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Sample records for differential luteolytic function

  1. Differential gene expression in the bovine corpus luteum during transition from early phase to midphase and its potential role in acquisition of luteolytic sensitivity to prostaglandin F2 alpha.

    PubMed

    Goravanahally, Madhusudan P; Salem, Mohamed; Yao, Jianbo; Inskeep, E Keith; Flores, Jorge A

    2009-05-01

    Prostaglandin F2 alpha (PGF(2alpha)) brings about regression of the bovine corpus luteum (CL). This luteolytic property of PGF(2alpha) is used in beef and dairy cattle to synchronize estrus. A limitation of this protocol is insensitivity of the early CL to luteolytic actions of PGF(2alpha). The mechanisms underlying this differential luteal sensitivity are poorly understood. The developing CL has a maximum number of PGF(2alpha) receptors; therefore, differences in signaling events may be responsible for luteal insensitivity. Hence, differential gene expression at two developmental stages of CL, Day 4 (D-4) and D-10 after estrus, might account for differences in signal transduction pathways associated with luteal sensitivity. This possibility was examined in these studies. Microarray analysis (n = 3 cows per stage) identified 167 genes that were differentially expressed (P < 0.05). These were categorized into genes involved in protein biosynthesis and modification (18.5%), transcription regulation and DNA biosynthesis (18.5%), miscellaneous (17.0%), cell signaling (12.0%), steroidogenesis and metabolism (10.2%), extracellular matrix and cytoskeletal proteins (9.5%), unknown functions (6.0%), protein degradation (5.3%), and antioxidant property (3.0%). Real-time PCR confirmed the differential expression of nine selected genes, including tyrosine 3-monooxygenase/tryptophan 5-monooxygense activation protein zeta polypeptide (YWHAZ) and regulator of G protein signaling 2 24-kDa (RGS2), observed in microarray. Furthermore, the in vivo effect of exogenous PGF(2alpha) (n = 3 cows per stage) on selected genes that were found to be differentially expressed during this developmental transition was examined. PGF(2alpha) increased the expression of a guanine nucleotide-binding protein (G protein) beta polypeptide 1 (GNB1) in D-4 CL and calcium/calmodulin-dependent kinase kinase 2 beta (CAMKK2) in D-10 CL. Therefore, GNB1, CAMKK2, YWHAZ, and RGS2 are candidate genes that may

  2. Using Differentials to Differentiate Trigonometric and Exponential Functions

    ERIC Educational Resources Information Center

    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.

  3. Differential dopamine function in fibromyalgia.

    PubMed

    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. PMID:26497890

  4. Detecting Differential Person Functioning in Emotional Intelligence

    ERIC Educational Resources Information Center

    Alsmadi, Yahia M.; Alsmadi, Abdalla A.

    2009-01-01

    Differential Item Functioning (DIF) is a widely used term in test development literature. It is very important to analyze test's data for DIF because It is a serious threat to validity. If the same data matrix was transposed, similar analysis can be carried for Differential Person Functioning (DPF). The purpose of this paper is to introduce and…

  5. Identifying Possible Sources of Differential Functioning Using Differential Bundle Functioning with Polytomously Scored Data

    ERIC Educational Resources Information Center

    McCarty, F. A.; Oshima, T. C.; Raju, Nambury S.

    2007-01-01

    Oshima, Raju, Flowers, and Slinde (1998) described procedures for identifying sources of differential functioning for dichotomous data using differential bundle functioning (DBF) derived from the differential functioning of items and test (DFIT) framework (Raju, van der Linden, & Fleer, 1995). The purpose of this study was to extend the procedures…

  6. Differential Item Functioning in Survey Research.

    ERIC Educational Resources Information Center

    Johanson, George A.; Johanson, Susan N.

    Differential item functioning (DIF), or item bias, occurs when individuals in a focal group respond differently to a test item than do individuals in a reference group even when comparisons are restricted to individuals with similar overall skill levels on the trait in question. It is common in constructing a questionnaire or survey to recommend…

  7. A Multilevel Assessment of Differential Item Functioning.

    ERIC Educational Resources Information Center

    Shen, Linjun

    A multilevel approach was proposed for the assessment of differential item functioning and compared with the traditional logistic regression approach. Data from the Comprehensive Osteopathic Medical Licensing Examination for 2,300 freshman osteopathic medical students were analyzed. The multilevel approach used three-level hierarchical generalized…

  8. Ramsay-Curve Differential Item Functioning

    ERIC Educational Resources Information Center

    Woods, Carol M.

    2011-01-01

    Differential item functioning (DIF) occurs when an item on a test, questionnaire, or interview has different measurement properties for one group of people versus another, irrespective of true group-mean differences on the constructs being measured. This article is focused on item response theory based likelihood ratio testing for DIF (IRT-LR or…

  9. Real and Artificial Differential Item Functioning

    ERIC Educational Resources Information Center

    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…

  10. Differential Item Functioning Analysis Using Rasch Item Information Functions

    ERIC Educational Resources Information Center

    Wyse, Adam E.; Mapuranga, Raymond

    2009-01-01

    Differential item functioning (DIF) analysis is a statistical technique used for ensuring the equity and fairness of educational assessments. This study formulates a new DIF analysis method using the information similarity index (ISI). ISI compares item information functions when data fits the Rasch model. Through simulations and an international…

  11. Monotone viable trajectories for functional differential inclusions

    NASA Astrophysics Data System (ADS)

    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.

  12. Synchronization with propagation - The functional differential equations

    NASA Astrophysics Data System (ADS)

    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.

  13. Radiative Damping and Functional Differential Equations

    NASA Astrophysics Data System (ADS)

    Raju, Suvrat; Raju, C. K.

    We propose a general technique to solve the classical many-body problem with radiative damping. We modify the short-distance structure of Maxwell electrodynamics. This allows us to avoid runaway solutions as if we had a covariant model of extended particles. The resulting equations of motion are functional differential equations (FDEs) rather than ordinary differential equations (ODEs). Using recently developed numerical techniques for stiff, retarded FDEs, we solve these equations for the one-body central force problem with radiative damping. Our results indicate that locally the magnitude of radiation damping may be well approximated by the standard third-order expression but the global properties of our solutions are dramatically different. We comment on the two-body problem and applications to quantum field theory and quantum mechanics.

  14. Differentiability of Lieb functional in electronic density functional theory

    NASA Astrophysics Data System (ADS)

    Lammert, Paul E.

    A solid understanding of the Lieb functional FL is important because of its centrality in the foundations of electronic density functional theory. A basic question is whether directional derivatives of FL at an ensemble-V-representable density are given by (minus) the potential. A widely accepted purported proof that FL is Gâteaux differentiable at EV-representable densities would say, ?yes.? But that proof is fallacious, as shown here. FL is not Gâteaux differentiable in the normal sense, nor is it continuous. By means of a constructive approach, however, we are able to show that the derivative of FL at an EV-representable density ?0 in the direction of ?1 is given by the potential if ?0 and ?1 are everywhere strictly greater than zero, and they and the ground state wave function have square integrable derivatives through second order.

  15. Multiple-Group Noncompensatory Differential Item Functioning in Raju's Differential Functioning of Items and Tests

    ERIC Educational Resources Information Center

    Oshima, T. C.; Wright, Keith; White, Nick

    2015-01-01

    Raju, van der Linden, and Fleer (1995) introduced a framework for differential functioning of items and tests (DFIT) for unidimensional dichotomous models. Since then, DFIT has been shown to be a quite versatile framework as it can handle polytomous as well as multidimensional models both at the item and test levels. However, DFIT is still limited…

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

    ERIC Educational Resources Information Center

    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…

  17. Generalized Halanay inequalities for dissipativity of Volterra functional differential equations

    NASA Astrophysics Data System (ADS)

    Wen, Liping; Yu, Yuexin; Wang, Wansheng

    2008-11-01

    This paper is concerned with the dissipativity of theoretical solutions to nonlinear Volterra functional differential equations (VFDEs). At first, we give some generalizations of Halanay's inequality which play an important role in study of dissipativity and stability of differential equations. Then, by applying the generalization of Halanay's inequality, the dissipativity results of VFDEs are obtained, which provides unified theoretical foundation for the dissipativity analysis of systems in ordinary differential equations (ODEs), delay differential equations (DDEs), integro-differential equations (IDEs), Volterra delay-integro-differential equations (VDIDEs) and VFDEs of other type which appear in practice.

  18. Legendre-tau approximations for functional differential equations

    NASA Technical Reports Server (NTRS)

    Ito, K.; Teglas, R.

    1986-01-01

    The numerical approximation of solutions to linear retarded functional differential equations are considered using the so-called Legendre-tau method. The functional differential equation is first reformulated as a partial differential equation with a nonlocal boundary condition involving time-differentiation. The approximate solution is then represented as a truncated Legendre series with time-varying coefficients which satisfy a certain system of ordinary differential equations. The method is very easy to code and yields very accurate approximations. Convergence is established, various numerical examples are presented, and comparison between the latter and cubic spline approximation is made.

  19. Legendre-Tau approximations for functional differential equations

    NASA Technical Reports Server (NTRS)

    Ito, K.; Teglas, R.

    1983-01-01

    The numerical approximation of solutions to linear functional differential equations are considered using the so called Legendre tau method. The functional differential equation is first reformulated as a partial differential equation with a nonlocal boundary condition involving time differentiation. The approximate solution is then represented as a truncated Legendre series with time varying coefficients which satisfy a certain system of ordinary differential equations. The method is very easy to code and yields very accurate approximations. Convergence is established, various numerical examples are presented, and comparison between the latter and cubic spline approximations is made.

  20. Computations involving differential operators and their actions on functions

    NASA Technical Reports Server (NTRS)

    Crouch, Peter E.; Grossman, Robert; Larson, Richard

    1991-01-01

    The algorithms derived by Grossmann and Larson (1989) are further developed for rewriting expressions involving differential operators. The differential operators involved arise in the local analysis of nonlinear dynamical systems. These algorithms are extended in two different directions: the algorithms are generalized so that they apply to differential operators on groups and the data structures and algorithms are developed to compute symbolically the action of differential operators on functions. Both of these generalizations are needed for applications.

  1. Higher-order automatic differentiation of mathematical functions

    NASA Astrophysics Data System (ADS)

    Charpentier, Isabelle; Dal Cappello, Claude

    2015-04-01

    Functions of mathematical physics such as the Bessel functions, the Chebyshev polynomials, the Gauss hypergeometric function and so forth, have practical applications in many scientific domains. On the one hand, differentiation formulas provided in reference books apply to real or complex variables. These do not account for the chain rule. On the other hand, based on the chain rule, the automatic differentiation has become a natural tool in numerical modeling. Nevertheless automatic differentiation tools do not deal with the numerous mathematical functions. This paper describes formulas and provides codes for the higher-order automatic differentiation of mathematical functions. The first method is based on Faà di Bruno's formula that generalizes the chain rule. The second one makes use of the second order differential equation they satisfy. Both methods are exemplified with the aforementioned functions.

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

    ERIC Educational Resources Information Center

    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…

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

    ERIC Educational Resources Information Center

    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…

  4. Differentials of a State Reading Assessment: Item Functioning, Distractor Functioning, and Omission Frequency for Disability Categories

    ERIC Educational Resources Information Center

    Kato, Kentaro; Moen, Ross E.; Thurlow, Martha L.

    2009-01-01

    Large data sets from a state reading assessment for third and fifth graders were analyzed to examine differential item functioning (DIF), differential distractor functioning (DDF), and differential omission frequency (DOF) between students with particular categories of disabilities (speech/language impairments, learning disabilities, and emotional…

  5. Generating functionals and Lagrangian partial differential equations

    SciTech Connect

    Vankerschaver, Joris; Liao, Cuicui; Leok, Melvin

    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.

  6. Functional differentiability in time-dependent quantum mechanics

    SciTech Connect

    Penz, Markus Ruggenthaler, Michael

    2015-03-28

    In this work, we investigate the functional differentiability of the time-dependent many-body wave function and of derived quantities with respect to time-dependent potentials. For properly chosen Banach spaces of potentials and wave functions, Fréchet differentiability is proven. From this follows an estimate for the difference of two solutions to the time-dependent Schrödinger equation that evolve under the influence of different potentials. Such results can be applied directly to the one-particle density and to bounded operators, and present a rigorous formulation of non-equilibrium linear-response theory where the usual Lehmann representation of the linear-response kernel is not valid. Further, the Fréchet differentiability of the wave function provides a new route towards proving basic properties of time-dependent density-functional theory.

  7. Two temporal functions of Glass: Ommatidium patterning and photoreceptor differentiation.

    PubMed

    Liang, Xulong; Mahato, Simpla; Hemmerich, Chris; Zelhof, Andrew C

    2016-06-01

    Much progress has been made in elucidating the molecular networks required for specifying retinal cells, including photoreceptors, but the downstream mechanisms that maintain identity and regulate differentiation remain poorly understood. Here, we report that the transcription factor Glass has a dual role in establishing a functional Drosophila eye. Utilizing conditional rescue approaches, we confirm that persistent defects in ommatidium patterning combined with cell death correlate with the overall disruption of eye morphology in glass mutants. In addition, we reveal that Glass exhibits a separable role in regulating photoreceptor differentiation. In particular, we demonstrate the apparent loss of glass mutant photoreceptors is not only due to cell death but also a failure of the surviving photoreceptors to complete differentiation. Moreover, the late reintroduction of Glass in these developmentally stalled photoreceptors is capable of restoring differentiation in the absence of correct ommatidium patterning. Mechanistically, transcription profiling at the time of differentiation reveals that Glass is necessary for the expression of many genes implicated in differentiation, i.e. rhabdomere morphogenesis, phototransduction, and synaptogenesis. Specifically, we show Glass directly regulates the expression of Pph13, which encodes a transcription factor necessary for opsin expression and rhabdomere morphogenesis. Finally, we demonstrate the ability of Glass to choreograph photoreceptor differentiation is conserved between Drosophila and Tribolium, two holometabolous insects. Altogether, our work identifies a fundamental regulatory mechanism to generate the full complement of cells required for a functional rhabdomeric visual system and provides a critical framework to investigate the basis of differentiation and maintenance of photoreceptor identity. PMID:27105580

  8. Differential Forms Basis Functions for Better Conditioned Integral Equations

    SciTech Connect

    Fasenfest, B; White, D; Stowell, M; Rieben, R; Sharpe, R; Madsen, N; Rockway, J D; Champagne, N J; Jandhyala, V; Pingenot, J

    2005-01-13

    Differential forms offer a convenient way to classify physical quantities and set up computational problems. By observing the dimensionality and type of derivatives (divergence,curl,gradient) applied to a quantity, an appropriate differential form can be chosen for that quantity. To use these differential forms in a simulation, the forms must be discretized using basis functions. The 0-form through 2-form basis functions are formed for surfaces. Twisted 1-form and 2-form bases will be presented in this paper. Twisted 1-form (1-forms) basis functions ({Lambda}) are divergence-conforming edge basis functions with units m{sup -1}. They are appropriate for representing vector quantities with continuous normal components, and they belong to the same function space as the commonly used RWG bases [1]. They are used here to formulate the frequency-domain EFIE with Galerkin testing. The 2-form basis functions (f) are scalar basis functions with units m{sup -2} and with no enforced continuity between elements. At lowest order, the 2-form basis functions are similar to pulse basis functions. They are used here to formulate an electrostatic integral equation. It should be noted that the derivative of an n-form differential form basis function is an (n+1)-form, i.e. the derivative of a 1-form basis function is a 2-form. Because the basis functions are constructed such that they have spatial units, the spatial units are removed from the degrees of freedom, leading to a better-conditioned system matrix. In this conference paper, we look at the performance of these differential forms and bases by examining the conditioning of matrix systems for electrostatics and the EFIE. The meshes used were refined across the object to consider the behavior of these basis transforms for elements of different sizes.

  9. Regulatory T Cells: Differentiation and Function.

    PubMed

    Plitas, George; Rudensky, Alexander Y

    2016-09-01

    The immune system of vertebrate animals has evolved to mount an effective defense against a diverse set of pathogens while minimizing transient or lasting impairment in tissue function that could result from the inflammation caused by immune responses to infectious agents. In addition, misguided immune responses to "self" and dietary antigens, as well as to commensal microorganisms, can lead to a variety of inflammatory disorders, including autoimmunity, metabolic syndrome, allergies, and cancer. Regulatory T cells expressing the X chromosome-linked transcription factor Foxp3 suppress inflammatory responses in diverse biological settings and serve as a vital mechanism of negative regulation of immune-mediated inflammation. Cancer Immunol Res; 4(9); 721-5. ©2016 AACR. PMID:27590281

  10. Raju's Differential Functioning of Items and Tests (DFIT)

    ERIC Educational Resources Information Center

    Oshima, T. C.; Morris, S. B.

    2008-01-01

    Nambury S. Raju (1937-2005) developed two model-based indices for differential item functioning (DIF) during his prolific career in psychometrics. Both methods, Raju's area measures (Raju, 1988) and Raju's DFIT (Raju, van der Linden, & Fleer, 1995), are based on quantifying the gap between item characteristic functions (ICFs). This approach…

  11. Decisions that Make a Difference in Detecting Differential Item Functioning

    ERIC Educational Resources Information Center

    Sireci, Stephen G.; Rios, Joseph A.

    2013-01-01

    There are numerous statistical procedures for detecting items that function differently across subgroups of examinees that take a test or survey. However, in endeavouring to detect items that may function differentially, selection of the statistical method is only one of many important decisions. In this article, we discuss the important decisions…

  12. Green's function of the second order differential operator with involution

    NASA Astrophysics Data System (ADS)

    Ashyralyev, Allaberen; Sarsenbi, Abdisalam A.

    2016-08-01

    In the present paper, the Green's function of the second order differential operator L defined by formula L u =α u″ (x ) -u″ (-x ) =λ u (x ) ,-1 function is established.

  13. Functional Analysis and Characterization of Differential Coexpression Networks

    PubMed Central

    Hsu, Chia-Lang; Juan, Hsueh-Fen; Huang, Hsuan-Cheng

    2015-01-01

    Differential coexpression analysis is emerging as a complement to conventional differential gene expression analysis. The identified differential coexpression links can be assembled into a differential coexpression network (DCEN) in response to environmental stresses or genetic changes. Differential coexpression analyses have been successfully used to identify condition-specific modules; however, the structural properties and biological significance of general DCENs have not been well investigated. Here, we analyzed two independent Saccharomyces cerevisiae DCENs constructed from large-scale time-course gene expression profiles in response to different situations. Topological analyses show that DCENs are tree-like networks possessing scale-free characteristics, but not small-world. Functional analyses indicate that differentially coexpressed gene pairs in DCEN tend to link different biological processes, achieving complementary or synergistic effects. Furthermore, the gene pairs lacking common transcription factors are sensitive to perturbation and hence lead to differential coexpression. Based on these observations, we integrated transcriptional regulatory information into DCEN and identified transcription factors that might cause differential coexpression by gain or loss of activation in response to different situations. Collectively, our results not only uncover the unique structural characteristics of DCEN but also provide new insights into interpretation of DCEN to reveal its biological significance and infer the underlying gene regulatory dynamics. PMID:26282208

  14. Osteoblast differentiation is functionally associated with decreased AMP kinase activity.

    PubMed

    Kasai, Takayuki; Bandow, Kenjiro; Suzuki, Hiraku; Chiba, Norika; Kakimoto, Kyoko; Ohnishi, Tomokazu; Kawamoto, Shin-ichiro; Nagaoka, Eiichi; Matsuguchi, Tetsuya

    2009-12-01

    Osteoblasts, originating from mesenchymal stem cells, play a pivotal role in bone formation and mineralization. Several transcription factors including runt-related transcription factor 2 (Runx2) have been reported to be essential for osteoblast differentiation, whereas the cytoplasmic signal transduction pathways controlling the differentiation process have not been fully elucidated. AMP-activated protein kinase (AMPK) is a serine-threonine kinase generally regarded as a key regulator of cellular energy homeostasis, polarity, and division. Recent lines of evidence have indicated that the activity of the catalytic alpha subunit of AMPK is regulated through its phosphorylation by upstream AMPK kinases (AMPKKs) including LKB1. Here, we explored the role of AMPK in osteoblast differentiation using in vitro culture models. Phosphorylation of AMPKalpha was significantly decreased during osteoblastic differentiation in both primary osteoblasts and MC3T3-E1, a mouse osteoblastic cell line. Conversely, the terminal differentiation of primary osteoblasts and MC3T3-E1 cells, represented by matrix mineralization, was significantly inhibited by glucose restriction and stimulation with metformin, both of which are known activators of AMPK. Matrix mineralization of MC3T3-E1 cells was also inhibited by the forced expression of a constitutively active form of AMPKalpha. Metformin significantly inhibited gene expression of Runx2 along with osteoblast differentiation markers including osteocalcin (Ocn), bone sialo protein (Bsp), and osteopontin (Opn). Thus, our present data indicate that differentiation of osteoblasts is functionally associated with decreased AMPK activity. PMID:19725053

  15. Pharmacological Bypass of Cockayne Syndrome B Function in Neuronal Differentiation

    PubMed Central

    Wang, Yuming; Jones-Tabah, Jace; Chakravarty, Probir; Stewart, Aengus; Muotri, Alysson; Laposa, Rebecca R.; Svejstrup, Jesper Q.

    2016-01-01

    Summary Cockayne syndrome (CS) is a severe neurodevelopmental disorder characterized by growth abnormalities, premature aging, and photosensitivity. Mutation of Cockayne syndrome B (CSB) affects neuronal gene expression and differentiation, so we attempted to bypass its function by expressing downstream target genes. Intriguingly, ectopic expression of Synaptotagmin 9 (SYT9), a key component of the machinery controlling neurotrophin release, bypasses the need for CSB in neuritogenesis. Importantly, brain-derived neurotrophic factor (BDNF), a neurotrophin implicated in neuronal differentiation and synaptic modulation, and pharmacological mimics such as 7,8-dihydroxyflavone and amitriptyline can compensate for CSB deficiency in cell models of neuronal differentiation as well. SYT9 and BDNF are downregulated in CS patient brain tissue, further indicating that sub-optimal neurotrophin signaling underlies neurological defects in CS. In addition to shedding light on cellular mechanisms underlying CS and pointing to future avenues for pharmacological intervention, these data suggest an important role for SYT9 in neuronal differentiation. PMID:26972010

  16. HYPERDIRE-HYPERgeometric functions DIfferential REduction: Mathematica-based packages for the differential reduction of generalized hypergeometric functions: Lauricella function FC of three variables

    NASA Astrophysics Data System (ADS)

    Bytev, Vladimir V.; Kniehl, Bernd A.

    2016-09-01

    We present a further extension of the HYPERDIRE project, which is devoted to the creation of a set of Mathematica-based program packages for manipulations with Horn-type hypergeometric functions on the basis of differential equations. Specifically, we present the implementation of the differential reduction for the Lauricella function FC of three variables.

  17. Oligodendroglial differentiation induces mitochondrial genes and inhibition of mitochondrial function represses oligodendroglial differentiation

    PubMed Central

    Schoenfeld, Robert; Wong, Alice; Silva, Jillian; Li, Ming; Itoh, Aki; Horiuchi, Makoto; Itoh, Takayuki; Pleasure, David; Cortopassi, Gino

    2011-01-01

    Demyelination occurs in multiple inherited mitochondrial diseases. We studied which genes were induced as a consequence of differentiation in rodent and human oligodendroglia. Cholesterol, myelin and mitochondrial genes were significantly increased with oligodendroglial differentiation. Mitochondrial DNA content per cell and acetyl CoA-related transcripts increased significantly; thus, the large buildup of cholesterol necessary for myelination appears to require mitochondrial production of acetyl-CoA. Oligodendroglia were treated with low doses of the mitochondrial inhibitor rotenone to test the dependence of differentiation on mitochondrial function. Undifferentiated cells were resistant to rotenone, whereas differentiating cells were much more sensitive. Very low doses of rotenone that did not affect viability or ATP synthesis still inhibited differentiation, as measured by reduced levels of the myelin transcripts 2′,3′-Cyclic Nucleotide-3′-Phosphodiesterase and Myelin Basic Protein. Thus, mitochondrial transcripts and mtDNA are amplified during oligodendroglial differentiation, and differentiating oligodendroglia are especially sensitive to mitochondrial inhibition, suggesting mechanisms for demyelination observed in mitochondrial disease. PMID:20005986

  18. Differential Item Functioning (DIF): Current Problems and Future Directions

    ERIC Educational Resources Information Center

    Karami, Hossein; Salmani Nodoushan, Mohammad Ali

    2011-01-01

    With the rising concerns over the fairness of language tests, Differential Item Functioning (DIF) has been increasingly applied in bias analysis. Despite its widespread use in psychometric circles, DIF is facing a number of serious problems. This paper is an attempt to shed light on a number of the issues involved in DIF analysis. Specifically,…

  19. Detecting Differential Item Functioning Using Logistic Regression Procedures.

    ERIC Educational Resources Information Center

    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)

  20. The epigenetic landscape of mammary gland development and functional differentiation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Most of the development and functional differentiation in the mammary gland occur after birth. Epigenetics is defined as the stable alterations in gene expression potential that arise during development and proliferation. Epigenetic changes are mediated at the biochemical level by the chromatin conf...

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

    ERIC Educational Resources Information Center

    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. Effect of Multiple Testing Adjustment in Differential Item Functioning Detection

    ERIC Educational Resources Information Center

    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…

  3. Detection of Differential Item Functioning in Multiple Groups.

    ERIC Educational Resources Information Center

    Kim, Seock-Ho; And Others

    Detection of differential item functioning (DIF) is most often done between two groups of examinees under item response theory. It is sometimes important, however, to determine whether DIF is present in more than two groups. A method is presented for the detection of DIF in multiple groups. The method, the Q(sub j) statistic, is closely related to…

  4. Three Classes of Nonparametric Differential Step Functioning Effect Estimators

    ERIC Educational Resources Information Center

    Penfield, Randall D.

    2008-01-01

    The examination of measurement invariance in polytomous items is complicated by the possibility that the magnitude and sign of lack of invariance may vary across the steps underlying the set of polytomous response options, a concept referred to as differential step functioning (DSF). This article describes three classes of nonparametric DSF effect…

  5. Local Analytic Solutions of a Functional Differential Equation

    NASA Astrophysics Data System (ADS)

    Liu, Lingxia

    This paper is concerned with the existence of analytic solutions of an iterative functional differential equation. Employing the method of majorant series, we need to discuss the constant α given in Schröder transformation. we study analytic solutions of the equation in the case of α at resonance and the case of α near resonance under the Brjuno condition.

  6. Evaluating the Magnitude of Differential Item Functioning in Polytomous Items.

    ERIC Educational Resources Information Center

    Zwick, Rebecca; Thayer, Dorothy T.

    1996-01-01

    Two possible standard error formulas for the polytomous differential item functioning index proposed by N. J. Dorans and A. P. Schmitt (1991) were derived. These standard errors, and associated hypothesis-testing procedures, were evaluated through simulated data. The standard error that performed better is based on N. Mantel's (1963)…

  7. Real and Artificial Differential Item Functioning in Polytomous Items

    ERIC Educational Resources Information Center

    Andrich, David; Hagquist, Curt

    2015-01-01

    Differential item functioning (DIF) for an item between two groups is present if, for the same person location on a variable, persons from different groups have different expected values for their responses. Applying only to dichotomously scored items in the popular Mantel-Haenszel (MH) method for detecting DIF in which persons are classified by…

  8. IRT Differential Item Functioning: An Examination of Ability Scale Purifications.

    ERIC Educational Resources Information Center

    Lautenschlager, Gary J.; And Others

    1994-01-01

    Item response theory (IRT) differential item functioning (DIF) methods used to determine the accuracy of item classification as biased or unbiased were studied. Results from simulations show that the iterative linking and ability scale purification method can be more effective than iterative linking alone primarily by reducing false negatives.…

  9. Bounded and periodic solutions of nonlinear functional differential equations

    SciTech Connect

    Slyusarchuk, Vasilii E

    2012-05-31

    Conditions for the existence of bounded and periodic solutions of the nonlinear functional differential equation d{sup m}x(t)/dt{sup m} + (Fx)(t) = h(t), t element of R, are presented, involving local linear approximations to the operator F. Bibliography: 23 titles.

  10. Using Mixed Methods to Interpret Differential Item Functioning

    ERIC Educational Resources Information Center

    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…

  11. The Effects of Testlets on Reliability and Differential Item Functioning

    ERIC Educational Resources Information Center

    Teker, Gulsen Tasdelen; Dogan, Nuri

    2015-01-01

    Reliability and differential item functioning (DIF) analyses were conducted on testlets displaying local item dependence in this study. The data set employed in the research was obtained from the answers given by 1,500 students to the 20 items included in six testlets given in English Proficiency Exam by the School of Foreign Languages of a state…

  12. MIMIC Methods for Assessing Differential Item Functioning in Polytomous Items

    ERIC Educational Resources Information Center

    Wang, Wen-Chung; Shih, Ching-Lin

    2010-01-01

    Three multiple indicators-multiple causes (MIMIC) methods, namely, the standard MIMIC method (M-ST), the MIMIC method with scale purification (M-SP), and the MIMIC method with a pure anchor (M-PA), were developed to assess differential item functioning (DIF) in polytomous items. In a series of simulations, it appeared that all three methods…

  13. Advances in the Detection of Differentially Functioning Test Items.

    ERIC Educational Resources Information Center

    Hambleton, Ronald K.; And Others

    The development and evaluation of methods for detecting potentially biased items or differentially functioning items (DIF) represent a critical area of research for psychometricians because of the negative impact of biased items on test validity. A summary is provided of the authors' 12 years of research at the University of Massachusetts…

  14. Detection of Differential Item Functioning Using the Lasso Approach

    ERIC Educational Resources Information Center

    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,…

  15. An Analysis of Differential Item Functioning Based on Calculator Type.

    ERIC Educational Resources Information Center

    Schwarz, Richard; Rich, Changhua; Arenson, Ethan; Podrabsky, Tracy; Cook, Gary

    The effect of calculator type on student performance on a mathematics examination was studied. Differential item functioning (DIF) methodology was applied to examine group differences (calculator use) on item performance while conditioning on the relevant ability. Other survey questions were developed to ask students the extent to which they used…

  16. Testing for Differential Item Functioning with Measures of Partial Association

    ERIC Educational Resources Information Center

    Woods, Carol M.

    2009-01-01

    Differential item functioning (DIF) occurs when an item on a test or questionnaire has different measurement properties for one group of people versus another, irrespective of mean differences on the construct. There are many methods available for DIF assessment. The present article is focused on indices of partial association. A family of average…

  17. A Comparison of Methods for Detecting Differential Distractor Functioning

    ERIC Educational Resources Information Center

    Koon, Sharon

    2010-01-01

    This study examined the effectiveness of the odds-ratio method (Penfield, 2008) and the multinomial logistic regression method (Kato, Moen, & Thurlow, 2009) for measuring differential distractor functioning (DDF) effects in comparison to the standardized distractor analysis approach (Schmitt & Bleistein, 1987). Students classified as participating…

  18. Augmentation of differentiation and gap junction function by kaempferol in partially differentiated colon cancer cells.

    PubMed

    Nakamura, Yasushi; Chang, Chia-Cheng; Mori, Toshio; Sato, Kenji; Ohtsuki, Kozo; Upham, Brad L; Trosko, James E

    2005-03-01

    Kaempferol induces differentiation in partially differentiated colon cancer cells which express low levels of connexin43 protein and connexin43 mRNA (KNC cells). Differentiation was observed as changes in cell morphology and the activity of alkaline phosphatase. Increased differentiation in kaempferol-treated KNC cells correlated with restoration of gap junctional intercellular communication (GJIC), increased levels of connexin43 protein and its phosphorylation status. Phosphorylation (activation) of Stat3 and Erk was also reduced by kaempferol. An inhibitor of Stat3 phosphorylation also induced morphological changes in KNC cells similar to those in kaempferol-treated cells, suggesting that kaempferol-induced differentiation may be mediated by inhibition of Stat3 phosphorylation. These effects were not observed in HCT116 cells, a poorly differentiated colon cancer cell line deficient in expression of connexin43 mRNA and connexin43 protein. In conclusion, kaempferol might function as an anticancer agent by re-establishing GJIC through enhancement of the expression and phosphorylation of connexin43 protein in a tumorigenic colon cancer cell line that already expresses connexin43 mRNA via a Stat3-dependent mechanism. In contrast, kaempferol had no effect in a tumorigenic colon cancer cell line that did not express connexin43 mRNA and was deficient in GJIC. PMID:15618237

  19. Almost automorphic solutions for some partial functional differential equations

    NASA Astrophysics Data System (ADS)

    Ezzinbi, Khalil; N'guerekata, Gaston Mandata

    2007-04-01

    In this work, we study the existence of almost automorphic solutions for some partial functional differential equations. We prove that the existence of a bounded solution on implies the existence of an almost automorphic solution. Our results extend the classical known theorem by Bohr and Neugebauer on the existence of almost periodic solutions for inhomegeneous linear almost periodic differential equations. We give some applications to hyperbolic equations and Lotka-Volterra type equations used to describe the evolution of a single diffusive animal species.

  20. [FUNCTIONAL DIFFERENTIATION IN BRYOZOAN COLONY: A PROTEOMIC ANALYSIS].

    PubMed

    Kutyumov, V A; Maltseva, A L; Kotenko, N; Ostrovsky, A N

    2016-01-01

    Bryozoans are typical modular organisms. They consist of repetitive structural units, the zooids. Bryozoan colonies grow by zooidal budding, with the distribution pattern of the budding loci underlying the diversity of colony forms. Budding is usually restricted to the zooids at the periphery of the colony, which form a "growing edge" or local terminal growth zones. Non-budding parts of the colony can be functionally subdivided, too. In many species colonies consists of regular, often repetitive zones of feeding and non-feeding modules, associated with a periodical degeneration and regeneration of the polypide, retractile tentacle crown with a gut and the accompanying musculature. So, there is functional differentiation in bryozoan colonies but its mechanisms are unknown. Presumably, budding and/or polypide recycling in different colony parts are induced or inhibited by certain determinants of functional specialization. An effective tool of their identification is the comparison of proteomes of functionally different zones. Here we report the results of proteomic analysis of three bryozoan species from the White Sea, which have a different colony form: Flustrellidra hispida, Terminoflustra membranaceotruncata and Securiflustra securifrons. Using differential two-dimensional electrophoresis (2D-DIGE), we compared proteomes of the growing edge and the zones consisting of feeding and non-feeding zooids in these species. We estimated the overall proteome variability, revealed proteins whose relative abundance gradually changed along the proximal-distal colony axis and suggested that they might be involved in the functional differentiation of the colony. PMID:27220253

  1. Limited role of functional differentiation in early diversification of animals.

    PubMed

    Knope, M L; Heim, N A; Frishkoff, L O; Payne, J L

    2015-01-01

    The origin of most animal phyla and classes during the Cambrian explosion has been hypothesized to represent an 'early burst' of evolutionary exploration of functional ecological possibilities. However, the ecological history of marine animals has yet to be fully quantified, preventing an assessment of the early-burst model for functional ecology. Here we use ecological assignments for 18,621 marine animal genera to assess the relative timing of functional differentiation versus taxonomic diversification from the Cambrian to the present day. We find that functional diversity increased more slowly than would be expected given the history of taxonomic diversity. Contrary to previous inferences of rapid ecological differentiation from the early appearances of all well-fossilized phyla and classes, explicit coding of functional characteristics demonstrates that Cambrian genera occupied comparatively few modes of life. Functional diversity increased in the Ordovician and, especially, during the recoveries from the end-Permian and end-Cretaceous mass extinctions. Permanent shifts in the relationship between functional and taxonomic diversity following the era-bounding extinctions indicates a critical role for these biotic crises in coupling taxonomic and functional diversity. PMID:25737406

  2. Limited role of functional differentiation in early diversification of animals

    PubMed Central

    Knope, M.L.; Heim, N.A.; Frishkoff, L.O.; Payne, J.L.

    2015-01-01

    The origin of most animal phyla and classes during the Cambrian explosion has been hypothesized to represent an ‘early burst’ of evolutionary exploration of functional ecological possibilities. However, the ecological history of marine animals has yet to be fully quantified, preventing an assessment of the early-burst model for functional ecology. Here we use ecological assignments for 18,621 marine animal genera to assess the relative timing of functional differentiation versus taxonomic diversification from the Cambrian to the present day. We find that functional diversity increased more slowly than would be expected given the history of taxonomic diversity. Contrary to previous inferences of rapid ecological differentiation from the early appearances of all well-fossilized phyla and classes, explicit coding of functional characteristics demonstrates that Cambrian genera occupied comparatively few modes of life. Functional diversity increased in the Ordovician and, especially, during the recoveries from the end-Permian and end-Cretaceous mass extinctions. Permanent shifts in the relationship between functional and taxonomic diversity following the era-bounding extinctions indicates a critical role for these biotic crises in coupling taxonomic and functional diversity. PMID:25737406

  3. Sodium-Dependent Phosphate Transporters in Osteoclast Differentiation and Function

    PubMed Central

    Dolder, Silvia; Siegrist, Mark; Wagner, Carsten A.; Biber, Jürg; Hernando, Nati; Hofstetter, Willy

    2015-01-01

    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. PMID:25910236

  4. Rax regulates hypothalamic tanycyte differentiation and barrier function in mice

    PubMed Central

    Miranda-Angulo, Ana L.; Byerly, Mardi S.; Mesa, Janny; Wang, Hong; Blackshaw, Seth

    2013-01-01

    The wall of the ventral third ventricle is composed of two distinct cell populations: tanycytes and ependymal cells. Tanycytes regulate many aspects of hypothalamic physiology, but little is known about the transcriptional network that regulates their development and function. We observed that the retina and anterior neural fold homeobox transcription factor (Rax) is selectively expressed in hypothalamic tanycytes, and showed a complementary pattern of expression to markers of hypothalamic ependymal cells, such as Rarres2 (retinoic acid receptor responder). To determine whether Rax controls tanycyte differentiation and function, we generated Rax haploinsufficient mice and examined their cellular and molecular phenotype in adulthood. These mice appeared grossly normal, but careful examination revealed a thinning of the third ventricular wall and reduction of both tanycyte and ependymal markers. These experiments show that Rax is required for hypothalamic tanycyte and ependymal cell differentiation. Rax haploinsufficiency also resulted in the ectopic presence of ependymal cells in the α2 tanycytic zone, where few ependymal cells are normally found, suggesting that Rax is selectively required for α2 tanycyte differentiation. These changes in the ventricular wall were associated with reduced diffusion of Evans Blue tracer from the ventricle to the hypothalamic parenchyma, with no apparent repercussion on the gross anatomical or behavioral phenotype of these mice. In conclusion, we have provided evidence that Rax is required for the normal differentiation and patterning of hypothalamic tanycytes and ependymal cells, as well as for maintenance of the cerebrospinal fluid-hypothalamus barrier. PMID:23939786

  5. Differentiable exact penalty functions via Hestenis-Powell-Rockafellar`s augmented Lagrangian function

    SciTech Connect

    Li, Wu

    1994-12-31

    We study differentiable exact penalty functions, depending only on x, derived from Hestenes-Powell-Rockafellar`s quadratic augmented Lagrangian function for a minimization problem with two-sided inequality constraints by using Fletcher`s Lagrangian multiplier estimate. We also consider new penalty functions, depending only on the Lagrangian multiplier, derived from the augmented Lagrangian function. These penalty functions are particularly useful for quadratic programming problems.

  6. Optimized higher-order automatic differentiation for the Faddeeva function

    NASA Astrophysics Data System (ADS)

    Charpentier, Isabelle

    2016-08-01

    Considerable research efforts have been directed at implementing the Faddeeva function w(z) and its derivatives with respect to z, but these did not consider the key computing issue of a possible dependence of z on some variable t. The general case is to differentiate the compound function w(z(t)) = w ∘ z(t) with respect to t by applying the chain rule for a first order derivative, or Faà di Bruno's formula for higher-order ones. Higher-order automatic differentiation (HOAD) is an efficient and accurate technique for derivative calculation along scientific computing codes. Although codes are available for w(z) , a special symbolic HOAD is required to compute accurate higher-order derivatives for w ∘ z(t) in an efficient manner. A thorough evaluation is carried out considering a nontrivial case study in optics to support this assertion.

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

    SciTech Connect

    Macoch, Mélinda; Morzadec, Claudie; Fardel, Olivier; Vernhet, Laurent

    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

  8. Regulation of T Cell Differentiation and Function by EZH2.

    PubMed

    Karantanos, Theodoros; Chistofides, Anthos; Barhdan, Kankana; Li, Lequn; Boussiotis, Vassiliki A

    2016-01-01

    The enhancer of zeste homolog 2 (EZH2), one of the polycomb-group proteins, is the catalytic subunit of Polycomb-repressive complex 2 (PRC2) and induces the trimethylation of the histone H3 lysine 27 (H3K27me3) promoting epigenetic gene silencing. EZH2 contains a SET domain promoting the methyltransferase activity, while the three other protein components of PRC2, namely EED, SUZ12, and RpAp46/48, induce compaction of the chromatin permitting EZH2 enzymatic activity. Numerous studies highlight the role of this evolutionary conserved protein as a master regulator of differentiation in humans involved in the repression of the homeotic gene and the inactivation of X-chromosome. Through its effects in the epigenetic regulation of critical genes, EZH2 has been strongly linked to cell cycle progression, stem cell pluripotency, and cancer biology, being currently at the cutting edge of research. Most recently, EZH2 has been associated with hematopoietic stem cell proliferation and differentiation, thymopoiesis and lymphopoiesis. Several studies have evaluated the role of EZH2 in the regulation of T cell differentiation and plasticity as well as its implications in the development of autoimmune diseases and graft-versus-host disease (GVHD). The aim of this review is to summarize the current knowledge regarding the role of EZH2 in the regulation of the differentiation and function of T cells focusing on possible applications in various immune-mediated conditions, including autoimmune disorders and GVHD. PMID:27199994

  9. Osteoclast differentiation and function in aquaglyceroporin AQP9 null mice

    PubMed Central

    Liu, Yangjian; Song, Linhua; Wang, Yiding; Rojek, Aleksandra; Nielsen, Søren; Agre, Peter; Carbrey, Jennifer M.

    2008-01-01

    Background Information Osteoclasts are cells specialized for bone resorption and play important roles in bone growth and calcium homeostasis. Differentiation of osteoclasts involves fusion of bone marrow macrophage mononuclear precursors in response to extracellular signals. A dramatic increase in osteoclast cell volume occurs during osteoclast biogenesis and is believed to be mediated by Aquaporin 9 (AQP9), a membrane protein that can rapidly transport water and other small neutral solutes across cell membranes. Results Here we report an increase in expression of AQP9 during differentiation of a mouse macrophage cell line into osteoclasts. Bone marrow macrophages from wild type and AQP9 null mice differentiate into osteoclasts that have similar morphology, contain comparable numbers of nuclei, and digest synthetic bone to the same extent. Bones from wild type and AQP9 null mice contain similar numbers of osteoclasts and have comparable density and structure as measured by X-ray absorptiometry and micro-computed tomography. Conclusions Our data confirm that AQP9 expression rises during osteoclast biogenesis but indicate that AQP9 is not essential for osteoclast function or differentiation under normal physiological conditions. PMID:18666888

  10. Regulation of T Cell Differentiation and Function by EZH2

    PubMed Central

    Karantanos, Theodoros; Chistofides, Anthos; Barhdan, Kankana; Li, Lequn; Boussiotis, Vassiliki A.

    2016-01-01

    The enhancer of zeste homolog 2 (EZH2), one of the polycomb-group proteins, is the catalytic subunit of Polycomb-repressive complex 2 (PRC2) and induces the trimethylation of the histone H3 lysine 27 (H3K27me3) promoting epigenetic gene silencing. EZH2 contains a SET domain promoting the methyltransferase activity, while the three other protein components of PRC2, namely EED, SUZ12, and RpAp46/48, induce compaction of the chromatin permitting EZH2 enzymatic activity. Numerous studies highlight the role of this evolutionary conserved protein as a master regulator of differentiation in humans involved in the repression of the homeotic gene and the inactivation of X-chromosome. Through its effects in the epigenetic regulation of critical genes, EZH2 has been strongly linked to cell cycle progression, stem cell pluripotency, and cancer biology, being currently at the cutting edge of research. Most recently, EZH2 has been associated with hematopoietic stem cell proliferation and differentiation, thymopoiesis and lymphopoiesis. Several studies have evaluated the role of EZH2 in the regulation of T cell differentiation and plasticity as well as its implications in the development of autoimmune diseases and graft-versus-host disease (GVHD). The aim of this review is to summarize the current knowledge regarding the role of EZH2 in the regulation of the differentiation and function of T cells focusing on possible applications in various immune-mediated conditions, including autoimmune disorders and GVHD. PMID:27199994

  11. Control of functional differential equations to target sets in function space

    NASA Technical Reports Server (NTRS)

    Banks, H. T.; Kent, G. A.

    1971-01-01

    Optimal control of systems governed by functional differential equations of retarded and neutral type is considered. Problems with function space initial and terminal manifolds are investigated. Existence of optimal controls, regularity, and bang-bang properties are discussed. Necessary and sufficient conditions are derived, and several solved examples which illustrate the theory are presented.

  12. T follicular helper cell differentiation, function, and roles in disease

    PubMed Central

    Crotty, Shane

    2014-01-01

    Summary Follicular helper T (Tfh) cells are specialized providers of T cell help to B cells, and are essential for germinal center formation, affinity maturation, and the development of most high affinity antibodies and memory B cells. Tfh cell differentiation is a multi-stage, multi-factorial process involving B cell lymphoma 6 (Bcl6) and other transcription factors. This article reviews understanding of Tfh cell biology, including their differentiation, migration, transcriptional regulation, and B cell help functions. Tfh cells are critical components of many protective immune responses against pathogens. As such, there is strong interest in harnessing Tfh cells to improve vaccination strategies. Tfh cells also have roles in a range of other diseases, particularly autoimmune diseases. Overall, there have been dramatic advances in this young field, but there is much to be learned about Tfh cell biology in the interest of applying that knowledge to biomedical needs. PMID:25367570

  13. Neutrophil extracellular traps promote differentiation and function of fibroblasts.

    PubMed

    Chrysanthopoulou, Akrivi; Mitroulis, Ioannis; Apostolidou, Eirini; Arelaki, Stella; Mikroulis, Dimitrios; Konstantinidis, Theocharis; Sivridis, Efthimios; Koffa, Maria; Giatromanolaki, Alexandra; Boumpas, Dimitrios T; Ritis, Konstantinos; Kambas, Konstantinos

    2014-07-01

    Neutrophil activation by inflammatory stimuli and the release of extracellular chromatin structures (neutrophil extracellular traps - NETs) have been implicated in inflammatory disorders. Herein, we demonstrate that NETs released by neutrophils treated either with fibrosis-related agents, such as cigarette smoke, magnesium silicate, bleomycin, or with generic NET inducers, such as phorbol 12-myristate 13-acetate, induced activation of lung fibroblasts (LFs) and differentiation into myofibroblast (MF) phenotype. Interestingly, the aforementioned agents or IL-17 (a primary initiator of inflammation/fibrosis) had no direct effect on LF activation and differentiation. MFs treated with NETs demonstrated increased connective tissue growth factor expression, collagen production, and proliferation/migration. These fibrotic effects were significantly decreased after degradation of NETs with DNase1, heparin or myeloperoxidase inhibitor, indicating the key role of NET-derived components in LF differentiation and function. Furthermore, IL-17 was expressed in NETs and promoted the fibrotic activity of differentiated LFs but not their differentiation, suggesting that priming by DNA and histones is essential for IL-17-driven fibrosis. Additionally, autophagy was identified as the orchestrator of NET formation, as shown by inhibition studies using bafilomycin A1 or wortmannin. The above findings were further supported by the detection of NETs in close proximity to alpha-smooth muscle actin (α-SMA)-expressing fibroblasts in biopsies from patients with fibrotic interstitial lung disease or from skin scar tissue. Together, these data suggest that both autophagy and NETs are involved not only in inflammation but also in the ensuing fibrosis and thus may represent potential therapeutic targets in human fibrotic diseases. PMID:24740698

  14. Sirt6 regulates dendritic cell differentiation, maturation, and function

    PubMed Central

    Lasigliè, Denise; Boero, Silvia; Bauer, Inga; Morando, Sara; Damonte, Patrizia; Cea, Michele; Monacelli, Fiammetta; Odetti, Paizio; Ballestrero, Alberto; Uccelli, Antonio; Mostoslavsky, Raul; Poggi, Alessandro; Nencioni, Alessio

    2016-01-01

    Dendritic cells (DCs) are antigen-presenting cells that critically influence decisions about immune activation or tolerance. Impaired DC function is at the core of common chronic disorders and contributes to reduce immunocompetence during aging. Knowledge on the mechanisms regulating DC generation and function is necessary to understand the immune system and to prevent disease and immunosenescence. Here we show that the sirtuin Sirt6, which was previously linked to healthspan promotion, stimulates the development of myeloid, conventional DCs (cDCs). Sirt6-knockout (Sirt6KO) mice exhibit low frequencies of bone marrow cDC precursors and low yields of bone marrow-derived cDCs compared to wild-type (WT) animals. Sirt6KO cDCs express lower levels of class II MHC, of costimulatory molecules, and of the chemokine receptor CCR7, and are less immunostimulatory compared to WT cDCs. Similar effects in terms of differentiation and immunostimulatory capacity were observed in human monocyte-derived DCs in response to SIRT6 inhibition. Finally, while Sirt6KO cDCs show an overall reduction in their ability to produce IL-12, TNF-α and IL-6 secretion varies dependent on the stimulus, being reduced in response to CpG, but increased in response to other Toll-like receptor ligands. In conclusion, Sirt6 plays a crucial role in cDC differentiation and function and reduced Sirt6 activity may contribute to immunosenescence. PMID:26761436

  15. Formaldehyde exposure impairs the function and differentiation of NK cells.

    PubMed

    Kim, Eun-Mi; Lee, Hwa-Youn; Lee, Eun-Hee; Lee, Ki-Mo; Park, Min; Ji, Kon-Young; Jang, Ji-Hun; Jeong, Yun-Hwa; Lee, Kwang-Ho; Yoon, Il-Joo; Kim, Su-Man; Jeong, Moon-Jin; Kim, Kwang Dong; Kang, Hyung-Sik

    2013-11-25

    We investigated the cytotoxic effects of formaldehyde (FA) on lymphocytes. FA-exposed mice showed a profound reduction not only in the number of natural killer (NK) cells but also in the expression of NK cell-specific receptors, but these mice did not exhibit decreases in the numbers of T or B lymphocytes. FA exposure also induced decreases in NK cytolytic activity and in the expression of NK cell-associated genes, such as IFN-γ, perforin and CD122. To determine the effect of FA on tumorigenicity, C57BL/6 mice were subcutaneously injected with B16F10 melanoma cells after FA exposure. The mass of the B16F10 tumor and the concentration of extravascular polymorphonuclear leukocytes were greater than those in unexposed tumor-bearing control mice. The number and cytolytic activity of NK cells were also reduced in B16F10 tumor-bearing mice exposed to FA. To determine how FA reduces the NK cell number, NK precursor (pNK) cells were treated with FA, and the differentiation status of the NK cells was analyzed. NK cell differentiation was impaired by FA treatment in a concentration-dependent manner. These findings indicate that FA exposure may promote tumor progression by impairing NK cell function and differentiation. PMID:24060340

  16. Silibinin Regulates Lipid Metabolism and Differentiation in Functional Human Adipocytes

    PubMed Central

    Barbagallo, Ignazio; Vanella, Luca; Cambria, Maria T.; Tibullo, Daniele; Godos, Justyna; Guarnaccia, Laura; Zappalà, Agata; Galvano, Fabio; Li Volti, Giovanni

    2016-01-01

    Silibinin, a natural plant flavonolignan 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 remodeling 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. PMID:26834634

  17. IL-33 in T Cell Differentiation, Function, and Immune Homeostasis.

    PubMed

    Peine, Michael; Marek, Roman M; Löhning, Max

    2016-05-01

    Recent studies have highlighted a role for the alarmin interleukin (IL)-33 in CD4(+) and CD8(+) T cell activation and function, and have also revealed important distinctions. The IL-33 receptor ST2 is constitutively and abundantly expressed on T-helper-2 (Th2) and GATA-3(+) regulatory T cells in a GATA-3- and STAT5-dependent manner. Upon activation, Th1 and cytotoxic T cells express ST2 transiently, driven by T-bet and/or STAT4. We review these findings here, and critically examine evidence indicating that IL-33 enhances the differentiation and functionality of various T cell subsets through positive feedback loops involving lineage-specifying transcription factors. In this context, we discuss how quantitative and qualitative differences in ST2 expression between effector and GATA-3(+) regulatory T cells may contribute to immune homeostasis, and outline important areas of future inquiry. PMID:27055914

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

    PubMed

    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. PMID:26299706

  19. TCDD exposure disrupts mammary epithelial cell differentiation and function

    PubMed Central

    Collins, Loretta L.; Lew, Betina J.; Lawrence, B. Paige

    2011-01-01

    Mammary gland growth and differentiation during pregnancy is a developmental process that is sensitive to the toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). TCDD is a widespread environmental contaminant and a potent ligand for the aryl hydrocarbon receptor (AhR). We demonstrate reduced β-casein protein induction in mouse mammary glands and in cultured SCp2 mammary epithelial cells following exposure to TCDD. SCp2 cells exposed to TCDD also show reduced cell clustering and less alveolar-like structure formation. SCp2 cells express transcriptionally active AhR, and exposure to TCDD induces expression of the AhR target gene CYP1B1. Exposure to TCDD during pregnancy reduced expression of the cell adhesion molecule E-cadherin in the mammary gland and decreased phosphorylation of STAT5, a known regulator of β-casein gene expression. These data provide morphological and molecular evidence that TCDD-mediated AhR activation disrupts structural and functional differentiation of the mammary gland, and present an in vitro model for studying the effects of TCDD on mammary epithelial cell function. PMID:19490989

  20. The Epigenetic Landscape of Mammary Gland Development and Functional Differentiation

    PubMed Central

    Rijnkels, Monique; Kabotyanski, Elena; Montazer-Torbati, Mohamad B.; Beauvais, C. Hue; Vassetzky, Yegor; Rosen, Jeffrey M.; Devinoy, Eve

    2010-01-01

    Most of the development and functional differentiation in the mammary gland occur after birth. Epigenetics is defined as the stable alterations in gene expression potential that arise during development and proliferation. Epigenetic changes are mediated at the biochemical level by the chromatin conformation initiated by DNA methylation, histone variants, post-translational modifications of histones, non-histone chromatin proteins, and non-coding RNAs. Epigenetics plays a key role in development. However, very little is known about its role in the developing mammary gland or how it might integrate the many signalling pathways involved in mammary gland development and function that have been discovered during the past few decades. An inverse relationship between marks of closed (DNA methylation) or open chromatin (DnaseI hypersensitivity, certain histone modifications) and milk protein gene expression has been documented. Recent studies have shown that during development and functional differentiation, both global and local chromatin changes occur. Locally, chromatin at distal regulatory elements and promoters of milk protein genes gains a more open conformation. Furthermore, changes occur both in looping between regulatory elements and attachment to nuclear matrix. These changes are induced by developmental signals and environmental conditions. Additionally, distinct epigenetic patterns have been identified in mammary gland stem and progenitor cell sub-populations. Together, these findings suggest that epigenetics plays a role in mammary development and function. With the new tools for epigenomics developed in recent years, we now can begin to establish a framework for the role of epigenetics in mammary gland development and disease. PMID:20157770

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

    ERIC Educational Resources Information Center

    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…

  2. Exploration of the Validity of Gender Differences in Mathematics Assessment Using Differential Bundle Functioning

    ERIC Educational Resources Information Center

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

    2011-01-01

    The aims of this study are (a) to examine the sources of differential functioning by gender via differential bundle functioning (DBF) in mathematics assessment and (b) to use DBF to explore whether the differential functioning displayed is construct-relevant or construct-irrelevant. Three qualitatively different areas, namely curriculum domains,…

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

    NASA Astrophysics Data System (ADS)

    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.

  4. Regulation of epithelial function, differentiation, and remodeling in the epididymis

    PubMed Central

    Breton, Sylvie; Ruan, Ye Chun; Park, Yoo-Jin; Kim, Bongki

    2016-01-01

    The epididymis is a single convoluted tubule lined by a pseudostratified epithelium. Specialized epididymal epithelial cells, the so-called principal, basal, narrow, and clear cells, establish a unique luminal environment for the maturation and storage of spermatozoa. The epididymis is functionally and structurally divided into several segments and sub-segments that create regionally distinct luminal environments. This organ is immature at birth, and epithelial cells acquire their fully differentiated phenotype during an extended postnatal period, but the factors involved in this complex process remain incompletely characterized. In the adult epididymis, the establishment of an acidic luminal pH and low bicarbonate concentration in the epididymis contributes to preventing premature activation of spermatozoa during their maturation and storage. Clear cells are proton-secreting cells throughout the epididymis, but principal cells have distinct acid/base transport properties, depending on their localization within the epididymis. Basal cells are located in all epididymal segments, but they have a distinct morphology depending on the segment and species examined. How this structural plasticity of basal cells is regulated is discussed here. Also, the role of luminal factors and androgens in the regulation of epithelial cells is reviewed in relation to their respective localization in the proximal versus distal regions of the epididymis. Finally, we describe a novel role for CFTR in tubulogenesis and epithelial cell differentiation. PMID:26585699

  5. MicroRNA control of lymphocyte differentiation and function

    PubMed Central

    Belver, Laura; Papavasiliou, Nina F; Ramiro, Almudena R

    2011-01-01

    Summary MicroRNAs (miRNAs) are a class of endogenous, non-coding regulatory RNAs that control gene regulation by guiding silencing protein complexes to mRNA in a sequence-dependent manner. In this way miRNAs are able to repress gene expression post-transcriptionally by affecting mRNA stability or translation. These ubiquitous molecules play central roles in a wide range of biological processes, including cell proliferation, differentiation and apoptosis. Within the context of the immune system, genetic studies have identified distinct roles for specific miRNAs in gene regulation during development, activation and maturation. Conversely, dysregulation of miRNA expression has been specifically correlated with cancer. This review outlines our current understanding of miRNA function in lymphocytes as it impacts expression of protein-coding genes in the context of proper development, as well as oncogenesis. PMID:21353514

  6. Differential association between chronic cannabis use and brain function deficits.

    PubMed

    Soueif, M I

    1976-01-01

    To summarize, 12 objective tests that generated 16 test variables were administered to 850 male regular cannabis users and 839 nonusers. The tests were designed to assess various modalities, including speed of psychomotor performance, distance estimation, time estimation, immediate memory, and visuomotor coordination. Most of the test variables differentiated significantly between consumers and controls. At the same time, a significant second-order interaction emerged in most cases. This interaction meant that, under certain conditions that relate to the two dimensions "literacy-illiteracy" and/or "urbanism-ruralism," the superiority of controls over cannabis users became impressive, whereas under other conditions it almost disappeared. To account for this complex pattern of results, a working hypothesis was presented to the effect that "other conditions being equal, the lower the nondrug level of proficiency on tests of cognitive and psychomotor performance the smaller the size of function deficit associated with drug usage." For an empirical examination of the hypothesis, six predictions were formulated. Three predictions defined specific relationships between level of performance, on one hand, and each of three organismic variables, on the other: literacy, urbanism, and age. The remaining predictions delineated relationships to be expected between size of function deficit and the three organismic variables. All our predictions were confirmed, showing less function impairment to be contingent with cannabis usage among the illiterates, rurals, and older subjects. Level of cortical arousal was suggested as the central process associated with the three organismic variables. Because the version of our working hypothesis was formulated with reference to chronic material, the possibility of a transposition of the paradign to research on the acute effects of the drug was discussed. The suggestion was made that our working hypothesis, in either version, is capable of

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

    PubMed

    Kim, Yongkyu; Liesack, Werner

    2015-01-01

    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, they both

  8. Defining a Model for Mitochondrial Function in mESC Differentiation

    EPA Science Inventory

    Defining a Model for Mitochondrial Function in mESC DifferentiationDefining a Model for Mitochondrial Function in mESC Differentiation Differentiating embryonic stem cells (ESCs) undergo mitochondrial maturation leading to a switch from a system dependent upon glycolysis to a re...

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

    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. PMID:24792180

  11. Racial differences in hypertension knowledge: effects of differential item functioning.

    PubMed

    Ayotte, Brian J; Trivedi, Ranak; Bosworth, Hayden B

    2009-01-01

    Health-related knowledge is an important component in the self-management of chronic illnesses. The objective of this study was to more accurately assess racial differences in hypertension knowledge by using a latent variable modeling approach that controlled for sociodemographic factors and accounted for measurement issues in the assessment of hypertension knowledge. Cross-sectional data from 1,177 participants (45% African American; 35% female) were analyzed using a multiple indicator multiple causes (MIMIC) modeling approach. Available sociodemographic data included race, education, sex, financial status, and age. All participants completed six items on a hypertension knowledge questionnaire. Overall, the final model suggested that females, Whites, and patients with at least a high school diploma had higher latent knowledge scores than males, African Americans, and patients with less than a high school diploma, respectively. The model also detected differential item functioning (DIF) based on race for two of the items. Specifically, the error rate for African Americans was lower than would be expected given the lower level of latent knowledge on the items, on the questions related to: (a) the association between high blood pressure and kidney disease, and (b) the increased risk African Americans have for developing hypertension. Not accounting for DIF resulted in the difference between Whites and African Americans to be underestimated. These results are discussed in the context of the need for careful measurement of health-related constructs, and how measurement-related issues can result in an inaccurate estimation of racial differences in hypertension knowledge. PMID:19341159

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

    PubMed

    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. PMID:24956585

  13. Carcinoma origin dictates differential skewing of monocyte function

    PubMed Central

    Bögels, Marijn; Braster, Rens; Nijland, Philip G.; Gül, Nuray; van de Luijtgaarden, Wendy; Fijneman, Remond J.A.; Meijer, Gerrit A.; Jimenez, Connie R.; Beelen, Robert H.J.; van Egmond, Marjolein

    2012-01-01

    Macrophages are versatile cells, which phenotype is profoundly influenced by their environment. Pro-inflammatory classically activated or M1 macrophages, and anti-inflammatory alternatively-activated or M2 macrophages represent two extremes of a continuum of functional states. Consequently, macrophages that are present in tumors can exert tumor-promoting and tumor-suppressing activity, depending on the tumor milieu. In this study we investigated how human monocytes—the precursors of macrophages—are influenced by carcinoma cells of different origin. We demonstrate that monocytes, stimulated with breast cancer supernatant, showed increased expression of interleukin (IL)-10, IL-8 and chemokines CCL17 and CCL22, which are associated with an alternatively-activated phenotype. By contrast, monocytes that were cultured in supernatants of colon cancer cells produced more pro-inflammatory cytokines (e.g., IL-12 and TNFα) and reactive oxygen species. Secretome analysis revealed differential secretion of proteins by colon and breast cancer cell lines, of which the proteoglycan versican was exclusively secreted by colon carcinoma cell lines. Reducing active versican by blocking with monoclonal antibodies or shRNA diminished pro-inflammatory cytokine production by monocytes. Thus, colon carcinoma cells polarize monocytes toward a more classically-activated anti-tumorigenic phenotype, whereas breast carcinomas predispose monocytes toward an alternatively activated phenotype. Interestingly, presence of macrophages in breast or colon carcinomas correlates with poor or good prognosis in patients, respectively. The observed discrepancy in macrophage activation by either colon or breast carcinoma cells may therefore explain the dichotomy between patient prognosis and macrophage presence in these different tumors. Designing new therapies, directing development of monocytes toward M1 activated tumor macrophages in cancer patients, may have great clinical benefits. PMID:23162747

  14. Quasi-Newton methods for parameter estimation in functional differential equations

    NASA Technical Reports Server (NTRS)

    Brewer, Dennis W.

    1988-01-01

    A state-space approach to parameter estimation in linear functional differential equations is developed using the theory of linear evolution equations. A locally convergent quasi-Newton type algorithm is applied to distributed systems with particular emphasis on parameters that induce unbounded perturbations of the state. The algorithm is computationally implemented on several functional differential equations, including coefficient and delay estimation in linear delay-differential equations.

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

    ERIC Educational Resources Information Center

    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…

  16. A Generalized DIF Effect Variance Estimator for Measuring Unsigned Differential Test Functioning in Mixed Format Tests

    ERIC Educational Resources Information Center

    Penfield, Randall D.; Algina, James

    2006-01-01

    One approach to measuring unsigned differential test functioning is to estimate the variance of the differential item functioning (DIF) effect across the items of the test. This article proposes two estimators of the DIF effect variance for tests containing dichotomous and polytomous items. The proposed estimators are direct extensions of the…

  17. Genes associated with T helper 17 cell differentiation and function.

    PubMed

    Nalbant, Ayten; Eskier, Doga

    2016-01-01

    Interleukin-17 (IL-17)-producing T helper cells (Th17 cells) constitute a lineage of CD4 effector T helper cells that is distinct from the Th1 and Th2 CD4 phenotypes. In humans, Th17 differentiation is induced in the presence of the cytokines IL-1 beta, IL-6 and TGF beta, whereas IL-23 maintains Th17 survival. Effector human Th17 cells express several cytokines and cell surface markers, including IL-17A, IL-17F, IL-22, IL-26, CCR6 and TNFalpha. Studies on human cells have revealed that the RORC2 transcription factor plays an effective role in Th17 differentiation. Th17 cells contribute to the host immune response by involving various pathologies, including rheumatoid arthritis, multiple sclerosis and Crohn's disease. However, the full extent of their contribution to diseases is being investigated. The differentiation of Th17 cells is controlled by many transcription factors, including ROR gammat, IRF4, RUNX1, BATF, and STAT3. This review covers the general principles of CD4 T helper differentiation and the known transcription factors that play a role in the recently discovered Th17 cells. PMID:27100349

  18. Metabolic regulation of T cell differentiation and function

    PubMed Central

    Park, Benjamin V.; Pan, Fan

    2016-01-01

    Upon encountering pathogens, T cells mount immune responses by proliferating, increasing cellular mass and differentiating. These cellular changes impose significant energetic challenges on T cells. It was believed that TCR and cytokine-mediated signaling are dominant dictators of T cell-mediated immune responses. Recently, it was recognized that T cells utilize metabolic transporters and metabolic sensors that allow them to rapidly respond to nutrient-limiting inflammatory environments. Metabolic sensors allow T cells to find a balance between energy consumption (anabolic metabolism) and production (catabolic metabolism) in order to mount effective immune responses. Also, metabolic regulators interact with cytokine-dependent transcriptional regulators, suggesting a more integrative and advanced model of T cell activation and differentiation. In this review, we will discuss recent discoveries regarding the roles of metabolic regulators in effector and memory T cell development and their interaction with canonical transcription factors. PMID:26277275

  19. T Cell Receptor Signaling in the Control of Regulatory T Cell Differentiation and Function

    PubMed Central

    Li, Ming O.; Rudensky, Alexander Y.

    2016-01-01

    Regulatory T cells (TReg cells), a specialized T cell lineage, have a pivotal function in the control of self-tolerance and inflammatory responses. Recent studies have revealed a discrete mode of TCR signaling that regulates Treg cell differentiation, maintenance and function and that impacts on gene expression, metabolism, cell adhesion and migration of these cells. Here, we discuss the emerging understanding of TCR-guided differentiation of Treg cells in the context of their function in health and disease. PMID:27026074

  20. Some properties of solutions of a functional-differential equation of second order with delay.

    PubMed

    Ilea, Veronica Ana; Otrocol, Diana

    2014-01-01

    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. PMID:24683363

  1. Exploring Differential Bundle Functioning in Mathematics by Gender: The Effect of Hierarchical Modelling

    ERIC Educational Resources Information Center

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

    2013-01-01

    Researchers interested in exploring substantive group differences are increasingly attending to bundles of items (or testlets): the aim is to understand how gender differences, for instance, are explained by differential performances on different types or bundles of items, hence differential bundle functioning (DBF). Some previous work has…

  2. Analytical solution to a non-autonomous second order differential equation with modified hyperbolic tangent function

    NASA Astrophysics Data System (ADS)

    Fernández-Guasti, M.

    2015-03-01

    The solution to a non-autonomous second order ordinary differential equation is presented. The real function, dependent on the differentiation variable, is a squared hyperbolic tangent function plus a term that involves the quotient of hyperbolic functions. This function varies from one limiting value to another without having any singularities. The solution is remarkably simple and involves only trigonometric and hyperbolic trigonometric functions. The solution is analyzed in the context of wave propagation in an inhomogeneous one-dimensional medium. The profile is shown to act as a perfect anti-reflection interface, providing a possible alternative route to the fabrication of reflectionless surfaces.

  3. Collective Dynamics Differentiates Functional Divergence in Protein Evolution

    PubMed Central

    Glembo, Tyler J.; Farrell, Daniel W.; Gerek, Z. Nevin; Thorpe, M. F.; Ozkan, S. Banu

    2012-01-01

    Protein evolution is most commonly studied by analyzing related protein sequences and generating ancestral sequences through Bayesian and Maximum Likelihood methods, and/or by resurrecting ancestral proteins in the lab and performing ligand binding studies to determine function. Structural and dynamic evolution have largely been left out of molecular evolution studies. Here we incorporate both structure and dynamics to elucidate the molecular principles behind the divergence in the evolutionary path of the steroid receptor proteins. We determine the likely structure of three evolutionarily diverged ancestral steroid receptor proteins using the Zipping and Assembly Method with FRODA (ZAMF). Our predictions are within ∼2.7 Å all-atom RMSD of the respective crystal structures of the ancestral steroid receptors. Beyond static structure prediction, a particular feature of ZAMF is that it generates protein dynamics information. We investigate the differences in conformational dynamics of diverged proteins by obtaining the most collective motion through essential dynamics. Strikingly, our analysis shows that evolutionarily diverged proteins of the same family do not share the same dynamic subspace, while those sharing the same function are simultaneously clustered together and distant from those, that have functionally diverged. Dynamic analysis also enables those mutations that most affect dynamics to be identified. It correctly predicts all mutations (functional and permissive) necessary to evolve new function and ∼60% of permissive mutations necessary to recover ancestral function. PMID:22479170

  4. On the Relationship between Differential Item Functioning and Item Difficulty: An Issue of Methods? Item Response Theory Approach to Differential Item Functioning

    ERIC Educational Resources Information Center

    Santelices, Maria Veronica; Wilson, Mark

    2012-01-01

    The relationship between differential item functioning (DIF) and item difficulty on the SAT is such that more difficult items tended to exhibit DIF in favor of the focal group (usually minority groups). These results were reported by Kulick and Hu, and Freedle and have been enthusiastically discussed by more recent literature. Examining the…

  5. Mental Functioning, Perceptual Differentiation, Personality, and Achievement among Art and Non-Art Majors.

    ERIC Educational Resources Information Center

    Dorethy, Rex; Reeves, Dan

    1979-01-01

    College art majors, art education majors, and nonart majors were compared on measures of brain hemisphere dominance, general intelligence, brain functioning, visual perceptual differentiation, grade point average, flexibility-rigidity, and personal-social adjustment. (SJL)

  6. FETAL DEXAMETHASONE EXPOSURE ACCELERATES DEVELOPMENT OF RENAL FUNCTION: RELATIONSHIP TO DOSE, CELL DIFFERENTIATION AND GROWTH INHIBITION

    EPA Science Inventory

    Fetal exposure to high doses of glucocorticoids slows cellular development and impairs organ performance, in association with growth retardation. evertheless, low doses of glucocorticoids may enhance cell differentiation and accelerate specific functions. he current study examine...

  7. Directed Differentiation of Functional Astroglial Subtypes from Human Pluripotent Stem Cells

    PubMed Central

    Krencik, Robert; Zhang, Su-Chun

    2011-01-01

    Regionally and functionally diverse types of astrocytes exist throughout the central nervous system and participate in nearly every aspect of normal and abnormal neural function. Therefore, human astrocyte subtypes are a useful tool for understanding brain function, modulating disease processes, and promoting neural regeneration. Here we describe a protocol for directed differentiation and maintenance of functional astroglia from human pluripotent stem cells in a chemically defined system. Human stem cells are first differentiated to neuroepithelial cells with or without exogenous patterning molecules(days 0 –21). Regular dissociation of the neuroepithelial clusters in suspension, and in the presence of mitogens, permits generation of astroglial subtypes over along term expansion (days 21–90). Finally, the astroglial progenitors are either amplified for an extended time or differentiated to functional astrocytes upon removal of mitogens and the addition of CNTF ( days > 90). This method generates robust populations of functionally diversified astrocytes with high efficiency. PMID:22011653

  8. Regeneration niche differentiates functional strategies of desert woody plant species

    PubMed Central

    Briggs, John M.

    2010-01-01

    Plant communities vary dramatically in the number and relative abundance of species that exhibit facilitative interactions, which contributes substantially to variation in community structure and dynamics. Predicting species’ responses to neighbors based on readily measurable functional traits would provide important insight into the factors that structure plant communities. We measured a suite of functional traits on seedlings of 20 species and mature plants of 54 species of shrubs from three arid biogeographic regions. We hypothesized that species with different regeneration niches—those that require nurse plants for establishment (beneficiaries) versus those that do not (colonizers)—are functionally different. Indeed, seedlings of beneficiary species had lower relative growth rates, larger seeds and final biomass, allocated biomass toward roots and height at a cost to leaf mass fraction, and constructed costly, dense leaf and root tissues relative to colonizers. Likewise at maturity, beneficiaries had larger overall size and denser leaves coupled with greater water use efficiency than colonizers. In contrast to current hypotheses that suggest beneficiaries are less “stress-tolerant” than colonizers, beneficiaries exhibited conservative functional strategies suited to persistently dry, low light conditions beneath canopies, whereas colonizers exhibited opportunistic strategies that may be advantageous in fluctuating, open microenvironments. In addition, the signature of the regeneration niche at maturity indicates that facilitation expands the range of functional diversity within plant communities at all ontogenetic stages. This study demonstrates the utility of specific functional traits for predicting species’ regeneration niches in hot deserts, and provides a framework for studying facilitation in other severe environments. Electronic supplementary material The online version of this article (doi:10.1007/s00442-010-1741-y) contains supplementary

  9. Sexual Differentiation of Circadian Clock Function in the Adrenal Gland.

    PubMed

    Kloehn, Ian; Pillai, Savin B; Officer, Laurel; Klement, Claire; Gasser, Paul J; Evans, Jennifer A

    2016-05-01

    Sex differences in glucocorticoid production are associated with increased responsiveness of the adrenal gland in females. However, the adrenal-intrinsic mechanisms that establish sexual dimorphic function remain ill defined. Glucocorticoid production is gated at the molecular level by the circadian clock, which may contribute to sexual dimorphic adrenal function. Here we examine sex differences in the adrenal gland using an optical reporter of circadian clock function. Adrenal glands were cultured from male and female Period2::Luciferase (PER2::LUC) mice to assess clock function in vitro in real time. We confirm that there is a pronounced sex difference in the intrinsic capacity to sustain PER2::LUC rhythms in vitro, with higher amplitude rhythms in adrenal glands collected from males than from females. Changes in adrenal PER2::LUC rhythms over the reproductive life span implicate T as an important factor in driving sex differences in adrenal clock function. By directly manipulating hormone levels in adult mice in vivo, we demonstrate that T increases the amplitude of PER2::LUC rhythms in adrenal glands of both male and female mice. In contrast, we find little evidence that ovarian hormones modify adrenal clock function. Lastly, we find that T in vitro can increase the amplitude of PER2::LUC rhythms in male adrenals but not female adrenals, which suggests the existence of sex differences in the mechanisms of T action in vivo. Collectively these results reveal that activational effects of T alter circadian timekeeping in the adrenal gland, which may have implications for sex differences in stress reactivity and stress-related disorders. PMID:27007073

  10. Integral estimates for differentiable functions on irregular domains

    SciTech Connect

    Besov, Oleg V

    2011-02-11

    Integral representations for functions and their partial derivatives in terms of some fixed system of partial derivatives are constructed on irregular domains in a Euclidean space. Embedding theorems for Sobolev-type spaces into a Lebesgue space are established and the norms of the derivatives are estimated. Bibliography: 17 titles.

  11. Differential function of Themis CABIT domains during T cell development.

    PubMed

    Okada, Toshiyuki; Nitta, Takeshi; Kaji, Kentaro; Takashima, Akiko; Oda, Hiroyo; Tamehiro, Norimasa; Goto, Motohito; Okamura, Tadashi; Patrick, Michael S; Suzuki, Harumi

    2014-01-01

    Themis (also named Gasp) is a newly identified Grb2-binding protein that is essential for thymocyte positive selection. Despite the possible involvement of Themis in TCR-mediated signal transduction, its function remains unresolved and controversial. Themis contains two functionally uncharacterized regions called CABIT (cysteine-containing, all-β in Themis) domains, a nuclear localization signal (NLS), and a proline-rich sequence (PRS). To elucidate the role of these motifs in Themis's function in vivo, we established a series of mutant Themis transgenic mice on a Themis(-/-) background. Deletion of the highly conserved Core motif of CABIT1 or CABIT2 (Core1 or Core2, respectively), the NLS, or the PRS abolished Grb2-association, as well as TCR-dependent tyrosine-phosphorylation and the ability to induce positive selection in the thymus. The NLS and Core1 motifs were required for the nuclear localization of Themis, whereas Core2 and PRS were not. Furthermore, expression of ΔCore1- but not ΔCore2-Themis conferred dominant negative-type inhibition on T cell development. Collectively, our current results indicate that PRS, NLS, CABIT1, and CABIT2 are all required for positive selection, and that each of the CABIT domains exerts distinct functions during positive selection. PMID:24586531

  12. Differentiating High-Functioning Autism and Social Phobia

    ERIC Educational Resources Information Center

    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,…

  13. Numerical solution of distributed order fractional differential equations by hybrid functions

    NASA Astrophysics Data System (ADS)

    Mashayekhi, S.; Razzaghi, M.

    2016-06-01

    In this paper, a new numerical method for solving the distributed fractional differential equations is presented. The method is based upon hybrid functions approximation. The properties of hybrid functions consisting of block-pulse functions and Bernoulli polynomials are presented. The Riemann-Liouville fractional integral operator for hybrid functions is introduced. This operator is then utilized to reduce the solution of the distributed fractional differential equations to a system of algebraic equations. Illustrative examples are included to demonstrate the validity and applicability of the technique.

  14. Development and Demonstration of Multidimensional IRT-Based Internal Measures of Differential Functioning of Items and Tests.

    ERIC Educational Resources Information Center

    Oshima, T. C.; Raju, Nambury S. Rajo; Flowers, Claudia P.

    1997-01-01

    Defines and demonstrates a framework for studying differential item functioning and differential test functioning for tests that are intended to be multidimensional. The procedure, which is illustrated with simulated data, is an extension of the unidimensional differential functioning of items and tests approach (N. Raju, W. van der Linden, and P.…

  15. Decellularized Tracheal Extracellular Matrix Supports Epithelial Migration, Differentiation, and Function

    PubMed Central

    Kutten, Johannes C.; McGovern, David; Hobson, Christopher M.; Luffy, Sarah A.; Nieponice, Alejandro; Tobita, Kimimasa; Francis, Richard J.; Reynolds, Susan D.

    2015-01-01

    Tracheal loss is a source of significant morbidity for affected patients with no acceptable solution. Interest in engineering tracheal transplants has created a demand for small animal models of orthotopic tracheal transplantation. Here, we examine the use of a decellularized graft in a murine model of tracheal replacement. Fresh or decellularized tracheas harvested from age-matched female donor C57BL/6 mice were transplanted into syngeneic recipients. Tracheas were decellularized using repeated washes of water, 3% Triton X-100, and 3 M NaCl under cyclic pressure changes, followed by disinfection with 0.1% peracetic acid/4% ethanol, and terminal sterilization by gamma irradiation. Tracheas were explanted for immunolabeling at 1, 4, and 8 weeks following surgery. Video microscopy and computed tomography were performed to assess function and structure. Decellularized grafts supported complete reepithelialization by 8 weeks and motile cilia were observed. Cartilaginous portions of the trachea were maintained in mice receiving fresh transplants, but repopulation of the cartilage was not seen in mice receiving decellularized transplants. We observed superior postsurgical survival, weight gain, and ciliary function in mice receiving fresh transplants compared with those receiving decellularized transplants. The murine orthotopic tracheal transplant provides an appropriate model to assess the repopulation and functional regeneration of decellularized tracheal grafts. PMID:24980864

  16. A taxonomy of effect size measures for the differential functioning of items and scales.

    PubMed

    Meade, Adam W

    2010-07-01

    Much progress has been made in the past 2 decades with respect to methods of identifying measurement invariance or a lack thereof. Until now, the focus of these efforts has been to establish criteria for statistical significance in items and scales that function differently across samples. The power associated with tests of differential functioning, as with all significance tests, is affected by sample size and other considerations. Additionally, statistical significance need not imply practical importance. There is a strong need as such for meaningful effect size indicators to describe the extent to which items and scales function differently. Recently developed effect size measures show promise for providing a metric to describe the amount of differential functioning present between groups. Expanding upon recent developments, this article presents a taxonomy of potential differential functioning effect sizes; several new indices of item and scale differential functioning effect size are proposed and illustrated with 2 data samples. Software created for computing these indices and graphing item- and scale-level differential functioning is described. PMID:20604592

  17. Intrinsic functional connectivity differentiates minimally conscious from unresponsive patients.

    PubMed

    Demertzi, Athena; Antonopoulos, Georgios; Heine, Lizette; Voss, Henning U; Crone, Julia Sophia; de Los Angeles, Carlo; Bahri, Mohamed Ali; Di Perri, Carol; Vanhaudenhuyse, Audrey; Charland-Verville, Vanessa; Kronbichler, Martin; Trinka, Eugen; Phillips, Christophe; Gomez, Francisco; Tshibanda, Luaba; Soddu, Andrea; Schiff, Nicholas D; Whitfield-Gabrieli, Susan; Laureys, Steven

    2015-09-01

    Despite advances in resting state functional magnetic resonance imaging investigations, clinicians remain with the challenge of how to implement this paradigm on an individualized basis. Here, we assessed the clinical relevance of resting state functional magnetic resonance imaging acquisitions in patients with disorders of consciousness by means of a systems-level approach. Three clinical centres collected data from 73 patients in minimally conscious state, vegetative state/unresponsive wakefulness syndrome and coma. The main analysis was performed on the data set coming from one centre (Liège) including 51 patients (26 minimally conscious state, 19 vegetative state/unresponsive wakefulness syndrome, six coma; 15 females; mean age 49 ± 18 years, range 11-87; 16 traumatic, 32 non-traumatic of which 13 anoxic, three mixed; 35 patients assessed >1 month post-insult) for whom the clinical diagnosis with the Coma Recovery Scale-Revised was congruent with positron emission tomography scanning. Group-level functional connectivity was investigated for the default mode, frontoparietal, salience, auditory, sensorimotor and visual networks using a multiple-seed correlation approach. Between-group inferential statistics and machine learning were used to identify each network's capacity to discriminate between patients in minimally conscious state and vegetative state/unresponsive wakefulness syndrome. Data collected from 22 patients scanned in two other centres (Salzburg: 10 minimally conscious state, five vegetative state/unresponsive wakefulness syndrome; New York: five minimally conscious state, one vegetative state/unresponsive wakefulness syndrome, one emerged from minimally conscious state) were used to validate the classification with the selected features. Coma Recovery Scale-Revised total scores correlated with key regions of each network reflecting their involvement in consciousness-related processes. All networks had a high discriminative capacity (>80%) for

  18. Differential geometry of the Fermat quartic and theta functions

    NASA Astrophysics Data System (ADS)

    Hadnot, Jason

    2012-02-01

    The universal curve over a finite cover of the moduli space of elliptic curves with level four structure is embedded in C as the Fermat quartic and is parametrized via the four Jacobi theta functions. Constructions from completely integrable systems have shown the importance of looking at the curvature of certain spaces and here we compute sectional curvatures. For our computations, we choose the ambient Fubini-Study metric of C. We also derive several theta identities which arise from the quartic's holomorphic two-form.

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

    PubMed

    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. PMID:26801556

  20. On the representation of bicomplex pseudoanalytic functions by integro-differential operators

    NASA Astrophysics Data System (ADS)

    Berglez, Peter

    2016-06-01

    We consider a class of bicomplex pseudoanalytic functions which can be characterized by the generalized Bers-Vekua equation D w =c w * with c =γ-1(D γ ) where D represents the generalized Cauchy-Riemann operator of bicomplex analysis and γ a suitable solution of the differential equation DD*U - (n(n + 1)/(z + z*)2)U = 0, n ∈ ℕ. Using a particular Bäcklund transformation we succeed finding explicit representations for the solutions w by means of certain integro-differential operators. These operators act on bicomplex holomorphic functions. Some cases where the function γ is of particular form are investigated in detail.

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

    ERIC Educational Resources Information Center

    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…

  2. Analysis of Sources of Latent Class Differential Item Functioning in International Assessments

    ERIC Educational Resources Information Center

    Oliveri, Maria Elena; Ercikan, Kadriye; Zumbo, Bruno

    2013-01-01

    In this study, we investigated differential item functioning (DIF) and its sources using a latent class (LC) modeling approach. Potential sources of LC DIF related to instruction and teacher-related variables were investigated using substantive and three statistical approaches: descriptive discriminant function, multinomial logistic regression,…

  3. The Green's function of the second order differential operator with an involution and its application

    NASA Astrophysics Data System (ADS)

    Sarsenbi, Abdizhahan

    2015-09-01

    In this paper, the Green's function of a boundary boundary value problem with an involution is constructed. Applying the Green's function, a formula for expansion in the eigenfunctions of the spectral problem for a second order differential equation with an involution involving boundary conditions of Dirichlet type is presented.

  4. A Conceptual Analysis of Differential Item Functioning in Terms of a Multidimensional Item Response Model.

    ERIC Educational Resources Information Center

    Camilli, Gregory

    1992-01-01

    A mathematical model is proposed to describe how group differences in distributions of abilities, which are distinct from the target ability, influence the probability of a correct item response. In the multidimensional approach, differential item functioning is considered a function of the educational histories of the examinees. (SLD)

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

    ERIC Educational Resources Information Center

    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.

  6. Detection of Gender-Based Differential Item Functioning in a Mathematics Performance Assessment.

    ERIC Educational Resources Information Center

    Wang, Ning; Lane, Suzanne

    This study used three different differential item functioning (DIF) procedures to examine the extent to which items in a mathematics performance assessment functioned differently for matched gender groups. In addition to examining the appropriateness of individual items in terms of DIF with respect to gender, an attempt was made to identify…

  7. The method of local linear approximation in the theory of nonlinear functional-differential equations

    SciTech Connect

    Slyusarchuk, Vasilii E

    2010-10-06

    Conditions for the existence of solutions to the nonlinear functional-differential equation (d{sup m}x(t))/dt{sup m} + (fx)(t)=h(t), t element of R in the space of functions bounded on the axes are obtained by using local linear approximation to the operator F. Bibliography: 21 items.

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

    ERIC Educational Resources Information Center

    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,…

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

    ERIC Educational Resources Information Center

    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…

  10. Systematically Differentiating Functions for Alternatively Spliced Isoforms through Integrating RNA-seq Data

    PubMed Central

    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. PMID:24244129

  11. Starches of varied digestibilities differentially modify intestinal function in rats.

    PubMed

    Lajvardi, A; Mazarin, G I; Gillespie, M B; Satchithanandam, S; Calvert, R J

    1993-12-01

    Starches of different digestibilities may enter the colon to different extents and alter colonic function. Male Fischer 344 rats were fed diets containing 25% cooked potato starch, arrowroot starch, high amylose cornstarch or raw potato starch for 6 wk. Fecal weight, transit time, colonic thymidine kinase activity (a marker for cell proliferation), and weight, starch content and pH of the cecum and proximal and distal colon were measured. Raw potato starch was much less completely digested than high amylose cornstarch, resulting in a 32-fold greater amount of undigested starch entering the cecum in the raw potato starch group. Both the high amylose cornstarch and raw potato starch diets significantly enhanced fecal weight and produced large intestinal hypertrophy, effects that were greatest in the raw potato starch group. Raw potato starch feeding was associated with the highest level of thymidine kinase activity, although the differences in thymidine kinase activity among the four groups were not significant. This diet also produced a 50% longer transit time. Entry of a large amount of raw potato starch into the colon resulted in greater luminal acidity, greater luminal bulk and slower transit. A much smaller amount of starch entered the colon in the high amylose cornstarch group and resulted in fecal bulking but no alteration in transit. PMID:8263598

  12. Differential regional effects of octreotide on human gastrointestinal motor function.

    PubMed Central

    von der Ohe, M R; Camilleri, M; Thomforde, G M; Klee, G G

    1995-01-01

    The effects of octreotide on regional motor function in the human gut are unclear. In a randomised, blinded study the effects of octreotide (50 micrograms, subcutaneously, three times daily) and placebo on gastric, small bowel, and colonic transit, and colonic motility and tone were assessed in 12 healthy volunteers whose colon had been cleansed. Octreotide accelerated initial gastric emptying (p = 0.05), inhibited small bowel transit (p < 0.01), and reduced ileocolonic bolus transfers (p < 0.05). Colonic transit was unaltered by octreotide; the postprandial colonic tonic response was inhibited (p < 0.05 v placebo), whereas colonic phasic pressure activity was increased by octreotide (p < 0.05 v placebo). These data support the use of octreotide in diarrhoeal states but not in diseases that cause small bowel stasis and bacterial overgrowth. Simultaneous measurements of colonic transit, tone, and phasic contractility are valid in studying the effects of pharmacological changes and may be applicable to the study of the human colon in health and disease. PMID:7797125

  13. Oscillations of solutions of vector differential equations of parabolic type with functional arguments

    NASA Astrophysics Data System (ADS)

    Minchev, Emil; Yoshida, Norio

    2003-02-01

    Vector parabolic differential equations with functional arguments are studied and the oscillations of solutions of boundary value problems are investigated. Our approach is to reduce the oscillation problems to the nonexistence of positive solutions of scalar differential inequalities by employing the concept of H-oscillation introduced by Domslak (see: R. Courant, D. Hilbert, Methods of Mathematical Physics, Vol. I, Interscience, New York, 1996), where H denotes a unit vector.

  14. Fisher information of special functions and second-order differential equations

    NASA Astrophysics Data System (ADS)

    Yáñez, R. J.; Sánchez-Moreno, P.; Zarzo, A.; Dehesa, J. S.

    2008-08-01

    We investigate a basic question of analytic information theory, namely, the evaluation of the Fisher information and the relative Fisher information with respect to a non-negative function, for the probability distributions obtained by squaring the special functions of mathematical physics which are solutions of second-order differential equations. We obtain explicit expressions for these information-theoretic properties via the expectation values of the coefficients of the differential equation. We illustrate our approach for various nonrelativistic D-dimensional wavefunctions and some special functions of physicomathematical interest. Emphasis is made in the Nikiforov-Uvarov hypergeometric-type functions, which include and generalize the Hermite functions and the Gauss and Kummer hypergeometric functions, among others.

  15. Rectifying and negative differential resistance behaviors of a functionalized Tour wire: The position effects of functional groups

    NASA Astrophysics Data System (ADS)

    Kwong, Gordon; Zhang, Zhenhua; Pan, Jinbo

    2011-09-01

    Based on Tour wire, we construct four D-π-A molecular devices with different positional functional groups, in an attempt to explore the position effects of functional groups on their electronic transport properties and to show that some interesting physical phenomena can emerge by only varying the position of functional groups. The first-principles calculations demonstrate that the position of functional groups can affect the rectifying behaviors (rectification direction and ratio) significantly and determines whether or not the negative differential resistance (NDR) can be observed as well as the physical origin of the NDR phenomenon.

  16. On Equiconvergence of Expansions in Trigonometric Fourier Series and in Principal Functions of Ordinary Differential Operators

    NASA Astrophysics Data System (ADS)

    Vagabov, A. I.

    1985-06-01

    A regularity concept is given for ordinary differential pencils of a general form in a space of vector-valued functions, and this concept is subjected to analysis. Theorems are established asserting that the Fourier series of an arbitrary vector-valued function in the system of eigenelements of the pencils is equiconvergent with the usual trigonometric Fourier series of the components of this vector-valued function. Bibliography: 7 titles.

  17. Normal Form of Saddle-Node-Hopf Bifurcation in Retarded Functional Differential Equations and Applications

    NASA Astrophysics Data System (ADS)

    Jiang, Heping; Jiang, Jiao; Song, Yongli

    In this paper, we firstly employ the normal form theory of delayed differential equations according to Faria and Magalhães to derive the normal form of saddle-node-Hopf bifurcation for the general retarded functional differential equations. Then, the dynamical behaviors of a Leslie-Gower predator-prey model with time delay and nonmonotonic functional response are considered. Specially, the dynamical classification near the saddle-node-Hopf bifurcation point is investigated by using the normal form and the center manifold approaches. Finally, the numerical simulations are employed to support the theoretical results.

  18. Regulation of CFTR expression and function during differentiation of intestinal epithelial cells.

    PubMed Central

    Sood, R; Bear, C; Auerbach, W; Reyes, E; Jensen, T; Kartner, N; Riordan, J R; Buchwald, M

    1992-01-01

    CFTR, the protein defective in cystic fibrosis is regulated during differentiation of intestinal epithelial cells. The undifferentiated cells (Caco-2 and HT-29) show a lower level of CFTR mRNA, while a 10-fold increase is seen in differentiated cells. These differences correlate well with those of other intestinal-specific genes, including sucrase-isomaltase, villin and alpha 1-antitrypsin, indicating that the regulation is cell specific. In Caco-2 cells the increase in CFTR mRNA cannot be accounted for by increased transcription of the gene. These data indicate that CFTR mRNA stabilizing factor(s) might be present in differentiated cells. The higher levels of CFTR mRNA in differentiated cells are accompanied by decreased protein levels, indicating, as well, involvement of translational control in the regulation of CFTR in these cells. Finally, fully differentiated cells show lowered levels of cyclic AMP-activated C1- transport, the characteristic function of CFTR. Thus, CFTR function in differentiated cells is modulated by a complex interaction of regulatory elements. Caco-2 and HT-29 cells provide a suitable in vitro system in which to study the mechanism of regulation of CFTR. Images PMID:1378393

  19. Quantitative neuroproteomics: classical and novel tools for studying neural differentiation and function.

    PubMed

    Colucci-D'Amato, Luca; Farina, Annarita; Vissers, Johannes P C; Chambery, Angela

    2011-03-01

    Mechanisms underlying neural stem cell proliferation, differentiation and maturation play a critical role in the formation and wiring of neuronal connections. This process involves the activation of multiple serial events, which guide the undifferentiated cells to different lineages via distinctive developmental programs, forming neuronal circuits and thus shaping the adult nervous system. Furthermore, alterations within these strictly regulated pathways can lead to severe neurological and psychiatric diseases. In this framework, the investigation of the high dynamic protein expression changes and other factors affecting protein functions, for example post-translational modifications, the alterations of protein interaction networks, is of pivotal importance for the understanding of the molecular mechanisms responsible for cell differentiation. More recently, proteomic studies in neuroscience ("neuroproteomics") are receiving increased interest for the primary understanding of the regulatory networks underlying neuronal differentiation processes. Besides the classical two-dimensional-based proteomic strategies, the emerging platforms for LC-MS shotgun proteomic analysis hold great promise in unraveling the molecular basis of neural stem cell differentiation. In this review, recent advancements in label-free LC-MS quantitative neuroproteomics are highlighted as a new tool for the study of neural differentiation and functions, in comparison to mass spectrometry-based labeling approaches. The more commonly used protein profiling strategies and model systems for the analysis of neural differentiation are also discussed, along with the challenging proteomic approaches aimed to analyze the nervous system-specific organelles, the neural cells secretome and the specific protein interaction networks. PMID:20352529

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

    PubMed Central

    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

  1. Low-shear modelled microgravity environment maintains morphology and differentiated functionality of primary porcine hepatocyte cultures.

    PubMed

    Nelson, Leonard J; Walker, Simon W; Hayes, Peter C; Plevris, John N

    2010-01-01

    Hepatocytes cultured in conventional static culture rapidly lose polarity and differentiated function. This could be explained by gravity-induced sedimentation, which prevents formation of complete three-dimensional (3D) cell-cell/cell-matrix interactions and disrupts integrin-mediated signals (including the most abundant hepatic integrin alpha(5)beta(1)), important for cellular polarity and differentiation. Cell culture in a low fluid shear modelled microgravity (about 10(-2) g) environment promotes spatial colocation/self-aggregation of dissociated cells and induction of 3D differentiated liver morphology. Previously, we demonstrated the utility of a NASA rotary bioreactor in maintaining key metabolic functions and 3D aggregate formation of high-density primary porcine hepatocyte cultures over 21 days. Using serum-free chemically defined medium, without confounding interactions of exogenous bioscaffolding or bioenhancing surface materials, we investigated features of hepatic cellular polarity and differentiated functionality, including expression of hepatic integrin alpha(5), as markers of functional morphology. We report here that in the absence of exogenous biomatrix scaffolding, hepatocytes cultured in serum-free chemically defined medium in a microgravity environment rapidly (<24 h) form macroscopic (2-5 mm), compacted 3D hepatospheroid structures consisting of a shell of glycogen-positive viable cells circumscribing a core of eosinophilic cells. The spheroid shell layers exhibited ultrastructural, morphological and functional features of differentiated, polarized hepatic tissue including strong expression of the integrin alpha(5) subunit, functional bile canaliculi, albumin synthesis, and fine ultrastructure reminiscent of in vivo hepatic tissue. The low fluid shear microgravity environment may promote tissue-like self-organization of dissociated cells, and offer advantages over spheroids cultured in conventional formats to delineate optimal conditions for

  2. Comparison of Differential Item Functioning Determination Techniques: HGLM, LR and IRT-LR

    ERIC Educational Resources Information Center

    Acar, Tulin; Kelecioglu, Hulya

    2010-01-01

    The aim of this research is to determine differential item functioning (DIF) by hierarchical linear modeling (HGLM) on test items and comparing these results by the DIF results determined by logistic regression (LR) and IRT-likelihood ratio (IRT-LR) techniques. Investigating the concordance between the techniques in determining the items with DIF,…

  3. Correlates of Communalities as Matching Variables in Differential Item Functioning Analyses

    ERIC Educational Resources Information Center

    Yildirim, Huseyin H.; Yildirim, Selda

    2011-01-01

    Multivariate matching in Differential Item Functioning (DIF) analyses may contribute to understand the sources of DIF. In this context, detecting appropriate additional matching variables is a crucial issue. This present article argues that the variables which are correlated with communalities in item difficulties can be used as an additional…

  4. Group-Specific Effects of Matching Subtest Contamination on the Identification of Differential Item Functioning

    ERIC Educational Resources Information Center

    Keiffer, Elizabeth Ann

    2011-01-01

    A differential item functioning (DIF) simulation study was conducted to explore the type and level of impact that contamination had on type I error and power rates in DIF analyses when the suspect item favored the same or opposite group as the DIF items in the matching subtest. Type I error and power rates were displayed separately for the…

  5. Explaining Crossing DIF in Polytomous Items Using Differential Step Functioning Effects

    ERIC Educational Resources Information Center

    Penfield, Randall D.

    2010-01-01

    Crossing, or intersecting, differential item functioning (DIF) is a form of nonuniform DIF that exists when the sign of the between-group difference in expected item performance changes across the latent trait continuum. The presence of crossing DIF presents a problem for many statistics developed for evaluating DIF because positive and negative…

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

    ERIC Educational Resources Information Center

    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…

  7. Investigating Gender Differential Item Functioning across Countries and Test Languages for PISA Science Items

    ERIC Educational Resources Information Center

    Le, Luc T.

    2009-01-01

    This study uses PISA cycle 3 field trial data to investigate the relationships between gender differential item functioning (DIF) across countries and test languages for science items and their formats and the four other dimensions defined in PISA framework: focus, context, competency, and scientific knowledge. The data used were collected from 60…

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

    PubMed Central

    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

  9. Quantitative characterization of x-ray differential interference contrast microscopy using modulation transfer function

    NASA Astrophysics Data System (ADS)

    Nakamura, Takashi; Chang, Chang

    2011-08-01

    Performance of two types of differential interference contrast objectives, i.e., the XOR pattern and the zone-plate doublet, is quantitatively characterized and compared using modulation transfer function. Effects of partial coherence, finite absorption and phase in a complex object, as well as bias retardation are also examined.

  10. Quantitative characterization of x-ray differential interference contrast microscopy using modulation transfer function.

    PubMed

    Nakamura, Takashi; Chang, Chang

    2011-08-01

    Performance of two types of differential interference contrast objectives, i.e., the XOR pattern and the zone-plate doublet, is quantitatively characterized and compared using modulation transfer function. Effects of partial coherence, finite absorption and phase in a complex object, as well as bias retardation are also examined. PMID:21934894

  11. Evaluation of Model Selection Strategies for Cross-Level Two-Way Differential Item Functioning Analysis

    ERIC Educational Resources Information Center

    Patarapichayatham, Chalie; Kamata, Akihito; Kanjanawasee, Sirichai

    2012-01-01

    Model specification issues on the cross-level two-way differential item functioning model were previously investigated by Patarapichayatham et al. (2009). Their study clarified that an incorrect model specification can easily lead to biased estimates of key parameters. The objective of this article is to provide further insights on the issue by…

  12. Differential Tendencies To Guess as a Function of Gender and Lingual-Cultural Reference Group.

    ERIC Educational Resources Information Center

    Gafni, Naomi; Estela, Melamed

    The objective of this study was to investigate differential tendencies to avoid guessing as a function of three variables: (1) lingual-cultural-group; (2) gender; and (3) examination year. The Psychometric Entrance Test (PET) for universities in Israel was used, which is administered in Hebrew, Arabic, English, French, Spanish, and Russian. The…

  13. Differential Effects of a Tier Two Behavior Intervention Based on Function of Problem Behavior

    ERIC Educational Resources Information Center

    McIntosh, Kent; Campbell, Amy L.; Carter, Deborah Russell; Dickey, Celeste Rossetto

    2009-01-01

    The purpose of this study was to investigate the effectiveness of a tier two daily behavior card intervention and differential effects based on function of problem behavior. The participants were 36 elementary school students nominated for additional intervention beyond universal School-Wide Positive Behavior Support. Measures included…

  14. Assessing the Item Response Theory with Covariate (IRT-C) Procedure for Ascertaining Differential Item Functioning

    ERIC Educational Resources Information Center

    Tay, Louis; Vermunt, Jeroen K.; Wang, Chun

    2013-01-01

    We evaluate the item response theory with covariates (IRT-C) procedure for assessing differential item functioning (DIF) without preknowledge of anchor items (Tay, Newman, & Vermunt, 2011). This procedure begins with a fully constrained baseline model, and candidate items are tested for uniform and/or nonuniform DIF using the Wald statistic.…

  15. Detecting and Analyzing Differential Item Functioning in an Essay Test Using the Partial Credit Model.

    ERIC Educational Resources Information Center

    Ferrara, Steven; Walker-Bartnick, Leslie

    A procedure was developed to detect differential item functioning (DIF) in a standardized essay test using the Partial Credit Model, the general polychotomous form of the Rasch model. Using a panel of experts in the writing process, hypothesized explanations for DIF at some score points were developed. Data for the study included averaged…

  16. Item Purification in Differential Item Functioning Using Generalized Linear Mixed Models

    ERIC Educational Resources Information Center

    Liu, Qian

    2011-01-01

    For this dissertation, four item purification procedures were implemented onto the generalized linear mixed model for differential item functioning (DIF) analysis, and the performance of these item purification procedures was investigated through a series of simulations. Among the four procedures, forward and generalized linear mixed model (GLMM)…

  17. Recursive Partitioning to Identify Potential Causes of Differential Item Functioning in Cross-National Data

    ERIC Educational Resources Information Center

    Finch, W. Holmes; Hernández Finch, Maria E.; French, Brian F.

    2016-01-01

    Differential item functioning (DIF) assessment is key in score validation. When DIF is present scores may not accurately reflect the construct of interest for some groups of examinees, leading to incorrect conclusions from the scores. Given rising immigration, and the increased reliance of educational policymakers on cross-national assessments…

  18. Utility of the Mantel-Haenszel Procedure for Detecting Differential Item Functioning in Small Samples

    ERIC Educational Resources Information Center

    Fidalgo, Angel M.; Ferreres, Doris; Muniz, Jose

    2004-01-01

    Sample-size restrictions limit the contingency table approaches based on asymptotic distributions, such as the Mantel-Haenszel (MH) procedure, for detecting differential item functioning (DIF) in many practical applications. Within this framework, the present study investigated the power and Type I error performance of empirical and inferential…

  19. Detecting Native Language Group Differences at the Subskills Level of Reading: A Differential Skill Functioning Approach

    ERIC Educational Resources Information Center

    Li, Hongli; Suen, Hoi K.

    2013-01-01

    Differential skill functioning (DSF) exists when examinees from different groups have different probabilities of successful performance in a certain subskill underlying the measured construct, given that they have the same ability on the overall construct. Using a DSF approach, this study examined the differences between two native language…

  20. An Examination of Differential Item Functioning on the Vanderbilt Assessment of Leadership in Education

    ERIC Educational Resources Information Center

    Polikoff, Morgan S.; May, Henry; Porter, Andrew C.; Elliott, Stephen N.; Goldring, Ellen; Murphy, Joseph

    2009-01-01

    The Vanderbilt Assessment of Leadership in Education is a 360-degree assessment of the effectiveness of principals' learning-centered leadership behaviors. In this report, we present results from a differential item functioning (DIF) study of the assessment. Using data from a national field trial, we searched for evidence of DIF on school level,…

  1. Differential Item Functioning Detection across Two Methods of Defining Group Comparisons: Pairwise and Composite Group Comparisons

    ERIC Educational Resources Information Center

    Sari, Halil Ibrahim; Huggins, Anne Corinne

    2015-01-01

    This study compares two methods of defining groups for the detection of differential item functioning (DIF): (a) pairwise comparisons and (b) composite group comparisons. We aim to emphasize and empirically support the notion that the choice of pairwise versus composite group definitions in DIF is a reflection of how one defines fairness in DIF…

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

    ERIC Educational Resources Information Center

    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,…

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

    ERIC Educational Resources Information Center

    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,…

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

    ERIC Educational Resources Information Center

    Kelderman, Henk; Macready, George B.

    1990-01-01

    Loglinear latent class models are used to detect differential item functioning (DIF). Likelihood ratio tests for assessing the presence of various types of DIF are described, and these methods are illustrated through the analysis of a "real world" data set. (TJH)

  5. Cauchy problem and Green's functions for first order differential operators and algebraic quantization

    SciTech Connect

    Muehlhoff, Rainer

    2011-02-15

    Existence and uniqueness of advanced and retarded fundamental solutions (Green's functions) and of global solutions to the Cauchy problem is proved for a general class of first order linear differential operators on vector bundles over globally hyperbolic Lorentzian manifolds. This is a core ingredient to CAR-/CCR-algebraic constructions of quantum field theories on curved spacetimes, particularly for higher spin field equations.

  6. DIFFERENTIAL ITEM FUNCTIONING AT POST ASSESSMENT BETWEEN TREATMENT AND CONTROL GROUPS FROM AN INCREASE IN KNOWLEDGE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    There has been some concern that participation in an intervention and exposure to a measurement instrument can distort subsequent responses to a questionnaire, thereby biasing results. Differential Item Functioning (DIF) analysis with Item Response Modeling (IRM) can test these effects by testing f...

  7. Assessing Motor Skills as a Differentiating Feature between High Functioning Autism and Asperger's Disorder

    ERIC Educational Resources Information Center

    Cid, Maria R.

    2011-01-01

    The purpose of this research was to investigate if motor skills could be used as a differentiating feature between Asperger's Disorder (AD) and High Functioning (HFA) in children under the age of 9 years, 0 months, in order to provide additional information regarding the usefulness and validity of distinguishing these two disorders. There is…

  8. RIM: A Random Item Mixture Model to Detect Differential Item Functioning

    ERIC Educational Resources Information Center

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

    2010-01-01

    In this paper we present a new methodology for detecting differential item functioning (DIF). We introduce a DIF model, called the random item mixture (RIM), that is based on a Rasch model with random item difficulties (besides the common random person abilities). In addition, a mixture model is assumed for the item difficulties such that the…

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

    ERIC Educational Resources Information Center

    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…

  10. Gender-Related Differential Item Functioning on a Middle-School Mathematics Performance Assessment.

    ERIC Educational Resources Information Center

    Lane, Suzanne; And Others

    This study examined gender-related differential item functioning (DIF) using a mathematics performance assessment, the QUASAR Cognitive Assessment Instrument (QCAI), administered to middle school students. The QCAI was developed for the Quantitative Understanding: Amplifying Student Achievement and Reading (QUASAR) project, which focuses on…

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

    ERIC Educational Resources Information Center

    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…

  12. Potential Sources of Differential Item Functioning in the Adaptation of Tests

    ERIC Educational Resources Information Center

    Elosua, Paula; Lopez-Jauregui, Alicia

    2007-01-01

    This report shows a classification of differential item functioning (DIF) sources that have an effect on the adaptation of tests. This classification is based on linguistic and cultural criteria. Four general DIF sources are distinguished: cultural relevance, translation problems, morph syntactical differences, and semantic differences. The…

  13. Identification of Differential Item Functioning in Multiple-Group Settings: A Multivariate Outlier Detection Approach

    ERIC Educational Resources Information Center

    Magis, David; De Boeck, Paul

    2011-01-01

    We focus on the identification of differential item functioning (DIF) when more than two groups of examinees are considered. We propose to consider items as elements of a multivariate space, where DIF items are outlying elements. Following this approach, the situation of multiple groups is a quite natural case. A robust statistics technique is…

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

    ERIC Educational Resources Information Center

    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…

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

    ERIC Educational Resources Information Center

    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.…

  16. High-Stakes Tests for Students with Specific Learning Disabilities: Disability-Based Differential Item Functioning

    ERIC Educational Resources Information Center

    Anjorin, Idayatou

    2009-01-01

    Students with learning disabilities are increasingly included in state accountability systems. The purpose of this study was to investigate disability-based differential item functioning (DIF) on a statewide high-stakes mathematics test administered in the Spring of 2003 to all students seeking a high-school diploma in one state in the eastern…

  17. Identifying Differential Item Functioning in Multi-Stage Computer Adaptive Testing

    ERIC Educational Resources Information Center

    Gierl, Mark J.; Lai, Hollis; Li, Johnson

    2013-01-01

    The purpose of this study is to evaluate the performance of CATSIB (Computer Adaptive Testing-Simultaneous Item Bias Test) for detecting differential item functioning (DIF) when items in the matching and studied subtest are administered adaptively in the context of a realistic multi-stage adaptive test (MST). MST was simulated using a 4-item…

  18. The MIMIC Method with Scale Purification for Detecting Differential Item Functioning

    ERIC Educational Resources Information Center

    Wang, Wen-Chung; Shih, Ching-Lin; Yang, Chih-Chien

    2009-01-01

    This study implements a scale purification procedure onto the standard MIMIC method for differential item functioning (DIF) detection and assesses its performance through a series of simulations. It is found that the MIMIC method with scale purification (denoted as M-SP) outperforms the standard MIMIC method (denoted as M-ST) in controlling…

  19. Differential Item Functioning Analysis of Math Performance of Hispanic, Asian, and White NAEP Respondents.

    ERIC Educational Resources Information Center

    Rock, Donald; Chan, Kaling

    The differential item functioning of mathematics performance of Hispanic, Asian, and White students on the National Assessment of Educational Progress (NAEP) was studied, using a modification of the Mantel-Haenszel Procedure. The sample for grades 3, 7, and 11, respectively, included: (1) 1,367, 1,570, and 1,580 Whites; (2) 265, 613, and 760…

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

    ERIC Educational Resources Information Center

    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…

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

    ERIC Educational Resources Information Center

    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…

  2. Content Analysis of Gender-Related Differential Item Functioning TIMSS Items in Mathematics in Jordan

    ERIC Educational Resources Information Center

    Innabi, Hanan; Dodeen, Hamzeh

    2006-01-01

    The purpose of this study is to analyze items that exhibit gender-related Differential Item Functioning (DIF) in Mathematics in Jordan. Data was taken from the TIMSS 1999 of Jordan, which includes responses of 5, 299 eighth grade students. Mantel-Haenszel (MH) DIF procedure was applied to 124 multiple-choice items. The results showed that 37 items…

  3. Demonstrating the Utility of a Multilevel Model in the Assessment of Differential Item Functioning.

    ERIC Educational Resources Information Center

    Pommerich, Mary

    When tests contain few items, observed score may not be an accurate reflection of true score, and the Mantel Haenszel (MH) statistic may perform poorly in detecting differential item functioning. Applications of the MH procedure in such situations require an alternate strategy; one such strategy is to include background variables in the matching…

  4. An Analysis of Sex-Related Differential Item Functioning in Attitude Assessment.

    ERIC Educational Resources Information Center

    Dodeen, Hamzeh; Johanson, George A.

    2003-01-01

    Analyzed and classified items that display sex-related differential item functioning (DIF) in attitude assessment. Analyzed 982 items, from 23 real data sets, that measure attitudes. Found that sex DIF is common in attitude scales: more than 27 percent of items showed DIF related to sex, 15 percent of the items exhibited moderate to large DIF, and…

  5. Examining the Relationship between Race-Based Differential Item Functioning and Item Difficulty

    ERIC Educational Resources Information Center

    Scherbaum, Charles A.; Goldstein, Harold W.

    2008-01-01

    Recent research examining racial differences on standardized cognitive tests has focused on the impact of test item difficulty. Studies using data from the SAT and GRE have reported a correlation between item difficulty and differential item functioning (DIF) such that minority test takers are less likely than majority test takers to respond…

  6. Assessment of Differential Item Functioning under Cognitive Diagnosis Models: The DINA Model Example

    ERIC Educational Resources Information Center

    Li, Xiaomin; Wang, Wen-Chung

    2015-01-01

    The assessment of differential item functioning (DIF) is routinely conducted to ensure test fairness and validity. Although many DIF assessment methods have been developed in the context of classical test theory and item response theory, they are not applicable for cognitive diagnosis models (CDMs), as the underlying latent attributes of CDMs are…

  7. Iterative Purification and Effect Size Use with Logistic Regression for Differential Item Functioning Detection

    ERIC Educational Resources Information Center

    French, Brian F.; Maller, Susan J.

    2007-01-01

    Two unresolved implementation issues with logistic regression (LR) for differential item functioning (DIF) detection include ability purification and effect size use. Purification is suggested to control inaccuracies in DIF detection as a result of DIF items in the ability estimate. Additionally, effect size use may be beneficial in controlling…

  8. The Matching Criterion Purification for Differential Item Functioning Analyses in a Large-Scale Assessment

    ERIC Educational Resources Information Center

    Lee, HyeSun; Geisinger, Kurt F.

    2016-01-01

    The current study investigated the impact of matching criterion purification on the accuracy of differential item functioning (DIF) detection in large-scale assessments. The three matching approaches for DIF analyses (block-level matching, pooled booklet matching, and equated pooled booklet matching) were employed with the Mantel-Haenszel…

  9. A Comparison of Adjacent Categories and Cumulative Differential Step Functioning Effect Estimators

    ERIC Educational Resources Information Center

    Gattamorta, Karina A.; Penfield, Randall D.

    2012-01-01

    The study of measurement invariance in polytomous items that targets individual score levels is known as differential step functioning (DSF). The analysis of DSF requires the creation of a set of dichotomizations of the item response variable. There are two primary approaches for creating the set of dichotomizations to conduct a DSF analysis: the…

  10. Parent Ratings of ADHD Symptoms: Differential Symptom Functioning across Malaysian Malay and Chinese Children

    ERIC Educational Resources Information Center

    Gomez, Rapson; Vance, Alasdair

    2008-01-01

    This study examined differential symptom functioning (DSF) in ADHD symptoms across Malay and Chinese children in Malaysia. Malay (N = 571) and Chinese (N = 254) parents completed the Disruptive Behavior Rating Scale, which lists the DSM-IV ADHD symptoms. DSF was examined using the multiple indicators multiple causes (MIMIC) structural equation…

  11. The differentiation and protective function of cytolytic CD4 T cells in influenza infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    CD4 T cells that recognize peptide antigen in the context of Class II MHC can differentiate into various subsets that are characterized by their helper functions. However, increasing evidence indicates that CD4 cells with direct cytolytic activity play a role in chronic, as well as, acute infections...

  12. Testing for Nonuniform Differential Item Functioning with Multiple Indicator Multiple Cause Models

    ERIC Educational Resources Information Center

    Woods, Carol M.; Grimm, Kevin J.

    2011-01-01

    In extant literature, multiple indicator multiple cause (MIMIC) models have been presented for identifying items that display uniform differential item functioning (DIF) only, not nonuniform DIF. This article addresses, for apparently the first time, the use of MIMIC models for testing both uniform and nonuniform DIF with categorical indicators. A…

  13. A Comparison of Four Differential Item Functioning Procedures in the Presence of Multidimensionality

    ERIC Educational Resources Information Center

    Bastug, Özlem Yesim Özbek

    2016-01-01

    Differential item functioning (DIF), or item bias, is a relatively new concept. It has been one of the most controversial and the most studied subject in measurement theory. DIF occurs when people who have the same ability level but from different groups have a different probability of a correct response. According to Item Response Theory (IRT),…

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

    ERIC Educational Resources Information Center

    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…

  15. Comparing Methods of Assessing Differential Item Functioning in a Computerized Adaptive Testing Environment

    ERIC Educational Resources Information Center

    Lei, Pui-Wa; Chen, Shu-Ying; Yu, Lan

    2006-01-01

    Mantel-Haenszel and SIBTEST, which have known difficulty in detecting non-unidirectional differential item functioning (DIF), have been adapted with some success for computerized adaptive testing (CAT). This study adapts logistic regression (LR) and the item-response-theory-likelihood-ratio test (IRT-LRT), capable of detecting both unidirectional…

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

    ERIC Educational Resources Information Center

    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…

  17. Integrin-Linked Kinase Is Indispensable for Keratinocyte Differentiation and Epidermal Barrier Function.

    PubMed

    Sayedyahossein, Samar; Rudkouskaya, Alena; Leclerc, Valerie; Dagnino, Lina

    2016-02-01

    A functional permeability barrier is essential to prevent the passage of water and electrolytes, macromolecules, and pathogens through the epidermis. This is accomplished in terminally differentiated keratinocytes through formation of a cornified envelope and the assembly of tight intercellular junctions. Integrin-linked kinase (ILK) is a scaffold protein essential for hair follicle morphogenesis and epidermal attachment to the basement membrane. However, the biological functions of ILK in differentiated keratinocytes remain poorly understood. Furthermore, whether ILK is implicated in keratinocyte differentiation and intercellular junction formation has remained an unresolved issue. Here we describe a pivotal role for ILK in keratinocyte differentiation responses to increased extracellular Ca(2+), regulation of adherens and tight junction assembly, and the formation of an outside-in permeability barrier toward macromolecules. In the absence of ILK, the calcium sensing receptor, E-cadherin, and ZO-1 fail to translocate to the cell membrane, through mechanisms that involve abnormalities in microtubules and in RhoA activation. In situ, ILK-deficient epidermis exhibits reduced tight junction formation and increased outside-in permeability to a dextran tracer, indicating reduced barrier properties toward macromolecules. Therefore, ILK is an essential component of keratinocyte differentiation programs that contribute to epidermal integrity and the establishment of its barrier properties. PMID:26967476

  18. PTPN13 regulates cellular signalling and β-catenin function during megakaryocytic differentiation.

    PubMed

    Sardina, José L; López-Ruano, Guillermo; Prieto-Bermejo, Rodrigo; Sánchez-Sánchez, Beatriz; Pérez-Fernández, Alejandro; Sánchez-Abarca, Luis Ignacio; Pérez-Simón, José Antonio; Quintales, Luis; Sánchez-Yagüe, Jesús; Llanillo, Marcial; Antequera, Francisco; Hernández-Hernández, Angel

    2014-12-01

    PTPN13 is a high-molecular weight intracellular phosphatase with several isoforms that exhibits a highly modular structure. Although in recent years different roles have been described for PTPN13, we are still far from understanding its function in cell biology. Here we show that PTPN13 expression is activated during megakaryocytic differentiation at the protein and mRNA level. Our results show that the upregulation of PTPN13 inhibits megakaryocytic differentiation, while PTPN13 silencing triggers differentiation. The ability of PTPN13 to alter megakaryocytic differentiation can be explained by its capacity to regulate ERK and STAT signalling. Interestingly, the silencing of β-catenin produced the same effect as PTPN13 downregulation. We demonstrate that both proteins coimmunoprecipitate and colocalise. Moreover, we provide evidence showing that PTPN13 can regulate β-catenin phosphorylation, stability and transcriptional activity. Therefore, the ability of PTPN13 to control megakaryocytic differentiation must be intimately linked to the regulation of β-catenin function. Moreover, our results show for the first time that PTPN13 is stabilised upon Wnt signalling, which makes PTPN13 an important player in canonical Wnt signalling. Our results show that PTPN13 behaves as an important regulator of megakaryocytic differentiation in cell lines and also in murine haematopoietic progenitors. This importance can be explained by the ability of PTPN13 to regulate cellular signalling, and especially through the regulation of β-catenin stability and function. Our results hold true for different megakaryocytic cell lines and also for haematopoietic progenitors, suggesting that these two proteins may play a relevant role during in vivo megakaryopoiesis. PMID:25193362

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

    PubMed

    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. PMID:22952951

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

    NASA Astrophysics Data System (ADS)

    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.

  1. Viscoelastic Properties of Differentiating Blood Cells Are Fate- and Function-Dependent

    PubMed Central

    Ekpenyong, Andrew E.; Whyte, Graeme; Chalut, Kevin; Pagliara, Stefano; Lautenschläger, Franziska; Fiddler, Christine; Paschke, Stephan; Keyser, Ulrich F.; Chilvers, Edwin R.; Guck, Jochen

    2012-01-01

    Although cellular mechanical properties are known to alter during stem cell differentiation, understanding of the functional relevance of such alterations is incomplete. Here, we show that during the course of differentiation of human myeloid precursor cells into three different lineages, the cells alter their viscoelastic properties, measured using an optical stretcher, to suit their ultimate fate and function. Myeloid cells circulating in blood have to be advected through constrictions in blood vessels, engendering the need for compliance at short time-scales (differentiated cell types reduce their steady-state viscosity by more than 50% and show over 140% relative increase in their ability to migrate through tissue-like pores at long time-scales (>minutes), compared to undifferentiated cells. These findings suggest that reduction in steady-state viscosity is a physiological adaptation for enhanced migration through tissues. Our results indicate that the material properties of cells define their function, can be used as a cell differentiation marker and could serve as target for novel therapies. PMID:23028868

  2. Temperament and arousal systems: A new synthesis of differential psychology and functional neurochemistry.

    PubMed

    Trofimova, Irina; Robbins, Trevor W

    2016-05-01

    This paper critically reviews the unidimensional construct of General Arousal as utilised by models of temperament in differential psychology for example, to underlie 'Extraversion'. Evidence suggests that specialization within monoamine neurotransmitter systems contrasts with the attribution of a "general arousal" of the Ascending Reticular Activating System. Experimental findings show specialized roles of noradrenaline, dopamine, and serotonin systems in hypothetically mediating three complementary forms of arousal that are similar to three functional blocks described in classical models of behaviour within kinesiology, clinical neuropsychology, psychophysiology and temperament research. In spite of functional diversity of monoamine receptors, we suggest that their functionality can be classified using three universal aspects of actions related to expansion, to selection-integration and to maintenance of chosen behavioural alternatives. Monoamine systems also differentially regulate analytic vs. routine aspects of activities at cortical and striatal neural levels. A convergence between main temperament models in terms of traits related to described functional aspects of behavioural arousal also supports the idea of differentiation between these aspects analysed here in a functional perspective. PMID:26969100

  3. Analytic Solutions of a Second-Order Iterative Functional Differential Equations

    NASA Astrophysics Data System (ADS)

    Liu, Lingxia

    In this paper, the existence of analytic solutions of an iterative functional differential equation is studied. We reduce this problem to finding analytic solutions of a functional differential equation without iteration of the unknown function. For technical reasons, in previous work the constant α given in Schröder transformation is required to fulfill that α is off the unit circle or lies on the circle with the Diophantine condition. In this paper, we break the restraint of the Diophantine condition and obtain results of analytic solutions in the case of α at resonance, i.e., at a root of the unity and the case of α near resonance under the Brjuno condition.

  4. Functional maintenance of differentiated embryoid bodies in microfluidic systems: a platform for personalized medicine.

    PubMed

    Guven, Sinan; Lindsey, Jennifer S; Poudel, Ishwari; Chinthala, Sireesha; Nickerson, Michael D; Gerami-Naini, Behzad; Gurkan, Umut A; Anchan, Raymond M; Demirci, Utkan

    2015-03-01

    Hormone replacement therapies have become important for treating diseases such as premature ovarian failure or menopausal complications. The clinical use of bioidentical hormones might significantly reduce some of the potential risks reportedly associated with the use of synthetic hormones. In the present study, we demonstrate the utility and advantage of a microfluidic chip culture system to enhance the development of personalized, on-demand, treatment modules using embryoid bodies (EBs). Functional EBs cultured on microfluidic chips represent a platform for personalized, patient-specific treatment cassettes that can be cryopreserved until required for treatment. We assessed the viability, differentiation, and functionality of EBs cultured and cryopreserved in this system. During extended microfluidic culture, estradiol, progesterone, testosterone, and anti-müllerian hormone levels were measured, and the expression of differentiated steroidogenic cells was confirmed by immunocytochemistry assay for the ovarian tissue markers anti-müllerian hormone receptor type II, follicle-stimulating hormone receptor, and inhibin β-A and the estrogen biosynthesis enzyme aromatase. Our studies showed that under microfluidic conditions, differentiated steroidogenic EBs continued to secrete estradiol and progesterone at physiologically relevant concentrations (30-120 pg/ml and 150-450 pg/ml, respectively) for up to 21 days. Collectively, we have demonstrated for the first time the feasibility of using a microfluidic chip system with continuous flow for the differentiation and extended culture of functional steroidogenic stem cell-derived EBs, the differentiation of EBs into cells expressing ovarian antigens in a microfluidic system, and the ability to cryopreserve this system with restoration of growth and functionality on thawing. These results present a platform for the development of a new therapeutic system for personalized medicine. PMID:25666845

  5. Functional Maintenance of Differentiated Embryoid Bodies in Microfluidic Systems: A Platform for Personalized Medicine

    PubMed Central

    Guven, Sinan; Lindsey, Jennifer S.; Poudel, Ishwari; Chinthala, Sireesha; Nickerson, Michael D.; Gerami-Naini, Behzad; Gurkan, Umut A.

    2015-01-01

    Hormone replacement therapies have become important for treating diseases such as premature ovarian failure or menopausal complications. The clinical use of bioidentical hormones might significantly reduce some of the potential risks reportedly associated with the use of synthetic hormones. In the present study, we demonstrate the utility and advantage of a microfluidic chip culture system to enhance the development of personalized, on-demand, treatment modules using embryoid bodies (EBs). Functional EBs cultured on microfluidic chips represent a platform for personalized, patient-specific treatment cassettes that can be cryopreserved until required for treatment. We assessed the viability, differentiation, and functionality of EBs cultured and cryopreserved in this system. During extended microfluidic culture, estradiol, progesterone, testosterone, and anti-müllerian hormone levels were measured, and the expression of differentiated steroidogenic cells was confirmed by immunocytochemistry assay for the ovarian tissue markers anti-müllerian hormone receptor type II, follicle-stimulating hormone receptor, and inhibin β-A and the estrogen biosynthesis enzyme aromatase. Our studies showed that under microfluidic conditions, differentiated steroidogenic EBs continued to secrete estradiol and progesterone at physiologically relevant concentrations (30–120 pg/ml and 150–450 pg/ml, respectively) for up to 21 days. Collectively, we have demonstrated for the first time the feasibility of using a microfluidic chip system with continuous flow for the differentiation and extended culture of functional steroidogenic stem cell-derived EBs, the differentiation of EBs into cells expressing ovarian antigens in a microfluidic system, and the ability to cryopreserve this system with restoration of growth and functionality on thawing. These results present a platform for the development of a new therapeutic system for personalized medicine. PMID:25666845

  6. Differentiation-Inducing Factor-1 and -2 Function also as Modulators for Dictyostelium Chemotaxis

    PubMed Central

    Kuwayama, Hidekazu; Kubohara, Yuzuru

    2009-01-01

    Background In the early stages of development of the cellular slime mold Dictyostelium discoideum, chemotaxis toward cAMP plays a pivotal role in organizing discrete cells into a multicellular structure. In this process, a series of signaling molecules, such as G-protein-coupled cell surface receptors for cAMP, phosphatidylinositol metabolites, and cyclic nucleotides, function as the signal transducers for controlling dynamics of cytoskeleton. Differentiation-inducing factor-1 and -2 (DIF-1 and DIF-2) were originally identified as the factors (chlorinated alkylphenones) that induce Dictyostelium stalk cell differentiation, but it remained unknown whether the DIFs had any other physiologic functions. Methodology/Principal Findings To further elucidate the functions of DIFs, in the present study we investigated their effects on chemotaxis under various conditions. Quite interestingly, in shallow cAMP gradients, DIF-1 suppressed chemotaxis whereas DIF-2 promoted it greatly. Analyses with various mutants revealed that DIF-1 may inhibit chemotaxis, at least in part, via GbpB (a phosphodiesterase) and a decrease in the intracellular cGMP concentration ([cGMP]i). DIF-2, by contrast, may enhance chemotaxis, at least in part, via RegA (another phosphodiesterase) and an increase in [cGMP]i. Using null mutants for DimA and DimB, the transcription factors that are required for DIF-dependent prestalk differentiation, we also showed that the mechanisms for the modulation of chemotaxis by DIFs differ from those for the induction of cell differentiation by DIFs, at least in part. Conclusions/Significance Our findings indicate that DIF-1 and DIF-2 function as negative and positive modulators for Dictyostelium chemotaxis, respectively. To our knowledge, this is the first report in any organism of physiologic modulators (small molecules) for chemotaxis having differentiation-inducing activity. PMID:19684855

  7. Estimation of time- and state-dependent delays and other parameters in functional differential equations

    NASA Technical Reports Server (NTRS)

    Murphy, K. A.

    1990-01-01

    A parameter estimation algorithm is developed which can be used to estimate unknown time- or state-dependent delays and other parameters (e.g., initial condition) appearing within a nonlinear nonautonomous functional differential equation. The original infinite dimensional differential equation is approximated using linear splines, which are allowed to move with the variable delay. The variable delays are approximated using linear splines as well. The approximation scheme produces a system of ordinary differential equations with nice computational properties. The unknown parameters are estimated within the approximating systems by minimizing a least-squares fit-to-data criterion. Convergence theorems are proved for time-dependent delays and state-dependent delays within two classes, which say essentially that fitting the data by using approximations will, in the limit, provide a fit to the data using the original system. Numerical test examples are presented which illustrate the method for all types of delay.

  8. Estimation of time- and state-dependent delays and other parameters in functional differential equations

    NASA Technical Reports Server (NTRS)

    Murphy, K. A.

    1988-01-01

    A parameter estimation algorithm is developed which can be used to estimate unknown time- or state-dependent delays and other parameters (e.g., initial condition) appearing within a nonlinear nonautonomous functional differential equation. The original infinite dimensional differential equation is approximated using linear splines, which are allowed to move with the variable delay. The variable delays are approximated using linear splines as well. The approximation scheme produces a system of ordinary differential equations with nice computational properties. The unknown parameters are estimated within the approximating systems by minimizing a least-squares fit-to-data criterion. Convergence theorems are proved for time-dependent delays and state-dependent delays within two classes, which say essentially that fitting the data by using approximations will, in the limit, provide a fit to the data using the original system. Numerical test examples are presented which illustrate the method for all types of delay.

  9. Dynamic Functional Connectomics Signatures for Characterization and Differentiation of PTSD Patients

    PubMed Central

    Li, Xiang; Zhu, Dajiang; Jiang, Xi; Jin, Changfeng; Zhang, Xin; Guo, Lei; Zhang, Jing; Hu, Xiaoping; Li, Jingjiang; Liu, Tianming

    2013-01-01

    Functional connectomes have been recently shown to be powerful in characterizing brain conditions. However, many previous studies assumed temporal stationarity of functional connectomes, while their temporal dynamics are rarely explored. Here, based on the structural connectomes constructed from diffusion tensor imaging (DTI) data, functional connectomes are derived from resting-state fMRI (R-fMRI) data and are then temporally divided into quasi-stable segments via a sliding time window approach. After integrating and pooling over a large number of those temporally quasi-stable functional connectome segments from 44 post-traumatic stress disorder (PTSD) patients and 51 healthy controls, common functional connectome (CFC) patterns are derived via effective dictionary learning and sparse coding algorithms. It is found that there are 16 CFC patterns that are reproducible across healthy controls, and interestingly, two additional CFC patterns with altered connectivity patterns (termed signature functional connectome (SFC) here) exist dominantly in PTSD subjects. These two SFC patterns alone can successfully differentiate 80% of PTSD subjects from healthy controls with only 2% false positive. Furthermore, the temporal transition dynamics of CFC patterns in PTSD subjects are substantially different from those in healthy controls. These results have been replicated in separate testing datasets, suggesting that dynamic functional connectomics signatures can effectively characterize and differentiate PTSD patients. PMID:23671011

  10. Functional network analysis of genes differentially expressed during xylogenesis in soc1ful woody Arabidopsis plants.

    PubMed

    Davin, Nicolas; Edger, Patrick P; Hefer, Charles A; Mizrachi, Eshchar; Schuetz, Mathias; Smets, Erik; Myburg, Alexander A; Douglas, Carl J; Schranz, Michael E; Lens, Frederic

    2016-06-01

    Many plant genes are known to be involved in the development of cambium and wood, but how the expression and functional interaction of these genes determine the unique biology of wood remains largely unknown. We used the soc1ful loss of function mutant - the woodiest genotype known in the otherwise herbaceous model plant Arabidopsis - to investigate the expression and interactions of genes involved in secondary growth (wood formation). Detailed anatomical observations of the stem in combination with mRNA sequencing were used to assess transcriptome remodeling during xylogenesis in wild-type and woody soc1ful plants. To interpret the transcriptome changes, we constructed functional gene association networks of differentially expressed genes using the STRING database. This analysis revealed functionally enriched gene association hubs that are differentially expressed in herbaceous and woody tissues. In particular, we observed the differential expression of genes related to mechanical stress and jasmonate biosynthesis/signaling during wood formation in soc1ful plants that may be an effect of greater tension within woody tissues. Our results suggest that habit shifts from herbaceous to woody life forms observed in many angiosperm lineages could have evolved convergently by genetic changes that modulate the gene expression and interaction network, and thereby redeploy the conserved wood developmental program. PMID:26952251

  11. Divergent regulation of functionally distinct γ-tubulin complexes during differentiation.

    PubMed

    Muroyama, Andrew; Seldin, Lindsey; Lechler, Terry

    2016-06-20

    Differentiation induces the formation of noncentrosomal microtubule arrays in diverse tissues. The formation of these arrays requires loss of microtubule-organizing activity (MTOC) at the centrosome, but the mechanisms regulating this transition remain largely unexplored. Here, we use the robust loss of centrosomal MTOC activity in the epidermis to identify two pools of γ-tubulin that are biochemically and functionally distinct and differentially regulated. Nucleation-competent CDK5RAP2-γ-tubulin complexes were maintained at centrosomes upon initial epidermal differentiation. In contrast, Nedd1-γ-tubulin complexes did not promote nucleation but were required for anchoring of microtubules, a previously uncharacterized activity for this complex. Cell cycle exit specifically triggered loss of Nedd1-γ-tubulin complexes, providing a mechanistic link connecting MTOC activity and differentiation. Collectively, our studies demonstrate that distinct γ-tubulin complexes regulate different microtubule behaviors at the centrosome and show that differential regulation of these complexes drives loss of centrosomal MTOC activity. PMID:27298324

  12. Mesenchymal Stromal Cells Differentiating to Adipocytes Accumulate Autophagic Vesicles Instead of Functional Lipid Droplets.

    PubMed

    Gruia, Alexandra T; Suciu, Maria; Barbu-Tudoran, Lucian; Azghadi, Seyed Mohammad Reza; Cristea, Mirabela I; Nica, Dragos V; Vaduva, Adrian; Muntean, Danina; Mic, Ani Aurora; Mic, Felix A

    2016-04-01

    Adult bone marrow mesenchymal stromal cells (BMSCs) can easily be differentiated into a variety of cells. In vivo transplantation of BMSCs-differentiated cells has had limited success, suggesting that these cells may not be fully compatible with the cells they are intended to replace in vivo. We investigated the structural and functional features of BMSCs-derived adipocytes as compared with adipocytes from adipose tissue, and the structure and functionality of lipid vesicles formed during BMSCs differentiation to adipocytes. Gas chromatography-mass spectrometry showed fatty acid composition of BMSCs-derived adipocytes and adipocytes from the adipose tissue to be very different, as is the lipid rafts composition, caveolin-1 expression, caveolae distribution in their membranes, and the pattern of expression of fatty acid elongases. Confocal microscopy confirmed the absence from BMSCs-derived adipocytes of markers of lipid droplets. BMSCs-derived adipocytes cannot convert deuterated glucose into deuterated species of fatty acids and cannot uptake the deuterated fatty acid-bovine serum albumin complexes from the culture medium, suggesting that intra-cellular accumulation of lipids does not occur by lipogenesis. We noted that BMSCs differentiation to adipocytes is accompanied by an increase in autophagy. Autophagic vesicles accumulate in the cytoplasm of BMSCs-derived adipocytes and their size and distribution resembles that of Nile Red-stained lipid vesicles. Stimulation of autophagy in BMSCs triggers the intra-cellular accumulation of lipids, while inhibition of autophagy prevents this accumulation. In conclusion, differentiation of BMSCs-derived adipocytes leads to intra-cellular accumulation of autophagic vesicles rather than functional lipid droplets, suggesting that these cells are not authentic adipocytes. J. Cell. Physiol. 231: 863-875, 2016. © 2015 Wiley Periodicals, Inc. PMID:26332160

  13. An Efficient Spectral Method for Ordinary Differential Equations with Rational Function Coefficients

    NASA Technical Reports Server (NTRS)

    Coutsias, Evangelos A.; Torres, David; Hagstrom, Thomas

    1994-01-01

    We present some relations that allow the efficient approximate inversion of linear differential operators with rational function coefficients. We employ expansions in terms of a large class of orthogonal polynomial families, including all the classical orthogonal polynomials. These families obey a simple three-term recurrence relation for differentiation, which implies that on an appropriately restricted domain the differentiation operator has a unique banded inverse. The inverse is an integration operator for the family, and it is simply the tridiagonal coefficient matrix for the recurrence. Since in these families convolution operators (i.e. matrix representations of multiplication by a function) are banded for polynomials, we are able to obtain a banded representation for linear differential operators with rational coefficients. This leads to a method of solution of initial or boundary value problems that, besides having an operation count that scales linearly with the order of truncation N, is computationally well conditioned. Among the applications considered is the use of rational maps for the resolution of sharp interior layers.

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

    PubMed

    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. PMID:26416398

  15. A Parsimonious Statistical Method to Detect Groupwise Differentially Expressed Functional Connectivity Networks

    PubMed Central

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

    2016-01-01

    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. PMID:26416398

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

    ERIC Educational Resources Information Center

    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…

  17. A Comparison of Unidimensional and Three-Dimensional Differential Item Functioning Analysis Using Two-Dimensional Data

    ERIC Educational Resources Information Center

    Snow, Teresa K.; Oshima, T. C.

    2009-01-01

    Oshima, Raju, and Flowers demonstrated the use of an item response theory-based technique for analyzing differential item function (DIF) and differential test function for dichotomously scored data that are intended to be multidimensional. Their study assumed that the number of intended-to-be measured dimensions was correctly identified. In…

  18. Using Item Response Theory and Model-Data Fit to Conceptualize Differential Item and Person Functioning for Students with Disabilities

    ERIC Educational Resources Information Center

    Engelhard, George, Jr.

    2009-01-01

    The major purpose of this study is to describe a conceptual framework for examining differential item functioning (DIF) and differential person functioning (DPF) as types of model-data misfit within the context of assessing students with disabilities. Specifically, DIF and DPF can be viewed through the lens of residual analyses. Residual analyses…

  19. Differential relationships between personal and community stressors and children's neurocognitive functioning.

    PubMed

    Fishbein, Diana; Warner, Tara; Krebs, Christopher; Trevarthen, Nancy; Flannery, Barbara; Hammond, Jane

    2009-11-01

    Early adversity can alter development of neurocognition, including executive cognitive and emotional regulatory functions. This is the first study to explore differential relationships between personal (physical and emotional abuse and neglect, school and parental stressors) and community (neighborhood problems and witnessing neighborhood violence) stressors and neurocognition. Predominantly Latino children (n = 553) aged 10 to 12 years completed tasks measuring intelligence, impulsivity, problem solving, cognitive flexibility, decision making, and emotion attributions. Adjusting for age and parent education, bivariate regression analyses found exposure to personal stressors to be associated with relative deficits in at least one neurocognitive function. Community stressors were related to relative deficits in emotion attributions and problem solving. In multivariate analyses, neglect was related to misattributions of emotion and IQ deficits, and physical abuse was related to problem solving. Community stressors were not correlated with neurocognition when viewed relative to personal stressors. Stressor types were differentially associated with performance on specific neurocognitive tasks. PMID:18971345

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

    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. PMID:27425612

  2. Regeneration of Thyroid Function by Transplantation of Differentiated Pluripotent Stem Cells.

    PubMed

    Kurmann, Anita A; Serra, Maria; Hawkins, Finn; Rankin, Scott A; Mori, Munemasa; Astapova, Inna; Ullas, Soumya; Lin, Sui; Bilodeau, Melanie; Rossant, Janet; Jean, Jyh C; Ikonomou, Laertis; Deterding, Robin R; Shannon, John M; Zorn, Aaron M; Hollenberg, Anthony N; Kotton, Darrell N

    2015-11-01

    Differentiation of functional thyroid epithelia from pluripotent stem cells (PSCs) holds the potential for application in regenerative medicine. However, progress toward this goal is hampered by incomplete understanding of the signaling pathways needed for directed differentiation without forced overexpression of exogenous transgenes. Here we use mouse PSCs to identify key conserved roles for BMP and FGF signaling in regulating thyroid lineage specification from foregut endoderm in mouse and Xenopus. Thyroid progenitors derived from mouse PSCs can be matured into thyroid follicular organoids that provide functional secretion of thyroid hormones in vivo and rescue hypothyroid mice after transplantation. Moreover, by stimulating the same pathways, we were also able to derive human thyroid progenitors from normal and disease-specific iPSCs generated from patients with hypothyroidism resulting from NKX2-1 haploinsufficiency. Our studies have therefore uncovered the regulatory mechanisms that underlie early thyroid organogenesis and provide a significant step toward cell-based regenerative therapy for hypothyroidism. PMID:26593959

  3. Unsteady Solution of Non-Linear Differential Equations Using Walsh Function Series

    NASA Technical Reports Server (NTRS)

    Gnoffo, Peter A.

    2015-01-01

    Walsh functions form an orthonormal basis set consisting of square waves. The discontinuous nature of square waves make the system well suited for representing functions with discontinuities. The product of any two Walsh functions is another Walsh function - a feature that can radically change an algorithm for solving non-linear partial differential equations (PDEs). The solution algorithm of non-linear differential equations using Walsh function series is unique in that integrals and derivatives may be computed using simple matrix multiplication of series representations of functions. Solutions to PDEs are derived as functions of wave component amplitude. Three sample problems are presented to illustrate the Walsh function series approach to solving unsteady PDEs. These include an advection equation, a Burgers equation, and a Riemann problem. The sample problems demonstrate the use of the Walsh function solution algorithms, exploiting Fast Walsh Transforms in multi-dimensions (O(Nlog(N))). Details of a Fast Walsh Reciprocal, defined here for the first time, enable inversion of aWalsh Symmetric Matrix in O(Nlog(N)) operations. Walsh functions have been derived using a fractal recursion algorithm and these fractal patterns are observed in the progression of pairs of wave number amplitudes in the solutions. These patterns are most easily observed in a remapping defined as a fractal fingerprint (FFP). A prolongation of existing solutions to the next highest order exploits these patterns. The algorithms presented here are considered a work in progress that provide new alternatives and new insights into the solution of non-linear PDEs.

  4. Finite-difference models of ordinary differential equations - Influence of denominator functions

    NASA Technical Reports Server (NTRS)

    Mickens, Ronald E.; Smith, Arthur

    1990-01-01

    This paper discusses the influence on the solutions of finite-difference schemes of using a variety of denominator functions in the discrete modeling of the derivative for any ordinary differential equation. The results obtained are a consequence of using a generalized definition of the first derivative. A particular example of the linear decay equation is used to illustrate in detail the various solution possibilities that can occur.

  5. Differentiability of Palmer's linearization theorem and converse result for density functions

    NASA Astrophysics Data System (ADS)

    Castañeda, Álvaro; Robledo, Gonzalo

    2015-11-01

    We study differentiability properties in a particular case of the Palmer's linearization theorem, which states the existence of a homeomorphism H between the solutions of a linear ODE system having exponential dichotomy and a quasilinear system. Indeed, if the linear system is uniformly asymptotically stable, sufficient conditions ensuring that H is a C2 preserving orientation diffeomorphism are given. As an application, we generalize a converse result of density functions for a nonlinear system in the nonautonomous case.

  6. The DIF-Free-Then-DIF Strategy for the Assessment of Differential Item Functioning

    ERIC Educational Resources Information Center

    Wang, Wen-Chung; Shih, Ching-Lin; Sun, Guo-Wei

    2012-01-01

    The DIF-free-then-DIF (DFTD) strategy consists of two steps: (a) select a set of items that are the most likely to be DIF-free and (b) assess the other items for DIF (differential item functioning) using the designated items as anchors. The rank-based method together with the computer software IRTLRDIF can select a set of DIF-free polytomous items…

  7. Spatial congregation of STAT binding directs selective nuclear architecture during T-cell functional differentiation

    PubMed Central

    Hakim, Ofir; Sung, Myong-Hee; Nakayamada, Shingo; Voss, Ty C.; Baek, Songjoon; Hager, Gordon L.

    2013-01-01

    Higher-order genome organization shows tissue-specific patterns. However, functional relevance and the mechanisms shaping the genome architecture are poorly understood. Here we report a profound shift from promiscuous to highly selective genome organization that accompanies the effector lineage choice of differentiating T cells. As multipotent naive cells receive antigenic signals and commit to a T helper (Th) pathway, the genome-wide contacts of a lineage-specific cytokine locus are preferentially enriched for functionally relevant genes. Despite the establishment of divergent interactomes and global reprogramming of transcription in Th1 versus Th2, the overall expression status of the contact genes is surprisingly similar between the two lineages. Importantly, during differentiation, the genomic contacts are retained and strengthened precisely at DNA binding sites of the specific lineage-determining STAT transcription factor. In cells from the specific STAT knock-out mouse, the signature cytokine locus is unable to shed the promiscuous contacts established in the naive T cells, indicating the importance of genomic STAT binding. Altogether, the global aggregation of STAT binding loci from genic and nongenic regions highlights a new role for differentiation-promoting transcription factors in direct specification of higher-order nuclear architecture through interacting with regulatory regions. Such subnuclear environments have significant implications for efficient functioning of the mature effector lymphocytes. PMID:23212947

  8. From Monocytes to M1/M2 Macrophages: Phenotypical vs. Functional Differentiation

    PubMed Central

    Italiani, Paola; Boraschi, Diana

    2014-01-01

    Studies on monocyte and macrophage biology and differentiation have revealed the pleiotropic activities of these cells. Macrophages are tissue sentinels that maintain tissue integrity by eliminating/repairing damaged cells and matrices. In this M2-like mode, they can also promote tumor growth. Conversely, M1-like macrophages are key effector cells for the elimination of pathogens, virally infected, and cancer cells. Macrophage differentiation from monocytes occurs in the tissue in concomitance with the acquisition of a functional phenotype that depends on microenvironmental signals, thereby accounting for the many and apparently opposed macrophage functions. Many questions arise. When monocytes differentiate into macrophages in a tissue (concomitantly adopting a specific functional program, M1 or M2), do they all die during the inflammatory reaction, or do some of them survive? Do those that survive become quiescent tissue macrophages, able to react as naïve cells to a new challenge? Or, do monocyte-derived tissue macrophages conserve a “memory” of their past inflammatory activation? This review will address some of these important questions under the general framework of the role of monocytes and macrophages in the initiation, development, resolution, and chronicization of inflammation. PMID:25368618

  9. Cellular Trafficking of Phospholamban and Formation of Functional Sarcoplasmic Reticulum During Myocyte DIfferentiation

    SciTech Connect

    Stenoien, David L.; Knyushko, Tatyana V.; Londono, Monica P.; Opresko, Lee; Mayer, M. Uljana; Brady, Scott T.; Squier, Thomas C.; Bigelow, Diana J.

    2007-06-01

    The sarco/endoplasmic reticulum Ca-ATPase (SERCA) family members are transmembrane proteins that play an essential role in regulating intracellular calcium levels. Phospholamban (PLB), a 52 amino acid phosphoprotein, regulates SERCA activity in adult heart and skeletal muscle. Using the C2C12 myocyte cell line, we find endogenous PLB constitutively expressed in both myoblasts and myotubes, whereas SERCA expression coincides with activation of the differentiation program. PLB has a punctuate distribution in myoblasts changing to a reticular distribution in myotubes where it colocalizes with SERCAs. To examine the distribution and dynamics of PLB and SERCA, we expressed fluorescent fusion proteins (GFP, CFP, and YFP) of PLB and SERCA in myoblasts. Coexpressed PLB and SERCA localize to distinct cellular compartments in myoblasts but begin to colocalize as cells differentiate. Fluorescence Recovery After Photobleaching (FRAP) studies show different recovery patterns for each protein in myoblasts confirming their localization to distinct compartments. To extend these studies, we created stable cell lines expressing O6-alkylguanine-DNA alkyltransferase (AGT) fusions with PLB or SERCA to track their localization as myocytes differentiate. These experiments demonstrate that PLB localizes to punctate vesicles in myoblasts and adopts a reticular distribution that coincides with SERCA distribution after differentiation. Colocalization experiments indicate that a subset of PLB in myoblasts colocalizes with endosomes, Golgi, and the plasma membrane however PLB also localizes to other, as yet unidentified vesicles. Our results indicate that differentiation plays a critical role in regulating PLB distribution to ensure its colocalization within the same cellular compartment as SERCA in differentiated cells. The presence and altered distribution of PLB in undifferentiated myoblasts raises the possibility that this protein has additional functions distinct from SERCA regulation.

  10. New results for global exponential synchronization in neural networks via functional differential inclusions

    NASA Astrophysics Data System (ADS)

    Wang, Dongshu; Huang, Lihong; Tang, Longkun

    2015-08-01

    This paper is concerned with the synchronization dynamical behaviors for a class of delayed neural networks with discontinuous neuron activations. Continuous and discontinuous state feedback controller are designed such that the neural networks model can realize exponential complete synchronization in view of functional differential inclusions theory, Lyapunov functional method and inequality technique. The new proposed results here are very easy to verify and also applicable to neural networks with continuous activations. Finally, some numerical examples show the applicability and effectiveness of our main results.

  11. New results for global exponential synchronization in neural networks via functional differential inclusions.

    PubMed

    Wang, Dongshu; Huang, Lihong; Tang, Longkun

    2015-08-01

    This paper is concerned with the synchronization dynamical behaviors for a class of delayed neural networks with discontinuous neuron activations. Continuous and discontinuous state feedback controller are designed such that the neural networks model can realize exponential complete synchronization in view of functional differential inclusions theory, Lyapunov functional method and inequality technique. The new proposed results here are very easy to verify and also applicable to neural networks with continuous activations. Finally, some numerical examples show the applicability and effectiveness of our main results. PMID:26328554

  12. Age-related Differential Item Functioning for the Patient-Reported Outcomes Information System (PROMIS®) Physical Functioning Items

    PubMed Central

    Paz, Sylvia H; Spritzer, Karen L; Morales, Leo S; Hays, Ron D

    2013-01-01

    Purpose To evaluate the equivalence of the PROMIS® wave 1 physical functioning item bank, by age (50 years or older versus 18-49). Materials and methods A total of 114 physical functioning items with 5 response choices were administered to English- (n=1504) and Spanish-language (n=640) adults. Item frequencies, means and standard deviations, item-scale correlations, and internal consistency reliability were estimated. Differential Item Functioning (DIF) by age was evaluated. Results Thirty of the 114 items were fagged for DIF based on an R-squared of 0.02 or above criterion. The expected total score was higher for those respondents who were 18-49 than those who were 50 or older. Conclusions Those who were 50 years or older versus 18-49 years old with the same level of physical functioning responded differently to 30 of the 114 items in the PROMIS® physical functioning item bank. This study yields essential information about the equivalence of the physical functioning items in older versus younger individuals. PMID:24052925

  13. RotundRacGAP functions with Ras during spermatogenesis and retinal differentiation in Drosophila melanogaster.

    PubMed

    Bergeret, E; Pignot-Paintrand, I; Guichard, A; Raymond, K; Fauvarque, M O; Cazemajor, M; Griffin-Shea, R

    2001-09-01

    Our analysis of rotund (rn) null mutations in Drosophila melanogaster revealed that deletion of the rn locus affects both spermatid and retinal differentiation. In the male reproductive system, the absence of RnRacGAP induced small testes, empty seminal vesicles, short testicular cysts, reduced amounts of interspermatid membrane, the absence of individualization complexes, and incomplete mitochondrial condensation. Flagellar growth continued within the short rn null cysts to produce large bulbous terminations of intertwined mature flagella. Organization of the retina was also severely perturbed as evidenced by grossly misshapen ommatidia containing reduced numbers of photoreceptor and pigment cells. These morphological phenotypes were rescued by genomic rnRacGAP transgenes, demonstrating that RnRacGAP function is critical to spermatid and retinal differentiation. The testicular phenotypes were suppressed by heterozygous hypomorphic mutations in the Dras1 and drk genes, indicating cross talk between RacGAP-regulated signaling and that of the Ras pathway. The observed genetic interactions are consistent with a model in which Rac signaling is activated by Ras and negatively regulated by RnRacGAP during spermatid differentiation. RnRacGAP and Ras cross talk also operated during retinal differentiation; however, while the heterozygous hypomorphic drk mutation continued to act as a suppressor of the rn null mutation, the heterozygous hypomorphic Dras1 mutation induced novel retinal phenotypes. PMID:11509670

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

    PubMed

    Boly, Melanie; Sasai, Shuntaro; Gosseries, Olivia; Oizumi, Masafumi; Casali, Adenauer; Massimini, Marcello; Tononi, Giulio

    2015-01-01

    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. PMID:25970444

  15. Olig1 Function Is Required for Oligodendrocyte Differentiation in the Mouse Brain

    PubMed Central

    Dai, Jinxiang; Bercury, Kathryn K.; Ahrendsen, Jared T.

    2015-01-01

    Oligodendrocyte differentiation and myelination are tightly regulated processes orchestrated by a complex transcriptional network. Two bHLH transcription factors in this network, Olig1 and Olig2, are expressed exclusively by oligodendrocytes after late embryonic development. Although the role of Olig2 in the lineage is well established, the role of Olig1 is still unclear. The current studies analyzed the function of Olig1 in oligodendrocyte differentiation and developmental myelination in brain. Both oligodendrocyte progenitor cell commitment and oligodendrocyte differentiation were impaired in the corpus callosum of Olig1-null mice, resulting in hypomyelination throughout adulthood in the brain. As seen in previous studies with this mouse line, although there was an early myelination deficit in the spinal cord, essentially full recovery with normal spinal cord myelination was seen. Intriguingly, this regional difference may be partially attributed to compensatory upregulation of Olig2 protein expression in the spinal cord after Olig1 deletion, which is not seen in brain. The current study demonstrates a unique role for Olig1 in promoting oligodendrocyte progenitor cell commitment, differentiation, and subsequent myelination primarily in brain, but not spinal cord. PMID:25762682

  16. Olig1 function is required for oligodendrocyte differentiation in the mouse brain.

    PubMed

    Dai, Jinxiang; Bercury, Kathryn K; Ahrendsen, Jared T; Macklin, Wendy B

    2015-03-11

    Oligodendrocyte differentiation and myelination are tightly regulated processes orchestrated by a complex transcriptional network. Two bHLH transcription factors in this network, Olig1 and Olig2, are expressed exclusively by oligodendrocytes after late embryonic development. Although the role of Olig2 in the lineage is well established, the role of Olig1 is still unclear. The current studies analyzed the function of Olig1 in oligodendrocyte differentiation and developmental myelination in brain. Both oligodendrocyte progenitor cell commitment and oligodendrocyte differentiation were impaired in the corpus callosum of Olig1-null mice, resulting in hypomyelination throughout adulthood in the brain. As seen in previous studies with this mouse line, although there was an early myelination deficit in the spinal cord, essentially full recovery with normal spinal cord myelination was seen. Intriguingly, this regional difference may be partially attributed to compensatory upregulation of Olig2 protein expression in the spinal cord after Olig1 deletion, which is not seen in brain. The current study demonstrates a unique role for Olig1 in promoting oligodendrocyte progenitor cell commitment, differentiation, and subsequent myelination primarily in brain, but not spinal cord. PMID:25762682

  17. Cardiogenic differentiation of mesenchymal stem cells with gold nanoparticle loaded functionalized nanofibers.

    PubMed

    Sridhar, Sreepathy; Venugopal, Jayarama Reddy; Sridhar, Radhakrishnan; Ramakrishna, Seeram

    2015-10-01

    Cardiac tissue engineering promises to revolutionize the treatment of patients with end-stage heart failure and provide new solutions to the serious problems of shortage of heart donors. The influence of extracellular matrix (ECM) plays an influential role along with nanostructured components for guided stem cell differentiation. Hence, nanoparticle embedded Nanofibrous scaffolds of FDA approved polycaprolactone (PCL), Vitamin B12 (Vit B12), Aloe Vera(AV) and Silk fibroin(SF) was constructed to differentiate mesenchymal stem cells into cardiac lineage. Cardiomyocytes (CM) and Mesenchymal stem cells (MSC) were co-cultured on these fabricated nanofibrous scaffolds for the regeneration of infarcted myocardium. Results demonstrated that synthesized gold nanoparticles were of the size 16 nm and the nanoparticle loaded nanofibrous scaffold has a mechanical strength of 2.56 MPa matching that of the native myocardium. The gold nanoparticle blended PCL scaffolds were found to be enhancing the MSCs proliferation and differentiation into cardiogenesis. Most importantly the phenotype and cardiac marker expression in differentiated MSCs were highly resonated in gold nanoparticle loaded nanofibrous scaffolds. The appropriate mechanical strength provided by the functionalized nanofibrous scaffolds profoundly supported MSCs to produce contractile proteins and achieve typical cardiac phenotype. PMID:26209968

  18. Differentiation and functional connection of vascular elements in compatible and incompatible pear/quince internode micrografts.

    PubMed

    Espen, Luca; Cocucci, Maurizio; Sacchi, Gian Attilio

    2005-11-01

    Micrografts of internodes excised from in vitro grown pear plants (Pyrus communis L. cv. 'Bosc' (B) and cv. 'Butirra Hardy' (BH)) and quince (Cydonia oblonga Mill. East Malling clone C (EMC)), were cultured aseptically to test the effectiveness of their functional vascular reconnection in relation to incompatibility-compatibility relationships that these genotypes exhibit in the field. The incompatible heterograft (B/EMC) showed a marked delay in internode cohesion compared with the autografts (both B/B and BH/BH) and the compatible heterograft (BH/EMC). Even when fused, the translocation of [14C]-sorbitol from upper to lower internode was lower in B/EMC micrografts than in the other combinations. Epifluorescence studies performed with carboxyfluorescin, a specific phloem probe, indicated that the limited translocation was caused by a delay in the establishment of functional phloem continuity between the two internodes. In the B/EMC combination, new differentiated tracheary elements (TE) in the parenchyma tissue at the graft interface between the two internodes were not detected until 30 days after grafting, whereas in the BH/EMC heterograft and both autografts, new xylem connections appeared to cross the interface 20 days after grafting. Immunohistochemical detection (terminal nick-end labeling assay) of the number of cells undergoing nuclear DNA fragmentation at the graft interface confirmed that the limited and delayed TE differentiation in B/EMC heterografts was associated with a decrease in the activity of programmed cell death processes involved in the differentiation of TE. PMID:16105809

  19. Pax3 functions at a nodal point in melanocyte stem cell differentiation.

    PubMed

    Lang, Deborah; Lu, Min Min; Huang, Li; Engleka, Kurt A; Zhang, Maozhen; Chu, Emily Y; Lipner, Shari; Skoultchi, Arthur; Millar, Sarah E; Epstein, Jonathan A

    2005-02-24

    Most stem cells are not totipotent. Instead, they are partially committed but remain undifferentiated. Upon appropriate stimulation they are capable of regenerating mature cell types. Little is known about the genetic programmes that maintain the undifferentiated phenotype of lineage-restricted stem cells. Here we describe the molecular details of a nodal point in adult melanocyte stem cell differentiation in which Pax3 simultaneously functions to initiate a melanogenic cascade while acting downstream to prevent terminal differentiation. Pax3 activates expression of Mitf, a transcription factor critical for melanogenesis, while at the same time it competes with Mitf for occupancy of an enhancer required for expression of dopachrome tautomerase, an enzyme that functions in melanin synthesis. Pax3-expressing melanoblasts are thus committed but undifferentiated until Pax3-mediated repression is relieved by activated beta-catenin. Thus, a stem cell transcription factor can both determine cell fate and simultaneously maintain an undifferentiated state, leaving a cell poised to differentiate in response to external stimuli. PMID:15729346

  20. Dicer1-miR-328-Bace1 signalling controls brown adipose tissue differentiation and function.

    PubMed

    Oliverio, Matteo; Schmidt, Elena; Mauer, Jan; Baitzel, Catherina; Hansmeier, Nils; Khani, Sajjad; Konieczka, Sandra; Pradas-Juni, Marta; Brodesser, Susanne; Van, Trieu-My; Bartsch, Deniz; Brönneke, Hella S; Heine, Markus; Hilpert, Hans; Tarcitano, Emilio; Garinis, George A; Frommolt, Peter; Heeren, Joerg; Mori, Marcelo A; Brüning, Jens C; Kornfeld, Jan-Wilhelm

    2016-03-01

    Activation of brown adipose tissue (BAT) controls energy homeostasis in rodents and humans and has emerged as an innovative strategy for the treatment of obesity and type 2 diabetes mellitus. Here we show that ageing- and obesity-associated dysfunction of brown fat coincides with global microRNA downregulation due to reduced expression of the microRNA-processing node Dicer1. Consequently, heterozygosity of Dicer1 in BAT aggravated diet-induced-obesity (DIO)-evoked deterioration of glucose metabolism. Analyses of differential microRNA expression during preadipocyte commitment and mouse models of progeria, longevity and DIO identified miR-328 as a regulator of BAT differentiation. Reducing miR-328 blocked preadipocyte commitment, whereas miR-328 overexpression instigated BAT differentiation and impaired muscle progenitor commitment-partly through silencing of the β-secretase Bace1. Loss of Bace1 enhanced brown preadipocyte specification in vitro and was overexpressed in BAT of obese and progeroid mice. In vivo Bace1 inhibition delayed DIO-induced weight gain and improved glucose tolerance and insulin sensitivity. These experiments reveal Dicer1-miR-328-Bace1 signalling as a determinant of BAT function, and highlight the potential of Bace1 inhibition as a therapeutic approach to improve not only neurodegenerative diseases but also ageing- and obesity-associated impairments of BAT function. PMID:26900752

  1. FIDEA: a server for the functional interpretation of differential expression analysis.

    PubMed

    D'Andrea, Daniel; Grassi, Luigi; Mazzapioda, Mariagiovanna; Tramontano, Anna

    2013-07-01

    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. PMID:23754850

  2. Dynamic competition between large-scale functional networks differentiates fear conditioning and extinction in humans.

    PubMed

    Marstaller, Lars; Burianová, Hana; Reutens, David C

    2016-07-01

    The high evolutionary value of learning when to respond to threats or when to inhibit previously learned associations after changing threat contingencies is reflected in dedicated networks in the animal and human brain. Recent evidence further suggests that adaptive learning may be dependent on the dynamic interaction of meta-stable functional brain networks. However, it is still unclear which functional brain networks compete with each other to facilitate associative learning and how changes in threat contingencies affect this competition. The aim of this study was to assess the dynamic competition between large-scale networks related to associative learning in the human brain by combining a repeated differential conditioning and extinction paradigm with independent component analysis of functional magnetic resonance imaging data. The results (i) identify three task-related networks involved in initial and sustained conditioning as well as extinction, and demonstrate that (ii) the two main networks that underlie sustained conditioning and extinction are anti-correlated with each other and (iii) the dynamic competition between these two networks is modulated in response to changes in associative contingencies. These findings provide novel evidence for the view that dynamic competition between large-scale functional networks differentiates fear conditioning from extinction learning in the healthy brain and suggest that dysfunctional network dynamics might contribute to learning-related neuropsychiatric disorders. PMID:27079532

  3. Multivoxel patterns reveal functionally differentiated networks underlying auditory feedback processing of speech.

    PubMed

    Zheng, Zane Z; Vicente-Grabovetsky, Alejandro; MacDonald, Ewen N; Munhall, Kevin G; Cusack, Rhodri; Johnsrude, Ingrid S

    2013-03-01

    The everyday act of speaking involves the complex processes of speech motor control. An important component of control is monitoring, detection, and processing of errors when auditory feedback does not correspond to the intended motor gesture. Here we show, using fMRI and converging operations 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 human participants were vocalizing monosyllabic words, and to present the same auditory stimuli while participants were passively listening. Whole-brain analysis of neural-pattern similarity revealed three functional networks that were differentially sensitive to distorted auditory feedback during vocalization, compared with during passive listening. One network of regions appears to encode an "error signal" regardless of acoustic features of the error: this network, including right angular gyrus, right supplementary motor area, and bilateral cerebellum, yielded consistent neural patterns across acoustically different, distorted feedback types, only during articulation (not during passive listening). In contrast, a frontotemporal network appears sensitive to the speech features of auditory stimuli during passive listening; this preference for speech features was diminished when the same stimuli were presented as auditory concomitants of vocalization. A third network, showing a distinct functional pattern from the other two, appears to capture aspects of both neural response profiles. Together, our findings suggest that auditory feedback processing during speech motor control may rely on multiple, interactive, functionally differentiated neural systems. PMID:23467350

  4. Urinary NGAL Levels Correlate with Differential Renal Function in Patients with Ureteropelvic Junction Obstruction Undergoing Pyeloplasty

    PubMed Central

    Cost, Nicholas G.; Noh, Paul H.; Devarajan, Prasad; Ivancic, Vesna; Reddy, Pramod P.; Minevich, Eugene; Bennett, Michael; Haffner, Christopher; Schulte, Marion; DeFoor, W. Robert

    2014-01-01

    Purpose: Recent investigations described the use of NGAL, a sensitive biomarker for kidney injury, in the setting of ureteropelvic junction obstruction. We prospectively evaluated urinary NGAL levels in the affected renal pelvis and bladder of children with ureteropelvic junction obstruction undergoing unilateral dismembered pyeloplasty. Our hypothesis was that higher NGAL in the kidney and bladder would correlate with decreased ipsilateral differential function. Materials and Methods: We performed a prospective cohort study in patients treated with unilateral dismembered pyeloplasty from 2010 to 2012. Urine was obtained intraoperatively from the bladder and obstructed renal pelvis. A control population of unaffected children was recruited to provide a voided bladder specimen. Bladder NGAL levels were compared between the study and control populations. We tested our study hypothesis by correlating bladder and renal pelvic NGAL levels with the differential renal function of the affected kidney. Results: A total of 61 patients with a median age at surgery of 1.62 years (range 0.12 to 18.7) were enrolled in the study. Median bladder NGAL was 18.6 ng/mg (range 1.4-1,650.8) and median renal pelvic NGAL was 26.2 ng/mg (range 1.2-18,034.5, p = 0.004). Median bladder NGAL was significantly higher than in controls (p = 0.004). The correlation of bladder and renal pelvic NGAL with differential renal function was r = −0.359 (p = 0.004) and r = −0.383 (p = 0.002), respectively. Conclusions: Bladder NGAL is increased in children with ureteropelvic junction obstruction. Renal pelvic and bladder normalized urinary NGAL levels correlate inversely with the relative function of the affected kidney in cases of unilateral ureteropelvic junction obstruction. PMID:23791906

  5. Differentiation and function of group 3 innate lymphoid cells, from embryo to adult.

    PubMed

    van de Pavert, Serge A; Vivier, Eric

    2016-01-01

    Group 3 innate lymphoid cells (ILC3) represent a heterogeneous population of cells that share the nuclear hormone receptor RORγt (retinoic acid receptor-related orphan receptor γt) as a master regulator for differentiation and function. ILC3 can be divided into two major subsets based on the cell surface expression of the natural cytotoxicity receptor (NCR), NKp46. A subset of NCR(-) ILC3 includes the previously known lymphoid-tissue inducer cells that are essential for the embryonic formation of peripheral lymph nodes and Peyer's patches. After birth, the NCR(-) and NCR(+) ILC3 contribute to the maintenance of health but also to inflammation in mucosal tissues. This review will describe the differentiation pathways of ILC3, their involvement in the development of the adaptive immune system and their role in the establishment and maintenance of gut immunity. PMID:26374472

  6. Tissue-specific DNA demethylation is required for proper B-cell differentiation and function.

    PubMed

    Orlanski, Shari; Labi, Verena; Reizel, Yitzhak; Spiro, Adam; Lichtenstein, Michal; Levin-Klein, Rena; Koralov, Sergei B; Skversky, Yael; Rajewsky, Klaus; Cedar, Howard; Bergman, Yehudit

    2016-05-01

    There is ample evidence that somatic cell differentiation during development is accompanied by extensive DNA demethylation of specific sites that vary between cell types. Although the mechanism of this process has not yet been elucidated, it is likely to involve the conversion of 5mC to 5hmC by Tet enzymes. We show that a Tet2/Tet3 conditional knockout at early stages of B-cell development largely prevents lineage-specific programmed demethylation events. This lack of demethylation affects the expression of nearby B-cell lineage genes by impairing enhancer activity, thus causing defects in B-cell differentiation and function. Thus, tissue-specific DNA demethylation appears to be necessary for proper somatic cell development in vivo. PMID:27091986

  7. Electrical double layers and differential capacitance in molten salts from density functional theory

    DOE PAGESBeta

    Frischknecht, Amalie L.; Halligan, Deaglan O.; Parks, Michael L.

    2014-08-05

    Classical density functional theory (DFT) is used to calculate the structure of the electrical double layer and the differential capacitance of model molten salts. The DFT is shown to give good qualitative agreement with Monte Carlo simulations in the molten salt regime. The DFT is then applied to three common molten salts, KCl, LiCl, and LiKCl, modeled as charged hard spheres near a planar charged surface. The DFT predicts strong layering of the ions near the surface, with the oscillatory density profiles extending to larger distances for larger electrostatic interactions resulting from either lower temperature or lower dielectric constant. Inmore » conclusion, overall the differential capacitance is found to be bell-shaped, in agreement with recent theories and simulations for ionic liquids and molten salts, but contrary to the results of the classical Gouy-Chapman theory.« less

  8. Electrical double layers and differential capacitance in molten salts from density functional theory

    SciTech Connect

    Frischknecht, Amalie L.; Halligan, Deaglan O.; Parks, Michael L.

    2014-08-05

    Classical density functional theory (DFT) is used to calculate the structure of the electrical double layer and the differential capacitance of model molten salts. The DFT is shown to give good qualitative agreement with Monte Carlo simulations in the molten salt regime. The DFT is then applied to three common molten salts, KCl, LiCl, and LiKCl, modeled as charged hard spheres near a planar charged surface. The DFT predicts strong layering of the ions near the surface, with the oscillatory density profiles extending to larger distances for larger electrostatic interactions resulting from either lower temperature or lower dielectric constant. In conclusion, overall the differential capacitance is found to be bell-shaped, in agreement with recent theories and simulations for ionic liquids and molten salts, but contrary to the results of the classical Gouy-Chapman theory.

  9. Notch gain of function inhibits chondrocyte differentiation via Rbpj-dependent suppression of Sox9

    PubMed Central

    Chen, Shan; Tao, Jianning; Bae, Yangjin; Jiang, Ming-Ming; Bertin, Terry; Chen, Yuqing; Yang, Tao; Lee, Brendan

    2013-01-01

    Abstract Notch signaling plays a critical role during development by directing the binary cell fate decision between progenitors and differentiated cells. Previous studies have shown sustained Notch activation in cartilage leads to chondrodysplasia. Genetic evidence indicates that Notch regulates limb bud mesenchymal stem cell differentiation into chondrocytes via an Rbpj-dependent Notch pathway. However, it is still unknown how Notch governs chondrogenesis in the axial skeleton where Notch serves a primary patterning function. We hypothesized that both Rbpj-dependent and Rbpj-independent Notch signaling mechanisms might be involved. Cartilage-specific Notch gain-of-function (GOF) mutant mice display chondrodysplasia accompanied by loss of Sox9 expression in vertebrae. To evaluate the contribution of an Rbpj-dependent Notch signaling to this phenotype, we deleted Rbpj on the Notch GOF background. These mice showed persistent spine abnormalities characterized by “butterfly” vertebrae suggesting that removal of Rbpj does not fully rescue the axial skeleton deformities caused by Notch GOF. However, Sox9 protein level was restored in Rbpj-deficient Notch GOF mice compared with Notch GOF mutants, demonstrating that regulation of Sox9 expression is canonical or Rbpj-dependent. To further understand the molecular basis of this regulation, we performed chromatin immunoprecipitation (ChIP) assays and detected the recruitment of the Rbpj/NICD transcription complex to Rbpj-binding sites upstream of the Sox9 promoter. The association of the Rbpj/NICD complex with the Sox9 promoter is associated with transcriptional repression of Sox9 in a cellular model of chondrocyte differentiation. Hence, Notch negatively regulates chondrocyte differentiation in the axial skeleton by suppressing Sox9 transcription, and Rbpj-independent Notch signaling mechanisms may also contribute to axial skeletogenesis. PMID:22991339

  10. Notch gain of function inhibits chondrocyte differentiation via Rbpj-dependent suppression of Sox9.

    PubMed

    Chen, Shan; Tao, Jianning; Bae, Yangjin; Jiang, Ming-Ming; Bertin, Terry; Chen, Yuqing; Yang, Tao; Lee, Brendan

    2013-03-01

    Notch signaling plays a critical role during development by directing the binary cell fate decision between progenitors and differentiated cells. Previous studies have shown sustained Notch activation in cartilage leads to chondrodysplasia. Genetic evidence indicates that Notch regulates limb bud mesenchymal stem cell differentiation into chondrocytes via an Rbpj-dependent Notch pathway. However, it is still unknown how Notch governs chondrogenesis in the axial skeleton where Notch serves a primary patterning function. We hypothesized that both Rbpj-dependent and Rbpj-independent Notch signaling mechanisms might be involved. Cartilage-specific Notch gain-of-function (GOF) mutant mice display chondrodysplasia accompanied by loss of Sox9 expression in vertebrae. To evaluate the contribution of an Rbpj-dependent Notch signaling to this phenotype, we deleted Rbpj on the Notch GOF background. These mice showed persistent spine abnormalities characterized by "butterfly" vertebrae suggesting that removal of Rbpj does not fully rescue the axial skeleton deformities caused by Notch GOF. However, Sox9 protein level was restored in Rbpj-deficient Notch GOF mice compared with Notch GOF mutants, demonstrating that regulation of Sox9 expression is canonical or Rbpj-dependent. To further understand the molecular basis of this regulation, we performed chromatin immunoprecipitation (ChIP) assays and detected the recruitment of the Rbpj/NICD transcription complex to Rbpj-binding sites upstream of the Sox9 promoter. The association of the Rbpj/NICD complex with the Sox9 promoter is associated with transcriptional repression of Sox9 in a cellular model of chondrocyte differentiation. Hence, Notch negatively regulates chondrocyte differentiation in the axial skeleton by suppressing Sox9 transcription, and Rbpj-independent Notch signaling mechanisms may also contribute to axial skeletogenesis. PMID:22991339