PSG College of Arts and Science, Coimbatore 641 014, Tamil Nadu (India)], E-mail: angurajpsg@yahoo.com; Mallika Arjunan, M. [Department of Mathematics, PSG College of Arts and Science, Coimbatore 641 014, Tamil Nadu (India)], E-mail: arjunphd07@yahoo.co.in

    2009-02-28

    In this work, we establish a sufficient condition for the controllability of the first-order impulsive neutral functional differential inclusions with infinite delay in Banach spaces. The results are obtained by using the Dhage's fixed point theorem.

  17. The Impact of Missing Data on the Detection of Nonuniform Differential Item Functioning

    Science.gov (United States)

    Finch, W. Holmes

    2011-01-01

    Missing information is a ubiquitous aspect of data analysis, including responses to items on cognitive and affective instruments. Although the broader statistical literature describes missing data methods, relatively little work has focused on this issue in the context of differential item functioning (DIF) detection. Such prior research has…

  18. An Introduction to Missing Data in the Context of Differential Item Functioning

    Science.gov (United States)

    Banks, Kathleen

    2015-01-01

    This article introduces practitioners and researchers to the topic of missing data in the context of differential item functioning (DIF), reviews the current literature on the issue, discusses implications of the review, and offers suggestions for future research. A total of nine studies were reviewed. All of these studies determined what effect…

  19. A Monte Carlo Study Investigating Missing Data, Differential Item Functioning, and Effect Size

    Science.gov (United States)

    Garrett, Phyllis

    2009-01-01

    The use of polytomous items in assessments has increased over the years, and as a result, the validity of these assessments has been a concern. Differential item functioning (DIF) and missing data are two factors that may adversely affect assessment validity. Both factors have been studied separately, but DIF and missing data are likely to occur…

  20. A simulation study provided sample size guidance for differential item functioning (DIF) studies using short scales

    DEFF Research Database (Denmark)

    Scott, Neil W; Fayers, Peter M; Aaronson, Neil K;

    2009-01-01

    Differential item functioning (DIF) analyses are increasingly used to evaluate health-related quality of life (HRQoL) instruments, which often include relatively short subscales. Computer simulations were used to explore how various factors including scale length affect analysis of DIF by ordinal...

  1. Differential Item Functioning Analysis of the 2003-04 NHANES Physical Activity Questionnaire

    Science.gov (United States)

    Gao, Yong; Zhu, Weimo

    2011-01-01

    Using differential item functioning (DIF) analyses, this study examined whether there were any DIF items in the National Health and Nutrition Examination Survey (NHANES) physical activity (PA) questionnaire. A subset of adult data from the 2003-04 NHANES study (n = 3,083) was used. PA items related to respondents' occupational, transportation,…

  2. Existence and regularity of local solutions to partial neutral functional differential equations with infinite delay

    Directory of Open Access Journals (Sweden)

    Hassane Bouzahir

    2006-08-01

    Full Text Available In this paper, we establish results concerning, existence, uniqueness, global continuation, and regularity of integral solutions to some partial neutral functional differential equations with infinite delay. These equations find their origin in the description of heat flow models, viscoelastic and thermoviscoelastic materials, and lossless transmission lines models; see for example [15] and [38].

  3. Differentiation of Cognitive Abilities as a Function of Neuroticism Level: A Measurement Equivalence/Invariance Analysis

    Science.gov (United States)

    Bonaccio, Silvia; Reeve, Charlie L.

    2006-01-01

    This paper investigates the differentiation of cognitive abilities as a function of neuroticism. Specifically, we examine Eysenck and White's [Eysenck, H. J., and White, P. O. (1964). Personality and the measurement of intelligence. British Journal of Educational Psychology, 24, 197-201.] hypothesis that cognitive abilities are less differentiated…

  4. Myogenic Differentiation of Mouse Embryonic Stem Cells That Lack a Functional Pax7 Gene

    Science.gov (United States)

    Czerwinska, Areta M.; Grabowska, Iwona; Archacka, Karolina; Bem, Joanna; Swierczek, Barbara; Helinska, Anita; Streminska, Wladyslawa; Fogtman, Anna; Iwanicka-Nowicka, Roksana; Koblowska, Marta

    2016-01-01

    The transcription factor Pax7 plays a key role during embryonic myogenesis and sustains the proper function of satellite cells, which serve as adult skeletal muscle stem cells. Overexpression of Pax7 has been shown to promote the myogenic differentiation of pluripotent stem cells. However, the effects of the absence of functional Pax7 in differentiating embryonic stem cells (ESCs) have not yet been directly tested. Herein, we studied mouse stem cells that lacked a functional Pax7 gene and characterized the differentiation of these stem cells under conditions that promoted the derivation of myoblasts in vitro. We analyzed the expression of myogenic factors, such as myogenic regulatory factors and muscle-specific microRNAs, in wild-type and mutant cells. Finally, we compared the transcriptome of both types of cells and did not find substantial differences in the expression of genes related to the regulation of myogenesis. As a result, we showed that the absence of functional Pax7 does not prevent the in vitro myogenic differentiation of ESCs. PMID:26649785

  5. Differential Item Functioning Analysis of the 2003-04 NHANES Physical Activity Questionnaire

    Science.gov (United States)

    Gao, Yong; Zhu, Weimo

    2011-01-01

    Using differential item functioning (DIF) analyses, this study examined whether there were any DIF items in the National Health and Nutrition Examination Survey (NHANES) physical activity (PA) questionnaire. A subset of adult data from the 2003-04 NHANES study (n = 3,083) was used. PA items related to respondents' occupational, transportation,…

  6. Detection of Differential Item Functioning for More than Two Groups: A Monte Carlo Comparison of Methods

    Science.gov (United States)

    Finch, W. Holmes

    2016-01-01

    Differential item functioning (DIF) assessment is a crucial component in test construction, serving as the primary way in which instrument developers ensure that measures perform in the same way for multiple groups within the population. When such is not the case, scores may not accurately reflect the trait of interest for all individuals in the…

  7. Green function of the double fractional Fokker-Planck equation: Path integral and stochastic differential equations

    OpenAIRE

    Kleinert, H.; Zatloukal, V.

    2015-01-01

    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.

  8. PERIODIC SOLUTIONS TO A HIGH-ORDER NEUTRAL FUNCTIONAL DIFFERENTIAL EQUATION

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    In this paper,using the principle of a priori boundedness,we study the existence and uniqueness of periodic solutions to a high-order neutral functional differential equation.Some new results for the existence and uniqueness of the periodic solution are obtained.

  9. Does Gender-Specific Differential Item Functioning Affect the Structure in Vocational Interest Inventories?

    Science.gov (United States)

    Beinicke, Andrea; Pässler, Katja; Hell, Benedikt

    2014-01-01

    The study investigates consequences of eliminating items showing gender-specific differential item functioning (DIF) on the psychometric structure of a standard RIASEC interest inventory. Holland's hexagonal model was tested for structural invariance using a confirmatory methodological approach (confirmatory factor analysis and randomization…

  10. A PRIORI BOUNDS FOR PERIODIC SOLUTIONS TO A FUNCTIONAL DIFFERENTIAL EQUATION WITH DELAY

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    A priori bounds are established for periodic solutions to a functional differential equation with delay.By means of these bounds,an existence theorem for periodic solutions is obtained using Mawhin's continuation theorem.Our work generalizes the known result.

  11. Simple proofs of nowhere-differentiability for Weierstrass' function and cases of slow growth

    DEFF Research Database (Denmark)

    Johnsen, Jon

    Using a few basics from integration theory, a short proof of nowhere-differentiability of Weierstrass functions is given. Restated in terms of the Fourier transformation, the method consists of a second microlocalisation, which is used to derive two general results on existence of nowhere...

  12. Simple proofs of nowhere-differentiability for Weierstrass' function and cases of slow growth

    DEFF Research Database (Denmark)

    Johnsen, Jon

    2010-01-01

    Using a few basics from integration theory, a short proof of nowhere-differentiability of Weierstrass functions is given. Restated in terms of the Fourier transformation, the method consists in principle of a second microlocalisation, which is used to derive two general results on existence...

  13. Differential Item Functioning By Sex and Race in The Hogan Personality Inventory

    Science.gov (United States)

    Sheppard, Richard; Han, Kyunghee; Colarelli, Stephen M.; Dai, Guangdong; King, Daniel W.

    2006-01-01

    The authors examined measurement bias in the Hogan Personality Inventory by investigating differential item functioning (DIF) across sex and two racial groups (Caucasian and Black). The sample consisted of 1,579 Caucasians (1,023 men, 556 women) and 523 Blacks (321 men, 202 women) who were applying for entry-level, unskilled jobs in factories.…

  14. Power and Sample Size Calculations for Logistic Regression Tests for Differential Item Functioning

    Science.gov (United States)

    Li, Zhushan

    2014-01-01

    Logistic regression is a popular method for detecting uniform and nonuniform differential item functioning (DIF) effects. Theoretical formulas for the power and sample size calculations are derived for likelihood ratio tests and Wald tests based on the asymptotic distribution of the maximum likelihood estimators for the logistic regression model.…

  15. A Simulation Study of Methods for Assessing Differential Item Functioning in Computer-Adaptive Tests.

    Science.gov (United States)

    Zwick, Rebecca; And Others

    Simulated data were used to investigate the performance of modified versions of the Mantel-Haenszel and standardization methods of differential item functioning (DIF) analysis in computer-adaptive tests (CATs). Each "examinee" received 25 items out of a 75-item pool. A three-parameter logistic item response model was assumed, and…

  16. Studying Differential Item Functioning via Latent Variable Modeling: A Note on a Multiple-Testing Procedure

    Science.gov (United States)

    Raykov, Tenko; Marcoulides, George A.; Lee, Chun-Lung; Chang, Chi

    2013-01-01

    This note is concerned with a latent variable modeling approach for the study of differential item functioning in a multigroup setting. A multiple-testing procedure that can be used to evaluate group differences in response probabilities on individual items is discussed. The method is readily employed when the aim is also to locate possible…

  17. Global attractivity of the zero solution of a class of functional differential equations and its applications

    Institute of Scientific and Technical Information of China (English)

    庾建设

    1996-01-01

    The global attractivity of the zero solution of the delay functional differential equation x(t)+ [1+x(t)]F(t, x(·)) =0 is studied by using a new technique. When this result is applied to some special delay bio-mathematics models, some conjectures and open problems appearing in literature are solved, and many known results are improved.

  18. Parent Ratings of ADHD Symptoms: Generalized Partial Credit Model Analysis of Differential Item Functioning across Gender

    Science.gov (United States)

    Gomez, Rapson

    2012-01-01

    Objective: Generalized partial credit model, which is based on item response theory (IRT), was used to test differential item functioning (DIF) for the "Diagnostic and Statistical Manual of Mental Disorders" (4th ed.), inattention (IA), and hyperactivity/impulsivity (HI) symptoms across boys and girls. Method: To accomplish this, parents completed…

  19. Evaluation of Two Types of Differential Item Functioning in Factor Mixture Models with Binary Outcomes

    Science.gov (United States)

    Lee, HwaYoung; Beretvas, S. Natasha

    2014-01-01

    Conventional differential item functioning (DIF) detection methods (e.g., the Mantel-Haenszel test) can be used to detect DIF only across observed groups, such as gender or ethnicity. However, research has found that DIF is not typically fully explained by an observed variable. True sources of DIF may include unobserved, latent variables, such as…

  20. 67 A Study of Cobb-Douglas Production Function with Differential Geometry

    Directory of Open Access Journals (Sweden)

    Alin Cristian Ioan

    2014-12-01

    Full Text Available In this paper we shall made an analysis of Cobb-Douglas production function from the differential point of view. We shall obtain some interesting results about the nature of the points of the surface, the total curvature, the conditions when a production function is minimal and finally we give the equations of the geodesics on the surface i.e. the curves of minimal length between two points.

  1. On the Multiplicity of a C∞-differentiable Function-germ

    Institute of Scientific and Technical Information of China (English)

    Xu XU

    2007-01-01

    Risler & Trotman in 1997 proved that the multiplicity of an analytic function germ is left-right lipschitz invariant,which provided a partial answer to Zariski conjecture.In this note,based on the recent work of Comte,Milman & Trotman,we generalize the work of them to prove that the multiplicity of a C-∞ differentiable function germ is also left-right lipschitz invariant.

  2. Molecular mechanisms regulating expression and function of transcription regulator "inhibitor of differentiation 3"

    Institute of Scientific and Technical Information of China (English)

    Robert Wai-sui LIM; Jin-mei WU

    2005-01-01

    The transcription factor antagonist inhibitor of differentiation 3 (Id3) has been implicated in many diverse developmental, physiological and pathophysiological processes. Its expression and function is subjected to many levels of complex regulation. This review summarizes the current understanding of these mechanisms and describes how they might be related to the diverse functions that have been attributed to the Id3 protein. Detailed understanding of these mechanisms should provide insights towards the development of therapeutic approaches to various diseases, including cancer and atherogenesis.

  3. Novel Functional Changes during Podocyte Differentiation: Increase of Oxidative Resistance and H-Ferritin Expression

    Directory of Open Access Journals (Sweden)

    Emese Bányai

    2014-01-01

    Full Text Available Podocytes are highly specialized, arborized epithelial cells covering the outer surface of the glomerular tuft in the kidney. Terminally differentiated podocytes are unable to go through cell division and hereby they are lacking a key property for regeneration after a toxic injury. Podocytes are long-lived cells but, to date, little is known about the mechanisms that support their stress resistance. Our aim was to investigate whether the well-known morphological changes during podocyte differentiation are accompanied by changes in oxidative resistance in a manner that could support their long-term survival. We used a conditionally immortalized human podocyte cell line to study the morphological and functional changes during differentiation. We followed the differentiation process for 14 days by time-lapse microscopy. During this period nondifferentiated podocytes gradually transformed into large, nonproliferating, frequently multinucleated cells, with enlarged nuclei and opened chromatin structure. We observed that differentiated podocytes were highly resistant to oxidants such as H2O2 and heme when applied separately or in combination, whereas undifferentiated cells were prone to such challenges. Elevated oxidative resistance of differentiated podocytes was associated with increased activities of antioxidant enzymes and H-ferritin expression. Immunohistochemical analysis of normal human kidney specimens revealed that podocytes highly express H-ferritin in vivo as well.

  4. Surviving endoplasmic reticulum stress is coupled to altered chondrocyte differentiation and function.

    Directory of Open Access Journals (Sweden)

    Kwok Yeung Tsang

    2007-03-01

    Full Text Available In protein folding and secretion disorders, activation of endoplasmic reticulum (ER stress signaling (ERSS protects cells, alleviating stress that would otherwise trigger apoptosis. Whether the stress-surviving cells resume normal function is not known. We studied the in vivo impact of ER stress in terminally differentiating hypertrophic chondrocytes (HCs during endochondral bone formation. In transgenic mice expressing mutant collagen X as a consequence of a 13-base pair deletion in Col10a1 (13del, misfolded alpha1(X chains accumulate in HCs and elicit ERSS. Histological and gene expression analyses showed that these chondrocytes survived ER stress, but terminal differentiation is interrupted, and endochondral bone formation is delayed, producing a chondrodysplasia phenotype. This altered differentiation involves cell-cycle re-entry, the re-expression of genes characteristic of a prehypertrophic-like state, and is cell-autonomous. Concomitantly, expression of Col10a1 and 13del mRNAs are reduced, and ER stress is alleviated. ERSS, abnormal chondrocyte differentiation, and altered growth plate architecture also occur in mice expressing mutant collagen II and aggrecan. Alteration of the differentiation program in chondrocytes expressing unfolded or misfolded proteins may be part of an adaptive response that facilitates survival and recovery from the ensuing ER stress. However, the altered differentiation disrupts the highly coordinated events of endochondral ossification culminating in chondrodysplasia.

  5. Yes-associated protein (YAP) transcriptional coactivator functions in balancing growth and differentiation in skin.

    Science.gov (United States)

    Zhang, Haiying; Pasolli, H Amalia; Fuchs, Elaine

    2011-02-01

    In mammals, skin begins as a single-layered epithelium, which, through a series of signals, either stratifies and differentiates to become epidermis or invaginates downward to make hair follicles (HFs). To achieve and maintain proper tissue architecture, keratinocytes must intricately balance growth and differentiation. Here, we uncover a critical and hitherto unappreciated role for Yes-associated protein (YAP), an evolutionarily conserved transcriptional coactivator with potent oncogenic potential. We show that YAP is highly expressed and nuclear in single-layered basal epidermal progenitors. Notably, nuclear YAP progressively declines with age and correlates with proliferative potential of epidermal progenitors. Shortly after initiation of HF morphogenesis, YAP translocates to the cytoplasm of differentiating cells. Through genetic analysis, we demonstrate a role for YAP in maintaining basal epidermal progenitors and regulating HF morphogenesis. YAP overexpression causes hair placodes to evaginate into epidermis rather than invaginate into dermis. YAP also expands basal epidermal progenitors, promotes proliferation, and inhibits terminal differentiation. In vitro gain-and-loss of function studies show that primary mouse keratinocytes (MKs) accelerate proliferation, suppress differentiation, and inhibit apoptosis when YAP is activated and reverse these features when YAP is inhibited. Finally, we identify Cyr61 as a target of YAP in MKs and demonstrate a requirement for TEA domain (TEAD) transcriptional factors to comediate YAP functions in MKs.

  6. 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.

  7. Tracking the Spatial and Functional Gradient of Monocyte-To-Macrophage Differentiation in Inflamed Lung.

    Science.gov (United States)

    Sen, Debasish; Jones, Stephen M; Oswald, Erin M; Pinkard, Henry; Corbin, Kaitlin; Krummel, Matthew F

    2016-01-01

    Myeloid-derived cells such as monocytes, dendritic cells (DCs), and macrophages are at the heart of the immune effector function in an inflammatory response. But because of the lack of an efficient imaging system to trace these cells live during their migration and maturation in their native environment at sub-cellular resolution, our knowledge is limited to data available from specific time-points analyzed by flow cytometry, histology, genomics and other immunological methods. Here, we have developed a ratiometric imaging method for measuring monocyte maturation in inflamed mouse lungs in situ using real-time using 2-photon imaging and complementary methods. We visualized that while undifferentiated monocytes were predominantly found only in the vasculature, a semi-differentiated monocyte/macrophage population could enter the tissue and resembled more mature and differentiated populations by morphology and surface phenotype. As these cells entered and differentiated, they were already selectively localized near inflamed airways and their entry was associated with changes in motility and morphology. We were able to visualize these during the act of differentiation, a process that can be demonstrated in this way to be faster on a per-cell basis under inflammatory conditions. Finally, our in situ analyses demonstrated increases, in the differentiating cells, for both antigen uptake and the ability to mediate interactions with T cells. This work, while largely confirming proposed models for in situ differentiation, provides important in situ data on the coordinated site-specific recruitment and differentiation of these cells and helps elaborate the predominance of immune pathology at the airways. Our novel imaging technology to trace immunogenic cell maturation in situ will complement existing information available on in situ differentiation deduced from other immunological methods, and assist better understanding of the spatio-temporal cellular behavior during an

  8. Human endometrial stromal stem cells differentiate into megakaryocytes with the ability to produce functional platelets.

    Directory of Open Access Journals (Sweden)

    Jinju Wang

    Full Text Available Human endometrium is a high dynamic tissue that contains endometrial stromal stem cells (hESSCs. The hESSCs have been differentiated into a number of cell lineages. However, differentiation of hESSCs into megakaryocytes (MKs has not yet been investigated. The aim of this study was to investigate the feasibility of MK generation from hESSCs and subsequent production of functional platelets (PLTs. In our study, hESSCs were cultured from endometrial stromal cells as confirmed by positive stromal cell specific markers (CD90 and CD29 and negative hematopoietic stem cell markers (CD45 and CD34 expression. Then, hESSCs were differentiated in a medium supplemented with thrombopoietin (TPO for 18 days. The MK differentiation was analyzed by flow cytometry and confocal microscopy. The differentiation medium was collected for PLT production analysis by flow cytometry, transmission electron microscopy and functional measurements. Our results show: 1 MKs were successfully generated from hESSCs as identified by expression of specific markers (CD41a: 1 ± 0.09% and 39 ± 3.0%; CD42b: 1.2 ± 0.06% and 28 ± 2.0%, control vs. differentiation accompanied with reduction of pluripotent transcription factors (Oct4 and Sox2 expression; 2 The level of PLTs in the differentiation medium was 16 ± 1 number/µl as determined by size (2-4 µm and CD41a expression (CD41a: 1 ± 0.4% and 90±2.0%, control vs. differentiation; 3 Generated PLTs were functional as evidenced by the up-regulation of CD62p expression and fibrinogen binding following thrombin stimulation; 4 Released PLTs showed similar ultra-structure characteristics (alpha granules, vacuoles and dense tubular system as PLTs from peripheral blood determined by electron microscopic analysis. Data demonstrate the feasibility of generating MKs from hESSCs, and that the generated MKs release functional PLTs. Therefore, hESSCs could be a potential new stem cell source for in vitro MK/PLT production.

  9. Human endometrial stromal stem cells differentiate into megakaryocytes with the ability to produce functional platelets.

    Science.gov (United States)

    Wang, Jinju; Chen, Shuzhen; Zhang, Cheng; Stegeman, Samantha; Pfaff-Amesse, Teresa; Zhang, Ying; Zhang, Wenfeng; Amesse, Lawrence; Chen, Yanfang

    2012-01-01

    Human endometrium is a high dynamic tissue that contains endometrial stromal stem cells (hESSCs). The hESSCs have been differentiated into a number of cell lineages. However, differentiation of hESSCs into megakaryocytes (MKs) has not yet been investigated. The aim of this study was to investigate the feasibility of MK generation from hESSCs and subsequent production of functional platelets (PLTs). In our study, hESSCs were cultured from endometrial stromal cells as confirmed by positive stromal cell specific markers (CD90 and CD29) and negative hematopoietic stem cell markers (CD45 and CD34) expression. Then, hESSCs were differentiated in a medium supplemented with thrombopoietin (TPO) for 18 days. The MK differentiation was analyzed by flow cytometry and confocal microscopy. The differentiation medium was collected for PLT production analysis by flow cytometry, transmission electron microscopy and functional measurements. Our results show: 1) MKs were successfully generated from hESSCs as identified by expression of specific markers (CD41a: 1 ± 0.09% and 39 ± 3.0%; CD42b: 1.2 ± 0.06% and 28 ± 2.0%, control vs. differentiation) accompanied with reduction of pluripotent transcription factors (Oct4 and Sox2) expression; 2) The level of PLTs in the differentiation medium was 16 ± 1 number/µl as determined by size (2-4 µm) and CD41a expression (CD41a: 1 ± 0.4% and 90±2.0%, control vs. differentiation); 3) Generated PLTs were functional as evidenced by the up-regulation of CD62p expression and fibrinogen binding following thrombin stimulation; 4) Released PLTs showed similar ultra-structure characteristics (alpha granules, vacuoles and dense tubular system) as PLTs from peripheral blood determined by electron microscopic analysis. Data demonstrate the feasibility of generating MKs from hESSCs, and that the generated MKs release functional PLTs. Therefore, hESSCs could be a potential new stem cell source for in vitro MK/PLT production.

  10. Soliton solution for nonlinear partial differential equations by cosine-function method

    Energy Technology Data Exchange (ETDEWEB)

    Ali, A.H.A. [Mathematics Department, Faculty of Science, Menoufia University, Shebein El-Koom (Egypt); Soliman, A.A. [Department of Mathematics, Faculty of Education (AL-Arish), Suez Canal University, AL-Arish 45111 (Egypt)], E-mail: asoliman_99@yahoo.com; Raslan, K.R. [Mathematics Department, Faculty of Science, Al-Azhar University, Nasr-City, Cairo (Egypt)

    2007-08-20

    In this Letter, we established a traveling wave solution by using Cosine-function algorithm for nonlinear partial differential equations. The method is used to obtain the exact solutions for five different types of nonlinear partial differential equations such as, general equal width wave equation (GEWE), general regularized long wave equation (GRLW), general Korteweg-de Vries equation (GKdV), general improved Korteweg-de Vries equation (GIKdV), and Coupled equal width wave equations (CEWE), which are the important soliton equations.

  11. Exponential rational function method for space-time fractional differential equations

    Science.gov (United States)

    Aksoy, Esin; Kaplan, Melike; Bekir, Ahmet

    2016-04-01

    In this paper, exponential rational function method is applied to obtain analytical solutions of the space-time fractional Fokas equation, the space-time fractional Zakharov Kuznetsov Benjamin Bona Mahony, and the space-time fractional coupled Burgers' equations. As a result, some exact solutions for them are successfully established. These solutions are constructed in fractional complex transform to convert fractional differential equations into ordinary differential equations. The fractional derivatives are described in Jumarie's modified Riemann-Liouville sense. The exact solutions obtained by the proposed method indicate that the approach is easy to implement and effective.

  12. Differentiation and function of human monocyte-derived dendritic cells under the influence of leflunomide

    Directory of Open Access Journals (Sweden)

    Stojić-Vukanić Z.

    2011-01-01

    Full Text Available Leflunomide is an immunosuppressive drug effective in experimental models of transplantation and autoimmune diseases and in the treatment of active rheumatoid arthritis (RA. Having in mind that it has been shown that some other immunosuppressive drugs (glucocorticoids, mycophenolate mofetil, sirolimus etc. impair dendritic cell (DC phenotype and function, we investigated the effect of A77 1726, an active metabolite of leflunomide, on the differentiation and function of human monocyte-derived dendritic cells (MDDC in vitro. Immature MDDC were generated by cultivating monocytes in medium supplemented with GM-CSF and IL-4. To induce maturation, immature MDDC were cultured for 2 additional days with LPS. A77 1726 (100 μM was added at the beginning of cultivation. Flow cytometric analysis showed that MDDC differentiated in the presence of A77 1726 exhibited an altered phenotype, with a down-regulated surface expression of CD80, CD86, CD54 and CD40 molecules. Furthermore, the continuous presence of A77 1726 during differentiation and maturation prevented successful maturation, judging by the decreased expression of maturation marker CD83, costimulatory and adhesive molecules on A77 1726-treated mature MDDC. In addition, A77 1726-pretreated MDDC exhibited a poor stimulatory capacity of the allogeneic T cells and a low production of IL-10 and IL-18. These data suggest that leflunomide impairs the differentiation, maturation and function of human MDDC in vitro, which is an additional mechanism of its immunosuppressive effect.

  13. Fractional Order Digital Differentiator Design Based on Power Function and Least squares

    Science.gov (United States)

    Kumar, Manjeet; Rawat, Tarun Kumar

    2016-10-01

    In this article, we propose the use of power function and least squares method for designing of a fractional order digital differentiator. The input signal is transformed into a power function by using Taylor series expansion, and its fractional derivative is computed using the Grunwald-Letnikov (G-L) definition. Next, the fractional order digital differentiator is modelled as a finite impulse response (FIR) system that yields fractional order derivative of the G-L type for a power function. The FIR system coefficients are obtained by using the least squares method. Two examples are used to demonstrate that the fractional derivative of the digital signals is computed by using the proposed technique. The results of the third and fourth examples reveal that the proposed technique gives superior performance in comparison with the existing techniques.

  14. SOME OSCILLATION CRITERIA FOR SECOND ORDER NONLINEAR FUNCTIONAL ORDINARY DIFFERENTIAL EQUATIONS

    Institute of Scientific and Technical Information of China (English)

    E.M.E. Zayed; M.A. El-Moneam

    2007-01-01

    The main objective of this article is to study the oscillatory behavior of the solutions of the following nonlinear functional differential equations (a(t)x'(t))' + δ1p(t)x'(t) + δ2q(t)f(x(g(t))) = 0,for 0 ≤ t0 ≤ t, where δ1 = ±1 and δ2 = ±1. The functions p,q,g : [t0, ∞) → R, f :R → R are continuous, a(t) > 0, p(t) ≥ 0,q(t) ≥ 0 for t ≥ t0, limt→∞ g(t) = ∞, and q is not identically zero on any subinterval of [t0, ∞). Moreover, the functions q(t),g(t), and a(t) are continuously differentiable.

  15. Potential energy function from differential cross-section data: An inverse quantum scattering theory approach

    Science.gov (United States)

    Lemes, N. H. T.; Borges, E.; Sousa, R. V.; Braga, J. P.

    Important physical and chemical information can be extracted from scattering experiments data. This kind of problem is usually ill-posed in the sense that one of the three conditions, existence, uniqueness, and continuity, is not satisfied. For example, the inversion of intermolecular potential functions from scattering data, such as experimental cross section, is an ill-posed problem which can be modeled as a Fredholm integral equation. In this work, an inversion method based on recursive neural networks is proposed to solve this inverse quantum scattering problem within the Born approximation. As physical example, the repulsive component of the potential function for the interaction Ar-Ar is obtained from differential cross-section data. The sensitivity of the potential energy function to be inverted, in relation to the differential cross-section data, is also analyzed. The present approach is simple, general, and numerically stable.

  16. Sociodemographic Factors Differentiating the Consumer and the Motivations for Functional Food Consumption.

    Science.gov (United States)

    Kraus, Artur; Annunziata, Azzurra; Vecchio, Riccardo

    2017-02-01

    The aim of this study was to determine the (1) role of gender, age, and education in the evaluation of multidimensional criteria of the purchase of functional products, which were (a) quality and organoleptic attributes, (b) attributes of packaging and labeling, (c) healthful properties, (d) functional components, (e) base product (carrier) and (2) most important motives for the purchase and consumption of functional food among consumers of different sociodemographic profiles. The data were collected in direct interviews. The sample (n = 200) consisted of 137 women and 63 men age 18-60 years. The research tool was a questionnaire divided into 4 sections. The first one included quality attributes. The second one included healthful properties, functional components, and carriers. The third one concerned the motives for purchasing functional food and included the consequences and values. In the fourth section the participants were asked about gender, age, and education. Gender, age, and education differentiated the criteria influencing the decision to purchase functional food. Women, older people (35-60 years), and those with university education attach the greatest importance to naturalness, nutritional value, freshness, food safety, and quality guarantee. Clear differences between men and women appear in the field of functional components, which are significantly more important for women than for men. Gender, age, and education essentially differentiate the preferences for base product (carrier). Young men prefer meat products in the role of functional carriers. In turn, women and older men prefer cereal products as basic functional carriers. Young consumers are more open to high-technology food processing. Motivations are differentiated by age and gender. Young men, as opposed to women and older men, attach less importance to functional and psychological consequences: improvement of health, healthy eating, conscious choice, and health promotion. Women and older

  17. Adult adipose-derived stromal cells differentiate into neurons with normal electrophysiological functions

    Institute of Scientific and Technical Information of China (English)

    Xiaodong Yuan; Yanan Cai; Ya Ou; Yanhui Lu

    2011-01-01

    β-mercaptoethanol was used to induce in vitro neuronal differentiation of adipose-derived stromal cells. Within an 8-hour period post-differentiation, the induced cells exhibited typical neuronal morphology, and expression of microtubule-associated protein 2 and neuron-specific enolase, which are markers of mature neurons, reached a peak at 5 hours. Specific organelle Nissl bodies of neurons were observed under transmission electron microscopy. Results of membrane potential showed that fluorescence intensity of cells was greater after 5 hours than adipose-derived stromal cells prior to induction. In addition, following stimulation with high-concentration potassium solution, fluorescence intensity increased. These experimental findings suggested that neurons differentiated from adipose-derived stromal cells and expressed mature K+ channels. In addition, following stimulation with high potassium solution, the membrane potential depolarized and fired an action potential, confirming that the induced cells possessed electrophysiological functions.

  18. Using Bioluminescence Resonance Energy Transfer (BRET) to Characterize Agonist-Induced Arrestin Recruitment to Modified and Unmodified G Protein-Coupled Receptors.

    Science.gov (United States)

    Donthamsetti, Prashant; Quejada, Jose Rafael; Javitch, Jonathan A; Gurevich, Vsevolod V; Lambert, Nevin A

    2015-09-01

    G protein-coupled receptors (GPCRs) represent ∼25% of current drug targets. Ligand binding to these receptors activates G proteins and arrestins, which are involved in differential signaling pathways. Because functionally selective or biased ligands activate one of these two pathways, they may be superior medications for certain diseases states. The identification of such ligands requires robust drug screening assays for both G protein and arrestin activity. This unit describes protocols for two bioluminescence resonance energy transfer (BRET)-based assays used to monitor arrestin recruitment to GPCRs. One assay requires modification of GPCRs by fusion to a BRET donor or acceptor moiety, whereas the other can detect arrestin recruitment to unmodified GPCRs.

  19. Carbonic Anhydrases Function in Anther Cell Differentiation Downstream of the Receptor-Like Kinase EMS1.

    Science.gov (United States)

    Huang, Jian; Li, Zhiyong; Biener, Gabriel; Xiong, Erhui; Malik, Shikha; Eaton, Nathan; Zhao, Catherine Z; Raicu, Valerica; Kong, Hongzhi; Zhao, Dazhong

    2017-06-01

    Plants extensively employ leucine-rich repeat receptor-like kinases (LRR-RLKs), the largest family of RLKs, to control a wide range of growth and developmental processes as well as defense responses. To date, only a few direct downstream effectors for LRR-RLKs have been identified. We previously showed that the LRR-RLK EMS1 (EXCESS MICROSPOROCYTES1) and its ligand TPD1 (TAPETUM DETERMINANT1) are required for the differentiation of somatic tapetal cells and reproductive microsporocytes during early anther development in Arabidopsis thaliana Here, we report the identification of β-carbonic anhydrases (βCAs) as the direct downstream targets of EMS1. EMS1 biochemically interacts with βCA proteins. Loss of function of βCA genes caused defective tapetal cell differentiation, while overexpression of βCA1 led to the formation of extra tapetal cells. EMS1 phosphorylates βCA1 at four sites, resulting in increased βCA1 activity. Furthermore, phosphorylation-blocking mutations impaired the function of βCA1 in tapetal cell differentiation; however, a phosphorylation mimic mutation promoted the formation of tapetal cells. βCAs are also involved in pH regulation in tapetal cells. Our findings highlight the role of βCA in controlling cell differentiation and provide insights into the posttranslational modification of carbonic anhydrases via receptor-like kinase-mediated phosphorylation. © 2017 American Society of Plant Biologists. All rights reserved.

  20. [Differentiation of functional cells from iPS cells by efficient gene transfer].

    Science.gov (United States)

    Kawabata, Kenji; Tashiro, Katsuhisa; Mizuguchi, Hiroyuki

    2010-11-01

    Induced pluripotent stem (iPS) cells, which are generated from somatic cells by transducing four genes, are expected to have broad application to regenerative medicine. Although establishment of an efficient gene transfer system for iPS cells is considered to be essential for differentiating them into functional cells, the detailed transduction characteristics of iPS cells have not been examined. By using an adenovirus (Ad) vector containing the cytomegalovirus enhancer/beta-actin (CA) promoters, we have developed an efficient transduction system for mouse mesenchymal stem cells and embryonic stem (ES) cells. Also, we applied our transduction system to mouse iPS cells and investigated whether efficient differentiation could be achieved by Ad vector-mediated transduction of a functional gene. As in the case of ES cells, the Ad vector could efficiently transduce transgenes into mouse iPS cells. We found that the CA promoter had potent transduction ability in iPS cells. Moreover, exogenous expression of a PPARγ gene or a Runx2 gene into mouse iPS cells by an optimized Ad vector enhanced adipocyte or osteoblast differentiation, respectively. These results suggest that Ad vector-mediated transient transduction is sufficient to promote cellular differentiation and that our transduction methods would be useful for therapeutic applications based on iPS cells.

  1. A parsimonious statistical method to detect groupwise differentially expressed functional connectivity networks.

    Science.gov (United States)

    Chen, Shuo; Kang, Jian; Xing, Yishi; Wang, Guoqing

    2015-12-01

    Group-level functional connectivity analyses often aim to detect the altered connectivity patterns between subgroups with different clinical or psychological experimental conditions, for example, comparing cases and healthy controls. We present a new statistical method to detect differentially expressed connectivity networks with significantly improved power and lower false-positive rates. The goal of our method was to capture most differentially expressed connections within networks of constrained numbers of brain regions (by the rule of parsimony). By virtue of parsimony, the false-positive individual connectivity edges within a network are effectively reduced, whereas the informative (differentially expressed) edges are allowed to borrow strength from each other to increase the overall power of the network. We develop a test statistic for each network in light of combinatorics graph theory, and provide p-values for the networks (in the weak sense) by using permutation test with multiple-testing adjustment. We validate and compare this new approach with existing methods, including false discovery rate and network-based statistic, via simulation studies and a resting-state functional magnetic resonance imaging case-control study. The results indicate that our method can identify differentially expressed connectivity networks, whereas existing methods are limited.

  2. It Might Not Make a Big DIF: Improved Differential Test Functioning Statistics That Account for Sampling Variability

    Science.gov (United States)

    Chalmers, R. Philip; Counsell, Alyssa; Flora, David B.

    2016-01-01

    Differential test functioning, or DTF, occurs when one or more items in a test demonstrate differential item functioning (DIF) and the aggregate of these effects are witnessed at the test level. In many applications, DTF can be more important than DIF when the overall effects of DIF at the test level can be quantified. However, optimal statistical…

  3. A New Method for Assessing the Statistical Significance in the Differential Functioning of Items and Tests (DFIT) Framework

    Science.gov (United States)

    Oshima, T. C.; Raju, Nambury S.; Nanda, Alice O.

    2006-01-01

    A new item parameter replication method is proposed for assessing the statistical significance of the noncompensatory differential item functioning (NCDIF) index associated with the differential functioning of items and tests framework. In this new method, a cutoff score for each item is determined by obtaining a (1-alpha ) percentile rank score…

  4. On the generalization of statistical thermodynamic functions by a Riccati differential equation.

    Science.gov (United States)

    Peña, J. J.; Rubio-Ponce, A.; Morales, J.

    2016-08-01

    In this work, we propose a non-linear differential equation of Riccati-type, where the standard partition function Z(T) is taken as its particular solution leading to their generalization Zg(T); from there, other related statistical thermodynamic functions are generalized. As an useful application of our proposal, other thermodynamic functions, namely, the internal energy, heat capacity, Helmholtz free energy and entropy, associated to the model of the ideal monatomic gas in D-dimensions are generalized. According to our results, thermodynamic properties derived from the standard partition functions by means of ordinary statistical mechanics are incomplete. In fact, although asymptotically with the increasing of temperature the generalized statistical thermodynamic functions reduce to the standard ones, these contain an extra term which is dominant at very low temperature indicating that standard findings should be corrected.

  5. Adaptive Neural Control of Nonaffine Nonlinear Systems without Differential Condition for Nonaffine Function

    Directory of Open Access Journals (Sweden)

    Chaojiao Sun

    2016-01-01

    Full Text Available An adaptive neural control scheme is proposed for nonaffine nonlinear system without using the implicit function theorem or mean value theorem. The differential conditions on nonaffine nonlinear functions are removed. The control-gain function is modeled with the nonaffine function probably being indifferentiable. Furthermore, only a semibounded condition for nonaffine nonlinear function is required in the proposed method, and the basic idea of invariant set theory is then constructively introduced to cope with the difficulty in the control design for nonaffine nonlinear systems. It is rigorously proved that all the closed-loop signals are bounded and the tracking error converges to a small residual set asymptotically. Finally, simulation examples are provided to demonstrate the effectiveness of the designed method.

  6. Recovery of partial differential operators on classes of periodic functions with mixed smoothness

    Science.gov (United States)

    Balgimbayeva, Sholpan

    2016-08-01

    We consider the problem of optimal linear recovery for mixed partial differential operator A on the unit ball SBpθ r(Tn) of the Nikol'skii-Besov space of periodic functions with mixed smoothness. We find error bounds sharp in order for optimal linear recovery of operator A on class SBpθ r(Tn) . As information IMδ(f ) about the functions f from class SBpθ r(Tn) we shall use Fourier coefficients with numbers from step "hyperbolic" cross. As the linear method using the information about Fourier coefficients, we shall consider action of the mixed partial differential operator A on the special "private" sum of decomposition on system (type as wavelets) trigonometric polynomials.

  7. Neurons Differentiated from Transplanted Stem Cells Respond Functionally to Acoustic Stimuli in the Awake Monkey Brain.

    Science.gov (United States)

    Wei, Jing-Kuan; Wang, Wen-Chao; Zhai, Rong-Wei; Zhang, Yu-Hua; Yang, Shang-Chuan; Rizak, Joshua; Li, Ling; Xu, Li-Qi; Liu, Li; Pan, Ming-Ke; Hu, Ying-Zhou; Ghanemi, Abdelaziz; Wu, Jing; Yang, Li-Chuan; Li, Hao; Lv, Long-Bao; Li, Jia-Li; Yao, Yong-Gang; Xu, Lin; Feng, Xiao-Li; Yin, Yong; Qin, Dong-Dong; Hu, Xin-Tian; Wang, Zheng-Bo

    2016-07-26

    Here, we examine whether neurons differentiated from transplanted stem cells can integrate into the host neural network and function in awake animals, a goal of transplanted stem cell therapy in the brain. We have developed a technique in which a small "hole" is created in the inferior colliculus (IC) of rhesus monkeys, then stem cells are transplanted in situ to allow for investigation of their integration into the auditory neural network. We found that some transplanted cells differentiated into mature neurons and formed synaptic input/output connections with the host neurons. In addition, c-Fos expression increased significantly in the cells after acoustic stimulation, and multichannel recordings indicated IC specific tuning activities in response to auditory stimulation. These results suggest that the transplanted cells have the potential to functionally integrate into the host neural network.

  8. Asymptotic and stable proper ties of general stochastic functional differential equations

    Institute of Scientific and Technical Information of China (English)

    Xiaojing Zhong; Feiqi Deng

    2014-01-01

    The asymptotic and stable properties of general stochastic functional differential equations are investigated by the multiple Lyapunov function method, which admits non-negative up-per bounds for the stochastic derivatives of the Lyapunov functions, a theorem for asymptotic properties of the LaSal e-type described by limit sets of the solutions of the equations is obtained. Based on the asymptotic properties to the limit set, a theorem of asymptotic stability of the stochastic functional differential equations is also established, which enables us to construct the Lyapunov functions more easily in application. Particularly, the wel-known classical theorem on stochastic stability is a special case of our result, the operator LV is not required to be negative which is more general to fulfil and the stochastic perturbation plays an important role in it. These show clearly the improvement of the traditional method to find the Lyapunov functions. A numerical simulation example is given to il ustrate the usage of the method.

  9. Differential Item Functioning on the International Personality Item Poolâ s Neuroticism Scale

    OpenAIRE

    McBride, Nadine LeBarron

    2008-01-01

    As use of the public-domain International Personality Item Pool (IPIP) scales has grown significantly over the past decade (Goldberg, Johnson, Eber, Hogan, Ashton, Cloninger, & Gough, 2006) research on the psychometric properties of the items and scales have become increasingly important. This research study examines the IPIP scale constructed to measure the Five Factor Model (FFM) domain of Neuroticism (as measured by the NEO-PI-R) for occurrences of differential functioning a...

  10. EXPONENTIAL ESTIMATE OF SOLUTION TO STOCHASTIC FUNCTIONAL DIFFERENTIAL EQUATIONS WITH INFINITE DELAY

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    In this paper, by the Burkholder-Davis-Gundy inequality and It formula, the exponential estimate of the solution to stochastic functional differential equations with infinite delay is established in the phase space BC((-∞,0];Rd). Furthermore, the sample Lyapunov exponent of the solution is obtained, which is less than a positive constant 2√K + 65K. Moreover, a pth moment of the solution is studied.

  11. Semigroup Approach to Semilinear Partial Functional Differential Equations with Infinite Delay

    Directory of Open Access Journals (Sweden)

    Hassane Bouzahir

    2007-02-01

    Full Text Available We describe a semigroup of abstract semilinear functional differential equations with infinite delay by the use of the Crandall Liggett theorem. We suppose that the linear part is not necessarily densely defined but satisfies the resolvent estimates of the Hille-Yosida theorem. We clarify the properties of the phase space ensuring equivalence between the equation under investigation and the nonlinear semigroup.

  12. Semigroup Approach to Semilinear Partial Functional Differential Equations with Infinite Delay

    Directory of Open Access Journals (Sweden)

    Bouzahir Hassane

    2007-01-01

    Full Text Available We describe a semigroup of abstract semilinear functional differential equations with infinite delay by the use of the Crandall Liggett theorem. We suppose that the linear part is not necessarily densely defined but satisfies the resolvent estimates of the Hille-Yosida theorem. We clarify the properties of the phase space ensuring equivalence between the equation under investigation and the nonlinear semigroup.

  13. Mild solutions for nonlocal fractional semilinear functional differential inclusions involving Caputo derivative

    Directory of Open Access Journals (Sweden)

    Ahmed G. Ibrahim

    2014-05-01

    Full Text Available In this paper, we prove various existence results of a mild solution for a fractional nonlocal functional semilinear differential inclusion involving Caputo derivative in Banach spaces. We consider the case when the values of the orient field are convex as well as nonconvex. Moreover, we study the topological structure of solution sets. Our results extend or generalize results proved in recent papers.

  14. Cherubism Gene Sh3bp2 is Important for Optimal Bone Formation, Osteoblast Differentiation and Function

    Science.gov (United States)

    Mukherjee, Padma M.; Wang, Chiachien J.; Chen, I-Ping; Jafarov, Toghrul; Olsen, Bjorn R.; Ueki, Yasuyoshi; Reichenberger, Ernst J.

    2012-01-01

    Introduction Cherubism is a human genetic disorder that causes bilateral symmetrical enlargement of the maxilla and mandible in children. It is caused by mutations in SH3BP2. The exact pathogenesis of the disorder is an area of active research. Sh3bp2 knock-in mice were developed by introducing a Pro416Arg mutation (Pro418Arg in humans) in the mouse genome. The osteoclast phenotype of this mouse model was recently described. Methods We examined the bone phenotype of the cherubism mouse model, the role of Sh3bp2 during bone formation, osteoblast differentiation and osteoblast function. Results We observed delays in early postnatal development of homozygous Sh3bp2KI/KI mice. Sh3bp2KI/KI mice exhibit increased growth plate thickness and significantly decreased trabecular bone thickness and reduced bone mineral density. Histomorphometric and μ-CT analyses reveal bone loss in cranial and appendicular skeleton. Sh3bp2KI/KI mice also exhibit a significant decrease in osteoid formation that indicates a defect in osteoblast function. Calvarial osteoblast cell cultures exhibit a decrease in alkaline phosphatase expression and mineralization suggesting reduced differentiation potential. Gene expression of osteoblast differentiation markers like collagen type-I, alkaline phosphatase and osteocalcin are decreased in osteoblast cultures from Sh3bp2KI/KI mice. Conclusions These data suggest that Sh3bp2 function regulates bone homeostasis not only through osteoclast-specific effects but also through effects on osteoblast differentiation and function. PMID:20691350

  15. Twistor quantization of the space of half-differentiable vector functions on the circle revisited

    Institute of Scientific and Technical Information of China (English)

    SERGEEV; Armen

    2009-01-01

    We discuss the twistor quantization problem for the classical system(Vd,Ad),represented by the phase space Vd,identified with the Sobolev space H 1/2 0 (S1,Rd)of half-differentiable vector functions on the circle,and the algebra of observables Ad,identified with the semi-direct product of the Heisenberg algebra of Vd and the algebra Vect(S1)of tangent vector fields on the circle.

  16. Fibonacci collocation method with a residual error Function to solve linear Volterra integro differential equations

    Directory of Open Access Journals (Sweden)

    Salih Yalcinbas

    2016-01-01

    Full Text Available In this paper, a new collocation method based on the Fibonacci polynomials is introduced to solve the high-order linear Volterra integro-differential equations under the conditions. Numerical examples are included to demonstrate the applicability and validity of the proposed method and comparisons are made with the existing results. In addition, an error estimation based on the residual functions is presented for this method. The approximate solutions are improved by using this error estimation.

  17. Perio dic Solutions for p-Laplacian Neutral Functional Differential Equation with a Deviating Argument

    Institute of Scientific and Technical Information of China (English)

    CHEN Wen-bin; GAO Fang; LU Shi-ping

    2013-01-01

    In this paper, by using the continuation theorem of coincidence degree theory and some analysis methods, we study a kind of periodic solutions to p-Laplacian neutral functional differential equation with a deviating argument (ϕp(x(t)-cx(t-σ))0)0+f(t, x0(t))+g(t, x(t-τ(t)))=e(t), some new results on the existence of periodic solutions is obtained.

  18. Differential item functioning (DIF) analyses of health-related quality of life instruments using logistic regression

    DEFF Research Database (Denmark)

    Scott, Neil W; Fayers, Peter M; Aaronson, Neil K

    2010-01-01

    Differential item functioning (DIF) methods can be used to determine whether different subgroups respond differently to particular items within a health-related quality of life (HRQoL) subscale, after allowing for overall subgroup differences in that scale. This article reviews issues that arise ...... when testing for DIF in HRQoL instruments. We focus on logistic regression methods, which are often used because of their efficiency, simplicity and ease of application....

  19. On the role of student understanding of function and rate of change in learning differential equations

    OpenAIRE

    Kuster Jr, George Emil

    2016-01-01

    In this research, I utilize the theoretical perspective Knowledge In Pieces to identify the knowledge resources students utilize while in the process of completing various differential equations tasks. In addition I explore how this utilization changes over the course of a semester, and how resources related to the concepts of function and rate of change supported the students in completing the tasks. I do so using data collected from a series of task-based individual interviews with two stud...

  20. Differential item functioning (DIF) analyses of health-related quality of life instruments using logistic regression

    DEFF Research Database (Denmark)

    Scott, Neil W.; Fayers, Peter M.; Aaronson, Neil K.

    2010-01-01

    Differential item functioning (DIF) methods can be used to determine whether different subgroups respond differently to particular items within a health-related quality of life (HRQoL) subscale, after allowing for overall subgroup differences in that scale. This article reviews issues that arise...... when testing for DIF in HRQoL instruments. We focus on logistic regression methods, which are often used because of their efficiency, simplicity and ease of application....

  1. Assessing Testlet Effect, Impact, Differential Testlet, and Item Functioning Using Cross-Classified Multilevel Measurement Modeling

    Directory of Open Access Journals (Sweden)

    Hamdollah Ravand

    2015-05-01

    Full Text Available The present study used the two-level testlet response model (MMMT-2 to assess impact, differential item functioning (DIF, and differential testlet functioning (DTLF in a reading comprehension test. The data came from 21,641 applicants into English Masters’ programs at Iranian state universities. Testlet effects were estimated, and items and testlets that were functioning differentially for test takers of different genders and majors were identified. Also parameter estimates obtained under MMMT-2 and those obtained under the two-level hierarchical generalized linear model (HGLM-2 were compared. The results indicated that ability estimates obtained under the two models were significantly different at the lower and upper ends of the ability distribution. In addition, it was found that ignoring local item dependence (LID would result in overestimation of the precision of the ability estimates. As for the difficulty of the items, the estimates obtained under the two models were almost the same, but standard errors were significantly different.

  2. Isotonic Modeling with Non-Differentiable Loss Functions with Application to Lasso Regularization.

    Science.gov (United States)

    Painsky, Amichai; Rosset, Saharon

    2016-02-01

    In this paper we present an algorithmic approach for fitting isotonic models under convex, yet non-differentiable, loss functions. It is a generalization of the greedy non-regret approach proposed by Luss and Rosset (2014) for differentiable loss functions, taking into account the sub-gradiental extensions required. We prove that our suggested algorithm solves the isotonic modeling problem while maintaining favorable computational and statistical properties. As our suggested algorithm may be used for any non-differentiable loss function, we focus our interest on isotonic modeling for either regression or two-class classification with appropriate log-likelihood loss and lasso penalty on the fitted values. This combination allows us to maintain the non-parametric nature of isotonic modeling, while controlling model complexity through regularization. We demonstrate the efficiency and usefulness of this approach on both synthetic and real world data. An implementation of our suggested solution is publicly available from the first author's website (https://sites.google.com/site/amichaipainsky/software).

  3. Functional dissection of HOXD cluster genes in regulation of neuroblastoma cell proliferation and differentiation.

    Directory of Open Access Journals (Sweden)

    Yunhong Zha

    Full Text Available Retinoic acid (RA can induce growth arrest and neuronal differentiation of neuroblastoma cells and has been used in clinic for treatment of neuroblastoma. It has been reported that RA induces the expression of several HOXD genes in human neuroblastoma cell lines, but their roles in RA action are largely unknown. The HOXD cluster contains nine genes (HOXD1, HOXD3, HOXD4, and HOXD8-13 that are positioned sequentially from 3' to 5', with HOXD1 at the 3' end and HOXD13 the 5' end. Here we show that all HOXD genes are induced by RA in the human neuroblastoma BE(2-C cells, with the genes located at the 3' end being activated generally earlier than those positioned more 5' within the cluster. Individual induction of HOXD8, HOXD9, HOXD10 or HOXD12 is sufficient to induce both growth arrest and neuronal differentiation, which is associated with downregulation of cell cycle-promoting genes and upregulation of neuronal differentiation genes. However, induction of other HOXD genes either has no effect (HOXD1 or has partial effects (HOXD3, HOXD4, HOXD11 and HOXD13 on BE(2-C cell proliferation or differentiation. We further show that knockdown of HOXD8 expression, but not that of HOXD9 expression, significantly inhibits the differentiation-inducing activity of RA. HOXD8 directly activates the transcription of HOXC9, a key effector of RA action in neuroblastoma cells. These findings highlight the distinct functions of HOXD genes in RA induction of neuroblastoma cell differentiation.

  4. cDNA cloning and function analysis of two novel erythroid differentiation related genes

    Institute of Scientific and Technical Information of China (English)

    WANG; Xin; (王鑫); WANG; Duncheng; (王敦成); CHEN; Xing; (陈兴),; HU; Meiru; (胡美茹); WANG; Jian'an; (王建安); LI; Yan; (黎燕); GUO; Ning; (郭宁); SHEN; Beifen; (沈倍奋)

    2001-01-01

    Our previous studies showed that some nuclear proteins that were expressed especially during terminal differentiation of erythroid cells might interact directly or indirectly with HS2 sequence to form the HS2-protein complexes and thus play an important role in the globin gene regulation and erythroid differentiation. Monoclonal antibodies against the nuclear proteins of terminal differentiated erythroid cells, including intermediate and late erythroblasts of human fetal liver and hemin induced K562 cells, were prepared by hybridoma technique. The monoclonal antibodies were used to screen l-gtll human cDNA expression library of fetal liver in order to obtain the rele-vant cDNA clones. By the analysis of their cDNA clones and the identification of the proteins' func-tions, the regulation mechanism of the HS2 binding proteins might be better understood. Two cDNA clones (GenBank accession number AF040247 and AF040248 respectively) were obtained and one of them owns a full length and the other encodes a protein characterized by a leucine-zipper domain. Both of them were expressed differentially in K562 cells and hemin-induced K562 cells. The evidence suggested that both of them were involved in erythroid differentiation. We investigat-ed the expression pattern of EDRF1 and EDRF2 by RT-PCR technique. The results of RT-PCR suggested that EDRF1 and EDRF2 might play a critical role in early stage of organ development and histological differentiation. EDRF1 and EDRF2 might start the program of erythroid develop-ment, and also regulate the development of erythroid tissue and the expression of globin gene at different stage of the development.

  5. cDNA cloning and function analysis of two novel erythroid differentiation related genes

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Our previous studies showed that some nuclear proteins that wereexpressed especially during terminal differentiation of erythroid cells might interact directly or indirectly with HS2 sequence to form the HS2-protein complexes and thus play an important role in the globin gene regulation and erythroid differentiation. Monoclonal antibodies against the nuclear proteins of terminal differentiated erythroid cells, including intermediate and late erythroblasts of human fetal liver and hemin induced K562 cells, were prepared by hybridoma technique. The monoclonal antibodies were used to screen l-gtll human cDNA expression library of fetal liver in order to obtain the rele-vant cDNA clones. By the analysis of their cDNA clones and the identification of the proteins' func-tions, the regulation mechanism of the HS2 binding proteins might be better understood. Two cDNA clones (GenBank accession number AF040247 and AF040248 respectively) were obtained and one of them owns a full length and the other encodes a protein characterized by a leucine-zipper domain. Both of them were expressed differentially in K562 cells and hemin-induced K562 cells. The evidence suggested that both of them were involved in erythroid differentiation. We investigat-ed the expression pattern of EDRF1 and EDRF2 by RT-PCR technique. The results of RT-PCR suggested that EDRF1 and EDRF2 might play a critical role in early stage of organ development and histological differentiation. EDRF1 and EDRF2 might start the program of erythroid develop-ment, and also regulate the development of erythroid tissue and the expression of globin gene at different stage of the development.

  6. A three critical point theorem for non-smooth functionals with application in differential inclusions

    Indian Academy of Sciences (India)

    Ghasem A Afrouzi; Mohammad B Ghaemi; Shirin Mir

    2015-11-01

    A variety of three-critical-point theorems have been established for nonsmooth functionals, based on a minimax inequality. In this paper, a generalized form of a recent result due to Ricceri is introduced for non-smooth functionals and by a few hypotheses, without any minimax inequality, the existence of at least three critical points with a uniform bound on the norms of solutions, is obtained. Also, as an application, our main theorem is used to obtain at least three anti-periodic solutions for a second order differential inclusion.

  7. Pointwise estimates of the Green's function of a second order differential operator with the variable coefficient

    Science.gov (United States)

    Ashyralyev, Allaberen; Tetikoglu, Fatih Sabahattin

    2015-09-01

    In this study, the Green's function of the second order differential operator Ax defined by the formula Axu =-a (x )ux x(x )+δ u (x ), δ ≥0 , a (x )=a (x +2 π ), x ∈ℝ1 with domain D (Ax)={ u (x ):u (x ),u '(x ),u″(x )∈C (ℝ1),u (x )=u (x +2 π ), x ∈ℝ1,∫0 2 π u (x )d x =0 } is presented. The estimates for the Green's function and it's derivative are obtained. The positivity of the operator Ax is proved.

  8. Exact solutions of some nonlinear partial differential equations using functional variable method

    Indian Academy of Sciences (India)

    A Nazarzadeh; M Eslami; M Mirzazadeh

    2013-08-01

    The functional variable method is a powerful solution method for obtaining exact solutions of some nonlinear partial differential equations. In this paper, the functional variable method is used to establish exact solutions of the generalized forms of Klein–Gordon equation, the (2 + 1)-dimensional Camassa–Holm Kadomtsev–Petviashvili equation and the higher-order nonlinear Schrödinger equation. By using this useful method, we found some exact solutions of the above-mentioned equations. The obtained solutions include solitary wave solutions, periodic wave solutions and combined formal solutions. It is shown that the proposed method is effective and general.

  9. Mathematical methods in physics partial differential equations, Fourier series, and special functions

    CERN Document Server

    Henner , Victor; Forinash , Kyle

    2009-01-01

    This book is a text on partial differential equations (PDEs) of mathematical physics and boundary value problems, trigonometric Fourier series, and special functions. This is the core content of many courses in the fields of engineering, physics, mathematics, and applied mathematics. The accompanying software provides a laboratory environment that allows the user to generate and model different physical situations and learn by experimentation. From this standpoint, the book along with the software can also be used as a reference book on PDEs, Fourier series and special functions for students a

  10. A role for inositol 1,4,5-trisphosphate in the initiation of agonist-induced contractions of dog tracheal smooth muscle.

    Science.gov (United States)

    Hashimoto, T; Hirata, M; Ito, Y

    1985-09-01

    To elucidate the role of inositol 1,4,5-trisphosphate (Ins-P3) in the initiation of agonist-induced contraction of the smooth muscle cells of the dog trachea, we investigated the effects of acetylcholine (ACh) on the concentrations of Ins-P3, phosphatidylinositol-4,5-bisphosphate (PI-P2) or phosphatidic acid (PA). The effects of Ins-P3 on the Ca2+ stored in the smooth muscle cells were also studied in saponin-permeabilized smooth muscle cells. A half maximal or maximal Ca2+ accumulation into the cells was observed in the dispersed single, smooth muscle cells treated by saponin, in free Ca2+ concentrations of 4.6 X 10(-7) or 5 X 10(-5)M, respectively. The ATP-dependent Ca2+ accumulation was maximal at 0.63 nmol/10(5) cells. Effects of Ins-P3 on stored Ca2+ were observed at a free Ca2+ concentration of 3.7 X 10(-7)M, which induces about half maximal ATP-dependent Ca2+-accumulation. Ins-P3 released the Ca2+ accumulated by ATP, in a dose-dependent manner. About 40% of the total Ca2+ was released following application of 3 microM Ins-P3. The release of stored Ca2+ induced by application of Ins-P3 was followed by its re-uptake into the smooth muscle cells. Thus, the stored Ca2+ was repeatedly released with repetitive applications of Ins-P3. Application of ACh (10(-5)M) to the dog trachea stimulated the production of Ins-P3 in the soluble fraction and 10s after this application, the relative amount of Ins-P3 was 290% of the control value. 6 Concomitantly, ACh (10- 5 M) either reduced or increased the contents ofphosphatidyl inositol 4,5-biphosphate (PI-P2) or phosphatidic acid (PA) in the lipid fraction ofthe smooth muscle cells to 60% or to 350% of the control value, respectively, thereby indicating that ACh stimulates the phosphodiesteric hydrolysis of PI-P2. 7 5-Hydroxytryptamine (5-HT; 10- 5M) also reduced or increased the contents of PI-P2 or PA to 80 or to 200% of the control values, respectively. However, neither histamine (10-5M), in the presence or absence of

  11. Higher-order corrections to the splitting functions from differential equations in QCD

    CERN Document Server

    Gituliar, O

    2016-01-01

    We report on the status an ab initio computation of the time-like splitting functions at next-to-next-to-leading order in QCD. Time-like splitting functions govern the collinear kinematics of inclusive hadron production in $e^+e^-$ annihilation and the evolution of the parton fragmentation distributions. Current knowledge about them at three loops has been inferred by means of crossing symmetry from their related space-like counterparts, the deep-inelastic structure functions and parton densities. In this approach certain parts of the off-diagonal quark-gluon splitting function are left undetermined, which calls for an independent calculation from first principles. We outline the method for calculating master integrals from differential equations which are required to attack the problem.

  12. Cation induced differential effect on structural and functional properties of Mycobacterium tuberculosis α-Isopropylmalate synthase

    Directory of Open Access Journals (Sweden)

    Bhakuni Vinod

    2007-06-01

    Full Text Available Abstract Background α-isopropylmalate synthase (MtαIPMS, an enzyme that catalyzes the first committed step of the leucine biosynthetic pathway of Mycobacterium tuberculosis is a potential drug target for the anti-tuberculosis drugs. Cations induce differential effect of activation and inhibition of MtαIPMS. To date no concrete mechanism for such an opposite effect of similarly charged cations on the functional activity of enzyme has been presented. Results Effect of cations on the structure and function of the MtαIPMS has been studied in detail. The studies for the first time demonstrate that different cations interact specifically at different sites in the enzyme and modulate the enzyme structure differentially. The inhibitors Zn2+ and Cd2+ ions interact directly with the catalytic domain of the enzyme and induce unfolding/denaturation of the domain. The activator K+ also interacts with the catalytic TIM barrel domain however, it does not induce any significant effect on the enzyme structure. Studies with isolated catalytic TIM barrel domain showed that it can carry out the catalytic function on its own but probably requires the non-catalytic C-terminal domain for optimum functioning. An important observation was that divalent cations induce significant interaction between the regulatory and the catalytic domain of MtαIPMS thus inducing structural cooperativity in the enzyme. This divalent cation induced structural cooperativity might result in modulation of activity of the catalytic domain by regulatory domain. Conclusion The studies for the first time demonstrate that different cations bind at different sites in the enzyme leading to their differential effects on the structure and functional activity of the enzyme.

  13. Functions of Heterogeneous Nuclear Ribonucleoproteins in Stem Cell Potency and Differentiation

    Directory of Open Access Journals (Sweden)

    Qishan Chen

    2013-01-01

    Full Text Available Stem cells possess huge importance in developmental biology, disease modelling, cell replacement therapy, and tissue engineering in regenerative medicine because they have the remarkable potential for self-renewal and to differentiate into almost all the cell types in the human body. Elucidation of molecular mechanisms regulating stem cell potency and differentiation is essential and critical for extensive application. Heterogeneous nuclear ribonucleoproteins (hnRNPs are modular proteins consisting of RNA-binding motifs and auxiliary domains characterized by extensive and divergent functions in nucleic acid metabolism. Multiple roles of hnRNPs in transcriptional and posttranscriptional regulation enable them to be effective gene expression regulators. More recent findings show that hnRNP proteins are crucial factors implicated in maintenance of stem cell self-renewal and pluripotency and cell differentiation. The hnRNPs interact with certain sequences in target gene promoter regions to initiate transcription. In addition, they recognize 3′UTR or 5′UTR of specific gene mRNA forming mRNP complex to regulate mRNA stability and translation. Both of these regulatory pathways lead to modulation of gene expression that is associated with stem cell proliferation, cell cycle control, pluripotency, and committed differentiation.

  14. Stimulus set meaningfulness and neurophysiological differentiation: a functional magnetic resonance imaging study.

    Directory of Open Access Journals (Sweden)

    Melanie Boly

    Full Text Available A meaningful set of stimuli, such as a sequence of frames from a movie, triggers a set of different experiences. By contrast, a meaningless set of stimuli, such as a sequence of 'TV noise' frames, triggers always the same experience--of seeing 'TV noise'--even though the stimuli themselves are as different from each other as the movie frames. We reasoned that the differentiation of cortical responses underlying the subject's experiences, as measured by Lempel-Ziv complexity (incompressibility of functional MRI images, should reflect the overall meaningfulness of a set of stimuli for the subject, rather than differences among the stimuli. We tested this hypothesis by quantifying the differentiation of brain activity patterns in response to a movie sequence, to the same movie scrambled in time, and to 'TV noise', where the pixels from each movie frame were scrambled in space. While overall cortical activation was strong and widespread in all conditions, the differentiation (Lempel-Ziv complexity of brain activation patterns was correlated with the meaningfulness of the stimulus set, being highest in the movie condition, intermediate in the scrambled movie condition, and minimal for 'TV noise'. Stimulus set meaningfulness was also associated with higher information integration among cortical regions. These results suggest that the differentiation of neural responses can be used to assess the meaningfulness of a given set of stimuli for a given subject, without the need to identify the features and categories that are relevant to the subject, nor the precise location of selective neural responses.

  15. β-catenin functions pleiotropically in differentiation and tumorigenesis in mouse embryo-derived stem cells.

    Directory of Open Access Journals (Sweden)

    Noriko Okumura

    Full Text Available The canonical Wnt/β-catenin signaling pathway plays a crucial role in the maintenance of the balance between proliferation and differentiation throughout embryogenesis and tissue homeostasis. β-Catenin, encoded by the Ctnnb1 gene, mediates an intracellular signaling cascade activated by Wnt. It also plays an important role in the maintenance of various types of stem cells including adult stem cells and cancer stem cells. However, it is unclear if β-catenin is required for the derivation of mouse embryo-derived stem cells. Here, we established β-catenin-deficient (β-cat(Δ/Δ mouse embryo-derived stem cells and showed that β-catenin is not essential for acquiring self-renewal potential in the derivation of mouse embryonic stem cells (ESCs. However, teratomas formed from embryo-derived β-cat(Δ/Δ ESCs were immature germ cell tumors without multilineage differentiated cell types. Re-expression of functional β-catenin eliminated their neoplastic, transformed phenotype and restored pluripotency, thereby rescuing the mutant ESCs. Our findings demonstrate that β-catenin has pleiotropic effects in ESCs; it is required for the differentiation of ESCs and prevents them from acquiring tumorigenic character. These results highlight β-catenin as the gatekeeper in differentiation and tumorigenesis in ESCs.

  16. The effects of luteolin on osteoclast differentiation, function in vitro and ovariectomy-induced bone loss.

    Science.gov (United States)

    Kim, Tae-Ho; Jung, Ji Won; Ha, Byung Geun; Hong, Jung Min; Park, Eui Kyun; Kim, Hyun-Ju; Kim, Shin-Yoon

    2011-01-01

    Flavonoids, a group of polyphenolic compounds abundant in plants, are known to prevent bone loss in ovariectomized (OVX) animal models. Inhibition of osteoclast differentiation and bone resorption is considered as an effective therapeutic approach in the treatment of postmenopausal bone loss. Luteolin, a plant flavonoid, has potent anti-inflammatory properties both in vivo and vitro. In this study, we found that luteolin markedly decreased the differentiation of both bone marrow mononuclear cells and Raw264.7 cells into osteoclasts. Luteolin also inhibited the bone resorptive activity of differentiated osteoclasts. We further investigated the effects of luteolin on ovariectomy-induced bone loss using micro-computed tomography, biomechanical tests and serum markers assay for bone remodeling. Oral administration of luteolin (5 and 20 mg/kg per day) to OVX mice caused significant increase in bone mineral density and bone mineral content of trabecular and cortical bones in the femur as compared to those of OVX controls, and prevented decreases of bone strength indexes induced by OVX surgery. Serum biochemical markers assays revealed that luteolin prevents OVX-induced increases in bone turnover. These data strongly suggest that luteolin has the potential for prevention of bone loss in postmenopausal osteoporosis by reducing both osteoclast differentiation and function. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. FIDEA: a server for the functional interpretation of differential expression analysis.

    KAUST Repository

    D'Andrea, Daniel

    2013-06-10

    The results of differential expression analyses provide scientists with hundreds to thousands of differentially expressed genes that need to be interpreted in light of the biology of the specific system under study. This requires mapping the genes to functional classifications that can be, for example, the KEGG pathways or InterPro families they belong to, their GO Molecular Function, Biological Process or Cellular Component. A statistically significant overrepresentation of one or more category terms in the set of differentially expressed genes is an essential step for the interpretation of the biological significance of the results. Ideally, the analysis should be performed by scientists who are well acquainted with the biological problem, as they have a wealth of knowledge about the system and can, more easily than a bioinformatician, discover less obvious and, therefore, more interesting relationships. To allow experimentalists to explore their data in an easy and at the same time exhaustive fashion within a single tool and to test their hypothesis quickly and effortlessly, we developed FIDEA. The FIDEA server is located at http://www.biocomputing.it/fidea; it is free and open to all users, and there is no login requirement.

  18. Neuron-NG2 Cell Synapses: Novel Functions for Regulating NG2 Cell Proliferation and Differentiation

    Directory of Open Access Journals (Sweden)

    Qian-Kun Yang

    2013-01-01

    Full Text Available NG2 cells are a population of CNS cells that are distinct from neurons, mature oligodendrocytes, astrocytes, and microglia. These cells can be identified by their NG2 proteoglycan expression. NG2 cells have a highly branched morphology, with abundant processes radiating from the cell body, and express a complex set of voltage-gated channels, AMPA/kainate, and GABA receptors. Neurons notably form classical and nonclassical synapses with NG2 cells, which have varied characteristics and functions. Neuron-NG2 cell synapses could fine-tune NG2 cell activities, including the NG2 cell cycle, differentiation, migration, and myelination, and may be a novel potential therapeutic target for NG2 cell-related diseases, such as hypoxia-ischemia injury and periventricular leukomalacia. Furthermore, neuron-NG2 cell synapses may be correlated with the plasticity of CNS in adulthood with the synaptic contacts passing onto their progenies during proliferation, and synaptic contacts decrease rapidly upon NG2 cell differentiation. In this review, we highlight the characteristics of classical and nonclassical neuron-NG2 cell synapses, the potential functions, and the fate of synaptic contacts during proliferation and differentiation, with the emphasis on the regulation of the NG2 cell cycle by neuron-NG2 cell synapses and their potential underlying mechanisms.

  19. Differential Regulation of Cardiac Function and Intracardiac Cytokines by Rapamycin in Healthy and Diabetic Rats

    Science.gov (United States)

    Luck, Christian; DeMarco, Vincent G.; Mahmood, Abuzar; Gavini, Madhavi P.

    2017-01-01

    Diabetes is comorbid with cardiovascular disease and impaired immunity. Rapamycin improves cardiac functions and extends lifespan by inhibiting the mechanistic target of rapamycin complex 1 (mTORC1). However, in diabetic murine models, Rapamycin elevates hyperglycemia and reduces longevity. Since Rapamycin is an immunosuppressant, we examined whether Rapamycin (750 μg/kg/day) modulates intracardiac cytokines, which affect the cardiac immune response, and cardiac function in male lean (ZL) and diabetic obese Zucker (ZO) rats. Rapamycin suppressed levels of fasting triglycerides, insulin, and uric acid in ZO but increased glucose. Although Rapamycin improved multiple diastolic parameters (E/E′, E′/A′, E/Vp) initially, these improvements were reversed or absent in ZO at the end of treatment, despite suppression of cardiac fibrosis and phosphoSer473Akt. Intracardiac cytokine protein profiling and Ingenuity® Pathway Analysis indicated suppression of intracardiac immune defense in ZO, in response to Rapamycin treatment in both ZO and ZL. Rapamycin increased fibrosis in ZL without increasing phosphoSer473Akt and differentially modulated anti-fibrotic IL-10, IFNγ, and GM-CSF in ZL and ZO. Therefore, fundamental difference in intracardiac host defense between diabetic ZO and healthy ZL, combined with differential regulation of intracardiac cytokines by Rapamycin in ZO and ZL hearts, underlies differential cardiac outcomes of Rapamycin treatment in health and diabetes. PMID:28408970

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

    Science.gov (United States)

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

    2017-02-01

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

  1. Differential Regulation of Cardiac Function and Intracardiac Cytokines by Rapamycin in Healthy and Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Christian Luck

    2017-01-01

    Full Text Available Diabetes is comorbid with cardiovascular disease and impaired immunity. Rapamycin improves cardiac functions and extends lifespan by inhibiting the mechanistic target of rapamycin complex 1 (mTORC1. However, in diabetic murine models, Rapamycin elevates hyperglycemia and reduces longevity. Since Rapamycin is an immunosuppressant, we examined whether Rapamycin (750 μg/kg/day modulates intracardiac cytokines, which affect the cardiac immune response, and cardiac function in male lean (ZL and diabetic obese Zucker (ZO rats. Rapamycin suppressed levels of fasting triglycerides, insulin, and uric acid in ZO but increased glucose. Although Rapamycin improved multiple diastolic parameters (E/E′, E′/A′, E/Vp initially, these improvements were reversed or absent in ZO at the end of treatment, despite suppression of cardiac fibrosis and phosphoSer473Akt. Intracardiac cytokine protein profiling and Ingenuity® Pathway Analysis indicated suppression of intracardiac immune defense in ZO, in response to Rapamycin treatment in both ZO and ZL. Rapamycin increased fibrosis in ZL without increasing phosphoSer473Akt and differentially modulated anti-fibrotic IL-10, IFNγ, and GM-CSF in ZL and ZO. Therefore, fundamental difference in intracardiac host defense between diabetic ZO and healthy ZL, combined with differential regulation of intracardiac cytokines by Rapamycin in ZO and ZL hearts, underlies differential cardiac outcomes of Rapamycin treatment in health and diabetes.

  2. MicroRNA: biogenetic and functional mechanisms and involvements in cell differentiation and cancer.

    Science.gov (United States)

    Tsuchiya, Soken; Okuno, Yasushi; Tsujimoto, Gozoh

    2006-08-01

    MicroRNAs (miRNAs) are endogenous small noncoding RNAs (20-23 nucleotides) that negatively regulate the gene expressions at the posttranscriptional level by base pairing to the 3' untranslated region of target messenger RNAs. Hundreds of miRNAs have been identified in humans and evolutionarily conserved from plants to animals. It is revealed that miRNAs regulate various physiological and pathological pathways such as cell differentiation, cell proliferation, and tumoriogenesis. By the computational analysis, it is predicted that 30% of protein-encoding genes are regulated by miRNAs. In this review, we discuss recent remarkable advances in the miRNA biogenetic and functional mechanisms and the involvements of miRNAs in cell differentiation, especially in hematopoietic lineages, and cancer. These evidences offer the possibility that miRNAs would be potentially useful for drug discovery.

  3. A function for Rac1 in the terminal differentiation and pigmentation of hair

    DEFF Research Database (Denmark)

    Behrendt, Kristina; Klatte, Jennifer; Pofahl, Ruth

    2012-01-01

    . Rescue mice showed a grey, dull hair coat, whereas that of wild-type and L61Rac1-transgenic mice was black and shiny. Hair analysis in rescue mice revealed altered structures of the hair shaft and the cuticle and disturbed organization of medulla cells and pigment distribution. Disorganization of medulla......The small GTPase Rac1 is ubiquitously expressed in proliferating and differentiating layers of the epidermis and hair follicles. Previously, Rac1 was shown to regulate stem cell behaviour in these compartments. We have asked whether Rac1 has, in addition, a specific, stem-cell-independent function...... in the regulation of terminal hair follicle differentiation. To address this, we have expressed a constitutively active mutant of Rac1, L61Rac1, only in the basal epidermal layer and outer root sheath of mice possessing an epidermis-specific deletion of endogenous Rac1, which experience severe hair loss...

  4. Functional differential equations for the q-Fourier transform of q-Gaussians

    Energy Technology Data Exchange (ETDEWEB)

    Umarov, S [Department of Mathematics, Tufts University, Medford, MA (United States); Queiros, S M Duarte, E-mail: sdqueiro@gmail.co [Unilever R and D Port Sunlight, Quarry Road East, Wirral, CH63 3JW (United Kingdom)

    2010-02-05

    In this paper the question 'is the q-Fourier transform of a q-Gaussian a q'-Gaussian (with some q') up to a constant factor?' is studied for the whole range of q in (- infty, 3). This question is connected with applicability of the q-Fourier transform in the study of limit processes in nonextensive statistical mechanics. Using the functional differential equation approach we prove that the answer is affirmative if and only if 1 <= q < 3, excluding two particular cases of q < 1, namely q=1/2 and q=2/3. Complementarily, we discuss some applications of the q-Fourier transform to nonlinear partial differential equations such as the porous medium equation.

  5. Detection and differentiation of influenza viruses with glycan-functionalized gold nanoparticles.

    Science.gov (United States)

    Zheng, Longtang; Wei, Jinhua; Lv, Xun; Bi, Yuhai; Wu, Peixing; Zhang, Zhenxing; Wang, Pengfei; Liu, Ruichen; Jiang, Jingwen; Cong, Haolong; Liang, Jingnan; Chen, Wenwen; Cao, Hongzhi; Liu, Wenjun; Gao, George F; Du, Yuguang; Jiang, Xingyu; Li, Xuebing

    2017-05-15

    Accurate diagnosis of influenza viruses is difficult and generally requires a complex process because of viral diversity and rapid mutability. In this study, we report a simple and rapid strategy for the detection and differentiation of influenza viruses using glycan-functionalized gold nanoparticles (gGNPs). This method is based on the aggregation of gGNP probes on the viral surface, which is mediated by the specific binding of the virus to the glycans. Using a set of gGNPs bearing different glycan structures, fourteen influenza virus strains, including the major subtypes currently circulating in human and avian populations, were readily differentiated from each other and from a human respiratory syncytial virus in a single-step colorimetric procedure. The results presented here demonstrate the potential of this gGNP-based system in the development of convenient and portable sensors for the clinical diagnosis and surveillance of influenza viruses.

  6. Usefulness of acoustic studies on the differential diagnostics of organic and functional dysphonia.

    Science.gov (United States)

    Pruszewicz, A; Obrebowski, A; Swidziński, P; Demeńko, G; Wika, T; Wojciechowska, A

    1991-01-01

    Phoniatric and acoustic examinations were carried out in a group of 30 patients with dysphonia, including 15 with organic type and 15 with functional type. A complex phoniatric assessment offered the possibility to differentiate between these two groups of pathological voices. This was achieved also on the basis of acoustic analysis of the voice by extracting characteristics such as: formant frequency, Fo and its range, percentage of noise in the analysed verbal text, mean and maximum values of jitter. The possibility of differential diagnosis of these two different types of dysphonia in acoustic studies was confirmed by clinical examinations. The acoustic studies presented can be regarded as a new approach to a fast and sufficiently precise method in the screening diagnostics of dysphonia conditioned by growth of the vocal fold mass.

  7. Human amnion epithelial cells can be induced to differentiate into functional insulin-producing cells

    Institute of Scientific and Technical Information of China (English)

    Yanan Hou; Qin Huang; Tianjin Liu; Lihe Guo

    2008-01-01

    Pancreatic islet transplantation has demonstrated that long-term insulin independence may be achieved in patients suffering from diabetes mellitus type 1. However, limited availability of islet tissue means that new sources of insulinproducing cells that are responsive to glucose are required. Here, we show that human amnion epithelial cells (HAEC) can be induced to differentiate into functional insulinproducing cells in vitro. After induction of differentiation, HAEC expressed multiple pancreatic --cell genes, including insulin, pancreas duodenum homeobox-1, paired box gene 6,NK2 transcription factor-related locus 2, Islet 1, glucokinase,and glucose transporter-2, and released C-peptide in a glucose-regulated manner in response to other extracellular stimulations. The transplantation of induced HAEC into streptozotocin-induced diabetic C57 mice reversed hyperglycemia, restored body weight, and maintained euglycemia for 30 d. These findings indicated that HAEC may be a new source for cell replacement therapy in type 1 diabetes.

  8. Effect of lamin A/C knockdown on osteoblast differentiation and function.

    Science.gov (United States)

    Akter, Rahima; Rivas, Daniel; Geneau, Graziello; Drissi, Hicham; Duque, Gustavo

    2009-02-01

    Recent studies have associated mutations in lamin A/C, a component of the nuclear lamina, with premature aging and severe bone loss. In this study, we hypothesized that reduced expression of lamin A/C has a negative impact on osteoblastogenesis and bone formation in vitro. We inhibited lamin A/C using increasing doses of lamin A/C siRNA in normal human osteoblasts and differentiating mesenchymal stem cells (MSCs). Untreated cells and cells treated with vehicle but without the siRNA-oligo were used as control. The level of effectiveness of siRNA was determined by RT-PCR, Western blot, and immunofluorescence. Nuclear blebbing, a typical finding of lamin A/C inhibition, was quantified using propidium iodine staining, and its effect on cell survival was determined using MTS-formazan. Furthermore, alizarin red and alkaline phosphatase staining were correlated with osteocalcin secretion and levels of expression of osteocalcin, osterix, bone sialoprotein, and Runx2. Finally, the nuclear binding activity of Runx2, an essential transcription factor for osteoblast differentiation, was assessed using ELISA and EMSA. A successful inhibitory effect on the lamin A/C gene at doses of 400-800 nM oligo was obtained without affecting cell survival. Whereas osteoblast function was significantly affected by lamin A/C inhibition, siRNA-treated MSC showed a higher incidence of nuclear changes, lower osteoblast differentiation, and enhanced adipocyte differentiation. Finally, lamin A/C knockdown reduced Runx2 nuclear binding activity without affecting Runx2 expression. In summary, our results indicate that lamin A/C is a new factor needed for osteoblast differentiation that plays an important role in the cellular mechanisms of age-related bone loss.

  9. Differentiating the stem cell pool of human hair follicle outer root sheath into functional melanocytes.

    Science.gov (United States)

    Schneider, Marie; Dieckmann, Christina; Rabe, Katrin; Simon, Jan-Christoph; Savkovic, Vuk

    2014-01-01

    Bench-to-Bedside concepts for regenerative therapy place significant weight on noninvasive approaches, with harvesting of the starting material as a header. This is particularly important in autologous treatments, which use one's bodily constituents for therapy. Precisely the stretch between obtaining therapeutic elements invasively and noninvasively places non-intrusive "sampling" rather than "biopsy" in the center of the road map of developing an autologous regenerative therapy. We focus on such a noninvasively available source of adult stem cells that we carry with us throughout our life, available at our fingertips-or shall we say hair roots, by a simple plucking of hair: the human hair follicle. This chapter describes an explant procedure for cultivating melanocytes differentiated from the stem cell pool of the hair follicle Outer Root Sheath (ORS). In vivo, the most abundant derivatives of the heterogeneous ORS stem cell pool are epidermal cells-melanocytes and keratinocytes which complete their differentiation-either spontaneously or upon picking up regenerative cues from damaged skin-and migrate from the ORS towards the adjacent regenerating area of the epidermis. We have taken advantage of the ORS developmental potential by optimizing explant primary culture, expansion and melanogenic differentiation of resident ORS stem cells towards end-stage melanocytes in order to obtain functional melanocytes noninvasively for the purposes of transplantation and use them for the treatment of depigmentation disorders. Our protocol specifies sampling of hair with their ORS, follicle medium-air interface primary culture, stimulation of cell outgrowth, adherent culture and differentiation of ORS stem cells and precursors towards fully functional melanocytes. Along with cultivation, we describe selection techniques for establishing and maintaining a pure melanocyte population and methods suitable for determining melanocyte identity.

  10. Initial function analysis of a novel erythroid differentiation related gene EDRF1

    Institute of Scientific and Technical Information of China (English)

    王敦成; 黎燕; 沈倍奋

    2001-01-01

    Erythroid differentiation depends on the establishment of specific patterns of gene expression. Hypersensitive site 2 (HS2, serving as a major enhancer of globin genes)-binding proteins may be involved in its natural open chromosomal environment formation. Previously we prepared monoclonal antibodies against HS2-binding nuclear proteins of terminal differentiated erythroid cells. By utilizing the monoclonal antibodies, we screened λ-gt11 human fetal liver cDNA expression library and obtained one cDNA clone, which was named erythroid differentiation related gene (EDRF1, Genbank accession number AF040247) , encompassing an entire open reading frame. We investigated the expression pattern of EDRF1 by RT-PCR technique. And a clue to the function of EDRF1 has been found from confirmation of high levels of EDRF1 mRNA in differentiated K562 and human fetal liver tissue. To illuminate the function of EDRF1 in K562 cells, sense and antisense EDRF1 constructs were prepared and transfected into K562 cells, α-globin mRNA was down-regulated and EpoR (erythropoietin receptor) mRNA expression was increased in antisense transfected cells. Cells transfected with sense construct grew more slowly than control cells suggested by [3H] thimidine incorporation experiments. Suppression of K562 proliferation was accompanied by increased spontaneous hemoglobin synthesis demonstrated by spectrometry.K562 cells transfected with sense construct exhibited reduced clongenicity compared with control cells in methycellulose culture. These data provided the evidence that EDRF1 can influence globin expression and hemoglobin synthesis in K562 cells and modulated self-renewal in K562 cells.

  11. Genes related to mitochondrial functions are differentially expressed in phosphine-resistant and -susceptible Tribolium castaneum.

    Science.gov (United States)

    Oppert, Brenda; Guedes, Raul N C; Aikins, Michael J; Perkin, Lindsey; Chen, Zhaorigetu; Phillips, Thomas W; Zhu, Kun Yan; Opit, George P; Hoon, Kelly; Sun, Yongming; Meredith, Gavin; Bramlett, Kelli; Hernandez, Natalie Supunpong; Sanderson, Brian; Taylor, Madison W; Dhingra, Dalia; Blakey, Brandon; Lorenzen, Marcé; Adedipe, Folukemi; Arthur, Frank

    2015-11-18

    Phosphine is a valuable fumigant to control pest populations in stored grains and grain products. However, recent studies indicate a substantial increase in phosphine resistance in stored product pests worldwide. To understand the molecular bases of phosphine resistance in insects, we used RNA-Seq to compare gene expression in phosphine-resistant and susceptible laboratory populations of the red flour beetle, Tribolium castaneum. Each population was evaluated as either phosphine-exposed or no phosphine (untreated controls) in triplicate biological replicates (12 samples total). Pairwise analysis indicated there were eight genes differentially expressed between susceptible and resistant insects not exposed to phosphine (i.e., basal expression) or those exposed to phopshine (>8-fold expression and 90 % C.I.). However, 214 genes were differentially expressed among all four treatment groups at a statistically significant level (ANOVA, p < 0.05). Increased expression of 44 cytochrome P450 genes was found in resistant vs. susceptible insects, and phosphine exposure resulted in additional increases of 21 of these genes, five of which were significant among all treatment groups (p < 0.05). Expression of two genes encoding anti-diruetic peptide was 2- to 8-fold reduced in phosphine-resistant insects, and when exposed to phosphine, expression was further reduced 36- to 500-fold compared to susceptible. Phosphine-resistant insects also displayed differential expression of cuticle, carbohydrate, protease, transporter, and many mitochondrial genes, among others. Gene ontology terms associated with mitochondrial functions (oxidation biological processes, monooxygenase and catalytic molecular functions, and iron, heme, and tetrapyyrole binding) were enriched in the significantly differentially expressed dataset. Sequence polymorphism was found in transcripts encoding a known phosphine resistance gene, dihydrolipoamide dehydrogenase, in both susceptible and resistant

  12. Differential Hydrological Grey Model (DHGM) with self-memory function and its application to flood forecasting

    Institute of Scientific and Technical Information of China (English)

    CHEN XiangDong; XIA Jun; XU Qian

    2009-01-01

    This paper addresses a problem of flood forecasting with the self-memory function. Considering flood forecasting's uncertainty and updating demand, a hybrid hydrological model, namely Differential Hydrological Grey Model with self-memory function (DHGM-SM), is developed. The model has two fold features. One is to establish a self-memorization equation linked with DHGM, that could extract useful information from past data series and realize updating of hydrological dynamic process. The other is that this model has higher efficiency relative to original hydrological model without self-memory function. This approach was applied to river flow forecasting of two representative basins in Tunxi of South China and Daqinggou of North China. It is shown that this hybrid method has satisfactory forecasting accuracy by examination of both calibration and validation.

  13. Negative differential conductance in two-dimensional C-functionalized boronitrene

    KAUST Repository

    Obodo, J T

    2015-09-10

    It recently has been demonstrated that the large band gap of boronitrene can be significantly reduced by C functionalization. We show that specific defect configurations even can result in metallicity, raising interest in the material for electronic applications. We thus study the transport properties of C-functionalized boronitrene using the non-equilibrium Green\\'s function formalism. We investigate various zigzag and armchair defect configurations, spanning wide band gap semiconducting to metallic states. Unusual I–V characteristics are found and explained in terms of the energy and bias-dependent transmission coefficient and wavefunction. In particular, we demonstrate negative differential conductance with high peak-to-valley ratios, depending on the details of the substitutional doping, and identify the finite bias effects that are responsible for this behavior.

  14. Differential effects of hunger and satiety on insular cortex and hypothalamic functional connectivity.

    Science.gov (United States)

    Wright, Hazel; Li, Xiaoyun; Fallon, Nicholas B; Crookall, Rebecca; Giesbrecht, Timo; Thomas, Anna; Halford, Jason C G; Harrold, Joanne; Stancak, Andrej

    2016-05-01

    The insula cortex and hypothalamus are implicated in eating behaviour, and contain receptor sites for peptides and hormones controlling energy balance. The insula encompasses multi-functional subregions, which display differential anatomical and functional connectivities with the rest of the brain. This study aimed to analyse the effect of fasting and satiation on the functional connectivity profiles of left and right anterior, middle, and posterior insula, and left and right hypothalamus. It was hypothesized that the profiles would be altered alongside changes in homeostatic energy balance. Nineteen healthy participants underwent two 7-min resting state functional magnetic resonance imaging scans, one when fasted and one when satiated. Functional connectivity between the left posterior insula and cerebellum/superior frontal gyrus, and between left hypothalamus and inferior frontal gyrus was stronger during fasting. Functional connectivity between the right middle insula and default mode structures (left and right posterior parietal cortex, cingulate cortex), and between right hypothalamus and superior parietal cortex was stronger during satiation. Differences in blood glucose levels between the scans accounted for several of the altered functional connectivities. The insula and hypothalamus appear to form a homeostatic energy balance network related to cognitive control of eating; prompting eating and preventing overeating when energy is depleted, and ending feeding or transferring attention away from food upon satiation. This study provides evidence of a lateralized dissociation of neural responses to energy modulations.

  15. Incorporation of functionalized gold nanoparticles into nanofibers for enhanced attachment and differentiation of mammalian cells

    Directory of Open Access Journals (Sweden)

    Jung Dongju

    2012-06-01

    Full Text Available Abstract Background Electrospun nanofibers have been widely used as substrata for mammalian cell culture owing to their structural similarity to natural extracellular matrices. Structurally consistent electrospun nanofibers can be produced with synthetic polymers but require chemical modification to graft cell-adhesive molecules to make the nanofibers functional. Development of a facile method of grafting functional molecules on the nanofibers will contribute to the production of diverse cell type-specific nanofiber substrata. Results Small molecules, peptides, and functionalized gold nanoparticles were successfully incorporated with polymethylglutarimide (PMGI nanofibers through electrospinning. The PMGI nanofibers functionalized by the grafted AuNPs, which were labeled with cell-adhesive peptides, enhanced HeLa cell attachment and potentiated cardiomyocyte differentiation of human pluripotent stem cells. Conclusions PMGI nanofibers can be functionalized simply by co-electrospinning with the grafting materials. In addition, grafting functionalized AuNPs enable high-density localization of the cell-adhesive peptides on the nanofiber. The results of the present study suggest that more cell type-specific synthetic substrata can be fabricated with molecule-doped nanofibers, in which diverse functional molecules are grafted alone or in combination with other molecules at different concentrations.

  16. On representation of solutions of nonlinear partial differential equations in the form of convergent special series with functional arbitrariness

    Science.gov (United States)

    Filimonov, M. Yu.

    2016-12-01

    An analytical method for representation of solutions of nonlinear partial differential equations in the form of special series with recurrently computed coefficients is presented. The coefficients recurrent obtaining from linear differential equations is achieved by specificity of the considered equations. It turns out that due to the functional arbitrariness which possibly is contained in special series, one can prove global convergence of the constructed series to solution of considered nonlinear partial differential equations.

  17. Assessment of various parameters in the estimation of differential renal function using technetium-99m mercaptoacetyltriglycine

    Energy Technology Data Exchange (ETDEWEB)

    Lythgoe, M.F.; Gordon, I.; Khader, Z.; Smith, T.; Anderson, P.J. [Department of Radiology, Great Ormond Street Hospital for Children NHS Trust, London (United Kingdom)

    1999-02-01

    Differential renal function (DRF) is an important parameter that should be assessed from virtually every dynamic renogram. With the introduction of technetium-99m mercaptoacetyltriglycine ({sup 99m}Tc-MAG3), a tracer with a high renal extraction, the estimation of DRF might hopefully become accurate and reproducible both between observers in the same institution and also between institutions. The aim of this study was to assess the effect of different parameters on the estimation of DRF. To this end we investigated two groups of children: group A, comprising 35 children with a single kidney (27 of whom had poor renal function), and group B, comprising 20 children with two kidneys and normal global function who also had an associated {sup 99m}Tc-dimercaptosuccinic acid scan ({sup 99m}Tc-DMSA). The variables assessed for their effect on the estimation of DRF were: different operators, the choice of renal regions of interest (ROIs), the applied background subtraction, and six different techniques for analysis of the renogram. The six techniques were based on: linear regression of the slopes in the Rutland-Patlak plot, matrix deconvolution, differential method, integral method, linear regression of the slope of the renograms, and the area under the curve of the renogram. The estimation of DRF was less dependent upon both observer and method in patients with two normally functioning kidneys than in patients with a single kidney. The inter-observer comparison among children in either group was not dependent on either ROI or background subtraction. However, in patients with poor renal function the method of choice for the estimation of DRF was dependent on background subtraction, though not ROI. In children with two kidneys and normal renal function, the estimation of DRF from the 24 techniques gave similar results. Methods that produced DRF values closest to expected results, from either group of children, were the Rutland-Patlak plot and matrix deconvolution methods

  18. Functional brain imaging in the dementias: role in early detection, differential diagnosis, and longitudinal studies

    Energy Technology Data Exchange (ETDEWEB)

    Devous, M.D. Sr. [Nuclear Medicine Center and Department of Radiology, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX (United States)

    2002-12-01

    This review considers the role of functional brain imaging techniques in the dementias. The substantial assistance that especially single-photon emission tomography and positron emission tomography can play in the initial diagnosis of dementia and in the differential diagnosis of the specific dementing disorder is discussed. These techniques alone essentially match the sensitivity and specificity of clinical diagnoses in distinguishing Alzheimer's dementia (AD) from age-matched controls, from frontal lobe dementia and vascular dementia, and even from Lewy body dementia. Newer analytic techniques such as voxel-based correlational analyses and discriminant function analyses enhance the power of such differential diagnoses. Functional brain imaging techniques can also significantly assist in patient screening for clinical trials. The correlation of the observed deficits with specific patterns of cognitive abnormalities permits enhanced patient management and treatment planning and improved longitudinal assessment of outcome. It is also noteworthy that the classic abnormalities of temporoparietal and posterior cingulate hypoperfusion or hypometabolism appear to be present prior to symptom onset. These abnormalities predict progression to AD in the presence of the earliest of symptoms, and are present even in cognitively normal but at-risk subjects, with a severity proportional to the risk status. Even greater predictive ability for progression to AD is obtained by combining measures of perfusion or metabolism with risk factors, tau protein levels, hippocampal N-Acetyl aspartate concentrations, or hippocampal volume measures. (orig.)

  19. Cerebral pathology and neuropsychological effects. Differential effects of cranial radiation as a function of age

    Energy Technology Data Exchange (ETDEWEB)

    Dowell, R.E. Jr.; Copeland, D.R.

    Cranial radiation therapy (CRT) has been associated with an increased incidence of neuropsychological impairments and pathologic changes in the CNS among children. However, findings regarding a causal relationship between CRT and neurobehavioral impairments and the differential impact of CRT as a function of treatment age have been equivocal. Inconsistent findings may be attributed to the current research focus on description of impairments to the neglect of a larger theoretical framework and the failure of investigators to integrate findings from the various disciplines involved in assessing CRT effects. Two theories regarding the etiology of CRT effects on neuropsychological functions have been proposed. The myelination hypothesis suggests that CRT effects are attributable to direct effects on myelin synthesis. Findings indicating that the child is in a state of particular vulnerability to teratogens due to the rapid growth phase of myelin during the first 48 months of life provide the basis for this hypothesis. The myelination hypothesis predicts a differential effect for CRT as a function of age/maturation. The vascular hypothesis proposes that CRT effects are due to pathological changes in vascular tissues. Results indicating prominent white matter changes among some CRT recipients provide the basis for this hypothesis. The vascular hypothesis predicts no age effect or an inverse age effect; it places more emphasis on the relationship between indices of cerebral blood flow and neuropsychological test performance. Two basic mechanisms underlying the effects of CRT are outlined to provide a theoretical framework on which future research may be based. 29 references.

  20. Cultivation of adult rat hepatocytes on 3T3 cells: expression of various liver differentiated functions.

    Science.gov (United States)

    Kuri-Harcuch, W; Mendoza-Figueroa, T

    1989-08-01

    Adult rat hepatocytes were maintained in culture for at least 1 month without losing the expression of their differentiated functions; they were cultured on lethally treated 3T3 fibroblasts inoculated at 35,000 cells/cm2 with medium containing 10-25 micrograms/ml hydrocortisone. Hepatocytes showed their typical morphology; they formed bile canaliculi, microvilli, and intercellular junctions with desmosomes and nexus; some formed structures that may resemble the perisinusoidal space of Disse. In addition, they showed DNA synthesis and expressed some liver-specific functions. They synthesized albumin and other proteins, which were exported to the culture medium. Like parenchymal liver cells in vivo, de novo fatty acid synthesis and esterification took place, and more than 80% of the lipids synthesized by the hepatocytes were secreted into the medium as triglycerides; they also showed cytochrome-P450 activity that was inducible with phenobarbital, suggesting that the hepatocytes have the capacity to metabolize drugs. These culture conditions allow the study of various hepatocyte differentiated functions, and they may provide the means to analyze the effect on liver of hormones, viruses and hepatotoxic chemicals and drugs; they may also indicate conditions adequate for serial growth of hepatocytes.

  1. Existence, uniqueness, and stability of stochastic neutral functional differential equations of Sobolev-type

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Xuetao; Zhu, Quanxin, E-mail: zqx22@126.com [School of Mathematical Sciences and Institute of Mathematics, Nanjing Normal University, Nanjing 210023, Jiangsu (China)

    2015-12-15

    In this paper, we are mainly concerned with a class of stochastic neutral functional differential equations of Sobolev-type with Poisson jumps. Under two different sets of conditions, we establish the existence of the mild solution by applying the Leray-Schauder alternative theory and the Sadakovskii’s fixed point theorem, respectively. Furthermore, we use the Bihari’s inequality to prove the Osgood type uniqueness. Also, the mean square exponential stability is investigated by applying the Gronwall inequality. Finally, two examples are given to illustrate the theory results.

  2. Differential item functioning (DIF) in the EORTC QLQ-C30

    DEFF Research Database (Denmark)

    Scott, Neil W; Fayers, Peter M; Aaronson, Neil K;

    2009-01-01

    Differential item functioning (DIF) analyses can be used to explore translation, cultural, gender or other differences in the performance of quality of life (QoL) instruments. These analyses are commonly performed using "baseline" or pretreatment data. We previously reported DIF analyses to examine...... the pattern of item responses for translations of the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 QoL instrument, using only data collected prior to cancer treatment. We now compare the consistency of these results with similar analyses of on-treatment and off...

  3. Discontinuous initial value problems for functional differential-algebraic equations of mixed type

    Science.gov (United States)

    d'Albis, H.; Augeraud-Véron, E.; Hupkes, H. J.

    We study the well-posedness of initial value problems for nonlinear functional differential-algebraic equations of mixed type. We are interested in solutions to such problems that admit a single jump discontinuity at time zero. We focus specially on the question whether unstable equilibria can be stabilized by appropriately choosing the size of the jump discontinuity. We illustrate our techniques by analytically studying an economic model for the interplay between inflation and interest rates. In particular, we investigate under which circumstances the central bank can prevent runaway inflation by appropriately hiking the interest rate.

  4. Modified extended tanh-function method for solving nonlinear partial differential equations

    Energy Technology Data Exchange (ETDEWEB)

    El-Wakil, S.A. [Department of Physics, Faculty of Science, Theoretical Research Group, Mansoura University, 35516 Mansoura (Egypt); Abdou, M.A. [Department of Physics, Faculty of Science, Theoretical Research Group, Mansoura University, 35516 Mansoura (Egypt)]. E-mail: m_abdou_eg@yahoo.com

    2007-03-15

    Based on computerized symbolic computation, modified extended tanh-method for constructing multiple travelling wave solutions of nonlinear evolution equations is presented and implemented in a computer algebraic system. Applying this method, with the aid of Maple, we consider some nonlinear evolution equations in mathematical physics such as the nonlinear partial differential equation, nonlinear Fisher-type equation, ZK-BBM equation, generalized Burgers-Fisher equation and Drinfeld-Sokolov system. As a result, we can successfully recover the previously known solitary wave solutions that had been found by the extended tanh-function method and other more sophisticated methods.

  5. Feedback control of nonlinear differential algebraic systems using Hamiltonian function method

    Institute of Scientific and Technical Information of China (English)

    LIU Yanhong; LI Chunwen; WU Rebing

    2006-01-01

    The stabilization and H∞ control of nonlinear differential algebraic systems (NDAS) are investigated using the Hamiltonian function method. Firstly, we put forward a novel dissipative Hamiltonian realization (DHR) structure and give the condition to complete the Hamiltonian realization. Then, based on the DHR, we present a criterion for the stability analysis of NDAS and construct a stabilization controller for NDAS in absence of disturbances. Finally, for NDAS in presence of disturbances, the L2 gain is analyzed via generalized Hamilton-Jacobi inequality and an H∞ control strategy is constructed. The proposed stabilization and robust controller can effectively take advantage of the structural characteristics of NDAS and is simple in form.

  6. [XS-DIF: program for analysis of Differential Item Functioning in Excel].

    Science.gov (United States)

    Ordóñez, Xavier G; Romero, Sonia J

    2007-02-01

    XS-DIF is a program for detection of Differential Item Functioning (DIF) using Item Response Theory (IRT). It calculates Lords Chi-Square, Raju's Signed Area and Unsigned Area, and Kim and Cohen's Closed-interval signed area and Closed-interval unsigned area. XS-DIF was designed to be executed in Excel 2000 and it has a capacity of analysis of up to 100 items. It is useful to support data analysis of research projects and in detection and teaching processes in DIF.

  7. The function of a regulatory gene,scrX related to differentiation in Streptomyces coelicolor

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    A new gene, scrX from Streptomyces coelicolor was cloned and sequenced. It consists of 660 base pair, encoding a peptide of 220 amino acids. There are three rare codons in scrX which are AAA, AAA and ATA. scrX gene may be a typical differentiation regulator which was strictly controlled at translational level. The comparison of amino acids also revealed that ScrX belonged to Ic1R family which acted in transcriptional regulation of prokaryote. Studies on gene function by gene disruption and complementation indicated that scrX may play a positive regulation role in spore formation of Streptomyces coelicolor.

  8. A Brief Survey on the Numerical Dynamics for Functional Differential Equations

    Science.gov (United States)

    Garay, Barnabas M.

    This is a survey on discretizing delay equations from a geometric-qualitative view-point. Concepts like compact attractors, hyperbolic periodic orbits, the saddle structure around hyperbolic equilibria, center-unstable manifolds of equilibria, inertial manifolds, structural stability, and Kamke monotonicity are considered. Error estimates for smooth and nonsmooth initial data in various Cj topologies are provided. The emphasis is put on Runge-Kutta methods with natural interpolants. The paper ends with a collection of the related results on retarded functional differential equations with bounded delay.

  9. Exact Values of Bernstein -Widths for Some Classes of Periodic Functions with Formal Self-Adjoint Linear Differential Operators

    Directory of Open Access Journals (Sweden)

    Guo Feng

    2008-01-01

    Full Text Available Abstract We consider the classes of periodic functions with formal self-adjoint linear differential operators , which include the classical Sobolev class as its special case. With the help of the spectral of linear differential equations, we find the exact values of Bernstein -width of the classes in the for .

  10. The role of costimulatory molecules in directing the functional differentiation of alloreactive T helper cells.

    Science.gov (United States)

    Magee, C N; Boenisch, O; Najafian, N

    2012-10-01

    Costimulatory molecules are a heterogenous group of cell surface molecules that act to amplify or counteract the initial activating signals provided to T cells from the T cell receptor following its interaction with an antigen/major histocompatibility complex, thereby influencing T cell differentiation and fate. Although costimulation was previously thought to be indispensable for T cell activation at all stages of development, it is now known that the requirements for costimulation, and the costimulatory molecules involved, vary according to the stage of T cell differentiation. The ability to influence T cell fate is of paramount interest in the field of transplantation as we seek therapeutic options that inhibit detrimental alloimmune responses whilst simultaneously promoting allograft tolerance. As with many immune mechanisms, there is a degree of functional overlap between certain costimulatory molecules, whereas some have diametrically opposite effects on different T cell subsets despite sharing common ligands. This is a critical point when considering these molecules as therapeutic targets in transplantation, as blockade of a costimulatory pathway, although desirable in itself, may prevent the ligation of an essential regulatory coinhibitory molecule. This review discusses the T helper cell lineages pertinent to transplantation and the costimulatory molecules involved in their differentiation. © Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.

  11. Effects of endocrine modulators on sexual differentiation and reproductive function in male Japanese quail.

    Science.gov (United States)

    Halldin, Krister; Axelsson, Jeanette; Brunström, Björn

    2005-04-15

    A number of environmental contaminants have been shown to interfere with the endocrine system. Many of these compounds bind to estrogen receptors, thereby potentially disrupting estrogen-regulated functions. In this paper, we review some background data on avian sexual differentiation and present some of the results from our studies on effects of estrogenic chemicals administered during sexual differentiation in the Japanese quail. Initially, our goal was to elucidate whether a decreased male sexual behavior in quail is a suitable endpoint for studying long-term effects of exposure to estrogenic compounds during sexual differentiation in ovo. We thereafter tested some environmental pollutants, suspected to act via mimicking estrogens, using the test system developed. Results from our studies on the synthetic estrogens ethinylestradiol and diethylstilbestrol, as well as the environmental pollutants bisphenol A, tetrabromobisphenol A, and o,p'-DDT are reviewed in this paper. We conclude that the Japanese quail is well suited as an animal model for studying various long-term effects after embryonic exposure to estrogenic compounds. Depressed sexual behavior proved to be the most sensitive of the variables studied in males and we find this endpoint appropriate for studying effects of endocrine modulating chemicals in the adult quail following embryonic exposure.

  12. Cdk4 functions in multiple cell types to control Drosophila intestinal stem cell proliferation and differentiation

    Directory of Open Access Journals (Sweden)

    Mojca Adlesic

    2016-03-01

    Full Text Available The proliferation of intestinal stem cells (ISCs and differentiation of enteroblasts to form mature enteroendocrine cells and enterocytes in the Drosophila intestinal epithelium must be tightly regulated to maintain homeostasis. We show that genetic modulation of CyclinD/Cdk4 activity or mTOR-dependent signalling cell-autonomously regulates enterocyte growth, which influences ISC proliferation and enteroblast differentiation. Increased enterocyte growth results in higher numbers of ISCs and defective enterocyte growth reduces ISC abundance and proliferation in the midgut. Adult midguts deficient for Cdk4 show severe disruption of intestinal homeostasis characterised by decreased ISC self-renewal, enteroblast differentiation defects and low enteroendocrine cell and enterocyte numbers. The ISC/enteroblast phenotypes result from a combination of cell autonomous and non-autonomous requirements for Cdk4 function. One non-autonomous consequence of Cdk4-dependent deficient enterocyte growth is high expression of Delta in ISCs and Delta retention in enteroblasts. We postulate that aberrant activation of the Delta–Notch pathway is a possible partial cause of lost ISC stemness. These results support the idea that enterocytes contribute to a putative stem cell niche that maintains intestinal homeostasis in the Drosophila anterior midgut.

  13. Differential PAX3 functions in normal skin melanocytes and melanoma cells.

    Science.gov (United States)

    Medic, Sandra; Rizos, Helen; Ziman, Mel

    2011-08-12

    The PAX3 transcription factor is the key regulator of melanocyte development during embryogenesis and is also frequently found in melanoma cells. While PAX3 is known to regulate melanocyte differentiation, survival, proliferation and migration during development, it is not clear if its function is maintained in adult melanocytes and melanoma cells. To clarify this we have assessed which genes are targeted by PAX3 in these cells. We show here that similar to its roles in development, PAX3 regulates complex differentiation networks in both melanoma cells and melanocytes, in order to maintain cells as "stem" cell-like (via NES and SOX9). We show also that mediators of migration (MCAM and CSPG4) are common to both cell types but more so in melanoma cells. By contrast, PAX3-mediated regulation of melanoma cell proliferation (through TPD52) and survival (via BCL2L1 and PTEN) differs from that in melanocytes. These results suggest that by controlling cell proliferation, survival and migration as well as maintaining a less differentiated "stem" cell like phenotype, PAX3 may contribute to melanoma development and progression.

  14. Mutational Signatures of De-Differentiation in Functional Non-Coding Regions of Melanoma Genomes

    Science.gov (United States)

    Parker, Stephen C. J.; Gartner, Jared; Cardenas-Navia, Isabel; Wei, Xiaomu; Ozel Abaan, Hatice; Ajay, Subramanian S.; Hansen, Nancy F.; Song, Lingyun; Bhanot, Umesh K.; Killian, J. Keith; Gindin, Yevgeniy; Walker, Robert L.; Meltzer, Paul S.; Mullikin, James C.; Furey, Terrence S.; Crawford, Gregory E.; Rosenberg, Steven A.; Samuels, Yardena; Margulies, Elliott H.

    2012-01-01

    Much emphasis has been placed on the identification, functional characterization, and therapeutic potential of somatic variants in tumor genomes. However, the majority of somatic variants lie outside coding regions and their role in cancer progression remains to be determined. In order to establish a system to test the functional importance of non-coding somatic variants in cancer, we created a low-passage cell culture of a metastatic melanoma tumor sample. As a foundation for interpreting functional assays, we performed whole-genome sequencing and analysis of this cell culture, the metastatic tumor from which it was derived, and the patient-matched normal genomes. When comparing somatic mutations identified in the cell culture and tissue genomes, we observe concordance at the majority of single nucleotide variants, whereas copy number changes are more variable. To understand the functional impact of non-coding somatic variation, we leveraged functional data generated by the ENCODE Project Consortium. We analyzed regulatory regions derived from multiple different cell types and found that melanocyte-specific regions are among the most depleted for somatic mutation accumulation. Significant depletion in other cell types suggests the metastatic melanoma cells de-differentiated to a more basal regulatory state. Experimental identification of genome-wide regulatory sites in two different melanoma samples supports this observation. Together, these results show that mutation accumulation in metastatic melanoma is nonrandom across the genome and that a de-differentiated regulatory architecture is common among different samples. Our findings enable identification of the underlying genetic components of melanoma and define the differences between a tissue-derived tumor sample and the cell culture created from it. Such information helps establish a broader mechanistic understanding of the linkage between non-coding genomic variations and the cellular evolution of cancer

  15. Mutational signatures of de-differentiation in functional non-coding regions of melanoma genomes.

    Directory of Open Access Journals (Sweden)

    Stephen C J Parker

    Full Text Available Much emphasis has been placed on the identification, functional characterization, and therapeutic potential of somatic variants in tumor genomes. However, the majority of somatic variants lie outside coding regions and their role in cancer progression remains to be determined. In order to establish a system to test the functional importance of non-coding somatic variants in cancer, we created a low-passage cell culture of a metastatic melanoma tumor sample. As a foundation for interpreting functional assays, we performed whole-genome sequencing and analysis of this cell culture, the metastatic tumor from which it was derived, and the patient-matched normal genomes. When comparing somatic mutations identified in the cell culture and tissue genomes, we observe concordance at the majority of single nucleotide variants, whereas copy number changes are more variable. To understand the functional impact of non-coding somatic variation, we leveraged functional data generated by the ENCODE Project Consortium. We analyzed regulatory regions derived from multiple different cell types and found that melanocyte-specific regions are among the most depleted for somatic mutation accumulation. Significant depletion in other cell types suggests the metastatic melanoma cells de-differentiated to a more basal regulatory state. Experimental identification of genome-wide regulatory sites in two different melanoma samples supports this observation. Together, these results show that mutation accumulation in metastatic melanoma is nonrandom across the genome and that a de-differentiated regulatory architecture is common among different samples. Our findings enable identification of the underlying genetic components of melanoma and define the differences between a tissue-derived tumor sample and the cell culture created from it. Such information helps establish a broader mechanistic understanding of the linkage between non-coding genomic variations and the cellular

  16. Bipolar and borderline patients display differential patterns of functional connectivity among resting state networks.

    Science.gov (United States)

    Das, Pritha; Calhoun, Vince; Malhi, Gin S

    2014-09-01

    Bipolar disorder (BD) and borderline personality (BPD) disorder share clinical features such as emotional lability and poor interpersonal functioning but the course of illness and treatment differs in these groups, which suggests that the underlying neurobiology of BD and BPD is likely to be different. Understanding the neural mechanisms behind the pathophysiology of BD and BPD will facilitate accurate diagnosis and inform the administration of targeted treatment. Since deficits in social cognition or emotion regulation or in the self-referential processing system can give rise to these clinical features, and impairment in these domains have been observed in both patient groups, functional connectivity within and between networks subserving these processes during resting was investigated using functional magnetic resonance imaging. Data were acquired from 16 patients with BD, 14 patients with BPD, and 13 healthy controls (HC) and functional connectivity strength was correlated with scores using the Difficulties in Emotion Regulation Scale. Functional network connectivity (FNC) patterns differentiated BD and BPD patients from HC. In BD, FNC was increased while in BPD it was decreased. In BD impaired FNC was evident primarily among networks involved in self-referential processing while in BPD it also involved the emotion regulatory network. Impaired FNC displayed an association with impulsivity in BPD and emotional clarity and emotional awareness in BD. This study shows that BD and BPD can perhaps be differentiated using resting state FNC approach and that the neural mechanisms underpinning overlapping symptoms discernibly differ between the groups. These findings provide a potential platform for elucidating the targeted effects of psychological interventions in both disorders.

  17. Chronic mitral regurgitation detected on cardiac MDCT: differentiation between functional and valvular aetiologies.

    LENUS (Irish Health Repository)

    Killeen, Ronan P

    2012-02-01

    OBJECTIVE: To determine whether cardiac computed tomography (MDCT) can differentiate between functional and valvular aetiologies of chronic mitral regurgitation (MR) compared with echocardiography (TTE). METHODS: Twenty-seven patients with functional or valvular MR diagnosed by TTE and 19 controls prospectively underwent cardiac MDCT. The morphological appearance of the mitral valve (MV) leaflets, MV geometry, MV leaflet angle, left ventricular (LV) sphericity and global\\/regional wall motion were analysed. The coronary arteries were evaluated for obstructive atherosclerosis. RESULTS: All control and MR cases were correctly identified by MDCT. Significant differences were detected between valvular and control groups for anterior leaflet length (30 +\\/- 7 mm vs. 22 +\\/- 4 mm, P < 0.02) and thickness (3.0 +\\/- 1 mm vs. 2.2 +\\/- 1 mm, P < 0.01). High-grade coronary stenosis was detected in all patients with functional MR compared with no controls (P < 0.001). Significant differences in those with\\/without MV prolapse were detected in MV tent area (-1.0 +\\/- 0.6 mm vs. 1.3 +\\/- 0.9 mm, P < 0.0001) and MV tent height (-0.7 +\\/- 0.3 mm vs. 0.8 +\\/- 0.8 mm, P < 0.0001). Posterior leaflet angle was significantly greater for functional MR (37.9 +\\/- 19.1 degrees vs. 22.9 +\\/- 14 degrees , P < 0.018) and less for valvular MR (0.6 +\\/- 35.5 degrees vs. 22.9 +\\/- 14 degrees, P < 0.017). Sensitivity, specificity, and positive and negative predictive values of MDCT were 100%, 95%, 96% and 100%. CONCLUSION: Cardiac MDCT allows the differentiation between functional and valvular causes of MR.

  18. Differential Functional Connectivity Alterations of Two Subdivisions within the Right dlPFC in Parkinson's Disease

    Science.gov (United States)

    Caspers, Julian; Mathys, Christian; Hoffstaedter, Felix; Südmeyer, Martin; Cieslik, Edna C.; Rubbert, Christian; Hartmann, Christian J.; Eickhoff, Claudia R.; Reetz, Kathrin; Grefkes, Christian; Michely, Jochen; Turowski, Bernd; Schnitzler, Alfons; Eickhoff, Simon B.

    2017-01-01

    Patients suffering from Parkinson's disease (PD) often show impairments in executive function (EF) like decision-making and action control. The right dorsolateral prefrontal cortex (dlPFC) has been strongly implicated in EF in healthy subjects and has repeatedly been reported to show alterations related to EF impairment in PD. Recently, two key regions for cognitive action control have been identified within the right dlPFC by co-activation based parcellation. While the posterior region is engaged in rather basal EF like stimulus integration and working memory, the anterior region has a more abstract, supervisory function. To investigate whether these functionally distinct subdivisions of right dlPFC are differentially affected in PD, we analyzed resting-state functional connectivity (FC) in 39 PD patients and 44 age- and gender-matched healthy controls. Patients were examined both after at least 12 h withdrawal of dopaminergic drugs (OFF) and under their regular dopaminergic medication (ON). We found that only the posterior right dlPFC subdivision shows FC alterations in PD, while the anterior part remains unaffected. PD-related decreased FC with posterior right dlPFC was found in the bilateral medial posterior parietal cortex (mPPC) and left dorsal premotor region (PMd) in the OFF state. In the medical ON, FC with left PMd normalized, while decoupling with bilateral mPPC remained. Furthermore, we observed increased FC between posterior right dlPFC and the bilateral dorsomedial prefrontal cortex (dmPFC) in PD in the ON state. Our findings point to differential disturbances of right dlPFC connectivity in PD, which relate to its hierarchical organization of EF processing by stronger affecting the functionally basal posterior aspect than the hierarchically higher anterior part. PMID:28611616

  19. Positional and functional mapping of a neuroblastoma differentiation gene on chromosome 11

    Directory of Open Access Journals (Sweden)

    Bader Scott

    2005-07-01

    Full Text Available Abstract Background Loss of chromosome 11q defines a subset of high-stage aggressive neuroblastomas. Deletions are typically large and mapping efforts have thus far not lead to a well defined consensus region, which hampers the identification of positional candidate tumour suppressor genes. In a previous study, functional evidence for a neuroblastoma suppressor gene on chromosome 11 was obtained through microcell mediated chromosome transfer, indicated by differentiation of neuroblastoma cells with loss of distal 11q upon introduction of chromosome 11. Interestingly, some of these microcell hybrid clones were shown to harbour deletions in the transferred chromosome 11. We decided to further exploit this model system as a means to identify candidate tumour suppressor or differentiation genes located on chromosome 11. Results In a first step, we performed high-resolution arrayCGH DNA copy-number analysis in order to evaluate the chromosome 11 status in the hybrids. Several deletions in both parental and transferred chromosomes in the investigated microcell hybrids were observed. Subsequent correlation of these deletion events with the observed morphological changes lead to the delineation of three putative regions on chromosome 11: 11q25, 11p13->11p15.1 and 11p15.3, that may harbour the responsible differentiation gene. Conclusion Using an available model system, we were able to put forward some candidate regions that may be involved in neuroblastoma. Additional studies will be required to clarify the putative role of the genes located in these chromosomal segments in the observed differentiation phenotype specifically or in neuroblastoma pathogenesis in general.

  20. Identification of new differentially methylated genes that have potential functional consequences in prostate cancer.

    Directory of Open Access Journals (Sweden)

    Jin W Kim

    Full Text Available Many differentially methylated genes have been identified in prostate cancer (PCa, primarily using candidate gene-based assays. Recently, several global DNA methylation profiles have been reported in PCa, however, each of these has weaknesses in terms of ability to observe global DNA methylation alterations in PCa. We hypothesize that there remains unidentified aberrant DNA methylation in PCa, which may be identified using higher resolution assay methods. We used the newly developed Illumina HumanMethylation450 BeadChip in PCa (n = 19 and adjacent normal tissues (n = 4 and combined these with gene expression data for identifying new DNA methylation that may have functional consequences in PCa development and progression. We also confirmed our methylation results in an independent data set. Two aberrant DNA methylation genes were validated among an additional 56 PCa samples and 55 adjacent normal tissues. A total 28,735 CpG sites showed significant differences in DNA methylation (FDR adjusted P<0.05, defined as a mean methylation difference of at least 20% between PCa and normal samples. Furthermore, a total of 122 genes had more than one differentially methylated CpG site in their promoter region and a gene expression pattern that was inverse to the direction of change in DNA methylation (e.g. decreased expression with increased methylation, and vice-versa. Aberrant DNA methylation of two genes, AOX1 and SPON2, were confirmed via bisulfate sequencing, with most of the respective CpG sites showing significant differences between tumor samples and normal tissues. The AOX1 promoter region showed hypermethylation in 92.6% of 54 tested PCa samples in contrast to only three out of 53 tested normal tissues. This study used a new BeadChip combined with gene expression data in PCa to identify novel differentially methylated CpG sites located within genes. The newly identified differentially methylated genes may be used as biomarkers for PCa diagnosis.

  1. Differential Abundance of Microbial Functional Groups along the Elevation Gradient from the Coast to the Luquillo Mountains

    Science.gov (United States)

    Microbial communities respond to multiple abiotic and biotic factors that change along elevation gradients. We compare changes in microbial community composition in soil and review previous research on differential abundance of microbial functional groups along an elevation gradi...

  2. Generalizations on Some Hermite-Hadamard Type Inequalities for Differentiable Convex Functions with Applications to Weighted Means

    Directory of Open Access Journals (Sweden)

    Banyat Sroysang

    2014-01-01

    Full Text Available Some new Hermite-Hadamard type inequalities for differentiable convex functions were presented by Xi and Qi. In this paper, we present new generalizations on the Xi-Qi inequalities.

  3. Effects of Radioiodine Treatment on Salivary Gland Function in Patients with Differentiated Thyroid Carcinoma : A Prospective Study

    NARCIS (Netherlands)

    Klein Hesselink, Esther; Brouwers, Adrienne H.; Jong, de Johan R.; van der Horst-Schrivers, Anouk N. A.; Coppes, Rob P.; Lefrandt, Joop D.; Jager, Piet L.; Vissink, Arjan; Links, Thera P.

    2016-01-01

    Complaints of a dry mouth (xerostomia) and sialoadenitis are frequent side effects of radioiodine treatment in differentiated thyroid cancer (DTC) patients. However, detailed prospective data on alterations in salivary gland functioning after radioiodine treatment (I-131) are scarce. Therefore, the

  4. PPAR agonist-induced reduction of Mcp1 in atherosclerotic plaques of obese, insulin-resistant mice depends on adiponectin-induced Irak3 expression.

    Directory of Open Access Journals (Sweden)

    Maarten Hulsmans

    Full Text Available Synthetic peroxisome proliferator-activated receptor (PPAR agonists are used to treat dyslipidemia and insulin resistance. In this study, we examined molecular mechanisms that explain differential effects of a PPARα agonist (fenofibrate and a PPARγ agonist (rosiglitazone on macrophages during obesity-induced atherogenesis. Twelve-week-old mice with combined leptin and LDL-receptor deficiency (DKO were treated with fenofibrate, rosiglitazone or placebo for 12 weeks. Only rosiglitazone improved adipocyte function, restored insulin sensitivity, and inhibited atherosclerosis by decreasing lipid-loaded macrophages. In addition, it increased interleukin-1 receptor-associated kinase-3 (Irak3 and decreased monocyte chemoattractant protein-1 (Mcp1 expressions, indicative of a switch from M1 to M2 macrophages. The differences between fenofibrate and rosiglitazone were independent of Pparγ expression. In bone marrow-derived macrophages (BMDM, we identified the rosiglitazone-associated increase in adiponectin as cause of the increase in Irak3. Interestingly, the deletion of Irak3 in BMDM (IRAK3(-/- BMDM resulted in activation of the canonical NFκB signaling pathway and increased Mcp1 protein secretion. Rosiglitazone could not decrease the elevated Mcp1 secretion in IRAK3(-/- BMDM directly and fenofibrate even increased the secretion, possibly due to increased mitochondrial reactive oxygen species production. Furthermore, aortic extracts of high-fat insulin-resistant LDL-receptor deficient mice, with lower adiponectin and Irak3 and higher Mcp1, showed accelerated atherosclerosis. In aggregate, our results emphasize an interaction between PPAR agonist-mediated increase in adiponectin and macrophage-associated Irak3 in the protection against atherosclerosis by PPAR agonists.

  5. PPAR Agonist-Induced Reduction of Mcp1 in Atherosclerotic Plaques of Obese, Insulin-Resistant Mice Depends on Adiponectin-Induced Irak3 Expression

    Science.gov (United States)

    Arnould, Thierry; Tsatsanis, Christos; Holvoet, Paul

    2013-01-01

    Synthetic peroxisome proliferator-activated receptor (PPAR) agonists are used to treat dyslipidemia and insulin resistance. In this study, we examined molecular mechanisms that explain differential effects of a PPARα agonist (fenofibrate) and a PPARγ agonist (rosiglitazone) on macrophages during obesity-induced atherogenesis. Twelve-week-old mice with combined leptin and LDL-receptor deficiency (DKO) were treated with fenofibrate, rosiglitazone or placebo for 12 weeks. Only rosiglitazone improved adipocyte function, restored insulin sensitivity, and inhibited atherosclerosis by decreasing lipid-loaded macrophages. In addition, it increased interleukin-1 receptor-associated kinase-3 (Irak3) and decreased monocyte chemoattractant protein-1 (Mcp1) expressions, indicative of a switch from M1 to M2 macrophages. The differences between fenofibrate and rosiglitazone were independent of Pparγ expression. In bone marrow-derived macrophages (BMDM), we identified the rosiglitazone-associated increase in adiponectin as cause of the increase in Irak3. Interestingly, the deletion of Irak3 in BMDM (IRAK3−/− BMDM) resulted in activation of the canonical NFκB signaling pathway and increased Mcp1 protein secretion. Rosiglitazone could not decrease the elevated Mcp1 secretion in IRAK3−/− BMDM directly and fenofibrate even increased the secretion, possibly due to increased mitochondrial reactive oxygen species production. Furthermore, aortic extracts of high-fat insulin-resistant LDL-receptor deficient mice, with lower adiponectin and Irak3 and higher Mcp1, showed accelerated atherosclerosis. In aggregate, our results emphasize an interaction between PPAR agonist-mediated increase in adiponectin and macrophage-associated Irak3 in the protection against atherosclerosis by PPAR agonists. PMID:23620818

  6. The practical impact of differential item functioning analyses in a health-related quality of life instrument

    DEFF Research Database (Denmark)

    Scott, Neil W; Fayers, Peter M; Aaronson, Neil K;

    2009-01-01

    Differential item functioning (DIF) analyses are commonly used to evaluate health-related quality of life (HRQoL) instruments. There is, however, a lack of consensus as to how to assess the practical impact of statistically significant DIF results.......Differential item functioning (DIF) analyses are commonly used to evaluate health-related quality of life (HRQoL) instruments. There is, however, a lack of consensus as to how to assess the practical impact of statistically significant DIF results....

  7. Few items in the thyroid-related quality of life instrument ThyPRO exhibited differential item functioning

    DEFF Research Database (Denmark)

    Watt, Torquil; Grønvold, Mogens; Hegedüs, Laszlo;

    2014-01-01

    To evaluate the extent of differential item functioning (DIF) within the thyroid-specific quality of life patient-reported outcome measure, ThyPRO, according to sex, age, education and thyroid diagnosis.......To evaluate the extent of differential item functioning (DIF) within the thyroid-specific quality of life patient-reported outcome measure, ThyPRO, according to sex, age, education and thyroid diagnosis....

  8. Integral theorems for functions and differential forms in C(m)

    CERN Document Server

    Rocha-Chavez, Reynaldo; Sommen, Frank

    2001-01-01

    The theory of holomorphic functions of several complex variables emerged from the attempt to generalize the theory in one variable to the multidimensional situation. Research in this area has led to the discovery of many sophisticated facts, structures, ideas, relations, and applications. This deepening of knowledge, however, has also revealed more and more paradoxical differences between the structures of the two theories. The authors of this Research Note were driven by the quest to construct a theory in several complex variables that has the same structure as the one-variable theory. That is, they sought a reproducing kernel for the whole class that is universal and from same class. Integral Theorems for Functions and Differential Forms in Cm documents their success. Their highly original approach allowed them to obtain new results and refine some well-known results from the classical theory of several complex variables. The ''hyperholomorphic" theory they developed proved to be a kind of direct sum of fun...

  9. Boundary and initial value problems for second-order neutral functional differential equations

    Directory of Open Access Journals (Sweden)

    Hoan Hoa Le

    2006-05-01

    Full Text Available In this paper, we consider the three-point boundary-value problem for the second order neutral functional differential equation $$ u''+ f(t,u_t, u'(t= 0, quad 0 leq tleq 1, $$ with the three-point boundary condition $u_0= phi$, $u(1 = u(eta$. Under suitable assumptions on the function $f$ we prove the existence, uniqueness and continuous dependence of solutions. As an application of the methods used, we study the existence of solutions for the same equation with a ``mixed" boundary condition $u_0 = phi, u(1 = alpha [u'(eta - u'(0]$, or with an initial condition $ u_0 = phi, u'(0 =0$. For the initial-value problem, the uniqueness and continuous dependence of solutions are also considered. Furthermore, the paper shows that the solution set of the initial-value problem is nonempty, compact and connected. Our approach is based on the fixed point theory.

  10. Biological Sensitivity to Family Income: Differential Effects on Early Executive Functioning.

    Science.gov (United States)

    Obradović, Jelena; Portilla, Ximena A; Ballard, Parissa J

    2016-01-01

    The study examined how the interplay between children's cortisol response and family income is related to executive function (EF) skills. The sample included one hundred and two 5- to 6-year-olds (64% minority). EF skills were measured using laboratory tasks and observer ratings. Physiological reactivity was assessed via cortisol response during a laboratory visit. A consistent, positive association between family income and EF skills emerged only for children who showed high cortisol response, a marker of biological sensitivity to context. In contrast, family income was not related to EF skills in children who displayed low cortisol response. Follow-up analyses revealed a disordinal interaction, suggesting that differential susceptibility can be detected at the level of basic cognitive and self-regulatory skills that support adaptive functioning.

  11. Diverse Functions of VDUP1 in Cell Proliferation, Differentiation, and Diseases

    Institute of Scientific and Technical Information of China (English)

    Sang Yong Kim; Hyun-Woo Suh; Jin Woong Chung; Suk-Ran Yoon; Inpyo Choi

    2007-01-01

    Vitamin D3 up-regulated protein 1 (VDUP1) is a multifunctional protein involved in maintaining cellular homeostasis. VDUP1 is induced by a variety of stresses. Inversely, VDUP1 is often reduced in various tumor tissues and cell lines. Over-expression of VDUP1 inhibits cell proliferation through cell cycle arrest. VDUP1 interacts with thioredoxin (Trx) and negatively regulates the expression and antioxidant function of Trx which is involved in redox regulation. VDUP1-/- mice are more susceptible to carcinogenesis than wild-type mice and are defective in establishing immune system including the development and function of natural killer cells. Furthermore, VDUP1-/-mice show impaired Kreb cycle-mediated fatty acid utilization. In this review, we have discussed the multifunctional roles of VDUP1 in diverse cellular responses, in particular its relation to proliferation, apoptosis,differentiation, and diseases such as cancer and stress-related diseases.

  12. Differential Hydrological Grey Model (DHGM) with self-memory function and its application to flood forecasting

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    This paper addresses a problem of flood forecasting with the self-memory function. Considering flood forecasting’s uncertainty and updating demand, a hybrid hydrological model, namely Differential Hy- drological Grey Model with self-memory function (DHGM-SM), is developed. The model has two fold features. One is to establish a self-memorization equation linked with DHGM, that could extract useful information from past data series and realize updating of hydrological dynamic process. The other is that this model has higher efficiency relative to original hydrological model without self-memory func- tion. This approach was applied to river flow forecasting of two representative basins in Tunxi of South China and Daqinggou of North China. It is shown that this hybrid method has satisfactory forecasting accuracy by examination of both calibration and validation.

  13. Retinoblastoma protein functions as a molecular switch determining white versus brown adipocyte differentiation

    DEFF Research Database (Denmark)

    Hansen, Jacob B; Jørgensen, Claus; Petersen, Rasmus K

    2004-01-01

    Adipocyte precursor cells give raise to two major cell populations with different physiological roles: white and brown adipocytes. Here we demonstrate that the retinoblastoma protein (pRB) regulates white vs. brown adipocyte differentiation. Functional inactivation of pRB in wild-type mouse embryo...... into adipocytes with a gene expression pattern and mitochondria content resembling brown adipose tissue. pRB-deficient MEFs exhibit an increased expression of the Forkhead transcription factor Foxc2 and its target gene cAMP-dependent protein kinase regulatory subunit RIalpha, resulting in increased c...... transdifferentiation of white into brown adipocytes in response to beta3-adrenergic receptor agonist treatment. We propose that pRB acts as a molecular switch determining white vs. brown adipogenesis, suggesting a previously uncharacterized function of this key cell cycle regulator in adipocyte lineage commitment...

  14. The Positive Properties of Green’s Function for Fractional Differential Equations and Its Applications

    Directory of Open Access Journals (Sweden)

    Fuquan Jiang

    2013-01-01

    Full Text Available We consider the properties of Green’s function for the nonlinear fractional differential equation boundary value problem: D0+αu(t+f(t,u(t+e(t=0,0function, we give some multiple positive solutions for singular boundary value problems by means of Schauder fixed-point theorem.

  15. Substance use disorder symptoms: evidence of differential item functioning by age.

    Science.gov (United States)

    Conrad, Kendon J; Dennis, Michael L; Bezruczko, Nikolaus; Funk, Rodney R; Riley, Barth B

    2007-01-01

    This study examined the applicability of substance abuse diagnostic criteria for adolescents, young adults, and adults using the Global Appraisal of Individual Need's Substance Problems Scale (SPS) from 7,408 clients. Rasch analysis was used to: 1) evaluate whether the SPS operationalized a single reliable dimension, and 2) examine the extent to which the severity of each symptom and the overall test functioned the same or differently by age. Rasch analysis indicated that the SPS was unidimensional with a person reliability of .84. Eight symptoms were significantly different between adolescents and adults. Young adult calibrations tended to fall between adolescents and adults. Differential test functioning was clinically negligible for adolescents but resulted in about 7% more adults being classified as high need. These findings have theoretical implications for screening and treatment of adolescents vs. adults. SPS can be used across age groups though age-specific calibrations enable greater precision of measurement.

  16. Differential role of SLP-76 domains in T cell development and function.

    Science.gov (United States)

    Kumar, Lalit; Pivniouk, Vadim; de la Fuente, Miguel A; Laouini, Dhafer; Geha, Raif S

    2002-01-22

    The adapter SLP-76 is essential for thymocyte development. SLP-76(-/-) mice were reconstituted with SLP-76 deletion mutant transgenes to examine the role of SLP-76 domains in T cell development and function. The N-terminal domain deletion mutant completely failed to restore thymocyte development. Mice reconstituted with Gads-binding site and SH2 domain deletion mutants had decreased thymic cellularity, impaired transition from double to single positive thymocytes, and decreased numbers of mature T cells in the spleen. Calcium mobilization and extracellular signal-regulated protein kinase activation were decreased in the Gads-binding site mutant but almost normal in the SH2 domain mutant. T cells from both mutants failed to proliferate following T cell antigen receptor ligation. Nevertheless, both mutants mounted partial cutaneous hypersensitivity responses and normal T cell dependent IgG1 antibody responses. These results indicate differential roles for SLP-76 domains in T cell development, proliferation and effector functions.

  17. Exponential Stability of Neutral Stochastic Functional Differential Equations with Two-Time-Scale Markovian Switching

    Directory of Open Access Journals (Sweden)

    Junhao Hu

    2014-01-01

    Full Text Available We develop exponential stability of neutral stochastic functional differential equations with two-time-scale Markovian switching modeled by a continuous-time Markov chain which has a large state space. To overcome the computational effort and the complexity, we split the large-scale system into several classes and lump the states in each class into one class by the different states of changes of the subsystems; then, we give a limit system to effectively “replace” the large-scale system. Under suitable conditions, using the stability of the limit system as a bridge, the desired asymptotic properties of the large-scale system with Brownian motion and Poisson jump are obtained by utilizing perturbed Lyapunov function methods and Razumikhin-type criteria. Two examples are provided to demonstrate our results.

  18. Inhibition of differentiation and function of osteoclasts by dimethyl sulfoxide (DMSO).

    Science.gov (United States)

    Yang, Chunxi; Madhu, Vedavathi; Thomas, Candace; Yang, Xinlin; Du, Xeujun; Dighe, Abhijit S; Cui, Quanjun

    2015-12-01

    Dimethyl sulfoxide (DMSO) is an FDA-approved organosulfur solvent that is reported to have therapeutic value in osteoarthritis and osteopenia. DMSO is used as a cryoprotectant for the cryopreservation of bone grafts and mesenchymal stem cells which are later used for bone repair. It is also used as a solvent in the preparation of various scaffolds used for bone tissue engineering purposes. DMSO has been reported to inhibit osteoclast formation in vitro but the mechanism involved has remained elusive. We investigated the effect of DMSO on osteoclast differentiation and function using a conventional model system of RAW 264.7 cells. The differentiation of RAW 264.7 cells was induced by adding 50 ng/ml RANKL and the effect of DMSO (0.01 and 1% v/v) on RANKL-induced osteoclastogenesis was investigated. Addition of 1% DMSO significantly inhibited RANKL-induced formation of TRAP+, multinucleated, mature osteoclasts and osteoclast late-stage precursors (c-Kit(-) c-Fms(+) Mac-1(+) RANK(+)). While DMSO did not inhibit proliferation per se, it did inhibit the effect of RANKL on proliferation of RAW 264.7 cells. Key genes related to osteoclast function (TRAP, Integrin αVβ3, Cathepsin K and MMP9) were significantly down-regulated by DMSO. RANKL-induced expression of RANK gene was significantly reduced in the presence of DMSO. Our data, and reports from other investigators, that DMSO enhances osteoblastic differentiation of mesenchymal stem cells and also prevents bone loss in ovarietcomized rats, suggest that DMSO has tremendous potential in the treatment of osteoporosis and bone diseases arising from uncontrolled activities of the osteoclasts.

  19. A canonical system of differential equations arising from the Riemann zeta-function

    CERN Document Server

    Suzuki, Masatoshi

    2012-01-01

    This paper has two main results, which relate to a criteria for the Riemann hypothesis via the family of functions $\\Theta_\\omega(z)=\\xi(1/2-\\omega-iz)/\\xi(1/2+\\omega-iz)$, where $\\omega>0$ is a real parameter and $\\xi(s)$ is the Riemann xi-function. The first main result is necessary and sufficient conditions for $\\Theta_\\omega$ to be a meromorphic inner function in the upper half-plane. It is related to the Riemann hypothesis directly whether $\\Theta_\\omega$ is a meromorphic inner function. In comparison with this, a relation of the Riemann hypothesis and the second main result is indirect. It relates to the theory of de Branges, which associates a meromorphic inner function and a canonical system of linear differential equations (in the sense of de Branges). As the second main result, the canonical system associated with $\\Theta_\\omega$ is constructed explicitly and unconditionally under the restriction of the parameter $\\omega >1$ by applying a method of J.-F. Burnol in his recent work on the gamma functi...

  20. The tumor suppressors pRB and p53 as regulators of adipocyte differentiation and function

    DEFF Research Database (Denmark)

    Hallenborg, Philip; Feddersen, Søren; Madsen, Lise

    2009-01-01

    BACKGROUND: The retinoblastoma protein (pRB) and p53 are crucial members of regulatory networks controlling the cell cycle and apoptosis, and a hallmark of virtually all cancers is dysregulation of expression or function of pRB or p53. Although they are best known for their role in cancer develop...... of energy metabolism and homeostasis. RESULTS/CONCLUSIONS: pRB is required for adipose conversion and also involved in determining its mitochondrial capacity. p53 inhibits adipogenesis and results suggest that it is involved in maintaining function of adipose tissue.......BACKGROUND: The retinoblastoma protein (pRB) and p53 are crucial members of regulatory networks controlling the cell cycle and apoptosis, and a hallmark of virtually all cancers is dysregulation of expression or function of pRB or p53. Although they are best known for their role in cancer...... development, it is now evident that both are implicated in metabolism and cellular development. OBJECTIVE/METHODS: To review the role of pRB and p53 in adipocyte differentiation and function emphasizing that pRB and p53, via their effects on adipocyte development and function, play a role in the regulation...

  1. Cryptic diversity and ecosystem functioning: a complex tale of differential effects on decomposition.

    Science.gov (United States)

    De Meester, N; Gingold, R; Rigaux, A; Derycke, S; Moens, T

    2016-10-01

    Marine ecosystems are experiencing accelerating population and species loss. Some ecosystem functions are decreasing and there is growing interest in the link between biodiversity and ecosystem functioning. The role of cryptic (morphologically identical but genetically distinct) species in this biodiversity-ecosystem functioning link is unclear and has not yet been formally tested. We tested if there is a differential effect of four cryptic species of the bacterivorous nematode Litoditis marina on the decomposition process of macroalgae. Bacterivorous nematodes can stimulate or slow down bacterial activity and modify the bacterial assemblage composition. Moreover, we tested if interspecific interactions among the four cryptic species influence the decomposition process. A laboratory experiment with both mono- and multispecific nematode cultures was conducted, and loss of organic matter and the activity of two key extracellular enzymes for the degradation of phytodetritus were assessed. L. marina mainly influenced qualitative aspects of the decomposition process rather than its overall rate: an effect of the nematodes on the enzymatic activities became manifest, although no clear nematode effect on bulk organic matter weight loss was found. We also demonstrated that species-specific effects on the decomposition process existed. Combining the four cryptic species resulted in high competition, with one dominant species, but without complete exclusion of other species. These interspecific interactions translated into different effects on the decomposition process. The species-specific differences indicated that each cryptic species may play an important and distinct role in ecosystem functioning. Functional differences may result in coexistence among very similar species.

  2. Role of Ets Proteins in Development, Differentiation, and Function of T-Cell Subsets.

    Science.gov (United States)

    Liu, Mian; Gao, Weiwu; van Velkinburgh, Jennifer C; Wu, Yuzhang; Ni, Bing; Tian, Yi

    2016-03-01

    Through positive selection, double-positive cells in the thymus differentiate into CD4(+) or CD8(+) T single-positive cells that subsequently develop into different types of effective T cells, such as T-helper and cytotoxic T lymphocyte cells, that play distinctive roles in the immune system. Development, differentiation, and function of thymocytes and CD4(+) and CD8(+) T cells are controlled by a multitude of secreted and intracellular factors, ranging from cytokine signaling modules to transcription factors and epigenetic modifiers. Members of the E26 transformation specific (Ets) family of transcription factors, in particular, are potent regulators of these CD4(+) or CD8(+) T-cell processes. In this review, we summarize and discuss the functions and underlying mechanisms of the Ets family members that have been characterized as involved in these processes. Ongoing research of these factors is expected to identify practical applications for the Ets family members as novel therapeutic targets for inflammation-related diseases. © 2015 Wiley Periodicals, Inc.

  3. An analysis of differential item functioning by gender in the Learning Disability Screening Questionnaire (LDSQ).

    Science.gov (United States)

    Murray, Aja Louise; Booth, Tom; McKenzie, Karen

    2015-04-01

    The Learning Disability Screening Questionnaire (LDSQ; McKenzie & Paxton, 2006) was developed as a brief screen for intellectual disability. Although several previous studies have evaluated the LDSQ with respect to its utility as a clinical and research tool, no studies have considered the fairness of the test across males and females. In the current study we, therefore, used a multi-group item response theory approach to assess differential item functioning across gender in a sample of 211 males and 132 females assessed in clinical and forensic settings. Although the test did not show evidence of differential item functioning by gender, it was necessary to exclude one item due to estimation problems and to combine two very highly related items (concerning reading and writing ability) into a single literacy item Thus, in addition to being generally supportive of the utility of the LDSQ, our results also highlight possible areas of weakness in the tool and suggest possible amendments that could be made to test content to improve the test in future revisions. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Suppression of Sin3A activity promotes differentiation of pluripotent cells into functional neurons

    Science.gov (United States)

    Halder, Debasish; Lee, Chang-Hee; Hyun, Ji Young; Chang, Gyeong-Eon; Cheong, Eunji; Shin, Injae

    2017-01-01

    Sin3 is a transcriptional corepressor for REST silencing machinery that represses multiple neuronal genes in non-neuronal cells. However, functions of Sin3 (Sin3A and Sin3B) in suppression of neuronal phenotypes are not well characterized. Herein we show that Sin3A knockdown impedes the repressive activity of REST and enhances differentiation of pluripotent P19 cells into electrophysiologically active neurons without inducing astrogenesis. It is also found that silencing Sin3B induces neurogenesis of P19 cells with a lower efficiency than Sin3A knockdown. The results suggest that Sin3A has a more profound effect on REST repressive machinery for silencing neuronal genes in P19 cells than Sin3B. Furthermore, we show that a peptide inhibitor of Sin3A-REST interactions promotes differentiation of P19 cells into functional neurons. Observations made in studies using genetic deletion and a synthetic inhibitor suggests that Sin3A plays an important role in the repression of neuronal genes by the REST regulatory mechanism. PMID:28303954

  5. A Nanoscale Interface Promoting Molecular and Functional Differentiation of Neural Cells

    Science.gov (United States)

    Posati, Tamara; Pistone, Assunta; Saracino, Emanuela; Formaggio, Francesco; Mola, Maria Grazia; Troni, Elisabetta; Sagnella, Anna; Nocchetti, Morena; Barbalinardo, Marianna; Valle, Francesco; Bonetti, Simone; Caprini, Marco; Nicchia, Grazia Paola; Zamboni, Roberto; Muccini, Michele; Benfenati, Valentina

    2016-01-01

    Potassium channels and aquaporins expressed by astrocytes are key players in the maintenance of cerebral homeostasis and in brain pathophysiologies. One major challenge in the study of astrocyte membrane channels in vitro, is that their expression pattern does not resemble the one observed in vivo. Nanostructured interfaces represent a significant resource to control the cellular behaviour and functionalities at micro and nanoscale as well as to generate novel and more reliable models to study astrocytes in vitro. However, the potential of nanotechnologies in the manipulation of astrocytes ion channels and aquaporins has never been previously reported. Hydrotalcite-like compounds (HTlc) are layered materials with increasing potential as biocompatible nanoscale interface. Here, we evaluate the effect of the interaction of HTlc nanoparticles films with primary rat neocortical astrocytes. We show that HTlc films are biocompatible and do not promote gliotic reaction, while favouring astrocytes differentiation by induction of F-actin fibre alignment and vinculin polarization. Western Blot, Immunofluorescence and patch-clamp revealed that differentiation was accompanied by molecular and functional up-regulation of both inward rectifying potassium channel Kir 4.1 and aquaporin 4, AQP4. The reported results pave the way to engineering novel in vitro models to study astrocytes in a in vivo like condition. PMID:27503424

  6. A Nanoscale Interface Promoting Molecular and Functional Differentiation of Neural Cells

    Science.gov (United States)

    Posati, Tamara; Pistone, Assunta; Saracino, Emanuela; Formaggio, Francesco; Mola, Maria Grazia; Troni, Elisabetta; Sagnella, Anna; Nocchetti, Morena; Barbalinardo, Marianna; Valle, Francesco; Bonetti, Simone; Caprini, Marco; Nicchia, Grazia Paola; Zamboni, Roberto; Muccini, Michele; Benfenati, Valentina

    2016-08-01

    Potassium channels and aquaporins expressed by astrocytes are key players in the maintenance of cerebral homeostasis and in brain pathophysiologies. One major challenge in the study of astrocyte membrane channels in vitro, is that their expression pattern does not resemble the one observed in vivo. Nanostructured interfaces represent a significant resource to control the cellular behaviour and functionalities at micro and nanoscale as well as to generate novel and more reliable models to study astrocytes in vitro. However, the potential of nanotechnologies in the manipulation of astrocytes ion channels and aquaporins has never been previously reported. Hydrotalcite-like compounds (HTlc) are layered materials with increasing potential as biocompatible nanoscale interface. Here, we evaluate the effect of the interaction of HTlc nanoparticles films with primary rat neocortical astrocytes. We show that HTlc films are biocompatible and do not promote gliotic reaction, while favouring astrocytes differentiation by induction of F-actin fibre alignment and vinculin polarization. Western Blot, Immunofluorescence and patch-clamp revealed that differentiation was accompanied by molecular and functional up-regulation of both inward rectifying potassium channel Kir 4.1 and aquaporin 4, AQP4. The reported results pave the way to engineering novel in vitro models to study astrocytes in a in vivo like condition.

  7. Structural and Mutational Analysis of Functional Differentiation between Synaptotagmins-1 and -7

    Energy Technology Data Exchange (ETDEWEB)

    Xue, Mingshan; Craig, Timothy K.; Shin, Ok-Ho; Li, Liyi; Brautigam, Chad A.; Tomchick, Diana R.; Südhof, Thomas C.; Rosenmund, Christian; Rizo, Josep (Baylor); (UTSMC); (Texas)

    2012-01-20

    Synaptotagmins are known to mediate diverse forms of Ca{sup 2+}-triggered exocytosis through their C{sub 2} domains, but the principles underlying functional differentiation among them are unclear. Synaptotagmin-1 functions as a Ca{sup 2+} sensor in neurotransmitter release at central nervous system synapses, but synaptotagmin-7 does not, and yet both isoforms act as Ca{sup 2+} sensors in chromaffin cells. To shed light into this apparent paradox, we have performed rescue experiments in neurons from synaptotagmin-1 knockout mice using a chimera that contains the synaptotagmin-1 sequence with its C{sub 2}B domain replaced by the synaptotagmin-7 C{sub 2}B domain (Syt1/7). Rescue was not achieved either with the WT Syt1/7 chimera or with nine mutants where residues that are distinct in synaptotagmin-7 were restored to those present in synaptotagmin-1. To investigate whether these results arise because of unique conformational features of the synaptotagmin-7 C{sub 2}B domain, we determined its crystal structure at 1.44 {angstrom} resolution. The synaptotagmin-7 C{sub 2}B domain structure is very similar to that of the synaptotagmin-1 C{sub 2}B domain and contains three Ca{sup 2+}-binding sites. Two of the Ca{sup 2+}-binding sites of the synaptotagmin-7 C{sub 2}B domain are also present in the synaptotagmin-1 C{sub 2}B domain and have analogous ligands to those determined for the latter by NMR spectroscopy, suggesting that a discrepancy observed in a crystal structure of the synaptotagmin-1 C{sub 2}B domain arose from crystal contacts. Overall, our results suggest that functional differentiation in synaptotagmins arises in part from subtle sequence changes that yield dramatic functional differences.

  8. Structural and mutational analysis of functional differentiation between synaptotagmins-1 and -7.

    Directory of Open Access Journals (Sweden)

    Mingshan Xue

    Full Text Available Synaptotagmins are known to mediate diverse forms of Ca2+-triggered exocytosis through their C2 domains, but the principles underlying functional differentiation among them are unclear. Synaptotagmin-1 functions as a Ca2+ sensor in neurotransmitter release at central nervous system synapses, but synaptotagmin-7 does not, and yet both isoforms act as Ca2+ sensors in chromaffin cells. To shed light into this apparent paradox, we have performed rescue experiments in neurons from synaptotagmin-1 knockout mice using a chimera that contains the synaptotagmin-1 sequence with its C2B domain replaced by the synaptotagmin-7 C2B domain (Syt1/7. Rescue was not achieved either with the WT Syt1/7 chimera or with nine mutants where residues that are distinct in synaptotagmin-7 were restored to those present in synaptotagmin-1. To investigate whether these results arise because of unique conformational features of the synaptotagmin-7 C2B domain, we determined its crystal structure at 1.44 A resolution. The synaptotagmin-7 C2B domain structure is very similar to that of the synaptotagmin-1 C2B domain and contains three Ca2+-binding sites. Two of the Ca2+-binding sites of the synaptotagmin-7 C2B domain are also present in the synaptotagmin-1 C2B domain and have analogous ligands to those determined for the latter by NMR spectroscopy, suggesting that a discrepancy observed in a crystal structure of the synaptotagmin-1 C2B domain arose from crystal contacts. Overall, our results suggest that functional differentiation in synaptotagmins arises in part from subtle sequence changes that yield dramatic functional differences.

  9. Holistic systems biology approaches to molecular mechanisms of human helper T cell differentiation to functionally distinct subsets.

    Science.gov (United States)

    Chen, Z; Lönnberg, T; Lahesmaa, R

    2013-08-01

    Current knowledge of helper T cell differentiation largely relies on data generated from mouse studies. To develop therapeutical strategies combating human diseases, understanding the molecular mechanisms how human naïve T cells differentiate to functionally distinct T helper (Th) subsets as well as studies on human differentiated Th cell subsets is particularly valuable. Systems biology approaches provide a holistic view of the processes of T helper differentiation, enable discovery of new factors and pathways involved and generation of new hypotheses to be tested to improve our understanding of human Th cell differentiation and immune-mediated diseases. Here, we summarize studies where high-throughput systems biology approaches have been exploited to human primary T cells. These studies reveal new factors and signalling pathways influencing T cell differentiation towards distinct subsets, important for immune regulation. Such information provides new insights into T cell biology and into targeting immune system for therapeutic interventions.

  10. Increased mitochondrial function downstream from KDM5A histone demethylase rescues differentiation in pRB-deficient cells.

    Science.gov (United States)

    Váraljai, Renáta; Islam, Abul B M M K; Beshiri, Michael L; Rehman, Jalees; Lopez-Bigas, Nuria; Benevolenskaya, Elizaveta V

    2015-09-01

    The retinoblastoma tumor suppressor protein pRb restricts cell growth through inhibition of cell cycle progression. Increasing evidence suggests that pRb also promotes differentiation, but the mechanisms are poorly understood, and the key question remains as to how differentiation in tumor cells can be enhanced in order to diminish their aggressive potential. Previously, we identified the histone demethylase KDM5A (lysine [K]-specific demethylase 5A), which demethylates histone H3 on Lys4 (H3K4), as a pRB-interacting protein counteracting pRB's role in promoting differentiation. Here we show that loss of Kdm5a restores differentiation through increasing mitochondrial respiration. This metabolic effect is both necessary and sufficient to induce the expression of a network of cell type-specific signaling and structural genes. Importantly, the regulatory functions of pRB in the cell cycle and differentiation are distinct because although restoring differentiation requires intact mitochondrial function, it does not necessitate cell cycle exit. Cells lacking Rb1 exhibit defective mitochondria and decreased oxygen consumption. Kdm5a is a direct repressor of metabolic regulatory genes, thus explaining the compensatory role of Kdm5a deletion in restoring mitochondrial function and differentiation. Significantly, activation of mitochondrial function by the mitochondrial biogenesis regulator Pgc-1α (peroxisome proliferator-activated receptor γ-coactivator 1α; also called PPARGC1A) a coactivator of the Kdm5a target genes, is sufficient to override the differentiation block. Overexpression of Pgc-1α, like KDM5A deletion, inhibits cell growth in RB-negative human cancer cell lines. The rescue of differentiation by loss of KDM5A or by activation of mitochondrial biogenesis reveals the switch to oxidative phosphorylation as an essential step in restoring differentiation and a less aggressive cancer phenotype.

  11. Differential Item and Person Functioning in Large-Scale Writing Assessments within the Context of the SAT®. Research Report 2013-6

    Science.gov (United States)

    Engelhard, George, Jr.; Wind, Stefanie A.; Kobrin, Jennifer L.; Chajewski, Michael

    2013-01-01

    The purpose of this study is to illustrate the use of explanatory models based on Rasch measurement theory to detect systematic relationships between student and item characteristics and achievement differences using differential item functioning (DIF), differential group functioning (DGF), and differential person functioning (DPF) techniques. The…

  12. Initial function analysis of a novel erythroid differentiation related gene EDRF1

    Institute of Scientific and Technical Information of China (English)

    WANG; Duncheng(

    2001-01-01

    [1]Migliaccio, A. R, Vannucchi, A. M., Migliaccio, G., Molecular control of erythroid differentiation, International Journal of Hematology, 1996, 64(1): 1-29.[2]Migliaccio, A. R., Migliaccio, G., The making of an erythroid cell, Biotherapy, 1998, 10(2): 251-268.[3]Higgs, D. R., Sharpe, J. A., Wood, W. G., Understanding α-globin gene expression a step towards effective gene therapy,Seminars in Hematology, 1998, 35(1): 93-104.[4]Crosstey, M., Merika, M., Orkin, S. H., Self-association of the erythroid transcription factor GATA-1 mediated by its zinc finger domains, Mol. Cell Biol., 1992, 15: 2448-2456.[5]Wang. X., Chen, S. P., Xue, S. R, Preparation and determination of monoclonal antibodies against the proteins related to erythroid differentiation, Acta Anatomica Sinica, 1997, 28(2): 187-191.[6]Wang. X., Liu, P. X., Zhang, J. B. et al., Appearance of some novel proteins binding enhancer element of globin genes (HS2) during erythroid terminal differentiation, Acta Anatomica Sinica, 1994, 25(4): 379-384.[7]Wang. X.. Wang, D. C., Chen, X. et al., cDNA cloning and function analysis of two novel erythroid differentiation related genes. Science in China, Ser. C, 2001, 44(1): 99-105.[8]Wu, H., Liu, X.. Jaenisch, R. et al., Generation of committed erythroid BFU-E and CFR-E progenitors does not require erythropoietin or the erythropoietin receptor, Cell, 1995, 83 (1): 59-64.[9]Partington, G. A., Patient, R. K., Phosphorylation of GATA-1 increases its DNA-binding affinity and is correlated with induction of human K562 erythroleukaemia cells, Nucleic Acids Res., 1999, 27(4): 1168-1175.[10].Canelles, M., Delgado, M. D., Hyland, K. M. et al., Max and inhibitory c-Myc mutants induce erythroid differentiation and resistance to apoptosis in human myeloid leukemia cells, Oncogene, 1997, 14(11): 1315- 1127.Acknowledgements This work was supported by National High Technology Programs of China (Grant No.102-08-01-03) and Natural Science Fund

  13. Aberrant functional connectivity differentiates retrosplenial cortex from posterior cingulate cortex in prodromal Alzheimer's disease.

    Science.gov (United States)

    Dillen, Kim N H; Jacobs, Heidi I L; Kukolja, Juraj; von Reutern, Boris; Richter, Nils; Onur, Özgür A; Dronse, Julian; Langen, Karl-Josef; Fink, Gereon R

    2016-08-01

    The posterior cingulate cortex (PCC) is a key hub of the default mode network, a resting-state network involved in episodic memory, showing functional connectivity (FC) changes in Alzheimer's disease (AD). However, PCC is a cytoarchitectonically heterogeneous region. Specifically, the retrosplenial cortex (RSC), often subsumed under the PCC, is an area functionally and microanatomically distinct from PCC. To investigate FC patterns of RSC and PCC separately, we used resting-state functional magnetic resonance imaging in healthy aging participants, patients with subjective cognitive impairment, and prodromal AD. Compared to the other 2 groups, we found higher FC from RSC to frontal cortex in subjective cognitive impairment but higher FC to occipital cortex in prodromal AD. Conversely, FC from PCC to the lingual gyrus was higher in prodromal AD. Furthermore, data indicate that RSC and PCC are characterized by differential FC patterns represented by hub-specific interactions with memory and attentions scores in prodromal AD compared to cognitively normal individuals, possibly reflecting compensatory mechanisms for RSC and neurodegenerative processes for PCC. Data thus confirm and extend previous studies suggesting that the RSC is functionally distinct from PCC.

  14. Application of functional analysis to perturbation theory of differential equations. [nonlinear perturbation of the harmonic oscillator

    Science.gov (United States)

    Bogdan, V. M.; Bond, V. B.

    1980-01-01

    The deviation of the solution of the differential equation y' = f(t, y), y(O) = y sub O from the solution of the perturbed system z' = f(t, z) + g(t, z), z(O) = z sub O was investigated for the case where f and g are continuous functions on I x R sup n into R sup n, where I = (o, a) or I = (o, infinity). These functions are assumed to satisfy the Lipschitz condition in the variable z. The space Lip(I) of all such functions with suitable norms forms a Banach space. By introducing a suitable norm in the space of continuous functions C(I), introducing the problem can be reduced to an equivalent problem in terminology of operators in such spaces. A theorem on existence and uniqueness of the solution is presented by means of Banach space technique. Norm estimates on the rate of growth of such solutions are found. As a consequence, estimates of deviation of a solution due to perturbation are obtained. Continuity of the solution on the initial data and on the perturbation is established. A nonlinear perturbation of the harmonic oscillator is considered a perturbation of equations of the restricted three body problem linearized at libration point.

  15. Memory functioning and negative symptoms as differential predictors of social problem solving skills in schizophrenia.

    Science.gov (United States)

    Ventura, Joseph; Tom, Shelley R; Jetton, Chris; Kern, Robert S

    2013-02-01

    Neurocognition in general, and memory functioning in particular, as well as symptoms have all been shown to be related to social problem solving (SPS) in schizophrenia. However, few studies have directly compared the relative contribution of neurocognition vs. psychiatric symptoms to the components of SPS. Sixty outpatients (aged 21-65) who met DSM-IV criteria for schizophrenia or schizoaffective disorder were administered a broad battery of memory tests and assessed for severity of positive and negative symptoms as part of a baseline assessment of a study of psychiatric rehabilitation. Multiple regression analyses were used to examine the contribution of memory functioning vs. symptoms on receiving, processing, and sending skill areas of social problem solving ability. An index of verbal learning was the strongest predictor of processing skills whereas negative symptoms were the strongest predictor of sending skills. Positive symptoms were not related to any of the three skill areas of social problem solving. Memory functioning and psychiatric symptoms differentially predict selected areas of social problem solving ability in persons with schizophrenia. Consistent with other reports, positive symptoms were not related to social problem solving. Consideration of both neurocognition and negative symptoms may be important to the development of rehabilitation interventions in this area of functioning. Copyright © 2012 Elsevier B.V. All rights reserved.

  16. Differential effects of childhood trauma subtypes on fatigue and physical functioning in chronic fatigue syndrome.

    Science.gov (United States)

    De Venter, Maud; Illegems, Jela; Van Royen, Rita; Moorkens, Greta; Sabbe, Bernard G C; Van Den Eede, Filip

    2017-07-19

    There is wide consensus that childhood trauma plays an important role in the aetiology of chronic fatigue syndrome (CFS). The current study examines the differential effects of childhood trauma subtypes on fatigue and physical functioning in individuals suffering from CFS. Participants were 155 well-documented adult, predominantly female CFS patients receiving treatment at the outpatient treatment centre for CFS of the Antwerp University Hospital in Belgium. Stepwise regression analyses were conducted with outcomes of the total score of the Checklist Individual Strength (CIS) measuring fatigue and the scores on the physical functioning subscale of the Medical Outcomes Short Form 36 Health Status Survey (SF-36) as the dependent variables, and the scores on the five subscales of the Traumatic Experiences Checklist (TEC) as the independent variables. The patients' fatigue (β=1.38; p=0.025) and physical functioning scores (β=-1.79; p=0.034) were significantly predicted by childhood sexual harassment. There were no significant effects of emotional neglect, emotional abuse, bodily threat, or sexual abuse during childhood. Of the childhood trauma subtypes investigated, sexual harassment emerged as the most important predictor of fatigue and poor physical functioning in the CFS patients assessed. These findings have to be taken into account in further clinical research and in the assessment and treatment of individuals coping with chronic fatigue syndrome. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Differential sensitivity of cranial and limb motor function to nigrostriatal dopamine depletion.

    Science.gov (United States)

    Plowman, Emily K; Maling, Nicholas; Rivera, Benjamin J; Larson, Krista; Thomas, Nagheme J; Fowler, Stephen C; Manfredsson, Fredric P; Shrivastav, Rahul; Kleim, Jeffrey A

    2013-01-15

    The present study determined the differential effects of unilateral striatal dopamine depletion on cranial motor versus limb motor function. Forty male Long Evans rats were first trained on a comprehensive motor testing battery that dissociated cranial versus limb motor function and included: cylinder forepaw placement, single pellet reaching, vermicelli pasta handling; sunflower seed opening, pasta biting acoustics, and a licking task. Following baseline testing, animals were randomized to either a 6-hydroxydopamine (6-OHDA) (n=20) or control (n=20) group. Animals in the 6-OHDA group received unilateral intrastriatal 6-OHDA infusions to induce striatal dopamine depletion. Six-weeks following infusion, all animals were re-tested on the same battery of motor tests. Near infrared densitometry was performed on sections taken through the striatum that were immunohistochemically stained for tyrosine hydroxylase (TH). Animals in the 6-OHDA condition showed a mean reduction in TH staining of 88.27%. Although 6-OHDA animals were significantly impaired on all motor tasks, limb motor deficits were more severe than cranial motor impairments. Further, performance on limb motor tasks was correlated with degree of TH depletion while performance on cranial motor impairments showed no significant correlation. These results suggest that limb motor function may be more sensitive to striatal dopaminergic depletion than cranial motor function and is consistent with the clinical observation that therapies targeting the nigrostriatal dopaminergic system in Parkinson's disease are more effective for limb motor symptoms than cranial motor impairments. Published by Elsevier B.V.

  18. Enhanced Stem Cell Osteogenic Differentiation by Bioactive Glass Functionalized Graphene Oxide Substrates

    Directory of Open Access Journals (Sweden)

    Xiaoju Mo

    2016-01-01

    Full Text Available An unmet need in engineered bone regeneration is to develop scaffolds capable of manipulating stem cells osteogenesis. Graphene oxide (GO has been widely used as a biomaterial for various biomedical applications. However, it remains challenging to functionalize GO as ideal platform for specifically directing stem cell osteogenesis. Herein, we report facile functionalization of GO with dopamine and subsequent bioactive glass (BG to enhance stem cell adhesion, spreading, and osteogenic differentiation. On the basis of graphene, we obtained dopamine functionalized graphene oxide/bioactive glass (DGO/BG hybrid scaffolds containing different content of DGO by loading BG nanoparticles on graphene oxide surface using sol-gel method. To enhance the dispersion stability and facilitate subsequent nucleation of BG in GO, firstly, dopamine (DA was used to modify GO. Then, the modified GO was functionalized with bioactive glass (BG using sol-gel method. The adhesion, spreading, and osteoinductive effects of DGO/BG scaffold on rat bone marrow mesenchymal stem cells (rBMSCs were evaluated. DGO/BG hybrid scaffolds with different content of DGO could influence rBMSCs’ behavior. The highest expression level of osteogenic markers suggests that the DGO/BG hybrid scaffolds have great potential or elicit desired bone reparative outcome.

  19. Ethnic differential item functioning in the assessment of quality of life in cancer patients

    Directory of Open Access Journals (Sweden)

    Gotay Carolyn C

    2005-10-01

    Full Text Available Abstract Background Past research has shown that Filipino cancer patients report lower levels of quality of life (QoL than other ethnic groups. One possible explanation for this is that Filipinos do not define QoL in the same manner as others, resulting in bias in their assessments. Hence, Filipinos would not necessarily have lower QoL. Methods Item response theory methods were used to assess differential item functioning (DIF in the quality of life (measured by the EORTC QLQ-C30 of cancer patients across four ethnic groups (Caucasian, Filipino, Hawaiian, and Japanese. The sample consisted of 359 cancer patients. Results Results showed the presence of DIF on several items, indicating ethnic differences in the assessment of quality of life. Relative to the Caucasian and Japanese groups, items related to physical functioning, cognitive functioning, social functioning, nausea and vomiting, and financial difficulties exhibited DIF for Filipinos. On these items Filipinos exhibited either higher or lower QoL scores, even though their overall QoL was the same. Conclusion This evidence may explain why Filipinos have previously been found to have lower overall QoL. Although Filipinos score lower on QoL than other groups, this may not reflect lower QoL, but rather differences in how QoL is defined. The presence of DIF did not appear, however, to alter the psychometric properties of the QLQ-C30.

  20. Differentiations and Functional State of Osteogenic Cells in Conditions of Microgravity

    Science.gov (United States)

    Onishchenko, Ganna; Rodionova, Natalia; Markevich, Ganna; Markevich, Ganna

    The space flight factors (space radiation, magnetic fields etc.) affect considerably the state of bone tissue, leading to the development of osteoporosis and osteopenia in the bone skeleton. Many aspects of reactions of bone tissue cells still remain unclear until now. With the use of electron microscopy and autoradiography with 3H-thymidine we studied the samples gathered from the femoral bone epiphyses and metaphyses of rats flown on board American Spacelab -2 and in experiments with modeling of microgravity ("tail suspension" method). In our work the main attention is focused on studying the ultrastructure and metabolism of osteogenetic cells. The degree of differentiation and functional state are evaluated according to the degree of development of organelles for specific biosynthesis: rough endoplasmic reticulum (RER), Golgy complex (GC), as well as the state of mitochondria and cell nucleus. As compared with a control, the population of osteogenetic cells from zones of bone reconstruction shows a decrease in the number of functionally active forms. We can judge of this from the reduction volume of RER, GC, mitochondria in osteoblasts. RER loses architectonics typical for osteoblasts and, as against the control, is represented by short narrow canaliculi distributed throughout the cy-toplasm; some canals disintegrate. GC is slightly pronounced, mitochondria become smaller in size and acquire an optically dark matrix. These phenomena are supposed to be associated with the desorganization of microtubules and microfilaments in the cells under microgravity condi-tions. The number of degrading and apoptotic cells increases in the population of osteoblasts. The dynamics of labeled cells following various intervals after 3H-thymidine injection testifies to a delay in the rates of osteoblasts' differentiation and their transformation to osteocytes in the experiment animals. A lower 3H-glycine uptake by the osteogenic cells and bone matrix as compared with a control is

  1. Differential PAX3 functions in normal skin melanocytes and melanoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Medic, Sandra [School of Exercise, Biomedical and Health Sciences, Edith Cowan University, Perth, WA (Australia); Rizos, Helen [Westmead Institute for Cancer Research and Melanoma Institute of Australia, University of Sydney at Westmead Millennium Institute, Westmead, NSW (Australia); Ziman, Mel, E-mail: m.ziman@ecu.edu.au [School of Exercise, Biomedical and Health Sciences, Edith Cowan University, Perth, WA (Australia); School of Pathology and Laboratory Medicine, University of Western Australia, Perth, WA (Australia)

    2011-08-12

    Highlights: {yields} PAX3 retains embryonic roles in adult melanocytes and melanoma cells. {yields} Promotes 'stem' cell-like phenotype via NES and SOX9 in both cells types. {yields} Regulates melanoma and melanocyte migration through MCAM and CSPG4. {yields} PAX3 regulates melanoma but not melanocyte proliferation via TPD52. {yields} Regulates melanoma cell (but not melanocyte) survival via BCL2L1 and PTEN. -- Abstract: The PAX3 transcription factor is the key regulator of melanocyte development during embryogenesis and is also frequently found in melanoma cells. While PAX3 is known to regulate melanocyte differentiation, survival, proliferation and migration during development, it is not clear if its function is maintained in adult melanocytes and melanoma cells. To clarify this we have assessed which genes are targeted by PAX3 in these cells. We show here that similar to its roles in development, PAX3 regulates complex differentiation networks in both melanoma cells and melanocytes, in order to maintain cells as 'stem' cell-like (via NES and SOX9). We show also that mediators of migration (MCAM and CSPG4) are common to both cell types but more so in melanoma cells. By contrast, PAX3-mediated regulation of melanoma cell proliferation (through TPD52) and survival (via BCL2L1 and PTEN) differs from that in melanocytes. These results suggest that by controlling cell proliferation, survival and migration as well as maintaining a less differentiated 'stem' cell like phenotype, PAX3 may contribute to melanoma development and progression.

  2. Smad3 signaling is required for satellite cell function and myogenic differentiation of myoblasts

    Institute of Scientific and Technical Information of China (English)

    Xiaojia Ge; Ravi Kambadur; Craig McFarlane; Anuradha Vajjala; Sudarsanareddy Lokireddy; Zhi Hui Ng; Chek Kun Tan; Nguan Soon Tan; Walter Wahli; Mridula Sharma

    2011-01-01

    TGF-β and myostatin are the two most important regulators of muscle growth.Both growth factors have been shown to signal through a Smad3-dependent pathway.However to date,the role of Smad3 in muscle growth and differentiation is not investigated.Here,we demonstrate that Smad3-null mice have decreased muscle mass and pronounced skeletal muscle atrophy.Consistent with this,we also find increased protein ubiquitination and elevated levels of the ubiquitin E3 ligase MuRF1 in muscle tissue isolated from Smad3-null mice.Loss of Smad3 also led to defective satellite cell (SC) functionality.Smad3-null SCs showed reduced propensity for self-renewal,which may lead to a progressive loss of SC number.Indeed,decreased SC number was observed in skeletal muscle from Smad3- null mice showing signs of severe muscle wasting.Further in vitro analysis of primary myoblast cultures identified that Smad3-nuil myoblasts exhibit impaired proliferation,differentiation and fusion,resulting in the formation of atrophied myotubes.A search for the molecular mechanism revealed that loss of Smad3 results in increased myostatin expression in Smad3-null muscle and myoblasts.Given that myostatin is a negative regulator,we hypothesize that increased myostatin levels are responsible for the atrophic phenotype in Smad3-null mice.Consistent with this theory,inactivation of myostatin in Smad3-null mice rescues the muscle atrophy phenotype.

  3. Laminin and biomimetic extracellular elasticity enhance functional differentiation in mammary epithelia

    Energy Technology Data Exchange (ETDEWEB)

    Alcaraz, Jordi; Xu, Ren; Mori, Hidetoshi; Nelson, Celeste M.; Mroue, Rana; Spencer, Virginia A.; Brownfield, Doug; Radisky, Derek C.; Bustamante, Carlos; Bissell, Mina J.

    2008-10-20

    In the mammary gland, epithelial cells are embedded in a 'soft' environment and become functionally differentiated in culture when exposed to a laminin-rich extracellular matrix gel. Here, we define the processes by which mammary epithelial cells integrate biochemical and mechanical extracellular cues to maintain their differentiated phenotype. We used single cells cultured on top of gels in conditions permissive for {beta}-casein expression using atomic force microscopy to measure the elasticity of the cells and their underlying substrata. We found that maintenance of {beta}-casein expression required both laminin signalling and a 'soft' extracellular matrix, as is the case in normal tissues in vivo, and biomimetic intracellular elasticity, as is the case in primary mammary epithelial organoids. Conversely, two hallmarks of breast cancer development, stiffening of the extracellular matrix and loss of laminin signalling, led to the loss of {beta}-casein expression and non-biomimetic intracellular elasticity. Our data indicate that tissue-specific gene expression is controlled by both the tissues unique biochemical milieu and mechanical properties, processes involved in maintenance of tissue integrity and protection against tumorigenesis.

  4. Stimulation of differentiated functions in human melanoma cells by tumor-promoting agents and dimethyl sulfoxide

    Energy Technology Data Exchange (ETDEWEB)

    Huberman, E.; Heckman, C.; Langenbach, R.

    1979-07-01

    Treatment of cultured human HO melanoma cells with the mouse skin tumor promoter phorbol-12-myristate-13-acetate (PMA) at 5 x 10/sup -10/ to 5 x 10/sup -7/ M resulted in a dose-related inhibition of growth and a stimulation of differentiated functions. These included melanin synthesis and formation of dendrite-like structues. Higher doses of phorbol dibutyrate, a less potent tumor promoter, were required to produce an effect comparable to that of PMA for dendrite induction. Phorbol and two other phorbal esters, which lack tumor-promoting activity, were either inactive or elicited a poor response. In addition to morphological changes, treatment with PMA altered glucosamine incorporation into membrane gangliosides. After PMA treatment, glucosamine incorporation increased 8- to 10 fold in the G/sub m3/ ganglioside and decreased 2-fold in the G/sub m1/ ganglioside, as compared to phorbol or untreated control. Inhibition of cell growth and stimulation of melanin synthesis were also observed after treatment of the HO cells with dimethyl sulfoxide. Unlike the tumor-promoting agents, dimethyl sulfoxide did not induce the formation of dendrite-like structures in the cells. These findings indicate that HO melanoma cells can be stimulated into terminally differentiated cells after treatment with tumor-promoting agents such as phorbol diesters.

  5. Differential item functioning due to gender between depression and anxiety items among Chilean adolescents.

    Science.gov (United States)

    Bares, Cristina; Andrade, Fernando; Delva, Jorge; Grogan-Kaylor, Andrew; Kamata, Akihito

    2012-07-01

    Although much is known about the higher prevalence of anxiety and depressive disorders among adolescent females, less is known about the differential item endorsement due to gender in items of scales commonly used to measure anxiety and depression. We conducted a study to examine if adolescent males and females from Chile differed on how they endorsed the items of the Youth Self Report (YSR) anxious/depressed problem scale. We used data from a cross-sectional sample consisting of 925 participants (mean age = 14, SD 1.3, 49% females) of low to lower-middle socioeconomic status. A two-parameter logistic (2PL) IRT DIF model was fit. s revealed differential item functioning (DIF) by gender for six of the 13 items, with adolescent females being more likely to endorse a depression item while males were found more likely to endorse anxiety items. Findings suggest that items found in commonly used measures of anxiety and depression symptoms may not equally capture the true levels of these behavioural problems in adolescent males and females. Given the high levels of mental disorders in Chile and the surrounding countries, further attention should be focused on increasing the number of empirical studies examining potential gender differences in the assessment of mental health problems among Latin American populations to better aid our understanding of the phenomenology and determinants of these problems in the region.

  6. The medial prefrontal and orbitofrontal cortices differentially regulate dopamine system function.

    Science.gov (United States)

    Lodge, Daniel J

    2011-05-01

    The prefrontal cortex (PFC) is essential for top-down control over higher-order executive function. In this study we demonstrate that the medial prefrontal cortex (mPFC) and orbitofrontal cortex (OFC) differentially regulate VTA dopamine neuron activity, and furthermore, the pattern of activity in the PFC drastically alters the dopamine neuron response. Thus, although single-pulse activation of the mPFC either excites or inhibits equivalent numbers of dopamine neurons, activation of the OFC induces a primarily inhibitory response. Moreover, activation of the PFC with a pattern that mimics spontaneous burst firing of pyramidal neurons produces a strikingly different response. Specifically, burst-like activation of the mPFC induces a massive increase in dopamine neuron firing, whereas a similar pattern of OFC activation largely inhibits dopamine activity. Taken together, these data demonstrate that the mPFC and OFC differentially regulate dopamine neuron activity, and that the pattern of cortical activation is critical for determining dopamine system output.

  7. Laminin and biomimetic extracellular elasticity enhance functional differentiation in mammary epithelia

    Science.gov (United States)

    Alcaraz, Jordi; Xu, Ren; Mori, Hidetoshi; Nelson, Celeste M; Mroue, Rana; Spencer, Virginia A; Brownfield, Doug; Radisky, Derek C; Bustamante, Carlos; Bissell, Mina J

    2008-01-01

    In the mammary gland, epithelial cells are embedded in a ‘soft' environment and become functionally differentiated in culture when exposed to a laminin-rich extracellular matrix gel. Here, we define the processes by which mammary epithelial cells integrate biochemical and mechanical extracellular cues to maintain their differentiated phenotype. We used single cells cultured on top of gels in conditions permissive for β-casein expression using atomic force microscopy to measure the elasticity of the cells and their underlying substrata. We found that maintenance of β-casein expression required both laminin signalling and a ‘soft' extracellular matrix, as is the case in normal tissues in vivo, and biomimetic intracellular elasticity, as is the case in primary mammary epithelial organoids. Conversely, two hallmarks of breast cancer development, stiffening of the extracellular matrix and loss of laminin signalling, led to the loss of β-casein expression and non-biomimetic intracellular elasticity. Our data indicate that tissue-specific gene expression is controlled by both the tissues' unique biochemical milieu and mechanical properties, processes involved in maintenance of tissue integrity and protection against tumorigenesis. PMID:18843297

  8. The function of a regulatory gene, scrX related to differentiation in Streptomyces coelicolor

    Institute of Scientific and Technical Information of China (English)

    杨海花; 田宇清; 贾君永; 谭华荣

    2000-01-01

    A new gene, scrX from Streptomyces coelicolor was cloned and sequenced. It consists of 660 base pair, encoding a peptide of 220 amino acids. There are three rare codons in scrX which are AAA, AAA and ATA. scrXgene may be a typical differentiation regulator which was strictly controlled at translational level. The comparison of amino acids also revealed that ScrX belonged to Id R family which acted in transcriptional regulation of prokaryote. Studies on gene function by gene disruption and complementation indicated that scrX may play a positive regulation role in spore formation of Streptomyces coelicolor.A new gene, scrX from Streptomyces coelicolor was cloned and sequenced. It consists of 660 base pair, encoding a peptide of 220 amino acids. There are three rare codons in scrX which are AAA, AAA and ATA. scrXgene may be a typical differentiation regulator which was strictly controlled at translational level. The comparison of amino acids also revealed that ScrX belonged to Id R family which acted in tra

  9. Assessing T lymphocyte function and differentiation by genetically encoded reporter systems.

    Science.gov (United States)

    Hoekstra, Mirjam E; Dijkgraaf, Feline E; Schumacher, Ton N; Rohr, Jan C

    2015-07-01

    Upon infection, antigen-specific T lymphocytes become activated, proliferate, differentiate, and acquire various effector functions. Much of our understanding of the molecular mechanisms underlying these processes derives from studies leveraging gene deletion, RNAi, and overexpression approaches. However, these perturbations do not inform on the regulation of gene activity under physiological conditions. Genetic reporter systems that couple biological events to detectable output signals are capable of providing this information. Here, we review the reporter approaches being currently used to investigate various aspects of T cell behavior, and discuss advantages and disadvantages inherent to different designs. We outline emerging applications based on recent advances in other fields, and highlight the potential of synthetic biology and genome engineering to address open questions in the field.

  10. An Introduction to Missing Data in the Context of Differential Item Functioning

    Directory of Open Access Journals (Sweden)

    Kathleen Banks

    2015-04-01

    Full Text Available This article introduces practitioners and researchers to the topic of missing data in the context of differential item functioning (DIF, reviews the current literature on the issue, discusses implications of the review, and offers suggestions for future research. A total of nine studies were reviewed. All of these studies determined what effect particular missing data techniques would have on the results of certain DIF detection procedures under various conditions. The most important finding of this review involved the use of zero imputation as a missing data technique. The review shows that zero imputation can lead to inflated Type I errors, especially in cases where the examinees ability level has not been taken into consideration.

  11. [Analysis of the gender variable in the EDTC using differential item functioning techniques].

    Science.gov (United States)

    Escorial, Sergio; Navas, María J

    2006-05-01

    The aim of this work is to analyze the gender differences in the scales of a recently constructed test: the so-called EDTC. This test measures the following traits: sensation seeking, fearlessness, and impulsivity. Gender differences will be studied using Differential Item Functioning (DIF) techniques, in order to determine whether these differences are true differences in the assessed dimensions or if, on the contrary, they are the result of a mere artefact of the measuring instrument used. The methods used to study DIF are standardization, SIBTEST, logistic regression, Lord's chi 2 test, and indices based on the DFIT model. Despite the fact that some items with DIF exist, the gender differences observed seem to be the result of true differences in the measured personality constructs and they don't seem to be artificially produced by a bias in the test items.

  12. On the set of zero coefficients of a function satisfying a linear differential equation

    CERN Document Server

    Bell, Jason P; Yeats, Karen

    2011-01-01

    Let $K$ be a field of characteristic zero and suppose that $f:\\mathbb{N}\\to K$ satisfies a recurrence of the form $$f(n)\\ =\\ \\sum_{i=1}^d P_i(n) f(n-i),$$ for $n$ sufficiently large, where $P_1(z),...,P_d(z)$ are polynomials in $K[z]$. Given that $P_d(z)$ is a nonzero constant polynomial, we show that the set of $n\\in \\mathbb{N}$ for which $f(n)=0$ is a union of finitely many arithmetic progressions and a finite set. This generalizes the Skolem-Mahler-Lech theorem, which assumes that $f(n)$ satisfies a linear recurrence. We discuss examples and connections to the set of zero coefficients of a power series satisfying a homogeneous linear differential equation with rational function coefficients.

  13. Speech disturbances and quality of life in schizophrenia: differential impacts on functioning and life satisfaction.

    Science.gov (United States)

    Tan, Eric J; Thomas, Neil; Rossell, Susan L

    2014-04-01

    Speech disturbances in schizophrenia impact on the individual's communicative ability. Although they are considered a core feature of schizophrenia, comparatively little work has been done to examine their impact on the life experiences of patients. This study aimed to examine the relationship between schizophrenia speech disturbances, including those traditionally known as formal thought disorder (TD), and quality of life (QoL). It assessed effects on functioning (objective QoL) and satisfaction (subjective QoL) concurrently, while controlling for the influence of neurocognition and depression. Fifty-four patients with schizophrenia/schizoaffective disorder were administered the MATRICS Consensus Cognitive Battery (MCCB), the PANSS, MADRS (with separate ratings for negative TD [verbal underproductivity] and positive TD [verbal disorganisation and pressured speech]) and Lehman's QOLI assessing both objective and subjective QoL. Ratings of positive and negative TD, depression, and general neurocognition were entered into hierarchical regressions to explore their relationship with both life functioning and satisfaction. Verbal underproductivity was a significant predictor of objective QoL, while pressured speech had a trend association with subjective QoL. This suggests a differential relationship between speech disturbances and QoL. Verbal underproductivity seems to affect daily functioning and relations with others, while pressured speech is predictive of satisfaction with life. The impact of verbal underproductivity on QoL suggests it to be an important target for rehabilitation in schizophrenia. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Proteome analysis of functionally differentiated bovine (Bos indicus) mammary epithelial cells isolated from milk

    KAUST Repository

    Janjanam, Jagadeesh

    2013-10-01

    Mammary gland is made up of a branching network of ducts that end in alveoli. Terminally differentiated mammary epithelial cells (MECs) constitute the innermost layer of aveoli. They are milk-secreting cuboidal cells that secrete milk proteins during lactation. Little is known about the expression profile of proteins in the metabolically active MECs during lactation or their functional role in the lactation process. In the present investigation, we have reported the proteome map of MECs in lactating cows using 2DE MALDI-TOF/TOF MS and 1D-Gel-LC-MS/MS. MECs were isolated from milk using immunomagnetic beads and confirmed by RT-PCR and Western blotting. The 1D-Gel-LC-MS/MS and 2DE-MS/MS based approaches led to identification of 431 and 134 proteins, respectively, with a total of 497 unique proteins. Proteins identified in this study were clustered into functional groups using bioinformatics tools. Pathway analysis of the identified proteins revealed 28 pathways (p < 0.05) providing evidence for involvement of various proteins in lactation function. This study further provides experimental evidence for the presence of many proteins that have been predicted in annotated bovine genome. The data generated further provide a set of bovine MEC-specific proteins that will help the researchers to understand the molecular events taking place during lactation. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Energy metabolism drives myeloid-derived suppressor cell differentiation and functions in pathology.

    Science.gov (United States)

    Sica, Antonio; Strauss, Laura

    2017-08-01

    Over the last decade, a heterogeneous population of immature myeloid cells with major regulatory functions has been described in cancer and other pathologic conditions and ultimately defined as MDSCs. Most of the early work on the origins and functions of MDSCs has been in murine and human tumor bearers in which MDSCs are known to be immunosuppressive and to result in both reduced immune surveillance and antitumor cytotoxicity. More recent studies, however, suggest that expansion of these immature myeloid cells may be linked to most, if not all, chronic and acute inflammatory processes. The universal expansion to inflammatory stimuli of MDSCs suggests that these cells may be more of a normal component of the inflammatory response (emergency myelopoiesis) than simply a pathologic response to a growing tumor. Instead of an adverse immunosuppressive response, expansion of these immature myeloid cell populations may result from a complex balance between increased immune surveillance and dampened adaptive immune responses that are common to many inflammatory responses. Within this scenario, new pathways of metabolic reprogramming are emerging as drivers of MDSC differentiation and functions in cancer and inflammatory disorders, crucially linking metabolic syndrome to inflammatory processes. © Society for Leukocyte Biology.

  16. Predicting recovery of cognitive function soon after stroke: differential modeling of logarithmic and linear regression.

    Science.gov (United States)

    Suzuki, Makoto; Sugimura, Yuko; Yamada, Sumio; Omori, Yoshitsugu; Miyamoto, Masaaki; Yamamoto, Jun-ichi

    2013-01-01

    Cognitive disorders in the acute stage of stroke are common and are important independent predictors of adverse outcome in the long term. Despite the impact of cognitive disorders on both patients and their families, it is still difficult to predict the extent or duration of cognitive impairments. The objective of the present study was, therefore, to provide data on predicting the recovery of cognitive function soon after stroke by differential modeling with logarithmic and linear regression. This study included two rounds of data collection comprising 57 stroke patients enrolled in the first round for the purpose of identifying the time course of cognitive recovery in the early-phase group data, and 43 stroke patients in the second round for the purpose of ensuring that the correlation of the early-phase group data applied to the prediction of each individual's degree of cognitive recovery. In the first round, Mini-Mental State Examination (MMSE) scores were assessed 3 times during hospitalization, and the scores were regressed on the logarithm and linear of time. In the second round, calculations of MMSE scores were made for the first two scoring times after admission to tailor the structures of logarithmic and linear regression formulae to fit an individual's degree of functional recovery. The time course of early-phase recovery for cognitive functions resembled both logarithmic and linear functions. However, MMSE scores sampled at two baseline points based on logarithmic regression modeling could estimate prediction of cognitive recovery more accurately than could linear regression modeling (logarithmic modeling, R(2) = 0.676, Plinear regression modeling, R(2) = 0.598, P<0.0001). Logarithmic modeling based on MMSE scores could accurately predict the recovery of cognitive function soon after the occurrence of stroke. This logarithmic modeling with mathematical procedures is simple enough to be adopted in daily clinical practice.

  17. Predicting recovery of cognitive function soon after stroke: differential modeling of logarithmic and linear regression.

    Directory of Open Access Journals (Sweden)

    Makoto Suzuki

    Full Text Available Cognitive disorders in the acute stage of stroke are common and are important independent predictors of adverse outcome in the long term. Despite the impact of cognitive disorders on both patients and their families, it is still difficult to predict the extent or duration of cognitive impairments. The objective of the present study was, therefore, to provide data on predicting the recovery of cognitive function soon after stroke by differential modeling with logarithmic and linear regression. This study included two rounds of data collection comprising 57 stroke patients enrolled in the first round for the purpose of identifying the time course of cognitive recovery in the early-phase group data, and 43 stroke patients in the second round for the purpose of ensuring that the correlation of the early-phase group data applied to the prediction of each individual's degree of cognitive recovery. In the first round, Mini-Mental State Examination (MMSE scores were assessed 3 times during hospitalization, and the scores were regressed on the logarithm and linear of time. In the second round, calculations of MMSE scores were made for the first two scoring times after admission to tailor the structures of logarithmic and linear regression formulae to fit an individual's degree of functional recovery. The time course of early-phase recovery for cognitive functions resembled both logarithmic and linear functions. However, MMSE scores sampled at two baseline points based on logarithmic regression modeling could estimate prediction of cognitive recovery more accurately than could linear regression modeling (logarithmic modeling, R(2 = 0.676, P<0.0001; linear regression modeling, R(2 = 0.598, P<0.0001. Logarithmic modeling based on MMSE scores could accurately predict the recovery of cognitive function soon after the occurrence of stroke. This logarithmic modeling with mathematical procedures is simple enough to be adopted in daily clinical practice.

  18. Differential Item Functioning of the Psychological Domain of the Menopause Rating Scale

    Science.gov (United States)

    Portela-Buelvas, Katherin; Oviedo, Heidi C.; Herazo, Edwin; Campo-Arias, Adalberto

    2016-01-01

    Introduction. Quality of life could be quantified with the Menopause Rating Scale (MRS), which evaluates the severity of somatic, psychological, and urogenital symptoms in menopause. However, differential item functioning (DIF) analysis has not been applied previously. Objective. To establish the DIF of the psychological domain of the MRS in Colombian women. Methods. 4,009 women aged between 40 and 59 years, who participated in the CAVIMEC (Calidad de Vida en la Menopausia y Etnias Colombianas) project, were included. Average age was 49.0 ± 5.9 years. Women were classified in mestizo, Afro-Colombian, and indigenous. The results were presented as averages and standard deviation (X ± SD). A p value <0.001 was considered statistically significant. Results. In mestizo women, the highest X ± SD were obtained in physical and mental exhaustion (PME) (0.86 ± 0.93) and the lowest ones in anxiety (0.44 ± 0.79). In Afro-Colombian women, an average score of 0.99 ± 1.07 for PME and 0.63 ± 0.88 for anxiety was gotten. Indigenous women obtained an increased average score for PME (1.33 ± 0.93). The lowest score was evidenced in depressive mood (0.50 ± 0.81), which is different from other Colombian women (p < 0.001). Conclusions. The psychological items of the MRS show differential functioning according to the ethnic group, which may induce systematic error in the measurement of the construct. PMID:27847825

  19. Differential Item Functioning of the Psychological Domain of the Menopause Rating Scale.

    Science.gov (United States)

    Monterrosa-Castro, Alvaro; Portela-Buelvas, Katherin; Oviedo, Heidi C; Herazo, Edwin; Campo-Arias, Adalberto

    2016-01-01

    Introduction. Quality of life could be quantified with the Menopause Rating Scale (MRS), which evaluates the severity of somatic, psychological, and urogenital symptoms in menopause. However, differential item functioning (DIF) analysis has not been applied previously. Objective. To establish the DIF of the psychological domain of the MRS in Colombian women. Methods. 4,009 women aged between 40 and 59 years, who participated in the CAVIMEC (Calidad de Vida en la Menopausia y Etnias Colombianas) project, were included. Average age was 49.0 ± 5.9 years. Women were classified in mestizo, Afro-Colombian, and indigenous. The results were presented as averages and standard deviation (X ± SD). A p value <0.001 was considered statistically significant. Results. In mestizo women, the highest X ± SD were obtained in physical and mental exhaustion (PME) (0.86 ± 0.93) and the lowest ones in anxiety (0.44 ± 0.79). In Afro-Colombian women, an average score of 0.99 ± 1.07 for PME and 0.63 ± 0.88 for anxiety was gotten. Indigenous women obtained an increased average score for PME (1.33 ± 0.93). The lowest score was evidenced in depressive mood (0.50 ± 0.81), which is different from other Colombian women (p < 0.001). Conclusions. The psychological items of the MRS show differential functioning according to the ethnic group, which may induce systematic error in the measurement of the construct.

  20. Estimates for derivatives of the Green functions for the noncoercive differential operators on homogeneous manifolds of negative curvature, II

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    Roman Urban

    2003-08-01

    Full Text Available We consider the Green functions for second order non-coercive differential operators on homogeneous manifolds of negative curvature, being a semi-direct product of a nilpotent Lie group $N$ and $A=mathbb{R}^+$. We obtain estimates for the mixed derivatives of the Green functions that complements a previous work by the same author [17].