Sample records for iv canonical problem

  1. On two mathematical problems of canonical quantization. IV

    NASA Astrophysics Data System (ADS)

    Kirillov, A. I.

    1992-11-01

    A method for solving the problem of reconstructing a measure beginning with its logarithmic derivative is presented. The method completes that of solving the stochastic differential equation via Dirichlet forms proposed by S. Albeverio and M. Rockner. As a result one obtains the mathematical apparatus for the stochastic quantization. The apparatus is applied to prove the existence of the Feynman-Kac measure of the sine-Gordon and λφ2n/(1 + K2φ2n)-models. A synthesis of both mathematical problems of canonical quantization is obtained in the form of a second-order martingale problem for vacuum noise. It is shown that in stochastic mechanics the martingale problem is an analog of Newton's second law and enables us to find the Nelson's stochastic trajectories without determining the wave functions.

  2. A Problem-Centered Approach to Canonical Matrix Forms

    ERIC Educational Resources Information Center

    Sylvestre, Jeremy

    2014-01-01

    This article outlines a problem-centered approach to the topic of canonical matrix forms in a second linear algebra course. In this approach, abstract theory, including such topics as eigenvalues, generalized eigenspaces, invariant subspaces, independent subspaces, nilpotency, and cyclic spaces, is developed in response to the patterns discovered…

  3. Axis IV--psychosocial and environmental problems--in the DSM-IV.

    PubMed

    Ramirez, A; Ekselius, L; Ramklint, M

    2013-11-01

    The aim of this study was to further explore the properties of axis IV in the Diagnostic and statistical manual of mental disorders, 4th edition (DSM-IV). In a naturalistic cross-sectional design, a group (n = 163) of young (18-25 years old) Swedish psychiatric outpatients was assessed according to DSM-IV. Psychosocial and environmental problems/axis IV were evaluated through structured interviewing by a social worker and by self-assessment on a questionnaire. Reliability between professional assessment and self-assessment of axis IV was examined. Concurrent validity of axis IV was also examined. Reliability between professional and self-assessed axis IV was fair to almost perfect, 0.31-0.83, according to prevalence and bias-adjusted kappa. Categories of psychosocial stress and environmental problems were related to the presence of axis I disorders, co-morbidity, personality disorders and decreasing Global Assessment of Functioning (GAF) values. The revised axis IV according to DSM-IV seems to have concurrent validity, but is still hampered by limited reliability. © 2013 John Wiley & Sons Ltd.

  4. Construction Method of Analytical Solutions to the Mathematical Physics Boundary Problems for Non-Canonical Domains

    NASA Astrophysics Data System (ADS)

    Mobarakeh, Pouyan Shakeri; Grinchenko, Victor T.

    2015-06-01

    The majority of practical cases of acoustics problems requires solving the boundary problems in non-canonical domains. Therefore construction of analytical solutions of mathematical physics boundary problems for non-canonical domains is both lucrative from the academic viewpoint, and very instrumental for elaboration of efficient algorithms of quantitative estimation of the field characteristics under study. One of the main solving ideologies for such problems is based on the superposition method that allows one to analyze a wide class of specific problems with domains which can be constructed as the union of canonically-shaped subdomains. It is also assumed that an analytical solution (or quasi-solution) can be constructed for each subdomain in one form or another. However, this case implies some difficulties in the construction of calculation algorithms, insofar as the boundary conditions are incompletely defined in the intervals, where the functions appearing in the general solution are orthogonal to each other. We discuss several typical examples of problems with such difficulties, we study their nature and identify the optimal methods to overcome them.

  5. Canonical Transformations of Kepler Trajectories

    ERIC Educational Resources Information Center

    Mostowski, Jan

    2010-01-01

    In this paper, canonical transformations generated by constants of motion in the case of the Kepler problem are discussed. It is shown that canonical transformations generated by angular momentum are rotations of the trajectory. Particular attention is paid to canonical transformations generated by the Runge-Lenz vector. It is shown that these…

  6. Attention Problems and Stability of WISC-IV Scores Among Clinically Referred Children.

    PubMed

    Green Bartoi, Marla; Issner, Jaclyn Beth; Hetterscheidt, Lesley; January, Alicia M; Kuentzel, Jeffrey Garth; Barnett, Douglas

    2015-01-01

    We examined the stability of Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV) scores among 51 diverse, clinically referred 8- to 16-year-olds (M(age) = 11.24 years, SD = 2.36). Children were referred to and tested at an urban, university-based training clinic; 70% of eligible children completed follow-up testing 12 months to 40 months later (M = 22.05, SD = 5.94). Stability for index scores ranged from .58 (Processing Speed) to .81 (Verbal Comprehension), with a stability of .86 for Full-Scale IQ. Subtest score stability ranged from .35 (Letter-Number Sequencing) to .81 (Vocabulary). Indexes believed to be more susceptible to concentration (Processing Speed and Working Memory) had lower stability. We also examined attention problems as a potential moderating factor of WISC-IV index and subtest score stability. Children with attention problems had significantly lower stability for Digit Span and Matrix Reasoning subtests compared with children without attention problems. These results provide support for the temporal stability of the WISC-IV and also provide some support for the idea that attention problems contribute to children producing less stable IQ estimates when completing the WISC-IV. We hope our report encourages further examination of this hypothesis and its implications.

  7. The issue of gauge choice in the Landau problem and the physics of canonical and mechanical orbital angular momenta

    NASA Astrophysics Data System (ADS)

    Wakamatsu, M.; Kitadono, Y.; Zhang, P.-M.

    2018-05-01

    One intriguing issue in the nucleon spin decomposition problem is the existence of two types of decompositions, which are representably characterized by two different orbital angular momenta (OAMs) of quarks. The one is the mechanical OAM, while the other is the so-called gauge-invariant canonical (g.i.c.) OAM, the concept of which was introduced by Chen et al. An especially delicate quantity is the g.i.c. OAM, which must be distinguished from the ordinary (gauge-variant) canonical OAM. We find that, owing to its analytically solvable nature, the famous Landau problem offers an ideal tool to understand the difference and the physical meaning of the above three OAMs, i.e. the standard canonical OAM, g.i.c. OAM, and the mechanical OAM. We analyze these three OAMs in two different formulations of the Landau problem, first in the standard (gauge-fixed) formulation and second in the gauge-invariant (but path-dependent) formulation of DeWitt. Especially interesting is the latter formalism. It is shown that the choice of path has an intimate connection with the choice of gauge, but they are not necessarily equivalent. Then, we answer the question about what is the consequence of a particular choice of path in DeWitt's formalism. This analysis also clarifies the implication of the gauge symmetry hidden in the concept of g.i.c. OAM. Finally, we show that the finding above offers a clear understanding about the uniqueness or non-uniqueness problem of the nucleon spin decomposition, which arises from the arbitrariness in the definition of the so-called physical component of the gauge field.

  8. Random discrete linear canonical transform.

    PubMed

    Wei, Deyun; Wang, Ruikui; Li, Yuan-Min

    2016-12-01

    Linear canonical transforms (LCTs) are a family of integral transforms with wide applications in optical, acoustical, electromagnetic, and other wave propagation problems. In this paper, we propose the random discrete linear canonical transform (RDLCT) by randomizing the kernel transform matrix of the discrete linear canonical transform (DLCT). The RDLCT inherits excellent mathematical properties from the DLCT along with some fantastic features of its own. It has a greater degree of randomness because of the randomization in terms of both eigenvectors and eigenvalues. Numerical simulations demonstrate that the RDLCT has an important feature that the magnitude and phase of its output are both random. As an important application of the RDLCT, it can be used for image encryption. The simulation results demonstrate that the proposed encryption method is a security-enhanced image encryption scheme.

  9. Restoring canonical partition functions from imaginary chemical potential

    NASA Astrophysics Data System (ADS)

    Bornyakov, V. G.; Boyda, D.; Goy, V.; Molochkov, A.; Nakamura, A.; Nikolaev, A.; Zakharov, V. I.

    2018-03-01

    Using GPGPU techniques and multi-precision calculation we developed the code to study QCD phase transition line in the canonical approach. The canonical approach is a powerful tool to investigate sign problem in Lattice QCD. The central part of the canonical approach is the fugacity expansion of the grand canonical partition functions. Canonical partition functions Zn(T) are coefficients of this expansion. Using various methods we study properties of Zn(T). At the last step we perform cubic spline for temperature dependence of Zn(T) at fixed n and compute baryon number susceptibility χB/T2 as function of temperature. After that we compute numerically ∂χ/∂T and restore crossover line in QCD phase diagram. We use improved Wilson fermions and Iwasaki gauge action on the 163 × 4 lattice with mπ/mρ = 0.8 as a sandbox to check the canonical approach. In this framework we obtain coefficient in parametrization of crossover line Tc(µ2B) = Tc(C-ĸµ2B/T2c) with ĸ = -0.0453 ± 0.0099.

  10. Canonical forms of multidimensional steady inviscid flows

    NASA Technical Reports Server (NTRS)

    Taasan, Shlomo

    1993-01-01

    Canonical forms and canonical variables for inviscid flow problems are derived. In these forms the components of the system governed by different types of operators (elliptic and hyperbolic) are separated. Both the incompressible and compressible cases are analyzed, and their similarities and differences are discussed. The canonical forms obtained are block upper triangular operator form in which the elliptic and non-elliptic parts reside in different blocks. The full nonlinear equations are treated without using any linearization process. This form enables a better analysis of the equations as well as better numerical treatment. These forms are the analog of the decomposition of the one dimensional Euler equations into characteristic directions and Riemann invariants.

  11. Parallel Prebiotic Origin of Canonical and Non-Canonical Purine Nucleosides

    NASA Astrophysics Data System (ADS)

    Becker, S.; Carell, T.

    2017-07-01

    RNA of all living organisms is highly modified. It is unclear if these non-canonical bases are ancestors of an early Earth or biological inventions. We investigated a prebiotic pathway that leads to canonical and non-canonical purine nucleosides.

  12. LCPT: a program for finding linear canonical transformations. [In MACSYMA

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Char, B.W.; McNamara, B.

    This article describes a MACSYMA program to compute symbolically a canonical linear transformation between coordinate systems. The difficulties in implementation of this canonical small physics problem are also discussed, along with the implications that may be drawn from such difficulties about widespread MACSYMA usage by the community of computational/theoretical physicists.

  13. Computation of canonical correlation and best predictable aspect of future for time series

    NASA Technical Reports Server (NTRS)

    Pourahmadi, Mohsen; Miamee, A. G.

    1989-01-01

    The canonical correlation between the (infinite) past and future of a stationary time series is shown to be the limit of the canonical correlation between the (infinite) past and (finite) future, and computation of the latter is reduced to a (generalized) eigenvalue problem involving (finite) matrices. This provides a convenient and essentially, finite-dimensional algorithm for computing canonical correlations and components of a time series. An upper bound is conjectured for the largest canonical correlation.

  14. Canonical-ensemble state-averaged complete active space self-consistent field (SA-CASSCF) strategy for problems with more diabatic than adiabatic states: Charge-bond resonance in monomethine cyanines

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Olsen, Seth, E-mail: seth.olsen@uq.edu.au

    2015-01-28

    This paper reviews basic results from a theory of the a priori classical probabilities (weights) in state-averaged complete active space self-consistent field (SA-CASSCF) models. It addresses how the classical probabilities limit the invariance of the self-consistency condition to transformations of the complete active space configuration interaction (CAS-CI) problem. Such transformations are of interest for choosing representations of the SA-CASSCF solution that are diabatic with respect to some interaction. I achieve the known result that a SA-CASSCF can be self-consistently transformed only within degenerate subspaces of the CAS-CI ensemble density matrix. For uniformly distributed (“microcanonical”) SA-CASSCF ensembles, self-consistency is invariant tomore » any unitary CAS-CI transformation that acts locally on the ensemble support. Most SA-CASSCF applications in current literature are microcanonical. A problem with microcanonical SA-CASSCF models for problems with “more diabatic than adiabatic” states is described. The problem is that not all diabatic energies and couplings are self-consistently resolvable. A canonical-ensemble SA-CASSCF strategy is proposed to solve the problem. For canonical-ensemble SA-CASSCF, the equilibrated ensemble is a Boltzmann density matrix parametrized by its own CAS-CI Hamiltonian and a Lagrange multiplier acting as an inverse “temperature,” unrelated to the physical temperature. Like the convergence criterion for microcanonical-ensemble SA-CASSCF, the equilibration condition for canonical-ensemble SA-CASSCF is invariant to transformations that act locally on the ensemble CAS-CI density matrix. The advantage of a canonical-ensemble description is that more adiabatic states can be included in the support of the ensemble without running into convergence problems. The constraint on the dimensionality of the problem is relieved by the introduction of an energy constraint. The method is illustrated with a complete active

  15. Canonical-ensemble state-averaged complete active space self-consistent field (SA-CASSCF) strategy for problems with more diabatic than adiabatic states: charge-bond resonance in monomethine cyanines.

    PubMed

    Olsen, Seth

    2015-01-28

    This paper reviews basic results from a theory of the a priori classical probabilities (weights) in state-averaged complete active space self-consistent field (SA-CASSCF) models. It addresses how the classical probabilities limit the invariance of the self-consistency condition to transformations of the complete active space configuration interaction (CAS-CI) problem. Such transformations are of interest for choosing representations of the SA-CASSCF solution that are diabatic with respect to some interaction. I achieve the known result that a SA-CASSCF can be self-consistently transformed only within degenerate subspaces of the CAS-CI ensemble density matrix. For uniformly distributed ("microcanonical") SA-CASSCF ensembles, self-consistency is invariant to any unitary CAS-CI transformation that acts locally on the ensemble support. Most SA-CASSCF applications in current literature are microcanonical. A problem with microcanonical SA-CASSCF models for problems with "more diabatic than adiabatic" states is described. The problem is that not all diabatic energies and couplings are self-consistently resolvable. A canonical-ensemble SA-CASSCF strategy is proposed to solve the problem. For canonical-ensemble SA-CASSCF, the equilibrated ensemble is a Boltzmann density matrix parametrized by its own CAS-CI Hamiltonian and a Lagrange multiplier acting as an inverse "temperature," unrelated to the physical temperature. Like the convergence criterion for microcanonical-ensemble SA-CASSCF, the equilibration condition for canonical-ensemble SA-CASSCF is invariant to transformations that act locally on the ensemble CAS-CI density matrix. The advantage of a canonical-ensemble description is that more adiabatic states can be included in the support of the ensemble without running into convergence problems. The constraint on the dimensionality of the problem is relieved by the introduction of an energy constraint. The method is illustrated with a complete active space valence

  16. Histories approach to general relativity: I. The spacetime character of the canonical description

    NASA Astrophysics Data System (ADS)

    Savvidou, Ntina

    2004-01-01

    The problem of time in canonical quantum gravity is related to the fact that the canonical description is based on the prior choice of a spacelike foliation, hence making a reference to a spacetime metric. However, the metric is expected to be a dynamical, fluctuating quantity in quantum gravity. We show how this problem can be solved in the histories formulation of general relativity. We implement the 3 + 1 decomposition using metric-dependent foliations which remain spacelike with respect to all possible Lorentzian metrics. This allows us to find an explicit relation of covariant and canonical quantities which preserves the spacetime character of the canonical description. In this new construction, we also have the coexistence of the spacetime diffeomorphisms group, Diff(M), and the Dirac algebra of constraints.

  17. Late onset canonical babbling: a possible early marker of abnormal development.

    PubMed

    Oller, D K; Eilers, R E; Neal, A R; Cobo-Lewis, A B

    1998-11-01

    By their 10th month of life, typically developing infants produce canonical babbling, which includes the well-formed syllables required for meaningful speech. Research suggests that emerging speech or language-related disorders might be associated with late onset of canonical babbling. Onset of canonical babbling was investigated for 1,536 high-risk infants, at about 10-months corrected age. Parental report by open-ended questionnaire was found to be an efficient method for ascertaining babbling status. Although delays were infrequent, they were often associated with genetic, neurological, anatomical, and/or physiological abnormalities. Over half the cases of late canonical babbling were not, at the time they were discovered associated with prior significant medical diagnoses. Late canonical-babbling onset may be a predictor of later developmental disabilities, including problems in speech, language, and reading.

  18. Generalization between canonical and non-canonical views in object recognition

    PubMed Central

    Ghose, Tandra; Liu, Zili

    2013-01-01

    Viewpoint generalization in object recognition is the process that allows recognition of a given 3D object from many different viewpoints despite variations in its 2D projections. We used the canonical view effects as a foundation to empirically test the validity of a major theory in object recognition, the view-approximation model (Poggio & Edelman, 1990). This model predicts that generalization should be better when an object is first seen from a non-canonical view and then a canonical view than when seen in the reversed order. We also manipulated object similarity to study the degree to which this view generalization was constrained by shape details and task instructions (object vs. image recognition). Old-new recognition performance for basic and subordinate level objects was measured in separate blocks. We found that for object recognition, view generalization between canonical and non-canonical views was comparable for basic level objects. For subordinate level objects, recognition performance was more accurate from non-canonical to canonical views than the other way around. When the task was changed from object recognition to image recognition, the pattern of the results reversed. Interestingly, participants responded “old” to “new” images of “old” objects with a substantially higher rate than to “new” objects, despite instructions to the contrary, thereby indicating involuntary view generalization. Our empirical findings are incompatible with the prediction of the view-approximation theory, and argue against the hypothesis that views are stored independently. PMID:23283692

  19. Intermediate inflation from a non-canonical scalar field

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rezazadeh, K.; Karami, K.; Karimi, P., E-mail: rezazadeh86@gmail.com, E-mail: KKarami@uok.ac.ir, E-mail: parvin.karimi67@yahoo.com

    2015-09-01

    We study the intermediate inflation in a non-canonical scalar field framework with a power-like Lagrangian. We show that in contrast with the standard canonical intermediate inflation, our non-canonical model is compatible with the observational results of Planck 2015. Also, we estimate the equilateral non-Gaussianity parameter which is in well agreement with the prediction of Planck 2015. Then, we obtain an approximation for the energy scale at the initial time of inflation and show that it can be of order of the Planck energy scale, i.e. M{sub P} ∼ 10{sup 18}GeV. We will see that after a short period of time, inflation entersmore » in the slow-roll regime that its energy scale is of order M{sub P}/100 ∼ 10{sup 16}GeV and the horizon exit takes place in this energy scale. We also examine an idea in our non-canonical model to overcome the central drawback of intermediate inflation which is the fact that inflation never ends. We solve this problem without disturbing significantly the nature of the intermediate inflation until the time of horizon exit.« less

  20. Constraints to solve parallelogram grid problems in 2D non separable linear canonical transform

    NASA Astrophysics Data System (ADS)

    Zhao, Liang; Healy, John J.; Muniraj, Inbarasan; Cui, Xiao-Guang; Malallah, Ra'ed; Ryle, James P.; Sheridan, John T.

    2017-05-01

    The 2D non-separable linear canonical transform (2D-NS-LCT) can model a range of various paraxial optical systems. Digital algorithms to evaluate the 2D-NS-LCTs are important in modeling the light field propagations and also of interest in many digital signal processing applications. In [Zhao 14] we have reported that a given 2D input image with rectangular shape/boundary, in general, results in a parallelogram output sampling grid (generally in an affine coordinates rather than in a Cartesian coordinates) thus limiting the further calculations, e.g. inverse transform. One possible solution is to use the interpolation techniques; however, it reduces the speed and accuracy of the numerical approximations. To alleviate this problem, in this paper, some constraints are derived under which the output samples are located in the Cartesian coordinates. Therefore, no interpolation operation is required and thus the calculation error can be significantly eliminated.

  1. Canonical methods in classical and quantum gravity: An invitation to canonical LQG

    NASA Astrophysics Data System (ADS)

    Reyes, Juan D.

    2018-04-01

    Loop Quantum Gravity (LQG) is a candidate quantum theory of gravity still under construction. LQG was originally conceived as a background independent canonical quantization of Einstein’s general relativity theory. This contribution provides some physical motivations and an overview of some mathematical tools employed in canonical Loop Quantum Gravity. First, Hamiltonian classical methods are reviewed from a geometric perspective. Canonical Dirac quantization of general gauge systems is sketched next. The Hamiltonian formultation of gravity in geometric ADM and connection-triad variables is then presented to finally lay down the canonical loop quantization program. The presentation is geared toward advanced undergradute or graduate students in physics and/or non-specialists curious about LQG.

  2. Canonical Descriptions of High Intensity Laser-Plasma Interaction

    NASA Astrophysics Data System (ADS)

    Le Cornu, B. J.

    The problem of laser-plasma interaction has been studied extensively in the context of inertial confinement fusion (ICF). These studies have focussed on effects like the nonlinear force, self-focusing, Rayleigh- Taylor instabilities, stimulated Brillouin scattering and stimulated Raman scattering observed in ICF schemes. However, there remains a large discrepancy between theory and experiment in the context of nuclear fusion schemes. Several authors have attempted to gain greater understanding of the physics involved by the application of standard or 'canonical' methods used in Lagrangian and Hamiltonian mechanics to the problem of plasma physics. This thesis presents a new canonical description of laser-plasma interaction based on the Podolsky Lagrangian. Finite self-energy of charged particles, incroporation of high-frequency effects and an ability to quantise are the main advantages of this new model. The nature of the Podolsky constant is also analysed in the context of plasma physics, specifically in terms of the plasma dispersion relation. A new gauge invariant expression of the energy-momentum tensor for any gauge invariant Lagrangian dependent on second order derivatives is derived for the first time. Finally, the transient and nontransient expressions of the nonlinear ponderomotive force in laser-plasma interaction are discussed and shown to be closely approximated by a canonical derivation of the electromagnetic Lagrangian, a fact that seems to have been missed in the literature.

  3. Revisiting Interpretation of Canonical Correlation Analysis: A Tutorial and Demonstration of Canonical Commonality Analysis

    ERIC Educational Resources Information Center

    Nimon, Kim; Henson, Robin K.; Gates, Michael S.

    2010-01-01

    In the face of multicollinearity, researchers face challenges interpreting canonical correlation analysis (CCA) results. Although standardized function and structure coefficients provide insight into the canonical variates produced, they fall short when researchers want to fully report canonical effects. This article revisits the interpretation of…

  4. Traditional Herbal Remedies for Burn Wound Healing in Canon of Avicenna

    PubMed Central

    Aliasl, Jale; Khoshzaban, Fariba

    2013-01-01

    Burns are a worldwide problem. The incidence of severe burns has been higher than the combined incidence of tuberculosis and HIV infections. Throughout history there have been many different treatments prescribed for burns. The Canon is the masterpiece of Avicenna’s medical books. The Canon includes a description of 785 simple drugs. Avicenna believed in burn treatment, which follows two goals. The first goal is prevention of blistering and the second goal is treatment of the burn wound after it has created blisters, cold drugs are suitable for the first goal and dry drugs with moderate in cold and hot qualities are better for second goal, this study reviewed remedies for burn wounds in Canon.

  5. Kernel canonical-correlation Granger causality for multiple time series

    NASA Astrophysics Data System (ADS)

    Wu, Guorong; Duan, Xujun; Liao, Wei; Gao, Qing; Chen, Huafu

    2011-04-01

    Canonical-correlation analysis as a multivariate statistical technique has been applied to multivariate Granger causality analysis to infer information flow in complex systems. It shows unique appeal and great superiority over the traditional vector autoregressive method, due to the simplified procedure that detects causal interaction between multiple time series, and the avoidance of potential model estimation problems. However, it is limited to the linear case. Here, we extend the framework of canonical correlation to include the estimation of multivariate nonlinear Granger causality for drawing inference about directed interaction. Its feasibility and effectiveness are verified on simulated data.

  6. Association Study between Lead and Zinc Accumulation at Different Physiological Systems of Cattle by Canonical Correlation and Canonical Correspondence Analyses

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Karmakar, Partha; Das, Pradip Kumar; Mondal, Seema Sarkar

    2010-10-26

    Pb pollution from automobile exhausts around highways is a persistent problem in India. Pb intoxication in mammalian body is a complex phenomenon which is influence by agonistic and antagonistic interactions of several other heavy metals and micronutrients. An attempt has been made to study the association between Pb and Zn accumulation in different physiological systems of cattles (n = 200) by application of both canonical correlation and canonical correspondence analyses. Pb was estimated from plasma, liver, bone, muscle, kidney, blood and milk where as Zn was measured from all these systems except bone, blood and milk. Both statistical techniques demonstratedmore » that there was a strong association among blood-Pb, liver-Zn, kidney-Zn and muscle-Zn. From observations, it can be assumed that Zn accumulation in cattles' muscle, liver and kidney directs Pb mobilization from those organs which in turn increases Pb pool in blood. It indicates antagonistic activity of Zn to the accumulation of Pb. Although there were some contradictions between the observations obtained from the two different statistical methods, the overall pattern of Pb accumulation in various organs as influenced by Zn were same. It is mainly due to the fact that canonical correlation is actually a special type of canonical correspondence analyses where linear relationship is followed between two groups of variables instead of Gaussian relationship.« less

  7. Association Study between Lead and Zinc Accumulation at Different Physiological Systems of Cattle by Canonical Correlation and Canonical Correspondence Analyses

    NASA Astrophysics Data System (ADS)

    Karmakar, Partha; Das, Pradip Kumar; Mondal, Seema Sarkar; Karmakar, Sougata; Mazumdar, Debasis

    2010-10-01

    Pb pollution from automobile exhausts around highways is a persistent problem in India. Pb intoxication in mammalian body is a complex phenomenon which is influence by agonistic and antagonistic interactions of several other heavy metals and micronutrients. An attempt has been made to study the association between Pb and Zn accumulation in different physiological systems of cattles (n = 200) by application of both canonical correlation and canonical correspondence analyses. Pb was estimated from plasma, liver, bone, muscle, kidney, blood and milk where as Zn was measured from all these systems except bone, blood and milk. Both statistical techniques demonstrated that there was a strong association among blood-Pb, liver-Zn, kidney-Zn and muscle-Zn. From observations, it can be assumed that Zn accumulation in cattles' muscle, liver and kidney directs Pb mobilization from those organs which in turn increases Pb pool in blood. It indicates antagonistic activity of Zn to the accumulation of Pb. Although there were some contradictions between the observations obtained from the two different statistical methods, the overall pattern of Pb accumulation in various organs as influenced by Zn were same. It is mainly due to the fact that canonical correlation is actually a special type of canonical correspondence analyses where linear relationship is followed between two groups of variables instead of Gaussian relationship.

  8. Normalization as a canonical neural computation

    PubMed Central

    Carandini, Matteo; Heeger, David J.

    2012-01-01

    There is increasing evidence that the brain relies on a set of canonical neural computations, repeating them across brain regions and modalities to apply similar operations to different problems. A promising candidate for such a computation is normalization, in which the responses of neurons are divided by a common factor that typically includes the summed activity of a pool of neurons. Normalization was developed to explain responses in the primary visual cortex and is now thought to operate throughout the visual system, and in many other sensory modalities and brain regions. Normalization may underlie operations such as the representation of odours, the modulatory effects of visual attention, the encoding of value and the integration of multisensory information. Its presence in such a diversity of neural systems in multiple species, from invertebrates to mammals, suggests that it serves as a canonical neural computation. PMID:22108672

  9. Quantum canonical ensemble: A projection operator approach

    NASA Astrophysics Data System (ADS)

    Magnus, Wim; Lemmens, Lucien; Brosens, Fons

    2017-09-01

    Knowing the exact number of particles N, and taking this knowledge into account, the quantum canonical ensemble imposes a constraint on the occupation number operators. The constraint particularly hampers the systematic calculation of the partition function and any relevant thermodynamic expectation value for arbitrary but fixed N. On the other hand, fixing only the average number of particles, one may remove the above constraint and simply factorize the traces in Fock space into traces over single-particle states. As is well known, that would be the strategy of the grand-canonical ensemble which, however, comes with an additional Lagrange multiplier to impose the average number of particles. The appearance of this multiplier can be avoided by invoking a projection operator that enables a constraint-free computation of the partition function and its derived quantities in the canonical ensemble, at the price of an angular or contour integration. Introduced in the recent past to handle various issues related to particle-number projected statistics, the projection operator approach proves beneficial to a wide variety of problems in condensed matter physics for which the canonical ensemble offers a natural and appropriate environment. In this light, we present a systematic treatment of the canonical ensemble that embeds the projection operator into the formalism of second quantization while explicitly fixing N, the very number of particles rather than the average. Being applicable to both bosonic and fermionic systems in arbitrary dimensions, transparent integral representations are provided for the partition function ZN and the Helmholtz free energy FN as well as for two- and four-point correlation functions. The chemical potential is not a Lagrange multiplier regulating the average particle number but can be extracted from FN+1 -FN, as illustrated for a two-dimensional fermion gas.

  10. Canonical Correlation: Terms and Descriptions.

    ERIC Educational Resources Information Center

    Pugh, Richard C.; Hu, Yuehluen

    The use of terms to describe and interpret results from canonical correlation analysis has been inconsistent across research studies. This study assembled the terminology related to the use and interpretation of canonical correlation analysis from research articles, textbooks, and computer manuals. Research articles using canonical correlation…

  11. Agonistic and Antagonistic Roles for TNIK and MINK in Non-Canonical and Canonical Wnt Signalling

    PubMed Central

    Mikryukov, Alexander; Moss, Tom

    2012-01-01

    Wnt signalling is a key regulatory factor in animal development and homeostasis and plays an important role in the establishment and progression of cancer. Wnt signals are predominantly transduced via the Frizzled family of serpentine receptors to two distinct pathways, the canonical ß-catenin pathway and a non-canonical pathway controlling planar cell polarity and convergent extension. Interference between these pathways is an important determinant of cellular and phenotypic responses, but is poorly understood. Here we show that TNIK (Traf2 and Nck-interacting kinase) and MINK (Misshapen/NIKs-related kinase) MAP4K signalling kinases are integral components of both canonical and non-canonical pathways in Xenopus. xTNIK and xMINK interact and are proteolytically cleaved in vivo to generate Kinase domain fragments that are active in signal transduction, and Citron-NIK-Homology (CNH) Domain fragments that are suppressive. The catalytic activity of the Kinase domain fragments of both xTNIK and xMINK mediate non-canonical signalling. However, while the Kinase domain fragments of xTNIK also mediate canonical signalling, the analogous fragments derived from xMINK strongly antagonize this signalling. Our data suggest that the proteolytic cleavage of xTNIK and xMINK determines their respective activities and is an important factor in controlling the balance between canonical and non-canonical Wnt signalling in vivo. PMID:22984420

  12. 2D non-separable linear canonical transform (2D-NS-LCT) based cryptography

    NASA Astrophysics Data System (ADS)

    Zhao, Liang; Muniraj, Inbarasan; Healy, John J.; Malallah, Ra'ed; Cui, Xiao-Guang; Ryle, James P.; Sheridan, John T.

    2017-05-01

    The 2D non-separable linear canonical transform (2D-NS-LCT) can describe a variety of paraxial optical systems. Digital algorithms to numerically evaluate the 2D-NS-LCTs are not only important in modeling the light field propagations but also of interest in various signal processing based applications, for instance optical encryption. Therefore, in this paper, for the first time, a 2D-NS-LCT based optical Double-random- Phase-Encryption (DRPE) system is proposed which offers encrypting information in multiple degrees of freedom. Compared with the traditional systems, i.e. (i) Fourier transform (FT); (ii) Fresnel transform (FST); (iii) Fractional Fourier transform (FRT); and (iv) Linear Canonical transform (LCT), based DRPE systems, the proposed system is more secure and robust as it encrypts the data with more degrees of freedom with an augmented key-space.

  13. Feedback linearization of singularly perturbed systems based on canonical similarity transformations

    NASA Astrophysics Data System (ADS)

    Kabanov, A. A.

    2018-05-01

    This paper discusses the problem of feedback linearization of a singularly perturbed system in a state-dependent coefficient form. The result is based on the introduction of a canonical similarity transformation. The transformation matrix is constructed from separate blocks for fast and slow part of an original singularly perturbed system. The transformed singular perturbed system has a linear canonical form that significantly simplifies a control design problem. Proposed similarity transformation allows accomplishing linearization of the system without considering the virtual output (as it is needed for normal form method), a technique of a transition from phase coordinates of the transformed system to state variables of the original system is simpler. The application of the proposed approach is illustrated through example.

  14. Base pair probability estimates improve the prediction accuracy of RNA non-canonical base pairs

    PubMed Central

    2017-01-01

    Prediction of RNA tertiary structure from sequence is an important problem, but generating accurate structure models for even short sequences remains difficult. Predictions of RNA tertiary structure tend to be least accurate in loop regions, where non-canonical pairs are important for determining the details of structure. Non-canonical pairs can be predicted using a knowledge-based model of structure that scores nucleotide cyclic motifs, or NCMs. In this work, a partition function algorithm is introduced that allows the estimation of base pairing probabilities for both canonical and non-canonical interactions. Pairs that are predicted to be probable are more likely to be found in the true structure than pairs of lower probability. Pair probability estimates can be further improved by predicting the structure conserved across multiple homologous sequences using the TurboFold algorithm. These pairing probabilities, used in concert with prior knowledge of the canonical secondary structure, allow accurate inference of non-canonical pairs, an important step towards accurate prediction of the full tertiary structure. Software to predict non-canonical base pairs and pairing probabilities is now provided as part of the RNAstructure software package. PMID:29107980

  15. Canonical and non-canonical mechanisms of Nrf2 activation.

    PubMed

    Silva-Islas, Carlos Alfredo; Maldonado, Perla D

    2018-06-15

    Nuclear Factor Erythroid 2-related factor 2 (Nrf2) is a transcription factor that regulates the expression of genes involved in the metabolism, immune response, cellular proliferation, and other processes; however, the attention has been focused on the study of its ability to induce the expression of proteins involved in the antioxidant defense. Nrf2 is mainly regulated by Kelch-like ECH-associated protein 1 (Keap1), an adapter substrate of Cullin 3 (Cul3) ubiquitin E3 ligase complex. Keap1 represses Nrf2 activity in the cytoplasm by its sequestering, ubiquitination and proteosomal degradation. Nrf2 activation, through the canonical mechanism, is carried out by electrophilic compounds and oxidative stress where some cysteine residues in Keap1 are oxidized, resulting in a decrease in Nrf2 ubiquitination and an increase in its nuclear translocation and activation. In the nucleus, Nrf2 induces a variety of genes involved in the antioxidant defense. Recently a new mechanism of Nrf2 activation has been described, called the non-canonical pathway, where proteins such as p62, p21, dipeptidyl peptidase III (DPP3), wilms tumor gene on X chromosome (WTX) and others are able to disrupt the Nrf2-Keap1 complex, by direct interaction with Keap1 decreasing Nrf2 ubiquitination and increasing its nuclear translocation and activation. In this review, the regulatory mechanisms involved in both canonical and non-canonical Nrf2 activation are discussed. Copyright © 2018. Published by Elsevier Ltd.

  16. The Problematics of Postmodernism: The Double-Voiced Honors Canon.

    ERIC Educational Resources Information Center

    McCracken, Tim

    Honors education is not immune from the current controversy concerning the role of the literary canon. Indeed, the problem seems especially crucial for honors programs, for their curriculums are often multi-disciplinary in their approaches to culture and history. The solution may lie in what Linda Hutcheon calls the "poetics of the…

  17. Problem-gambling severity, suicidality and DSM-IV Axis II personality disorders.

    PubMed

    Ronzitti, Silvia; Kraus, Shane W; Hoff, Rani A; Clerici, Massimo; Potenza, Marc N

    2018-07-01

    Despite the strong associations between personality disorders and problem/pathological gambling, few studies have investigated the relationships between personality disorders, problem-gambling severity and suicidal thoughts/behaviors. We examined the relationships between problem-gambling severity and personality disorders among individuals with differing levels of suicidality (none, thoughts alone, attempts). We analyzed data from 13,543 participants of the National Epidemiologic Survey of Alcohol and Related Conditions (NESARC) study. First, differences in sociodemographic characteristics and prevalence of personality disorders were analyzed according to problem-gambling severity and suicidality status. Second, we performed a logistic regression to assess among the relationship between problem-gambling severity and DSM-IV Axis II psychopathology according to suicidality level. At-risk or problem/pathological gambling groups showed higher rates of a wide range of personality disorders compared to non-gamblers. Logistic regression showed that at-risk pathological gamblers had a higher odds ratio for any personality disorder in the group with no history of suicidality, particularly for cluster-B personality disorders. Odds ratio interaction analysis identified the relationship between problem-gambling severity and personality disorders, particularly those in cluster B, differ according to suicidality status. Our findings suggest a complex relationship between suicidality, problem-gambling severity and personality disorders. The stronger relationship between problem-gambling severity and personality disorders in people with no suicidality as compared to some suicidality suggests that some of the relationship between greater problem-gambling severity and Axis II psychopathology is accounted for by increased suicidality. The findings have implications for clinical interventions targeting suicidality in individuals with gambling disorders. Published by Elsevier Ltd.

  18. Generalized canonical ensembles and ensemble equivalence

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Costeniuc, M.; Ellis, R.S.; Turkington, B.

    2006-02-15

    This paper is a companion piece to our previous work [J. Stat. Phys. 119, 1283 (2005)], which introduced a generalized canonical ensemble obtained by multiplying the usual Boltzmann weight factor e{sup -{beta}}{sup H} of the canonical ensemble with an exponential factor involving a continuous function g of the Hamiltonian H. We provide here a simplified introduction to our previous work, focusing now on a number of physical rather than mathematical aspects of the generalized canonical ensemble. The main result discussed is that, for suitable choices of g, the generalized canonical ensemble reproduces, in the thermodynamic limit, all the microcanonical equilibriummore » properties of the many-body system represented by H even if this system has a nonconcave microcanonical entropy function. This is something that in general the standard (g=0) canonical ensemble cannot achieve. Thus a virtue of the generalized canonical ensemble is that it can often be made equivalent to the microcanonical ensemble in cases in which the canonical ensemble cannot. The case of quadratic g functions is discussed in detail; it leads to the so-called Gaussian ensemble.« less

  19. Functional Multiple-Set Canonical Correlation Analysis

    ERIC Educational Resources Information Center

    Hwang, Heungsun; Jung, Kwanghee; Takane, Yoshio; Woodward, Todd S.

    2012-01-01

    We propose functional multiple-set canonical correlation analysis for exploring associations among multiple sets of functions. The proposed method includes functional canonical correlation analysis as a special case when only two sets of functions are considered. As in classical multiple-set canonical correlation analysis, computationally, the…

  20. K-Fold Crossvalidation in Canonical Analysis.

    ERIC Educational Resources Information Center

    Liang, Kun-Hsia; And Others

    1995-01-01

    A computer-assisted, K-fold cross-validation technique is discussed in the framework of canonical correlation analysis of randomly generated data sets. Analysis results suggest that this technique can effectively reduce the contamination of canonical variates and canonical correlations by sample-specific variance components. (Author/SLD)

  1. A canonical theory of dynamic decision-making.

    PubMed

    Fox, John; Cooper, Richard P; Glasspool, David W

    2013-01-01

    Decision-making behavior is studied in many very different fields, from medicine and economics to psychology and neuroscience, with major contributions from mathematics and statistics, computer science, AI, and other technical disciplines. However the conceptualization of what decision-making is and methods for studying it vary greatly and this has resulted in fragmentation of the field. A theory that can accommodate various perspectives may facilitate interdisciplinary working. We present such a theory in which decision-making is articulated as a set of canonical functions that are sufficiently general to accommodate diverse viewpoints, yet sufficiently precise that they can be instantiated in different ways for specific theoretical or practical purposes. The canons cover the whole decision cycle, from the framing of a decision based on the goals, beliefs, and background knowledge of the decision-maker to the formulation of decision options, establishing preferences over them, and making commitments. Commitments can lead to the initiation of new decisions and any step in the cycle can incorporate reasoning about previous decisions and the rationales for them, and lead to revising or abandoning existing commitments. The theory situates decision-making with respect to other high-level cognitive capabilities like problem solving, planning, and collaborative decision-making. The canonical approach is assessed in three domains: cognitive and neuropsychology, artificial intelligence, and decision engineering.

  2. A Canonical Theory of Dynamic Decision-Making

    PubMed Central

    Fox, John; Cooper, Richard P.; Glasspool, David W.

    2012-01-01

    Decision-making behavior is studied in many very different fields, from medicine and economics to psychology and neuroscience, with major contributions from mathematics and statistics, computer science, AI, and other technical disciplines. However the conceptualization of what decision-making is and methods for studying it vary greatly and this has resulted in fragmentation of the field. A theory that can accommodate various perspectives may facilitate interdisciplinary working. We present such a theory in which decision-making is articulated as a set of canonical functions that are sufficiently general to accommodate diverse viewpoints, yet sufficiently precise that they can be instantiated in different ways for specific theoretical or practical purposes. The canons cover the whole decision cycle, from the framing of a decision based on the goals, beliefs, and background knowledge of the decision-maker to the formulation of decision options, establishing preferences over them, and making commitments. Commitments can lead to the initiation of new decisions and any step in the cycle can incorporate reasoning about previous decisions and the rationales for them, and lead to revising or abandoning existing commitments. The theory situates decision-making with respect to other high-level cognitive capabilities like problem solving, planning, and collaborative decision-making. The canonical approach is assessed in three domains: cognitive and neuropsychology, artificial intelligence, and decision engineering. PMID:23565100

  3. A Numerical-Analytical Approach Based on Canonical Transformations for Computing Optimal Low-Thrust Transfers

    NASA Astrophysics Data System (ADS)

    da Silva Fernandes, S.; das Chagas Carvalho, F.; Bateli Romão, J. V.

    2018-04-01

    A numerical-analytical procedure based on infinitesimal canonical transformations is developed for computing optimal time-fixed low-thrust limited power transfers (no rendezvous) between coplanar orbits with small eccentricities in an inverse-square force field. The optimization problem is formulated as a Mayer problem with a set of non-singular orbital elements as state variables. Second order terms in eccentricity are considered in the development of the maximum Hamiltonian describing the optimal trajectories. The two-point boundary value problem of going from an initial orbit to a final orbit is solved by means of a two-stage Newton-Raphson algorithm which uses an infinitesimal canonical transformation. Numerical results are presented for some transfers between circular orbits with moderate radius ratio, including a preliminary analysis of Earth-Mars and Earth-Venus missions.

  4. Are neoclassical canons valid for southern Chinese faces?

    PubMed

    Jayaratne, Yasas S N; Deutsch, Curtis K; McGrath, Colman P J; Zwahlen, Roger A

    2012-01-01

    Proportions derived from neoclassical canons, initially described by Renaissance sculptors and painters, are still being employed as aesthetic guidelines during the clinical assessment of the facial morphology. 1. to determine the applicability of neoclassical canons for Southern Chinese faces and 2. to explore gender differences in relation to the applicability of the neoclassical canons and their variants. 3-D photographs acquired from 103 young adults (51 males and 52 females) without facial dysmorphology were used to test applicability of four neoclassical canons. Standard anthropometric measurements that determine the facial canons were made on these 3-D images. The validity of the canons as well as their different variants were quantified. The neoclassical cannons seldom applied to these individuals, and facial three-section and orbital canons did not apply at all. The orbitonasal canon was most frequently applicable, with a frequency of 19%. Significant sexual dimorphism was found relative to the prevalence of the variants of facial three-section and orbitonasal canons. The neoclassical canons did not appear to apply to our sample when rigorous quantitative measurements were employed. Thus, they should not be used as esthetic goals for craniofacial surgical interventions.

  5. Are Neoclassical Canons Valid for Southern Chinese Faces?

    PubMed Central

    Jayaratne, Yasas S. N.; Deutsch, Curtis K.; McGrath, Colman P. J.; Zwahlen, Roger A.

    2012-01-01

    Background Proportions derived from neoclassical canons, initially described by Renaissance sculptors and painters, are still being employed as aesthetic guidelines during the clinical assessment of the facial morphology. Objective 1. to determine the applicability of neoclassical canons for Southern Chinese faces and 2. to explore gender differences in relation to the applicability of the neoclassical canons and their variants. Methodology 3-D photographs acquired from 103 young adults (51 males and 52 females) without facial dysmorphology were used to test applicability of four neoclassical canons. Standard anthropometric measurements that determine the facial canons were made on these 3-D images. The validity of the canons as well as their different variants were quantified. Principal Findings The neoclassical cannons seldom applied to these individuals, and facial three-section and orbital canons did not apply at all. The orbitonasal canon was most frequently applicable, with a frequency of 19%. Significant sexual dimorphism was found relative to the prevalence of the variants of facial three-section and orbitonasal canons. Conclusion The neoclassical canons did not appear to apply to our sample when rigorous quantitative measurements were employed. Thus, they should not be used as esthetic goals for craniofacial surgical interventions. PMID:23285105

  6. Influence in Canonical Correlation Analysis.

    ERIC Educational Resources Information Center

    Romanazzi, Mario

    1992-01-01

    The perturbation theory of the generalized eigenproblem is used to derive influence functions of each squared canonical correlation coefficient and the corresponding canonical vector pair. Three sample versions of these functions are described, and some properties are noted. Two obvious applications, multiple correlation and correspondence…

  7. BMP regulates regional gene expression in the dorsal otocyst through canonical and non-canonical intracellular pathways

    PubMed Central

    2016-01-01

    The inner ear consists of two otocyst-derived, structurally and functionally distinct components: the dorsal vestibular and ventral auditory compartments. BMP signaling is required to form the vestibular compartment, but how it complements other required signaling molecules and acts intracellularly is unknown. Using spatially and temporally controlled delivery of signaling pathway regulators to developing chick otocysts, we show that BMP signaling regulates the expression of Dlx5 and Hmx3, both of which encode transcription factors essential for vestibular formation. However, although BMP regulates Dlx5 through the canonical SMAD pathway, surprisingly, it regulates Hmx3 through a non-canonical pathway involving both an increase in cAMP-dependent protein kinase A activity and the GLI3R to GLI3A ratio. Thus, both canonical and non-canonical BMP signaling establish the precise spatiotemporal expression of Dlx5 and Hmx3 during dorsal vestibular development. The identification of the non-canonical pathway suggests an intersection point between BMP and SHH signaling, which is required for ventral auditory development. PMID:27151948

  8. Refining inflation using non-canonical scalars

    NASA Astrophysics Data System (ADS)

    Unnikrishnan, Sanil; Sahni, Varun; Toporensky, Aleksey

    2012-08-01

    This paper revisits the Inflationary scenario within the framework of scalar field models possessing a non-canonical kinetic term. We obtain closed form solutions for all essential quantities associated with chaotic inflation including slow roll parameters, scalar and tensor power spectra, spectral indices, the tensor-to-scalar ratio, etc. We also examine the Hamilton-Jacobi equation and demonstrate the existence of an inflationary attractor. Our results highlight the fact that non-canonical scalars can significantly improve the viability of inflationary models. They accomplish this by decreasing the tensor-to-scalar ratio while simultaneously increasing the value of the scalar spectral index, thereby redeeming models which are incompatible with the cosmic microwave background (CMB) in their canonical version. For instance, the non-canonical version of the chaotic inflationary potential, V(phi) ~ λphi4, is found to agree with observations for values of λ as large as unity! The exponential potential can also provide a reasonable fit to CMB observations. A central result of this paper is that steep potentials (such as Vproptophi-n) usually associated with dark energy, can drive inflation in the non-canonical setting. Interestingly, non-canonical scalars violate the consistency relation r = -8nT, which emerges as a smoking gun test for this class of models.

  9. The canonical Wnt signaling pathway in autism.

    PubMed

    Zhang, Yinghua; Yuan, Xiangshan; Wang, Zhongping; Li, Ruixi

    2014-01-01

    Mounting attention is being focused on the canonical Wnt signaling pathway which has been implicated in the pathogenesis of autism in some our and other recent studies. The canonical Wnt pathway is involved in cell proliferation, differentiation and migration, especially during nervous system development. Given its various functions, dysfunction of the canonical Wnt pathway may exert adverse effects on neurodevelopment and therefore leads to the pathogenesis of autism. Here, we review human and animal studies that implicate the canonical Wnt signal transduction pathway in the pathogenesis of autism. We also describe the crosstalk between the canonical Wnt pathway and the Notch signaling pathway in several types of autism spectrum disorders, including Asperger syndrome and Fragile X. Further research on the crosstalk between the canonical Wnt signaling pathway and other signaling cascades in autism may be an efficient avenue to understand the etiology of autism and ultimately lead to alternative medications for autism-like phenotypes.

  10. Far-red fluorescent probes for canonical and non-canonical nucleic acid structures: current progress and future implications.

    PubMed

    Suseela, Y V; Narayanaswamy, Nagarjun; Pratihar, Sumon; Govindaraju, Thimmaiah

    2018-02-05

    The structural diversity and functional relevance of nucleic acids (NAs), mainly deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), are indispensable for almost all living organisms, with minute aberrations in their structure and function becoming causative factors in numerous human diseases. The standard structures of NAs, termed canonical structures, are supported by Watson-Crick hydrogen bonding. Under special physiological conditions, NAs adopt distinct spatial organisations, giving rise to non-canonical conformations supported by hydrogen bonding other than the Watson-Crick type; such non-canonical structures have a definite function in controlling gene expression and are considered as novel diagnostic and therapeutic targets. Development of molecular probes for these canonical and non-canonical DNA/RNA structures has been an active field of research. Among the numerous probes studied, probes with turn-on fluorescence in the far-red (600-750 nm) region are highly sought-after due to minimal autofluorescence and cellular damage. Far-red fluorescent probes are vital for real-time imaging of NAs in live cells as they provide good resolution and minimal perturbation of the cell under investigation. In this review, we present recent advances in the area of far-red fluorescent probes of DNA/RNA and non-canonical G-quadruplex structures. For the sake of continuity and completeness, we provide a brief overview of visible fluorescent probes. Utmost importance is given to design criteria, characteristic properties and biological applications, including in cellulo imaging, apart from critical discussion on limitations of the far-red fluorescent probes. Finally, we offer current and future prospects in targeting canonical and non-canonical NAs specific to cellular organelles, through sequence- and conformation-specific far-red fluorescent probes. We also cover their implications in chemical and molecular biology, with particular focus on decoding various disease

  11. Regularized Generalized Canonical Correlation Analysis

    ERIC Educational Resources Information Center

    Tenenhaus, Arthur; Tenenhaus, Michel

    2011-01-01

    Regularized generalized canonical correlation analysis (RGCCA) is a generalization of regularized canonical correlation analysis to three or more sets of variables. It constitutes a general framework for many multi-block data analysis methods. It combines the power of multi-block data analysis methods (maximization of well identified criteria) and…

  12. Positive geometries and canonical forms

    NASA Astrophysics Data System (ADS)

    Arkani-Hamed, Nima; Bai, Yuntao; Lam, Thomas

    2017-11-01

    Recent years have seen a surprising connection between the physics of scattering amplitudes and a class of mathematical objects — the positive Grassmannian, positive loop Grassmannians, tree and loop Amplituhedra — which have been loosely referred to as "positive geometries". The connection between the geometry and physics is provided by a unique differential form canonically determined by the property of having logarithmic singularities (only) on all the boundaries of the space, with residues on each boundary given by the canonical form on that boundary. The structures seen in the physical setting of the Amplituhedron are both rigid and rich enough to motivate an investigation of the notions of "positive geometries" and their associated "canonical forms" as objects of study in their own right, in a more general mathematical setting. In this paper we take the first steps in this direction. We begin by giving a precise definition of positive geometries and canonical forms, and introduce two general methods for finding forms for more complicated positive geometries from simpler ones — via "triangulation" on the one hand, and "push-forward" maps between geometries on the other. We present numerous examples of positive geometries in projective spaces, Grassmannians, and toric, cluster and flag varieties, both for the simplest "simplex-like" geometries and the richer "polytope-like" ones. We also illustrate a number of strategies for computing canonical forms for large classes of positive geometries, ranging from a direct determination exploiting knowledge of zeros and poles, to the use of the general triangulation and push-forward methods, to the representation of the form as volume integrals over dual geometries and contour integrals over auxiliary spaces. These methods yield interesting representations for the canonical forms of wide classes of positive geometries, ranging from the simplest Amplituhedra to new expressions for the volume of arbitrary convex

  13. Lessons from non-canonical splicing

    PubMed Central

    Ule, Jernej

    2016-01-01

    Recent improvements in experimental and computational techniques used to study the transcriptome have enabled an unprecedented view of RNA processing, revealing many previously unknown non-canonical splicing events. This includes cryptic events located far from the currently annotated exons, and unconventional splicing mechanisms that have important roles in regulating gene expression. These non-canonical splicing events are a major source of newly emerging transcripts during evolution, especially when they involve sequences derived from transposable elements. They are therefore under precise regulation and quality control, which minimises their potential to disrupt gene expression. While non-canonical splicing can lead to aberrant transcripts that cause many diseases, we also explain how it can be exploited for new therapeutic strategies. PMID:27240813

  14. A RE-DEFINITION OF EDUCATIONAL PROBLEMS OCCASIONED BY DESEGREGATION AND TITLE IV OF THE CIVIL RIGHTS ACT OF 1964.

    ERIC Educational Resources Information Center

    BLAKE, ELIAS, JR.

    THIS PAPER REVIEWS SOME OF THE PROBLEMS IN IMPLEMENTING TITLE IV OF THE CIVIL RIGHTS ACT OF 1964. THERE WAS CONFUSION ABOUT THE INTENT OF THE DIRECTIVES FOR INSTITUTES TO IMPROVE THE ABILITY OF SCHOOL PERSONNEL "TO DEAL EFFECTIVELY WITH SPECIAL EDUCATIONAL PROBLEMS" STEMMING FROM DESEGREGATION. THE TRAINING INSTITUTES ON TEACHING THE…

  15. Detecting epilepsy-related cognitive problems in clinically referred children with epilepsy: is the WISC-IV a useful tool?

    PubMed

    Sherman, Elisabeth M S; Brooks, Brian L; Fay-McClymont, Taryn B; MacAllister, William S

    2012-06-01

    The Wechsler Intelligence Scale for Children - Fourth Edition is the most widely used intelligence quotient (IQ) test in use today. However, despite numerous studies on IQ in childhood epilepsy, data exist almost exclusively from prior editions of the test, and no studies to date provide information on the sensitivity of specific WISC-IV scores (full-scale IQ [FSIQ], index, and subtest scores) to epilepsy-related cognitive impairments. The goal of this study was to determine the relative sensitivity of WISC-IV index and subscale scores in detecting cognitive problems in a group of clinically referred children with epilepsy compared to matched controls, and to define the relationship among WISC-IV scales, demographic factors, and epilepsy-related variables. WISC-IV data for children with epilepsy and high seizure burden were obtained from the Alberta Children's Hospital (ACH) and the New York University Comprehensive Epilepsy Center (NYU), two tertiary care medical centers for pediatric epilepsy. All children were clinically referred and received a standard assessment including WISC-IV. Matched controls were obtained from the WISC-IV Canadian and American standardization samples. WISC-IV scores from 212 children were included: 106 children with epilepsy (46 girls, 60 boys; mean age 11.0 years, standard deviation [SD] 3.1; parental education 14.5 years, SD 2.8), and 106 controls matched for age, gender, ethnicity, and parental education. Of the children with epilepsy, 44 had a clearly lateralized focus on electroencephalography (EEG) involving either the right or left hemisphere (26 left, 18 right). FSIQ for the epilepsy group was significantly lower than for controls, and 36.8% of children had IQs compatible with intellectual disability (FSIQ < 70), versus <1% of controls. In children with epilepsy, Working Memory and Processing Speed Index scores were lower than those for Verbal Comprehension and Perceptual Reasoning (p < 0.01). At the subtest level, scores for

  16. Non-canonical IDH1 and IDH2 mutations: a clonal and relevant event in an Italian cohort of gliomas classified according to the 2016 World Health Organization (WHO) criteria.

    PubMed

    Visani, Michela; Acquaviva, Giorgia; Marucci, Gianluca; Paccapelo, Alexandro; Mura, Antonella; Franceschi, Enrico; Grifoni, Daniela; Pession, Annalisa; Tallini, Giovanni; Brandes, Alba A; de Biase, Dario

    2017-11-01

    According to the 2016 World Health Organization (WHO) classification of tumors of the central nervous system, assessment of exon 4 mutations in isocitrate dehydrogenase 1 or 2 genes (IDH1 or IDH2) is an essential step in the characterization of gliomas. The p.R132H mutation is the most frequent alteration in IDH genes, however other non-canonical IDH mutations can be identified. The aim of this study is to investigate in depth the prevalence of non-R132H IDH ("non-canonical") mutations in brain tumors classified according to the 2016 WHO scheme and their clonal distribution in neoplastic cells. A total of 288 consecutive cases of brain gliomas (grade II-IV) were analyzed for exon 4 IDH1 and IDH2 mutations. IDH1 and IDH2 analysis was performed using next generation sequencing. Non-canonical IDH mutations were identified in 13/52 (25.0%) grade II gliomas (astrocytomas: 8/31, 25.8%; oligodendrogliomas: 5/21, 23.8%) and in 5/40 (12.5%) grade III gliomas (astrocytomas: 3/25, 12.0%; oligodendrogliomas: 2/15, 13.3%). They were not identified in 196 grade IV gliomas (192 glioblastomas, 4 gliosarcomas). In the large majority (>80%) of tumors IDH mutations, both IDH1-R132H and the non-canonical ones, were present in the large majority (>80%) of neoplastic cells. Our data highlight the importance of investigating not only the IDH1-R132H mutation but also the non-canonical ones. These mutations are clonally distributed, with proportions of mutated neoplastic cells overlapping with those of p.R132H, a finding consistent with their driver role in gliomagenesis.

  17. On a canonical quantization of 3D Anti de Sitter pure gravity

    NASA Astrophysics Data System (ADS)

    Kim, Jihun; Porrati, Massimo

    2015-10-01

    We perform a canonical quantization of pure gravity on AdS 3 using as a technical tool its equivalence at the classical level with a Chern-Simons theory with gauge group SL(2,{R})× SL(2,{R}) . We first quantize the theory canonically on an asymptotically AdS space -which is topologically the real line times a Riemann surface with one connected boundary. Using the "constrain first" approach we reduce canonical quantization to quantization of orbits of the Virasoro group and Kähler quantization of Teichmüller space. After explicitly computing the Kähler form for the torus with one boundary component and after extending that result to higher genus, we recover known results, such as that wave functions of SL(2,{R}) Chern-Simons theory are conformal blocks. We find new restrictions on the Hilbert space of pure gravity by imposing invariance under large diffeomorphisms and normalizability of the wave function. The Hilbert space of pure gravity is shown to be the target space of Conformal Field Theories with continuous spectrum and a lower bound on operator dimensions. A projection defined by topology changing amplitudes in Euclidean gravity is proposed. It defines an invariant subspace that allows for a dual interpretation in terms of a Liouville CFT. Problems and features of the CFT dual are assessed and a new definition of the Hilbert space, exempt from those problems, is proposed in the case of highly-curved AdS 3.

  18. A model of individualized canonical microcircuits supporting cognitive operations

    PubMed Central

    Peterson, Andre D. H.; Haueisen, Jens; Knösche, Thomas R.

    2017-01-01

    Major cognitive functions such as language, memory, and decision-making are thought to rely on distributed networks of a large number of basic elements, called canonical microcircuits. In this theoretical study we propose a novel canonical microcircuit model and find that it supports two basic computational operations: a gating mechanism and working memory. By means of bifurcation analysis we systematically investigate the dynamical behavior of the canonical microcircuit with respect to parameters that govern the local network balance, that is, the relationship between excitation and inhibition, and key intrinsic feedback architectures of canonical microcircuits. We relate the local behavior of the canonical microcircuit to cognitive processing and demonstrate how a network of interacting canonical microcircuits enables the establishment of spatiotemporal sequences in the context of syntax parsing during sentence comprehension. This study provides a framework for using individualized canonical microcircuits for the construction of biologically realistic networks supporting cognitive operations. PMID:29200435

  19. Distinct Effects of the mesenchymal dysplasia Gene Variant of Murine Patched-1 Protein on Canonical and Non-canonical Hedgehog Signaling Pathways*

    PubMed Central

    Harvey, Malcolm C.; Fleet, Andrew; Okolowsky, Nadia; Hamel, Paul A.

    2014-01-01

    Hedgehog (Hh) signaling requires regulation of the receptor Patched-1 (Ptch1), which, in turn, regulates Smoothened activity (canonical Hh signaling) as well as other non-canonical signaling pathways. The mutant Ptch1 allele mesenchymal dysplasia (mes), which truncates the Ptch1 C terminus, produces a limited spectrum of developmental defects in mice as well as deregulation of canonical Hh signaling in some, but not all, affected tissues. Paradoxically, mes suppresses canonical Hh signaling and binds to Hh ligands with an affinity similar to wild-type mouse Ptch1 (mPtch1). We characterized the distinct activities of the mes variant of mPtch1 mediating Hh signaling through both canonical and non-canonical pathways. We demonstrated that mPtch1 bound c-src in an Hh-regulated manner. Stimulation with Sonic Hedgehog (Shh) of primary mammary mesenchymal cells from wild-type and mes animals activated Erk1/2. Although Shh activated c-src in wild-type cells, c-src was constitutively activated in mes mesenchymal cells. Transient assays showed that wild-type mPtch1, mes, or mPtch1 lacking the C terminus repressed Hh signaling in Ptch1-deficient mouse embryo fibroblasts and that repression was reversed by Shh, revealing that the C terminus was dispensable for mPtch1-dependent regulation of canonical Hh signaling. In contrast to these transient assays, constitutively high levels of mGli1 but not mPtch1 were present in primary mammary mesenchymal cells from mes mice, whereas the expression of mPtch1 was similarly induced in both mes and wild-type cells. These data define a novel signal transduction pathway involving c-src that is activated by the Hh ligands and reveals the requirement for the C terminus of Ptch in regulation of canonical and non-canonical Hh signaling pathways. PMID:24570001

  20. Study of high-performance canonical molecular orbitals calculation for proteins

    NASA Astrophysics Data System (ADS)

    Hirano, Toshiyuki; Sato, Fumitoshi

    2017-11-01

    The canonical molecular orbital (CMO) calculation can help to understand chemical properties and reactions in proteins. However, it is difficult to perform the CMO calculation of proteins because of its self-consistent field (SCF) convergence problem and expensive computational cost. To certainly obtain the CMO of proteins, we work in research and development of high-performance CMO applications and perform experimental studies. We have proposed the third-generation density-functional calculation method of calculating the SCF, which is more advanced than the FILE and direct method. Our method is based on Cholesky decomposition for two-electron integrals calculation and the modified grid-free method for the pure-XC term evaluation. By using the third-generation density-functional calculation method, the Coulomb, the Fock-exchange, and the pure-XC terms can be given by simple linear algebraic procedure in the SCF loop. Therefore, we can expect to get a good parallel performance in solving the SCF problem by using a well-optimized linear algebra library such as BLAS on the distributed memory parallel computers. The third-generation density-functional calculation method is implemented to our program, ProteinDF. To achieve computing electronic structure of the large molecule, not only overcoming expensive computation cost and also good initial guess for safe SCF convergence are required. In order to prepare a precise initial guess for the macromolecular system, we have developed the quasi-canonical localized orbital (QCLO) method. The QCLO has the characteristics of both localized and canonical orbital in a certain region of the molecule. We have succeeded in the CMO calculations of proteins by using the QCLO method. For simplified and semi-automated calculation of the QCLO method, we have also developed a Python-based program, QCLObot.

  1. Canonical Representations of the Simple Map

    NASA Astrophysics Data System (ADS)

    Kerwin, Olivia; Punjabi, Alkesh; Ali, Halima; Boozer, Allen

    2007-11-01

    The simple map is the simplest map that has the topology of a divertor tokamak. The simple map has three canonical representations: (i) toroidal flux and poloidal angle (ψ,θ) as canonical coordinates, (ii) the physical variables (R,Z) or (X,Y) as canonical coordinates, and (iii) the action-angle (J,ζ) or magnetic variables (ψ,θ) as canonical coordinates. We give the derivation of the simple map in the (X,Y) representation. The simple map in this representation has been studied extensively (Ref. 1 and references therein). We calculate the magnetic coordinates for the simple map, construct the simple map in magnetic coordinates, and calculate generic topological effects of magnetic perturbations in divertor tokamaks using the map. We also construct the simple map in (ψ,θ) representation. Preliminary results of these studies will be presented. This work is supported by US DOE OFES DE-FG02-01ER54624 and DE-FG02-04ER54793. [1] A. Punjabi, H. Ali, T. Evans, and A. Boozer, Phys Lett A 364 140--145 (2007).

  2. El Escritor y las Normas del Canon Literario (The Writer and the Norms of the Literary Canon).

    ERIC Educational Resources Information Center

    Policarpo, Alcibiades

    This paper speculates about whether a literary canon exists in contemporary Latin American literature, particularly in the prose genre. The paper points to Carlos Fuentes, Gabriel Garcia Marquez, and Mario Vargas Llosa as the three authors who might form this traditional and liberal canon with their works "La Muerte de Artemio Cruz"…

  3. Canonical fluid thermodynamics

    NASA Technical Reports Server (NTRS)

    Schmid, L. A.

    1972-01-01

    The space-time integral of the thermodynamic pressure plays the role of the thermodynamic potential for compressible, adiabatic flow in the sense that the pressure integral for stable flow is less than for all slightly different flows. This stability criterion can be converted into a variational minimum principle by requiring the molar free-enthalpy and the temperature, which are the arguments of the pressure function, to be generalized velocities, that is, the proper-time derivatives of scalar spare-time functions which are generalized coordinates in the canonical formalism. In a fluid context, proper-time differentiation must be expressed in terms of three independent quantities that specify the fluid velocity. This can be done in several ways, all of which lead to different variants (canonical transformations) of the same constraint-free action integral whose Euler-Lagrange equations are just the well-known equations of motion for adiabatic compressible flow.

  4. Canonical considerations in corporate restructuring.

    PubMed

    Holland, S

    1985-03-01

    Religious institutes sponsoring Catholic health facilities face competitive economic pressures that impel them to seek corporate restructuring and joint ventures to fulfill their mission to the poor. They especially must look to the Church's Code of Canon Law to protect ecclesiastical goods and maintain their Catholic identity when entering such ventures. The U.S. bishops directives also assist in guaranteeing patient expectations that the health facility will observe the Church's ethical principles. Institutes first must ensure that subsidiaries will operate according to Catholic mission and philosophy. The canons delineate proper protection of assets and identify ends toward which the religious must apply temporal goods, such as supporting clergy and performing charitable works. Alienation, or conveyance of goods, is a critical consideration in such financial transactions; canons specify the institute's administrative limits and require superiors' written permission along with their councils' consent. All involved must be "thoroughly informed concerning the economic situation," show "just cause" for the transaction, and obtain expert estimates of property values. Religious administrators retain certain faith and executive obligations, such as amending the charter, appointing the board, and merging or dissolving the corporation. With the canons they help to ensure that collaborative efforts preserve the institute's corporate mission and allow religious to carry out their responsibility for ecclesiastical goods. Though alternatives to corporate ventures may be limited, options regarding how to structure and with whom to affiliate do exist. Sponsoring bodies dedicated to providing high-quality care must explore these options

  5. Canonical and Non-Canonical Autophagy in HIV-1 Replication Cycle

    PubMed Central

    Leymarie, Olivier; Lepont, Leslie; Berlioz-Torrent, Clarisse

    2017-01-01

    Autophagy is a lysosomal-dependent degradative process essential for maintaining cellular homeostasis, and is a key player in innate and adaptive immune responses to intracellular pathogens such as human immunodeficiency virus type 1 (HIV-1). In HIV-1 target cells, autophagy mechanisms can (i) selectively direct viral proteins and viruses for degradation; (ii) participate in the processing and presentation of viral-derived antigens through major histocompatibility complexes; and (iii) contribute to interferon production in response to HIV-1 infection. As a consequence, HIV-1 has evolved different strategies to finely regulate the autophagy pathway to favor its replication and dissemination. HIV-1 notably encodes accessory genes encoding Tat, Nef and Vpu proteins, which are able to perturb and hijack canonical and non-canonical autophagy mechanisms. This review outlines the current knowledge on the complex interplay between autophagy and HIV-1 replication cycle, providing an overview of the autophagy-mediated molecular processes deployed both by infected cells to combat the virus and by HIV-1 to evade antiviral response. PMID:28946621

  6. Simulation of gas adsorption on a surface and in slit pores with grand canonical and canonical kinetic Monte Carlo methods.

    PubMed

    Ustinov, E A; Do, D D

    2012-08-21

    We present for the first time in the literature a new scheme of kinetic Monte Carlo method applied on a grand canonical ensemble, which we call hereafter GC-kMC. It was shown recently that the kinetic Monte Carlo (kMC) scheme is a very effective tool for the analysis of equilibrium systems. It had been applied in a canonical ensemble to describe vapor-liquid equilibrium of argon over a wide range of temperatures, gas adsorption on a graphite open surface and in graphitic slit pores. However, in spite of the conformity of canonical and grand canonical ensembles, the latter is more relevant in the correct description of open systems; for example, the hysteresis loop observed in adsorption of gases in pores under sub-critical conditions can only be described with a grand canonical ensemble. Therefore, the present paper is aimed at an extension of the kMC to open systems. The developed GC-kMC was proved to be consistent with the results obtained with the canonical kMC (C-kMC) for argon adsorption on a graphite surface at 77 K and in graphitic slit pores at 87.3 K. We showed that in slit micropores the hexagonal packing in the layers adjacent to the pore walls is observed at high loadings even at temperatures above the triple point of the bulk phase. The potential and applicability of the GC-kMC are further shown with the correct description of the heat of adsorption and the pressure tensor of the adsorbed phase.

  7. Contextuality in canonical systems of random variables

    NASA Astrophysics Data System (ADS)

    Dzhafarov, Ehtibar N.; Cervantes, Víctor H.; Kujala, Janne V.

    2017-10-01

    Random variables representing measurements, broadly understood to include any responses to any inputs, form a system in which each of them is uniquely identified by its content (that which it measures) and its context (the conditions under which it is recorded). Two random variables are jointly distributed if and only if they share a context. In a canonical representation of a system, all random variables are binary, and every content-sharing pair of random variables has a unique maximal coupling (the joint distribution imposed on them so that they coincide with maximal possible probability). The system is contextual if these maximal couplings are incompatible with the joint distributions of the context-sharing random variables. We propose to represent any system of measurements in a canonical form and to consider the system contextual if and only if its canonical representation is contextual. As an illustration, we establish a criterion for contextuality of the canonical system consisting of all dichotomizations of a single pair of content-sharing categorical random variables. This article is part of the themed issue `Second quantum revolution: foundational questions'.

  8. THE TOPOLOGY OF CANONICAL FLUX TUBES IN FLARED JET GEOMETRY

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lavine, Eric Sander; You, Setthivoine, E-mail: Slavine2@uw.edu, E-mail: syou@aa.washington.edu

    2017-01-20

    Magnetized plasma jets are generally modeled as magnetic flux tubes filled with flowing plasma governed by magnetohydrodynamics (MHD). We outline here a more fundamental approach based on flux tubes of canonical vorticity, where canonical vorticity is defined as the circulation of the species’ canonical momentum. This approach extends the concept of magnetic flux tube evolution to include the effects of finite particle momentum and enables visualization of the topology of plasma jets in regimes beyond MHD. A flared, current-carrying magnetic flux tube in an ion-electron plasma with finite ion momentum is thus equivalent to either a pair of electron andmore » ion flow flux tubes, a pair of electron and ion canonical momentum flux tubes, or a pair of electron and ion canonical vorticity flux tubes. We examine the morphology of all these flux tubes for increasing electrical currents, different radial current profiles, different electron Mach numbers, and a fixed, flared, axisymmetric magnetic geometry. Calculations of gauge-invariant relative canonical helicities track the evolution of magnetic, cross, and kinetic helicities in the system, and show that ion flow fields can unwind to compensate for an increasing magnetic twist. The results demonstrate that including a species’ finite momentum can result in a very long collimated canonical vorticity flux tube even if the magnetic flux tube is flared. With finite momentum, particle density gradients must be normal to canonical vorticities, not to magnetic fields, so observations of collimated astrophysical jets could be images of canonical vorticity flux tubes instead of magnetic flux tubes.« less

  9. Non-canonical autophagy: an exception or an underestimated form of autophagy?

    PubMed

    Scarlatti, Francesca; Maffei, Roberta; Beau, Isabelle; Ghidoni, Riccardo; Codogno, Patrice

    2008-11-01

    Macroautophagy (hereafter called autophagy) is a dynamic and evolutionarily conserved process used to sequester and degrade cytoplasm and entire organelles in a sequestering vesicle with a double membrane, known as the autophagosome, which ultimately fuses with a lysosome to degrade its autophagic cargo. Recently, we have unraveled two distinct forms of autophagy in cancer cells, which we term canonical and non-canonical autophagy. In contrast to classical or canonical autophagy, non-canonical autophagy is a process that does not require the entire set of autophagy-related (Atg) proteins in particular Beclin 1, to form the autophagosome. Non-canonical autophagy is therefore not blocked by the knockdown of Beclin 1 or of its binding partner hVps34. Moreover overexpression of Bcl-2, which is known to block canonical starvation-induced autophagy by binding to Beclin 1, is unable to reverse the non-canonical autophagy triggered by the polyphenol resveratrol in the breast cancer MCF-7 cell line. In MCF-7 cells, at least, non-canonical autophagy is involved in the caspase-independent cell death induced by resveratrol.

  10. Neoclassical canons of facial beauty: Do we see the deviations?

    PubMed

    Pavlic, Andrej; Trinajstic Zrinski, Magda; Katic, Visnja; Spalj, Stjepan

    2017-05-01

    To explore the presence of neoclassical canons of facial beauty among young people in Croatia and to question possible psychosocial repercussions occurring in those who demonstrate deviations in relation to canons. The study was cross-sectional and the sample included 249 subjects (60% female) aged 12-39 (median 20). Their en face and profile photographs were taken in Natural Head Position. Photogrammetry included analysis of nine neoclassical canons of facial beauty originating from the Renaissance. Psychosocial issues were assessed using the Self-Esteem Scale, Big Five Inventory and three domains of Orthognathic Quality of Life Questionnaire. Significant deviations from neoclassical facial beauty canons were observed in 55-65% of adolescents and young adults. Gender and age showed no relation to deviations. The deviations from canons that influenced the quality of life were mainly those related to vertical facial proportions and demonstrated increased facial aesthetics concern and social impact, and higher self-reported treatment need (p < 0.05). Deviations from canons were not related to self-esteem but a decrease in openness, agreeableness and neuroticism was observed. Neoclassical canons were not valid for the majority of adolescents and young adults in Croatia. Only deviations from some canons appear to provoke mild psychosocial repercussions. Copyright © 2017 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  11. The Current Canon in British Romantics Studies.

    ERIC Educational Resources Information Center

    Linkin, Harriet Kramer

    1991-01-01

    Describes and reports on a survey of 164 U.S. universities to ascertain what is taught as the current canon of British Romantic literature. Asserts that the canon may now include Mary Shelley with the former standard six major male Romantic poets, indicating a significant emergence of a feminist perspective on British Romanticism in the classroom.…

  12. Multicollinearity in canonical correlation analysis in maize.

    PubMed

    Alves, B M; Cargnelutti Filho, A; Burin, C

    2017-03-30

    The objective of this study was to evaluate the effects of multicollinearity under two methods of canonical correlation analysis (with and without elimination of variables) in maize (Zea mays L.) crop. Seventy-six maize genotypes were evaluated in three experiments, conducted in a randomized block design with three replications, during the 2009/2010 crop season. Eleven agronomic variables (number of days from sowing until female flowering, number of days from sowing until male flowering, plant height, ear insertion height, ear placement, number of plants, number of ears, ear index, ear weight, grain yield, and one thousand grain weight), 12 protein-nutritional variables (crude protein, lysine, methionine, cysteine, threonine, tryptophan, valine, isoleucine, leucine, phenylalanine, histidine, and arginine), and 6 energetic-nutritional variables (apparent metabolizable energy, apparent metabolizable energy corrected for nitrogen, ether extract, crude fiber, starch, and amylose) were measured. A phenotypic correlation matrix was first generated among the 29 variables for each of the experiments. A multicollinearity diagnosis was later performed within each group of variables using methodologies such as variance inflation factor and condition number. Canonical correlation analysis was then performed, with and without the elimination of variables, among groups of agronomic and protein-nutritional, and agronomic and energetic-nutritional variables. The canonical correlation analysis in the presence of multicollinearity (without elimination of variables) overestimates the variability of canonical coefficients. The elimination of variables is an efficient method to circumvent multicollinearity in canonical correlation analysis.

  13. Mesenchymal stem cells promote the sustained expression of CD69 on activated T lymphocytes: roles of canonical and non-canonical NF-κB signalling

    PubMed Central

    Saldanha-Araujo, Felipe; Haddad, Rodrigo; de Farias, Kelen C R Malmegrim; Souza, Alessandra de Paula Alves; Palma, Patrícia V; Araujo, Amélia G; Orellana, Maristela D; Voltarelli, Julio C; Covas, Dimas T; Zago, Marco A; Panepucci, Rodrigo A

    2012-01-01

    Abstract Mesenchymal stem cells (MSCs) are known to induce the conversion of activated T cells into regulatory T cells in vitro. The marker CD69 is a target of canonical nuclear factor kappa-B (NF-κB) signalling and is transiently expressed upon activation; however, stable CD69 expression defines cells with immunoregulatory properties. Given its enormous therapeutic potential, we explored the molecular mechanisms underlying the induction of regulatory cells by MSCs. Peripheral blood CD3+ T cells were activated and cultured in the presence or absence of MSCs. CD4+ cell mRNA expression was then characterized by microarray analysis. The drug BAY11-7082 (BAY) and a siRNA against v-rel reticuloendotheliosis viral oncogene homolog B (RELB) were used to explore the differential roles of canonical and non-canonical NF-κB signalling, respectively. Flow cytometry and real-time PCR were used for analyses. Genes with immunoregulatory functions, CD69 and non-canonical NF-κB subunits (RELB and NFKB2) were all expressed at higher levels in lymphocytes co-cultured with MSCs. The frequency of CD69+ cells among lymphocytes cultured alone progressively decreased after activation. In contrast, the frequency of CD69+ cells increased significantly following activation in lymphocytes co-cultured with MSCs. Inhibition of canonical NF-κB signalling by BAY immediately following activation blocked the induction of CD69; however, inhibition of canonical NF-κB signalling on the third day further induced the expression of CD69. Furthermore, late expression of CD69 was inhibited by RELB siRNA. These results indicate that the canonical NF-κB pathway controls the early expression of CD69 after activation; however, in an immunoregulatory context, late and sustained CD69 expression is promoted by the non-canonical pathway and is inhibited by canonical NF-κB signalling. PMID:21777379

  14. Implementation of Real-Time Feedback Flow Control Algorithms on a Canonical Testbed

    NASA Technical Reports Server (NTRS)

    Tian, Ye; Song, Qi; Cattafesta, Louis

    2005-01-01

    This report summarizes the activities on "Implementation of Real-Time Feedback Flow Control Algorithms on a Canonical Testbed." The work summarized consists primarily of two parts. The first part summarizes our previous work and the extensions to adaptive ID and control algorithms. The second part concentrates on the validation of adaptive algorithms by applying them to a vibration beam test bed. Extensions to flow control problems are discussed.

  15. Canon Fodder: Young Adult Literature as a Tool for Critiquing Canonicity

    ERIC Educational Resources Information Center

    Hateley, Erica

    2013-01-01

    Young adult literature is a tool of socialisation and acculturation for young readers. This extends to endowing "reading" with particular significance in terms of what literature should be read and why. This paper considers some recent young adult fiction with an eye to its engagement with canonical literature and its representations of…

  16. Strongly contracted canonical transformation theory

    NASA Astrophysics Data System (ADS)

    Neuscamman, Eric; Yanai, Takeshi; Chan, Garnet Kin-Lic

    2010-01-01

    Canonical transformation (CT) theory describes dynamic correlation in multireference systems with large active spaces. Here we discuss CT theory's intruder state problem and why our previous approach of overlap matrix truncation becomes infeasible for sufficiently large active spaces. We propose the use of strongly and weakly contracted excitation operators as alternatives for dealing with intruder states in CT theory. The performance of these operators is evaluated for the H2O, N2, and NiO molecules, with comparisons made to complete active space second order perturbation theory and Davidson-corrected multireference configuration interaction theory. Finally, using a combination of strongly contracted CT theory and orbital-optimized density matrix renormalization group theory, we evaluate the singlet-triplet gap of free base porphin using an active space containing all 24 out-of-plane 2p orbitals. Modeling dynamic correlation with an active space of this size is currently only possible using CT theory.

  17. Synthetic resistivity calculations for the canonical depth-to-bedrock problem: A critical examination of the thin interbed problem and electrical equivalence theories

    NASA Astrophysics Data System (ADS)

    Weiss, C. J.; Knight, R.

    2009-05-01

    One of the key factors in the sensible inference of subsurface geologic properties from both field and laboratory experiments is the ability to quantify the linkages between the inherently fine-scale structures, such as bedding planes and fracture sets, and their macroscopic expression through geophysical interrogation. Central to this idea is the concept of a "minimal sampling volume" over which a given geophysical method responds to an effective medium property whose value is dictated by the geometry and distribution of sub- volume heterogeneities as well as the experiment design. In this contribution we explore the concept of effective resistivity volumes for the canonical depth-to-bedrock problem subject to industry-standard DC resistivity survey designs. Four models representing a sedimentary overburden and flat bedrock interface were analyzed through numerical experiments of six different resistivity arrays. In each of the four models, the sedimentary overburden consists of a thinly interbedded resistive and conductive laminations, with equivalent volume-averaged resistivity but differing lamination thickness, geometry, and layering sequence. The numerical experiments show striking differences in the apparent resistivity pseudo-sections which belie the volume-averaged equivalence of the models. These models constitute the synthetic data set offered for inversion in this Back to Basics Resistivity Modeling session and offer the promise to further our understanding of how the sampling volume, as affected by survey design, can be constrained by joint-array inversion of resistivity data.

  18. Production of non-canonical sentences in agrammatic aphasia: limits in representation or rule application?

    PubMed

    Burchert, Frank; Meissner, Nadine; De Bleser, Ria

    2008-02-01

    The study reported here compares two linguistically informed hypotheses on agrammatic sentence production, the TPH [Friedmann, N., & Grodzinsky, Y. (1997). Tense and agreement in agrammatic production: Pruning the syntactic tree. Brain and Language, 56, 397-425.] and the DOP [Bastiaanse, R., & van Zonneveld, R. (2005). Sentence production with verbs of alternating transitivity in agrammatic Broca's aphasia. Journal of Neurolinguistics, 18, 59-66]. To explain impaired production of non-canonical sentences in agrammatism, the TPH basically relies on deleted or pruned clause structure positions in the left periphery, whereas the DOP appeals to limitations in the application of movement rules. Certain non-canonical sentences such as object-questions and object-relative clauses require the availability of nodes in the left periphery as well as movement to these nodes. In languages with relatively fixed word order such as English, the relevant test cases generally involve a coincidence of left periphery and movement, such that the predictions of the TPH and the DOP are identical although for different reasons. In languages with relatively free word order such as German, on the other hand, it is possible to devise specific tests of the different predictions due to the availability of scrambling. Scrambled object sentences, for example, do not involve the left periphery but do require application of movement in a domain below the left periphery. A study was conducted with German agrammatic subjects which elicited canonical sentences without object movement and non-canonical scrambled sentences with object movement. The results show that agrammatic speakers have a particular problem with the production of scrambled sentences. Further evidence reported in the study from spontaneous speech, elicitation of object relatives, questions and passives and with different agrammatic subjects confirms that non-canonical sentences are generally harder to produce for agrammatics. These

  19. Interrelations between different canonical descriptions of dissipative systems

    NASA Astrophysics Data System (ADS)

    Schuch, D.; Guerrero, J.; López-Ruiz, F. F.; Aldaya, V.

    2015-04-01

    There are many approaches for the description of dissipative systems coupled to some kind of environment. This environment can be described in different ways; only effective models are being considered here. In the Bateman model, the environment is represented by one additional degree of freedom and the corresponding momentum. In two other canonical approaches, no environmental degree of freedom appears explicitly, but the canonical variables are connected with the physical ones via non-canonical transformations. The link between the Bateman approach and those without additional variables is achieved via comparison with a canonical approach using expanding coordinates, as, in this case, both Hamiltonians are constants of motion. This leads to constraints that allow for the elimination of the additional degree of freedom in the Bateman approach. These constraints are not unique. Several choices are studied explicitly, and the consequences for the physical interpretation of the additional variable in the Bateman model are discussed.

  20. Canonic FFT flow graphs for real-valued even/odd symmetric inputs

    NASA Astrophysics Data System (ADS)

    Lao, Yingjie; Parhi, Keshab K.

    2017-12-01

    Canonic real-valued fast Fourier transform (RFFT) has been proposed to reduce the arithmetic complexity by eliminating redundancies. In a canonic N-point RFFT, the number of signal values at each stage is canonic with respect to the number of signal values, i.e., N. The major advantage of the canonic RFFTs is that these require the least number of butterfly operations and only real datapaths when mapped to architectures. In this paper, we consider the FFT computation whose inputs are not only real but also even/odd symmetric, which indeed lead to the well-known discrete cosine and sine transforms (DCTs and DSTs). Novel algorithms for generating the flow graphs of canonic RFFTs with even/odd symmetric inputs are proposed. It is shown that the proposed algorithms lead to canonic structures with N/2 +1 signal values at each stage for an N-point real even symmetric FFT (REFFT) or N/2 -1 signal values at each stage for an N-point RFFT real odd symmetric FFT (ROFFT). In order to remove butterfly operations, several twiddle factor transformations are proposed in this paper. We also discuss the design of canonic REFFT for any composite length. Performances of the canonic REFFT/ROFFT are also discussed. It is shown that the flow graph of canonic REFFT/ROFFT has less number of interconnections, less butterfly operations, and less twiddle factor operations, compared to prior works.

  1. Dictionary-Based Tensor Canonical Polyadic Decomposition

    NASA Astrophysics Data System (ADS)

    Cohen, Jeremy Emile; Gillis, Nicolas

    2018-04-01

    To ensure interpretability of extracted sources in tensor decomposition, we introduce in this paper a dictionary-based tensor canonical polyadic decomposition which enforces one factor to belong exactly to a known dictionary. A new formulation of sparse coding is proposed which enables high dimensional tensors dictionary-based canonical polyadic decomposition. The benefits of using a dictionary in tensor decomposition models are explored both in terms of parameter identifiability and estimation accuracy. Performances of the proposed algorithms are evaluated on the decomposition of simulated data and the unmixing of hyperspectral images.

  2. The search of "canonical" explanations for the cerebral cortex.

    PubMed

    Plebe, Alessio

    2018-06-15

    This paper addresses a fundamental line of research in neuroscience: the identification of a putative neural processing core of the cerebral cortex, often claimed to be "canonical". This "canonical" core would be shared by the entire cortex, and would explain why it is so powerful and diversified in tasks and functions, yet so uniform in architecture. The purpose of this paper is to analyze the search for canonical explanations over the past 40 years, discussing the theoretical frameworks informing this research. It will highlight a bias that, in my opinion, has limited the success of this research project, that of overlooking the dimension of cortical development. The earliest explanation of the cerebral cortex as canonical was attempted by David Marr, deriving putative cortical circuits from general mathematical laws, loosely following a deductive-nomological account. Although Marr's theory turned out to be incorrect, one of its merits was to have put the issue of cortical circuit development at the top of his agenda. This aspect has been largely neglected in much of the research on canonical models that has followed. Models proposed in the 1980s were conceived as mechanistic. They identified a small number of components that interacted as a basic circuit, with each component defined as a function. More recent models have been presented as idealized canonical computations, distinct from mechanistic explanations, due to the lack of identifiable cortical components. Currently, the entire enterprise of coming up with a single canonical explanation has been criticized as being misguided, and the premise of the uniformity of the cortex has been strongly challenged. This debate is analyzed here. The legacy of the canonical circuit concept is reflected in both positive and negative ways in recent large-scale brain projects, such as the Human Brain Project. One positive aspect is that these projects might achieve the aim of producing detailed simulations of cortical

  3. Explicit high-order non-canonical symplectic particle-in-cell algorithms for Vlasov-Maxwell systems

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Xiao, Jianyuan; Qin, Hong; Liu, Jian

    2015-11-01

    Explicit high-order non-canonical symplectic particle-in-cell algorithms for classical particle-field systems governed by the Vlasov-Maxwell equations are developed. The algorithms conserve a discrete non-canonical symplectic structure derived from the Lagrangian of the particle-field system, which is naturally discrete in particles. The electromagnetic field is spatially discretized using the method of discrete exterior calculus with high-order interpolating differential forms for a cubic grid. The resulting time-domain Lagrangian assumes a non-canonical symplectic structure. It is also gauge invariant and conserves charge. The system is then solved using a structure-preserving splitting method discovered by He et al. [preprint arXiv: 1505.06076 (2015)], which produces fivemore » exactly soluble sub-systems, and high-order structure-preserving algorithms follow by combinations. The explicit, high-order, and conservative nature of the algorithms is especially suitable for long-term simulations of particle-field systems with extremely large number of degrees of freedom on massively parallel supercomputers. The algorithms have been tested and verified by the two physics problems, i.e., the nonlinear Landau damping and the electron Bernstein wave. (C) 2015 AIP Publishing LLC.« less

  4. Nonuniform fluids in the grand canonical ensemble

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Percus, J.K.

    1982-01-01

    Nonuniform simple classical fluids are considered quite generally. The grand canonical ensemble is particularly suitable, conceptually, in the leading approximation of local thermodynamics, which figuratively divides the system into approximately uniform spatial subsystems. The procedure is reviewed by which this approach is systematically corrected for slowly varying density profiles, and a model is suggested that carries the correction into the domain of local fluctuations. The latter is assessed for substrate bounded fluids, as well as for two-phase interfaces. The peculiarities of the grand ensemble in a two-phase region stem from the inherent very large number fluctuations. A primitive model showsmore » how these are quenched in the canonical ensemble. This is taken advantage of by applying the Kac-Siegert representation of the van der Waals decomposition with petit canonical corrections, to the two-phase regime.« less

  5. Canonical and non-canonical barriers facing antimiR cancer therapeutics.

    PubMed

    Cheng, Christopher J; Saltzman, W Mark; Slack, Frank J

    2013-01-01

    Once considered genetic "oddities", microRNAs (miRNAs) are now recognized as key epigenetic regulators of numerous biological processes, including some with a causal link to the pathogenesis, maintenance, and treatment of cancer. The crux of small RNA-based therapeutics lies in the antagonism of potent cellular targets; the main shortcoming of the field in general, lies in ineffective delivery. Inhibition of oncogenic miRNAs is a relatively nascent therapeutic concept, but as with predecessor RNA-based therapies, success hinges on delivery efficacy. This review will describes the canonical (e.g. pharmacokinetics and clearance, cellular uptake, endosome escape, etc.) and non-canonical (e.g. spatial localization and accessibility of miRNA, technical limitations of miRNA inhibition, off-target impacts, etc.) challenges to the delivery of antisense-based anti-miRNA therapeutics (i.e. antimiRs) for the treatment of cancer. Emphasis will be placed on how the current leading antimiR platforms-ranging from naked chemically modified oligonucleotides to nanoscale delivery vehicles-are affected by and overcome these barriers. The perplexity of antimiR delivery presents both engineering and biological hurdles that must be overcome in order to capitalize on the extensive pharmacological benefits of antagonizing tumor-associated miRNAs.

  6. Structuring Catholic Schools: Creative Imagination Meets Canon Law

    ERIC Educational Resources Information Center

    Brown, Phillip J.

    2010-01-01

    This paper will explore the underlying requirements of canon law for establishing and administering Catholic schools, with a view toward helping to arrive at creative solutions to the question of how best to structure these schools civilly and canonically in order to ensure their temporal, spiritual, and religious well-being, and to assure that…

  7. Canonical microcircuits for predictive coding

    PubMed Central

    Bastos, Andre M.; Usrey, W. Martin; Adams, Rick A.; Mangun, George R.; Fries, Pascal; Friston, Karl J.

    2013-01-01

    Summary This review considers the influential notion of a canonical (cortical) microcircuit in light of recent theories about neuronal processing. Specifically, we conciliate quantitative studies of microcircuitry and the functional logic of neuronal computations. We revisit the established idea that message passing among hierarchical cortical areas implements a form of Bayesian inference – paying careful attention to the implications for intrinsic connections among neuronal populations. By deriving canonical forms for these computations, one can associate specific neuronal populations with specific computational roles. This analysis discloses a remarkable correspondence between the microcircuitry of the cortical column and the connectivity implied by predictive coding. Furthermore, it provides some intuitive insights into the functional asymmetries between feedforward and feedback connections and the characteristic frequencies over which they operate. PMID:23177956

  8. Canonical Gravity, Non-Inertial Frames, Relativistic Metrology and Dark Matter

    NASA Astrophysics Data System (ADS)

    Lusanna, Luca

    Clock synchronization leads to the definition of instantaneous 3-spaces (to be used as Cauchy surfaces) in non-inertial frames, the only ones allowed by the equivalence principle. ADM canonical tetrad gravity in asymptotically Minkowskian space-times can be described in this framework. This allows to find the York canonical basis in which the inertial (gauge) and tidal (physical) degrees of freedom of the gravitational field can be identified. A Post-Minkowskian linearization with respect to the asymptotic Minkowski metric (asymptotic background) allows to solve the Dirac constraints in non-harmonic 3-orthogonal gauges and to find non-harmonic TT gravitational waves. The inertial gauge variable York time (the trace of the extrinsic curvature of the 3-space) describes the general relativistic freedom in clock synchronization. After a digression on the gauge problem in general relativity and its connection with relativistic metrology, it is shown that dark matter, whose experimental signatures are the rotation curves and the mass of galaxies, may be described (at least partially) as an inertial relativistic effect (absent in Newtonian gravity) connected with the York time, namely with the non-Euclidean nature of 3-spaces as 3-sub-manifolds of space-time.

  9. On the relativistic micro-canonical ensemble and relativistic kinetic theory for N relativistic particles in inertial and non-inertial rest frames

    NASA Astrophysics Data System (ADS)

    Alba, David; Crater, Horace W.; Lusanna, Luca

    2015-03-01

    A new formulation of relativistic classical mechanics allows a reconsideration of old unsolved problems in relativistic kinetic theory and in relativistic statistical mechanics. In particular a definition of the relativistic micro-canonical partition function is given strictly in terms of the Poincaré generators of an interacting N-particle system both in the inertial and non-inertial rest frames. The non-relativistic limit allows a definition of both the inertial and non-inertial micro-canonical ensemble in terms of the Galilei generators.

  10. Canonical quantization of general relativity in discrete space-times.

    PubMed

    Gambini, Rodolfo; Pullin, Jorge

    2003-01-17

    It has long been recognized that lattice gauge theory formulations, when applied to general relativity, conflict with the invariance of the theory under diffeomorphisms. We analyze discrete lattice general relativity and develop a canonical formalism that allows one to treat constrained theories in Lorentzian signature space-times. The presence of the lattice introduces a "dynamical gauge" fixing that makes the quantization of the theories conceptually clear, albeit computationally involved. The problem of a consistent algebra of constraints is automatically solved in our approach. The approach works successfully in other field theories as well, including topological theories. A simple cosmological application exhibits quantum elimination of the singularity at the big bang.

  11. Visual Search for Object Orientation Can Be Modulated by Canonical Orientation

    ERIC Educational Resources Information Center

    Ballaz, Cecile; Boutsen, Luc; Peyrin, Carole; Humphreys, Glyn W.; Marendaz, Christian

    2005-01-01

    The authors studied the influence of canonical orientation on visual search for object orientation. Displays consisted of pictures of animals whose axis of elongation was either vertical or tilted in their canonical orientation. Target orientation could be either congruent or incongruent with the object's canonical orientation. In Experiment 1,…

  12. Critical Literature Pedagogy: Teaching Canonical Literature for Critical Literacy

    ERIC Educational Resources Information Center

    Borsheim-Black, Carlin; Macaluso, Michael; Petrone, Robert

    2014-01-01

    This article introduces Critical Literature Pedagogy (CLP), a pedagogical framework for applying goals of critical literacy within the context of teaching canonical literature. Critical literacies encompass skills and dispositions to understand, question, and critique ideological messages of texts; because canonical literature is often…

  13. Canonical Formulation of Supermechanics

    NASA Astrophysics Data System (ADS)

    Matsumoto, S.

    1990-07-01

    The canonical formulation of a theory of dynamical systems with both Grassmann even and odd variables is investigated. The sufficient condition for the system being analytically solvable is given. The geodesic motion of a particle in the super Poincaré upper half plane is solved as an example.

  14. Controlled levels of canonical Wnt signaling are required for neural crest migration.

    PubMed

    Maj, Ewa; Künneke, Lutz; Loresch, Elisabeth; Grund, Anita; Melchert, Juliane; Pieler, Tomas; Aspelmeier, Timo; Borchers, Annette

    2016-09-01

    Canonical Wnt signaling plays a dominant role in the development of the neural crest (NC), a highly migratory cell population that generates a vast array of cell types. Canonical Wnt signaling is required for NC induction as well as differentiation, however its role in NC migration remains largely unknown. Analyzing nuclear localization of β-catenin as readout for canonical Wnt activity, we detect nuclear β-catenin in premigratory but not migratory Xenopus NC cells suggesting that canonical Wnt activity has to decrease to basal levels to enable NC migration. To define a possible function of canonical Wnt signaling in Xenopus NC migration, canonical Wnt signaling was modulated at different time points after NC induction. This was accomplished using either chemical modulators affecting β-catenin stability or inducible glucocorticoid fusion constructs of Lef/Tcf transcription factors. In vivo analysis of NC migration by whole mount in situ hybridization demonstrates that ectopic activation of canonical Wnt signaling inhibits cranial NC migration. Further, NC transplantation experiments confirm that this effect is tissue-autonomous. In addition, live-cell imaging in combination with biophysical data analysis of explanted NC cells confirms the in vivo findings and demonstrates that modulation of canonical Wnt signaling affects the ability of NC cells to perform single cell migration. Thus, our data support the hypothesis that canonical Wnt signaling needs to be tightly controlled to enable migration of NC cells. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Canonical structures for dispersive waves in shallow water

    NASA Astrophysics Data System (ADS)

    Neyzi, Fahrünisa; Nutku, Yavuz

    1987-07-01

    The canonical Hamiltonian structure of the equations of fluid dynamics obtained in the Boussinesq approximation are considered. New variational formulations of these equations are proposed and it is found that, as in the case of the KdV equation and the equations governing long waves in shallow water, they are degenerate Lagrangian systems. Therefore, in order to cast these equations into canonical form it is again necessary to use Dirac's theory of constraints. It is found that there are primary and secondary constraints which are second class and it is possible to construct the Hamiltonian in terms of canonical variables. Among the examples of Boussinesq equations that are discussed are the equations of Whitham-Broer-Kaup which Kupershmidt has recently expressed in symmetric form and shown to admit tri-Hamiltonian structure.

  16. Canonical partition functions: ideal quantum gases, interacting classical gases, and interacting quantum gases

    NASA Astrophysics Data System (ADS)

    Zhou, Chi-Chun; Dai, Wu-Sheng

    2018-02-01

    In statistical mechanics, for a system with a fixed number of particles, e.g. a finite-size system, strictly speaking, the thermodynamic quantity needs to be calculated in the canonical ensemble. Nevertheless, the calculation of the canonical partition function is difficult. In this paper, based on the mathematical theory of the symmetric function, we suggest a method for the calculation of the canonical partition function of ideal quantum gases, including ideal Bose, Fermi, and Gentile gases. Moreover, we express the canonical partition functions of interacting classical and quantum gases given by the classical and quantum cluster expansion methods in terms of the Bell polynomial in mathematics. The virial coefficients of ideal Bose, Fermi, and Gentile gases are calculated from the exact canonical partition function. The virial coefficients of interacting classical and quantum gases are calculated from the canonical partition function by using the expansion of the Bell polynomial, rather than calculated from the grand canonical potential.

  17. Canonical PSO Based K-Means Clustering Approach for Real Datasets.

    PubMed

    Dey, Lopamudra; Chakraborty, Sanjay

    2014-01-01

    "Clustering" the significance and application of this technique is spread over various fields. Clustering is an unsupervised process in data mining, that is why the proper evaluation of the results and measuring the compactness and separability of the clusters are important issues. The procedure of evaluating the results of a clustering algorithm is known as cluster validity measure. Different types of indexes are used to solve different types of problems and indices selection depends on the kind of available data. This paper first proposes Canonical PSO based K-means clustering algorithm and also analyses some important clustering indices (intercluster, intracluster) and then evaluates the effects of those indices on real-time air pollution database, wholesale customer, wine, and vehicle datasets using typical K-means, Canonical PSO based K-means, simple PSO based K-means, DBSCAN, and Hierarchical clustering algorithms. This paper also describes the nature of the clusters and finally compares the performances of these clustering algorithms according to the validity assessment. It also defines which algorithm will be more desirable among all these algorithms to make proper compact clusters on this particular real life datasets. It actually deals with the behaviour of these clustering algorithms with respect to validation indexes and represents their results of evaluation in terms of mathematical and graphical forms.

  18. A Canonical Analysis of Career Choice Crystallization and Vocational Maturity.

    ERIC Educational Resources Information Center

    Blustein, David L.

    1988-01-01

    Administered measures of vocational maturity and career choice crystallization to 158 community college students. Used canonical analysis to identify relationships between age, gender, career choice crystallization, and vocational maturity. Analysis yielded one significant canonical root, indicating most shared variance between variables was…

  19. Multidimensional correlation among plan complexity, quality and deliverability parameters for volumetric-modulated arc therapy using canonical correlation analysis.

    PubMed

    Shen, Lanxiao; Chen, Shan; Zhu, Xiaoyang; Han, Ce; Zheng, Xiaomin; Deng, Zhenxiang; Zhou, Yongqiang; Gong, Changfei; Xie, Congying; Jin, Xiance

    2018-03-01

    A multidimensional exploratory statistical method, canonical correlation analysis (CCA), was applied to evaluate the impact of complexity parameters on the plan quality and deliverability of volumetric-modulated arc therapy (VMAT) and to determine parameters in the generation of an ideal VMAT plan. Canonical correlations among complexity, quality and deliverability parameters of VMAT, as well as the contribution weights of different parameters were investigated with 71 two-arc VMAT nasopharyngeal cancer (NPC) patients, and further verified with 28 one-arc VMAT prostate cancer patients. The average MU and MU per control point (MU/CP) for two-arc VMAT plans were 702.6 ± 55.7 and 3.9 ± 0.3 versus 504.6 ± 99.2 and 5.6 ± 1.1 for one-arc VMAT plans, respectively. The individual volume-based 3D gamma passing rates of clinical target volume (γCTV) and planning target volume (γPTV) for NPC and prostate cancer patients were 85.7% ± 9.0% vs 92.6% ± 7.8%, and 88.0% ± 7.6% vs 91.2% ± 7.7%, respectively. Plan complexity parameters of NPC patients were correlated with plan quality (P = 0.047) and individual volume-based 3D gamma indices γ(IV) (P = 0.01), in which, MU/CP and segment area (SA) per control point (SA/CP) were weighted highly in correlation with γ(IV) , and SA/CP, percentage of CPs with SA < 5 × 5 cm2 (%SA < 5 × 5 cm2) and PTV volume were weighted highly in correlation with plan quality with coefficients of 0.98, 0.68 and -0.99, respectively. Further verification with one-arc VMAT plans demonstrated similar results. In conclusion, MU, SA-related parameters and PTV volume were found to have strong effects on the plan quality and deliverability.

  20. Multidimensional correlation among plan complexity, quality and deliverability parameters for volumetric-modulated arc therapy using canonical correlation analysis

    PubMed Central

    Shen, Lanxiao; Chen, Shan; Zhu, Xiaoyang; Han, Ce; Zheng, Xiaomin; Deng, Zhenxiang; Zhou, Yongqiang; Gong, Changfei; Jin, Xiance

    2018-01-01

    Abstract A multidimensional exploratory statistical method, canonical correlation analysis (CCA), was applied to evaluate the impact of complexity parameters on the plan quality and deliverability of volumetric-modulated arc therapy (VMAT) and to determine parameters in the generation of an ideal VMAT plan. Canonical correlations among complexity, quality and deliverability parameters of VMAT, as well as the contribution weights of different parameters were investigated with 71 two-arc VMAT nasopharyngeal cancer (NPC) patients, and further verified with 28 one-arc VMAT prostate cancer patients. The average MU and MU per control point (MU/CP) for two-arc VMAT plans were 702.6 ± 55.7 and 3.9 ± 0.3 versus 504.6 ± 99.2 and 5.6 ± 1.1 for one-arc VMAT plans, respectively. The individual volume-based 3D gamma passing rates of clinical target volume (γCTV) and planning target volume (γPTV) for NPC and prostate cancer patients were 85.7% ± 9.0% vs 92.6% ± 7.8%, and 88.0% ± 7.6% vs 91.2% ± 7.7%, respectively. Plan complexity parameters of NPC patients were correlated with plan quality (P = 0.047) and individual volume-based 3D gamma indices γ(IV) (P = 0.01), in which, MU/CP and segment area (SA) per control point (SA/CP) were weighted highly in correlation with γ(IV) , and SA/CP, percentage of CPs with SA < 5 × 5 cm2 (%SA < 5 × 5 cm2) and PTV volume were weighted highly in correlation with plan quality with coefficients of 0.98, 0.68 and −0.99, respectively. Further verification with one-arc VMAT plans demonstrated similar results. In conclusion, MU, SA-related parameters and PTV volume were found to have strong effects on the plan quality and deliverability. PMID:29415196

  1. BOOK REVIEW: Canonical Gravity and Applications: Cosmology, Black Holes, and Quantum Gravity Canonical Gravity and Applications: Cosmology, Black Holes, and Quantum Gravity

    NASA Astrophysics Data System (ADS)

    Husain, Viqar

    2012-03-01

    Research on quantum gravity from a non-perturbative 'quantization of geometry' perspective has been the focus of much research in the past two decades, due to the Ashtekar-Barbero Hamiltonian formulation of general relativity. This approach provides an SU(2) gauge field as the canonical configuration variable; the analogy with Yang-Mills theory at the kinematical level opened up some research space to reformulate the old Wheeler-DeWitt program into what is now known as loop quantum gravity (LQG). The author is known for his work in the LQG approach to cosmology, which was the first application of this formalism that provided the possibility of exploring physical questions. Therefore the flavour of the book is naturally informed by this history. The book is based on a set of graduate-level lectures designed to impart a working knowledge of the canonical approach to gravitation. It is more of a textbook than a treatise, unlike three other recent books in this area by Kiefer [1], Rovelli [2] and Thiemann [3]. The style and choice of topics of these authors are quite different; Kiefer's book provides a broad overview of the path integral and canonical quantization methods from a historical perspective, whereas Rovelli's book focuses on philosophical and formalistic aspects of the problems of time and observables, and gives a development of spin-foam ideas. Thiemann's is much more a mathematical physics book, focusing entirely on the theory of representing constraint operators on a Hilbert space and charting a mathematical trajectory toward a physical Hilbert space for quantum gravity. The significant difference from these books is that Bojowald covers mainly classical topics until the very last chapter, which contains the only discussion of quantization. In its coverage of classical gravity, the book has some content overlap with Poisson's book [4], and with Ryan and Shepley's older work on relativistic cosmology [5]; for instance the contents of chapter five of the

  2. Influence and canonical supremacy: an analysis of how George Herbert Mead demoted Charles Horton Cooley in the sociological canon.

    PubMed

    Jacobs, Glenn

    2009-01-01

    This analysis assesses the factors underlying Charles Horton Cooley's place in the sociological canon as they relate to George Herbert Mead's puzzling diatribe-echoed in secondary accounts-against Cooley's social psychology and view of the self published scarcely a year after his death. The illocutionary act of publishing his critique stands as an effort to project the image of Mead's intellectual self and enhance his standing among sociologists within and outside the orbit of the University of Chicago. It expressed Mead's ambivalence toward his precursor Cooley, whose influence he never fully acknowledged. In addition, it typifies the contending fractal distinctions of the scientifically discursive versus literary styles of Mead and Cooley, who both founded the interpretive sociological tradition. The contrasting styles and attitudes toward writing of the two figures are discussed, and their implications for the problems of scale that have stymied the symbolic interactionist tradition are explored.

  3. Canonical Wnt signaling in megakaryocytes regulates proplatelet formation

    PubMed Central

    Macaulay, Iain C.; Thon, Jonathan N.; Tijssen, Marloes R.; Steele, Brian M.; MacDonald, Bryan T.; Meade, Gerardene; Burns, Philippa; Rendon, Augusto; Salunkhe, Vishal; Murphy, Ronan P.; Bennett, Cavan; Watkins, Nicholas A.; He, Xi; Fitzgerald, Desmond J.; Italiano, Joseph E.

    2013-01-01

    Wnt signaling is involved in numerous aspects of vertebrate development and homeostasis, including the formation and function of blood cells. Here, we show that canonical and noncanonical Wnt signaling pathways are present and functional in megakaryocytes (MKs), with several Wnt effectors displaying MK-restricted expression. Using the CHRF288-11 cell line as a model for human MKs, the canonical Wnt3a signal was found to induce a time and dose-dependent increase in β-catenin expression. β-catenin accumulation was inhibited by the canonical antagonist dickkopf-1 (DKK1) and by the noncanonical agonist Wnt5a. Whole genome expression analysis demonstrated that Wnt3a and Wnt5a regulated distinct patterns of gene expression in MKs, and revealed a further interplay between canonical and noncanonical Wnt pathways. Fetal liver cells derived from low-density-lipoprotein receptor-related protein 6-deficient mice (LRP6−/−), generated dramatically reduced numbers of MKs in culture of lower ploidy (2N and 4N) than wild-type controls, implicating LRP6-dependent Wnt signaling in MK proliferation and maturation. Finally, in wild-type mature murine fetal liver-derived MKs, Wnt3a potently induced proplatelet formation, an effect that could be completely abrogated by DKK1. These data identify novel extrinsic regulators of proplatelet formation, and reveal a profound role for Wnt signaling in platelet production. PMID:23160460

  4. From Classical to Quantum: New Canonical Tools for the Dynamics of Gravity

    NASA Astrophysics Data System (ADS)

    Höhn, P. A.

    2012-05-01

    second part of this thesis, the paradigm of relational dynamics is considered. Dynamical observables in gravity are relational. Unfortunately, their construction and evaluation is notoriously difficult, especially in the quantum theory. An effective canonical framework is devised which permits to evaluate the semiclassical relational dynamics of constrained quantum systems by sidestepping technical problems associated with explicit constructions of physical Hilbert spaces. This effective approach is well-geared for addressing the concept of relational evolution in general quantum cosmological models since it (i) allows to depart from idealized relational `clock references’ and, instead, to employ generic degrees of freedom as imperfect relational `clocks’, (ii) enables one to systematically switch between different such `clocks’ and (iii) yields a consistent (temporally) local time evolution with transient observables so long as semiclassicality holds. These techniques are illustrated by toy models and, finally, are applied to a non-integrable cosmological model. It is argued that relational evolution is generically only a transient and semiclassical phenomenon

  5. The Brandeis Dice Problem and Statistical Mechanics

    NASA Astrophysics Data System (ADS)

    van Enk, Steven J.

    2014-11-01

    Jaynes invented the Brandeis Dice Problem as a simple illustration of the MaxEnt (Maximum Entropy) procedure that he had demonstrated to work so well in Statistical Mechanics. I construct here two alternative solutions to his toy problem. One, like Jaynes' solution, uses MaxEnt and yields an analog of the canonical ensemble, but at a different level of description. The other uses Bayesian updating and yields an analog of the micro-canonical ensemble. Both, unlike Jaynes' solution, yield error bars, whose operational merits I discuss. These two alternative solutions are not equivalent for the original Brandeis Dice Problem, but become so in what must, therefore, count as the analog of the thermodynamic limit, M-sided dice with M → ∞. Whereas the mathematical analogies between the dice problem and Stat Mech are quite close, there are physical properties that the former lacks but that are crucial to the workings of the latter. Stat Mech is more than just MaxEnt.

  6. Polynomial meta-models with canonical low-rank approximations: Numerical insights and comparison to sparse polynomial chaos expansions

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Konakli, Katerina, E-mail: konakli@ibk.baug.ethz.ch; Sudret, Bruno

    2016-09-15

    The growing need for uncertainty analysis of complex computational models has led to an expanding use of meta-models across engineering and sciences. The efficiency of meta-modeling techniques relies on their ability to provide statistically-equivalent analytical representations based on relatively few evaluations of the original model. Polynomial chaos expansions (PCE) have proven a powerful tool for developing meta-models in a wide range of applications; the key idea thereof is to expand the model response onto a basis made of multivariate polynomials obtained as tensor products of appropriate univariate polynomials. The classical PCE approach nevertheless faces the “curse of dimensionality”, namely themore » exponential increase of the basis size with increasing input dimension. To address this limitation, the sparse PCE technique has been proposed, in which the expansion is carried out on only a few relevant basis terms that are automatically selected by a suitable algorithm. An alternative for developing meta-models with polynomial functions in high-dimensional problems is offered by the newly emerged low-rank approximations (LRA) approach. By exploiting the tensor–product structure of the multivariate basis, LRA can provide polynomial representations in highly compressed formats. Through extensive numerical investigations, we herein first shed light on issues relating to the construction of canonical LRA with a particular greedy algorithm involving a sequential updating of the polynomial coefficients along separate dimensions. Specifically, we examine the selection of optimal rank, stopping criteria in the updating of the polynomial coefficients and error estimation. In the sequel, we confront canonical LRA to sparse PCE in structural-mechanics and heat-conduction applications based on finite-element solutions. Canonical LRA exhibit smaller errors than sparse PCE in cases when the number of available model evaluations is small with respect to the

  7. Reliability and Validity of Three Instruments (DSM-IV, CPGI, and PPGM) in the Assessment of Problem Gambling in South Korea.

    PubMed

    Back, Ki-Joon; Williams, Robert J; Lee, Choong-Ki

    2015-09-01

    Most research on the assessment, epidemiology, and treatment of problem gambling has occurred in Western jurisdictions. This potentially limits the cross-cultural validity of problem gambling assessment instruments as well as etiological models of problem gambling. The primary objective of the present research was to investigate the reliability and validity of three problem gambling assessment instruments within a South Korean context. A total of 4,330 South Korean adults participated in a comprehensive assessment of their gambling behavior that included the administration of the DSM-IV criteria for pathological gambling (NODS), the Canadian Problem Gambling Index (CPGI), and the Problem and Pathological Gambling Measure (PPGM). Cronbach alpha showed that all three instruments had good internal consistency. Concurrent validity was established by the significant associations observed between scores on the instruments and measures of gambling involvement (number of gambling formats engaged in; frequency of gambling; and gambling expenditure). Most importantly, kappa statistics showed that all instruments have satisfactory classification accuracy against clinical assessment of problem gambling conducted by South Korean clinicians (NODS κ = .66; PPGM κ = .62; CPGI κ = .51). These results confirm that Western-derived operationalizations of problem gambling have applicability in a South Korean setting.

  8. Canonical WNT signaling components in vascular development and barrier formation.

    PubMed

    Zhou, Yulian; Wang, Yanshu; Tischfield, Max; Williams, John; Smallwood, Philip M; Rattner, Amir; Taketo, Makoto M; Nathans, Jeremy

    2014-09-01

    Canonical WNT signaling is required for proper vascularization of the CNS during embryonic development. Here, we used mice with targeted mutations in genes encoding canonical WNT pathway members to evaluate the exact contribution of these components in CNS vascular development and in specification of the blood-brain barrier (BBB) and blood-retina barrier (BRB). We determined that vasculature in various CNS regions is differentially sensitive to perturbations in canonical WNT signaling. The closely related WNT signaling coreceptors LDL receptor-related protein 5 (LRP5) and LRP6 had redundant functions in brain vascular development and barrier maintenance; however, loss of LRP5 alone dramatically altered development of the retinal vasculature. The BBB in the cerebellum and pons/interpeduncular nuclei was highly sensitive to decrements in canonical WNT signaling, and WNT signaling was required to maintain plasticity of barrier properties in mature CNS vasculature. Brain and retinal vascular defects resulting from ablation of Norrin/Frizzled4 signaling were ameliorated by stabilizing β-catenin, while inhibition of β-catenin-dependent transcription recapitulated the vascular development and barrier defects associated with loss of receptor, coreceptor, or ligand, indicating that Norrin/Frizzled4 signaling acts predominantly through β-catenin-dependent transcriptional regulation. Together, these data strongly support a model in which identical or nearly identical canonical WNT signaling mechanisms mediate neural tube and retinal vascularization and maintain the BBB and BRB.

  9. Arabidopsis RNA Polymerases IV and V Are Required To Establish H3K9 Methylation, but Not Cytosine Methylation, on Geminivirus Chromatin

    PubMed Central

    Jackel, Jamie N.; Storer, Jessica M.; Coursey, Tami

    2016-01-01

    ABSTRACT In plants, RNA-directed DNA methylation (RdDM) employs small RNAs to target enzymes that methylate cytosine residues. Cytosine methylation and dimethylation of histone 3 lysine 9 (H3K9me2) are often linked. Together they condition an epigenetic defense that results in chromatin compaction and transcriptional silencing of transposons and viral chromatin. Canonical RdDM (Pol IV-RdDM), involving RNA polymerases IV and V (Pol IV and Pol V), was believed to be necessary to establish cytosine methylation, which in turn could recruit H3K9 methyltransferases. However, recent studies have revealed that a pathway involving Pol II and RNA-dependent RNA polymerase 6 (RDR6) (RDR6-RdDM) is likely responsible for establishing cytosine methylation at naive loci, while Pol IV-RdDM acts to reinforce and maintain it. We used the geminivirus Beet curly top virus (BCTV) as a model to examine the roles of Pol IV and Pol V in establishing repressive viral chromatin methylation. As geminivirus chromatin is formed de novo in infected cells, these viruses are unique models for processes involved in the establishment of epigenetic marks. We confirm that Pol IV and Pol V are not needed to establish viral DNA methylation but are essential for its amplification. Remarkably, however, both Pol IV and Pol V are required for deposition of H3K9me2 on viral chromatin. Our findings suggest that cytosine methylation alone is not sufficient to trigger de novo deposition of H3K9me2 and further that Pol IV-RdDM is responsible for recruiting H3K9 methyltransferases to viral chromatin. IMPORTANCE In plants, RNA-directed DNA methylation (RdDM) uses small RNAs to target cytosine methylation, which is often linked to H3K9me2. These epigenetic marks silence transposable elements and DNA virus genomes, but how they are established is not well understood. Canonical RdDM, involving Pol IV and Pol V, was thought to establish cytosine methylation that in turn could recruit H3K9 methyltransferases, but

  10. Arabidopsis RNA Polymerases IV and V Are Required To Establish H3K9 Methylation, but Not Cytosine Methylation, on Geminivirus Chromatin.

    PubMed

    Jackel, Jamie N; Storer, Jessica M; Coursey, Tami; Bisaro, David M

    2016-08-15

    In plants, RNA-directed DNA methylation (RdDM) employs small RNAs to target enzymes that methylate cytosine residues. Cytosine methylation and dimethylation of histone 3 lysine 9 (H3K9me2) are often linked. Together they condition an epigenetic defense that results in chromatin compaction and transcriptional silencing of transposons and viral chromatin. Canonical RdDM (Pol IV-RdDM), involving RNA polymerases IV and V (Pol IV and Pol V), was believed to be necessary to establish cytosine methylation, which in turn could recruit H3K9 methyltransferases. However, recent studies have revealed that a pathway involving Pol II and RNA-dependent RNA polymerase 6 (RDR6) (RDR6-RdDM) is likely responsible for establishing cytosine methylation at naive loci, while Pol IV-RdDM acts to reinforce and maintain it. We used the geminivirus Beet curly top virus (BCTV) as a model to examine the roles of Pol IV and Pol V in establishing repressive viral chromatin methylation. As geminivirus chromatin is formed de novo in infected cells, these viruses are unique models for processes involved in the establishment of epigenetic marks. We confirm that Pol IV and Pol V are not needed to establish viral DNA methylation but are essential for its amplification. Remarkably, however, both Pol IV and Pol V are required for deposition of H3K9me2 on viral chromatin. Our findings suggest that cytosine methylation alone is not sufficient to trigger de novo deposition of H3K9me2 and further that Pol IV-RdDM is responsible for recruiting H3K9 methyltransferases to viral chromatin. In plants, RNA-directed DNA methylation (RdDM) uses small RNAs to target cytosine methylation, which is often linked to H3K9me2. These epigenetic marks silence transposable elements and DNA virus genomes, but how they are established is not well understood. Canonical RdDM, involving Pol IV and Pol V, was thought to establish cytosine methylation that in turn could recruit H3K9 methyltransferases, but recent studies compel a

  11. Romanticism, Sexuality, and the Canon.

    ERIC Educational Resources Information Center

    Rowe, Kathleen K.

    1990-01-01

    Traces the Romanticism in the work and persona of film director Jean-Luc Godard. Examines the contradictions posed by Godard's politics and representations of sexuality. Asserts, that by bringing an ironic distance to the works of such canonized directors, viewers can take pleasure in those works despite their contradictions. (MM)

  12. Canonical PSO Based K-Means Clustering Approach for Real Datasets

    PubMed Central

    Dey, Lopamudra; Chakraborty, Sanjay

    2014-01-01

    “Clustering” the significance and application of this technique is spread over various fields. Clustering is an unsupervised process in data mining, that is why the proper evaluation of the results and measuring the compactness and separability of the clusters are important issues. The procedure of evaluating the results of a clustering algorithm is known as cluster validity measure. Different types of indexes are used to solve different types of problems and indices selection depends on the kind of available data. This paper first proposes Canonical PSO based K-means clustering algorithm and also analyses some important clustering indices (intercluster, intracluster) and then evaluates the effects of those indices on real-time air pollution database, wholesale customer, wine, and vehicle datasets using typical K-means, Canonical PSO based K-means, simple PSO based K-means, DBSCAN, and Hierarchical clustering algorithms. This paper also describes the nature of the clusters and finally compares the performances of these clustering algorithms according to the validity assessment. It also defines which algorithm will be more desirable among all these algorithms to make proper compact clusters on this particular real life datasets. It actually deals with the behaviour of these clustering algorithms with respect to validation indexes and represents their results of evaluation in terms of mathematical and graphical forms. PMID:27355083

  13. The Western Canon: The Books and School of the Ages.

    ERIC Educational Resources Information Center

    Bloom, Harold

    This book argues against the politicization of literature and presents a guide to the great works and essential writers of the ages, the "Western Canon." The book studies 26 writers and seeks to isolate the qualities that made these authors canonical, that is, authoritative in Western culture. Noting that although originally the…

  14. Role of a non-canonical surface of Rad6 in ubiquitin conjugating activity

    PubMed Central

    Kumar, Pankaj; Magala, Pearl; Geiger-Schuller, Kathryn R.; Majumdar, Ananya; Tolman, Joel R.; Wolberger, Cynthia

    2015-01-01

    Rad6 is a yeast E2 ubiquitin conjugating enzyme that monoubiquitinates histone H2B in conjunction with the E3, Bre1, but can non-specifically modify histones on its own. We determined the crystal structure of a Rad6∼Ub thioester mimic, which revealed a network of interactions in the crystal in which the ubiquitin in one conjugate contacts Rad6 in another. The region of Rad6 contacted is located on the distal face of Rad6 opposite the active site, but differs from the canonical E2 backside that mediates free ubiquitin binding and polyubiquitination activity in other E2 enzymes. We find that free ubiquitin interacts weakly with both non-canonical and canonical backside residues of Rad6 and that mutations of non-canonical residues have deleterious effects on Rad6 activity comparable to those observed to mutations in the canonical E2 backside. The effect of non-canonical backside mutations is similar in the presence and absence of Bre1, indicating that contacts with non-canonical backside residues govern the intrinsic activity of Rad6. Our findings shed light on the determinants of intrinsic Rad6 activity and reveal new ways in which contacts with an E2 backside can regulate ubiquitin conjugating activity. PMID:26286193

  15. Memory, Literacy, and Invention: Reimagining the Canon of Memory for the Writing Classroom

    ERIC Educational Resources Information Center

    Ryan, Kathleen J.

    2004-01-01

    This article challenges the assumption that the canon of memory means memorization and transcription, and, as a result, has little relevance for the writing classroom. An examination of the canon's historical legacy and its relationships to literacy and invention open a space for redefining the canon of memory as "rememoried knowing." In brief,…

  16. Canonical Word Order of Japanese Ditransitive Sentences: A Preliminary Investigation through a Grammaticality Judgment Survey

    ERIC Educational Resources Information Center

    Shigenaga, Yasumasa

    2014-01-01

    There have been three competing analyses regarding the canonical word order of Japanese ditransitive sentences: a) "S-'ga' IO-'ni' DO-'o' V" is the canonical word order rather than "S-'ga' DO-'o' IO-'ni' V", b) both word orders are canonical, and c) the canonical word order depends on the type of the verb. The present study…

  17. TCDD Inhibition of Canonical Wnt Signaling Disrupts Prostatic Bud Formation in Mouse Urogenital Sinus

    PubMed Central

    Peterson, Richard E.

    2013-01-01

    In mice, in utero exposure to 2,3,7,8-tetrachlorodibenzo-p- dioxin (TCDD) reduces the number of dorsolateral prostatic buds resulting in a smaller dorsolateral prostate and prevents formation of ventral buds culminating in ventral prostate agenesis. The genes and signaling pathways affected by TCDD that are responsible for disrupting prostate development are largely unknown. Here we show that treatment of urogenital sinus (UGS) organ cultures with known inhibitors of canonical Wnt signaling also inhibits prostatic bud formation. In support of the hypothesis that TCDD decreases canonical Wnt signaling, we identify inhibitory effects of TCDD on multiple components of the canonical Wnt signaling pathway in the UGS that temporally coincide with the inhibitory effect of TCDD on prostatic bud formation: (1) expression of R-spondins (Rspo2 and Rspo3) that promote canonical Wnt signaling is reduced; (2) expression of Lef1, Tcf1, and Wif1, established canonical Wnt target genes, is decreased; (3) expression of Lgr5, a RSPO receptor that activates canonical Wnt signaling, is reduced; and (4) expression of Dickkopfs (Dkks), inhibitors of canonical Wnt signaling, is not increased by TCDD. Thus, the TCDD-induced reduction in canonical Wnt signaling is associated with a decrease in activators (Rspo2 and Rspo3) rather than an increase in inhibitors (Dkk1 and Dkk2) of the pathway. This study focuses on determining whether treatment of TCDD-exposed UGS organ cultures with RSPO2 and/or RSPO3 is capable of rescuing the inhibitory effects of TCDD on canonical Wnt signaling and prostatic bud formation. We discovered that each RSPO alone or in combination partially rescues TCDD inhibition of both canonical Wnt signaling and prostatic bud formation. PMID:23429912

  18. TCDD inhibition of canonical Wnt signaling disrupts prostatic bud formation in mouse urogenital sinus.

    PubMed

    Branam, Amanda M; Davis, Nicole M; Moore, Robert W; Schneider, Andrew J; Vezina, Chad M; Peterson, Richard E

    2013-05-01

    In mice, in utero exposure to 2,3,7,8-tetrachlorodibenzo-p- dioxin (TCDD) reduces the number of dorsolateral prostatic buds resulting in a smaller dorsolateral prostate and prevents formation of ventral buds culminating in ventral prostate agenesis. The genes and signaling pathways affected by TCDD that are responsible for disrupting prostate development are largely unknown. Here we show that treatment of urogenital sinus (UGS) organ cultures with known inhibitors of canonical Wnt signaling also inhibits prostatic bud formation. In support of the hypothesis that TCDD decreases canonical Wnt signaling, we identify inhibitory effects of TCDD on multiple components of the canonical Wnt signaling pathway in the UGS that temporally coincide with the inhibitory effect of TCDD on prostatic bud formation: (1) expression of R-spondins (Rspo2 and Rspo3) that promote canonical Wnt signaling is reduced; (2) expression of Lef1, Tcf1, and Wif1, established canonical Wnt target genes, is decreased; (3) expression of Lgr5, a RSPO receptor that activates canonical Wnt signaling, is reduced; and (4) expression of Dickkopfs (Dkks), inhibitors of canonical Wnt signaling, is not increased by TCDD. Thus, the TCDD-induced reduction in canonical Wnt signaling is associated with a decrease in activators (Rspo2 and Rspo3) rather than an increase in inhibitors (Dkk1 and Dkk2) of the pathway. This study focuses on determining whether treatment of TCDD-exposed UGS organ cultures with RSPO2 and/or RSPO3 is capable of rescuing the inhibitory effects of TCDD on canonical Wnt signaling and prostatic bud formation. We discovered that each RSPO alone or in combination partially rescues TCDD inhibition of both canonical Wnt signaling and prostatic bud formation.

  19. Contribution of alpha3(IV)alpha4(IV)alpha5(IV) Collagen IV to the Mechanical Properties of the Glomerular Basement Membrane

    NASA Astrophysics Data System (ADS)

    Gyoneva, Lazarina

    The glomerular basement membrane (GBM) is a vital part of the blood-urine filtration barrier in the kidneys. In healthy GBMs, the main tension-resisting component is alpha3(IV)alpha4(IV)alpha5(IV) type IV collagen, but in some diseases it is replaced by other collagen IV isoforms. As a result, the GBM becomes leaky and disorganized, ultimately resulting in kidney failure. Our goal is to understanding the biomechanical aspects of the alpha3(IV)alpha4(IV)alpha5(IV) chains and how their absence could be responsible for (1) the initial injury to the GBM and (2) progression to kidney failure. A combination of experiments and computational models were designed for that purpose. A model basement membrane was used to compare experimentally the distensibility of tissues with the alpha3(IV)alpha4(IV)alpha5(IV) chains present and missing. The experiments showed basement membranes containing alpha3(IV)alpha4(IV)alpha5(IV) chains were less distensible. It has been postulated that the higher level of lateral cross-linking (supercoiling) in the alpha3(IV)alpha4(IV)alpha5(IV) networks contributes additional strength/stability to basement membranes. In a computational model of supercoiled networks, we found that supercoiling greatly increased the stiffness of collagen IV networks but only minimally decreased the permeability, which is well suited for the needs of the GBM. It is also known that the alpha3(IV)alpha4(IV)alpha5(IV) networks are more protected from enzymatic degradation, and we explored their significance in GBM remodeling. Our simulations showed that the more protected network was needed to prevent the system from entering a dangerous feedback cycle due to autoregulation mechanisms in the kidneys. Overall, the work adds to the evidence of biomechanical differences between the alpha3(IV)alpha4(IV)alpha5(IV) networks and other collagen IV networks, points to supercoiling as the main source of biomechanical differences, discusses the suitability of alpha3(IV)alpha4(IV

  20. Consistent Discretization and Canonical, Classical and Quantum Regge Calculus

    NASA Astrophysics Data System (ADS)

    Gambini, Rodolfo; Pullin, Jorge

    We apply the "consistent discretization" technique to the Regge action for (Euclidean and Lorentzian) general relativity in arbitrary number of dimensions. The result is a well-defined canonical theory that is free of constraints and where the dynamics is implemented as a canonical transformation. In the Lorentzian case, the framework appears to be naturally free of the "spikes" that plague traditional formulations. It also provides a well-defined recipe for determining the integration measure for quantum Regge calculus.

  1. A canonical state-space representation for SISO systems using multipoint Jordan CFE. [Continued-Fraction Expansion

    NASA Technical Reports Server (NTRS)

    Hwang, Chyi; Guo, Tong-Yi; Shieh, Leang-San

    1991-01-01

    A canonical state-space realization based on the multipoint Jordan continued-fraction expansion (CFE) is presented for single-input-single-output (SISO) systems. The similarity transformation matrix which relates the new canonical form to the phase-variable canonical form is also derived. The presented canonical state-space representation is particularly attractive for the application of SISO system theory in which a reduced-dimensional time-domain model is necessary.

  2. A field theory approach to the evolution of canonical helicity and energy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    You, S.

    A redefinition of the Lagrangian of a multi-particle system in fields reformulates the single-particle, kinetic, and fluid equations governing fluid and plasma dynamics as a single set of generalized Maxwell's equations and Ohm's law for canonical force-fields. The Lagrangian includes new terms representing the coupling between the motion of particle distributions, between distributions and electromagnetic fields, with relativistic contributions. The formulation shows that the concepts of self-organization and canonical helicity transport are applicable across single-particle, kinetic, and fluid regimes, at classical and relativistic scales. The theory gives the basis for comparing canonical helicity change to energy change in general systems.more » For example, in a fixed, isolated system subject to non-conservative forces, a species' canonical helicity changes less than total energy only if gradients in density or distribution function are shallow.« less

  3. Non-canonical modulators of nuclear receptors.

    PubMed

    Tice, Colin M; Zheng, Ya-Jun

    2016-09-01

    Like G protein-coupled receptors (GPCRs) and protein kinases, nuclear receptors (NRs) are a rich source of pharmaceutical targets. Over 80 NR-targeting drugs have been approved for 18 NRs. The focus of drug discovery in NRs has hitherto been on identifying ligands that bind to the canonical ligand binding pockets of the C-terminal ligand binding domains (LBDs). Due to the development of drug resistance and selectivity concerns, there has been considerable interest in exploring other, non-canonical ligand binding sites. Unfortunately, the potencies of compounds binding at other sites have generally not been sufficient for clinical development. However, the situation has changed dramatically over the last 3years, as compounds with sufficient potency have been reported for several NR targets. Here we review recent developments in this area from a medicinal chemistry point of view in the hope of stimulating further interest in this area of research. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Analysis of Plasma Detachment through Magnetic Nozzle via Canonical Field Theory

    NASA Astrophysics Data System (ADS)

    Takagaki, Yu

    In this paper, I have investigated the mechanism of plasma detachment through magnetic nozzle via canonical field theory, especially by considering canonical vorticity flux Psisigma contour and dissipative force vector Rsigma. As one of the most recent experimental proofs of plasma detachment, Olsen et al., observed and investigated three key indications of plasma detachment. However, after solving for numerical fits with their experimental data, I found that constant ion flux lines did not actually separate from constant magnetic flux lines. Thus, their first key indication becomes incorrect now. Whereas, my analytical results are consistent with the other two key indications. At the beginning, plasma detached from canonical vorticity flux contours due to non-zero dissipative force and attached on magnetic flux lines instead. However, vector Rsigma [is asymptotically equal to] 0 force makes plasma re-attach on canonical vorticity flux contours around the plume edge region. As the most significant and notable result through my analysis, I confirmed the existence of returning plasma flow around the plume edge region.

  5. Publication bias and the canonization of false facts.

    PubMed

    Nissen, Silas Boye; Magidson, Tali; Gross, Kevin; Bergstrom, Carl T

    2016-12-20

    Science is facing a "replication crisis" in which many experimental findings cannot be replicated and are likely to be false. Does this imply that many scientific facts are false as well? To find out, we explore the process by which a claim becomes fact. We model the community's confidence in a claim as a Markov process with successive published results shifting the degree of belief. Publication bias in favor of positive findings influences the distribution of published results. We find that unless a sufficient fraction of negative results are published, false claims frequently can become canonized as fact. Data-dredging, p-hacking, and similar behaviors exacerbate the problem. Should negative results become easier to publish as a claim approaches acceptance as a fact, however, true and false claims would be more readily distinguished. To the degree that the model reflects the real world, there may be serious concerns about the validity of purported facts in some disciplines.

  6. 37 CFR 10.21 - Canon 1.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2012-07-01 2012-07-01 false Canon 1. 10.21 Section 10.21 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE REPRESENTATION OF OTHERS BEFORE THE PATENT AND TRADEMARK OFFICE Patent and Trademark Office Code of Professional...

  7. 37 CFR 10.46 - Canon 3.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2012-07-01 2012-07-01 false Canon 3. 10.46 Section 10.46 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE REPRESENTATION OF OTHERS BEFORE THE PATENT AND TRADEMARK OFFICE Patent and Trademark Office Code of Professional...

  8. 37 CFR 10.21 - Canon 1.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Canon 1. 10.21 Section 10.21 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE REPRESENTATION OF OTHERS BEFORE THE PATENT AND TRADEMARK OFFICE Patent and Trademark Office Code of Professional...

  9. 37 CFR 10.30 - Canon 2.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Canon 2. 10.30 Section 10.30 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE REPRESENTATION OF OTHERS BEFORE THE PATENT AND TRADEMARK OFFICE Patent and Trademark Office Code of Professional...

  10. 37 CFR 10.56 - Canon 4.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2012-07-01 2012-07-01 false Canon 4. 10.56 Section 10.56 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE REPRESENTATION OF OTHERS BEFORE THE PATENT AND TRADEMARK OFFICE Patent and Trademark Office Code of Professional...

  11. 37 CFR 10.46 - Canon 3.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Canon 3. 10.46 Section 10.46 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE REPRESENTATION OF OTHERS BEFORE THE PATENT AND TRADEMARK OFFICE Patent and Trademark Office Code of Professional...

  12. 37 CFR 10.30 - Canon 2.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2012-07-01 2012-07-01 false Canon 2. 10.30 Section 10.30 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE REPRESENTATION OF OTHERS BEFORE THE PATENT AND TRADEMARK OFFICE Patent and Trademark Office Code of Professional...

  13. 37 CFR 10.56 - Canon 4.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Canon 4. 10.56 Section 10.56 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE REPRESENTATION OF OTHERS BEFORE THE PATENT AND TRADEMARK OFFICE Patent and Trademark Office Code of Professional...

  14. 37 CFR 10.61 - Canon 5.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2012-07-01 2012-07-01 false Canon 5. 10.61 Section 10.61 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE REPRESENTATION OF OTHERS BEFORE THE PATENT AND TRADEMARK OFFICE Patent and Trademark Office Code of Professional...

  15. Wnt3a regulates proliferation and migration of HUVEC via canonical and non-canonical Wnt signaling pathways

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Samarzija, Ivana; Sini, Patrizia; Schlange, Thomas

    2009-08-28

    Untangling the signaling pathways involved in endothelial cell biology is of central interest for the development of antiangiogenesis based therapies. Here we report that Wnt3a induces the proliferation and migration of HUVECs, but does not affect their survival. Wnt3a-induced proliferation was VEGFR signaling independent, but reduced upon CamKII inhibition. In a search for the downstream mediators of Wnt3a's effects on HUVEC biology, we found that Wnt3a treatment leads to phosphorylation of DVL3 and stabilization of {beta}-catenin. Moreover, under the same conditions we observed an upregulation in c-MYC, TIE-2 and GJA1 mRNA transcripts. Although treatment of HUVECs with Wnt5a induced DVL3more » phosphorylation, we did not observe any of the other effects seen upon Wnt3a stimulation. Taken together, our data indicate that Wnt3a induces canonical and non-canonical Wnt signaling in HUVECs, and stimulates their proliferation and migration.« less

  16. [3D structure of DKK1 indicates its involvement in both canonical and non-canonical Wnt pathways].

    PubMed

    Khalili, S; Rasaee, M J; Bamdad, T

    2017-01-01

    Dikkoppf-1 (DKK1) is an antagonist of the canonical Wnt signaling pathway. The importance of DKK1 as a diagnostic and therapeutic agent in a wide range of diseases along with its significance in a variety of biological processes accentuate the necessity to decipher its 3D structure that would pave the way towards the development of relevant selective inhibitors. A DKK1 structure model predicted by the Robetta server with structural refinements including a 10 ns molecular dynamics run was subjected to functional and docking analyses. We hypothesize that the N-terminal region of the DKK1 molecule could be functionally important for both canonical and noncanonical Wnt pathways. Moreover, it seems that DKK1 could be involved in interactions with the Frizzled receptors, leading to the activation of the Planar Cell Polarity (PCP) pathway (activation of Jun N-terminal kinase (JNK) Pathway) and Wnt/Ca^(2+) pathway (activation of CamKII).

  17. Body Aesthetic Preference in Preschoolers and Attraction to Canons Violation: An Exploratory Study.

    PubMed

    Di Dio, Cinzia; Berchio, Cristina; Massaro, Davide; Lombardi, Elisabetta; Gilli, Gabriella; Marchetti, Antonella

    2017-01-01

    Sensitivity to canons of beauty as represented in the human body-and as typically defined in the Western Culture-has been poorly studied in children. Current literature shows that infants as young as about three months are sensitive to the human body structure and its parts. Using a sample of 54 three- to five-year-old children, the present study investigated preference for drawings representing the "canonical" body structure, contrasting these with drawings showing the same bodies, but where the relation between trunk and legs was modified. It was hypothesized that preference for the canonical body structures would emerge as early as three years, increasing with age. Results only partially supported the hypothesis: while three-year-olds showed a significant preference for the canonical body structures as predicted, a significant preference reversal was found for the four-year-olds, with a tendency to return to preferring the canonical body at five years. The results are discussed in light of research findings associated with developmental theories hallmarking visual art perception in children.

  18. Remarks on the "Non-canonicity Puzzle": Lagrangian Symmetries of the Einstein-Hilbert Action

    NASA Astrophysics Data System (ADS)

    Kiriushcheva, N.; Komorowski, P. G.; Kuzmin, S. V.

    2012-07-01

    Given the non-canonical relationship between variables used in the Hamiltonian formulations of the Einstein-Hilbert action (due to Pirani, Schild, Skinner (PSS) and Dirac) and the Arnowitt-Deser-Misner (ADM) action, and the consequent difference in the gauge transformations generated by the first-class constraints of these two formulations, the assumption that the Lagrangians from which they were derived are equivalent leads to an apparent contradiction that has been called "the non-canonicity puzzle". In this work we shall investigate the group properties of two symmetries derived for the Einstein-Hilbert action: diffeomorphism, which follows from the PSS and Dirac formulations, and the one that arises from the ADM formulation. We demonstrate that unlike the diffeomorphism transformations, the ADM transformations (as well as others, which can be constructed for the Einstein-Hilbert Lagrangian using Noether's identities) do not form a group. This makes diffeomorphism transformations unique (the term "canonical" symmetry might be suggested). If the two Lagrangians are to be called equivalent, canonical symmetry must be preserved. The interplay between general covariance and the canonicity of the variables used is discussed.

  19. Complete Hamiltonian analysis of cosmological perturbations at all orders II: non-canonical scalar field

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Nandi, Debottam; Shankaranarayanan, S., E-mail: debottam@iisertvm.ac.in, E-mail: shanki@iisertvm.ac.in

    2016-10-01

    In this work, we present a consistent Hamiltonian analysis of cosmological perturbations for generalized non-canonical scalar fields. In order to do so, we introduce a new phase-space variable that is uniquely defined for different non-canonical scalar fields. We also show that this is the simplest and efficient way of expressing the Hamiltonian. We extend the Hamiltonian approach of [1] to non-canonical scalar field and obtain an unique expression of speed of sound in terms of phase-space variable. In order to invert generalized phase-space Hamilton's equations to Euler-Lagrange equations of motion, we prescribe a general inversion formulae and show that ourmore » approach for non-canonical scalar field is consistent. We also obtain the third and fourth order interaction Hamiltonian for generalized non-canonical scalar fields and briefly discuss the extension of our method to generalized Galilean scalar fields.« less

  20. Creativity and Brain-Functioning in Product Development Engineers: A Canonical Correlation Analysis

    ERIC Educational Resources Information Center

    Travis, Frederick; Lagrosen, Yvonne

    2014-01-01

    This study used canonical correlation analysis to explore the relation among scores on the Torrance test of figural and verbal creativity and demographic, psychological and physiological measures in Swedish product-development engineers. The first canonical variate included figural and verbal flexibility and originality as dependent measures and…

  1. Versions of the collocation and least squares method for solving biharmonic equations in non-canonical domains

    NASA Astrophysics Data System (ADS)

    Belyaev, V. A.; Shapeev, V. P.

    2017-10-01

    New versions of the collocations and least squares method of high-order accuracy are proposed and implemented for the numerical solution of the boundary value problems for the biharmonic equation in non-canonical domains. The solution of the biharmonic equation is used for simulating the stress-strain state of an isotropic plate under the action of transverse load. The differential problem is projected into a space of fourth-degree polynomials by the CLS method. The boundary conditions for the approximate solution are put down exactly on the boundary of the computational domain. The versions of the CLS method are implemented on the grids which are constructed in two different ways. It is shown that the approximate solution of problems converges with high order. Thus it matches with high accuracy with the analytical solution of the test problems in the case of known solution in the numerical experiments on the convergence of the solution of various problems on a sequence of grids.

  2. Drinfeld-Sokolov reduction in quantum algebras: canonical form of generating matrices

    NASA Astrophysics Data System (ADS)

    Gurevich, Dimitri; Saponov, Pavel; Talalaev, Dmitry

    2018-04-01

    We define the second canonical forms for the generating matrices of the Reflection Equation algebras and the braided Yangians, associated with all even skew-invertible involutive and Hecke symmetries. By using the Cayley-Hamilton identities for these matrices, we show that they are similar to their canonical forms in the sense of Chervov and Talalaev (J Math Sci (NY) 158:904-911, 2008).

  3. Fibrin-Enhanced Canonical Wnt Signaling Directs Plasminogen Expression in Cementoblasts

    PubMed Central

    Rahman, Saeed Ur; Ryoo, Hyun-Mo

    2017-01-01

    Cementum is a mineralized layer on the tooth’s root surface and facilitates the biomechanical anchoring of fibrous connective tissues as a part of tooth-supportive complexes. Previously, we observed that OCCM30 cementoblasts cultured on fibrin matrices underwent apoptosis due to fibrin degradation through the expression of proteases. Here, we demonstrated that OCCM30 on fibrin matrices (OCCM30-fibrin) enhanced canonical Wnt signaling, which directed to plasminogen expression. The OCCM30-fibrin showed higher levels of Wnt3a expression, nuclear translocation of β-catenin, and T-cell factor (TCF) optimal motif (TOP) reporter activity than the cells on tissue culture dishes (OCCM30-TCD), indicating that the OCCM30-fibrin enhanced canonical Wnt/β-catenin signaling. Also, OCCM30-fibrin expressed biomineralization-associated markers at higher levels than OCCM30-TCD, of which levels were further increased with LiCl, a Wnt signaling activator. The OCCM30 cementoblasts simultaneously showed that high levels of plasminogen, a critical component of fibrinolysis, were expressed in the OCCM30-fibrin. Activation of canonical Wnt signaling with LiCl treatment or with forced lymphoid enhancer factor 1 (LEF1)-expression increased the expression of plasminogen. On the contrary, the inhibition of canonical Wnt signaling with siRNAs against Wnt3a or β-catenin abrogated fibrin-enhanced plasminogen expression. Furthermore, there are three conserved putative response elements for the LEF1/β-catenin complex in the plasminogen proximal promoter regions (−900 to +54). Site-directed mutations and chromatin immunoprecipitation indicated that canonical Wnt signaling directed plasminogen expression. Taken together, this study suggests that fibrin-based materials can modulate functional periodontal formations in controlling cementoblast differentiation and fibrin degradation. PMID:29120400

  4. Algorithmic transformation of multi-loop master integrals to a canonical basis with CANONICA

    NASA Astrophysics Data System (ADS)

    Meyer, Christoph

    2018-01-01

    The integration of differential equations of Feynman integrals can be greatly facilitated by using a canonical basis. This paper presents the Mathematica package CANONICA, which implements a recently developed algorithm to automatize the transformation to a canonical basis. This represents the first publicly available implementation suitable for differential equations depending on multiple scales. In addition to the presentation of the package, this paper extends the description of some aspects of the algorithm, including a proof of the uniqueness of canonical forms up to constant transformations.

  5. Ancient origin and recent innovations of RNA polymerase IV and V

    DOE PAGES

    Huang, Yi; Kendall, Timmy; Forsythe, Evan S.; ...

    2015-03-12

    Small RNA-mediated chromatin modification is a conserved feature of eukaryotes. In flowering plants, the short interfering (si)RNAs that direct transcriptional silencing are abundant and subfunctionalization has led to specialized machinery responsible for synthesis and action of these small RNAs. In particular, plants possess polymerase (Pol) IV and Pol V, multi-subunit homologs of the canonical DNA-dependent RNA Pol II, as well as specialized members of the RNA-dependent RNA Polymerase (RDR), Dicer-like (DCL), and Argonaute (AGO) families. Together these enzymes are required for production and activity of Pol IV-dependent (p4-)siRNAs, which trigger RNA-directed DNA methylation (RdDM) at homologous sequences. p4-siRNAs accumulate highlymore » in developing endosperm, a specialized tissue found only in flowering plants, and are rare in nonflowering plants, suggesting that the evolution of flowers might coincide with the emergence of specialized RdDM machinery. Through comprehensive identification of RdDM genes from species representing the breadth of the land plant phylogeny, we describe the ancient origin of Pol IV and Pol V, suggesting that a nearly complete and functional RdDM pathway could have existed in the earliest land plants. We also uncover innovations in these enzymes that are coincident with the emergence of seed plants and flowering plants, and recent duplications that might indicate additional subfunctionalization. Phylogenetic analysis reveals rapid evolution of Pol IV and Pol V subunits relative to their Pol II counterparts and suggests that duplicates were retained and subfunctionalized through Escape from Adaptive Conflict. Finally, evolution within the carboxy-terminal domain of the Pol V largest subunit is particularly striking, where illegitimate recombination facilitated extreme sequence divergence.« less

  6. Ancient origin and recent innovations of RNA polymerase IV and V

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Huang, Yi; Kendall, Timmy; Forsythe, Evan S.

    Small RNA-mediated chromatin modification is a conserved feature of eukaryotes. In flowering plants, the short interfering (si)RNAs that direct transcriptional silencing are abundant and subfunctionalization has led to specialized machinery responsible for synthesis and action of these small RNAs. In particular, plants possess polymerase (Pol) IV and Pol V, multi-subunit homologs of the canonical DNA-dependent RNA Pol II, as well as specialized members of the RNA-dependent RNA Polymerase (RDR), Dicer-like (DCL), and Argonaute (AGO) families. Together these enzymes are required for production and activity of Pol IV-dependent (p4-)siRNAs, which trigger RNA-directed DNA methylation (RdDM) at homologous sequences. p4-siRNAs accumulate highlymore » in developing endosperm, a specialized tissue found only in flowering plants, and are rare in nonflowering plants, suggesting that the evolution of flowers might coincide with the emergence of specialized RdDM machinery. Through comprehensive identification of RdDM genes from species representing the breadth of the land plant phylogeny, we describe the ancient origin of Pol IV and Pol V, suggesting that a nearly complete and functional RdDM pathway could have existed in the earliest land plants. We also uncover innovations in these enzymes that are coincident with the emergence of seed plants and flowering plants, and recent duplications that might indicate additional subfunctionalization. Phylogenetic analysis reveals rapid evolution of Pol IV and Pol V subunits relative to their Pol II counterparts and suggests that duplicates were retained and subfunctionalized through Escape from Adaptive Conflict. Finally, evolution within the carboxy-terminal domain of the Pol V largest subunit is particularly striking, where illegitimate recombination facilitated extreme sequence divergence.« less

  7. Toddlers Default to Canonical Surface-to-Meaning Mapping When Learning Verbs

    PubMed Central

    Dautriche, Isabelle; Cristia, Alejandrina; Brusini, Perrine; Yuan, Sylvia; Fisher, Cynthia; Christophe, Anne

    2013-01-01

    Previous work has shown that toddlers readily encode each noun in the sentence as a distinct argument of the verb. However, languages allow multiple mappings between form and meaning which do not fit this canonical format. Two experiments examined French 28-month-olds’ interpretation of right-dislocated sentences (nouni-verb, nouni) where the presence of clear, language-specific cues should block such a canonical mapping. Toddlers (N = 96) interpreted novel verbs embedded in these sentences as transitive, disregarding prosodic cues to dislocation (Experiment 1) but correctly interpreted right-dislocated sentences containing well-known verbs (Experiment 2). These results suggest that toddlers can integrate multiple cues in ideal conditions, but default to canonical surface-to-meaning mapping when extracting structural information about novel verbs in semantically impoverished conditions. PMID:24117408

  8. Stabilizing canonical-ensemble calculations in the auxiliary-field Monte Carlo method

    NASA Astrophysics Data System (ADS)

    Gilbreth, C. N.; Alhassid, Y.

    2015-03-01

    Quantum Monte Carlo methods are powerful techniques for studying strongly interacting Fermi systems. However, implementing these methods on computers with finite-precision arithmetic requires careful attention to numerical stability. In the auxiliary-field Monte Carlo (AFMC) method, low-temperature or large-model-space calculations require numerically stabilized matrix multiplication. When adapting methods used in the grand-canonical ensemble to the canonical ensemble of fixed particle number, the numerical stabilization increases the number of required floating-point operations for computing observables by a factor of the size of the single-particle model space, and thus can greatly limit the systems that can be studied. We describe an improved method for stabilizing canonical-ensemble calculations in AFMC that exhibits better scaling, and present numerical tests that demonstrate the accuracy and improved performance of the method.

  9. What Is the Canon in American Politics? Analyses of Core Graduate Syllabi

    ERIC Educational Resources Information Center

    Diament, Sean M.; Howat, Adam J.; Lacombe, Matthew J.

    2017-01-01

    Many core graduate-level seminars claim to expose students to their discipline's "canon." The contents of this canon, however, can and do differ across departments and instructors. This project employs a survey of core American politics PhD seminar syllabi at highly ranked universities to construct a systematic account of the American…

  10. Canonical wnt signaling regulates hematopoiesis in a dosage-dependent fashion.

    PubMed

    Luis, Tiago C; Naber, Brigitta A E; Roozen, Paul P C; Brugman, Martijn H; de Haas, Edwin F E; Ghazvini, Mehrnaz; Fibbe, Willem E; van Dongen, Jacques J M; Fodde, Riccardo; Staal, Frank J T

    2011-10-04

    Canonical Wnt signaling has been implicated in the regulation of hematopoiesis. By employing a Wnt-reporter mouse, we observed that Wnt signaling is differentially activated during hematopoiesis, suggesting an important regulatory role for specific Wnt signaling levels. To investigate whether canonical Wnt signaling regulates hematopoiesis in a dosage-dependent fashion, we analyzed the effect of different mutations in the Adenomatous polyposis coli gene (Apc), a negative modulator of the canonical Wnt pathway. By combining different targeted hypomorphic alleles and a conditional deletion allele of Apc, a gradient of five different Wnt signaling levels was obtained in vivo. We here show that different, lineage-specific Wnt dosages regulate hematopoietic stem cells (HSCs), myeloid precursors, and T lymphoid precursors during hematopoiesis. Differential, lineage-specific optimal Wnt dosages provide a unifying concept that explains the differences reported among inducible gain-of-function approaches, leading to either HSC expansion or depletion of the HSC pool. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. Reading Canonical Texts in Multicultural Classrooms

    ERIC Educational Resources Information Center

    Shah, Mehrunissa

    2013-01-01

    This essay explores the complexity of imposing texts that are considered part of the English literary canon on students from multicultural backgrounds. It considers the rhetoric of the coalition government, in the recent drive to emphasize the importance of the literary heritage and return to English culture and how its impact has been felt in the…

  12. [Addictive behaviours from DSM-IV to DSM-5].

    PubMed

    van den Brink, W

    2014-01-01

    The 5th edition of the DSM was published in May, 2013. The new edition incorporates important changes in the classification of addiction. To compare the classification of addictive behaviours presented in DSM-IV with the classification presented in DSM-5 and to comment on the changes introduced into the new version. First of all, the historical developments of the concept of addiction and the classification of addictive behaviours up to DSM-IV are summarised. Then the changes that have been incorporated into DSM-5 are described. The main changes are: (1) DSM-IV substance related disorders and DSM-IV pathological gambling have been combined into one new DSM-5 category, namely 'Substance Related and Addictive Disorders'; (2) DSM-IV abuse and dependence have been combined into one new DSM-5 diagnosis, namely 'Substance Use Disorder'; (2a) the DSM-IV abuse criterion 'recurrent substance-related legal problems' and the DSM-5 criterion 'craving' has been introduced; and (2b) the criteria for (partial) remission have been sharpened. DSM-5 is an improvement on DSM-IV, but for the diagnosis of a psychiatric disorder and the treatment of a psychiatric patient, classification needs to be complemented with staging and profiling.

  13. Canonical Visual Size for Real-World Objects

    PubMed Central

    Konkle, Talia; Oliva, Aude

    2012-01-01

    Real-world objects can be viewed at a range of distances and thus can be experienced at a range of visual angles within the visual field. Given the large amount of visual size variation possible when observing objects, we examined how internal object representations represent visual size information. In a series of experiments which required observers to access existing object knowledge, we observed that real-world objects have a consistent visual size at which they are drawn, imagined, and preferentially viewed. Importantly, this visual size is proportional to the logarithm of the assumed size of the object in the world, and is best characterized not as a fixed visual angle, but by the ratio of the object and the frame of space around it. Akin to the previous literature on canonical perspective, we term this consistent visual size information the canonical visual size. PMID:20822298

  14. Self-and Peer Perspectives on Pathological Personality Traits and Interpersonal Problems

    ERIC Educational Resources Information Center

    Clifton, Allan; Turkheimer, Eric; Oltmanns, Thomas F.

    2005-01-01

    This study compares the relationship between personality disorders and interpersonal problems as obtained by self-report and peer-report measures. Participants (N=393) were administered self-and peer-report versions of the Peer Inventory for Personality Disorder and the Inventory of Interpersonal Problems-64. Canonical analyses demonstrated…

  15. Linear canonical transformations of coherent and squeezed states in the Wigner phase space

    NASA Technical Reports Server (NTRS)

    Han, D.; Kim, Y. S.; Noz, Marilyn E.

    1988-01-01

    It is shown that classical linear canonical transformations are possible in the Wigner phase space. Coherent and squeezed states are shown to be linear canonical transforms of the ground-state harmonic oscillator. It is therefore possible to evaluate the Wigner functions for coherent and squeezed states from that for the harmonic oscillator. Since the group of linear canonical transformations has a subgroup whose algebraic property is the same as that of the (2+1)-dimensional Lorentz group, it may be possible to test certain properties of the Lorentz group using optical devices. A possible experiment to measure the Wigner rotation angle is discussed.

  16. Measurements of the canonical helicity evolution of a gyrating kinked plasma column

    NASA Astrophysics Data System (ADS)

    von der Linden, Jens; Sears, Jason; Intrator, Thomas; You, Setthivoine

    2017-10-01

    Conversions between kinetic and magnetic energy occur over a wide range of plasma scales as exhibited in astrophysical and solar dynamos, and reconnection in the solar corona and laboratory experiments. Canonical flux tubes present the distinct advantage of reconciling all plasma regimes - e.g. kinetic, two-fluid, and MHD - with the topological concept of helicity: twists, writhes, and linkages. This poster presents the first visualization and analysis of the 3D dynamics of canonical flux tubes and their relative helicity evolution from experimental measurements. Ion and electron canonical flux tubes are visualized from Mach, triple, and Ḃ probe measurements at over 10,000 spatial locations of a gyrating kinked plasma column. The flux tubes co-gyrate with the peak density and electron temperature in and out of a measurement volume. The electron and ion canonical flux tubes twist with opposite handedness and the ion flux tube writhes around the electron flux tube. The relative cross helicity between the magnetic and ion flow vorticity flux tubes dominates the relative ion canonical helicity and is anticorrelated with the relative magnetic helicity. The 3D nature of the kink and a reverse eddy current affect the helicity evolution. This work is supported by DOE Grant DE-SC0010340 and the DOE Office of Science Graduate Student Research Program and prepared in part by LLNL under Contract DE-AC52-07NA27344. LLNL-ABS-734669.

  17. Spatio-Chromatic Adaptation via Higher-Order Canonical Correlation Analysis of Natural Images

    PubMed Central

    Gutmann, Michael U.; Laparra, Valero; Hyvärinen, Aapo; Malo, Jesús

    2014-01-01

    Independent component and canonical correlation analysis are two general-purpose statistical methods with wide applicability. In neuroscience, independent component analysis of chromatic natural images explains the spatio-chromatic structure of primary cortical receptive fields in terms of properties of the visual environment. Canonical correlation analysis explains similarly chromatic adaptation to different illuminations. But, as we show in this paper, neither of the two methods generalizes well to explain both spatio-chromatic processing and adaptation at the same time. We propose a statistical method which combines the desirable properties of independent component and canonical correlation analysis: It finds independent components in each data set which, across the two data sets, are related to each other via linear or higher-order correlations. The new method is as widely applicable as canonical correlation analysis, and also to more than two data sets. We call it higher-order canonical correlation analysis. When applied to chromatic natural images, we found that it provides a single (unified) statistical framework which accounts for both spatio-chromatic processing and adaptation. Filters with spatio-chromatic tuning properties as in the primary visual cortex emerged and corresponding-colors psychophysics was reproduced reasonably well. We used the new method to make a theory-driven testable prediction on how the neural response to colored patterns should change when the illumination changes. We predict shifts in the responses which are comparable to the shifts reported for chromatic contrast habituation. PMID:24533049

  18. Spatio-chromatic adaptation via higher-order canonical correlation analysis of natural images.

    PubMed

    Gutmann, Michael U; Laparra, Valero; Hyvärinen, Aapo; Malo, Jesús

    2014-01-01

    Independent component and canonical correlation analysis are two general-purpose statistical methods with wide applicability. In neuroscience, independent component analysis of chromatic natural images explains the spatio-chromatic structure of primary cortical receptive fields in terms of properties of the visual environment. Canonical correlation analysis explains similarly chromatic adaptation to different illuminations. But, as we show in this paper, neither of the two methods generalizes well to explain both spatio-chromatic processing and adaptation at the same time. We propose a statistical method which combines the desirable properties of independent component and canonical correlation analysis: It finds independent components in each data set which, across the two data sets, are related to each other via linear or higher-order correlations. The new method is as widely applicable as canonical correlation analysis, and also to more than two data sets. We call it higher-order canonical correlation analysis. When applied to chromatic natural images, we found that it provides a single (unified) statistical framework which accounts for both spatio-chromatic processing and adaptation. Filters with spatio-chromatic tuning properties as in the primary visual cortex emerged and corresponding-colors psychophysics was reproduced reasonably well. We used the new method to make a theory-driven testable prediction on how the neural response to colored patterns should change when the illumination changes. We predict shifts in the responses which are comparable to the shifts reported for chromatic contrast habituation.

  19. Are Young Children's Drawings Canonically Biased?

    ERIC Educational Resources Information Center

    Picard, Delphine; Durand, Karine

    2005-01-01

    In a between-subjects design, 4-to 6-year-olds were asked to draw from three-dimensional (3D) models, two-and-a-half-dimensional (212D) models with or without depth cues, or two-dimensional (2D) models of a familiar object (a saucepan) in noncanonical orientations (handle at the back or at the front). Results showed that canonical errors were…

  20. Canonical Statistical Model for Maximum Expected Immission of Wire Conductor in an Aperture Enclosure

    NASA Technical Reports Server (NTRS)

    Bremner, Paul G.; Vazquez, Gabriel; Christiano, Daniel J.; Trout, Dawn H.

    2016-01-01

    Prediction of the maximum expected electromagnetic pick-up of conductors inside a realistic shielding enclosure is an important canonical problem for system-level EMC design of space craft, launch vehicles, aircraft and automobiles. This paper introduces a simple statistical power balance model for prediction of the maximum expected current in a wire conductor inside an aperture enclosure. It calculates both the statistical mean and variance of the immission from the physical design parameters of the problem. Familiar probability density functions can then be used to predict the maximum expected immission for deign purposes. The statistical power balance model requires minimal EMC design information and solves orders of magnitude faster than existing numerical models, making it ultimately viable for scaled-up, full system-level modeling. Both experimental test results and full wave simulation results are used to validate the foundational model.

  1. Publication bias and the canonization of false facts

    PubMed Central

    Nissen, Silas Boye; Magidson, Tali; Gross, Kevin; Bergstrom, Carl T

    2016-01-01

    Science is facing a “replication crisis” in which many experimental findings cannot be replicated and are likely to be false. Does this imply that many scientific facts are false as well? To find out, we explore the process by which a claim becomes fact. We model the community’s confidence in a claim as a Markov process with successive published results shifting the degree of belief. Publication bias in favor of positive findings influences the distribution of published results. We find that unless a sufficient fraction of negative results are published, false claims frequently can become canonized as fact. Data-dredging, p-hacking, and similar behaviors exacerbate the problem. Should negative results become easier to publish as a claim approaches acceptance as a fact, however, true and false claims would be more readily distinguished. To the degree that the model reflects the real world, there may be serious concerns about the validity of purported facts in some disciplines. DOI: http://dx.doi.org/10.7554/eLife.21451.001 PMID:27995896

  2. Development of Canonical Transformations from Hamilton's Principle.

    ERIC Educational Resources Information Center

    Quade, C. Richard

    1979-01-01

    The theory of canonical transformations and its development are discussed with regard to its application to Hutton's principle. Included are the derivation of the equations of motion and a lack of symmetry in the formulaion with respect to Lagrangian and the fundamental commutator relations of quantum mechanics. (Author/SA)

  3. Identification of canonical neural events during continuous gameplay of an 8-bit style video game.

    PubMed

    Cavanagh, James F; Castellanos, Joel

    2016-06-01

    Cognitive neuroscience suffers from a unique and pervasive problem of generalizability. Since neural findings are often interpreted in the context of a specific manipulation during a carefully controlled task, it is hard to transfer knowledge from one task to another. In this report we address problems of generalizability with two methodological advancements. First, we aimed to transcend status quo experimental procedures with a continuous, engaging task environment. To this end, we created a novel 8-bit style continuous space shooter video game that elicits a multitude of goal-oriented events, such as crashing into a wall or blowing up an enemy with a missile. Second, we aimed to objectively define the psychological significance of these events. To achieve this aim, we used pattern classification of EEG data to derive predictive weights from carefully controlled pre-game exemplar events (oddball target detection and gambling wins and losses) and transferred those weights to EEG activities during video game events. All major goal-oriented events (crashes into the wall, crashes into an enemy, missile hit on an enemy) had a significant between-task transfer bias towards oddball target weights in the time range of the canonical P3, indicating the presence of similar salience detection processes. Missile hits on an enemy were specifically identified as gambling wins, confirming the hypothesis that this goal-oriented event was appetitive. These findings suggest that it is possible to identify the contribution of canonical neural activities during otherwise ambiguous and uncontrolled task performance. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Signature and Pathophysiology of Non-canonical Pores in Voltage-Dependent Cation Channels.

    PubMed

    Held, Katharina; Voets, Thomas; Vriens, Joris

    2016-01-01

    Opening and closing of voltage-gated cation channels allows the regulated flow of cations such as Na(+), K(+), and Ca(2+) across cell membranes, which steers essential physiological processes including shaping of action potentials and triggering Ca(2+)-dependent processes. Classical textbooks describe the voltage-gated cation channels as membrane proteins with a single, central aqueous pore. In recent years, however, evidence has accumulated for the existence of additional ion permeation pathways in this group of cation channels, distinct from the central pore, which here we collectively name non-canonical pores. Whereas the first non-canonical pores were unveiled only after making specific point mutations in the voltage-sensor region of voltage-gated Na(+) and K(+) channels, recent evidence indicates that they may also be functional in non-mutated channels. Moreover, several channelopathies have been linked to mutations that cause the appearance of a non-canonical ion permeation pathway as a new pathological mechanism. This review provides an integrated overview of the biophysical properties of non-canonical pores described in voltage-dependent cation channels (KV, NaV, Cav, Hv1, and TRPM3) and of the (patho)physiological impact of opening of such pores.

  5. Baryon number violation and novel canonical anti-commutation relations

    NASA Astrophysics Data System (ADS)

    Fujikawa, Kazuo; Tureanu, Anca

    2018-02-01

    The possible neutron-antineutron oscillation is described by an effective quadratic Lagrangian analogous to the BCS theory. It is shown that the conventional equal-time anti-commutation relations of the neutron variable n (t , x →) are modified by the baryon number violating terms. This is established by the Bjorken-Johnson-Low prescription and also by the canonical quantization combined with equations of motion. This novel canonical behavior can give rise to an important physical effect, which is illustrated by analyzing the Lagrangian that violates the baryon number but gives rise to the degenerate effective Majorana fermions and thus no neutron-antineutron oscillation. Technically, this model is neatly treated using a relativistic analogue of the Bogoliubov transformation.

  6. Attenuation of the Squared Canonical Correlation Coefficient under Varying Estimates of Score Reliability

    ERIC Educational Resources Information Center

    Wilson, Celia M.

    2010-01-01

    Research pertaining to the distortion of the squared canonical correlation coefficient has traditionally been limited to the effects of sampling error and associated correction formulas. The purpose of this study was to compare the degree of attenuation of the squared canonical correlation coefficient under varying conditions of score reliability.…

  7. SMAD4 feedback regulates the canonical TGF-β signaling pathway to control granulosa cell apoptosis.

    PubMed

    Du, Xing; Pan, Zengxiang; Li, Qiqi; Liu, Honglin; Li, Qifa

    2018-02-02

    Canonical TGF-β signals are transduced from the cell surface to the cytoplasm, and then translocated into the nucleus, a process that involves ligands (TGF-β1), receptors (TGFBR2/1), receptor-activated SMADs (SMAD2/3), and the common SMAD (SMAD4). Here we provide evidence that SMAD4, a core component of the canonical TGF-β signaling pathway, regulates the canonical TGF-β signaling pathway in porcine granulosa cells (GCs) through a feedback mechanism. Genome-wide analysis and qRT-PCR revealed that SMAD4 affected miRNA biogenesis in GCs. Interestingly, TGFBR2, the type II receptor of the canonical TGF-β signaling pathway, was downregulated in SMAD4-silenced GCs and found to be a common target of SMAD4-inhibited miRNAs. miR-425, the most significantly elevated miRNA in SMAD4-silenced GCs, mediated the SMAD4 feedback regulation of the TGF-β signaling pathway. This was accomplished through a direct interaction between the transcription factor SMAD4 and the miR-425 promoter, and a direct interaction between miR-425 and the TGFBR2 3'-UTR. Furthermore, miR-425 enhanced GC apoptosis by targeting TGFBR2 and the canonical TGF-β signaling pathway, which was rescued by SMAD4 and TGF-β1. Overall, our findings demonstrate that a positive feedback mechanism exists within the canonical TGF-β signaling pathway. This study also provides new insights into mechanism underlying the canonical TGF-β signaling pathway, which regulates GC function and follicular development.

  8. Canonical decomposition of magnetotelluric responses: Experiment on 1D anisotropic structures

    NASA Astrophysics Data System (ADS)

    Guo, Ze-qiu; Wei, Wen-bo; Ye, Gao-feng; Jin, Sheng; Jing, Jian-en

    2015-08-01

    Horizontal electrical heterogeneity of subsurface earth is mostly originated from structural complexity and electrical anisotropy, and local near-surface electrical heterogeneity will severely distort regional electromagnetic responses. Conventional distortion analyses for magnetotelluric soundings are primarily physical decomposition methods with respect to isotropic models, which mostly presume that the geoelectric distribution of geological structures is of local and regional patterns represented by 3D/2D models. Due to the widespread anisotropy of earth media, the confusion between 1D anisotropic responses and 2D isotropic responses, and the defects of physical decomposition methods, we propose to conduct modeling experiments with canonical decomposition in terms of 1D layered anisotropic models, and the method is one of the mathematical decomposition methods based on eigenstate analyses differentiated from distortion analyses, which can be used to recover electrical information such as strike directions, and maximum and minimum conductivity. We tested this method with numerical simulation experiments on several 1D synthetic models, which turned out that canonical decomposition is quite effective to reveal geological anisotropic information. Finally, for the background of anisotropy from previous study by geological and seismological methods, canonical decomposition is applied to real data acquired in North China Craton for 1D anisotropy analyses, and the result shows that, with effective modeling and cautious interpretation, canonical decomposition could be another good method to detect anisotropy of geological media.

  9. Kernel-aligned multi-view canonical correlation analysis for image recognition

    NASA Astrophysics Data System (ADS)

    Su, Shuzhi; Ge, Hongwei; Yuan, Yun-Hao

    2016-09-01

    Existing kernel-based correlation analysis methods mainly adopt a single kernel in each view. However, only a single kernel is usually insufficient to characterize nonlinear distribution information of a view. To solve the problem, we transform each original feature vector into a 2-dimensional feature matrix by means of kernel alignment, and then propose a novel kernel-aligned multi-view canonical correlation analysis (KAMCCA) method on the basis of the feature matrices. Our proposed method can simultaneously employ multiple kernels to better capture the nonlinear distribution information of each view, so that correlation features learned by KAMCCA can have well discriminating power in real-world image recognition. Extensive experiments are designed on five real-world image datasets, including NIR face images, thermal face images, visible face images, handwritten digit images, and object images. Promising experimental results on the datasets have manifested the effectiveness of our proposed method.

  10. The Problem Novel in a Conservative Age.

    ERIC Educational Resources Information Center

    LeMieux, A. C.

    1998-01-01

    Considers both the writing of and current attacks on young adolescent literature problem novels. Suggests that, judging from the lists of challenged and banned books, there are a lot of people in today's conservative climate who feel they have the right, or even the obligation, to define the literary canon. (RS)

  11. Swarms with canonical active Brownian motion.

    PubMed

    Glück, Alexander; Hüffel, Helmuth; Ilijić, Saša

    2011-05-01

    We present a swarm model of Brownian particles with harmonic interactions, where the individuals undergo canonical active Brownian motion, i.e., each Brownian particle can convert internal energy to mechanical energy of motion. We assume the existence of a single global internal energy of the system. Numerical simulations show amorphous swarming behavior as well as static configurations. Analytic understanding of the system is provided by studying stability properties of equilibria.

  12. Foundations of Education: Texts and the Canon.

    ERIC Educational Resources Information Center

    Gottlieb, Esther E.

    This paper attempts to outline the textual canon of the foundations of education in U.S. teacher education programs. Background research for the project included a review of selected texts and samples of course syllabi. Analysis of the contents and prefaces of the two volumes of "Reading in the Foundations of Education" (published in…

  13. Canonical Drude Weight for Non-integrable Quantum Spin Chains

    NASA Astrophysics Data System (ADS)

    Mastropietro, Vieri; Porta, Marcello

    2018-03-01

    The Drude weight is a central quantity for the transport properties of quantum spin chains. The canonical definition of Drude weight is directly related to Kubo formula of conductivity. However, the difficulty in the evaluation of such expression has led to several alternative formulations, accessible to different methods. In particular, the Euclidean, or imaginary-time, Drude weight can be studied via rigorous renormalization group. As a result, in the past years several universality results have been proven for such quantity at zero temperature; remarkably, the proofs work for both integrable and non-integrable quantum spin chains. Here we establish the equivalence of Euclidean and canonical Drude weights at zero temperature. Our proof is based on rigorous renormalization group methods, Ward identities, and complex analytic ideas.

  14. Grand canonical ensemble Monte Carlo simulation of the dCpG/proflavine crystal hydrate.

    PubMed

    Resat, H; Mezei, M

    1996-09-01

    The grand canonical ensemble Monte Carlo molecular simulation method is used to investigate hydration patterns in the crystal hydrate structure of the dCpG/proflavine intercalated complex. The objective of this study is to show by example that the recently advocated grand canonical ensemble simulation is a computationally efficient method for determining the positions of the hydrating water molecules in protein and nucleic acid structures. A detailed molecular simulation convergence analysis and an analogous comparison of the theoretical results with experiments clearly show that the grand ensemble simulations can be far more advantageous than the comparable canonical ensemble simulations.

  15. Reliability of DSM-IV Symptom Ratings of ADHD: Implications for DSM-V

    ERIC Educational Resources Information Center

    Solanto, Mary V.; Alvir, Jose

    2009-01-01

    Objective: The objective of this study was to examine the intrarater reliability of "DSM-IV" ADHD symptoms. Method: Two-hundred-two children referred for attention problems and 49 comparison children (all 7-12 years) were rated by parents and teachers on the identical "DSM-IV" items presented in two different formats, the…

  16. Clinical Trials With Large Numbers of Variables: Important Advantages of Canonical Analysis.

    PubMed

    Cleophas, Ton J

    2016-01-01

    Canonical analysis assesses the combined effects of a set of predictor variables on a set of outcome variables, but it is little used in clinical trials despite the omnipresence of multiple variables. The aim of this study was to assess the performance of canonical analysis as compared with traditional multivariate methods using multivariate analysis of covariance (MANCOVA). As an example, a simulated data file with 12 gene expression levels and 4 drug efficacy scores was used. The correlation coefficient between the 12 predictor and 4 outcome variables was 0.87 (P = 0.0001) meaning that 76% of the variability in the outcome variables was explained by the 12 covariates. Repeated testing after the removal of 5 unimportant predictor and 1 outcome variable produced virtually the same overall result. The MANCOVA identified identical unimportant variables, but it was unable to provide overall statistics. (1) Canonical analysis is remarkable, because it can handle many more variables than traditional multivariate methods such as MANCOVA can. (2) At the same time, it accounts for the relative importance of the separate variables, their interactions and differences in units. (3) Canonical analysis provides overall statistics of the effects of sets of variables, whereas traditional multivariate methods only provide the statistics of the separate variables. (4) Unlike other methods for combining the effects of multiple variables such as factor analysis/partial least squares, canonical analysis is scientifically entirely rigorous. (5) Limitations include that it is less flexible than factor analysis/partial least squares, because only 2 sets of variables are used and because multiple solutions instead of one is offered. We do hope that this article will stimulate clinical investigators to start using this remarkable method.

  17. Measurements of the Canonical Helicity Evolution of a Gyrating Kinked Flux Rope

    NASA Astrophysics Data System (ADS)

    von der Linden, J.; Sears, J.; Intrator, T.; You, S.

    2017-12-01

    Magnetic structures in the solar corona and planetary magnetospheres are often modelled as magnetic flux ropes governed by magnetohydrodynamics (MHD); however, inside these structures, as exhibited in reconnection, conversions between magnetic and kinetic energies occur over a wide range of scales. Flux ropes based on the flux of canonical momentum circulation extend the flux rope concept to include effects of finite particle momentum and present the distinct advantage of reconciling all plasma regimes - e.g. kinetic, two-fluid, and MHD - with the topological concept of helicity: twists, writhes, and linkages. This presentation shows the first visualization and analysis of the 3D dynamics of canonical flux ropes and their relative helicity evolution from laboratory measurements. Ion and electron canonical flux ropes are visualized from a dataset of Mach, triple, and Ḃ probe measurements at over 10,000 spatial locations of a gyrating kinked flux rope. The flux ropes co-gyrate with the peak density and electron temperature in and out of a measurement volume. The electron and ion canonical flux ropes twist with opposite handedness and the ion flux ropes writhe around the electron flux ropes. The relative cross helicity between the magnetic and ion flow vorticity flux ropes dominates the relative ion canonical helicity and is anti-correlated with the relative magnetic helicity. The 3D nature of the kink and a reverse eddy current affect the helicity evolution. This work is supported by DOE Grant DE-SC0010340 and the DOE Office of Science Graduate Student Research Program and prepared in part by LLNL under Contract DE-AC52-07NA27344. LLNL-ABS-735426

  18. Relationship between organisational commitment and burnout syndrome: a canonical correlation approach.

    PubMed

    Enginyurt, Ozgur; Cankaya, Soner; Aksay, Kadir; Tunc, Taner; Koc, Bozkurt; Bas, Orhan; Ozer, Erdal

    2016-04-01

    Objective Burnout syndrome can significantly reduce the performance of health workers. Although many factors have been identified as antecedents of burnout, few studies have investigated the role of organisational commitment in its development. The purpose of the present study was to examine the relationships between subdimensions of burnout syndrome (emotional exhaustion, depersonalisation and personal accomplishment) and subdimensions of organisational commitment (affective commitment, continuance commitment and normative commitment). Methods The present study was a cross-sectional survey of physicians and other healthcare employees working in the Ministry of Health Ordu University Education and Research Hospital. The sample consisted of 486 healthcare workers. Data were collected using the Maslach Burnout Inventory and the Organisation Commitment Scale, and were analysed using the canonical correlation approach. Results The first of three canonical correlation coefficients between pairs of canonical variables (Ui , burnout syndrome and Vi, organisational commitment) was found to be statistically significant. Emotional exhaustion was found to contribute most towards the explanatory capacity of canonical variables estimated from the subdimensions of burnout syndrome, whereas affective commitment provided the largest contribution towards the explanatory capacity of canonical variables estimated from the subdimensions of organisational commitment. Conclusions The results of the present study indicate that affective commitment is the primary determinant of burnout syndrome in healthcare professionals. What is known about the topic? Organisational commitment and burnout syndrome are the most important criteria in predicting health workforce performance. An increasing number of studies in recent years have clearly indicated the field's continued relevance and importance. Conversely, canonical correlation analysis (CCA) is a technique for describing the relationship

  19. A general transformation to canonical form for potentials in pairwise interatomic interactions.

    PubMed

    Walton, Jay R; Rivera-Rivera, Luis A; Lucchese, Robert R; Bevan, John W

    2015-06-14

    A generalized formulation of explicit force-based transformations is introduced to investigate the concept of a canonical potential in both fundamental chemical and intermolecular bonding. Different classes of representative ground electronic state pairwise interatomic interactions are referenced to a chosen canonical potential illustrating application of such transformations. Specifically, accurately determined potentials of the diatomic molecules H2, H2(+), HF, LiH, argon dimer, and one-dimensional dissociative coordinates in Ar-HBr, OC-HF, and OC-Cl2 are investigated throughout their bound potentials. Advantages of the current formulation for accurately evaluating equilibrium dissociation energies and a fundamentally different unified perspective on nature of intermolecular interactions will be emphasized. In particular, this canonical approach has significance to previous assertions that there is no very fundamental distinction between van der Waals bonding and covalent bonding or for that matter hydrogen and halogen bonds.

  20. Canonical field anticommutators in the extended gauged Rarita-Schwinger theory

    NASA Astrophysics Data System (ADS)

    Adler, Stephen L.; Henneaux, Marc; Pais, Pablo

    2017-10-01

    We reexamine canonical quantization of the gauged Rarita-Schwinger theory using the extended theory, incorporating a dimension 1/2 auxiliary spin-1/2 field Λ , in which there is an exact off-shell gauge invariance. In Λ =0 gauge, which reduces to the original unextended theory, our results agree with those found by Johnson and Sudarshan, and later verified by Velo and Zwanziger, which give a canonical Rarita-Schwinger field Dirac bracket that is singular for small gauge fields. In gauge covariant radiation gauge, the Dirac bracket of the Rarita-Schwinger fields is nonsingular, but does not correspond to a positive semidefinite anticommutator, and the Dirac bracket of the auxiliary fields has a singularity of the same form as found in the unextended theory. These results indicate that gauged Rarita-Schwinger theory is somewhat pathological, and cannot be canonically quantized within a conventional positive semidefinite metric Hilbert space. We leave open the questions of whether consistent quantizations can be achieved by using an indefinite metric Hilbert space, by path integral methods, or by appropriate couplings to conventional dimension 3/2 spin-1/2 fields.

  1. Multiset canonical correlations analysis and multispectral, truly multitemporal remote sensing data.

    PubMed

    Nielsen, Allan Aasbjerg

    2002-01-01

    This paper describes two- and multiset canonical correlations analysis (CCA) for data fusion, multisource, multiset, or multitemporal exploratory data analysis. These techniques transform multivariate multiset data into new orthogonal variables called canonical variates (CVs) which, when applied in remote sensing, exhibit ever-decreasing similarity (as expressed by correlation measures) over sets consisting of 1) spectral variables at fixed points in time (R-mode analysis), or 2) temporal variables with fixed wavelengths (T-mode analysis). The CVs are invariant to linear and affine transformations of the original variables within sets which means, for example, that the R-mode CVs are insensitive to changes over time in offset and gain in a measuring device. In a case study, CVs are calculated from Landsat Thematic Mapper (TM) data with six spectral bands over six consecutive years. Both Rand T-mode CVs clearly exhibit the desired characteristic: they show maximum similarity for the low-order canonical variates and minimum similarity for the high-order canonical variates. These characteristics are seen both visually and in objective measures. The results from the multiset CCA R- and T-mode analyses are very different. This difference is ascribed to the noise structure in the data. The CCA methods are related to partial least squares (PLS) methods. This paper very briefly describes multiset CCA-based multiset PLS. Also, the CCA methods can be applied as multivariate extensions to empirical orthogonal functions (EOF) techniques. Multiset CCA is well-suited for inclusion in geographical information systems (GIS).

  2. Infants' Recognition of Objects Using Canonical Color

    ERIC Educational Resources Information Center

    Kimura, Atsushi; Wada, Yuji; Yang, Jiale; Otsuka, Yumiko; Dan, Ippeita; Masuda, Tomohiro; Kanazawa, So; Yamaguchi, Masami K.

    2010-01-01

    We explored infants' ability to recognize the canonical colors of daily objects, including two color-specific objects (human face and fruit) and a non-color-specific object (flower), by using a preferential looking technique. A total of 58 infants between 5 and 8 months of age were tested with a stimulus composed of two color pictures of an object…

  3. Psychosocial stressors and the prognosis of major depression: a test of Axis IV

    PubMed Central

    Gilman, Stephen E.; Trinh, Nhi-Ha; Smoller, Jordan W.; Fava, Maurizio; Murphy, Jane M.; Breslau, Joshua

    2013-01-01

    Background Axis IV is for reporting “psychosocial and environmental problems that may affect the diagnosis, treatment, and prognosis of mental disorders.” No studies have examined the prognostic value of Axis IV in DSM-IV. Method We analyzed data from 2,497 participants in the National Epidemiologic Survey on Alcohol and Related Conditions with major depressive episode (MDE). We hypothesized that psychosocial stressors predict a poor prognosis of MDE. Secondarily, we hypothesized that psychosocial stressors predict a poor prognosis of anxiety and substance use disorders. Stressors were defined according to DSM-IV’s taxonomy, and empirically using latent class analysis. Results Primary support group problems, occupational problems, and childhood adversity increased the risks of depressive episodes and suicidal ideation by 20–30%. Associations of the empirically derived classes of stressors with depression were larger in magnitude. Economic stressors conferred a 1.5-fold increase in risk for a depressive episode (CI=1.2–1.9); financial and interpersonal instability conferred a 1.3-fold increased risk of recurrent depression (CI=1.1–1.6). These two classes of stressors also predicted the recurrence of anxiety and substance use disorders. Stressors were not related to suicidal ideation independent from depression severity. Conclusions Psychosocial and environmental problems are associated with the prognosis of MDE and other Axis I disorders. Though DSM-IV’s taxonomy of stressors stands to be improved, these results provide empirical support for the prognostic value of Axis IV. Future work is needed to determine the reliability of Axis IV assessments in clinical practice, and the usefulness of this information to improving the clinical course of mental disorders. PMID:22640506

  4. Canonical ensemble ground state and correlation entropy of Bose-Einstein condensate

    NASA Astrophysics Data System (ADS)

    Svidzinsky, Anatoly; Kim, Moochan; Agarwal, Girish; Scully, Marlan O.

    2018-01-01

    Constraint of a fixed total number of particles yields a correlation between the fluctuation of particles in different states in the canonical ensemble. Here we show that, below the temperature of Bose-Einstein condensation (BEC), the correlation part of the entropy of an ideal Bose gas is cancelled by the ground-state contribution. Thus, in the BEC region, the thermodynamic properties of the gas in the canonical ensemble can be described accurately in a simplified model which excludes the ground state and assumes no correlation between excited levels.

  5. Grand canonical ensemble Monte Carlo simulation of the dCpG/proflavine crystal hydrate.

    PubMed Central

    Resat, H; Mezei, M

    1996-01-01

    The grand canonical ensemble Monte Carlo molecular simulation method is used to investigate hydration patterns in the crystal hydrate structure of the dCpG/proflavine intercalated complex. The objective of this study is to show by example that the recently advocated grand canonical ensemble simulation is a computationally efficient method for determining the positions of the hydrating water molecules in protein and nucleic acid structures. A detailed molecular simulation convergence analysis and an analogous comparison of the theoretical results with experiments clearly show that the grand ensemble simulations can be far more advantageous than the comparable canonical ensemble simulations. Images FIGURE 5 FIGURE 7 PMID:8873992

  6. Automatic generation and analysis of solar cell IV curves

    DOEpatents

    Kraft, Steven M.; Jones, Jason C.

    2014-06-03

    A photovoltaic system includes multiple strings of solar panels and a device presenting a DC load to the strings of solar panels. Output currents of the strings of solar panels may be sensed and provided to a computer that generates current-voltage (IV) curves of the strings of solar panels. Output voltages of the string of solar panels may be sensed at the string or at the device presenting the DC load. The DC load may be varied. Output currents of the strings of solar panels responsive to the variation of the DC load are sensed to generate IV curves of the strings of solar panels. IV curves may be compared and analyzed to evaluate performance of and detect problems with a string of solar panels.

  7. Bach, Beethoven, Bourdieu: "Cultural Capital" and the Scholastic Canon in England's A-Level Examinations

    ERIC Educational Resources Information Center

    Legg, Robert

    2012-01-01

    This article applies Bourdieu's notion of "cultural capital" to historical, documentary research which investigates the construction of a scholastic canon within England's A-level music examinations. A digest of the ways in which this canon evolved between 1951 and 1986 is presented in support of the idea that examiners' responses to…

  8. Representations of spacetime diffeomorphisms. I. Canonical parametrized field theories

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Isham, C.J.; Kuchar, K.V.

    The super-Hamiltonian and supermomentum in canonical geometrodynamics or in a parametried field theory on a given Riemannian background have Poisson brackets which obey the Dirac relations. By smearing the supermomentum with vector fields VepsilonL Diff..sigma.. on the space manifold ..sigma.., the Lie algebra L Diff ..sigma.. of the spatial diffeomorphism group Diff ..sigma.. can be mapped antihomomorphically into the Poisson bracket algebra on the phase space of the system. The explicit dependence of the Poisson brackets between two super-Hamiltonians on canonical coordinates (spatial metrics in geometrodynamics and embedding variables in parametrized theories) is usually regarded as an indication that themore » Dirac relations cannot be connected with a representation of the complete Lie algebra L Diff M of spacetime diffeomorphisms.« less

  9. 37 CFR 10.20 - Canons and Disciplinary Rules.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2012-07-01 2012-07-01 false Canons and Disciplinary Rules. 10.20 Section 10.20 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE REPRESENTATION OF OTHERS BEFORE THE PATENT AND TRADEMARK OFFICE Patent and Trademark...

  10. 37 CFR 10.20 - Canons and Disciplinary Rules.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Canons and Disciplinary Rules. 10.20 Section 10.20 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE REPRESENTATION OF OTHERS BEFORE THE PATENT AND TRADEMARK OFFICE Patent and Trademark...

  11. Non-canonical NOTCH3 signalling limits tumour angiogenesis.

    PubMed

    Lin, Shuheng; Negulescu, Ana; Bulusu, Sirisha; Gibert, Benjamin; Delcros, Jean-Guy; Ducarouge, Benjamin; Rama, Nicolas; Gadot, Nicolas; Treilleux, Isabelle; Saintigny, Pierre; Meurette, Olivier; Mehlen, Patrick

    2017-07-18

    Notch signalling is a causal determinant of cancer and efforts have been made to develop targeted therapies to inhibit the so-called canonical pathway. Here we describe an unexpected pro-apoptotic role of Notch3 in regulating tumour angiogenesis independently of the Notch canonical pathway. The Notch3 ligand Jagged-1 is upregulated in a fraction of human cancer and our data support the view that Jagged-1, produced by cancer cells, is inhibiting the apoptosis induced by the aberrant Notch3 expression in tumour vasculature. We thus present Notch3 as a dependence receptor inducing endothelial cell death while this pro-apoptotic activity is blocked by Jagged-1. Along this line, using Notch3 mutant mice, we demonstrate that tumour growth and angiogenesis are increased when Notch3 is silenced in the stroma. Consequently, we show that the well-documented anti-tumour effect mediated by γ-secretase inhibition is at least in part dependent on the apoptosis triggered by Notch3 in endothelial cells.

  12. Non-canonical NOTCH3 signalling limits tumour angiogenesis

    PubMed Central

    Lin, Shuheng; Negulescu, Ana; Bulusu, Sirisha; Gibert, Benjamin; Delcros, Jean-Guy; Ducarouge, Benjamin; Rama, Nicolas; Gadot, Nicolas; Treilleux, Isabelle; Saintigny, Pierre; Meurette, Olivier; Mehlen, Patrick

    2017-01-01

    Notch signalling is a causal determinant of cancer and efforts have been made to develop targeted therapies to inhibit the so-called canonical pathway. Here we describe an unexpected pro-apoptotic role of Notch3 in regulating tumour angiogenesis independently of the Notch canonical pathway. The Notch3 ligand Jagged-1 is upregulated in a fraction of human cancer and our data support the view that Jagged-1, produced by cancer cells, is inhibiting the apoptosis induced by the aberrant Notch3 expression in tumour vasculature. We thus present Notch3 as a dependence receptor inducing endothelial cell death while this pro-apoptotic activity is blocked by Jagged-1. Along this line, using Notch3 mutant mice, we demonstrate that tumour growth and angiogenesis are increased when Notch3 is silenced in the stroma. Consequently, we show that the well-documented anti-tumour effect mediated by γ-secretase inhibition is at least in part dependent on the apoptosis triggered by Notch3 in endothelial cells. PMID:28719575

  13. Avicenna's Canon of Medicine and modern urology: part II: bladder calculi.

    PubMed

    Madineh, Sayed Mohammad Ali

    2009-01-01

    In the previous issue of the Urology Journal, a comparison of Avicenna's Canon of Medicine with modern urologic findings was done in part I of this article, addressing bladder anatomy and physiology and bladder calculi. In part II of this review, the remaining chapters of the Canon of Medicine on bladder calculi are reviewed. Avicenna points to perineal urethrostomy (perineostomy), which is today performed as the last therapeutic line or as a temporary remedy before surgical treatment. He also describes surgery via transperineal route and warns the surgeon of the proximity of vasa deferentia, prostate gland, and neurovascular bundle and their exposure in this position. Usage of grasping forceps for removal of bladder calculus and emphasis on removing all calculus fragments are the interesting points of this chapter. Avicenna explains a technique similar to the use of a Babcock forceps for prevention of calculus migration. Complications of bladder calculus surgery and cystostomy are also addressed with scientific precision in the Canon. It is noteworthy that 8 centuries before Fournier described necrotizing fasciitis in male genitalia, Avicenna had described Fournier gangrene in his book.

  14. Enabling grand-canonical Monte Carlo: extending the flexibility of GROMACS through the GromPy python interface module.

    PubMed

    Pool, René; Heringa, Jaap; Hoefling, Martin; Schulz, Roland; Smith, Jeremy C; Feenstra, K Anton

    2012-05-05

    We report on a python interface to the GROMACS molecular simulation package, GromPy (available at https://github.com/GromPy). This application programming interface (API) uses the ctypes python module that allows function calls to shared libraries, for example, written in C. To the best of our knowledge, this is the first reported interface to the GROMACS library that uses direct library calls. GromPy can be used for extending the current GROMACS simulation and analysis modes. In this work, we demonstrate that the interface enables hybrid Monte-Carlo/molecular dynamics (MD) simulations in the grand-canonical ensemble, a simulation mode that is currently not implemented in GROMACS. For this application, the interplay between GromPy and GROMACS requires only minor modifications of the GROMACS source code, not affecting the operation, efficiency, and performance of the GROMACS applications. We validate the grand-canonical application against MD in the canonical ensemble by comparison of equations of state. The results of the grand-canonical simulations are in complete agreement with MD in the canonical ensemble. The python overhead of the grand-canonical scheme is only minimal. Copyright © 2012 Wiley Periodicals, Inc.

  15. Validation of the Portuguese DSM-IV-MR-J.

    PubMed

    Calado, Filipa; Alexandre, Joana; Griffiths, Mark D

    2016-01-01

    Youth problem gambling is viewed as an emergent public health issue in many countries, and is also an emerging area of public concern in Portugal. However, there is currently no Portuguese instrument that focuses specifically on the measurement of problem gambling among young people. Consequently, the present study aimed to validate the DSM-IV-MR-J for use among Portuguese adolescents and to examine its' psychometric properties. A cross-cultural adaption of this instrument to the Portuguese language was performed using the translation and back translation method. The final version of the instrument was administered to 753 Portuguese high school and first year college students. The findings revealed an acceptable internal reliability and replicated the one-factor structure of this scale. Based on these findings, the Portuguese DSM-IV-MR-J appears to be a valid and reliable instrument, and provides a much needed psychometric tool for the development of more research on youth gambling in Portugal.

  16. New approach to canonical partition functions computation in Nf=2 lattice QCD at finite baryon density

    NASA Astrophysics Data System (ADS)

    Bornyakov, V. G.; Boyda, D. L.; Goy, V. A.; Molochkov, A. V.; Nakamura, Atsushi; Nikolaev, A. A.; Zakharov, V. I.

    2017-05-01

    We propose and test a new approach to computation of canonical partition functions in lattice QCD at finite density. We suggest a few steps procedure. We first compute numerically the quark number density for imaginary chemical potential i μq I . Then we restore the grand canonical partition function for imaginary chemical potential using the fitting procedure for the quark number density. Finally we compute the canonical partition functions using high precision numerical Fourier transformation. Additionally we compute the canonical partition functions using the known method of the hopping parameter expansion and compare results obtained by two methods in the deconfining as well as in the confining phases. The agreement between two methods indicates the validity of the new method. Our numerical results are obtained in two flavor lattice QCD with clover improved Wilson fermions.

  17. Application of Canonical Effective Methods to Background-Independent Theories

    NASA Astrophysics Data System (ADS)

    Buyukcam, Umut

    Effective formalisms play an important role in analyzing phenomena above some given length scale when complete theories are not accessible. In diverse exotic but physically important cases, the usual path-integral techniques used in a standard Quantum Field Theory approach seldom serve as adequate tools. This thesis exposes a new effective method for quantum systems, called the Canonical Effective Method, which owns particularly wide applicability in backgroundindependent theories as in the case of gravitational phenomena. The central purpose of this work is to employ these techniques to obtain semi-classical dynamics from canonical quantum gravity theories. Application to non-associative quantum mechanics is developed and testable results are obtained. Types of non-associative algebras relevant for magnetic-monopole systems are discussed. Possible modifications of hypersurface deformation algebra and the emergence of effective space-times are presented. iii.

  18. TRUMP; transient and steady state temperature distribution. [IBM360,370; CDC7600; FORTRAN IV (95%) and BAL (5%) (IBM); FORTRAN IV (CDC)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Elrod, D.C.; Turner, W.D.

    TRUMP solves a general nonlinear parabolic partial differential equation describing flow in various kinds of potential fields, such as fields of temperature, pressure, or electricity and magnetism; simultaneously, it will solve two additional equations representing, in thermal problems, heat production by decomposition of two reactants having rate constants with a general Arrhenius temperature dependence. Steady-state and transient flow in one, two, or three dimensions are considered in geometrical configurations having simple or complex shapes and structures. Problem parameters may vary with spatial position, time, or primary dependent variables--temperature, pressure, or field strength. Initial conditions may vary with spatial position, andmore » among the criteria that may be specified for ending a problem are upper and lower limits on the size of the primary dependent variable, upper limits on the problem time or on the number of time-steps or on the computer time, and attainment of steady state.IBM360,370;CDC7600; FORTRAN IV (95%) and BAL (5%) (IBM); FORTRAN IV (CDC); OS/360 (IBM360), OS/370 (IBM370), SCOPE 2.1.5 (CDC7600); As dimensioned, the program requires 400K bytes of storage on an IBM370 and 145,100 (octal) words on a CDC7600.« less

  19. Dipeptidyl peptidase IV activity and/or structure homologs: Contributing factors in the pathogenesis of rheumatoid arthritis?

    PubMed Central

    Sedo, Aleksi; Duke-Cohan, Jonathan S; Balaziova, Eva; Sedova, Liliana R

    2005-01-01

    Several of the proinflammatory peptides involved in rheumatoid arthritis pathogenesis, including peptides induced downstream of tumor necrosis factor-α as well as the monocyte/T cell-attracting chemokines RANTES and stromal cell-derived factor (SDF)-1α and the neuropeptides vasoactive intestinal peptide (VIP) and substance P, have their biological half-lives controlled by dipeptidyl peptidase IV (DPPIV). Proteolysis by DPPIV regulates not only the half-life but also receptor preference and downstream signaling. In this article, we examine the role of DPPIV homologs, including CD26, the canonical DPPIV, and their substrates in the pathogenesis of rheumatoid arthritis. The differing specific activities of the DPPIV family members and their differential inhibitor response provide new insights into therapeutic design. PMID:16277701

  20. Test Review: Advanced Clinical Solutions for WAIS-IV and WMS-IV

    ERIC Educational Resources Information Center

    Chu, Yiting; Lai, Mark H. C.; Xu, Yining; Zhou, Yuanyuan

    2012-01-01

    The authors review the "Advanced Clinical Solutions for WAIS-IV and WMS-IV". The "Advanced Clinical Solutions (ACS) for the Wechsler Adult Intelligence Scale-Fourth Edition" (WAIS-IV; Wechsler, 2008) and the "Wechsler Memory Scale-Fourth Edition" (WMS-IV; Wechsler, 2009) was published by Pearson in 2009. It is a…

  1. Connecting the Canon to Current Young Adult Literature

    ERIC Educational Resources Information Center

    Rybakova, Katie; Roccanti, Rikki

    2016-01-01

    In this article we discuss the respective roles of young adult literature and literary texts in the secondary level English Language Arts classroom and explore the connections that can be made between popular young adult books and the traditional canon. We provide examples showing how young adult literature bestsellers such as "The Book…

  2. The Canon, the Web, and the Long Tail

    ERIC Educational Resources Information Center

    Sanderhoff, Merete

    2017-01-01

    This article argues that releasing images of artworks into the public domain creates a new possibility for the public to challenge the canon or create their own, based on access to previously inaccessible images. Through the dissemination of openly licensed artworks across the Internet, museums can support the public in expanding their engagement…

  3. The canonical way to make a heart: β-catenin and plakoglobin in heart development and remodeling.

    PubMed

    Piven, Oksana O; Winata, Cecilia L

    2017-12-01

    The main mediator of the canonical Wnt pathway, β-catenin, is a major effector of embryonic development, postnatal tissue homeostasis, and adult tissue regeneration. The requirement for β-catenin in cardiogenesis and embryogenesis has been well established. However, many questions regarding the molecular mechanisms by which β-catenin and canonical Wnt signaling regulate these developmental processes remain unanswered. An interesting question that emerged from our studies concerns how β-catenin signaling is modulated through interaction with other factors. Recent experimental data implicate new players in canonical Wnt signaling, particularly those which modulate β-catenin function in many its biological processes, including cardiogenesis. One of the interesting candidates is plakoglobin, a little-studied member of the catenin family which shares several mechanistic and functional features with its close relative, β-catenin. Here we have focused on the function of β-catenin in cardiogenesis. We also summarize findings on plakoglobin signaling function and discuss possible interplays between β-catenin and plakoglobin in the regulation of embryonic heart development. Impact statement Heart development, function, and remodeling are complex processes orchestrated by multiple signaling networks. This review examines our current knowledge of the role of canonical Wnt signaling in cardiogenesis and heart remodeling, focusing primarily on the mechanistic action of its effector β-catenin. We summarize the generally accepted understanding of the field based on experimental in vitro and in vivo data, and address unresolved questions in the field, specifically relating to the role of canonical Wnt signaling in heart maturation and regeneration. What are the modulators of canonical Wnt, and particularly what are the potential roles of plakoglobin, a close relative of β-catenin, in regulating Wnt signaling?Answers to these questions will enhance our understanding of the

  4. WNT16 antagonises excessive canonical WNT activation and protects cartilage in osteoarthritis.

    PubMed

    Nalesso, Giovanna; Thomas, Bethan Lynne; Sherwood, Joanna Claire; Yu, Jing; Addimanda, Olga; Eldridge, Suzanne Elizabeth; Thorup, Anne-Sophie; Dale, Leslie; Schett, Georg; Zwerina, Jochen; Eltawil, Noha; Pitzalis, Costantino; Dell'Accio, Francesco

    2017-01-01

    Both excessive and insufficient activation of WNT signalling results in cartilage breakdown and osteoarthritis. WNT16 is upregulated in the articular cartilage following injury and in osteoarthritis. Here, we investigate the function of WNT16 in osteoarthritis and the downstream molecular mechanisms. Osteoarthritis was induced by destabilisation of the medial meniscus in wild-type and WNT16-deficient mice. Molecular mechanisms and downstream effects were studied in vitro and in vivo in primary cartilage progenitor cells and primary chondrocytes. The pathway downstream of WNT16 was studied in primary chondrocytes and using the axis duplication assay in Xenopus. WNT16-deficient mice developed more severe osteoarthritis with reduced expression of lubricin and increased chondrocyte apoptosis. WNT16 supported the phenotype of cartilage superficial-zone progenitor cells and lubricin expression. Increased osteoarthritis in WNT16-deficient mice was associated with excessive activation of canonical WNT signalling. In vitro, high doses of WNT16 weakly activated canonical WNT signalling, but, in co-stimulation experiments, WNT16 reduced the capacity of WNT3a to activate the canonical WNT pathway. In vivo, WNT16 rescued the WNT8-induced primary axis duplication in Xenopus embryos. In osteoarthritis, WNT16 maintains a balanced canonical WNT signalling and prevents detrimental excessive activation, thereby supporting the homeostasis of progenitor cells. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  5. Grand canonical electronic density-functional theory: Algorithms and applications to electrochemistry.

    PubMed

    Sundararaman, Ravishankar; Goddard, William A; Arias, Tomas A

    2017-03-21

    First-principles calculations combining density-functional theory and continuum solvation models enable realistic theoretical modeling and design of electrochemical systems. When a reaction proceeds in such systems, the number of electrons in the portion of the system treated quantum mechanically changes continuously, with a balancing charge appearing in the continuum electrolyte. A grand-canonical ensemble of electrons at a chemical potential set by the electrode potential is therefore the ideal description of such systems that directly mimics the experimental condition. We present two distinct algorithms: a self-consistent field method and a direct variational free energy minimization method using auxiliary Hamiltonians (GC-AuxH), to solve the Kohn-Sham equations of electronic density-functional theory directly in the grand canonical ensemble at fixed potential. Both methods substantially improve performance compared to a sequence of conventional fixed-number calculations targeting the desired potential, with the GC-AuxH method additionally exhibiting reliable and smooth exponential convergence of the grand free energy. Finally, we apply grand-canonical density-functional theory to the under-potential deposition of copper on platinum from chloride-containing electrolytes and show that chloride desorption, not partial copper monolayer formation, is responsible for the second voltammetric peak.

  6. Length-independent structural similarities enrich the antibody CDR canonical class model.

    PubMed

    Nowak, Jaroslaw; Baker, Terry; Georges, Guy; Kelm, Sebastian; Klostermann, Stefan; Shi, Jiye; Sridharan, Sudharsan; Deane, Charlotte M

    2016-01-01

    Complementarity-determining regions (CDRs) are antibody loops that make up the antigen binding site. Here, we show that all CDR types have structurally similar loops of different lengths. Based on these findings, we created length-independent canonical classes for the non-H3 CDRs. Our length variable structural clusters show strong sequence patterns suggesting either that they evolved from the same original structure or result from some form of convergence. We find that our length-independent method not only clusters a larger number of CDRs, but also predicts canonical class from sequence better than the standard length-dependent approach. To demonstrate the usefulness of our findings, we predicted cluster membership of CDR-L3 sequences from 3 next-generation sequencing datasets of the antibody repertoire (over 1,000,000 sequences). Using the length-independent clusters, we can structurally classify an additional 135,000 sequences, which represents a ∼20% improvement over the standard approach. This suggests that our length-independent canonical classes might be a highly prevalent feature of antibody space, and could substantially improve our ability to accurately predict the structure of novel CDRs identified by next-generation sequencing.

  7. Vocal patterns in infants with autism spectrum disorder: canonical babbling status and vocalization frequency.

    PubMed

    Patten, Elena; Belardi, Katie; Baranek, Grace T; Watson, Linda R; Labban, Jeffrey D; Oller, D Kimbrough

    2014-10-01

    Canonical babbling is a critical milestone for speech development and is usually well in place by 10 months. The possibility that infants with autism spectrum disorder (ASD) show late onset of canonical babbling has so far eluded evaluation. Rate of vocalization or "volubility" has also been suggested as possibly aberrant in infants with ASD. We conducted a retrospective video study examining vocalizations of 37 infants at 9-12 and 15-18 months. Twenty-three of the 37 infants were later diagnosed with ASD and indeed produced low rates of canonical babbling and low volubility by comparison with the 14 typically developing infants. The study thus supports suggestions that very early vocal patterns may prove to be a useful component of early screening and diagnosis of ASD.

  8. Exact solution for an optimal impermeable parachute problem

    NASA Astrophysics Data System (ADS)

    Lupu, Mircea; Scheiber, Ernest

    2002-10-01

    In the paper there are solved direct and inverse boundary problems and analytical solutions are obtained for optimization problems in the case of some nonlinear integral operators. It is modeled the plane potential flow of an inviscid, incompressible and nonlimited fluid jet, witch encounters a symmetrical, curvilinear obstacle--the deflector of maximal drag. There are derived integral singular equations, for direct and inverse problems and the movement in the auxiliary canonical half-plane is obtained. Next, the optimization problem is solved in an analytical manner. The design of the optimal airfoil is performed and finally, numerical computations concerning the drag coefficient and other geometrical and aerodynamical parameters are carried out. This model corresponds to the Helmholtz impermeable parachute problem.

  9. Structural characterization of ribosome recruitment and translocation by type IV IRES.

    PubMed

    Murray, Jason; Savva, Christos G; Shin, Byung-Sik; Dever, Thomas E; Ramakrishnan, V; Fernández, Israel S

    2016-05-09

    Viral mRNA sequences with a type IV IRES are able to initiate translation without any host initiation factors. Initial recruitment of the small ribosomal subunit as well as two translocation steps before the first peptidyl transfer are essential for the initiation of translation by these mRNAs. Using electron cryomicroscopy (cryo-EM) we have structurally characterized at high resolution how the Cricket Paralysis Virus Internal Ribosomal Entry Site (CrPV-IRES) binds the small ribosomal subunit (40S) and the translocation intermediate stabilized by elongation factor 2 (eEF2). The CrPV-IRES restricts tvhe otherwise flexible 40S head to a conformation compatible with binding the large ribosomal subunit (60S). Once the 60S is recruited, the binary CrPV-IRES/80S complex oscillates between canonical and rotated states (Fernández et al., 2014; Koh et al., 2014), as seen for pre-translocation complexes with tRNAs. Elongation factor eEF2 with a GTP analog stabilizes the ribosome-IRES complex in a rotated state with an extra ~3 degrees of rotation. Key residues in domain IV of eEF2 interact with pseudoknot I (PKI) of the CrPV-IRES stabilizing it in a conformation reminiscent of a hybrid tRNA state. The structure explains how diphthamide, a eukaryotic and archaeal specific post-translational modification of a histidine residue of eEF2, is involved in translocation.

  10. Structural characterization of ribosome recruitment and translocation by type IV IRES

    PubMed Central

    Murray, Jason; Savva, Christos G; Shin, Byung-Sik; Dever, Thomas E; Ramakrishnan, V; Fernández, Israel S

    2016-01-01

    Viral mRNA sequences with a type IV IRES are able to initiate translation without any host initiation factors. Initial recruitment of the small ribosomal subunit as well as two translocation steps before the first peptidyl transfer are essential for the initiation of translation by these mRNAs. Using electron cryomicroscopy (cryo-EM) we have structurally characterized at high resolution how the Cricket Paralysis Virus Internal Ribosomal Entry Site (CrPV-IRES) binds the small ribosomal subunit (40S) and the translocation intermediate stabilized by elongation factor 2 (eEF2). The CrPV-IRES restricts the otherwise flexible 40S head to a conformation compatible with binding the large ribosomal subunit (60S). Once the 60S is recruited, the binary CrPV-IRES/80S complex oscillates between canonical and rotated states (Fernández et al., 2014; Koh et al., 2014), as seen for pre-translocation complexes with tRNAs. Elongation factor eEF2 with a GTP analog stabilizes the ribosome-IRES complex in a rotated state with an extra ~3 degrees of rotation. Key residues in domain IV of eEF2 interact with pseudoknot I (PKI) of the CrPV-IRES stabilizing it in a conformation reminiscent of a hybrid tRNA state. The structure explains how diphthamide, a eukaryotic and archaeal specific post-translational modification of a histidine residue of eEF2, is involved in translocation. DOI: http://dx.doi.org/10.7554/eLife.13567.001 PMID:27159451

  11. Canonical transformation path to gauge theories of gravity

    NASA Astrophysics Data System (ADS)

    Struckmeier, J.; Muench, J.; Vasak, D.; Kirsch, J.; Hanauske, M.; Stoecker, H.

    2017-06-01

    In this paper, the generic part of the gauge theory of gravity is derived, based merely on the action principle and on the general principle of relativity. We apply the canonical transformation framework to formulate geometrodynamics as a gauge theory. The starting point of our paper is constituted by the general De Donder-Weyl Hamiltonian of a system of scalar and vector fields, which is supposed to be form-invariant under (global) Lorentz transformations. Following the reasoning of gauge theories, the corresponding locally form-invariant system is worked out by means of canonical transformations. The canonical transformation approach ensures by construction that the form of the action functional is maintained. We thus encounter amended Hamiltonian systems which are form-invariant under arbitrary spacetime transformations. This amended system complies with the general principle of relativity and describes both, the dynamics of the given physical system's fields and their coupling to those quantities which describe the dynamics of the spacetime geometry. In this way, it is unambiguously determined how spin-0 and spin-1 fields couple to the dynamics of spacetime. A term that describes the dynamics of the "free" gauge fields must finally be added to the amended Hamiltonian, as common to all gauge theories, to allow for a dynamic spacetime geometry. The choice of this "dynamics" Hamiltonian is outside of the scope of gauge theory as presented in this paper. It accounts for the remaining indefiniteness of any gauge theory of gravity and must be chosen "by hand" on the basis of physical reasoning. The final Hamiltonian of the gauge theory of gravity is shown to be at least quadratic in the conjugate momenta of the gauge fields—this is beyond the Einstein-Hilbert theory of general relativity.

  12. Contraction of high eccentricity satellite orbits using uniformly regular KS canonical elements with oblate diurnally varying atmosphere.

    NASA Astrophysics Data System (ADS)

    Raj, Xavier James

    2016-07-01

    Accurate orbit prediction of an artificial satellite under the influence of air drag is one of the most difficult and untraceable problem in orbital dynamics. The orbital decay of these satellites is mainly controlled by the atmospheric drag effects. The effects of the atmosphere are difficult to determine, since the atmospheric density undergoes large fluctuations. The classical Newtonian equations of motion, which is non linear is not suitable for long-term integration. Many transformations have emerged in the literature to stabilize the equations of motion either to reduce the accumulation of local numerical errors or allowing the use of large integration step sizes, or both in the transformed space. One such transformation is known as KS transformation by Kustaanheimo and Stiefel, who regularized the nonlinear Kepler equations of motion and reduced it into linear differential equations of a harmonic oscillator of constant frequency. The method of KS total energy element equations has been found to be a very powerful method for obtaining numerical as well as analytical solution with respect to any type of perturbing forces, as the equations are less sensitive to round off and truncation errors. The uniformly regular KS canonical equations are a particular canonical form of the KS differential equations, where all the ten KS Canonical elements αi and βi are constant for unperturbed motion. These equations permit the uniform formulation of the basic laws of elliptic, parabolic and hyperbolic motion. Using these equations, developed analytical solution for short term orbit predictions with respect to Earth's zonal harmonic terms J2, J3, J4. Further, these equations were utilized to include the canonical forces and analytical theories with air drag were developed for low eccentricity orbits (e < 0.2) with different atmospheric models. Using uniformly regular KS canonical elements developed analytical theory for high eccentricity (e > 0.2) orbits by assuming the

  13. Gossypol induces pyroptosis in mouse macrophages via a non-canonical inflammasome pathway

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lin, Qiu-Ru; Li, Chen-Guang; Zha, Qing-Bing

    Gossypol, a polyphenolic compound isolated from cottonseeds, has been reported to possess many pharmacological activities, but whether it can influence inflammasome activation remains unclear. In this study, we found that in mouse macrophages, gossypol induced cell death characterized by rapid membrane rupture and robust release of HMGB1 and pro-caspase-11 comparable to ATP treatment, suggesting an induction of pyroptotic cell death. Unlike ATP, gossypol induced much low levels of mature interleukin-1β (IL-1β) secretion from mouse peritoneal macrophages primed with LPS, although it caused pro-IL-1β release similar to that of ATP. Consistent with this, activated caspase-1 responsible for pro-IL-1β maturation was undetectablemore » in gossypol-treated peritoneal macrophages. Besides, RAW 264.7 cells lacking ASC expression and caspase-1 activation also underwent pyroptotic cell death upon gossypol treatment. In further support of pyroptosis induction, both pan-caspase inhibitor and caspase-1 subfamily inhibitor, but not caspase-3 inhibitor, could sharply suppress gossypol-induced cell death. Other canonical pyroptotic inhibitors, including potassium chloride and N-acetyl-L-cysteine, could suppress ATP-induced pyroptosis but failed to inhibit or even enhanced gossypol-induced cell death, whereas nonspecific pore-formation inhibitor glycine could attenuate this process, suggesting involvement of a non-canonical pathway. Of note, gossypol treatment eliminated thioglycollate-induced macrophages in the peritoneal cavity with recruitment of other leukocytes. Moreover, gossypol administration markedly decreased the survival of mice in a bacterial sepsis model. Collectively, these results suggested that gossypol induced pyroptosis in mouse macrophages via a non-canonical inflammasome pathway, which raises a concern for its in vivo cytotoxicity to macrophages. - Highlights: • Gossypol induces pyroptosis in mouse peritoneal and RAW 264.7 macrophages. • In LPS

  14. Renal hypodysplasia associates with a WNT4 variant that causes aberrant canonical WNT signaling.

    PubMed

    Vivante, Asaf; Mark-Danieli, Michal; Davidovits, Miriam; Harari-Steinberg, Orit; Omer, Dorit; Gnatek, Yehudit; Cleper, Roxana; Landau, Daniel; Kovalski, Yael; Weissman, Irit; Eisenstein, Israel; Soudack, Michalle; Wolf, Haike Reznik; Issler, Naomi; Lotan, Danny; Anikster, Yair; Dekel, Benjamin

    2013-03-01

    Abnormal differentiation of the renal stem/progenitor pool into kidney tissue can lead to renal hypodysplasia (RHD), but the underlying causes of RHD are not well understood. In this multicenter study, we identified 20 Israeli pedigrees with isolated familial, nonsyndromic RHD and screened for mutations in candidate genes involved in kidney development, including PAX2, HNF1B, EYA1, SIX1, SIX2, SALL1, GDNF, WNT4, and WT1. In addition to previously reported RHD-causing genes, we found that two affected brothers were heterozygous for a missense variant in the WNT4 gene. Functional analysis of this variant revealed both antagonistic and agonistic canonical WNT stimuli, dependent on cell type. In HEK293 cells, WNT4 inhibited WNT3A induced canonical activation, and the WNT4 variant significantly enhanced this inhibition of the canonical WNT pathway. In contrast, in primary cultures of human fetal kidney cells, which maintain WNT activation and more closely represent WNT signaling in renal progenitors during nephrogenesis, this mutation caused significant loss of function, resulting in diminished canonical WNT/β-catenin signaling. In conclusion, heterozygous WNT4 variants are likely to play a causative role in renal hypodysplasia.

  15. Renal Hypodysplasia Associates with a Wnt4 Variant that Causes Aberrant Canonical Wnt Signaling

    PubMed Central

    Vivante, Asaf; Mark-Danieli, Michal; Davidovits, Miriam; Harari-Steinberg, Orit; Omer, Dorit; Gnatek, Yehudit; Cleper, Roxana; Landau, Daniel; Kovalski, Yael; Weissman, Irit; Eisenstein, Israel; Soudack, Michalle; Wolf, Haike Reznik; Issler, Naomi; Lotan, Danny; Anikster, Yair

    2013-01-01

    Abnormal differentiation of the renal stem/progenitor pool into kidney tissue can lead to renal hypodysplasia (RHD), but the underlying causes of RHD are not well understood. In this multicenter study, we identified 20 Israeli pedigrees with isolated familial, nonsyndromic RHD and screened for mutations in candidate genes involved in kidney development, including PAX2, HNF1B, EYA1, SIX1, SIX2, SALL1, GDNF, WNT4, and WT1. In addition to previously reported RHD-causing genes, we found that two affected brothers were heterozygous for a missense variant in the WNT4 gene. Functional analysis of this variant revealed both antagonistic and agonistic canonical WNT stimuli, dependent on cell type. In HEK293 cells, WNT4 inhibited WNT3A induced canonical activation, and the WNT4 variant significantly enhanced this inhibition of the canonical WNT pathway. In contrast, in primary cultures of human fetal kidney cells, which maintain WNT activation and more closely represent WNT signaling in renal progenitors during nephrogenesis, this mutation caused significant loss of function, resulting in diminished canonical WNT/β-catenin signaling. In conclusion, heterozygous WNT4 variants are likely to play a causative role in renal hypodysplasia. PMID:23520208

  16. Non-canonical microRNAs miR-320 and miR-702 promote proliferation in Dgcr8-deficient embryonic stem cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kim, Byeong-Moo; Department of Medicine, Harvard Medical School, Boston, MA 02115; Choi, Michael Y., E-mail: mchoi@partners.org

    2012-09-21

    Highlights: Black-Right-Pointing-Pointer Embryonic stem cells (ESCs) lacking non-canonical miRNAs proliferate slower. Black-Right-Pointing-Pointer miR-320 and miR-702 are two non-canonical miRNAs expressed in ESCs. Black-Right-Pointing-Pointer miR-320 and miR-702 promote proliferation of Dgcr8-deficient ESCs. Black-Right-Pointing-Pointer miR-320 targets p57 and helps to release Dgcr8-deficient ESCs from G1 arrest. Black-Right-Pointing-Pointer miR-702 targets p21 and helps to release Dgcr8-deficient ESCs from G1 arrest. -- Abstract: MicroRNAs are known to contribute significantly to stem cell phenotype by post-transcriptionally regulating gene expression. Most of our knowledge of microRNAs comes from the study of canonical microRNAs that require two sequential cleavages by the Drosha/Dgcr8 heterodimer and Dicer to generatemore » mature products. In contrast, non-canonical microRNAs bypass the cleavage by the Drosha/Dgcr8 heterodimer within the nucleus but still require cytoplasmic cleavage by Dicer. The function of non-canonical microRNAs in embryonic stem cells (ESCs) remains obscure. It has been hypothesized that non-canonical microRNAs have important roles in ESCs based upon the phenotypes of ESC lines that lack these specific classes of microRNAs; Dicer-deficient ESCs lacking both canonical and non-canonical microRNAs have much more severe proliferation defect than Dgcr8-deficient ESCs lacking only canonical microRNAs. Using these cell lines, we identified two non-canonical microRNAs, miR-320 and miR-702, that promote proliferation of Dgcr8-deficient ESCs by releasing them from G1 arrest. This is accomplished by targeting the 3 Prime -untranslated regions of the cell cycle inhibitors p57 and p21 and thereby inhibiting their expression. This is the first report of the crucial role of non-canonical microRNAs in ESCs.« less

  17. Vocal patterns in infants with Autism Spectrum Disorder: Canonical babbling status and vocalization frequency

    PubMed Central

    Patten, Elena; Belardi, Katie; Baranek, Grace T.; Watson, Linda R.; Labban, Jeffrey D.; Oller, D. Kimbrough

    2014-01-01

    Canonical babbling is a critical milestone for speech development and is usually well in place by 10 months. The possibility that infants with ASD show late onset of canonical babbling has so far eluded evaluation. Rate of vocalization or “volubility” has also been suggested as possibly aberrant in infants with ASD. We conducted a retrospective video study examining vocalizations of 37 infants at 9–12 and 15–18 months. Twenty-three of the 37 infants were later diagnosed with ASD and indeed produced low rates of canonical babbling and low volubility by comparison with the 14 typically developing infants. The study thus supports suggestions that very early vocal patterns may prove to be a useful component of early screening and diagnosis of ASD. PMID:24482292

  18. Carbon-14 decay as a source of non-canonical bases in DNA.

    PubMed

    Sassi, Michel; Carter, Damien J; Uberuaga, Blas P; Stanek, Chris R; Marks, Nigel A

    2014-01-01

    Significant experimental effort has been applied to study radioactive beta-decay in biological systems. Atomic-scale knowledge of this transmutation process is lacking due to the absence of computer simulations. Carbon-14 is an important beta-emitter, being ubiquitous in the environment and an intrinsic part of the genetic code. Over a lifetime, around 50 billion (14)C decays occur within human DNA. We apply ab initio molecular dynamics to quantify (14)C-induced bond rupture in a variety of organic molecules, including DNA base pairs. We show that double bonds and ring structures confer radiation resistance. These features, present in the canonical bases of the DNA, enhance their resistance to (14)C-induced bond-breaking. In contrast, the sugar group of the DNA and RNA backbone is vulnerable to single-strand breaking. We also show that Carbon-14 decay provides a mechanism for creating mutagenic wobble-type mispairs. The observation that DNA has a resistance to natural radioactivity has not previously been recognized. We show that (14)C decay can be a source for generating non-canonical bases. Our findings raise questions such as how the genetic apparatus deals with the appearance of an extra nitrogen in the canonical bases. It is not obvious whether or not the DNA repair mechanism detects this modification nor how DNA replication is affected by a non-canonical nucleobase. Accordingly, (14)C may prove to be a source of genetic alteration that is impossible to avoid due to the universal presence of radiocarbon in the environment. © 2013.

  19. Cable Connected Spinning Spacecraft, 1. the Canonical Equations, 2. Urban Mass Transportation, 3

    NASA Technical Reports Server (NTRS)

    Sitchin, A.

    1972-01-01

    Work on the dynamics of cable-connected spinning spacecraft was completed by formulating the equations of motion by both the canonical equations and Lagrange's equations and programming them for numerical solution on a digital computer. These energy-based formulations will permit future addition of the effect of cable mass. Comparative runs indicate that the canonical formulation requires less computer time. Available literature on urban mass transportation was surveyed. Areas of the private rapid transit concept of urban transportation are also studied.

  20. Incidence Rate of Canonical vs. Derived Medical Terminology in Natural Language.

    PubMed

    Topac, Vasile; Jurcau, Daniel-Alexandru; Stoicu-Tivadar, Vasile

    2015-01-01

    Medical terminology appears in the natural language in multiple forms: canonical, derived or inflected form. This research presents an analysis of the form in which medical terminology appears in Romanian and English language. The sources of medical language used for the study are web pages presenting medical information for patients and other lay users. The results show that, in English, medical terminology tends to appear more in canonical form while, in the case of Romanian, it is the opposite. This paper also presents the service that was created to perform this analysis. This tool is available for the general public, and it is designed to be easily extensible, allowing the addition of other languages.

  1. RNA Pol IV and V in Gene Silencing: Rebel Polymerases Evolving Away From Pol II’s Rules

    PubMed Central

    Zhou, Ming; Law, Julie A.

    2015-01-01

    Noncoding RNAs regulate gene expression at both the transcriptional and post-transcriptional levels, and play critical roles in development, imprinting and the maintenance of genome integrity in eukaryotic organisms [1–3]. Therefore, it is important to understand how the production of such RNAs are controlled. In addition to the three canonical DNA dependent RNA polymerases (Pol) Pol I, II and III, two non-redundant plant-specific RNA polymerases, Pol IV and Pol V, have been identified and shown to generate noncoding RNAs that are required for transcriptional gene silencing via the RNA-directed DNA methylation (RdDM) pathway. Thus, somewhat paradoxically, transcription is required for gene silencing. This paradox extends beyond plants, as silencing pathways in yeast, fungi, flies, worms, and mammals also require transcriptional machinery [4,5]. As plants have evolved specialized RNA polymerases to carry out gene silencing in a manner that is separate from the essential roles of Pol II, their characterization offers unique insight into how RNA polymerases facilitate gene silencing. In this review, we focus on the mechanisms of Pol IV and Pol V function, including their compositions, their transcripts, and their modes of recruitment to chromatin. PMID:26344361

  2. Grand canonical electronic density-functional theory: Algorithms and applications to electrochemistry

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sundararaman, Ravishankar; Goddard, III, William A.; Arias, Tomas A.

    First-principles calculations combining density-functional theory and continuum solvation models enable realistic theoretical modeling and design of electrochemical systems. When a reaction proceeds in such systems, the number of electrons in the portion of the system treated quantum mechanically changes continuously, with a balancing charge appearing in the continuum electrolyte. A grand-canonical ensemble of electrons at a chemical potential set by the electrode potential is therefore the ideal description of such systems that directly mimics the experimental condition. We present two distinct algorithms: a self-consistent field method and a direct variational free energy minimization method using auxiliary Hamiltonians (GC-AuxH), to solvemore » the Kohn-Sham equations of electronic density-functional theory directly in the grand canonical ensemble at fixed potential. Both methods substantially improve performance compared to a sequence of conventional fixed-number calculations targeting the desired potential, with the GC-AuxH method additionally exhibiting reliable and smooth exponential convergence of the grand free energy. Lastly, we apply grand-canonical density-functional theory to the under-potential deposition of copper on platinum from chloride-containing electrolytes and show that chloride desorption, not partial copper monolayer formation, is responsible for the second voltammetric peak.« less

  3. Stable micron-scale holes are a general feature of canonical holins

    PubMed Central

    Savva, Christos G.; Dewey, Jill S.; Moussa, Samir H.; To, Kam H.; Holzenburg, Andreas; Young, Ry

    2014-01-01

    Summary At a programmed time in phage infection cycles, canonical holins suddenly trigger to cause lethal damage to the cytoplasmic membrane, resulting in the cessation of respiration and the non-specific release of pre-folded, fully active endolysins to the periplasm. For the paradigm holin S105 of lambda, triggering is correlated with the formation of micron-scale membrane holes, visible as interruptions in the bilayer in cryo-electron microscopic images and tomographic reconstructions. Here we report that the size distribution of the holes is stable for long periods after triggering. Moreover, early triggering caused by an early lysis allele of S105 formed approximately the same number of holes, but the lesions were significantly smaller. In contrast, early triggering prematurely induced by energy poisons resulted in many fewer visible holes, consistent with previous sizing studies. Importantly, the unrelated canonical holins P2 Y and T4 T were found to cause the formation of holes of approximately the same size and number as for lambda. In contrast, no such lesions were visible after triggering of the pinholin S2168. These results generalize the hole formation phenomenon for canonical holins. A model is presented suggesting the unprecedentedly large size of these holes is related to the timing mechanism. PMID:24164554

  4. Stable micron-scale holes are a general feature of canonical holins.

    PubMed

    Savva, Christos G; Dewey, Jill S; Moussa, Samir H; To, Kam H; Holzenburg, Andreas; Young, Ry

    2014-01-01

    At a programmed time in phage infection cycles, canonical holins suddenly trigger to cause lethal damage to the cytoplasmic membrane, resulting in the cessation of respiration and the non-specific release of pre-folded, fully active endolysins to the periplasm. For the paradigm holin S105 of lambda, triggering is correlated with the formation of micron-scale membrane holes, visible as interruptions in the bilayer in cryo-electron microscopic images and tomographic reconstructions. Here we report that the size distribution of the holes is stable for long periods after triggering. Moreover, early triggering caused by an early lysis allele of S105 formed approximately the same number of holes, but the lesions were significantly smaller. In contrast, early triggering prematurely induced by energy poisons resulted in many fewer visible holes, consistent with previous sizing studies. Importantly, the unrelated canonical holins P2 Y and T4 T were found to cause the formation of holes of approximately the same size and number as for lambda. In contrast, no such lesions were visible after triggering of the pinholin S(21) 68. These results generalize the hole formation phenomenon for canonical holins. A model is presented suggesting the unprecedentedly large size of these holes is related to the timing mechanism. © 2013 John Wiley & Sons Ltd.

  5. Grand canonical electronic density-functional theory: Algorithms and applications to electrochemistry

    DOE PAGES

    Sundararaman, Ravishankar; Goddard, III, William A.; Arias, Tomas A.

    2017-03-16

    First-principles calculations combining density-functional theory and continuum solvation models enable realistic theoretical modeling and design of electrochemical systems. When a reaction proceeds in such systems, the number of electrons in the portion of the system treated quantum mechanically changes continuously, with a balancing charge appearing in the continuum electrolyte. A grand-canonical ensemble of electrons at a chemical potential set by the electrode potential is therefore the ideal description of such systems that directly mimics the experimental condition. We present two distinct algorithms: a self-consistent field method and a direct variational free energy minimization method using auxiliary Hamiltonians (GC-AuxH), to solvemore » the Kohn-Sham equations of electronic density-functional theory directly in the grand canonical ensemble at fixed potential. Both methods substantially improve performance compared to a sequence of conventional fixed-number calculations targeting the desired potential, with the GC-AuxH method additionally exhibiting reliable and smooth exponential convergence of the grand free energy. Lastly, we apply grand-canonical density-functional theory to the under-potential deposition of copper on platinum from chloride-containing electrolytes and show that chloride desorption, not partial copper monolayer formation, is responsible for the second voltammetric peak.« less

  6. The tangled web of non-canonical Wnt signalling in neural migration.

    PubMed

    Clark, Charlotte E J; Nourse, C Cathrin; Cooper, Helen M

    2012-01-01

    In all multicellular animals, successful embryogenesis is dependent on the ability of cells to detect the status of the local environment and respond appropriately. The nature of the extracellular environment is communicated to the intracellular compartment by ligand/receptor interactions at the cell surface. The Wnt canonical and non-canonical signalling pathways are found in the most primitive metazoans, and they play an essential role in the most fundamental developmental processes in all multicellular organisms. Vertebrates have expanded the number of Wnts and Frizzled receptors and have additionally evolved novel Wnt receptor families (Ryk, Ror). The multiplicity of potential interactions between Wnts, their receptors and downstream effectors has exponentially increased the complexity of the signal transduction network. Signalling through each of the Wnt pathways, as well as crosstalk between them, plays a critical role in the establishment of the complex architecture of the vertebrate central nervous system. In this review, we explore the signalling networks triggered by non-canonical Wnt/receptor interactions, focussing on the emerging roles of the non-conventional Wnt receptors Ryk and Ror. We describe the role of these pathways in neural tube formation and axon guidance where Wnt signalling controls tissue polarity, coordinated cell migration and axon guidance via remodelling of the cytoskeleton. Copyright © 2012 S. Karger AG, Basel.

  7. Steady-state global optimization of metabolic non-linear dynamic models through recasting into power-law canonical models

    PubMed Central

    2011-01-01

    Background Design of newly engineered microbial strains for biotechnological purposes would greatly benefit from the development of realistic mathematical models for the processes to be optimized. Such models can then be analyzed and, with the development and application of appropriate optimization techniques, one could identify the modifications that need to be made to the organism in order to achieve the desired biotechnological goal. As appropriate models to perform such an analysis are necessarily non-linear and typically non-convex, finding their global optimum is a challenging task. Canonical modeling techniques, such as Generalized Mass Action (GMA) models based on the power-law formalism, offer a possible solution to this problem because they have a mathematical structure that enables the development of specific algorithms for global optimization. Results Based on the GMA canonical representation, we have developed in previous works a highly efficient optimization algorithm and a set of related strategies for understanding the evolution of adaptive responses in cellular metabolism. Here, we explore the possibility of recasting kinetic non-linear models into an equivalent GMA model, so that global optimization on the recast GMA model can be performed. With this technique, optimization is greatly facilitated and the results are transposable to the original non-linear problem. This procedure is straightforward for a particular class of non-linear models known as Saturable and Cooperative (SC) models that extend the power-law formalism to deal with saturation and cooperativity. Conclusions Our results show that recasting non-linear kinetic models into GMA models is indeed an appropriate strategy that helps overcoming some of the numerical difficulties that arise during the global optimization task. PMID:21867520

  8. Gpr124 controls CNS angiogenesis and blood-brain barrier integrity by promoting ligand-specific canonical wnt signaling.

    PubMed

    Zhou, Yulian; Nathans, Jeremy

    2014-10-27

    Canonical Wnt signaling in endothelial cells (ECs) is required for vascularization of the central nervous system (CNS) and for formation and maintenance of barrier properties unique to CNS vasculature. Gpr124 is an orphan member of the adhesion G protein-coupled receptor family that is expressed in ECs and is essential for CNS angiogenesis and barrier formation via an unknown mechanism. Using canonical Wnt signaling assays in cell culture and genetic loss- and gain-of-function experiments in mice, we show that Gpr124 functions as a coactivator of Wnt7a- and Wnt7b-stimulated canonical Wnt signaling via a Frizzled receptor and Lrp coreceptor and that Gpr124-stimulated signaling functions in concert with Norrin/Frizzled4 signaling to control CNS vascular development. These experiments identify Gpr124 as a ligand-specific coactivator of canonical Wnt signaling.

  9. Analysis of Phoenix Anomalies and IV and V Findings Applied to the GRAIL Mission

    NASA Technical Reports Server (NTRS)

    Larson, Steve

    2012-01-01

    Analysis of patterns in IV&V findings and their correlation with post-launch anomalies allowed GRAIL to make more efficient use of IV&V services . Fewer issues. . Higher fix rate. . Better communication. . Increased volume of potential issues vetted, at lower cost. . Hard to make predictions of post-launch performance based on IV&V findings . Phoenix made sound fix/use as-is decisions . Things that were fixed eliminated some problems, but hard to quantify. . Broad predictive success in one area, but inverse relationship in others.

  10. Relaxation in a two-body Fermi-Pasta-Ulam system in the canonical ensemble

    NASA Astrophysics Data System (ADS)

    Sen, Surajit; Barrett, Tyler

    The study of the dynamics of the Fermi-Pasta-Ulam (FPU) chain remains a challenging problem. Inspired by the recent work of Onorato et al. on thermalization in the FPU system, we report a study of relaxation processes in a two-body FPU system in the canonical ensemble. The studies have been carried out using the Recurrence Relations Method introduced by Zwanzig, Mori, Lee and others. We have obtained exact analytical expressions for the first thirteen levels of the continued fraction representation of the Laplace transformed velocity autocorrelation function of the system. Using simple and reasonable extrapolation schemes and known limits we are able to estimate the relaxation behavior of the oscillators in the two-body FPU system and recover the expected behavior in the harmonic limit. Generalizations of the calculations to larger systems will be discussed.

  11. Extended canonical field theory of matter and space-time

    NASA Astrophysics Data System (ADS)

    Struckmeier, J.; Vasak, D.; matter, H. Stoecker Field theory of; space-time

    2015-11-01

    Any physical theory that follows from an action principle should be invariant in its form under mappings of the reference frame in order to comply with the general principle of relativity. The required form-invariance of the action principle implies that the mapping must constitute a particular extended canonical transformation. In the realm of the covariant Hamiltonian formulation of field theory, the term ``extended'' implies that not only the fields but also the space-time geometry is subject to transformation. A canonical transformation maintains the general form of the action principle by simultaneously defining the appropriate transformation rules for the fields, the conjugate momentum fields, and the transformation rule for the Hamiltonian. Provided that the given system of fields exhibits a particular global symmetry, the associated extended canonical transformation determines an amended Hamiltonian that is form-invariant under the corresponding local symmetry. This will be worked out for a Hamiltonian system of scalar and vector fields that is presupposed to be form-invariant under space-time transformations xμ\\mapsto Xμ with partial Xμ/partial xν=const., hence under global space-time transformations such as the Poincaré transformation. The corresponding amended system that is form-invariant under local space-time transformations partial Xμ/partial xν≠qconst. then describes the coupling of the fields to the space-time geometry and thus yields the dynamics of space-time that is associated with the given physical system. Non-zero spin matter determines thereby the space-time curvature via a well-defined source term in a covariant Poisson-type equation for the Riemann tensor.

  12. Canonical form of master equations and characterization of non-Markovianity

    NASA Astrophysics Data System (ADS)

    Hall, Michael J. W.; Cresser, James D.; Li, Li; Andersson, Erika

    2014-04-01

    Master equations govern the time evolution of a quantum system interacting with an environment, and may be written in a variety of forms. Time-independent or memoryless master equations, in particular, can be cast in the well-known Lindblad form. Any time-local master equation, Markovian or non-Markovian, may in fact also be written in a Lindblad-like form. A diagonalization procedure results in a unique, and in this sense canonical, representation of the equation, which may be used to fully characterize the non-Markovianity of the time evolution. Recently, several different measures of non-Markovianity have been presented which reflect, to varying degrees, the appearance of negative decoherence rates in the Lindblad-like form of the master equation. We therefore propose using the negative decoherence rates themselves, as they appear in the canonical form of the master equation, to completely characterize non-Markovianity. The advantages of this are especially apparent when more than one decoherence channel is present. We show that a measure proposed by Rivas et al. [Phys. Rev. Lett. 105, 050403 (2010), 10.1103/PhysRevLett.105.050403] is a surprisingly simple function of the canonical decoherence rates, and give an example of a master equation that is non-Markovian for all times t >0, but to which nearly all proposed measures are blind. We also give necessary and sufficient conditions for trace distance and volume measures to witness non-Markovianity, in terms of the Bloch damping matrix.

  13. Common position of indels that cause deviations from canonical genome organization in different measles virus strains.

    PubMed

    Ivancic-Jelecki, Jelena; Slovic, Anamarija; Šantak, Maja; Tešović, Goran; Forcic, Dubravko

    2016-07-29

    The canonical genome organization of measles virus (MV) is characterized by total size of 15 894 nucleotides (nts) and defined length of every genomic region, both coding and non-coding. Only rarely have reports of strains possessing non-canonical genomic properties (possessing indels, with or without the change of total genome length) been published. The observed mutations are mutually compensatory in a sense that the total genome length remains polyhexameric. Although programmed and highly precise pseudo-templated nucleotide additions during transcription are inherent to polymerases of all viruses belonging to family Paramyxoviridae, a similar mechanism that would serve to non-randomly correct genome length, if an indel has occurred during replication, has so far not been described in the context of a complete virus genome. We compiled all complete MV genomic sequences (64 in total) available in open access sequence databases. Multiple sequence comparisons and phylogenetic analyses were performed with the aim of exploring whether non-recombinant and non-evolutionary linked measles strains that show deviations from canonical genome organization possess a common genetic characteristic. In 11 MV sequences we detected deviations from canonical genome organization due to short indels located within homopolymeric stretches or next to them. In nine out of 11 identified non-canonical MV sequences, a common feature was observed: one mutation, either an insertion or a deletion, was located in a 28 nts long region in F gene 5' untranslated region (positions 5051-5078 in genomic cDNA of canonical strains). This segment is composed of five tandemly linked homopolymeric stretches, its consensus sequence is G6-7C7-8A6-7G1-3C5-6. Although none of the mononucleotide repeats within this segment has fixed length, the total number of nts in canonical strains is always 28. These nine non-canonical strains, as well as the tenth (not mutated in 5051-5078 segment), can be grouped in

  14. Induction of Canonical Wnt Signaling by the Alarmins S100A8/A9 in Murine Knee Joints: Implications for Osteoarthritis.

    PubMed

    van den Bosch, Martijn H; Blom, Arjen B; Schelbergen, Rik F P; Vogl, Thomas; Roth, Johannes P; Slöetjes, Annet W; van den Berg, Wim B; van der Kraan, Peter M; van Lent, Peter L E M

    2016-01-01

    Both alarmins S100A8/A9 and canonical Wnt signaling have been found to play active roles in the development of experimental osteoarthritis (OA). However, what activates canonical Wnt signaling remains unknown. This study was undertaken to investigate whether S100A8 induces canonical Wnt signaling and whether S100 proteins exert their effects via activation of Wnt signaling. Expression of the genes for S100A8/A9 and Wnt signaling pathway members was measured in an experimental OA model. Selected Wnt signaling pathway members were overexpressed, and levels of S100A8/A9 were measured. Activation of canonical Wnt signaling was determined after injection of S100A8 into naive joints and induction of collagenase-induced OA in S100A9-deficient mice. Expression of Wnt signaling pathway members was tested in macrophages and fibroblasts after S100A8 stimulation. Canonical Wnt signaling was inhibited in vivo to determine if the effects of S100A8 injections were dependent on Wnt signaling. The alarmins S100A8/A9 and members of the Wnt signaling pathway showed coinciding expression in synovial tissue in an experimental OA model. Synovial overexpression of selected Wnt signaling pathway members did not result in increased expression of S100 proteins. In contrast, intraarticular injection of S100A8 increased canonical Wnt signaling, whereas canonical Wnt signaling was decreased after induction of experimental OA in S100A9-deficient mice. S100A8 stimulation of macrophages, but not fibroblasts, resulted in increased expression of canonical Wnt signaling members. Overexpression of Dkk-1 to inhibit canonical Wnt signaling decreased the induction of matrix metalloproteinase 3, interleukin-6, and macrophage inflammatory protein 1α after injection of S100A8. Our findings indicate that the alarmin S100A8 induces canonical Wnt signaling in macrophages and murine knee joints. The effects of S100A8 are partially dependent on activation of canonical Wnt signaling. © 2016, American College

  15. BOOK REVIEW: Modern Canonical Quantum General Relativity

    NASA Astrophysics Data System (ADS)

    Kiefer, Claus

    2008-06-01

    The open problem of constructing a consistent and experimentally tested quantum theory of the gravitational field has its place at the heart of fundamental physics. The main approaches can be roughly divided into two classes: either one seeks a unified quantum framework of all interactions or one starts with a direct quantization of general relativity. In the first class, string theory (M-theory) is the only known example. In the second class, one can make an additional methodological distinction: while covariant approaches such as path-integral quantization use the four-dimensional metric as an essential ingredient of their formalism, canonical approaches start with a foliation of spacetime into spacelike hypersurfaces in order to arrive at a Hamiltonian formulation. The present book is devoted to one of the canonical approaches—loop quantum gravity. It is named modern canonical quantum general relativity by the author because it uses connections and holonomies as central variables, which are analogous to the variables used in Yang Mills theories. In fact, the canonically conjugate variables are a holonomy of a connection and the flux of a non-Abelian electric field. This has to be contrasted with the older geometrodynamical approach in which the metric of three-dimensional space and the second fundamental form are the fundamental entities, an approach which is still actively being pursued. It is the author's ambition to present loop quantum gravity in a way in which every step is formulated in a mathematically rigorous form. In his own words: 'loop quantum gravity is an attempt to construct a mathematically rigorous, background-independent, non-perturbative quantum field theory of Lorentzian general relativity and all known matter in four spacetime dimensions, not more and not less'. The formal Leitmotiv of loop quantum gravity is background independence. Non-gravitational theories are usually quantized on a given non-dynamical background. In contrast, due to

  16. Geometric integrator for simulations in the canonical ensemble

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tapias, Diego, E-mail: diego.tapias@nucleares.unam.mx; Sanders, David P., E-mail: dpsanders@ciencias.unam.mx; Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139

    2016-08-28

    We introduce a geometric integrator for molecular dynamics simulations of physical systems in the canonical ensemble that preserves the invariant distribution in equations arising from the density dynamics algorithm, with any possible type of thermostat. Our integrator thus constitutes a unified framework that allows the study and comparison of different thermostats and of their influence on the equilibrium and non-equilibrium (thermo-)dynamic properties of a system. To show the validity and the generality of the integrator, we implement it with a second-order, time-reversible method and apply it to the simulation of a Lennard-Jones system with three different thermostats, obtaining good conservationmore » of the geometrical properties and recovering the expected thermodynamic results. Moreover, to show the advantage of our geometric integrator over a non-geometric one, we compare the results with those obtained by using the non-geometric Gear integrator, which is frequently used to perform simulations in the canonical ensemble. The non-geometric integrator induces a drift in the invariant quantity, while our integrator has no such drift, thus ensuring that the system is effectively sampling the correct ensemble.« less

  17. On the use and computation of the Jordan canonical form in system theory

    NASA Technical Reports Server (NTRS)

    Sridhar, B.; Jordan, D.

    1974-01-01

    This paper investigates various aspects of the application of the Jordan canonical form of a matrix in system theory and develops a computational approach to determining the Jordan form for a given matrix. Applications include pole placement, controllability and observability studies, serving as an intermediate step in yielding other canonical forms, and theorem proving. The computational method developed in this paper is both simple and efficient. The method is based on the definition of a generalized eigenvector and a natural extension of Gauss elimination techniques. Examples are included for demonstration purposes.

  18. Servo-hydraulic actuator in controllable canonical form: Identification and experimental validation

    NASA Astrophysics Data System (ADS)

    Maghareh, Amin; Silva, Christian E.; Dyke, Shirley J.

    2018-02-01

    Hydraulic actuators have been widely used to experimentally examine structural behavior at multiple scales. Real-time hybrid simulation (RTHS) is one innovative testing method that largely relies on such servo-hydraulic actuators. In RTHS, interface conditions must be enforced in real time, and controllers are often used to achieve tracking of the desired displacements. Thus, neglecting the dynamics of hydraulic transfer system may result either in system instability or sub-optimal performance. Herein, we propose a nonlinear dynamical model for a servo-hydraulic actuator (a.k.a. hydraulic transfer system) coupled with a nonlinear physical specimen. The nonlinear dynamical model is transformed into controllable canonical form for further tracking control design purposes. Through a number of experiments, the controllable canonical model is validated.

  19. A canonical form of the equation of motion of linear dynamical systems

    NASA Astrophysics Data System (ADS)

    Kawano, Daniel T.; Salsa, Rubens Goncalves; Ma, Fai; Morzfeld, Matthias

    2018-03-01

    The equation of motion of a discrete linear system has the form of a second-order ordinary differential equation with three real and square coefficient matrices. It is shown that, for almost all linear systems, such an equation can always be converted by an invertible transformation into a canonical form specified by two diagonal coefficient matrices associated with the generalized acceleration and displacement. This canonical form of the equation of motion is unique up to an equivalence class for non-defective systems. As an important by-product, a damped linear system that possesses three symmetric and positive definite coefficients can always be recast as an undamped and decoupled system.

  20. Astragaloside IV prevents damage to human mesangial cells through the inhibition of the NADPH oxidase/ROS/Akt/NF‑κB pathway under high glucose conditions.

    PubMed

    Sun, Li; Li, Weiping; Li, Weizu; Xiong, Li; Li, Guiping; Ma, Rong

    2014-07-01

    Glomerular hypertrophy and hyperfiltration are the two major pathological characteristics of the early stages of diabetic nephropathy (DN), which are respectively related to mesangial cell (MC) proliferation and a decrease in calcium influx conducted by canonical transient receptor potential cation channel 6 (TRPC6). The marked increase in the production of reactive oxygen species (ROS) induced by hyperglycemia is the main sponsor of multiple pathological pathways in DN. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is an important source of ROS production in MCs. Astragaloside IV (AS‑IV) is an active ingredient of Radix Astragali which has a potent antioxidative effect. In this study, we aimed to investigate whether high glucose (HG)‑induced NADPH oxidase activation and ROS production contribute to MC proliferation and the downregulation of TRPC6 expression; we also wished to determine the effects of AS‑IV on MCs under HG conditions. Using a human glomerular mesangial cell line, we found that treatment with AS‑IV for 48 h markedly attenuated HG‑induced proliferation and the hypertrophy of MCs in a dose‑dependent manner. The intracellular ROS level was also markedly reduced following treatment with AS‑IV. In addition, the enhanced activity of NADPH oxidase and the expression level of NADPH oxidase 4 (Nox4) protein were decreased. Treatment with AS‑IV also inhibited the phosphorylation level of Akt and IκBα in the MCs. In addition, TRPC6 protein expression and the intracellular free calcium concentration were also markedly reduced following treatment with AS‑IV under HG conditions. These results suggest that AS‑IV inhibits HG‑induced mesangial cell proliferation and glomerular contractile dysfunction through the NADPH oxidase/ROS/Akt/nuclear factor‑κB (NF‑κB) pathway, providing a new perspective for the clinical treatment of DN.

  1. Basic Brackets of a 2D Model for the Hodge Theory Without its Canonical Conjugate Momenta

    NASA Astrophysics Data System (ADS)

    Kumar, R.; Gupta, S.; Malik, R. P.

    2016-06-01

    We deduce the canonical brackets for a two (1+1)-dimensional (2D) free Abelian 1-form gauge theory by exploiting the beauty and strength of the continuous symmetries of a Becchi-Rouet-Stora-Tyutin (BRST) invariant Lagrangian density that respects, in totality, six continuous symmetries. These symmetries entail upon this model to become a field theoretic example of Hodge theory. Taken together, these symmetries enforce the existence of exactly the same canonical brackets amongst the creation and annihilation operators that are found to exist within the standard canonical quantization scheme. These creation and annihilation operators appear in the normal mode expansion of the basic fields of this theory. In other words, we provide an alternative to the canonical method of quantization for our present model of Hodge theory where the continuous internal symmetries play a decisive role. We conjecture that our method of quantization is valid for a class of field theories that are tractable physical examples for the Hodge theory. This statement is true in any arbitrary dimension of spacetime.

  2. Region 8: Colorado Canon City Adequate Letter (8/17/2011)

    EPA Pesticide Factsheets

    This May 4, 2011 letter from EPA to Chistopher E. Urbina M.D., MPH, Colorado Department of Public Health and Environment states that EPA has found that the Canon City PM10 maintenance plan and the 2020 motor vehicle emissions budget (MVEB) adequate

  3. Toward canonical ensemble distribution from self-guided Langevin dynamics simulation

    NASA Astrophysics Data System (ADS)

    Wu, Xiongwu; Brooks, Bernard R.

    2011-04-01

    This work derives a quantitative description of the conformational distribution in self-guided Langevin dynamics (SGLD) simulations. SGLD simulations employ guiding forces calculated from local average momentums to enhance low-frequency motion. This enhancement in low-frequency motion dramatically accelerates conformational search efficiency, but also induces certain perturbations in conformational distribution. Through the local averaging, we separate properties of molecular systems into low-frequency and high-frequency portions. The guiding force effect on the conformational distribution is quantitatively described using these low-frequency and high-frequency properties. This quantitative relation provides a way to convert between a canonical ensemble and a self-guided ensemble. Using example systems, we demonstrated how to utilize the relation to obtain canonical ensemble properties and conformational distributions from SGLD simulations. This development makes SGLD not only an efficient approach for conformational searching, but also an accurate means for conformational sampling.

  4. A path-integral approach to the problem of time

    NASA Astrophysics Data System (ADS)

    Amaral, M. M.; Bojowald, Martin

    2018-01-01

    Quantum transition amplitudes are formulated for model systems with local internal time, using intuition from path integrals. The amplitudes are shown to be more regular near a turning point of internal time than could be expected based on existing canonical treatments. In particular, a successful transition through a turning point is provided in the model systems, together with a new definition of such a transition in general terms. Some of the results rely on a fruitful relation between the problem of time and general Gribov problems.

  5. Ethnic Rhinoplasty in Female Patients: The Neoclassical Canons Revisited.

    PubMed

    Saad, Ahmad; Hewett, Sierra; Nolte, Megan; Delaunay, Flore; Saad, Mariam; Cohen, Steven R

    2018-04-01

    Despite the substantial amount of research devoted to objectively defining facial attractiveness, the canons have remained a paradigm of aesthetic facial analysis, yet their omnipresence in clinical assessments revealed their limitations outside of a subset of North American Caucasians, leading to criticism about their validity as a standard of facial beauty. In an effort to introduce more objective treatment planning into ethnic rhinoplasty, we compared neoclassical canons and other current standards pertaining to nasal proportions to anatomic proportions of attractive individuals from seven different ethnic backgrounds. Beauty pageant winners (Miss Universe and Miss World nominees) between 2005 and 2015 were selected and assigned to one of seven regionally defined ethnic groups. Anteroposterior and lateral images were obtained through Google, Wikipedia, Miss Universe, and Miss World Web sites. Anthropometry of facial features was performed via Adobe Photoshop TM. Individual facial measurements were then standardized to proportions and compared to the neoclassical canons. Our data reflected an ethnic-dependent preference for the multiple fitness model. Wide-set eyes, larger mouth widths, and smaller noses were significantly relevant in Eastern Mediterranean and European ethnic groups. Exceptions lied within East African and Asian groups. As in the attractive face, the concept of the ideal nasal anatomy varies between different ethnicities. Using objective criteria and proportions of beauty to plan and execute rhinoplasty in different ethnicities can help the surgeon plan and deliver results that are in harmony with patients' individual background and facial anatomy. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

  6. XEDAR activates the non-canonical NF-κB pathway

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Verhelst, Kelly, E-mail: Kelly.Verhelst@irc.VIB-UGent.be; Department of Biomedical Molecular Biology, Ghent University, Ghent; Gardam, Sandra, E-mail: s.gardam@garvan.org.au

    2015-09-18

    Members of the tumor necrosis factor receptor (TNFR) superfamily are involved in a number of physiological and pathological responses by activating a wide variety of intracellular signaling pathways. The X-linked ectodermal dysplasia receptor (XEDAR; also known as EDA2R or TNFRSF27) is a member of the TNFR superfamily that is highly expressed in ectodermal derivatives during embryonic development and binds to ectodysplasin-A2 (EDA-A2), a member of the TNF family that is encoded by the anhidrotic ectodermal dysplasia (EDA) gene. Although XEDAR was first described in the year 2000, its function and molecular mechanism of action is still largely unclear. XEDAR hasmore » been reported to activate canonical nuclear factor κB (NF-κB) signaling and mitogen-activated protein (MAP) kinases. Here we report that XEDAR is also able to trigger the non-canonical NF-κB pathway, characterized by the processing of p100 (NF-κB2) into p52, followed by nuclear translocation of p52 and RelB. We provide evidence that XEDAR-induced p100 processing relies on the binding of XEDAR to TRAF3 and TRAF6, and requires the kinase activity of NIK and IKKα. We also show that XEDAR stimulation results in NIK accumulation and that p100 processing is negatively regulated by TRAF3, cIAP1 and A20. - Highlights: • XEDAR activates the non-canonical NF-κB pathway. • XEDAR-induced processing of p100 depends on XEDAR interaction with TRAF3 and TRAF6. • XEDAR-induced processing of p100 depends on NIK and IKKα activity. • Overexpression of XEDAR leads to NIK accumulation. • XEDAR-induced processing of p100 is negatively regulated by TRAF3 cIAP1 and A20.« less

  7. The classical dynamic symmetry for the U(1) -Kepler problems

    NASA Astrophysics Data System (ADS)

    Bouarroudj, Sofiane; Meng, Guowu

    2018-01-01

    For the Jordan algebra of hermitian matrices of order n ≥ 2, we let X be its submanifold consisting of rank-one semi-positive definite elements. The composition of the cotangent bundle map πX: T∗ X → X with the canonical map X → CP n - 1 (i.e., the map that sends a given hermitian matrix to its column space), pulls back the Kähler form of the Fubini-Study metric on CP n - 1 to a real closed differential two-form ωK on T∗ X. Let ωX be the canonical symplectic form on T∗ X and μ a real number. A standard fact says that ωμ ≔ωX + 2 μωK turns T∗ X into a symplectic manifold, hence a Poisson manifold with Poisson bracket {,}μ. In this article we exhibit a Poisson realization of the simple real Lie algebra su(n , n) on the Poisson manifold (T∗ X ,{,}μ) , i.e., a Lie algebra homomorphism from su(n , n) to (C∞(T∗ X , R) ,{,}μ). Consequently one obtains the Laplace-Runge-Lenz vector for the classical U(1) -Kepler problem of level n and magnetic charge μ. Since the McIntosh-Cisneros-Zwanziger-Kepler problems (MICZ-Kepler Problems) are the U(1) -Kepler problems of level 2, the work presented here is a direct generalization of the work by A. Barut and G. Bornzin (1971) on the classical dynamic symmetry for the MICZ-Kepler problems.

  8. Comparison of Penalty Functions for Sparse Canonical Correlation Analysis

    PubMed Central

    Chalise, Prabhakar; Fridley, Brooke L.

    2011-01-01

    Canonical correlation analysis (CCA) is a widely used multivariate method for assessing the association between two sets of variables. However, when the number of variables far exceeds the number of subjects, such in the case of large-scale genomic studies, the traditional CCA method is not appropriate. In addition, when the variables are highly correlated the sample covariance matrices become unstable or undefined. To overcome these two issues, sparse canonical correlation analysis (SCCA) for multiple data sets has been proposed using a Lasso type of penalty. However, these methods do not have direct control over sparsity of solution. An additional step that uses Bayesian Information Criterion (BIC) has also been suggested to further filter out unimportant features. In this paper, a comparison of four penalty functions (Lasso, Elastic-net, SCAD and Hard-threshold) for SCCA with and without the BIC filtering step have been carried out using both real and simulated genotypic and mRNA expression data. This study indicates that the SCAD penalty with BIC filter would be a preferable penalty function for application of SCCA to genomic data. PMID:21984855

  9. Establishing the Canon: George Ripley and his alchemical sources.

    PubMed

    Rampling, Jennifer M

    2008-11-01

    George Ripley, Canon of Bridlington (ca. 1415 to ca. 1490) was one of England's most famous alchemists, whose alchemical opera attracted study and commentary throughout the sixteenth and seventeenth centuries, and were printed and translated both in England and abroad. Yet Ripley's frequently baffling texts have proved resistant to scholarly interpretation. This paper attempts to unravel some of Ripley's alchemical theories and practice, firstly by identifying his major sources, and secondly by gauging his response to these texts. For instance, although Ripley's interest in the corpus of alchemical texts pseudonymously attributed to Ramon Lull is well documented, it transpires that his best known work, the Compound of Alchemy, or Twelve Gates, is actually based not on a Lullian work, but on a Latin treatise that Ripley attributed to the little-known alchemist, Guido de Montanor. Further clues to Ripley's alchemical thought can be obtained by considering his handling of a potential conflict between his two authorities, Lull and Guido. The resulting insights into Ripley's alchemy provide an instrument for assessing which of Ripley's pseudoepigraphic works can be truly called "canonical".

  10. Interstellar C IV and Si IV column densities toward early-type stars

    NASA Technical Reports Server (NTRS)

    Bruhweiler, F. C.; Kondo, Y.; Mccluskey, G. E.

    1980-01-01

    Equivalent widths and deduced column densities of Si IV and C IV are examined for 18 early-type close binaries, and physical processes responsible for the origin of these ions in the interstellar medium are investigated. The available C IV/Si IV column density ratios typically lie within a narrow range from 0.8 to 4.5, and there is evidence that the column density of C IV is higher than that of N V along most lines of sight, suggesting that C IV is not formed in the same hot region as O VI. In addition, the existence of regions with a narrowly defined new temperature range around 50,000 deg K is indicated. The detection of the semitorrid gas of Bruhweiler, Kondo, and McCluskey (1978, 1979) is substantiated, and the relation of this gas to the observations of coronal gas in the galactic halo is discussed.

  11. Gender and the Contemporary Educational Canon in the UK

    ERIC Educational Resources Information Center

    Elliott, Victoria

    2017-01-01

    This paper presents an analysis of the gender of the authors and the main characters of the set texts for English examinations taken at age 16 in England, Northern Ireland, Scotland and Wales. It presents an argument for why representation within the canon is important and places this within the context of recent educational reform in England and…

  12. Robust nonlinear canonical correlation analysis: application to seasonal climate forecasting

    NASA Astrophysics Data System (ADS)

    Cannon, A. J.; Hsieh, W. W.

    2008-02-01

    Robust variants of nonlinear canonical correlation analysis (NLCCA) are introduced to improve performance on datasets with low signal-to-noise ratios, for example those encountered when making seasonal climate forecasts. The neural network model architecture of standard NLCCA is kept intact, but the cost functions used to set the model parameters are replaced with more robust variants. The Pearson product-moment correlation in the double-barreled network is replaced by the biweight midcorrelation, and the mean squared error (mse) in the inverse mapping networks can be replaced by the mean absolute error (mae). Robust variants of NLCCA are demonstrated on a synthetic dataset and are used to forecast sea surface temperatures in the tropical Pacific Ocean based on the sea level pressure field. Results suggest that adoption of the biweight midcorrelation can lead to improved performance, especially when a strong, common event exists in both predictor/predictand datasets. Replacing the mse by the mae leads to improved performance on the synthetic dataset, but not on the climate dataset except at the longest lead time, which suggests that the appropriate cost function for the inverse mapping networks is more problem dependent.

  13. A Synthetic Alternative to Canonical One-Carbon Metabolism.

    PubMed

    Bouzon, Madeleine; Perret, Alain; Loreau, Olivier; Delmas, Valérie; Perchat, Nadia; Weissenbach, Jean; Taran, Frédéric; Marlière, Philippe

    2017-08-18

    One-carbon metabolism is an ubiquitous metabolic pathway that encompasses the reactions transferring formyl-, hydroxymethyl- and methyl-groups bound to tetrahydrofolate for the synthesis of purine nucleotides, thymidylate, methionine and dehydropantoate, the precursor of coenzyme A. An alternative cyclic pathway was designed that substitutes 4-hydroxy-2-oxobutanoic acid (HOB), a compound absent from known metabolism, for the amino acids serine and glycine as one-carbon donors. It involves two novel reactions, the transamination of l-homoserine and the transfer of a one-carbon unit from HOB to tetrahydrofolate releasing pyruvate as coproduct. Since canonical reactions regenerate l-homoserine from pyruvate by carboxylation and subsequent reduction, every one-carbon moiety made available for anabolic reactions originates from CO 2 . The HOB-dependent pathway was established in an Escherichia coli auxotroph selected for prototrophy using long-term cultivation protocols. Genetic, metabolic and biochemical evidence support the emergence of a functional HOB-dependent one-carbon pathway achieved with the recruitment of the two enzymes l-homoserine transaminase and HOB-hydroxymethyltransferase and of HOB as an essential metabolic intermediate. Escherichia coli biochemical reprogramming was achieved by minimally altering canonical metabolism and leveraging on natural selection mechanisms, thereby launching the resulting strain on an evolutionary trajectory diverging from all known extant species.

  14. Multivariable extrapolation of grand canonical free energy landscapes

    NASA Astrophysics Data System (ADS)

    Mahynski, Nathan A.; Errington, Jeffrey R.; Shen, Vincent K.

    2017-12-01

    We derive an approach for extrapolating the free energy landscape of multicomponent systems in the grand canonical ensemble, obtained from flat-histogram Monte Carlo simulations, from one set of temperature and chemical potentials to another. This is accomplished by expanding the landscape in a Taylor series at each value of the order parameter which defines its macrostate phase space. The coefficients in each Taylor polynomial are known exactly from fluctuation formulas, which may be computed by measuring the appropriate moments of extensive variables that fluctuate in this ensemble. Here we derive the expressions necessary to define these coefficients up to arbitrary order. In principle, this enables a single flat-histogram simulation to provide complete thermodynamic information over a broad range of temperatures and chemical potentials. Using this, we also show how to combine a small number of simulations, each performed at different conditions, in a thermodynamically consistent fashion to accurately compute properties at arbitrary temperatures and chemical potentials. This method may significantly increase the computational efficiency of biased grand canonical Monte Carlo simulations, especially for multicomponent mixtures. Although approximate, this approach is amenable to high-throughput and data-intensive investigations where it is preferable to have a large quantity of reasonably accurate simulation data, rather than a smaller amount with a higher accuracy.

  15. Shannon information entropy in the canonical genetic code.

    PubMed

    Nemzer, Louis R

    2017-02-21

    The Shannon entropy measures the expected information value of messages. As with thermodynamic entropy, the Shannon entropy is only defined within a system that identifies at the outset the collections of possible messages, analogous to microstates, that will be considered indistinguishable macrostates. This fundamental insight is applied here for the first time to amino acid alphabets, which group the twenty common amino acids into families based on chemical and physical similarities. To evaluate these schemas objectively, a novel quantitative method is introduced based the inherent redundancy in the canonical genetic code. Each alphabet is taken as a separate system that partitions the 64 possible RNA codons, the microstates, into families, the macrostates. By calculating the normalized mutual information, which measures the reduction in Shannon entropy, conveyed by single nucleotide messages, groupings that best leverage this aspect of fault tolerance in the code are identified. The relative importance of properties related to protein folding - like hydropathy and size - and function, including side-chain acidity, can also be estimated. This approach allows the quantification of the average information value of nucleotide positions, which can shed light on the coevolution of the canonical genetic code with the tRNA-protein translation mechanism. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Structure of multiphoton quantum optics. I. Canonical formalism and homodyne squeezed states

    NASA Astrophysics Data System (ADS)

    dell'Anno, Fabio; de Siena, Silvio; Illuminati, Fabrizio

    2004-03-01

    We introduce a formalism of nonlinear canonical transformations for general systems of multiphoton quantum optics. For single-mode systems the transformations depend on a tunable free parameter, the homodyne local-oscillator angle; for n -mode systems they depend on n heterodyne mixing angles. The canonical formalism realizes nontrivial mixing of pairs of conjugate quadratures of the electromagnetic field in terms of homodyne variables for single-mode systems, and in terms of heterodyne variables for multimode systems. In the first instance the transformations yield nonquadratic model Hamiltonians of degenerate multiphoton processes and define a class of non-Gaussian, nonclassical multiphoton states that exhibit properties of coherence and squeezing. We show that such homodyne multiphoton squeezed states are generated by unitary operators with a nonlinear time evolution that realizes the homodyne mixing of a pair of conjugate quadratures. Tuning of the local-oscillator angle allows us to vary at will the statistical properties of such states. We discuss the relevance of the formalism for the study of degenerate (up-)down-conversion processes. In a companion paper [

    F. Dell’Anno, S. De Siena, and F. Illuminati, 69, 033813 (2004)
    ], we provide the extension of the nonlinear canonical formalism to multimode systems, we introduce the associated heterodyne multiphoton squeezed states, and we discuss their possible experimental realization.

  17. Catechistic Teaching, National Canons, and the Regimentation of Students' Voice

    ERIC Educational Resources Information Center

    Kroon, Sjaak

    2013-01-01

    Drawing on key incident analysis of classroom transcripts from Bashkortostan, France, North Korea, and Suriname, this article discusses the relationship between an increasingly canonical content of education and the discursive organization of teaching processes at the expense of both teachers' and students' voice. It argues that canonical…

  18. Glucocorticoid suppresses the canonical Wnt signal in cultured human osteoblasts

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ohnaka, Keizo; Tanabe, Mizuho; Kawate, Hisaya

    2005-04-01

    To explore the mechanism of glucocorticoid-induced osteoporosis, we investigated the effect of glucocorticoid on canonical Wnt signaling that emerged as a novel key pathway for promoting bone formation. Wnt3a increased the T-cell factor (Tcf)/lymphoid enhancer factor (Lef)-dependent transcriptional activity in primary cultured human osteoblasts. Dexamethasone suppressed this transcriptional activity in a dose-dependent manner, while 1,25-dihydroxyvitamin D3 increased this transcriptional activity. LiCl, an inhibitor of glycogen synthase kinase-3{beta}, also enhanced the Tcf/Lef-dependent transcriptional activity, which was, however, not inhibited by dexamethasone. The addition of anti-dickkopf-1 antibody partially restored the transcriptional activity suppressed by dexamethasone. Dexamethasone decreased the cytosolic amount of {beta}-cateninmore » accumulated by Wnt3a and also inhibited the nuclear translocation of {beta}-catenin induced by Wnt3a. These data suggest that glucocorticoid suppresses the canonical Wnt signal in cultured human osteoblasts, partially through the enhancement of the dickkopf-1 production.« less

  19. A canonical correlation neural network for multicollinearity and functional data.

    PubMed

    Gou, Zhenkun; Fyfe, Colin

    2004-03-01

    We review a recent neural implementation of Canonical Correlation Analysis and show, using ideas suggested by Ridge Regression, how to make the algorithm robust. The network is shown to operate on data sets which exhibit multicollinearity. We develop a second model which not only performs as well on multicollinear data but also on general data sets. This model allows us to vary a single parameter so that the network is capable of performing Partial Least Squares regression (at one extreme) to Canonical Correlation Analysis (at the other)and every intermediate operation between the two. On multicollinear data, the parameter setting is shown to be important but on more general data no particular parameter setting is required. Finally, we develop a second penalty term which acts on such data as a smoother in that the resulting weight vectors are much smoother and more interpretable than the weights without the robustification term. We illustrate our algorithms on both artificial and real data.

  20. From grand-canonical density functional theory towards rational compound design

    NASA Astrophysics Data System (ADS)

    von Lilienfeld, Anatole

    2008-03-01

    The fundamental challenge of rational compound design, ie the reverse engineering of chemical compounds with predefined specific properties, originates in the high-dimensional combinatorial nature of chemical space. Chemical space is the hyper-space of a given set of molecular observables that is spanned by the grand-canonical variables (particle densities of electrons and nuclei) which define chemical composition. A brief but rigorous description of chemical space within the molecular grand-canonical ensemble multi-component density functional theory framework will be given [1]. Numerical results will be presented for intermolecular energies as a continuous function of alchemical variations within a neutral and isoelectronic 10 proton system, including CH4, NH3, H2O, and HF, interacting with formic acid [2]. Furthermore, engineering the Fermi level through alchemical generation of boron-nitrogen doped mutants of benzene shall be discussed [3].[1] von Lilienfeld and Tuckerman JCP 125 154104 (2006)[2] von Lilienfeld and Tuckerman JCTC 3 1083 (2007)[3] Marcon et al. JCP 127 064305 (2007)

  1. The Ecology of Early Childhood Risk: A Canonical Correlation Analysis of Children’s Adjustment, Family, and Community Context in a High-Risk Sample

    PubMed Central

    Aiyer, Sophie M.; Wilson, Melvin N.; Shaw, Daniel S.; Dishion, Thomas J.

    2013-01-01

    The ecology of the emergence of psycho-pathology in early childhood is often approached by the analysis of a limited number of contextual risk factors. In the present study, we provide a comprehensive analysis of ecological risk by conducting a canonical correlation analysis of 13 risk factors at child age 2 and seven narrow-band scales of internalizing and externalizing problem behaviors at child age 4, using a sample of 364 geographically and ethnically diverse, disadvantaged primary caregivers, alternative caregivers, and preschool-age children. Participants were recruited from Special Supplemental Nutrition Program for Women, Infants, and Children sites and were screened for family risk. Canonical correlation analysis revealed that (1) a first latent combination of family and individual risks of caregivers predicted combinations of child emotional and behavioral problems, and that (2) a second latent combination of contextual and structural risks predicted child somatic complaints. Specifically, (1) the combination of chaotic home, conflict with child, parental depression, and parenting hassles predicted a co-occurrence of internalizing and externalizing behaviors, and (2) the combination of father absence, perceived discrimination, neighborhood danger, and fewer children living in the home predicted child somatic complaints. The research findings are discussed in terms of the development of psychopathology, as well as the potential prevention needs of families in high-risk contexts. PMID:23700232

  2. Kato expansion in quantum canonical perturbation theory

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Nikolaev, Andrey, E-mail: Andrey.Nikolaev@rdtex.ru

    2016-06-15

    This work establishes a connection between canonical perturbation series in quantum mechanics and a Kato expansion for the resolvent of the Liouville superoperator. Our approach leads to an explicit expression for a generator of a block-diagonalizing Dyson’s ordered exponential in arbitrary perturbation order. Unitary intertwining of perturbed and unperturbed averaging superprojectors allows for a description of ambiguities in the generator and block-diagonalized Hamiltonian. We compare the efficiency of the corresponding computational algorithm with the efficiencies of the Van Vleck and Magnus methods for high perturbative orders.

  3. Influences of Problem Format and SES on Preschoolers' Understanding of Approximate Addition

    ERIC Educational Resources Information Center

    McNeil, Nicole M.; Fuhs, Mary Wagner; Keultjes, M. Claire; Gibson, Matthew H.

    2011-01-01

    Recent studies suggest that 5-year-olds can add and compare large numerical quantities through approximate representations of number. However, the nature of this understanding and its susceptibility to environmental influences remain unclear. We examined whether children's early competence depends on the canonical problem format (i.e., arithmetic…

  4. Long-term forecasting of meteorological time series using Nonlinear Canonical Correlation Analysis (NLCCA)

    NASA Astrophysics Data System (ADS)

    Woldesellasse, H. T.; Marpu, P. R.; Ouarda, T.

    2016-12-01

    Wind is one of the crucial renewable energy sources which is expected to bring solutions to the challenges of clean energy and the global issue of climate change. A number of linear and nonlinear multivariate techniques has been used to predict the stochastic character of wind speed. A wind forecast with good accuracy has a positive impact on the reduction of electricity system cost and is essential for the effective grid management. Over the past years, few studies have been done on the assessment of teleconnections and its possible effects on the long-term wind speed variability in the UAE region. In this study Nonlinear Canonical Correlation Analysis (NLCCA) method is applied to study the relationship between global climate oscillation indices and meteorological variables, with a major emphasis on wind speed and wind direction, of Abu Dhabi, UAE. The wind dataset was obtained from six ground stations. The first mode of NLCCA is capable of capturing the nonlinear mode of the climate indices at different seasons, showing the symmetry between the warm states and the cool states. The strength of the nonlinear canonical correlation between the two sets of variables varies with the lead/lag time. The performance of the models is assessed by calculating error indices such as the root mean square error (RMSE) and Mean absolute error (MAE). The results indicated that NLCCA models provide more accurate information about the nonlinear intrinsic behaviour of the dataset of variables than linear CCA model in terms of the correlation and root mean square error. Key words: Nonlinear Canonical Correlation Analysis (NLCCA), Canonical Correlation Analysis, Neural Network, Climate Indices, wind speed, wind direction

  5. Gender Differences in and the Relationships Between Social Anxiety and Problematic Internet Use: Canonical Analysis

    PubMed Central

    Özteke Kozan, Hatice İrem; Kesici, Şahin

    2018-01-01

    Background The cognitive-behavioral model of problematic Internet use (PIU) proposes that psychological well-being is associated with specific thoughts and behaviors on the Internet. Hence, there is growing concern that PIU is associated with psychological impairments. Objective Given the proposal of gender schema theory and social role theory, men and women are predisposed to experience social anxiety and engage in Internet use differently. Thus, an investigation of gender differences in these areas is warranted. According to the cognitive-behavioral model of PIU, social anxiety is associated with specific cognitions and behaviors on the Internet. Thus, an investigation of the association between social anxiety and PIU is essential. In addition, research that takes into account the multidimensional nature of social anxiety and PIU is lacking. Therefore, this study aimed to explore multivariate gender differences in and the relationships between social anxiety and PIU. Methods Participants included 505 college students, of whom 241 (47.7%) were women and 264 (52.3%) were men. Participants’ ages ranged from 18 to 22 years, with a mean age of 20.34 (SD=1.16). The Social Anxiety Scale and Problematic Internet Use Scale were used in data collection. Multivariate analysis of variance (MANOVA) and canonical correlation analysis were used. Results Mean differences between men and women were not statistically significant in social anxiety (λ=.02, F3,501=2.47, P=.06). In all three PIU dimensions, men scored higher than women, and MANOVA shows that multivariate difference was statistically significant (λ=.94, F3,501=10.69, P<.001). Of the canonical correlation functions computed for men, only the first was significant (Rc=.43, λ=.78, χ29=64.7, P<.001) and accounted for 19% of the overlapping variance. Similarly, only the first canonical function was significant for women (Rc=.36, λ=.87, χ29=33.9, P<.001), which accounted for 13% of the overlapping variance

  6. A Multifunctional Sensor in Ternary Solution Using Canonical Correlations for Variable Links Assessment

    PubMed Central

    Liu, Dan; Wang, Qisong; Liu, Xin; Niu, Ruixin; Zhang, Yan; Sun, Jinwei

    2016-01-01

    Accurately measuring the oil content and salt content of crude oil is very important for both estimating oil reserves and predicting the lifetime of an oil well. There are some problems with the current methods such as high cost, low precision, and difficulties in operation. To solve these problems, we present a multifunctional sensor, which applies, respectively, conductivity method and ultrasound method to measure the contents of oil, water, and salt. Based on cross sensitivity theory, these two transducers are ideally integrated for simplifying the structure. A concentration test of ternary solutions is carried out to testify its effectiveness, and then Canonical Correlation Analysis is applied to evaluate the data. From the perspective of statistics, the sensor inputs, for instance, oil concentration, salt concentration, and temperature, are closely related to its outputs including output voltage and time of flight of ultrasound wave, which further identify the correctness of the sensing theory and the feasibility of the integrated design. Combined with reconstruction algorithms, the sensor can realize the content measurement of the solution precisely. The potential development of the proposed sensor and method in the aspect of online test for crude oil is of important reference and practical value. PMID:27775640

  7. Hierarchical Type Stability Criteria for Delayed Neural Networks via Canonical Bessel-Legendre Inequalities.

    PubMed

    Zhang, Xian-Ming; Han, Qing-Long; Zeng, Zhigang

    2018-05-01

    This paper is concerned with global asymptotic stability of delayed neural networks. Notice that a Bessel-Legendre inequality plays a key role in deriving less conservative stability criteria for delayed neural networks. However, this inequality is in the form of Legendre polynomials and the integral interval is fixed on . As a result, the application scope of the Bessel-Legendre inequality is limited. This paper aims to develop the Bessel-Legendre inequality method so that less conservative stability criteria are expected. First, by introducing a canonical orthogonal polynomial sequel, a canonical Bessel-Legendre inequality and its affine version are established, which are not explicitly in the form of Legendre polynomials. Moreover, the integral interval is shifted to a general one . Second, by introducing a proper augmented Lyapunov-Krasovskii functional, which is tailored for the canonical Bessel-Legendre inequality, some sufficient conditions on global asymptotic stability are formulated for neural networks with constant delays and neural networks with time-varying delays, respectively. These conditions are proven to have a hierarchical feature: the higher level of hierarchy, the less conservatism of the stability criterion. Finally, three numerical examples are given to illustrate the efficiency of the proposed stability criteria.

  8. ESEA Title IV-C Innovation Administration Manual for South Carolina.

    ERIC Educational Resources Information Center

    South Carolina State Dept. of Education, Columbia. Office of Federal Programs.

    The intent of Title IV-C of the Elementary and Secondary Education Act (the Education Amendments of 1974) is to establish innovative and exemplary projects that provide creative or imaginative solutions to problems in the areas of supplementary centers and services, health and nutritional demonstrations, and dropout prevention. The purposes of…

  9. Statistical field theory with constraints: Application to critical Casimir forces in the canonical ensemble.

    PubMed

    Gross, Markus; Gambassi, Andrea; Dietrich, S

    2017-08-01

    The effect of imposing a constraint on a fluctuating scalar order parameter field in a system of finite volume is studied within statistical field theory. The canonical ensemble, corresponding to a fixed total integrated order parameter (e.g., the total number of particles), is obtained as a special case of the theory. A perturbative expansion is developed which allows one to systematically determine the constraint-induced finite-volume corrections to the free energy and to correlation functions. In particular, we focus on the Landau-Ginzburg model in a film geometry (i.e., in a rectangular parallelepiped with a small aspect ratio) with periodic, Dirichlet, or Neumann boundary conditions in the transverse direction and periodic boundary conditions in the remaining, lateral directions. Within the expansion in terms of ε=4-d, where d is the spatial dimension of the bulk, the finite-size contribution to the free energy of the confined system and the associated critical Casimir force are calculated to leading order in ε and are compared to the corresponding expressions for an unconstrained (grand canonical) system. The constraint restricts the fluctuations within the system and it accordingly modifies the residual finite-size free energy. The resulting critical Casimir force is shown to depend on whether it is defined by assuming a fixed transverse area or a fixed total volume. In the former case, the constraint is typically found to significantly enhance the attractive character of the force as compared to the grand canonical case. In contrast to the grand canonical Casimir force, which, for supercritical temperatures, vanishes in the limit of thick films, in the canonical case with fixed transverse area the critical Casimir force attains for thick films a negative value for all boundary conditions studied here. Typically, the dependence of the critical Casimir force both on the temperaturelike and on the fieldlike scaling variables is different in the two ensembles.

  10. Statistical field theory with constraints: Application to critical Casimir forces in the canonical ensemble

    NASA Astrophysics Data System (ADS)

    Gross, Markus; Gambassi, Andrea; Dietrich, S.

    2017-08-01

    The effect of imposing a constraint on a fluctuating scalar order parameter field in a system of finite volume is studied within statistical field theory. The canonical ensemble, corresponding to a fixed total integrated order parameter (e.g., the total number of particles), is obtained as a special case of the theory. A perturbative expansion is developed which allows one to systematically determine the constraint-induced finite-volume corrections to the free energy and to correlation functions. In particular, we focus on the Landau-Ginzburg model in a film geometry (i.e., in a rectangular parallelepiped with a small aspect ratio) with periodic, Dirichlet, or Neumann boundary conditions in the transverse direction and periodic boundary conditions in the remaining, lateral directions. Within the expansion in terms of ɛ =4 -d , where d is the spatial dimension of the bulk, the finite-size contribution to the free energy of the confined system and the associated critical Casimir force are calculated to leading order in ɛ and are compared to the corresponding expressions for an unconstrained (grand canonical) system. The constraint restricts the fluctuations within the system and it accordingly modifies the residual finite-size free energy. The resulting critical Casimir force is shown to depend on whether it is defined by assuming a fixed transverse area or a fixed total volume. In the former case, the constraint is typically found to significantly enhance the attractive character of the force as compared to the grand canonical case. In contrast to the grand canonical Casimir force, which, for supercritical temperatures, vanishes in the limit of thick films, in the canonical case with fixed transverse area the critical Casimir force attains for thick films a negative value for all boundary conditions studied here. Typically, the dependence of the critical Casimir force both on the temperaturelike and on the fieldlike scaling variables is different in the two

  11. 4-O-Methylhonokiol Protects HaCaT Cells from TGF-β1-Induced Cell Cycle Arrest by Regulating Canonical and Non-Canonical Pathways of TGF-β Signaling

    PubMed Central

    Kim, Sang-Cheol; Kang, Jung-Il; Hyun, Jin-Won; Kang, Ji-Hoon; Koh, Young-Sang; Kim, Young-Heui; Kim, Ki-Ho; Ko, Ji-Hee; Yoo, Eun-Sook; Kang, Hee-Kyoung

    2017-01-01

    4-O-methylhonokiol, a neolignan compound from Magnolia Officinalis, has been reported to have various biological activities including hair growth promoting effect. However, although transforming growth factor-β (TGF-β) signal pathway has an essential role in the regression induction of hair growth, the effect of 4-O-methylhonokiol on the TGF-β signal pathway has not yet been elucidated. We thus examined the effect of 4-O-methylhonokiol on TGF-β-induced canonical and noncanonical pathways in HaCaT human keratinocytes. When HaCaT cells were pretreated with 4-O-methylhonokiol, TGF-β1-induced G1/G0 phase arrest and TGF-β1-induced p21 expression were decreased. Moreover, 4-O-methylhonokiol inhibited nuclear translocation of Smad2/3, Smad4 and Sp1 in TGF-β1-induced canonical pathway. We observed that ERK phosphorylation by TGF-β1 was significantly attenuated by treatment with 4-O-methylhonokiol. 4-O-methylhonokiol inhibited TGF-β1-induced reactive oxygen species (ROS) production and reduced the increase of NADPH oxidase 4 (NOX4) mRNA level in TGF-β1-induced noncanonical pathway. These results indicate that 4-O-methylhonokiol could inhibit TGF-β1-induced cell cycle arrest through inhibition of canonical and noncanonical pathways in human keratinocyte HaCaT cell and that 4-O-methylhonokiol might have protective action on TGF-β1-induced cell cycle arrest. PMID:28190316

  12. 4-O-Methylhonokiol Protects HaCaT Cells from TGF-β1-Induced Cell Cycle Arrest by Regulating Canonical and Non-Canonical Pathways of TGF-β Signaling.

    PubMed

    Kim, Sang-Cheol; Kang, Jung-Il; Hyun, Jin-Won; Kang, Ji-Hoon; Koh, Young-Sang; Kim, Young-Heui; Kim, Ki-Ho; Ko, Ji-Hee; Yoo, Eun-Sook; Kang, Hee-Kyoung

    2017-07-01

    4- O -methylhonokiol, a neolignan compound from Magnolia Officinalis , has been reported to have various biological activities including hair growth promoting effect. However, although transforming growth factor-β (TGF-β) signal pathway has an essential role in the regression induction of hair growth, the effect of 4- O -methylhonokiol on the TGF-β signal pathway has not yet been elucidated. We thus examined the effect of 4- O -methylhonokiol on TGF-β-induced canonical and noncanonical pathways in HaCaT human keratinocytes. When HaCaT cells were pretreated with 4- O -methylhonokiol, TGF-β1-induced G1/G0 phase arrest and TGF-β1-induced p21 expression were decreased. Moreover, 4- O -methylhonokiol inhibited nuclear translocation of Smad2/3, Smad4 and Sp1 in TGF-β1-induced canonical pathway. We observed that ERK phosphorylation by TGF-β1 was significantly attenuated by treatment with 4- O -methylhonokiol. 4- O -methylhonokiol inhibited TGF-β1-induced reactive oxygen species (ROS) production and reduced the increase of NADPH oxidase 4 (NOX4) mRNA level in TGF-β1-induced noncanonical pathway. These results indicate that 4- O -methylhonokiol could inhibit TGF-β1-induced cell cycle arrest through inhibition of canonical and noncanonical pathways in human keratinocyte HaCaT cell and that 4- O -methylhonokiol might have protective action on TGF-β1-induced cell cycle arrest.

  13. Cloning, expression, and functional analysis of molecular motor pilT and pilU genes of type IV pili in Acidithiobacillus ferrooxidans.

    PubMed

    Li, Yongquan; Huang, Shuangsheng; Zhang, Xiaosu; Huang, Tao; Li, Hongyu

    2013-02-01

    PilT is a hexameric ATPase required for type IV pili (Tfp) retraction in gram-negative bacterium. Retraction of Tfp mediates intimate attachment and motility on inorganic solid surfaces. We investigated the cloning and expression of pilT and pilU genes of Acidithiobacillus ferrooxidans strains ATCC 23270, and the results indicate that PilT and PilU contain the canonical conserved AIRNLIRE and GMQTXXXXLXXL motifs that are the characteristic motifs of the PilT protein family; PilT and PilU also contain the canonical nucleotide-binding motifs, named with Walker A box (GxxGxGKT/S) and Walker B box (hhhhDE), respectively. The pilT and pilU genes were expressed to produce 37.1- and 42.0-kDa proteins, respectively, and co-transcribed induced by 10 % mineral powder. However, ATPase activity of PilT was distinctly higher than those of PilU. These results indicated that the PilT protein was the real molecular motor of Tfp, while PilU could play a key role in the assembly, modification, and twitching motility of Tfp in A. ferrooxidans. However, PilT and PilU were nonetheless interrelated in the forming and function of the molecular motor of Tfp.

  14. The Quality of Life of Hemodialysis Patients Is Affected Not Only by Medical but also Psychosocial Factors: a Canonical Correlation Study.

    PubMed

    Kim, Kyungmin; Kang, Gun Woo; Woo, Jungmin

    2018-04-02

    The quality of life (QoL) of patients with end-stage renal disease (ESRD) is very poor, plausibly due to both psychosocial and medical factors. This study aimed to determine the relationship among psychosocial factors, medical factors, and QoL in patients with ESRD undergoing hemodialysis (HD). In total, 55 male and 47 female patients were evaluated (mean age, 57.1 ± 12.0 years). The QoL was evaluated using the Korean version of World Health Organization Quality of Life Scale-Abbreviated Version. The psychosocial factors were evaluated using the Hospital Anxiety and Depression Scale, Multidimensional Scale of Perceived Social Support, Montreal Cognitive Assessment, Pittsburgh Sleep Quality Index, and Zarit Burden Interview. The medical factors were assessed using laboratory examinations. Correlation and canonical correlation analyses were performed to investigate the association patterns. The QoL was significantly correlated with the psychosocial factors, and to a lesser extent with the medical factors. The medical and psychosocial factors were also correlated. The canonical correlation analysis indicated a correlation between QoL and psychosocial factors (1st canonical correlation = 0.696, P < 0.001; 2nd canonical correlation = 0.421, P = 0.191), but not medical factors (1st canonical correlation = 0.478, P = 0.475; 2nd canonical correlation = 0.419, P = 0.751). The medical and psychosocial factors were also correlated (1st canonical correlation = 0.689, P < 0.001; 2nd canonical correlation = 0.603, P = 0.009). Psychosocial factors influence QoL in patients with ESRD, and should thus be carefully considered when caring for these patients in clinical practice. © 2018 The Korean Academy of Medical Sciences.

  15. The non-canonical Wnt receptor Ryk regulates hematopoietic stem cell repopulation in part by controlling proliferation and apoptosis.

    PubMed

    Famili, Farbod; Perez, Laura Garcia; Naber, Brigitta Ae; Noordermeer, Jasprina N; Fradkin, Lee G; Staal, Frank Jt

    2016-11-24

    The development of blood and immune cells requires strict control by various signaling pathways in order to regulate self-renewal, differentiation and apoptosis in stem and progenitor cells. Recent evidence indicates critical roles for the canonical and non-canonical Wnt pathways in hematopoiesis. The non-canonical Wnt pathway is important for establishment of cell polarity and cell migration and regulates apoptosis in the thymus. We here investigate the role of the non-canonical Wnt receptor Ryk in hematopoiesis and lymphoid development. We show that there are dynamic changes in Ryk expression during development and in different hematopoietic tissues. Functionally, Ryk regulates NK cell development in a temporal fashion. Moreover, Ryk-deficient mice show diminished, but not absent self-renewal of hematopoietic stem cells (HSC), via effects on mildly increased proliferation and apoptosis. Thus, Ryk deficiency in HSCs from fetal liver reduces their quiescence, leading to proliferation-induced apoptosis and decreased self-renewal.

  16. Structure of multiphoton quantum optics. I. Canonical formalism and homodyne squeezed states

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Dell'Anno, Fabio; De Siena, Silvio; Illuminati, Fabrizio

    2004-03-01

    We introduce a formalism of nonlinear canonical transformations for general systems of multiphoton quantum optics. For single-mode systems the transformations depend on a tunable free parameter, the homodyne local-oscillator angle; for n-mode systems they depend on n heterodyne mixing angles. The canonical formalism realizes nontrivial mixing of pairs of conjugate quadratures of the electromagnetic field in terms of homodyne variables for single-mode systems, and in terms of heterodyne variables for multimode systems. In the first instance the transformations yield nonquadratic model Hamiltonians of degenerate multiphoton processes and define a class of non-Gaussian, nonclassical multiphoton states that exhibit properties of coherencemore » and squeezing. We show that such homodyne multiphoton squeezed states are generated by unitary operators with a nonlinear time evolution that realizes the homodyne mixing of a pair of conjugate quadratures. Tuning of the local-oscillator angle allows us to vary at will the statistical properties of such states. We discuss the relevance of the formalism for the study of degenerate (up-)down-conversion processes. In a companion paper [F. Dell'Anno, S. De Siena, and F. Illuminati, 69, 033813 (2004)], we provide the extension of the nonlinear canonical formalism to multimode systems, we introduce the associated heterodyne multiphoton squeezed states, and we discuss their possible experimental realization.« less

  17. Correlations of occupation numbers in the canonical ensemble and application to a Bose-Einstein condensate in a one-dimensional harmonic trap

    NASA Astrophysics Data System (ADS)

    Giraud, Olivier; Grabsch, Aurélien; Texier, Christophe

    2018-05-01

    We study statistical properties of N noninteracting identical bosons or fermions in the canonical ensemble. We derive several general representations for the p -point correlation function of occupation numbers n1⋯np ¯. We demonstrate that it can be expressed as a ratio of two p ×p determinants involving the (canonical) mean occupations n1¯, ..., np¯, which can themselves be conveniently expressed in terms of the k -body partition functions (with k ≤N ). We draw some connection with the theory of symmetric functions and obtain an expression of the correlation function in terms of Schur functions. Our findings are illustrated by revisiting the problem of Bose-Einstein condensation in a one-dimensional harmonic trap, for which we get analytical results. We get the moments of the occupation numbers and the correlation between ground-state and excited-state occupancies. In the temperature regime dominated by quantum correlations, the distribution of the ground-state occupancy is shown to be a truncated Gumbel law. The Gumbel law, describing extreme-value statistics, is obtained when the temperature is much smaller than the Bose-Einstein temperature.

  18. The non-canonical functions of the heme oxygenases

    PubMed Central

    Tibullo, Daniele; Forte, Stefano; Zappalà, Agata; Volti, Giovanni Li

    2016-01-01

    Heme oxygenase (HO) isoforms catalyze the conversion of heme to carbon monoxide (CO) and biliverdin with a concurrent release of iron, which can drive the synthesis of ferritin for iron sequestration. Most of the studies so far were directed at evaluating the protective effect of these enzymes because of their ability to generate antioxidant and antiapoptotic molecules such as CO and bilirubin. Recent evidences are suggesting that HO may possess other important physiological functions, which are not related to its enzymatic activity and for which we would like to introduce for the first time the term “non canonical functions”. Recent evidence suggest that both HO isoforms may form protein-protein interactions (i.e. cytochrome P450, adiponectin, CD91) thus serving as chaperone-like protein. In addition, truncated HO-1 isoform was localized in the nuclear compartment under certain experimental conditions (i.e. excitotoxicity, hypoxia) regulating the activity of important nuclear transcription factors (i.e. Nrf2) and DNA repair. In the present review, we discuss three potential signaling mechanisms that we refer to as the non-canonical functions of the HO isoforms: protein-protein interaction, intracellular compartmentalization, and extracellular secretion. The aim of the present review is to describe each of this mechanism and all the aspects warranting additional studies in order to unravel all the functions of the HO system. PMID:27626166

  19. Hospitalization Costs for Patients Undergoing Orthopedic Surgery Treated With Intravenous Acetaminophen (IV-APAP) Plus Other IV Analgesics or IV Opioid Monotherapy for Postoperative Pain.

    PubMed

    Maiese, Brett A; Pham, An T; Shah, Manasee V; Eaddy, Michael T; Lunacsek, Orsolya E; Wan, George J

    2017-02-01

    To assess the impact on hospitalization costs of multimodal analgesia (MMA), including intravenous acetaminophen (IV-APAP), versus IV opioid monotherapy for postoperative pain management in patients undergoing orthopedic surgery. Utilizing the Truven Health MarketScan ® Hospital Drug Database (HDD), patients undergoing total knee arthroplasty (TKA), total hip arthroplasty (THA), or surgical repair of hip fracture between 1/1/2011 and 8/31/2014 were separated into postoperative pain management groups: MMA with IV-APAP plus other IV analgesics (IV-APAP group) or an IV opioid monotherapy group. All patients could have received oral analgesics. Baseline characteristics and total hospitalization costs were compared. Additionally, an inverse probability treatment weighting [IPTW] with propensity scores analysis further assessed hospitalization cost differences. The IV-APAP group (n = 33,954) and IV opioid monotherapy group (n = 110,300) differed significantly (P < 0.0001) across baseline characteristics, though the differences may not have been clinically meaningful. Total hospitalization costs (mean ± standard deviation) were significantly lower for the IV-APAP group than the IV opioid monotherapy group (US$12,540 ± $9564 vs. $13,242 ± $35,825; P < 0.0001). Medical costs accounted for $701 of the $702 between-group difference. Pharmacy costs were similar between groups. Results of the IPTW-adjusted analysis further supported the statistically significant cost difference. Patients undergoing orthopedic surgery who received MMA for postoperative pain management, including IV-APAP, had significantly lower total costs than patients who received IV opioid monotherapy. This difference was driven by medical costs; importantly, there was no difference in pharmacy costs. Generalizability of the results may be limited to patients admitted to hospitals similar to those included in HDD. Dosing could not be determined, so it was not possible to quantify utilization

  20. Coding principles of the canonical cortical microcircuit in the avian brain

    PubMed Central

    Calabrese, Ana; Woolley, Sarah M. N.

    2015-01-01

    Mammalian neocortex is characterized by a layered architecture and a common or “canonical” microcircuit governing information flow among layers. This microcircuit is thought to underlie the computations required for complex behavior. Despite the absence of a six-layered cortex, birds are capable of complex cognition and behavior. In addition, the avian auditory pallium is composed of adjacent information-processing regions with genetically identified neuron types and projections among regions comparable with those found in the neocortex. Here, we show that the avian auditory pallium exhibits the same information-processing principles that define the canonical cortical microcircuit, long thought to have evolved only in mammals. These results suggest that the canonical cortical microcircuit evolved in a common ancestor of mammals and birds and provide a physiological explanation for the evolution of neural processes that give rise to complex behavior in the absence of cortical lamination. PMID:25691736

  1. Relationship between climatic variables and the variation in bulk tank milk composition using canonical correlation analysis.

    PubMed

    Stürmer, Morgana; Busanello, Marcos; Velho, João Pedro; Heck, Vanessa Isabel; Haygert-Velho, Ione Maria Pereira

    2018-06-04

    A number of studies have addressed the relations between climatic variables and milk composition, but these works used univariate statistical approaches. In our study, we used a multivariate approach (canonical correlation) to study the impact of climatic variables on milk composition, price, and monthly milk production at a dairy farm using bulk tank milk data. Data on milk composition, price, and monthly milk production were obtained from a dairy company that purchased the milk from the farm, while climatic variable data were obtained from the National Institute of Meteorology (INMET). The data are from January 2014 to December 2016. Univariate correlation analysis and canonical correlation analysis were performed. Few correlations between the climatic variables and milk composition were found using a univariate approach. However, using canonical correlation analysis, we found a strong and significant correlation (r c  = 0.95, p value = 0.0029). Lactose, ambient temperature measures (mean, minimum, and maximum), and temperature-humidity index (THI) were found to be the most important variables for the canonical correlation. Our study indicated that 10.2% of the variation in milk composition, pricing, and monthly milk production can be explained by climatic variables. Ambient temperature variables, together with THI, seem to have the most influence on variation in milk composition.

  2. Zwitterionic versus canonical amino acids over the various defects in zeolites: A two-layer ONIOM calculation

    PubMed Central

    Yang, Gang; Zhou, Lijun

    2014-01-01

    Defects are often considered as the active sites for chemical reactions. Here a variety of defects in zeolites are used to stabilize zwitterionic glycine that is not self-stable in gas phase; in addition, effects of acidic strengths and zeolite channels on zwitterionic stabilization are demonstrated. Glycine zwitterions can be stabilized by all these defects and energetically prefer to canonical structures over Al and Ga Lewis acidic sites rather than Ti Lewis acidic site, silanol and titanol hydroxyls. For titanol (Ti-OH), glycine interacts with framework Ti and hydroxyl sites competitively, and the former with Lewis acidity predominates. The transformations from canonical to zwitterionic glycine are obviously more facile over Al and Ga Lewis acidic sites than over Ti Lewis acidic site, titanol and silanol hydroxyls. Charge transfers that generally increase with adsorption energies are found to largely decide the zwitterionic stabilization effects. Zeolite channels play a significant role during the stabilization process. In absence of zeolite channels, canonical structures predominate for all defects; glycine zwitterions remain stable over Al and Ga Lewis acidic sites and only with synergy of H-bonding interactions can exist over Ti Lewis acidic site, while automatically transform to canonical structures over silanol and titanol hydroxyls. PMID:25307449

  3. Relationship between climatic variables and the variation in bulk tank milk composition using canonical correlation analysis

    NASA Astrophysics Data System (ADS)

    Stürmer, Morgana; Busanello, Marcos; Velho, João Pedro; Heck, Vanessa Isabel; Haygert-Velho, Ione Maria Pereira

    2018-06-01

    A number of studies have addressed the relations between climatic variables and milk composition, but these works used univariate statistical approaches. In our study, we used a multivariate approach (canonical correlation) to study the impact of climatic variables on milk composition, price, and monthly milk production at a dairy farm using bulk tank milk data. Data on milk composition, price, and monthly milk production were obtained from a dairy company that purchased the milk from the farm, while climatic variable data were obtained from the National Institute of Meteorology (INMET). The data are from January 2014 to December 2016. Univariate correlation analysis and canonical correlation analysis were performed. Few correlations between the climatic variables and milk composition were found using a univariate approach. However, using canonical correlation analysis, we found a strong and significant correlation (r c = 0.95, p value = 0.0029). Lactose, ambient temperature measures (mean, minimum, and maximum), and temperature-humidity index (THI) were found to be the most important variables for the canonical correlation. Our study indicated that 10.2% of the variation in milk composition, pricing, and monthly milk production can be explained by climatic variables. Ambient temperature variables, together with THI, seem to have the most influence on variation in milk composition.

  4. Canonical Wnt Signaling as a Specific Marker for Normal and Tumorigenic Mammary Stem Cells

    DTIC Science & Technology

    2012-02-01

    These cells were identified by  flow   cytometry  to detect cells that were positive for CD24 and CD49f.   2. We have established that activation of Wnt...09-1-0072 TITLE: Canonical Wnt Signaling as a Specific marker for Normal and Tumorigenic Mammary Stem Cells PRINCIPAL...activation of canonical Wnt signaling may be a very specific marker for mammary stem cells and be a target for transformation that results in the

  5. Interglomerular Connectivity within the Canonical and GC-D/Necklace Olfactory Subsystems

    PubMed Central

    Puche, Adam C.; Munger, Steven D.

    2016-01-01

    The mammalian main olfactory system contains several subsystems that differ not only in the receptors they express and the glomerular targets they innervate within the main olfactory bulb (MOB), but also in the strategies they use to process odor information. The canonical main olfactory system employs a combinatorial coding strategy that represents odorant identity as a pattern of glomerular activity. By contrast, the "GC-D/necklace" olfactory subsystem—formed by olfactory sensory neurons expressing the receptor guanylyl cyclase GC-D and their target necklace glomeruli (NGs) encircling the caudal MOB—is critical for the detection of a small number of semiochemicals that promote the acquisition of food preferences. The formation of these socially-transmitted food preferences requires the animal to integrate information about two types of olfactory stimuli: these specialized social chemosignals and the food odors themselves. However, the neural mechanisms with which the GC-D/necklace subsystem processes this information are unclear. We used stimulus-induced increases in intrinsic fluorescence signals to map functional circuitry associated with NGs and canonical glomeruli (CGs) in the MOB. As expected, CG-associated activity spread laterally through both the glomerular and external plexiform layers associated with activated glomeruli. Activation of CGs or NGs resulted in activity spread between the two types of glomeruli; there was no evidence of preferential connectivity between individual necklace glomeruli. These results support previous anatomical findings that suggest the canonical and GC-D/necklace subsystems are functionally connected and may integrate general odor and semiochemical information in the MOB. PMID:27902696

  6. Preserving Catholic identity in mergers--an ethical and Canon Law perspective.

    PubMed

    Vowell, T H

    1992-03-01

    A merger or joint venture between a Catholic healthcare facility and a non-Catholic healthcare facility that provides procedures the Catholic Church believes to violate moral principles raises a number of issues to be considered by diocesan bishops. The 1983 Code of Canon Law provides bishops with guidelines to help establish the Catholicity of a Catholic hospital that has affiliated with a non-Catholic hospital. The diocesan bishop exercises his authority through a threefold ministry of teaching, sanctifying, and governing. These ministries stand as a reminder of his decision-making authority in matters that affect the spiritual state and growth of those entrusted to his care. Catholic identity, as it is presented in the Code of Canon Law, can be determined through the presence of a relationship between an institution and ecclesiastical authorities, the legal establishment of the entity, and a degree of control that the Church exercises over the institution. When evaluating a possible merger of joint venture between a Catholic hospital and a non-Catholic hospital that is performing procedures not in accord with Catholic Church teaching, the diocesan bishop must consider what limits must be observed. The good effects of the affiliation must be intended and direct, and the harmful effects must be perceived as unintended and indirect. The difficulties in determining and protecting the identity of Catholic hospitals in possible mergers or joint ventures should not prevent facilities from considering alternative forms of corporate structures. The Code of Canon Law and the Church's ethical teachings provide guidelines to ensure these possibilities.

  7. Robust Requirements Tracing via Internet Search Technology: Improving an IV and V Technique. Phase 2

    NASA Technical Reports Server (NTRS)

    Hayes, Jane; Dekhtyar, Alex

    2004-01-01

    There are three major objectives to this phase of the work. (1) Improvement of Information Retrieval (IR) methods for Independent Verification and Validation (IV&V) requirements tracing. Information Retrieval methods are typically developed for very large (order of millions - tens of millions and more documents) document collections and therefore, most successfully used methods somewhat sacrifice precision and recall in order to achieve efficiency. At the same time typical IR systems treat all user queries as independent of each other and assume that relevance of documents to queries is subjective for each user. The IV&V requirements tracing problem has a much smaller data set to operate on, even for large software development projects; the set of queries is predetermined by the high-level specification document and individual requirements considered as query input to IR methods are not necessarily independent from each other. Namely, knowledge about the links for one requirement may be helpful in determining the links of another requirement. Finally, while the final decision on the exact form of the traceability matrix still belongs to the IV&V analyst, his/her decisions are much less arbitrary than those of an Internet search engine user. All this suggests that the information available to us in the framework of the IV&V tracing problem can be successfully leveraged to enhance standard IR techniques, which in turn would lead to increased recall and precision. We developed several new methods during Phase II; (2) IV&V requirements tracing IR toolkit. Based on the methods developed in Phase I and their improvements developed in Phase II, we built a toolkit of IR methods for IV&V requirements tracing. The toolkit has been integrated, at the data level, with SAIC's SuperTracePlus (STP) tool; (3) Toolkit testing. We tested the methods included in the IV&V requirements tracing IR toolkit on a number of projects.

  8. The Life and Death of Axis IV: Caught in the Quest for a Theory of Mental Disorder

    ERIC Educational Resources Information Center

    Probst, Barbara

    2014-01-01

    Axis IV, one of the five dimensions of clinical description, has provided a way to report psychosocial and environmental problems that may affect the diagnosis, treatment, and/or prognosis of a psychiatric disorder. Originally conceived in DSM-III as a way to rate and rank the severity of particular environmental stressors, axis IV was simplified…

  9. Arsenic Induces Polyadenylation of Canonical Histone mRNA by Down-regulating Stem-Loop-binding Protein Gene Expression*

    PubMed Central

    Brocato, Jason; Fang, Lei; Chervona, Yana; Chen, Danqi; Kiok, Kathrin; Sun, Hong; Tseng, Hsiang-Chi; Xu, Dazhong; Shamy, Magdy; Jin, Chunyuan; Costa, Max

    2014-01-01

    The replication-dependent histone genes are the only metazoan genes whose messenger RNA (mRNA) does not terminate with a poly(A) tail at the 3′-end. Instead, the histone mRNAs display a stem-loop structure at their 3′-end. Stem-loop-binding protein (SLBP) binds the stem-loop and regulates canonical histone mRNA metabolism. Here we report that exposure to arsenic, a carcinogenic metal, decreased cellular levels of SLBP by inducing its proteasomal degradation and inhibiting SLBP transcription via epigenetic mechanisms. Notably, arsenic exposure dramatically increased polyadenylation of canonical histone H3.1 mRNA possibly through down-regulation of SLBP expression. The polyadenylated H3.1 mRNA induced by arsenic was not susceptible to normal degradation that occurs at the end of S phase, resulting in continued presence into mitosis, increased total H3.1 mRNA, and increased H3 protein levels. Excess expression of canonical histones have been shown to increase sensitivity to DNA damage as well as increase the frequency of missing chromosomes and induce genomic instability. Thus, polyadenylation of canonical histone mRNA following arsenic exposure may contribute to arsenic-induced carcinogenesis. PMID:25266719

  10. A Laboratory Astrophysical Jet to Study Canonical Flux Tubes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    You, Setthivoine

    Understanding the interaction between plasma flows and magnetic fields remains a fundamental problem in plasma physics, with important applications to astrophysics, fusion energy, and advanced space propulsion. For example, flows are of primary importance in astrophysical jets even if it is not fully understood how jets become so long without becoming unstable. Theories for the origin of magnetic fields in the cosmos rely on flowing charged fluids that should generate magnetic fields, yet this remains to be demonstrated experimentally. Fusion energy reactors can be made smaller with flows that improve stability and confinement. Advanced space propulsion could be more efficientmore » with collimated and stable plasma flows through magnetic nozzles but must eventually detach from the nozzle. In all these cases, there appears to be a spontaneous emergence of flowing and/or magnetic structures, suggesting a form of self-organization in plasmas. Beyond satisfying simple intellectual curiosity, understanding plasma self-organization could enable the development of methods to control plasma structures for fusion energy, space propulsion, and other applications. The research project has therefore built a theory and an experiment to investigate the interaction between magnetic fields and plasma flows. The theory is called canonical field theory for short, and the experiment is called Mochi after a rice cake filled with surprising, yet delicious fillings.« less

  11. The O IV and S IV intercombination lines in solar and stellar ultraviolet spectra

    NASA Technical Reports Server (NTRS)

    Cook, J. W.; Keenan, F. P.; Dufton, P. L.; Kingston, A. E.; Pradhan, A. K.; Zhang, H. L.; Doyle, J. G.; Hayes, M. A.

    1995-01-01

    New calculations of O IV electron density diagnostic emission-line ratios involving the 1399.8, 1401.2, 1404.8, and 14076.4 A transitions are presented. A comparison of these calculations with observational data from a quiet solar region, a sunspot, and an active region obtained with the High Resolution Telescope and Spectrograph (HRTS), two flares observed with the SO82B spectrograph on board Skylab, and Hubble Space Telescope (HST) observations by the Goddard High Resolution Spectrograph (GHRS) of Capella, gives good results using the ratio R(sub 1) = I(1407.4 A)/I(1401.2 A). However, the electron density obtained using the ratio R(sub 2) = I(1407.4 A)/I(1404.8 A) is often an order of magnitude smaller. The O IV 1404.8 A line is blended with the S IV 1404.8 A line, and we investigate whether this ratio may still be used as a density diagnostic if the S IV 1406.1 A line intensity is used to correct for the presence of S IV 1404.8 A, using previous S IV calculations by Dufton et al. We still find systematic differences compared to density determinations from line ratios that do not involve the O IV 1404.8 A line, which we suggest are due to errors in earlier theoretical calculations of the S IV atomic data, and also possibly to previously unconsidered fluorescent pumping of the upper level of the S IV 1404.8 A transition.

  12. An Item Response Theory Analysis of DSM-IV Cannabis Abuse and Dependence Criteria in Adolescents

    PubMed Central

    Hartman, Christie A.; Gelhorn, Heather; Crowley, Thomas J.; Sakai, Joseph T.; Stallings, Michael; Young, Susan E.; Rhee, Soo Hyun; Corley, Robin; Hewitt, John K.; Hopfer, Christian J.

    2008-01-01

    Objective To examine three aspects of adolescent cannabis problems: 1) do DSM-IV cannabis abuse and dependence criteria represent two different levels of severity of substance involvement, 2) to what degree do each of the 11 abuse and dependence criteria assess adolescent cannabis problems, and 3) do the DSM-IV items function similarly across different adolescent populations? Method We examined 5587 adolescents aged 11–19, including 615 youth in treatment for substance use disorders, 179 adjudicated youth, and 4793 youth from the community. All subjects were assessed with a structured diagnostic interview. Item response theory was utilized to analyze symptom endorsement patterns. Results Abuse and dependence criteria were not found to represent different levels of severity of problem cannabis use in any of the samples. Among the 11 abuse and dependence criteria, Problems cutting down and Legal problems were the least informative for distinguishing problem users. Two dependence criteria and three of the four abuse criteria indicated different severities of cannabis problems across samples. Conclusions We found little evidence to support the idea that abuse and dependence are separate constructs for adolescent cannabis problems. Furthermore, certain abuse criteria may indicate severe substance problems while specific dependence items may indicate less severe problems. The abuse items in particular need further study. These results have implications for the refinement of the current substance use disorder criteria for DSM-V. PMID:18176333

  13. Anomaly-free cosmological perturbations in effective canonical quantum gravity

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Barrau, Aurelien; Bojowald, Martin; Kagan, Mikhail

    2015-05-01

    This article lays out a complete framework for an effective theory of cosmological perturbations with corrections from canonical quantum gravity. Since several examples exist for quantum-gravity effects that change the structure of space-time, the classical perturbative treatment must be rethought carefully. The present discussion provides a unified picture of several previous works, together with new treatments of higher-order perturbations and the specification of initial states.

  14. Regulation of mitochondrial bioenergetics by the non-canonical roles of mitochondrial dynamics proteins in the heart.

    PubMed

    Wang, Wang; Fernandez-Sanz, Celia; Sheu, Shey-Shing

    2018-05-01

    Recent advancement in mitochondrial research has significantly extended our knowledge on the role and regulation of mitochondria in health and disease. One important breakthrough is the delineation of how mitochondrial morphological changes, termed mitochondrial dynamics, are coupled to the bioenergetics and signaling functions of mitochondria. In general, it is believed that fusion leads to an increased mitochondrial respiration efficiency and resistance to stress-induced dysfunction while fission does the contrary. This concept seems not applicable to adult cardiomyocytes. The mitochondria in adult cardiomyocytes exhibit fragmented morphology (tilted towards fission) and show less networking and movement as compared to other cell types. However, being the most energy-demanding cells, cardiomyocytes in the adult heart possess vast number of mitochondria, high level of energy flow, and abundant mitochondrial dynamics proteins. This apparent discrepancy could be explained by recently identified new functions of the mitochondrial dynamics proteins. These "non-canonical" roles of mitochondrial dynamics proteins range from controlling inter-organelle communication to regulating cell viability and survival under metabolic stresses. Here, we summarize the newly identified non-canonical roles of mitochondrial dynamics proteins. We focus on how these fission and fusion independent roles of dynamics proteins regulate mitochondrial bioenergetics. We also discuss potential molecular mechanisms, unique intracellular location, and the cardiovascular disease relevance of these non-canonical roles of the dynamics proteins. We propose that future studies are warranted to differentiate the canonical and non-canonical roles of dynamics proteins and to identify new approaches for the treatment of heart diseases. This article is part of a Special issue entitled Cardiac adaptations to obesity, diabetes and insulin resistance, edited by Professors Jan F.C. Glatz, Jason R.B. Dyck and

  15. Medical Problems. Child Health and Safety Series (Module IV).

    ERIC Educational Resources Information Center

    Iscoe, Louise; And Others

    This manual for child care personnel in day care homes and centers provides guidelines and information on the detection, treatment, and control of medical problems of children. Introductory materials focus on signs of illness which carepersons can recognize. Section II concentrates on insect, animal and human bites. Section III discusses skin…

  16. Functions of the APC tumor suppressor protein dependent and independent of canonical WNT signaling: implications for therapeutic targeting.

    PubMed

    Hankey, William; Frankel, Wendy L; Groden, Joanna

    2018-03-01

    The acquisition of biallelic mutations in the APC gene is a rate-limiting step in the development of most colorectal cancers and occurs in the earliest lesions. APC encodes a 312-kDa protein that localizes to multiple subcellular compartments and performs diverse functions. APC participates in a cytoplasmic complex that promotes the destruction of the transcriptional licensing factor β-catenin; APC mutations that abolish this function trigger constitutive activation of the canonical WNT signaling pathway, a characteristic found in almost all colorectal cancers. By negatively regulating canonical WNT signaling, APC counteracts proliferation, promotes differentiation, facilitates apoptosis, and suppresses invasion and tumor progression. APC further antagonizes canonical WNT signaling by interacting with and counteracting β-catenin in the nucleus. APC also suppresses tumor initiation and progression in the colorectal epithelium through functions that are independent of canonical WNT signaling. APC regulates the mitotic spindle to facilitate proper chromosome segregation, localizes to the cell periphery and cell protrusions to establish cell polarity and appropriate directional migration, and inhibits DNA replication by interacting directly with DNA. Mutations in APC are often frameshifts, insertions, or deletions that introduce premature stop codons and lead to the production of truncated APC proteins that lack its normal functions and possess tumorigenic properties. Therapeutic approaches in development for the treatment of APC-deficient tumors are focused on the inhibition of canonical WNT signaling, especially through targets downstream of APC in the pathway, or on the restoration of wild-type APC expression.

  17. Functions of the APC tumor suppressor protein dependent and independent of canonical WNT signaling: Implications for therapeutic targeting

    PubMed Central

    Hankey, William; Frankel, Wendy L.

    2018-01-01

    The acquisition of biallelic mutations in the APC gene is a rate-limiting step in the development of most colorectal cancers and occurs in the earliest lesions. APC encodes a 312-kDa protein that localizes to multiple subcellular compartments and performs diverse functions. APC participates in a cytoplasmic complex that promotes the destruction of the transcriptional licensing factor β-catenin; APC mutations that abolish this function trigger constitutive activation of the canonical WNT signaling pathway, a characteristic found in almost all colorectal cancers. By negatively regulating canonical WNT signaling, APC counteracts proliferation, promotes differentiation, facilitates apoptosis and suppresses invasion and tumor progression. APC further antagonizes canonical WNT signaling by interacting with and counteracting β-catenin in the nucleus. APC also suppresses tumor initiation and progression in the colorectal epithelium through functions that are independent of canonical WNT signaling. APC regulates the mitotic spindle to facilitate proper chromosome segregation, localizes to the cell periphery and cell protrusions to establish cell polarity and appropriate directional migration, and inhibits DNA replication by interacting directly with DNA. Mutations in APC are often frameshifts, insertions or deletions that introduce premature stop codons and lead to the production of truncated APC proteins that lack its normal functions and possess tumorigenic properties. Therapeutic approaches in development for the treatment of APC-deficient tumors are focused on the inhibition of canonical WNT signaling, especially through targets downstream of APC in the pathway, or on the restoration of wild-type APC expression. PMID:29318445

  18. Investigating the Relationship between Conceptual and Procedural Errors in the Domain of Probability Problem-Solving.

    ERIC Educational Resources Information Center

    O'Connell, Ann Aileen

    The relationships among types of errors observed during probability problem solving were studied. Subjects were 50 graduate students in an introductory probability and statistics course. Errors were classified as text comprehension, conceptual, procedural, and arithmetic. Canonical correlation analysis was conducted on the frequencies of specific…

  19. Generalized prolate spheroidal wave functions for optical finite fractional Fourier and linear canonical transforms.

    PubMed

    Pei, Soo-Chang; Ding, Jian-Jiun

    2005-03-01

    Prolate spheroidal wave functions (PSWFs) are known to be useful for analyzing the properties of the finite-extension Fourier transform (fi-FT). We extend the theory of PSWFs for the finite-extension fractional Fourier transform, the finite-extension linear canonical transform, and the finite-extension offset linear canonical transform. These finite transforms are more flexible than the fi-FT and can model much more generalized optical systems. We also illustrate how to use the generalized prolate spheroidal functions we derive to analyze the energy-preservation ratio, the self-imaging phenomenon, and the resonance phenomenon of the finite-sized one-stage or multiple-stage optical systems.

  20. On unified modeling, theory, and method for solving multi-scale global optimization problems

    NASA Astrophysics Data System (ADS)

    Gao, David Yang

    2016-10-01

    A unified model is proposed for general optimization problems in multi-scale complex systems. Based on this model and necessary assumptions in physics, the canonical duality theory is presented in a precise way to include traditional duality theories and popular methods as special applications. Two conjectures on NP-hardness are proposed, which should play important roles for correctly understanding and efficiently solving challenging real-world problems. Applications are illustrated for both nonconvex continuous optimization and mixed integer nonlinear programming.

  1. The Canon and Cultural Studies: Culture and Anarchy in Gotham City.

    ERIC Educational Resources Information Center

    DeBona, Guerric

    1997-01-01

    Finds that including media studies at the end of a traditional literature course is an effective pedagogical instrument for instigating discussion regarding the literary canon, since students recognize and address the important contribution of popular culture when it is in dialogue with more traditional material. Selects the film…

  2. Diagnostic orphans: comparing self-report lifetime course to groups with DSM-IV alcohol abuse and dependence.

    PubMed

    McBride, Orla; Adamson, Gary; Bunting, Brendan; McCann, Siobhan

    2009-01-01

    Research has highlighted the significant alcohol symptoms and mental health problems experienced by diagnostic orphans - individuals who experience 1-2 criteria of DSM-IV alcohol dependence but do not meet the criteria for a DSM-IV alcohol use disorder. This study used a sub-sample (n=34827) from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), and formed mutually exclusive groups to compare the self-report retrospective course of diagnostic orphans to individuals with DSM-IV abuse and dependence. Multinomial logistic regressions were conducted to examine the associations between the groups and a range of demographic and clinical variables. Collectively, the findings demonstrate that diagnostic orphans shared similar characteristics to the abuse and dependence groups, but appeared to experience specific comorbid mental health problems. Orphan status has the potential to be a persistent condition and may result in significant dysfunction. In conclusion, diagnostic orphans represent a distinct group that may benefit from cost-effective treatment or intervention, designed to prevent the escalation of alcohol symptoms.

  3. Advantages and Disadvantages of the Amplatzer Vascular Plug IV in Visceral Embolization: Report of 50 Placements

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Pech, Maciej, E-mail: maciej.pech@med.ovgu.de; Mohnike, Konrad; Wieners, Gero

    2011-10-15

    Purpose: We describe our initial clinical experience in artificial embolization with the Amplatzer Vascular Plug IV (VP IV), a further development of the Vascular Plug family already in routine use. Methods: Results from 50 embolization procedures conducted with the VP IV in 44 patients are summarized. Results: All 50 embolizations were successful, although two required the technique to be modified because of problems with jamming of the screw thread and thus with disconnection of the plug. This was associated with large branching angles. Conclusions: With experience, the VP IV can be used safely and effectively, and it expands the spectrummore » of possible embolizations in interventional radiology. Its greatest disadvantage is its relatively poor positional controllability.« less

  4. Alcohol use, alcohol problems, and problem behavior engagement among students at two schools in northern Mexico

    PubMed Central

    Mancha, Brent E.; Rojas, Vanessa C.; Latimer, William W.

    2012-01-01

    This study examined the association between alcohol use problem severity, defined by number of DSM-IV alcohol Abuse and Dependence symptoms and frequency of alcohol use, and problem behavior engagement among Mexican students. A confidential survey was administered to 1229 students in grades 7–12 at two schools in a northern border city in Mexico. Youths were categorized into five groups based on their alcohol use frequency and symptoms of DSM-IV alcohol Abuse and Dependence, specifically: no lifetime alcohol use, lifetime alcohol use but none in the past year, past year alcohol use, one or two alcohol Abuse or Dependence symptoms, and three or more alcohol Abuse or Dependence symptoms. The association between five levels of alcohol use problem severity and three problem behaviors, lifetime marijuana use, lifetime sexual intercourse, and past year arrest/law trouble, was examined using chi-square or Fisher’s exact tests. Several alcohol use problem severity categories were significantly different with respect to rates of lifetime marijuana use, lifetime sexual intercourse, and past year arrest/law trouble. Higher alcohol use problem severity was associated with greater endorsement of problem behaviors. Knowing about variations in adolescent alcohol use and alcohol problems may be instrumental in determining if youths are also engaging in a range of other risk behaviors. Considering varying levels of alcohol use and alcohol problems is important for effective targeted prevention and treatment interventions. PMID:22840814

  5. Multilayer adsorption of C2H4 and CF4 on graphite: Grand Canonical Monte Carlo simulation

    NASA Astrophysics Data System (ADS)

    Abdelatif, H.; Drir, M.

    2016-11-01

    We study the phase transitions in adsorbed multilayers by Grand Canonical Monte Carlo simulations (GCMC) of the lattice-gas model. The focus will be on ethylene (C2H4) and tetrafluoromethane (CF4) on a homogeneous graphite surface. Earlier simulations of these systems investigated structural properties, dynamical behaviors of adsorbed films and thermodynamic quantities such as isosteric heat. The main purpose of this study is to consider the adsorbed multilayers by the evaluation of the layering behavior, the wetting phenomena and the critical temperatures. The isotherms obtained for temperature from 50 K to 170 K reproduce a number of interesting features observed experimentally: (i) we observe an important number of layers in contrast with previous simulations, (ii) a finite number of layers at saturated pressure for low temperatures are found, (iii) the isotherms present vertical steps typical of layer-by-layer growth, at higher temperatures these distinct layers tend to disappear signifying that the film thickness increases continuously, (iv) a thin film to thick film transition near the triple point temperature is noticed. In addition to this qualitative description, quantitative information are determined including temperatures and relative pressures of layers formation, layer-critical-point temperatures and phase diagrams. Comparing the two systems, ethylene/graphite and tetrafluoromethane/graphite, we observe a qualitatively similar behavior.

  6. Gender Differences in and the Relationships Between Social Anxiety and Problematic Internet Use: Canonical Analysis.

    PubMed

    Baloğlu, Mustafa; Özteke Kozan, Hatice İrem; Kesici, Şahin

    2018-01-24

    The cognitive-behavioral model of problematic Internet use (PIU) proposes that psychological well-being is associated with specific thoughts and behaviors on the Internet. Hence, there is growing concern that PIU is associated with psychological impairments. Given the proposal of gender schema theory and social role theory, men and women are predisposed to experience social anxiety and engage in Internet use differently. Thus, an investigation of gender differences in these areas is warranted. According to the cognitive-behavioral model of PIU, social anxiety is associated with specific cognitions and behaviors on the Internet. Thus, an investigation of the association between social anxiety and PIU is essential. In addition, research that takes into account the multidimensional nature of social anxiety and PIU is lacking. Therefore, this study aimed to explore multivariate gender differences in and the relationships between social anxiety and PIU. Participants included 505 college students, of whom 241 (47.7%) were women and 264 (52.3%) were men. Participants' ages ranged from 18 to 22 years, with a mean age of 20.34 (SD=1.16). The Social Anxiety Scale and Problematic Internet Use Scale were used in data collection. Multivariate analysis of variance (MANOVA) and canonical correlation analysis were used. Mean differences between men and women were not statistically significant in social anxiety (λ=.02, F3,501=2.47, P=.06). In all three PIU dimensions, men scored higher than women, and MANOVA shows that multivariate difference was statistically significant (λ=.94, F3,501=10.69, P<.001). Of the canonical correlation functions computed for men, only the first was significant (Rc=.43, λ=.78, χ29=64.7, P<.001) and accounted for 19% of the overlapping variance. Similarly, only the first canonical function was significant for women (Rc=.36, λ=.87, χ29=33.9, P<.001), which accounted for 13% of the overlapping variance. On the basis of the findings, we conclude that

  7. Toward a generalized equation for the Reynolds stress: Turbulence momentum balance in non-canonical flows

    NASA Astrophysics Data System (ADS)

    Lee, T.-W.

    2017-11-01

    Recently, we developed a theoretical basis for determination of the Reynolds stress in canonical flows. Writing momentum balance for a control volume moving at the local mean velocity, along with a differential transform ∂/∂x =C1 U∂/∂y , a turbulence momentum balance is discovered which includes the Reynolds stress as a function of root turbulence parameters: ∂(u'v')/∂y = -C1 U∂u'2/∂y +νm∂2urms'/∂y2 . Then, the Reynolds stress can simply be computed by integrating in the y-direction using the right-hand side (RHS). This is obviously a far simplification of complex modeling of the Reynolds stress, but contains the correct physics, as borne out by comparisons with experimental and DNS data in canonical flows in our earlier works (e.g. in APS 2016). The RHS contains only two parameters, U and u'. In this work, we seek extensions of this solution to non-canonical flows such as wakes, flow over a step, and mixing layers. Comparisons with experimental and DNS data will be presented.

  8. Installation Restoration Program. Phase II: Stage 1 Problem Confirmation Study, Duluth International Airport, Duluth, Minnesota.

    DTIC Science & Technology

    1984-10-01

    8 iii "i t-. Table of Contents (cont.) Section Title Page -APPENDIX A Acronyms, Definitions, Nomenclature and Units of Measure B Scope of Work, Task...Identification/Records Search Phase II - Problem Confirmation and Quantification Phase III - Technology Base Development Phase IV - Corrective Action Only...Problem Identification/Records Search Phase II - Problem Confirmation and Quantification Phase III - Technology Base Development Phase IV - Corrective

  9. GRB 060614 in the canonical fireshell model

    NASA Astrophysics Data System (ADS)

    Caito, L.; Bernardini, M. G.; Bianco, C. L.; Dainotti, M. G.; Guida, R.; Ruffini, R.

    2008-10-01

    Gamma-Ray Burst (GRB) 060614 is the first nearby long duration GRB clearly not associated to any bright Ib/c Supernova. The explosion of this burst undermines one of the fundamental assumptions of the standard scenario and opens new horizons and hints of investigation. GRB 060614, hardly classifiable as a short GRB, is not either a ``typical'' long GRB since it occurs in a low star forming region. Moreover, it presents deep similarities with GRB 970228, which is the prototype of the ``fake'' short bursts, or better canonical GRBs disguised as short ones. Within the ``fireshell'' model ([1]), we test if this ``anomalous'' source can be a disguised short GRB([2]).

  10. Uncertainty relations, zero point energy and the linear canonical group

    NASA Technical Reports Server (NTRS)

    Sudarshan, E. C. G.

    1993-01-01

    The close relationship between the zero point energy, the uncertainty relations, coherent states, squeezed states, and correlated states for one mode is investigated. This group-theoretic perspective enables the parametrization and identification of their multimode generalization. In particular the generalized Schroedinger-Robertson uncertainty relations are analyzed. An elementary method of determining the canonical structure of the generalized correlated states is presented.

  11. Phase transition and thermodynamic geometry of f (R ) AdS black holes in the grand canonical ensemble

    NASA Astrophysics Data System (ADS)

    Li, Gu-Qiang; Mo, Jie-Xiong

    2016-06-01

    The phase transition of a four-dimensional charged AdS black hole solution in the R +f (R ) gravity with constant curvature is investigated in the grand canonical ensemble, where we find novel characteristics quite different from that in the canonical ensemble. There exists no critical point for T -S curve while in former research critical point was found for both the T -S curve and T -r+ curve when the electric charge of f (R ) black holes is kept fixed. Moreover, we derive the explicit expression for the specific heat, the analog of volume expansion coefficient and isothermal compressibility coefficient when the electric potential of f (R ) AdS black hole is fixed. The specific heat CΦ encounters a divergence when 0 <Φ b . This finding also differs from the result in the canonical ensemble, where there may be two, one or no divergence points for the specific heat CQ . To examine the phase structure newly found in the grand canonical ensemble, we appeal to the well-known thermodynamic geometry tools and derive the analytic expressions for both the Weinhold scalar curvature and Ruppeiner scalar curvature. It is shown that they diverge exactly where the specific heat CΦ diverges.

  12. Complexation-assisted reduction: complexes of glutaroimide-dioxime with tetravalent actinides (Np( iv ) and Th( iv ))

    DOE PAGES

    Zhang, Zhicheng; Parker, Bernard F.; Lohrey, Trevor D.; ...

    2018-01-01

    Glutaroimide-dioxime forms strong complexes with Np( iv ) and Th( iv ) in aqueous solution and in crystals. The formation of Np( iv ) complexes from initial Np( v ) is interpreted by a complexation-assisted reduction mechanism.

  13. Complexation-assisted reduction: complexes of glutaroimide-dioxime with tetravalent actinides (Np( iv ) and Th( iv ))

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhang, Zhicheng; Parker, Bernard F.; Lohrey, Trevor D.

    Glutaroimide-dioxime forms strong complexes with Np( iv ) and Th( iv ) in aqueous solution and in crystals. The formation of Np( iv ) complexes from initial Np( v ) is interpreted by a complexation-assisted reduction mechanism.

  14. Latent classes of emotional and behavioural problems in epidemiological and referred samples and their relations to DSM-IV diagnoses.

    PubMed

    Bianchi, Valentina; Brambilla, Paolo; Garzitto, Marco; Colombo, Paola; Fornasari, Livia; Bellina, Monica; Bonivento, Carolina; Tesei, Alessandra; Piccin, Sara; Conte, Stefania; Perna, Giampaolo; Frigerio, Alessandra; Castiglioni, Isabella; Fabbro, Franco; Molteni, Massimo; Nobile, Maria

    2017-05-01

    Researchers' interest have recently moved toward the identification of recurrent psychopathological profiles characterized by concurrent elevations on different behavioural and emotional traits. This new strategy turned to be useful in terms of diagnosis and outcome prediction. We used a person-centred statistical approach to examine whether different groups could be identified in a referred sample and in a general-population sample of children and adolescents, and we investigated their relation to DSM-IV diagnoses. A latent class analysis (LCA) was performed on the Child Behaviour Checklist (CBCL) syndrome scales of the referred sample (N = 1225), of the general-population sample (N = 3418), and of the total sample. Models estimating 1-class through 5-class solutions were compared and agreement in the classification of subjects was evaluated. Chi square analyses, a logistic regression, and a multinomial logistic regression analysis were used to investigate the relations between classes and diagnoses. In the two samples and in the total sample, the best-fitting models were 4-class solutions. The identified classes were Internalizing Problems (15.68%), Severe Dysregulated (7.82%), Attention/Hyperactivity (10.19%), and Low Problems (66.32%). Subsequent analyses indicated a significant relationship between diagnoses and classes as well as a main association between the severe dysregulated class and comorbidity. Our data suggested the presence of four different psychopathological profiles related to different outcomes in terms of psychopathological diagnoses. In particular, our results underline the presence of a profile characterized by severe emotional and behavioural dysregulation that is mostly associated with the presence of multiple diagnosis.

  15. CaV channels and cancer: canonical functions indicate benefits of repurposed drugs as cancer therapeutics.

    PubMed

    Buchanan, Paul J; McCloskey, Karen D

    2016-10-01

    The importance of ion channels in the hallmarks of many cancers is increasingly recognised. This article reviews current knowledge of the expression of members of the voltage-gated calcium channel family (Ca V ) in cancer at the gene and protein level and discusses their potential functional roles. The ten members of the Ca V channel family are classified according to expression of their pore-forming α-subunit; moreover, co-expression of accessory α2δ, β and γ confers a spectrum of biophysical characteristics including voltage dependence of activation and inactivation, current amplitude and activation/inactivation kinetics. Ca V channels have traditionally been studied in excitable cells including neurones, smooth muscle, skeletal muscle and cardiac cells, and drugs targeting the channels are used in the treatment of hypertension and epilepsy. There is emerging evidence that several Ca V channels are differentially expressed in cancer cells compared to their normal counterparts. Interestingly, a number of Ca V channels also have non-canonical functions and are involved in transcriptional regulation of the expression of other proteins including potassium channels. Pharmacological studies show that Ca V canonical function contributes to the fundamental biology of proliferation, cell-cycle progression and apoptosis. This raises the intriguing possibility that calcium channel blockers, approved for the treatment of other conditions, could be repurposed to treat particular cancers. Further research will reveal the full extent of both the canonical and non-canonical functions of Ca V channels in cancer and whether calcium channel blockers are beneficial in cancer treatment.

  16. Supramolecular Organization of the α121-α565 Collagen IV Network*

    PubMed Central

    Robertson, Wesley E.; Rose, Kristie L.; Hudson, Billy G.; Vanacore, Roberto M.

    2014-01-01

    Collagen IV is a family of 6 chains (α1-α6), that form triple-helical protomers that assemble into supramolecular networks. Two distinct networks with chain compositions of α121 and α345 have been established. These oligomerize into separate α121 and α345 networks by a homotypic interaction through their trimeric noncollagenous (NC1) domains, forming α121 and α345 NC1 hexamers, respectively. These are stabilized by novel sulfilimine (SN) cross-links, a covalent cross-link that forms between Met93 and Hyl211 at the trimer-trimer interface. A third network with a composition of α1256 has been proposed, but its supramolecular organization has not been established. In this study we investigated the supramolecular organization of this network by determining the chain identity of sulfilimine-cross-linked NC1 domains derived from the α1256 NC1 hexamer. High resolution mass spectrometry analyses of peptides revealed that sulfilimine bonds specifically cross-link α1 to α5 and α2 to α6 NC1 domains, thus providing the spatial orientation between interacting α121 and α565 trimers. Using this information, we constructed a three-dimensional homology model in which the α565 trimer shows a good chemical and structural complementarity to the α121 trimer. Our studies provide the first chemical evidence for an α565 protomer and its heterotypic interaction with the α121 protomer. Moreover, our findings, in conjunction with our previous studies, establish that the six collagen IV chains are organized into three canonical protomers α121, α345, and α565 forming three distinct networks: α121, α345, and α121-α565, each of which is stabilized by sulfilimine bonds between their C-terminal NC1 domains. PMID:25006246

  17. 41 CFR 102-173.90 - Are there any special restrictions on the use and registration of canonical, or category names...

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... restrictions on the use and registration of canonical, or category names like recreation.gov? 102-173.90... (Continued) FEDERAL MANAGEMENT REGULATION TELECOMMUNICATIONS 173-INTERNET GOV DOMAIN Registration § 102-173... like recreation.gov? Yes, canonical names registration request must provide access coverage for the...

  18. 41 CFR 102-173.90 - Are there any special restrictions on the use and registration of canonical, or category names...

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... restrictions on the use and registration of canonical, or category names like recreation.gov? 102-173.90... (Continued) FEDERAL MANAGEMENT REGULATION TELECOMMUNICATIONS 173-INTERNET GOV DOMAIN Registration § 102-173... like recreation.gov? Yes, canonical names registration request must provide access coverage for the...

  19. 41 CFR 102-173.90 - Are there any special restrictions on the use and registration of canonical, or category names...

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... restrictions on the use and registration of canonical, or category names like recreation.gov? 102-173.90... (Continued) FEDERAL MANAGEMENT REGULATION TELECOMMUNICATIONS 173-INTERNET GOV DOMAIN Registration § 102-173... like recreation.gov? Yes, canonical names registration request must provide access coverage for the...

  20. 41 CFR 102-173.90 - Are there any special restrictions on the use and registration of canonical, or category names...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... restrictions on the use and registration of canonical, or category names like recreation.gov? 102-173.90... (Continued) FEDERAL MANAGEMENT REGULATION TELECOMMUNICATIONS 173-INTERNET GOV DOMAIN Registration § 102-173... like recreation.gov? Yes, canonical names registration request must provide access coverage for the...

  1. 41 CFR 102-173.90 - Are there any special restrictions on the use and registration of canonical, or category names...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... restrictions on the use and registration of canonical, or category names like recreation.gov? 102-173.90... (Continued) FEDERAL MANAGEMENT REGULATION TELECOMMUNICATIONS 173-INTERNET GOV DOMAIN Registration § 102-173... like recreation.gov? Yes, canonical names registration request must provide access coverage for the...

  2. The role of word order in the interpretation of canonical and non-canonical graphic symbol utterances: A developmental study.

    PubMed

    Trudeau, Natacha; Morford, Jill P; Sutton, Ann

    2010-06-01

    Graphic symbols are often used to represent words in Augmentative and Alternative Communication systems. Previous findings suggest that different processes operate when using graphic symbols and when using speech. This study assessed the ability of native speakers of French with no communication disorders from four age groups to interpret graphic-symbol sequences of varying length and canonicity. Results reveal that, as they get older, participants show an increase in their capacity to interpret graphic-symbol sequences. Constituent order played an important role in the interpretation of the sequences. However, the specific word-order strategies used varied depending on the age group and the type of sequence presented.

  3. Havelock Ellis's literary criticism, canon formation, and the heterosexual Shakespeare.

    PubMed

    Radel, Nicholas F

    2009-01-01

    Famous as the author of an early full-length scientific study of sexual inversion or homosexuality, English sexologist Havelock Ellis was also a literary critic responsible for initiating publication of the famous Mermaid Series of "The Best of Plays of the Old Dramatists" in the late-nineteenth century. Personally editing the first volume of plays by Christopher Marlowe and a later collection by tragedian John Ford, Ellis associated these playwrights here and in his scientific work, Sexual Inversion, with ideas about normative and so-called abnormal sexualities at the start of the twentieth century. Ellis, thus, helped give expression to a literary canon of early English dramatists in which modern, anachronistic ideas about sexual subjectivity play a part. While this article does not claim that Ellis was the necessary source for later criticism, it shows how, over the whole of the twentieth century, Shakespeare's priority in the literary canon came to be posited at least in part on his apparent sexual normality in contrast with a supposedly homosexual Christopher Marlowe and other playwrights such as Ford or Francis Beaumont and John Fletcher associated with varying degrees of sexual difference.

  4. A New Ensemble Canonical Correlation Prediction Scheme for Seasonal Precipitation

    NASA Technical Reports Server (NTRS)

    Kim, Kyu-Myong; Lau, William K. M.; Li, Guilong; Shen, Samuel S. P.; Lau, William K. M. (Technical Monitor)

    2001-01-01

    Department of Mathematical Sciences, University of Alberta, Edmonton, Canada This paper describes the fundamental theory of the ensemble canonical correlation (ECC) algorithm for the seasonal climate forecasting. The algorithm is a statistical regression sch eme based on maximal correlation between the predictor and predictand. The prediction error is estimated by a spectral method using the basis of empirical orthogonal functions. The ECC algorithm treats the predictors and predictands as continuous fields and is an improvement from the traditional canonical correlation prediction. The improvements include the use of area-factor, estimation of prediction error, and the optimal ensemble of multiple forecasts. The ECC is applied to the seasonal forecasting over various parts of the world. The example presented here is for the North America precipitation. The predictor is the sea surface temperature (SST) from different ocean basins. The Climate Prediction Center's reconstructed SST (1951-1999) is used as the predictor's historical data. The optimally interpolated global monthly precipitation is used as the predictand?s historical data. Our forecast experiments show that the ECC algorithm renders very high skill and the optimal ensemble is very important to the high value.

  5. Data analytics using canonical correlation analysis and Monte Carlo simulation

    NASA Astrophysics Data System (ADS)

    Rickman, Jeffrey M.; Wang, Yan; Rollett, Anthony D.; Harmer, Martin P.; Compson, Charles

    2017-07-01

    A canonical correlation analysis is a generic parametric model used in the statistical analysis of data involving interrelated or interdependent input and output variables. It is especially useful in data analytics as a dimensional reduction strategy that simplifies a complex, multidimensional parameter space by identifying a relatively few combinations of variables that are maximally correlated. One shortcoming of the canonical correlation analysis, however, is that it provides only a linear combination of variables that maximizes these correlations. With this in mind, we describe here a versatile, Monte-Carlo based methodology that is useful in identifying non-linear functions of the variables that lead to strong input/output correlations. We demonstrate that our approach leads to a substantial enhancement of correlations, as illustrated by two experimental applications of substantial interest to the materials science community, namely: (1) determining the interdependence of processing and microstructural variables associated with doped polycrystalline aluminas, and (2) relating microstructural decriptors to the electrical and optoelectronic properties of thin-film solar cells based on CuInSe2 absorbers. Finally, we describe how this approach facilitates experimental planning and process control.

  6. Problem Gambling in New Mexico: 1996 and 1998

    ERIC Educational Resources Information Center

    Starling, Randall; Blankenship, Jason; May, Philip; Woodall, Gill

    2009-01-01

    Included in both the 1996 and 1998 Survey of Gambling Behavior in New Mexico was a scale of individual problem gambling. To assess problems related to gambling behavior, questions were developed using the DSM-IV criteria for pathological gambling. The purpose of this paper is to describe problem gamblers in New Mexico. Descriptive data indicate…

  7. New QCD sum rules based on canonical commutation relations

    NASA Astrophysics Data System (ADS)

    Hayata, Tomoya

    2012-04-01

    New derivation of QCD sum rules by canonical commutators is developed. It is the simple and straightforward generalization of Thomas-Reiche-Kuhn sum rule on the basis of Kugo-Ojima operator formalism of a non-abelian gauge theory and a suitable subtraction of UV divergences. By applying the method to the vector and axial vector current in QCD, the exact Weinberg’s sum rules are examined. Vector current sum rules and new fractional power sum rules are also discussed.

  8. Queueing analysis of a canonical model of real-time multiprocessors

    NASA Technical Reports Server (NTRS)

    Krishna, C. M.; Shin, K. G.

    1983-01-01

    A logical classification of multiprocessor structures from the point of view of control applications is presented. A computation of the response time distribution for a canonical model of a real time multiprocessor is presented. The multiprocessor is approximated by a blocking model. Two separate models are derived: one created from the system's point of view, and the other from the point of view of an incoming task.

  9. On the Problems of Construction and Statistical Inference Associated with a Generalization of Canonical Variables.

    DTIC Science & Technology

    1982-02-01

    of them are pre- sented in this paper. As an application, important practical problems similar to the one posed by Gnanadesikan (1977), p. 77 can be... Gnanadesikan and Wilk (1969) to search for a non-linear combination, giving rise to non-linear first principal component. So, a p-dinensional vector can...distribution, Gnanadesikan and Gupta (1970) and earlier Eaton (1967) have considered the problem of ranking the r underlying populations according to the

  10. Transcriptional oscillation of canonical clock genes in mouse peripheral tissues

    PubMed Central

    Yamamoto, Takuro; Nakahata, Yasukazu; Soma, Haruhiko; Akashi, Makoto; Mamine, Takayoshi; Takumi, Toru

    2004-01-01

    Background The circadian rhythm of about 24 hours is a fundamental physiological function observed in almost all organisms from prokaryotes to humans. Identification of clock genes has allowed us to study the molecular bases for circadian behaviors and temporal physiological processes such as hormonal secretion, and has prompted the idea that molecular clocks reside not only in a central pacemaker, the suprachiasmatic nuclei (SCN) of hypothalamus in mammals, but also in peripheral tissues, even in immortalized cells. Furthermore, previous molecular dissection revealed that the mechanism of circadian oscillation at a molecular level is based on transcriptional regulation of clock and clock-controlled genes. Results We systematically analyzed the mRNA expression of clock and clock-controlled genes in mouse peripheral tissues. Eight genes (mBmal1, mNpas2, mRev-erbα, mDbp, mRev-erbβ, mPer3, mPer1 and mPer2; given in the temporal order of the rhythm peak) showed robust circadian expressions of mRNAs in all tissues except testis, suggesting that these genes are core molecules of the molecular biological clock. The bioinformatics analysis revealed that these genes have one or a combination of 3 transcriptional elements (RORE, DBPE, and E-box), which are conserved among human, mouse, and rat genome sequences, and indicated that these 3 elements may be responsible for the biological timing of expression of canonical clock genes. Conclusions The observation of oscillatory profiles of canonical clock genes is not only useful for physiological and pathological examination of the circadian clock in various organs but also important for systematic understanding of transcriptional regulation on a genome-wide basis. Our finding of the oscillatory expression of canonical clock genes with a temporal order provides us an interesting hypothesis, that cyclic timing of all clock and clock-controlled genes may be dependent on several transcriptional elements including 3 known elements

  11. Individual differences in posttraumatic distress: problems with the DSM-IV model.

    PubMed

    Bowman, M L

    1999-02-01

    To evaluate the evidence concerning the role of threatening life events in accounting for clinically significant posttraumatic stress responses. Research was examined to review the epidemiology, evidence of dose-response relations, and individual difference factors in accounting for variations in conditions, including posttraumatic stress disorder, after exposure to threatening events. The evidence is significantly discrepant from the clinical Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) model. Greater distress arises from individual differences than from event characteristics. Important individual differences that interact with threat exposures include trait negative affectivity (neuroticism); beliefs about emotions, the self, the world, and the sources and consequences of danger; and prevent acts, disorders, and intelligence. Reasons for the discrepancies between the evidence and the current model of posttraumatic distress are proposed. In accounting for responses to threatening life events, the relatively minor contribution of event qualities compared with individual differences has significant treatment implications. Treatment approaches assuming that toxic event exposure creates a posttraumatic disorder fail to consider individual differences that could improve treatment efficacy.

  12. Statistics Anxiety and Worry: The Roles of Worry Beliefs, Negative Problem Orientation, and Cognitive Avoidance

    ERIC Educational Resources Information Center

    Williams, Amanda S.

    2015-01-01

    Statistics anxiety is a common problem for graduate students. This study explores the multivariate relationship between a set of worry-related variables and six types of statistics anxiety. Canonical correlation analysis indicates a significant relationship between the two sets of variables. Findings suggest that students who are more intolerant…

  13. Structure–Function Dissection of the Frizzled Receptor in Drosophila melanogaster Suggests Different Mechanisms of Action in Planar Polarity and Canonical Wnt Signaling

    PubMed Central

    Strutt, David; Madder, Daisy; Artymiuk, Peter J.

    2012-01-01

    Members of the Frizzled family of sevenpass transmembrane receptors signal via the canonical Wnt pathway and also via noncanonical pathways of which the best characterized is the planar polarity pathway. Activation of both canonical and planar polarity signaling requires interaction between Frizzled receptors and cytoplasmic proteins of the Dishevelled family; however, there has been some dispute regarding whether the Frizzled–Dishevelled interactions are the same in both cases. Studies looking at mutated forms of Dishevelled suggested that stable recruitment of Dishevelled to membranes by Frizzled was required only for planar polarity activity, implying that qualitatively different Frizzled–Dishevelled interactions underlie canonical signaling. Conversely, studies looking at the sequence requirements of Frizzled receptors in the fruit fly Drosophila melanogaster for canonical and planar polarity signaling have concluded that there is most likely a common mechanism of action. To understand better Frizzled receptor function, we have carried out a large-scale mutagenesis in Drosophila to isolate novel mutations in frizzled that affect planar polarity activity and have identified a group of missense mutations in cytosolic-facing regions of the Frizzled receptor that block Dishevelled recruitment. Interestingly, although some of these affect both planar polarity and canonical activity, as previously reported for similar lesions, we find a subset that affect only planar polarity activity. These results support the view that qualitatively different Frizzled–Dishevelled interactions underlie planar polarity and canonical Wnt signaling. PMID:23023003

  14. Comparative Analysis of Inpatient Costs for Obstetrics and Gynecology Surgery Patients Treated With IV Acetaminophen and IV Opioids Versus IV Opioid-only Analgesia for Postoperative Pain.

    PubMed

    Hansen, Ryan N; Pham, An T; Lovelace, Belinda; Balaban, Stela; Wan, George J

    2017-10-01

    Recovery from obstetrics and gynecology (OB/GYN) surgery, including hysterectomy and cesarean section delivery, aims to restore function while minimizing hospital length of stay (LOS) and medical expenditures. Our analyses compare OB/GYN surgery patients who received combination intravenous (IV) acetaminophen and IV opioid analgesia with those who received IV opioid-only analgesia and estimate differences in LOS, hospitalization costs, and opioid consumption. We performed a retrospective analysis of the Premier Database between January 2009 and June 2015, comparing OB/GYN surgery patients who received postoperative pain management with combination IV acetaminophen and IV opioids with those who received only IV opioids starting on the day of surgery and continuing up to the second postoperative day. We performed instrumental variable 2-stage least-squares regressions controlling for patient and hospital covariates to compare the LOS, hospitalization costs, and daily opioid doses (morphine equivalent dose) of IV acetaminophen recipients with that of opioid-only analgesia patients. We identified 225 142 OB/GYN surgery patients who were eligible for our study of whom 89 568 (40%) had been managed with IV acetaminophen and opioids. Participants averaged 36 years of age and were predominantly non-Hispanic Caucasians (60%). Multivariable regression models estimated statistically significant differences in hospitalization cost and opioid use with IV acetaminophen associated with $484.4 lower total hospitalization costs (95% CI = -$760.4 to -$208.4; P = 0.0006) and 8.2 mg lower daily opioid use (95% CI = -10.0 to -6.4), whereas the difference in LOS was not significant, at -0.09 days (95% CI = -0.19 to 0.01; P = 0.07). Compared with IV opioid-only analgesia, managing post-OB/GYN surgery pain with the addition of IV acetaminophen is associated with decreased hospitalization costs and reduced opioid use.

  15. Interactions between TGF-β1, canonical WNT/β-catenin pathway and PPAR γ in radiation-induced fibrosis

    PubMed Central

    Vallée, Alexandre; Lecarpentier, Yves; Guillevin, Rémy; Vallée, Jean-Noël

    2017-01-01

    Radiation therapy induces DNA damage and inflammation leading to fibrosis. Fibrosis can occur 4 to 12 months after radiation therapy. This process worsens with time and years. Radiation-induced fibrosis is characterized by fibroblasts proliferation, myofibroblast differentiation, and synthesis of collagen, proteoglycans and extracellular matrix. Myofibroblasts are non-muscle cells that can contract and relax. Myofibroblasts evolve towards irreversible retraction during fibrosis process. In this review, we discussed the interplays between transforming growth factor-β1 (TGF-β1), canonical WNT/β-catenin pathway and peroxisome proliferator-activated receptor gamma (PPAR γ) in regulating the molecular mechanisms underlying the radiation-induced fibrosis, and the potential role of PPAR γ agonists. Overexpression of TGF-β and canonical WNT/β-catenin pathway stimulate fibroblasts accumulation and myofibroblast differentiation whereas PPAR γ expression decreases due to the opposite interplay of canonical WNT/β-catenin pathway. Both TGF-β1 and canonical WNT/β-catenin pathway stimulate each other through the Smad pathway and non-Smad pathways such as phosphatidylinositol 3-kinase/serine/threonine kinase (PI3K/Akt) signaling. WNT/β-catenin pathway and PPAR γ interact in an opposite manner. PPAR γ agonists decrease β-catenin levels through activation of inhibitors of the WNT pathway such as Smad7, glycogen synthase kinase-3 (GSK-3 β) and dickkopf-related protein 1 (DKK1). PPAR γ agonists also stimulate phosphatase and tensin homolog (PTEN) expression, which decreases both TGF-β1 and PI3K/Akt pathways. PPAR γ agonists by activating Smad7 decrease Smads pathway and then TGF-β signaling leading to decrease radiation-induced fibrosis. TGF-β1 and canonical WNT/β-catenin pathway promote radiation-induced fibrosis whereas PPAR γ agonists can prevent radiation-induced fibrosis. PMID:29163854

  16. On the control canonical structure of a class of scalar input systems

    NASA Technical Reports Server (NTRS)

    Teglas, R.

    1983-01-01

    A discrete finite dimensional system, nonharmonic Fourier series and controllability, reduction to canonical form, and spectral synthesis are considered. The extent to which the eigenvalue associated with a controllable pair of a certain type may be modified via continuous linear state feedback is demonstrated.

  17. WIF1 re-expression in glioblastoma inhibits migration through attenuation of non-canonical WNT signaling by downregulating the lncRNA MALAT1.

    PubMed

    Vassallo, I; Zinn, P; Lai, M; Rajakannu, P; Hamou, M-F; Hegi, M E

    2016-01-07

    Glioblastoma is the most aggressive primary brain tumor in adults and due to the invasive nature cannot be completely removed. The WNT inhibitory factor 1 (WIF1), a secreted inhibitor of WNTs, is systematically downregulated in glioblastoma and acts as strong tumor suppressor. The aim of this study was the dissection of WIF1-associated tumor-suppressing effects mediated by canonical and non-canonical WNT signaling. We found that WIF1 besides inhibiting the canonical WNT pathway selectively downregulates the WNT/calcium pathway associated with significant reduction of p38-MAPK (p38-mitogen-activated protein kinase) phosphorylation. Knockdown of WNT5A, the only WNT ligand overexpressed in glioblastoma, phenocopied this inhibitory effect. WIF1 expression inhibited cell migration in vitro and in an orthotopic brain tumor model, in accordance with the known regulatory function of the WNT/Ca(2+) pathway on migration and invasion. In search of a mediator for this function differential gene expression profiles of WIF1-expressing cells were performed. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a long non-coding RNA and key positive regulator of invasion, emerged as the top downregulated gene. Indeed, knockdown of MALAT1 reduced migration in glioblastoma cells, without effect on proliferation. Hence, loss of WIF1 enhances the migratory potential of glioblastoma through WNT5A that activates the WNT/Ca(2+) pathway and MALAT1. These data suggest the involvement of canonical and non-canonical WNT pathways in glioblastoma promoting key features associated with this deadly disease, proliferation on one hand and invasion on the other. Successful targeting will require a dual strategy affecting both canonical and non-canonical WNT pathways.

  18. New insights into transcription fidelity: thermal stability of non-canonical structures in template DNA regulates transcriptional arrest, pause, and slippage.

    PubMed

    Tateishi-Karimata, Hisae; Isono, Noburu; Sugimoto, Naoki

    2014-01-01

    The thermal stability and topology of non-canonical structures of G-quadruplexes and hairpins in template DNA were investigated, and the effect of non-canonical structures on transcription fidelity was evaluated quantitatively. We designed ten template DNAs: A linear sequence that does not have significant higher-order structure, three sequences that form hairpin structures, and six sequences that form G-quadruplex structures with different stabilities. Templates with non-canonical structures induced the production of an arrested, a slipped, and a full-length transcript, whereas the linear sequence produced only a full-length transcript. The efficiency of production for run-off transcripts (full-length and slipped transcripts) from templates that formed the non-canonical structures was lower than that from the linear. G-quadruplex structures were more effective inhibitors of full-length product formation than were hairpin structure even when the stability of the G-quadruplex in an aqueous solution was the same as that of the hairpin. We considered that intra-polymerase conditions may differentially affect the stability of non-canonical structures. The values of transcription efficiencies of run-off or arrest transcripts were correlated with stabilities of non-canonical structures in the intra-polymerase condition mimicked by 20 wt% polyethylene glycol (PEG). Transcriptional arrest was induced when the stability of the G-quadruplex structure (-ΔG°37) in the presence of 20 wt% PEG was more than 8.2 kcal mol(-1). Thus, values of stability in the presence of 20 wt% PEG are an important indicator of transcription perturbation. Our results further our understanding of the impact of template structure on the transcription process and may guide logical design of transcription-regulating drugs.

  19. New Insights into Transcription Fidelity: Thermal Stability of Non-Canonical Structures in Template DNA Regulates Transcriptional Arrest, Pause, and Slippage

    PubMed Central

    Tateishi-Karimata, Hisae; Isono, Noburu; Sugimoto, Naoki

    2014-01-01

    The thermal stability and topology of non-canonical structures of G-quadruplexes and hairpins in template DNA were investigated, and the effect of non-canonical structures on transcription fidelity was evaluated quantitatively. We designed ten template DNAs: A linear sequence that does not have significant higher-order structure, three sequences that form hairpin structures, and six sequences that form G-quadruplex structures with different stabilities. Templates with non-canonical structures induced the production of an arrested, a slipped, and a full-length transcript, whereas the linear sequence produced only a full-length transcript. The efficiency of production for run-off transcripts (full-length and slipped transcripts) from templates that formed the non-canonical structures was lower than that from the linear. G-quadruplex structures were more effective inhibitors of full-length product formation than were hairpin structure even when the stability of the G-quadruplex in an aqueous solution was the same as that of the hairpin. We considered that intra-polymerase conditions may differentially affect the stability of non-canonical structures. The values of transcription efficiencies of run-off or arrest transcripts were correlated with stabilities of non-canonical structures in the intra-polymerase condition mimicked by 20 wt% polyethylene glycol (PEG). Transcriptional arrest was induced when the stability of the G-quadruplex structure (−ΔGo 37) in the presence of 20 wt% PEG was more than 8.2 kcal mol−1. Thus, values of stability in the presence of 20 wt% PEG are an important indicator of transcription perturbation. Our results further our understanding of the impact of template structure on the transcription process and may guide logical design of transcription-regulating drugs. PMID:24594642

  20. Canonical WNT signalling determines lineage specificity in Wilms tumour.

    PubMed

    Fukuzawa, R; Anaka, M R; Weeks, R J; Morison, I M; Reeve, A E

    2009-02-26

    Wilms tumours (WTs) have two distinct types of histology with or without ectopic mesenchymal elements, suggesting that WTs arise from either the mesenchymal or epithelial nephrogenic lineages. Regardless of the presence or absence of CTNNB1 mutations, nuclear accumulation of beta-catenin is often observed in WTs with ectopic mesenchymal elements. Here, we addressed the relationship between the WNT-signalling pathway and lineage in WTs by examining CTNNB1 and WT1 mutations, nuclear accumulation of beta-catenin, tumour histology and gene expression profiles. In addition, we screened for mutations in WTX, which has been proposed to be a negative regulator of the canonical WNT-signalling pathway. Unsupervised clustering analysis identified two classes of tumours: mesenchymal lineage WNT-dependent tumours, and epithelial lineage WNT-independent tumours. In contrast to the mesenchymal lineage specificity of CTNNB1 mutations, WTX mutations were surprisingly observed in both lineages. WTX-mutant WTs with ectopic mesenchymal elements had nuclear accumulation of beta-catenin, upregulation of WNT target genes and an association with CTNNB1 mutations in exon 7 or 8. However, epithelial lineage WTs with WTX mutations had no indications of active WNT signalling, suggesting that the involvement of WTX in the WNT-signalling pathway may be lineage dependent, and that WTX may have an alternative function to its role in the canonical WNT-signalling pathway.

  1. Spontaneous CRISPR loci generation in vivo by non-canonical spacer integration

    PubMed Central

    Nivala, Jeff; Shipman, Seth L.; Church, George M.

    2018-01-01

    The adaptation phase of CRISPR-Cas immunity depends on the precise integration of short segments of foreign DNA (spacers) into a specific genomic location within the CRISPR locus by the Cas1-Cas2 integration complex. Although off-target spacer integration outside of canonical CRISPR arrays has been described in vitro, no evidence of non-specific integration activity has been found in vivo. Here, we show that non-canonical off-target integrations can occur within bacterial chromosomes at locations that resemble the native CRISPR locus by characterizing hundreds of off-target integration locations within Escherichia coli. Considering whether such promiscuous Cas1-Cas2 activity could have an evolutionary role through the genesis of neo-CRISPR loci, we combed existing CRISPR databases and available genomes for evidence of off-target integration activity. This search uncovered several putative instances of naturally occurring off-target spacer integration events within the genomes of Yersinia pestis and Sulfolobus islandicus. These results are important in understanding alternative routes to CRISPR array genesis and evolution, as well as in the use of spacer acquisition in technological applications. PMID:29379209

  2. Intelligent Virtual Station (IVS)

    NASA Technical Reports Server (NTRS)

    2002-01-01

    The Intelligent Virtual Station (IVS) is enabling the integration of design, training, and operations capabilities into an intelligent virtual station for the International Space Station (ISS). A viewgraph of the IVS Remote Server is presented.

  3. Binding of canonical Wnt ligands to their receptor complexes occurs in ordered plasma membrane environments.

    PubMed

    Sezgin, Erdinc; Azbazdar, Yagmur; Ng, Xue W; Teh, Cathleen; Simons, Kai; Weidinger, Gilbert; Wohland, Thorsten; Eggeling, Christian; Ozhan, Gunes

    2017-08-01

    While the cytosolic events of Wnt/β-catenin signaling (canonical Wnt signaling) pathway have been widely studied, only little is known about the molecular mechanisms involved in Wnt binding to its receptors at the plasma membrane. Here, we reveal the influence of the immediate plasma membrane environment on the canonical Wnt-receptor interaction. While the receptors are distributed both in ordered and disordered environments, Wnt binding to its receptors selectively occurs in more ordered membrane environments which appear to cointernalize with the Wnt-receptor complex. Moreover, Wnt/β-catenin signaling is significantly reduced when the membrane order is disturbed by specific inhibitors of certain lipids that prefer to localize at the ordered environments. Similarly, a reduction in Wnt signaling activity is observed in Niemann-Pick Type C disease cells where trafficking of ordered membrane lipid components to the plasma membrane is genetically impaired. We thus conclude that ordered plasma membrane environments are essential for binding of canonical Wnts to their receptor complexes and downstream signaling activity. © 2017 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

  4. Canonical-ensemble extended Lagrangian Born-Oppenheimer molecular dynamics for the linear scaling density functional theory.

    PubMed

    Hirakawa, Teruo; Suzuki, Teppei; Bowler, David R; Miyazaki, Tsuyoshi

    2017-10-11

    We discuss the development and implementation of a constant temperature (NVT) molecular dynamics scheme that combines the Nosé-Hoover chain thermostat with the extended Lagrangian Born-Oppenheimer molecular dynamics (BOMD) scheme, using a linear scaling density functional theory (DFT) approach. An integration scheme for this canonical-ensemble extended Lagrangian BOMD is developed and discussed in the context of the Liouville operator formulation. Linear scaling DFT canonical-ensemble extended Lagrangian BOMD simulations are tested on bulk silicon and silicon carbide systems to evaluate our integration scheme. The results show that the conserved quantity remains stable with no systematic drift even in the presence of the thermostat.

  5. Comparative Analysis of Length of Stay and Inpatient Costs for Orthopedic Surgery Patients Treated with IV Acetaminophen and IV Opioids vs. IV Opioids Alone for Post-Operative Pain.

    PubMed

    Hansen, Ryan N; Pham, An; Strassels, Scott A; Balaban, Stela; Wan, George J

    2016-09-01

    Recovery from orthopedic surgery is oriented towards restoring functional health outcomes while reducing hospital length of stay (LOS) and medical expenditures. Optimal pain management is a key to reaching these objectives. We sought to compare orthopedic surgery patients who received combination intravenous (IV) acetaminophen and IV opioid analgesia to those who received IV opioids alone and compared the two groups on LOS and hospitalization costs. We performed a retrospective analysis of the Premier Database (Premier, Inc.; between January 2009 and June 2015) comparing orthopedic surgery patients who received post-operative pain management with combination IV acetaminophen and IV opioids to those who received only IV opioids starting on the day of surgery and continuing up to the second post-operative day. The quarterly rate of IV acetaminophen use for all hospitalizations by hospital served as the instrumental variable in two-stage least squares regressions controlling for patient and hospital covariates to compare the LOS and hospitalization costs of IV acetaminophen recipients to opioid monotherapy patients. We identified 4,85,895 orthopedic surgery patients with 1,74,805 (36%) who had received IV acetaminophen. Study subjects averaged 64 years of age and were predominantly non-Hispanic Caucasians (78%) and female (58%). The mean unadjusted LOS for IV acetaminophen patients was 3.2 days [standard deviation (SD) 2.6] compared to 3.9 days (SD 3.9) with only IV opioids (P < 0.0001). Average unadjusted hospitalization costs were $19,024.9 (SD $13,113.7) for IV acetaminophen patients and $19,927.6 (SD $19,578.8) for IV opioid patients (P < 0.0001). These differences remained statistically significant in our instrumental variable models, with IV acetaminophen associated with 0.51 days shorter hospitalization [95% confidence interval (CI) -0.58 to -0.44, P < 0.0001] and $634.8 lower hospitalization costs (95% CI -$1032.5 to -$237.1, P = 0.0018). Compared

  6. Non-canonical active site architecture of the radical SAM thiamin pyrimidine synthase.

    PubMed

    Fenwick, Michael K; Mehta, Angad P; Zhang, Yang; Abdelwahed, Sameh H; Begley, Tadhg P; Ealick, Steven E

    2015-03-27

    Radical S-adenosylmethionine (SAM) enzymes use a [4Fe-4S] cluster to generate a 5'-deoxyadenosyl radical. Canonical radical SAM enzymes are characterized by a β-barrel-like fold and SAM anchors to the differentiated iron of the cluster, which is located near the amino terminus and within the β-barrel, through its amino and carboxylate groups. Here we show that ThiC, the thiamin pyrimidine synthase in plants and bacteria, contains a tethered cluster-binding domain at its carboxy terminus that moves in and out of the active site during catalysis. In contrast to canonical radical SAM enzymes, we predict that SAM anchors to an additional active site metal through its amino and carboxylate groups. Superimposition of the catalytic domains of ThiC and glutamate mutase shows that these two enzymes share similar active site architectures, thus providing strong evidence for an evolutionary link between the radical SAM and adenosylcobalamin-dependent enzyme superfamilies.

  7. Non-canonical active site architecture of the radical SAM thiamin pyrimidine synthase

    DOE PAGES

    Fenwick, Michael K.; Mehta, Angad P.; Zhang, Yang; ...

    2015-03-27

    Radical S-adenosylmethionine (SAM) enzymes use a [4Fe-4S] cluster to generate a 5'-deoxyadenosyl radical. Canonical radical SAM enzymes are characterized by a β-barrel-like fold and SAM anchors to the differentiated iron of the cluster, which is located near the amino terminus and within the β-barrel, through its amino and carboxylate groups. Here we show that ThiC, the thiamin pyrimidine synthase in plants and bacteria, contains a tethered cluster-binding domain at its carboxy terminus that moves in and out of the active site during catalysis. In contrast to canonical radical SAM enzymes, we predict that SAM anchors to an additional active sitemore » metal through its amino and carboxylate groups. Superimposition of the catalytic domains of ThiC and glutamate mutase shows that these two enzymes share similar active site architectures, thus providing strong evidence for an evolutionary link between the radical SAM and adenosylcobalamin-dependent enzyme superfamilies.« less

  8. Force-momentum-based self-guided Langevin dynamics: A rapid sampling method that approaches the canonical ensemble

    NASA Astrophysics Data System (ADS)

    Wu, Xiongwu; Brooks, Bernard R.

    2011-11-01

    The self-guided Langevin dynamics (SGLD) is a method to accelerate conformational searching. This method is unique in the way that it selectively enhances and suppresses molecular motions based on their frequency to accelerate conformational searching without modifying energy surfaces or raising temperatures. It has been applied to studies of many long time scale events, such as protein folding. Recent progress in the understanding of the conformational distribution in SGLD simulations makes SGLD also an accurate method for quantitative studies. The SGLD partition function provides a way to convert the SGLD conformational distribution to the canonical ensemble distribution and to calculate ensemble average properties through reweighting. Based on the SGLD partition function, this work presents a force-momentum-based self-guided Langevin dynamics (SGLDfp) simulation method to directly sample the canonical ensemble. This method includes interaction forces in its guiding force to compensate the perturbation caused by the momentum-based guiding force so that it can approximately sample the canonical ensemble. Using several example systems, we demonstrate that SGLDfp simulations can approximately maintain the canonical ensemble distribution and significantly accelerate conformational searching. With optimal parameters, SGLDfp and SGLD simulations can cross energy barriers of more than 15 kT and 20 kT, respectively, at similar rates for LD simulations to cross energy barriers of 10 kT. The SGLDfp method is size extensive and works well for large systems. For studies where preserving accessible conformational space is critical, such as free energy calculations and protein folding studies, SGLDfp is an efficient approach to search and sample the conformational space.

  9. Identification of novel dipeptidyl peptidase IV (DPP-IV) inhibitory peptides in camel milk protein hydrolysates.

    PubMed

    Nongonierma, Alice B; Paolella, Sara; Mudgil, Priti; Maqsood, Sajid; FitzGerald, Richard J

    2018-04-01

    Nine novel dipeptidyl peptidase IV (DPP-IV) inhibitory peptides (FLQY, FQLGASPY, ILDKEGIDY, ILELA, LLQLEAIR, LPVP, LQALHQGQIV, MPVQA and SPVVPF) were identified in camel milk proteins hydrolysed with trypsin. This was achieved using a sequential approach combining liquid chromatography tandem mass spectrometry (LC-MS/MS), qualitative/quantitative structure activity relationship (QSAR) and confirmatory studies with synthetic peptides. The most potent camel milk protein-derived DPP-IV inhibitory peptides, LPVP and MPVQA, had DPP-IV half maximal inhibitory concentrations (IC 50 ) of 87.0 ± 3.2 and 93.3 ± 8.0 µM, respectively. DPP-IV inhibitory peptide sequences identified within camel and bovine milk protein hydrolysates generated under the same hydrolysis conditions differ. This was linked to differences in enzyme selectivity for peptide bond cleavage of camel and bovine milk proteins as well as dissimilarities in their amino acid sequences. Camel milk proteins contain novel DPP-IV inhibitory peptides which may play a role in the regulation of glycaemia in humans. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Canonical Nonlinear Viscous Core Solution in pipe and elliptical geometry

    NASA Astrophysics Data System (ADS)

    Ozcakir, Ozge

    2016-11-01

    In an earlier paper (Ozcakir et al. (2016)), two new nonlinear traveling wave solutions were found with collapsing structure towards the center of the pipe as Reynolds number R -> ∞ , which were called Nonlinear Viscous Core (NVC) states. Asymptotic scaling arguments suggested that the NVC state collapse rate scales as R - 1 / 4 where axial, radial and azimuthal velocity perturbations from Hagen-Poiseuille flow scale as R - 1 / 2, R - 3 / 4 and R - 3 / 4 respectively, while (1 - c) = O (R - 1 / 2) where c is the traveling wave speed. The theoretical scaling results were roughly consistent with full Navier-Stokes numerical computations in the range 105 < R <106 . In the present paper, through numerical solutions, we show that the scaled parameter free canonical differential equations derived in Ozcakir et al. (2016) indeed has solution that satisfies requisite far-field conditions. We also show that these are in good agreement with full Navier-Stokes calculations in a larger R range than previously calculated (R upto 106). Further, we extend our study to NVC states for pipes with elliptical cross-section and identify similar canonical structure in these cases. National Science Foundation NSF-DMS-1515755, EPSRC Grant EP/1037948/1.

  11. Canonical formulation and conserved charges of double field theory

    DOE PAGES

    Naseer, Usman

    2015-10-26

    We provide the canonical formulation of double field theory. It is shown that this dynamics is subject to primary and secondary constraints. The Poisson bracket algebra of secondary constraints is shown to close on-shell according to the C-bracket. We also give a systematic way of writing boundary integrals in doubled geometry. Finally, by including appropriate boundary terms in the double field theory Hamiltonian, expressions for conserved energy and momentum of an asymptotically flat doubled space-time are obtained and applied to a number of solutions.

  12. The WD40 domain of ATG16L1 is required for its non-canonical role in lipidation of LC3 at single membranes.

    PubMed

    Fletcher, Katherine; Ulferts, Rachel; Jacquin, Elise; Veith, Talitha; Gammoh, Noor; Arasteh, Julia M; Mayer, Ulrike; Carding, Simon R; Wileman, Thomas; Beale, Rupert; Florey, Oliver

    2018-02-15

    A hallmark of macroautophagy is the covalent lipidation of LC3 and insertion into the double-membrane phagophore, which is driven by the ATG16L1/ATG5-ATG12 complex. In contrast, non-canonical autophagy is a pathway through which LC3 is lipidated and inserted into single membranes, particularly endolysosomal vacuoles during cell engulfment events such as LC3-associated phagocytosis. Factors controlling the targeting of ATG16L1 to phagophores are dispensable for non-canonical autophagy, for which the mechanism of ATG16L1 recruitment is unknown. Here we show that the WD repeat-containing C-terminal domain (WD40 CTD) of ATG16L1 is essential for LC3 recruitment to endolysosomal membranes during non-canonical autophagy, but dispensable for canonical autophagy. Using this strategy to inhibit non-canonical autophagy specifically, we show a reduction of MHC class II antigen presentation in dendritic cells from mice lacking the WD40 CTD Further, we demonstrate activation of non-canonical autophagy dependent on the WD40 CTD during influenza A virus infection. This suggests dependence on WD40 CTD distinguishes between macroautophagy and non-canonical use of autophagy machinery. © 2018 The Authors. Published under the terms of the CC BY 4.0 license.

  13. Problem of time: facets and Machian strategy.

    PubMed

    Anderson, Edward

    2014-10-01

    The problem of time is that "time" in each of ordinary quantum theory and general relativity are mutually incompatible notions. This causes difficulties in trying to put these two theories together to form a theory of quantum gravity. The problem of time has eight facets in canonical approaches. I clarify that all but one of these facets already occur at the classical level, and reconceptualize and re-name some of these facets as follows. The frozen formalism problem becomes temporal relationalism, the thin sandwich problem becomes configurational relationalism, via the notion of best matching. The problem of observables becomes the problem of beables, and the functional evolution problem becomes the constraint closure problem. I also outline how each of the global and multiple-choice problems of time have their own plurality of facets. This article additionally contains a local resolution to the problem of time at the conceptual level and which is actually realizable for the relational triangle and minisuperspace models. This resolution is, moreover, Machian, and has three levels: classical, semiclassical, and a combined semiclassical-histories-timeless records scheme. I end by delineating the current frontiers of this program toward resolution of the problem of time in the cases of full general relativity and of slightly inhomogeneous cosmology. © 2014 New York Academy of Sciences.

  14. Determine the Role of Canonical Wnt Signaling in Ovarian Tumorigenesis

    DTIC Science & Technology

    2015-12-01

    studies have shown that oxphos is increased during OIS, leading to an increase in oxygen consumption (Fig. 1).38,42,52 This is likely due to increased TCA...senescent cells display an increase in oxygen consumption but no appreciable increase in ATP levels. The mechanism by which increased fatty acid...benign ovarian tumors into invasive EOCs, and to investigate the effects of inhibition of the canonical Wnt signaling on malignant behavior of EOC cells

  15. Common molecular determinants of tarantula huwentoxin-IV inhibition of Na+ channel voltage sensors in domains II and IV.

    PubMed

    Xiao, Yucheng; Jackson, James O; Liang, Songping; Cummins, Theodore R

    2011-08-05

    The voltage sensors of domains II and IV of sodium channels are important determinants of activation and inactivation, respectively. Animal toxins that alter electrophysiological excitability of muscles and neurons often modify sodium channel activation by selectively interacting with domain II and inactivation by selectively interacting with domain IV. This suggests that there may be substantial differences between the toxin-binding sites in these two important domains. Here we explore the ability of the tarantula huwentoxin-IV (HWTX-IV) to inhibit the activity of the domain II and IV voltage sensors. HWTX-IV is specific for domain II, and we identify five residues in the S1-S2 (Glu-753) and S3-S4 (Glu-811, Leu-814, Asp-816, and Glu-818) regions of domain II that are crucial for inhibition of activation by HWTX-IV. These data indicate that a single residue in the S3-S4 linker (Glu-818 in hNav1.7) is crucial for allowing HWTX-IV to interact with the other key residues and trap the voltage sensor in the closed configuration. Mutagenesis analysis indicates that the five corresponding residues in domain IV are all critical for endowing HWTX-IV with the ability to inhibit fast inactivation. Our data suggest that the toxin-binding motif in domain II is conserved in domain IV. Increasing our understanding of the molecular determinants of toxin interactions with voltage-gated sodium channels may permit development of enhanced isoform-specific voltage-gating modifiers.

  16. Momentum distribution functions in ensembles: the inequivalence of microcannonical and canonical ensembles in a finite ultracold system.

    PubMed

    Wang, Pei; Xianlong, Gao; Li, Haibin

    2013-08-01

    It is demonstrated in many thermodynamic textbooks that the equivalence of the different ensembles is achieved in the thermodynamic limit. In this present work we discuss the inequivalence of microcanonical and canonical ensembles in a finite ultracold system at low energies. We calculate the microcanonical momentum distribution function (MDF) in a system of identical fermions (bosons). We find that the microcanonical MDF deviates from the canonical one, which is the Fermi-Dirac (Bose-Einstein) function, in a finite system at low energies where the single-particle density of states and its inverse are finite.

  17. Solution of the sign problem in the Potts model at fixed fermion number

    NASA Astrophysics Data System (ADS)

    Alexandru, Andrei; Bergner, Georg; Schaich, David; Wenger, Urs

    2018-06-01

    We consider the heavy-dense limit of QCD at finite fermion density in the canonical formulation and approximate it by a three-state Potts model. In the strong-coupling limit, the model is free of the sign problem. Away from the strong coupling, the sign problem is solved by employing a cluster algorithm which allows to average each cluster over the Z (3 ) sectors. Improved estimators for physical quantities can be constructed by taking into account the triality of the clusters, that is, their transformation properties with respect to Z (3 ) transformations.

  18. Impeding 99Tc(IV) mobility in novel waste forms

    PubMed Central

    Lee, Mal-Soon; Um, Wooyong; Wang, Guohui; Kruger, Albert A.; Lukens, Wayne W.; Rousseau, Roger; Glezakou, Vassiliki-Alexandra

    2016-01-01

    Technetium (99Tc) is an abundant, long-lived radioactive fission product whose mobility in the subsurface is largely governed by its oxidation state. Tc immobilization is crucial for radioactive waste management and environmental remediation. Tc(IV) incorporation in spinels has been proposed as a novel method to increase Tc retention in glass waste forms during vitrification. However, experiments under high-temperature and oxic conditions show reoxidation of Tc(IV) to volatile pertechnetate, Tc(VII). Here we examine this problem with ab initio molecular dynamics simulations and propose that, at elevated temperatures, doping with first row transition metal can significantly enhance Tc retention in magnetite in the order Co>Zn>Ni. Experiments with doped spinels at 700 °C provide quantitative confirmation of the theoretical predictions in the same order. This work highlights the power of modern, state-of-the-art simulations to provide essential insights and generate theory-inspired design criteria of complex materials at elevated temperatures. PMID:27357121

  19. 45 CFR 1355.21 - E and IV-B.

    Code of Federal Regulations, 2010 CFR

    1996-10-01

    ... requirements for titles IV PUBLIC WELFARE Regulations Relating to Public Welfare (Continued) OFFICE OF HUMAN.... 1355.21 State plan requirements for titles IV-E and IV-B. (a) The State plans for titles IV-E and IV-B... contained in section 471(a)(8) of the Act. (b) The State plans for titles IV-E and IV-B must provide for...

  20. 4-Hydroxynonenal activates Src through a non-canonical pathway that involves EGFR/PTP1B

    PubMed Central

    Zhang, Hongqiao; Forman, Henry Jay

    2015-01-01

    Src, a non-receptor protein tyrosine kinase involved in many biological processes, can be activated through both redox-dependent and independent mechanisms. 4-Hydroxy-2-nonenal (HNE) is a lipid peroxidation product that is increased in pathophysiological conditions associated with Src activation. This study examined how HNE activates human c-Src. In the canonical pathway Src activation is initiated by dephosphorylation of pTyr530 followed by conformational change that causes Src auto-phosphorylation at Tyr419 and its activation. HNE increased Src activation in both dose- and time-dependent manner, while it also increased Src phosphorylation at Tyr530 (pTyr530 Src), suggesting that HNE activated Src via a non-canonical mechanism. Protein tyrosine phosphatase 1B inhibitor (539741), at concentrations that increased basal pTyr530 Src, also increased basal Src activity and significantly reduced HNE-mediated Src activation. The EGFR inhibitor, AG1478, and EGFR silencing, abrogated HNE-mediated EGFR activation and inhibited basal and HNE-induced Src activity. In addition, AG1478 also eliminated the increase of basal Src activation by a PTP1B inhibitor. Taken together these data suggest that HNE can activate Src partly through a non-canonical pathway involving activation of EGFR and inhibition of PTP1B. PMID:26453921

  1. Babbling development as seen in canonical babbling ratios: A naturalistic evaluation of all-day recordings.

    PubMed

    Lee, Chia-Cheng; Jhang, Yuna; Relyea, George; Chen, Li-Mei; Oller, D Kimbrough

    2018-02-01

    Canonical babbling (CB) is critical in forming foundations for speech. Research has shown that the emergence of CB precedes first words, predicts language outcomes, and is delayed in infants with several communicative disorders. We seek a naturalistic portrayal of CB development, using all-day home recordings to evaluate the influences of age, language, and social circumstances on infant CB production. Thus we address the nature of very early language foundations and how they can be modulated. This is the first study to evaluate possible interactions of language and social circumstance in the development of babbling. We examined the effects of age (6 and 11 months), language/culture (English and Chinese), and social circumstances (during infant-directed speech [IDS], during infant overhearing of adult-directed speech [ADS], or when infants were alone) on canonical babbling ratios (CBR = canonical syllables/total syllables). The results showed a three-way interaction of infant age by infant language/culture by social circumstance. The complexity of the results forces us to recognize that a variety of factors can interact in the development of foundations for language, and that both the infant vocal response to the language/culture environment and the language/culture environment of the infant may change across age. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. IVS Pilot Project - Tropospheric Parameters

    NASA Astrophysics Data System (ADS)

    Boehm, J.; Schuh, H.; Engelhardt, G.; MacMillan, D.; Lanotte, R.; Tomasi, P.; Vereshchagina, I.; Haas, R.; Negusini, M.; Gubanov, V.

    2003-04-01

    In April 2002 the IVS (International VLBI Service for Geodesy and Astrometry) set up the IVS Pilot Project - Tropospheric Parameters and the Institute of Geodesy and Geophysics (IGG), Vienna, was asked to coordinate the project. After a call for participation six IVS Analysis Centers have joined the project and submitted their estimates of tropospheric parameters (wet and total zenith delays, horizontal gradients) for all IVS-R1 and IVS-R4 sessions since January 1st, 2002, on a regular basis. Using a two-step procedure the individual submissions are combined to stable and robust tropospheric parameters with 1h resolution and high accuracy. The zenith delays derived by VLBI are also compared with those provided by IGS (International GPS Service). At collocated sites (VLBI and GPS antennas at the same station) rather constant biases are found between the GPS and VLBI derived zenith delays, although both techniques are subject to the same tropospheric delays. Possible reasons for these biases are discussed.

  3. The canonical semantic network supports residual language function in chronic post-stroke aphasia

    PubMed Central

    Griffis, Joseph C.; Nenert, Rodolphe; Allendorfer, Jane B.; Vannest, Jennifer; Holland, Scott; Dietz, Aimee; Szaflarski, Jerzy P.

    2016-01-01

    Current theories of language recovery after stroke are limited by a reliance on small studies. Here, we aimed to test predictions of current theory and resolve inconsistencies regarding right hemispheric contributions to long-term recovery. We first defined the canonical semantic network in 43 healthy controls. Then, in a group of 43 patients with chronic post-stroke aphasia, we tested whether activity in this network predicted performance on measures of semantic comprehension, naming, and fluency while controlling for lesion volume effects. Canonical network activation accounted for 22–33% of the variance in language test scores. Whole-brain analyses corroborated these findings, and revealed a core set of regions showing positive relationships to all language measures. We next evaluated the relationship between activation magnitudes in left and right hemispheric portions of the network, and characterized how right hemispheric activation related to the extent of left hemispheric damage. Activation magnitudes in each hemispheric network were strongly correlated, but four right frontal regions showed heightened activity in patients with large lesions. Activity in two of these regions (inferior frontal gyrus pars opercularis and supplementary motor area) was associated with better language abilities in patients with larger lesions, but poorer language abilities in patients with smaller lesions. Our results indicate that bilateral language networks support language processing after stroke, and that right hemispheric activations related to extensive left hemisphere damage occur outside of the canonical semantic network and differentially relate to behavior depending on the extent of left hemispheric damage. PMID:27981674

  4. A Study of Selected Problems in Armor Operations

    DTIC Science & Technology

    1978-11-01

    of external environmental cond~tions on the internal environment of a buttoned-up tank. Another effort was a study of problems in escape and...Test site configuration: Study II ......... ... IV-16 FIG. IVT4. Mean time to lay on target .... ........ .... IV-20 TABLES Chapter III Table III-I...L., and Ton, W. H. Study of the Psychological (and Associated Physiological) Effjcts on a Tank Crew Resulting From Being Buttoned Up, ARI Research

  5. Structure activity relationship modelling of milk protein-derived peptides with dipeptidyl peptidase IV (DPP-IV) inhibitory activity.

    PubMed

    Nongonierma, Alice B; FitzGerald, Richard J

    2016-05-01

    Quantitative structure activity type models were developed in an attempt to predict the key features of peptide sequences having dipeptidyl peptidase IV (DPP-IV) inhibitory activity. The models were then employed to help predict the potential of peptides, which are currently reported in the literature to be present in the intestinal tract of humans following milk/dairy product ingestion, to act as inhibitors of DPP-IV. Two models (z- and v-scale) for short (2-5 amino acid residues) bovine milk peptides, behaving as competitive inhibitors of DPP-IV, were developed. The z- and the v-scale models (p<0.05, R(2) of 0.829 and 0.815, respectively) were then applied to 56 milk protein-derived peptides previously reported in the literature to be found in the intestinal tract of humans which possessed a structural feature of DPP-IV inhibitory peptides (P at the N2 position). Ten of these peptides were synthetized and tested for their in vitro DPP-IV inhibitory properties. There was no agreement between the predicted and experimentally determined DPP-IV half maximal inhibitory concentrations (IC50) for the competitive peptide inhibitors. However, the ranking for DPP-IV inhibitory potency of the competitive peptide inhibitors was conserved. Furthermore, potent in vitro DPP-IV inhibitory activity was observed with two peptides, LPVPQ (IC50=43.8±8.8μM) and IPM (IC50=69.5±8.7μM). Peptides present within the gastrointestinal tract of human may have promise for the development of natural DPP-IV inhibitors for the management of serum glucose. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Ligand-activated epidermal growth factor receptor (EGFR) signaling governs endocytic trafficking of unliganded receptor monomers by non-canonical phosphorylation.

    PubMed

    Tanaka, Tomohiro; Zhou, Yue; Ozawa, Tatsuhiko; Okizono, Ryuya; Banba, Ayako; Yamamura, Tomohiro; Oga, Eiji; Muraguchi, Atsushi; Sakurai, Hiroaki

    2018-02-16

    The canonical description of transmembrane receptor function is initial binding of ligand, followed by initiation of intracellular signaling and then internalization en route to degradation or recycling to the cell surface. It is known that low concentrations of extracellular ligand lead to a higher proportion of receptor that is recycled and that non-canonical mechanisms of receptor activation, including phosphorylation by the kinase p38, can induce internalization and recycling. However, no connections have been made between these pathways; i.e. it has yet to be established what happens to unbound receptors following stimulation with ligand. Here we demonstrate that a minimal level of activation of epidermal growth factor receptor (EGFR) tyrosine kinase by low levels of ligand is sufficient to fully activate downstream mitogen-activated protein kinase (MAPK) pathways, with most of the remaining unbound EGFR molecules being efficiently phosphorylated at intracellular serine/threonine residues by activated mitogen-activated protein kinase. This non-canonical, p38-mediated phosphorylation of the C-tail of EGFR, near Ser-1015, induces the clathrin-mediated endocytosis of the unliganded EGFR monomers, which occurs slightly later than the canonical endocytosis of ligand-bound EGFR dimers via tyrosine autophosphorylation. EGFR endocytosed via the non-canonical pathway is largely recycled back to the plasma membrane as functional receptors, whereas p38-independent populations are mainly sorted for lysosomal degradation. Moreover, ligand concentrations balance these endocytic trafficking pathways. These results demonstrate that ligand-activated EGFR signaling controls unliganded receptors through feedback phosphorylation, identifying a dual-mode regulation of the endocytic trafficking dynamics of EGFR. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. The biochemistry and immunology of non-canonical forms of HLA-B27.

    PubMed

    Shaw, Jacqueline; Hatano, Hiroko; Kollnberger, Simon

    2014-01-01

    HLA-B27 (B27) is strongly associated with the spondyloarthritides. B27 is expressed at the cell surface of antigen presenting cells (APC) both as canonical β2m-associated and non-canonical β2m-free heavy chain (FHC) forms which include B27 dimers (termed B272). B27 FHC forms arise in an endosomal compartment from recycling β2m-associated B27. Formation of cell surface FHC dimers is critically dependent on an unpaired reactive cysteine 67 in the α1 helix of the class I heavy chain. HLA-B27 also form redox-inducible β2m-associated dimers on exosomes and apoptosing cells. By contrast with cell surface expressed cysteine 67-dependent heavy chain dimers these dimers are dependent on a cytoplasmic cysteine 325 for their formation. HLA-B27 binds to immunoregulatory receptors including members of the Killer cell Immunoglobulin-like (KIR) and Leukocyte Immunoglobulin-like receptor family. B27 FHC bind to different but overlapping sets of these immunoreceptors compared to classical β2m-associated HLA-B27. B27 FHC bind more strongly to KIR3DL2 and LILRB2 immune receptor than other β2m-associated HLA-class I ligands. Genetic studies have implicated genes which control production of the important proinflammatory cytokine IL-17 in the pathogenesis of spondyloarthritis. Cell surface HLA-B27 FHC binding to these immune receptors or acting through other mechanisms could impact on the pathogenesis of spondyloarthritis by promoting immune cell production of IL-17. Here we review the literature on these non-canonical forms of HLA-B27 and the immune receptors they bind to and discuss the possible relevance of these interactions to the pathogenesis of spondyloarthropathy. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Linear canonical transformations of coherent and squeezed states in the Wigner phase space. II - Quantitative analysis

    NASA Technical Reports Server (NTRS)

    Han, D.; Kim, Y. S.; Noz, Marilyn E.

    1989-01-01

    It is possible to calculate expectation values and transition probabilities from the Wigner phase-space distribution function. Based on the canonical transformation properties of the Wigner function, an algorithm is developed for calculating these quantities in quantum optics for coherent and squeezed states. It is shown that the expectation value of a dynamical variable can be written in terms of its vacuum expectation value of the canonically transformed variable. Parallel-axis theorems are established for the photon number and its variant. It is also shown that the transition probability between two squeezed states can be reduced to that of the transition from one squeezed state to vacuum.

  9. The relationship between procrastination, learning strategies and statistics anxiety among Iranian college students: a canonical correlation analysis.

    PubMed

    Vahedi, Shahrum; Farrokhi, Farahman; Gahramani, Farahnaz; Issazadegan, Ali

    2012-01-01

    Approximately 66-80%of graduate students experience statistics anxiety and some researchers propose that many students identify statistics courses as the most anxiety-inducing courses in their academic curriculums. As such, it is likely that statistics anxiety is, in part, responsible for many students delaying enrollment in these courses for as long as possible. This paper proposes a canonical model by treating academic procrastination (AP), learning strategies (LS) as predictor variables and statistics anxiety (SA) as explained variables. A questionnaire survey was used for data collection and 246-college female student participated in this study. To examine the mutually independent relations between procrastination, learning strategies and statistics anxiety variables, a canonical correlation analysis was computed. Findings show that two canonical functions were statistically significant. The set of variables (metacognitive self-regulation, source management, preparing homework, preparing for test and preparing term papers) helped predict changes of statistics anxiety with respect to fearful behavior, Attitude towards math and class, Performance, but not Anxiety. These findings could be used in educational and psychological interventions in the context of statistics anxiety reduction.

  10. Long-Term IQ Stability Using the WISC-IV and WAIS-IV among a Sample of Special Education Students

    ERIC Educational Resources Information Center

    Spector, Hayley

    2013-01-01

    The present study investigated the stability of scores on the WISC-IV and WAIS-IV over an approximate six-year period. Previous research using older versions of the WISC and WAIS have suggested that these scales demonstrate strong stability of scores. Since research that has compared the stability of scores between the WISC-IV and the WAIS-IV is…

  11. [The evolution of the canons law code and the mental nature reasons of marital incapacity during the last 25 years].

    PubMed

    Drogowski, Marian

    2010-01-01

    The aim of the article was to investigate how during the last 25 years of implementation of the new canons law code changed the use of these new law regulations by the church lawyers as well as the mental causes for marital incapacity. The basis of investigation was the analysis of 135 forensic-psychiatric opinions made by the author for the Metropolitan Tribunal of Gniezno in the legal proceedings carried out in the years 1984-2008. On the basis of the analysis, the author got the following results. During the first 10 years of implementation of the new canon law code, the legal proceedings were carried on mostly of no 1 or together of no 1 and no 3 canon 1095, but during the last 15 years mostly of no 3 this canon of mental incapacity to undertaking the essentials marital duties. The mental causes of the marital incapacity also changed very significantly in this time. During the first 15 years, there were serious mental disorders such as schizophrenia, epilepsy or oligophrenia, but during the last 10 years the main causes of incapacity to undertaking the essential marital duties were personality disorders, alcohol dependences or psychosexual deviations.

  12. Equicontrollability and the model following problem

    NASA Technical Reports Server (NTRS)

    Curran, R. T.

    1971-01-01

    Equicontrollability and its application to the linear time-invariant model-following problem are discussed. The problem is presented in the form of two systems, the plant and the model. The requirement is to find a controller to apply to the plant so that the resultant compensated plant behaves, in an input-output sense, the same as the model. All systems are assumed to be linear and time-invariant. The basic approach is to find suitable equicontrollable realizations of the plant and model and to utilize feedback so as to produce a controller of minimal state dimension. The concept of equicontrollability is a generalization of control canonical (phase variable) form applied to multivariable systems. It allows one to visualize clearly the effects of feedback and to pinpoint the parameters of a multivariable system which are invariant under feedback. The basic contributions are the development of equicontrollable form; solution of the model-following problem in an entirely algorithmic way, suitable for computer programming; and resolution of questions on system decoupling.

  13. Babbling in children with neurodevelopmental disability and validity of a simplified way of measuring canonical babbling ratio.

    PubMed

    Nyman, Anna; Lohmander, Anette

    2018-01-01

    Babbling is an important precursor to speech, but has not yet been thoroughly investigated in children with neurodevelopmental disabilities. Canonical babbling ratio (CBR) is a commonly used but time-consuming measure for quantifying babbling. The aim of this study was twofold: to validate a simplified version of the CBR (CBR UTTER ), and to use this measure to determine if early precursors to speech and language development could be detected in children with different neurodevelopmental disabilities. Two different data sets were used. In Part I, CBR UTTER was compared to two other CBR measures using previously obtained phonetic transcriptions of 3571 utterances from 38 audio recordings of 12-18 month old children with and without cleft palate. In CBR UTTER , number of canonical utterances was divided by total number of utterances. In CBR syl , number of canonical syllables was divided by total number of syllables. In CBR utt , number of canonical syllables was divided by total number of utterances. High agreement was seen between CBR UTTER and CBR syl , suggesting CBR UTTER as an alternative. In Part II, babbling in children with neurodevelopmental disability was examined. Eighteen children aged 12-22 months with Down syndrome, cerebral palsy or developmental delay were audio-video recorded during interaction with a parent. Recordings were analysed by observation of babbling, consonant production, calculation of CBR UTTER , and compared to data from controls. The study group showed significantly lower occurrence of all variables, except for of plosives. The long-term relevance of the findings for the speech and language development of the children needs to be investigated.

  14. Children's Problems Predict Adults' "DSM-IV" Disorders across 24 Years

    ERIC Educational Resources Information Center

    Reef, Joni; van Meurs, Inge; Verhulst, Frank C.; van der Ende, Jan

    2010-01-01

    Objective: The goal of this study was to determine continuities of a broad range of psychopathology from childhood into middle adulthood in a general population sample across a 24-year follow-up. Method: In 1983, parent ratings of children's problems were collected with the Child Behavior Checklist (CBCL) in a general population sample of 2,076…

  15. Interpreting medium ring canonical conformers by a triangular plane tessellation of the macrocycle

    NASA Astrophysics Data System (ADS)

    Khalili, Pegah; Barnett, Christopher B.; Naidoo, Kevin J.

    2013-05-01

    Cyclic conformational coordinates are essential for the distinction of molecular ring conformers as the use of Cremer-Pople coordinates have illustrated for five- and six-membered rings. Here, by tessellating medium rings into triangular planes and using the relative angles made between triangular planes we are able to assign macrocyclic pucker conformations into canonical pucker conformers such as chairs, boats, etc. We show that the definition is straightforward compared with other methods popularly used for small rings and that it is computationally simple to implement for complex macrocyclic rings. These cyclic conformational coordinates directly couple to the motion of individual nodes of a ring. Therefore, they are useful for correlating the physical properties of macrocycles with their ring pucker and measuring the dynamic ring conformational behavior. We illustrate the triangular tessellation, assignment, and pucker analysis on 7- and 8-membered rings. Sets of canonical states are given for cycloheptane and cyclooctane that have been previously experimentally analysed.

  16. The Xenopus Tgfbi is required for embryogenesis through regulation of canonical Wnt signalling.

    PubMed

    Wang, Feng; Hu, Wanzhou; Xian, Jian; Ohnuma, Shin-ichi; Brenton, James D

    2013-07-01

    Tgfbi, a fasciclin family extracellular matrix protein, has various roles in human diseases from corneal dystrophies to cancer. However, the molecular mechanisms that underlie its functions are poorly understood. Here, we studied the role of Tgfbi during Xenopus embryogenesis. During gastrulation and immediately after, Xtgfbi is expressed at developmentally important signaling centers including the dorsal marginal zone, notochord and floorplate. Xtgfbi knockdown by anti-sense morpholinos causes defective organizer induction, patterning and differentiation of muscle, neuron and neural crests, similar to suppression of canonical Wnt signaling. In Xenopus embryos and animal caps as well as DLD-1 cells, we show that Tgfbi is strongly required for the full activation of the canonical Wnt pathway by promoting phosphorylation of GSK3β and consequently enhancing the stabilization and nuclear localization of β-catenin. Further analysis shows that Tgfbi is likely to promote GSK3β phosphorylation through integrin-linked kinase. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Canonical gravity, diffeomorphisms and objective histories

    NASA Astrophysics Data System (ADS)

    Samuel, Joseph

    2000-11-01

    This paper discusses the implementation of diffeomorphism invariance in purely Hamiltonian formulations of general relativity. We observe that, if a constrained Hamiltonian formulation derives from a manifestly covariant Lagrangian, the diffeomorphism invariance of the Lagrangian results in the following properties of the constrained Hamiltonian theory: the diffeomorphisms are generated by constraints on the phase space so that: (a) the algebra of the generators reflects the algebra of the diffeomorphism group; (b) the Poisson brackets of the basic fields with the generators reflects the spacetime transformation properties of these basic fields. This suggests that in a purely Hamiltonian approach the requirement of diffeomorphism invariance should be interpreted to include (b) and not just (a) as one might naively suppose. Giving up (b) amounts to giving up objective histories, even at the classical level. This observation has implications for loop quantum gravity which are spelled out in a companion paper. We also describe an analogy between canonical gravity and relativistic particle dynamics to illustrate our main point.

  18. Non-canonical distribution and non-equilibrium transport beyond weak system-bath coupling regime: A polaron transformation approach

    NASA Astrophysics Data System (ADS)

    Xu, Dazhi; Cao, Jianshu

    2016-08-01

    The concept of polaron, emerged from condense matter physics, describes the dynamical interaction of moving particle with its surrounding bosonic modes. This concept has been developed into a useful method to treat open quantum systems with a complete range of system-bath coupling strength. Especially, the polaron transformation approach shows its validity in the intermediate coupling regime, in which the Redfield equation or Fermi's golden rule will fail. In the polaron frame, the equilibrium distribution carried out by perturbative expansion presents a deviation from the canonical distribution, which is beyond the usual weak coupling assumption in thermodynamics. A polaron transformed Redfield equation (PTRE) not only reproduces the dissipative quantum dynamics but also provides an accurate and efficient way to calculate the non-equilibrium steady states. Applications of the PTRE approach to problems such as exciton diffusion, heat transport and light-harvesting energy transfer are presented.

  19. 45 CFR 1355.21 - Plan requirements for titles IV-E and IV-B.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... agency and the Indian Tribe must make available for public review and inspection the Child and Family... 45 Public Welfare 4 2012-10-01 2012-10-01 false Plan requirements for titles IV-E and IV-B. 1355.21 Section 1355.21 Public Welfare Regulations Relating to Public Welfare (Continued) OFFICE OF HUMAN...

  20. 45 CFR 1355.21 - Plan requirements for titles IV-E and IV-B.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... agency and the Indian Tribe must make available for public review and inspection the Child and Family... 45 Public Welfare 4 2014-10-01 2014-10-01 false Plan requirements for titles IV-E and IV-B. 1355.21 Section 1355.21 Public Welfare Regulations Relating to Public Welfare (Continued) OFFICE OF HUMAN...

  1. Glomerular basement membrane injuries in IgA nephropathy evaluated by double immunostaining for α5(IV) and α2(IV) chains of type IV collagen and low-vacuum scanning electron microscopy.

    PubMed

    Masuda, Yukinari; Yamanaka, Nobuaki; Ishikawa, Arimi; Kataoka, Mitue; Arai, Takashi; Wakamatsu, Kyoko; Kuwahara, Naomi; Nagahama, Kiyotaka; Ichikawa, Kaori; Shimizu, Akira

    2015-06-01

    The glomerulus contains well-developed capillaries, which are at risk of injury due to high hydrostatic pressure, hyperfiltration, hypertension and inflammation. However, the pathological alterations of the injured glomerular basement membrane (GBM), the main component of the glomerular filtration barrier, are still uncertain in cases of glomerulonephritis. We examined the alterations of the GBM in 50 renal biopsy cases with IgA nephropathy (31.8 ± 17.6 years old) using double immunostaining for the α2(IV) and α5(IV) chains of type IV collagen, and examining the ultrastructural alterations by transmission electron microscopy (TEM) and low-vacuum scanning electron microscopy (LV-SEM). The GBM of IgA nephropathy cases showed various morphological and qualitative alterations. In the TEM findings, thinning, gaps, rupture, thickening with a lamellar and reticular structure and double contours were detected in the GBM. Double immunostaining for α5(IV) and α2(IV) showed thickening of the GBM with reduced α5(IV) and increased α2(IV), or mosaic images of α5(IV) and α2(IV), and holes, fractures, spiny projections and rupture of α5(IV) in the GBM. In addition, LV-SEM showed an etched image and multiple holes in a widening and wavy GBM. These findings might be associated with the development of a brittle GBM in IgA nephropathy. Glomerular basement membrane alterations were frequently noted in IgA nephropathy, and were easily evaluated by double immunostaining for α2(IV) and α5(IV) of type IV collagen and LV-SEM. The application of these analyses to human renal biopsy specimens may enhance our understanding of the alterations of the GBM that occur in human glomerular diseases.

  2. Finite temperature grand canonical ensemble study of the minimum electrophilicity principle.

    PubMed

    Miranda-Quintana, Ramón Alain; Chattaraj, Pratim K; Ayers, Paul W

    2017-09-28

    We analyze the minimum electrophilicity principle of conceptual density functional theory using the framework of the finite temperature grand canonical ensemble. We provide support for this principle, both for the cases of systems evolving from a non-equilibrium to an equilibrium state and for the change from one equilibrium state to another. In doing so, we clearly delineate the cases where this principle can, or cannot, be used.

  3. The Education of Royalty in the Eighteenth Century: George IV and William IV

    ERIC Educational Resources Information Center

    Clarke, M. L.

    1978-01-01

    George IV, the Prince of Wales, and William IV, his younger brother, both the sons of George III, were given all the educational advantage one could be granted in the eighteenth century. The precise curriculum and practices of their teachers are discussed with an evaluation of both students as a moral for future consideration. (RK)

  4. Singular cosmological evolution using canonical and ghost scalar fields

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Nojiri, Shin'ichi; Odintsov, S.D.; Oikonomou, V.K.

    2015-09-01

    We demonstrate that finite time singularities of Type IV can be consistently incorporated in the Universe's cosmological evolution, either appearing in the inflationary era, or in the late-time regime. While using only one scalar field instabilities can in principle occur at the time of the phantom-divide crossing, when two fields are involved we are able to avoid such instabilities. Additionally, the two-field scalar-tensor theories prove to be able to offer a plethora of possible viable cosmological scenarios, at which various types of cosmological singularities can be realized. Amongst others, it is possible to describe inflation with the appearance of amore » Type IV singularity, and phantom late-time acceleration which ends in a Big Rip. Finally, for completeness, we also present the Type IV realization in the context of suitably reconstructed F(R) gravity.« less

  5. Canonical angular momentum compression near the Brillouin limit

    NASA Astrophysics Data System (ADS)

    Jeong, E.; Gilson, E.; Fajans, J.

    2000-10-01

    Near the Brillouin limit, the angular momentum of a trapped, T=0, pure-electron plasma approaches zero. If the plasma expands axially, its density would appear to drop. However, the plasma's canonical angular momentum is not changed by an axial expansion, so the plasma must stay near the Brillouin limit; thus the plasma's density cannot change when it is expanded. The only way for the plasma density to remain constant as the plasma length increases is for the plasma radius to decrease. Dynamically, this decrease is caused by the polarization drift induced by a small decrease in the density. In this poster we present preliminary experimental evidence demonstrating this radial compression. This work was supported by the ONR.

  6. Canonical TGF-β Signaling Negatively Regulates Neuronal Morphogenesis through TGIF/Smad Complex-Mediated CRMP2 Suppression.

    PubMed

    Nakashima, Hideyuki; Tsujimura, Keita; Irie, Koichiro; Ishizu, Masataka; Pan, Miao; Kameda, Tomonori; Nakashima, Kinichi

    2018-05-16

    Functional neuronal connectivity requires proper neuronal morphogenesis and its dysregulation causes neurodevelopmental diseases. Transforming growth factor-β (TGF-β) family cytokines play pivotal roles in development, but little is known about their contribution to morphological development of neurons. Here we show that the Smad-dependent canonical signaling of TGF-β family cytokines negatively regulates neuronal morphogenesis during brain development. Mechanistically, activated Smads form a complex with transcriptional repressor TG-interacting factor (TGIF), and downregulate the expression of a neuronal polarity regulator, collapsin response mediator protein 2. We also demonstrate that TGF-β family signaling inhibits neurite elongation of human induced pluripotent stem cell-derived neurons. Furthermore, the expression of TGF-β receptor 1, Smad4, or TGIF, which have mutations found in patients with neurodevelopmental disorders, disrupted neuronal morphogenesis in both mouse (male and female) and human (female) neurons. Together, these findings suggest that the regulation of neuronal morphogenesis by an evolutionarily conserved function of TGF-β signaling is involved in the pathogenesis of neurodevelopmental diseases. SIGNIFICANCE STATEMENT Canonical transforming growth factor-β (TGF-β) signaling plays a crucial role in multiple organ development, including brain, and mutations in components of the signaling pathway associated with several human developmental disorders. In this study, we found that Smads/TG-interacting factor-dependent canonical TGF-β signaling regulates neuronal morphogenesis through the suppression of collapsin response mediator protein-2 (CRMP2) expression during brain development, and that function of this signaling is evolutionarily conserved in the mammalian brain. Mutations in canonical TGF-β signaling factors identified in patients with neurodevelopmental disorders disrupt the morphological development of neurons. Thus, our

  7. RNAHelix: computational modeling of nucleic acid structures with Watson-Crick and non-canonical base pairs.

    PubMed

    Bhattacharyya, Dhananjay; Halder, Sukanya; Basu, Sankar; Mukherjee, Debasish; Kumar, Prasun; Bansal, Manju

    2017-02-01

    Comprehensive analyses of structural features of non-canonical base pairs within a nucleic acid double helix are limited by the availability of a small number of three dimensional structures. Therefore, a procedure for model building of double helices containing any given nucleotide sequence and base pairing information, either canonical or non-canonical, is seriously needed. Here we describe a program RNAHelix, which is an updated version of our widely used software, NUCGEN. The program can regenerate duplexes using the dinucleotide step and base pair orientation parameters for a given double helical DNA or RNA sequence with defined Watson-Crick or non-Watson-Crick base pairs. The original structure and the corresponding regenerated structure of double helices were found to be very close, as indicated by the small RMSD values between positions of the corresponding atoms. Structures of several usual and unusual double helices have been regenerated and compared with their original structures in terms of base pair RMSD, torsion angles and electrostatic potentials and very high agreements have been noted. RNAHelix can also be used to generate a structure with a sequence completely different from an experimentally determined one or to introduce single to multiple mutation, but with the same set of parameters and hence can also be an important tool in homology modeling and study of mutation induced structural changes.

  8. “Whatdunit?” Sentence Comprehension Abilities of Children With SLI: Sensitivity to Word Order in Canonical and Noncanonical Structures

    PubMed Central

    Gillam, Ronald B.; Evans, Julia L.; Sergeev, Alexander V.

    2017-01-01

    Purpose With Aim 1, we compared the comprehension of and sensitivity to canonical and noncanonical word order structures in school-age children with specific language impairment (SLI) and same-age typically developing (TD) children. Aim 2 centered on the developmental improvement of sentence comprehension in the groups. With Aim 3, we compared the comprehension error patterns of the groups. Method Using a “Whatdunit” agent selection task, 117 children with SLI and 117 TD children (ages 7:0–11:11, years:months) propensity matched on age, gender, mother's education, and family income pointed to the picture that best represented the agent in semantically implausible canonical structures (subject–verb–object, subject relative) and noncanonical structures (passive, object relative). Results The SLI group performed worse than the TD group across sentence types. TD children demonstrated developmental improvement across each sentence type, but children with SLI showed improvement only for canonical sentences. Both groups chose the object noun as agent significantly more often than the noun appearing in a prepositional phrase. Conclusions In the absence of semantic–pragmatic cues, comprehension of canonical and noncanonical sentences by children with SLI is limited, with noncanonical sentence comprehension being disproportionately limited. The children's ability to make proper semantic role assignments to the noun arguments in sentences, especially noncanonical, is significantly hindered. PMID:28832884

  9. A Non-canonical Feedback Circuit for Rapid Interactions between Somatosensory Cortices.

    PubMed

    Minamisawa, Genki; Kwon, Sung Eun; Chevée, Maxime; Brown, Solange P; O'Connor, Daniel H

    2018-05-29

    Sensory perception depends on interactions among cortical areas. These interactions are mediated by canonical patterns of connectivity in which higher areas send feedback projections to lower areas via neurons in superficial and deep layers. Here, we probed the circuit basis of interactions among two areas critical for touch perception in mice, whisker primary (wS1) and secondary (wS2) somatosensory cortices. Neurons in layer 4 of wS2 (S2 L4 ) formed a major feedback pathway to wS1. Feedback from wS2 to wS1 was organized somatotopically. Spikes evoked by whisker deflections occurred nearly as rapidly in wS2 as in wS1, including among putative S2 L4 → S1 feedback neurons. Axons from S2 L4 → S1 neurons sent stimulus orientation-specific activity to wS1. Optogenetic excitation of S2 L4 neurons modulated activity across both wS2 and wS1, while inhibition of S2 L4 reduced orientation tuning among wS1 neurons. Thus, a non-canonical feedback circuit, originating in layer 4 of S2, rapidly modulates early tactile processing. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  10. Endothelial RSPO3 Controls Vascular Stability and Pruning through Non-canonical WNT/Ca(2+)/NFAT Signaling.

    PubMed

    Scholz, Beate; Korn, Claudia; Wojtarowicz, Jessica; Mogler, Carolin; Augustin, Iris; Boutros, Michael; Niehrs, Christof; Augustin, Hellmut G

    2016-01-11

    The WNT signaling enhancer R-spondin3 (RSPO3) is prominently expressed in the vasculature. Correspondingly, embryonic lethality of Rspo3-deficient mice is caused by vessel remodeling defects. Yet the mechanisms underlying vascular RSPO3 function remain elusive. Inducible endothelial Rspo3 deletion (Rspo3-iECKO) resulted in perturbed developmental and tumor vascular remodeling. Endothelial cell apoptosis and vascular pruning led to reduced microvessel density in Rspo3-iECKO mice. Rspo3-iECKO mice strikingly phenocopied the non-canonical WNT signaling-induced vascular defects of mice deleted for the WNT secretion factor Evi/Wls. An endothelial screen for RSPO3 and EVI/WLS co-regulated genes identified Rnf213, Usp18, and Trim30α. RNF213 targets filamin A and NFAT1 for proteasomal degradation attenuating non-canonical WNT/Ca(2+) signaling. Likewise, USP18 and TRIM5α inhibited NFAT1 activation. Consequently, NFAT protein levels were decreased in endothelial cells of Rspo3-iECKO mice and pharmacological NFAT inhibition phenocopied Rspo3-iECKO mice. The data identify endothelial RSPO3-driven non-canonical WNT/Ca(2+)/NFAT signaling as a critical maintenance pathway of the remodeling vasculature. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. The School Canon as a Battlefield. A Baptismal Font without a Child

    ERIC Educational Resources Information Center

    Pavlovets, M. G.

    2017-01-01

    This article describes the history and fierce controversy that has flared up in Russia regarding the composition of the school canon (SC), which is a list of literary works that students are required to study in literature classes, as well as the very need for such a list in the first place. The history, which goes back to the time of the first…

  12. On canonical cylinder sections for accurate determination of contact angle in microgravity

    NASA Technical Reports Server (NTRS)

    Concus, Paul; Finn, Robert; Zabihi, Farhad

    1992-01-01

    Large shifts of liquid arising from small changes in certain container shapes in zero gravity can be used as a basis for accurately determining contact angle. Canonical geometries for this purpose, recently developed mathematically, are investigated here computationally. It is found that the desired nearly-discontinuous behavior can be obtained and that the shifts of liquid have sufficient volume to be readily observed.

  13. Enhanced 99Tc retention in glass waste form using Tc(IV)-incorporated Fe minerals

    DOE PAGES

    Um, Wooyong; Luksic, Steven A.; Wang, Guohui; ...

    2017-09-07

    We present that technetium ( 99Tc) immobilization by doping into iron oxide mineral phases may alleviate the problems with Tc volatility during vitrification of nuclear waste. Because reduced Tc, Tc(IV), substitutes for Fe(III) in the crystal structure by a process of Tc reduction from Tc(VII) to Tc(IV) followed by co-precipitation of Fe oxide minerals, two Tc-incorporated Fe minerals (Tc-goethite and Tc-magnetite/maghemite) were prepared and tested for Tc retention in glass melt samples at temperatures between 600 and 1000 °C. After being cooled, the solid glass specimens prepared at different temperatures at 600, 800, and 1000 °C were analyzed for Tcmore » oxidation state using Tc K-edge XANES. In most samples, Tc was partially (<60%) oxidized from Tc(IV) to Tc(VII) as the melt temperature increased up to 600 °C. However, most of Tc(IV) was completely (>95%) oxidized to Tc(VII) at temperature above 800 °C. Tc retention in glass melt samples prepared using Tc-incorporated Fe minerals were slightly higher (~10%) than in glass prepared using KTcO4 because of limited and delayed Tc volatilization.« less

  14. Enhanced 99Tc retention in glass waste form using Tc(IV)-incorporated Fe minerals

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Um, Wooyong; Luksic, Steven A.; Wang, Guohui

    We present that technetium ( 99Tc) immobilization by doping into iron oxide mineral phases may alleviate the problems with Tc volatility during vitrification of nuclear waste. Because reduced Tc, Tc(IV), substitutes for Fe(III) in the crystal structure by a process of Tc reduction from Tc(VII) to Tc(IV) followed by co-precipitation of Fe oxide minerals, two Tc-incorporated Fe minerals (Tc-goethite and Tc-magnetite/maghemite) were prepared and tested for Tc retention in glass melt samples at temperatures between 600 and 1000 °C. After being cooled, the solid glass specimens prepared at different temperatures at 600, 800, and 1000 °C were analyzed for Tcmore » oxidation state using Tc K-edge XANES. In most samples, Tc was partially (<60%) oxidized from Tc(IV) to Tc(VII) as the melt temperature increased up to 600 °C. However, most of Tc(IV) was completely (>95%) oxidized to Tc(VII) at temperature above 800 °C. Tc retention in glass melt samples prepared using Tc-incorporated Fe minerals were slightly higher (~10%) than in glass prepared using KTcO4 because of limited and delayed Tc volatilization.« less

  15. A Survey of Inhalant Use Disorders among Delinquent Youth: Prevalence, Clinical Features, and Latent Structure of DSM-IV Diagnostic Criteria

    PubMed Central

    Howard, Matthew O; Perron, Brian E

    2009-01-01

    Background Inhalant use is among the most pernicious and poorly understood forms of adolescent substance use. Many youth in the juvenile justice system have used inhalants, but little is known about inhalant use disorders (IUDs) in antisocial youth populations. The purpose of this study was to examine the prevalence, clinical features, and latent structure of DSM-IV IUDs in a state population of antisocial youth. Methods Cross-sectional survey conducted in 2003. Of 740 youth residing in Missouri State Division of Youth Services' (MDYS) residential treatment facilities at the time the study was conducted, 723 (97.7%) completed interviews. Eighty-seven percent were male, with a mean age of 15.5 (SD = 1.2). Nearly 4 in 10 youth (38.5%; n = 279) reported lifetime inhalant use. Youth ranged from very mildly to severely antisocial. Results Of 279 inhalant users, 52 (18.6%) met DSM-IV inhalant abuse criteria and 79 (28.3%) met inhalant dependence criteria. Five of 10 IUD criteria were met by > 10% of the total sample. Latent class analyses demonstrated a substantial concordance between DSM-IV-defined IUDs and an empirically-derived classification based on responses to DSM-IV IUD diagnostic criteria. Conclusion IUDs and constituent criteria were prevalent among youth in the juvenile justice system. Two groups of problem inhalant users were identified, symptomatic users-DSM-IV inhalant abuse and highly symptomatic users-DSM-IV inhalant dependence, which differed primarily in severity of inhalant-related problems. Inhalant screening, prevention and treatment efforts in juvenile justice settings are rarely delivered, but critically needed. PMID:19267939

  16. Canonical Wnt signaling differently modulates osteogenic differentiation of mesenchymal stem cells derived from bone marrow and from periodontal ligament under inflammatory conditions.

    PubMed

    Liu, Wenjia; Konermann, Anna; Guo, Tao; Jäger, Andreas; Zhang, Liqiang; Jin, Yan

    2014-03-01

    Cellular plasticity and complex functional requirements of the periodontal ligament (PDL) assume a local stem cell (SC) niche to maintain tissue homeostasis and repair. Here, pathological alterations caused by inflammatory insults might impact the regenerative capacities of these cells. As bone homeostasis is fundamentally controlled by Wnt-mediated signals, it was the aim of this study to characterize the SC-like capacities of cells derived from PDL and to investigate their involvement in bone pathophysiology especially regarding the canonical Wnt pathway. PDLSCs were investigated for their SC characteristics via analysis of cell surface marker expression, colony forming unit efficiency, proliferation, osteogenic differentiation and adipogenic differentiation, and compared to bone marrow derived mesenchymal SCs (BMMSCs). To determine the impact of both inflammation and the canonical Wnt pathway on osteogenic differentiation, cells were challenged with TNF-α, maintained with or without Wnt3a or DKK-1 under osteogenic induction conditions and investigated for p-IκBα, p-NF-κB, p-Akt, β-catenin, p-GSK-3β, ALP and Runx2. PDLSCs exhibit weaker adipogenic and osteogenic differentiation capacities compared to BMMSCs. TNF-α inhibited osteogenic differentiation of PDLSCs more than BMMSCs mainly through regulating canonical Wnt pathway. Blocking the canonical Wnt pathway by DKK-1 reconstituted osteogenic differentiation of PDLSCs under inflammatory conditions, whereas activation by Wnt3a increased osteogenic differentiation of BMMSCs. Our results suggest a diverse regulation of the inhibitory effect of TNF-α in BMMSCs and PDLSCs via canonical Wnt pathway modulation. These findings provide novel insights on PDLSC SC-like capacities and their involvement in bone pathophysiology under the impact of the canonical Wnt pathway. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Chromogenic Detection of Dipeptidyl Peptidase IV (DPP-IV) Activity using Peptide-Functionalized Gold Nanoparticles

    NASA Astrophysics Data System (ADS)

    Abul-Huda, Yasin Mohammad

    Metal nanoparticles offer a useful platform for a wide range of biological applications especially for biosensing, bioimaging and drug delivery. This thesis presents a body of original research describing the synthesis, characterisation and development of a novel and convenient biosensing assay for detection of dipeptidyl peptidase IV (DPP-IV) enzyme activity using peptide functionalized gold nanoparticles. The distinctive optical and physical properties of gold nanoparticles (Au NP) were harnessed for the development of a colorimetric assay for rapid sensing of DPP-IV activities and screening DPP-IV inhbitors. The citrate reduction method for Au NPs synthesis was optimised and several potential peptide substrates (GPDC, VP-EN-DC, C/G dipeptide, GPG-EN-PEG4-LA, GPDCALNNC) were designed to provide substrates that mimic the DPP-IV natural substrates. The performances of the substrate functionalized Au NPs were assessed for their appropriateness for the detection of the enzyme activity. Addition of DPP-IV to the solutions containing the functionalized Au NPs resulted in cleavage of the substrate and thus causing the aggregation of the Au NPs which in turn led to a shift of the surface plasmon peak toward longer wavelengths, and a change of the colour of the colloidal suspension from red to blue. Overall, real-time detection of DPP-IV activity over a broader range (0-40 U/L) with high selectivity and stability was obtained, thus providing a method that can be used to determine the levels of DPP-IV/CD26 in biological fluids such as serum and plasma. Further assay developments were conducted to overcome limitations encountered with the original Au NP assay, especially the narrow dynamic linear range and stability in high ionic strength solutions. Validation and comparison of the Au NP assay developed has revealed that this method is highly correlated to the gold standard chromogenic Gly-Pro-pNA method for detection of enzyme activity in biological samples. Very good

  18. A new randomized Kaczmarz based kernel canonical correlation analysis algorithm with applications to information retrieval.

    PubMed

    Cai, Jia; Tang, Yi

    2018-02-01

    Canonical correlation analysis (CCA) is a powerful statistical tool for detecting the linear relationship between two sets of multivariate variables. Kernel generalization of it, namely, kernel CCA is proposed to describe nonlinear relationship between two variables. Although kernel CCA can achieve dimensionality reduction results for high-dimensional data feature selection problem, it also yields the so called over-fitting phenomenon. In this paper, we consider a new kernel CCA algorithm via randomized Kaczmarz method. The main contributions of the paper are: (1) A new kernel CCA algorithm is developed, (2) theoretical convergence of the proposed algorithm is addressed by means of scaled condition number, (3) a lower bound which addresses the minimum number of iterations is presented. We test on both synthetic dataset and several real-world datasets in cross-language document retrieval and content-based image retrieval to demonstrate the effectiveness of the proposed algorithm. Numerical results imply the performance and efficiency of the new algorithm, which is competitive with several state-of-the-art kernel CCA methods. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Multireference quantum chemistry through a joint density matrix renormalization group and canonical transformation theory.

    PubMed

    Yanai, Takeshi; Kurashige, Yuki; Neuscamman, Eric; Chan, Garnet Kin-Lic

    2010-01-14

    We describe the joint application of the density matrix renormalization group and canonical transformation theory to multireference quantum chemistry. The density matrix renormalization group provides the ability to describe static correlation in large active spaces, while the canonical transformation theory provides a high-order description of the dynamic correlation effects. We demonstrate the joint theory in two benchmark systems designed to test the dynamic and static correlation capabilities of the methods, namely, (i) total correlation energies in long polyenes and (ii) the isomerization curve of the [Cu(2)O(2)](2+) core. The largest complete active spaces and atomic orbital basis sets treated by the joint DMRG-CT theory in these systems correspond to a (24e,24o) active space and 268 atomic orbitals in the polyenes and a (28e,32o) active space and 278 atomic orbitals in [Cu(2)O(2)](2+).

  20. NATIONAL COASTAL CONDITION REPORT IV | Science ...

    EPA Pesticide Factsheets

    The National Coastal Condition Report IV (NCCR IV) is the fourth in a series of environmental assessments of U.S. coastal waters and the Great Lakes. The report includes assessments of all the nation’s estuaries in the contiguous 48 states and Puerto Rico, south-eastern Alaska, Hawaii, the U.S. Virgin Islands, Guam, and American Samoa. The NCCR IV presents four main types of data: (1) coastal monitoring data, (2) coastal ocean/ offshore monitoring data, (3) offshore fisheries data, and (4) assessment and advisory data (new to NCCR IV). The NCCR IV relies heavily on coastal monitoring data from EPA’s National Coastal Assessment (NCA) to assess coastal condition by evaluating five indicators of condition—water quality, sediment quality, benthic community condition, coastal habitat loss, and fish tissue contaminants. To assess and report on the condition of the nation's coastal resources

  1. [Strategy to strengthen health research capabilities in regional public universities: the role of the Mining Canon and the Instituto Nacional de Salud].

    PubMed

    Romaní, Franco; Cabezas, César; Espinoza, Manuel; Minaya, Gabriela; Huaripata, José; Ureta, Juan Manuel; Yazuda, Myriam; Gastañaga, María del Carmen; Miraval, María Luz; Aparco, Juan Pablo; Anaya, Elizabeth; Castro, José; Esquivel, Silvia

    2012-01-01

    The development of scientific health research requires a sustained and articulated research system that is consistent with the research priorities, as well as both internal and external funding, and availability of competent human resources. The Mining Canon, a constitutional right, has been partly used to foster applied scientific research in public universities (PU). In addition, the National Health Institute (INSTITUTO NACIONAL DE SALUD - INS) is devoted, among others, to promoting, managing and disseminating health research development at a national level. As part of these activities, a technical team was created to provide technical assistance to PU for research development using Mining Canon funds by making local adjustments to research protocols promoted by the INS and assumed by the professors-researchers at the Universities. This article aims at describing the reality of research at Peruvian public universities that have access to Mining Canon funds, as well as to elaborate on the work the INS is carrying out in order to strengthen research capabilities, starting with the development of research proposals that could potentially be funded by the Mining Canon.

  2. Actinide Corroles: Synthesis and Characterization of Thorium(IV) and Uranium(IV) bis(-chloride) Dimers

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ward, Ashleigh L.; Buckley, Heather L.; Gryko, Daniel T.

    2013-12-01

    The first synthesis and structural characterization of actinide corroles is presented. Thorium(IV) and uranium(IV) macrocycles of Mes2(p-OMePh)corrole were synthesised and characterized by single-crystal X-ray diffraction, UV-Visible spectroscopy, variable-temperature 1H NMR, ESI mass spectrometry and cyclic voltammetry.

  3. Absence of high-temperature ballistic transport in the spin-1/2 XXX chain within the grand-canonical ensemble

    NASA Astrophysics Data System (ADS)

    Carmelo, J. M. P.; Prosen, T.

    2017-01-01

    Whether in the thermodynamic limit, vanishing magnetic field h → 0, and nonzero temperature the spin stiffness of the spin-1/2 XXX Heisenberg chain is finite or vanishes within the grand-canonical ensemble remains an unsolved and controversial issue, as different approaches yield contradictory results. Here we provide an upper bound on the stiffness and show that within that ensemble it vanishes for h → 0 in the thermodynamic limit of chain length L → ∞, at high temperatures T → ∞. Our approach uses a representation in terms of the L physical spins 1/2. For all configurations that generate the exact spin-S energy and momentum eigenstates such a configuration involves a number 2S of unpaired spins 1/2 in multiplet configurations and L - 2 S spins 1/2 that are paired within Msp = L / 2 - S spin-singlet pairs. The Bethe-ansatz strings of length n = 1 and n > 1 describe a single unbound spin-singlet pair and a configuration within which n pairs are bound, respectively. In the case of n > 1 pairs this holds both for ideal and deformed strings associated with n complex rapidities with the same real part. The use of such a spin 1/2 representation provides useful physical information on the problem under investigation in contrast to often less controllable numerical studies. Our results provide strong evidence for the absence of ballistic transport in the spin-1/2 XXX Heisenberg chain in the thermodynamic limit, for high temperatures T → ∞, vanishing magnetic field h → 0 and within the grand-canonical ensemble.

  4. Mechanisms of chiral discrimination by topoisomerase IV

    PubMed Central

    Neuman, K. C.; Charvin, G.; Bensimon, D.; Croquette, V.

    2009-01-01

    Topoisomerase IV (Topo IV), an essential ATP-dependent bacterial type II topoisomerase, transports one segment of DNA through a transient double-strand break in a second segment of DNA. In vivo, Topo IV unlinks catenated chromosomes before cell division and relaxes positive supercoils generated during DNA replication. In vitro, Topo IV relaxes positive supercoils at least 20-fold faster than negative supercoils. The mechanisms underlying this chiral discrimination by Topo IV and other type II topoisomerases remain speculative. We used magnetic tweezers to measure the relaxation rates of single and multiple DNA crossings by Topo IV. These measurements allowed us to determine unambiguously the relative importance of DNA crossing geometry and enzymatic processivity in chiral discrimination by Topo IV. Our results indicate that Topo IV binds and passes DNA strands juxtaposed in a nearly perpendicular orientation and that relaxation of negative supercoiled DNA is perfectly distributive. Together, these results suggest that chiral discrimination arises primarily from dramatic differences in the processivity of relaxing positive and negative supercoiled DNA: Topo IV is highly processive on positively supercoiled DNA, whereas it is perfectly distributive on negatively supercoiled DNA. These results provide fresh insight into topoisomerase mechanisms and lead to a model that reconciles contradictory aspects of previous findings while providing a framework to interpret future results. PMID:19359479

  5. Nitrogen removal capacity and bacterial community dynamics of a Canon biofilter system at different organic matter concentrations.

    PubMed

    García-Ruiz, María J; Maza-Márquez, Paula; González-López, Jesús; Osorio, Francisco

    2018-02-01

    Three Canon bench-scale bioreactors with a volume of 2 L operating in parallel were configured as submerged biofilters. In the present study we investigated the effects of a high ammonium concentration (320 mgNH 4 + · L -1 ) and different concentrations of organic matter (0, 100 and 400 mgCOD·L -1 ) on the nitrogen removal capacity and the bacterial community structure. After 60 days, the Canon biofilters operated properly under concentrations of 0 and 100 mgCOD·L -1 of organic matter, with nitrogen removal efficiencies up to 85%. However, a higher concentration of organic matter (400 mgCOD·L -1 ) produced a partial inhibition of nitrogen removal (68.1% efficiency). The addition of higher concentrations of organic matter a modified the bacterial community structure in the Canon biofilter, increasing the proliferation of heterotrophic bacteria related to the genera of Thauera, Longilinea, Ornatilinea, Thermomarinilinea, unclassified Chlorobiales and Denitratisoma. However, heterotrophic bacteria co-exist with Nitrosomonas and Candidatus Scalindua. Thus, our study confirms the co-existence of different microbial activities (AOB, Anammox and denitrification) and the adaptation of a fixed-biofilm system to different concentrations of organic matter. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. The Relationship Between Procrastination, Learning Strategies and Statistics Anxiety Among Iranian College Students: A Canonical Correlation Analysis

    PubMed Central

    Vahedi, Shahrum; Farrokhi, Farahman; Gahramani, Farahnaz; Issazadegan, Ali

    2012-01-01

    Objective: Approximately 66-80%of graduate students experience statistics anxiety and some researchers propose that many students identify statistics courses as the most anxiety-inducing courses in their academic curriculums. As such, it is likely that statistics anxiety is, in part, responsible for many students delaying enrollment in these courses for as long as possible. This paper proposes a canonical model by treating academic procrastination (AP), learning strategies (LS) as predictor variables and statistics anxiety (SA) as explained variables. Methods: A questionnaire survey was used for data collection and 246-college female student participated in this study. To examine the mutually independent relations between procrastination, learning strategies and statistics anxiety variables, a canonical correlation analysis was computed. Results: Findings show that two canonical functions were statistically significant. The set of variables (metacognitive self-regulation, source management, preparing homework, preparing for test and preparing term papers) helped predict changes of statistics anxiety with respect to fearful behavior, Attitude towards math and class, Performance, but not Anxiety. Conclusion: These findings could be used in educational and psychological interventions in the context of statistics anxiety reduction. PMID:24644468

  7. A Retrospective Video Analysis of Canonical Babbling and Volubility in Infants with Fragile X Syndrome at 9 – 12 Months of Age

    PubMed Central

    Belardi, Katie; Watson, Linda R.; Faldowski, Richard A.; Hazlett, Heather; Crais, Elizabeth; Baranek, Grace T.; McComish, Cara; Patten, Elena; Oller, D. Kimbrough

    2017-01-01

    An infant’s vocal capacity develops significantly during the first year of life. Research suggests early measures of pre-speech development, such as canonical babbling and volubility, can differentiate typical versus disordered development. This study offers a new contribution by comparing early vocal development in 10 infants with Fragile X syndrome and 14 with typical development. Results suggest infants with Fragile X syndrome produce fewer syllables and have significantly lower canonical babbling ratios (i.e., canonical syllables/total syllables) compared to infants who are typically developing. Furthermore, the particular measures of babbling were strong predictors of group membership, adding evidence regarding the possible utility of these markers in early identification. PMID:28247019

  8. Teaching and Using Multicultural Literature in Grades 9-12: Moving beyond the Canon.

    ERIC Educational Resources Information Center

    Willis, Arlette Ingram, Ed.

    Designed to help move literature beyond the canon to include the works of many underrepresented Americans, this book contains a collection of writings which discuss multicultural literature for secondary classrooms. It attempts to bring together the literature written by people of color living in the United States. Themes which emerge in the book…

  9. Impeding 99Tc(IV) mobility in novel waste forms

    DOE PAGES

    Lee, Mal-Soon; Um, Wooyong; Wang, Guohui; ...

    2016-06-30

    Technetium ( 99Tc) is a long-lived radioactive fission product whose mobility in the subsurface is largely governed by its oxidation state1. Immobilization of Tc in mineral substrates is crucial for radioactive waste management and environmental remediation. Tc(IV) incorporation in spinels2, 3 has been proposed as a novel method to increase Tc retention in glass waste forms. However, experiments with Tc-magnetite under high temperature and oxic conditions showed re-oxidation of Tc(IV) to volatile pertechnetate Tc(VII)O4-.4, 5 Here we address this problem with large-scale ab initio molecular dynamics simulations and propose that elevated temperatures, 1st row transition metal dopants can significantly enhancemore » Tc retention in the order Co > Zn > Ni. Experiments with doped spinels at T=700 ºC provided quantitative confirmation of increased Tc retention in the same order predicted by theory. This work highlights the power of modern state-of-the-art simulations to provide essential insights and generate bottom-up design criteria of complex oxide materials at elevated temperatures.« less

  10. Enhanced 99 Tc retention in glass waste form using Tc(IV)-incorporated Fe minerals

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Um, Wooyong; Luksic, Steven A.; Wang, Guohui

    Technetium (99Tc) immobilization by doping into iron oxide mineral phases may alleviate the problems with Tc volatility during vitrification of nuclear waste. Reduced Tc, Tc(IV), substitutes for Fe(III) in the crystal structure by a process of Tc reduction from Tc(VII) to Tc(IV) followed by co-precipitation of Fe oxide minerals. Two Tc-incorporated Fe minerals (Tc-goethite and Tc-magnetite/maghemite) were prepared and tested for Tc retention in glass melt samples at temperatures between 600 – 1,000 oC. After being cooled, the solid glass specimens prepared at different temperatures were analyzed for Tc oxidation state using Tc K-edge XANES. In most samples, Tc wasmore » partially oxidized from Tc(IV) to Tc(VII) as the melt temperature increased. However, Tc retention in glass melt samples prepared using Tc-incorporated Fe minerals were moderately higher than in glass prepared using KTcO4 because of limited and delayed Tc volatilization.« less

  11. A united event grand canonical Monte Carlo study of partially doped polyaniline

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Byshkin, M. S., E-mail: mbyshkin@unisa.it, E-mail: gmilano@unisa.it; Correa, A.; Buonocore, F.

    2013-12-28

    A Grand Canonical Monte Carlo scheme, based on united events combining protonation/deprotonation and insertion/deletion of HCl molecules is proposed for the generation of polyaniline structures at intermediate doping levels between 0% (PANI EB) and 100% (PANI ES). A procedure based on this scheme and subsequent structure relaxations using molecular dynamics is described and validated. Using the proposed scheme and the corresponding procedure, atomistic models of amorphous PANI-HCl structures were generated and studied at different doping levels. Density, structure factors, and solubility parameters were calculated. Their values agree well with available experimental data. The interactions of HCl with PANI have beenmore » studied and distribution of their energies has been analyzed. The procedure has also been extended to the generation of PANI models including adsorbed water and the effect of inclusion of water molecules on PANI properties has also been modeled and discussed. The protocol described here is general and the proposed United Event Grand Canonical Monte Carlo scheme can be easily extended to similar polymeric materials used in gas sensing and to other systems involving adsorption and chemical reactions steps.« less

  12. Core Canonical Pathways Involved in Developing Human Glioblastoma Multiforme (GBM).

    PubMed

    Ghosh, Somiranjan; Dutta, Sisir; Thorne, Gabriel; Boston, Ava; Barfield, Alexis; Banerjee, Narendra; Walker, Rayshawn; Banerjee, Hirendra Nath

    2017-02-01

    Glioblastoma multiforme (GBM) is the most common and aggressive type of the primary brain tumors with pathologic hallmarks of necrosis and vascular proliferation. The diagnosis of GBM is currently mostly based on histological examination of brain tumor tissues, after radiological characterization and surgical biopsy. The ability to characterize tumors comprehensively at the molecular level raises the possibility that diagnosis can be made based on molecular profiling with or without histological examination, rather than solely on histological phenotype. The development of novel genomic and proteomic techniques will foster in the identification of such diagnostic and prognostic molecular markers. We analyzed the global differential gene expression of a GBM cell line HTB15 in comparison to normal human Astrocytes, and established a few canonical pathways that are important in determining the molecular mechanisms of cancer using global gene expression microarray, coupled with the Ingenuity Pathway Analysis ( IPA ®). Overall, we revealed a discrete gene expression profile in the experimental model that resembled progression of GBM cancer. The canonical pathway analysis showed the involvement of genes that differentially expressed in such a disease condition that included Inositol pathway, Polo like kinases, nNOS signaling , and Tetrapyrrole biosynthesis . Our findings established that the gene expression pattern of this dreaded brain cancer will probably help the cancer research community by finding out newer therapeutic strategies to combat this dreaded cancer type that leads to the identification of high-risk population in this category, with almost hundred percent mortality rate.

  13. Cost-effectiveness of oral ibandronate compared with intravenous (i.v.) zoledronic acid or i.v. generic pamidronate in breast cancer patients with metastatic bone disease undergoing i.v. chemotherapy.

    PubMed

    De Cock, E; Hutton, J; Canney, P; Body, J J; Barrett-Lee, P; Neary, M P; Lewis, G

    2005-12-01

    Ibandronate is the first third-generation bisphosphonate to have both oral and intravenous (i.v.) efficacy. An incremental cost-effectiveness model compared oral ibandronate with i.v. zoledronic acid and i.v. generic pamidronate in female breast cancer patients with metastatic bone disease, undergoing i.v. chemotherapy. A global economic model was adapted to the UK National Health Service (NHS), with primary outcomes of direct healthcare costs and quality-adjusted life years (QALYs). Efficacy, measured as relative risk reduction of skeletal-related events (SREs), was obtained from clinical trials. Resource use data for i.v. bisphosphonates and the cost of managing SREs were obtained from published studies. Hospital management and SRE treatment costs were taken from unit cost databases. Monthly drug acquisition costs were obtained from the British National Formulary. Utility scores were applied to time with/without an SRE to adjust survival for quality of life. Model design and inputs were validated through expert UK clinician review. Total cost, including drug acquisition, was pound 386 less per patient with oral ibandronate vs. i.v. zoledronic acid and pound 224 less vs. i.v. generic pamidronate. Oral ibandronate gained 0.019 and 0.02 QALYs vs. i.v. zoledronic acid and i.v. pamidronate, respectively, making it the economically dominant option. At a threshold of pound 30,000 per QALY, oral ibandronate was cost-effective vs. zoledronic acid in 85% of simulations and vs. pamidronate in 79%. Oral ibandronate is a cost-effective treatment for metastatic bone disease from breast cancer due to reduced SREs, bone pain, and cost savings from avoidance of resource use commonly associated with bisphosphonate infusions.

  14. Correcting C IV-based virial black hole masses

    NASA Astrophysics Data System (ADS)

    Coatman, Liam; Hewett, Paul C.; Banerji, Manda; Richards, Gordon T.; Hennawi, Joseph F.; Prochaska, J. Xavier

    2017-02-01

    The C IVλλ1498,1501 broad emission line is visible in optical spectra to redshifts exceeding z ˜ 5. C IV has long been known to exhibit significant displacements to the blue and these `blueshifts' almost certainly signal the presence of strong outflows. As a consequence, single-epoch virial black hole (BH) mass estimates derived from C IV velocity widths are known to be systematically biased compared to masses from the hydrogen Balmer lines. Using a large sample of 230 high-luminosity (LBol = 1045.5-1048 erg s-1), redshift 1.5 < z < 4.0 quasars with both C IV and Balmer line spectra, we have quantified the bias in C IV BH masses as a function of the C IV blueshift. C IV BH masses are shown to be a factor of 5 larger than the corresponding Balmer-line masses at C IV blueshifts of 3000 km s-1and are overestimated by almost an order of magnitude at the most extreme blueshifts, ≳5000 km s-1. Using the monotonically increasing relationship between the C IV blueshift and the mass ratio BH(C IV)/BH(Hα), we derive an empirical correction to all C IV BH masses. The scatter between the corrected C IV masses and the Balmer masses is 0.24 dex at low C IV blueshifts (˜0 km s-1) and just 0.10 dex at high blueshifts (˜3000 km s-1), compared to 0.40 dex before the correction. The correction depends only on the C IV line properties - i.e. full width at half-maximum and blueshift - and can therefore be applied to all quasars where C IV emission line properties have been measured, enabling the derivation of unbiased virial BH-mass estimates for the majority of high-luminosity, high-redshift, spectroscopically confirmed quasars in the literature.

  15. 75 FR 2787 - Airworthiness Directives; Turbomeca Turmo IV A and IV C Turboshaft Engines

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-19

    ... inspection before the first flight of the day, an oil leak was found on an engine deck. A circumferential... inspection before the first flight of the day, an oil leak was found on an engine deck. A circumferential... Airworthiness Directives; Turbomeca Turmo IV A and IV C Turboshaft Engines AGENCY: Federal Aviation...

  16. 45 CFR 1355.21 - State plan requirements for titles IV-E and IV-B.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... and the Indian Tribe must make available for public review and inspection the Child and Family... 45 Public Welfare 4 2011-10-01 2011-10-01 false State plan requirements for titles IV-E and IV-B. 1355.21 Section 1355.21 Public Welfare Regulations Relating to Public Welfare (Continued) OFFICE OF...

  17. The MAX IV storage ring project

    PubMed Central

    Tavares, Pedro F.; Leemann, Simon C.; Sjöström, Magnus; Andersson, Åke

    2014-01-01

    The MAX IV facility, currently under construction in Lund, Sweden, features two electron storage rings operated at 3 GeV and 1.5 GeV and optimized for the hard X-ray and soft X-ray/VUV spectral ranges, respectively. A 3 GeV linear accelerator serves as a full-energy injector into both rings as well as a driver for a short-pulse facility, in which undulators produce X-ray pulses as short as 100 fs. The 3 GeV ring employs a multibend achromat (MBA) lattice to achieve, in a relatively short circumference of 528 m, a bare lattice emittance of 0.33 nm rad, which reduces to 0.2 nm rad as insertion devices are added. The engineering implementation of the MBA lattice raises several technological problems. The large number of strong magnets per achromat calls for a compact design featuring small-gap combined-function magnets grouped into cells and sharing a common iron yoke. The small apertures lead to a low-conductance vacuum chamber design that relies on the chamber itself as a distributed copper absorber for the heat deposited by synchrotron radiation, while non-evaporable getter (NEG) coating provides for reduced photodesorption yields and distributed pumping. Finally, a low main frequency (100 MHz) is chosen for the RF system yielding long bunches, which are further elongated by passively operated third-harmonic Landau cavities, thus alleviating collective effects, both coherent (e.g. resistive wall instabilities) and incoherent (intrabeam scattering). In this paper, we focus on the MAX IV 3 GeV ring and present the lattice design as well as the engineering solutions to the challenges inherent to such a design. As the first realisation of a light source based on the MBA concept, the MAX IV 3 GeV ring offers an opportunity for validation of concepts that are likely to be essential ingredients of future diffraction-limited light sources. PMID:25177978

  18. Hmga2 is required for canonical WNT signaling during lung development

    PubMed Central

    2014-01-01

    Background The high-mobility-group (HMG) proteins are the most abundant non-histone chromatin-associated proteins. HMG proteins are present at high levels in various undifferentiated tissues during embryonic development and their levels are strongly reduced in the corresponding adult tissues, where they have been implicated in maintaining and activating stem/progenitor cells. Here we deciphered the role of the high-mobility-group AT-hook protein 2 (HMGA2) during lung development by analyzing the lung of Hmga2-deficient mice (Hmga2 −/− ). Results We found that Hmga2 is expressed in the mouse embryonic lung at the distal airways. Analysis of Hmga2 −/− mice showed that Hmga2 is required for proper cell proliferation and distal epithelium differentiation during embryonic lung development. Hmga2 knockout led to enhanced canonical WNT signaling due to an increased expression of secreted WNT glycoproteins Wnt2b, Wnt7b and Wnt11 as well as a reduction of the WNT signaling antagonizing proteins GATA-binding protein 6 and frizzled homolog 2. Analysis of siRNA-mediated loss-of-function experiments in embryonic lung explant culture confirmed the role of Hmga2 as a key regulator of distal lung epithelium differentiation and supported the causal involvement of enhanced canonical WNT signaling in mediating the effect of Hmga2-loss-of-fuction. Finally, we found that HMGA2 directly regulates Gata6 and thereby modulates Fzd2 expression. Conclusions Our results support that Hmga2 regulates canonical WNT signaling at different points of the pathway. Increased expression of the secreted WNT glycoproteins might explain a paracrine effect by which Hmga2-knockout enhanced cell proliferation in the mesenchyme of the developing lung. In addition, HMGA2-mediated direct regulation of Gata6 is crucial for fine-tuning the activity of WNT signaling in the airway epithelium. Our results are the starting point for future studies investigating the relevance of Hmga2-mediated regulation of

  19. Multiple Time-Step Dual-Hamiltonian Hybrid Molecular Dynamics — Monte Carlo Canonical Propagation Algorithm

    PubMed Central

    Weare, Jonathan; Dinner, Aaron R.; Roux, Benoît

    2016-01-01

    A multiple time-step integrator based on a dual Hamiltonian and a hybrid method combining molecular dynamics (MD) and Monte Carlo (MC) is proposed to sample systems in the canonical ensemble. The Dual Hamiltonian Multiple Time-Step (DHMTS) algorithm is based on two similar Hamiltonians: a computationally expensive one that serves as a reference and a computationally inexpensive one to which the workload is shifted. The central assumption is that the difference between the two Hamiltonians is slowly varying. Earlier work has shown that such dual Hamiltonian multiple time-step schemes effectively precondition nonlinear differential equations for dynamics by reformulating them into a recursive root finding problem that can be solved by propagating a correction term through an internal loop, analogous to RESPA. Of special interest in the present context, a hybrid MD-MC version of the DHMTS algorithm is introduced to enforce detailed balance via a Metropolis acceptance criterion and ensure consistency with the Boltzmann distribution. The Metropolis criterion suppresses the discretization errors normally associated with the propagation according to the computationally inexpensive Hamiltonian, treating the discretization error as an external work. Illustrative tests are carried out to demonstrate the effectiveness of the method. PMID:26918826

  20. Accumulation of Succinate in Cardiac Ischemia Primarily Occurs via Canonical Krebs Cycle Activity.

    PubMed

    Zhang, Jimmy; Wang, Yves T; Miller, James H; Day, Mary M; Munger, Joshua C; Brookes, Paul S

    2018-05-29

    Succinate accumulates during ischemia, and its oxidation at reperfusion drives injury. The mechanism of ischemic succinate accumulation is controversial and is proposed to involve reversal of mitochondrial complex II. Herein, using stable-isotope-resolved metabolomics, we demonstrate that complex II reversal is possible in hypoxic mitochondria but is not the primary succinate source in hypoxic cardiomyocytes or ischemic hearts. Rather, in these intact systems succinate primarily originates from canonical Krebs cycle activity, partly supported by aminotransferase anaplerosis and glycolysis from glycogen. Augmentation of canonical Krebs cycle activity with dimethyl-α-ketoglutarate both increases ischemic succinate accumulation and drives substrate-level phosphorylation by succinyl-CoA synthetase, improving ischemic energetics. Although two-thirds of ischemic succinate accumulation is extracellular, the remaining one-third is metabolized during early reperfusion, wherein acute complex II inhibition is protective. These results highlight a bifunctional role for succinate: its complex-II-independent accumulation being beneficial in ischemia and its complex-II-dependent oxidation being detrimental at reperfusion. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  1. Canonical phase diagrams of the 1D Falicov-Kimball model at T = O

    NASA Astrophysics Data System (ADS)

    Gajek, Z.; Jȩdrzejewski, J.; Lemański, R.

    1996-02-01

    The Falicov-Kimball model of spinless quantum electrons hopping on a 1-dimensional lattice and of immobile classical ions occupying some lattice sites, with only intrasite coupling between those particles, have been studied at zero temperature by means of well-controlled numerical procedures. For selected values of the unique coupling parameter U the restricted phase diagrams (based on all the periodic configurations of localized particles (ions) with period not greater than 16 lattice constants, typically) have been constructed in the grand-canonical ensemble. Then these diagrams have been translated into the canonical ensemble. Compared to the diagrams obtained in other studies our ones contain more details, in particular they give better insight into the way the mixtures of periodic phases are formed. Our study has revealed several families of new characteristic phases like the generalized most homogeneous and the generalized crenel phases, a first example of a structural phase transition and a tendency to build up an additional symmetry - the hole-particle symmetry with respect to the ions (electrons) only, as U decreases.

  2. Canonical correlation analysis of synchronous neural interactions and cognitive deficits in Alzheimer's dementia

    NASA Astrophysics Data System (ADS)

    Karageorgiou, Elissaios; Lewis, Scott M.; Riley McCarten, J.; Leuthold, Arthur C.; Hemmy, Laura S.; McPherson, Susan E.; Rottunda, Susan J.; Rubins, David M.; Georgopoulos, Apostolos P.

    2012-10-01

    In previous work (Georgopoulos et al 2007 J. Neural Eng. 4 349-55) we reported on the use of magnetoencephalographic (MEG) synchronous neural interactions (SNI) as a functional biomarker in Alzheimer's dementia (AD) diagnosis. Here we report on the application of canonical correlation analysis to investigate the relations between SNI and cognitive neuropsychological (NP) domains in AD patients. First, we performed individual correlations between each SNI and each NP, which provided an initial link between SNI and specific cognitive tests. Next, we performed factor analysis on each set, followed by a canonical correlation analysis between the derived SNI and NP factors. This last analysis optimally associated the entire MEG signal with cognitive function. The results revealed that SNI as a whole were mostly associated with memory and language, and, slightly less, executive function, processing speed and visuospatial abilities, thus differentiating functions subserved by the frontoparietal and the temporal cortices. These findings provide a direct interpretation of the information carried by the SNI and set the basis for identifying specific neural disease phenotypes according to cognitive deficits.

  3. [Non-linear canonical correlation analysis between anthropometric indicators and multiple metabolic abnormalities].

    PubMed

    Fu, Xiaoli; Liu, Li; Ping, Zhiguang; Li, Linlin

    2013-09-01

    To define the general correlation between anthropometric indicators and multiple metabolic abnormalities, and to put forward some particular suggestions for the prevention of multiple metabolic abnormalities. A random cluster sampling was carried out in one county of Henan Province. Questionnaire, physical examination and biochemical tests were admitted to the adult inhabitants. Non-linear canonical correlation analysis (NLCCA) was applied with OVERALS of SPSS 13.0. The coefficients of canonical correlation and multiple correlation were calculated. The plot of centroids labeled by variables showed the correlation among various indicators. In total, 2,914 objects were investigated. It included 1,134 (38.9%) males and 1,780 (61.1%) females (60.0%). The average age was (50.58 +/- 13.70) years old. The fitting result of NLCCA were as follows: the loss of 0.577 accounting for 28.8% of the total variation was relatively small, and indicated that the two sets of variables of this study, namely sets of biochemical indicators (including serum total cholesterol, total triglyceride, high-density lipoprotein cholesterol, low density lipoprotein cholesterol and fasting plasma glucose) and sets of others (including gender, BMI and waist circumference) were closely related and often changed synchronously. Multivariate correlation coefficient showed that internal indicators of the above two sets were closely related respectively and often showed the multiple anomalies of the same set. The diagram of the center of gravity of the association of various indicators showed that the symptoms of metabolic abnormalities increased with age. Women were more liable to have metabolic abnormalities. Overweight and obese people often suffer multiple metabolic disorders. Waist circumference was positively correlated with metabolic abnormalities. (1) Biochemical indicators and anthropometric often change in combination. (2) Much attention should be paid to older people especially middle-aged or

  4. Canonical Correlational Models of Students' Perceptions of Assessment Tasks, Motivational Orientations, and Learning Strategies

    ERIC Educational Resources Information Center

    Alkharusi, Hussain

    2013-01-01

    The present study aims at deriving correlational models of students' perceptions of assessment tasks, motivational orientations, and learning strategies using canonical analyses. Data were collected from 198 Omani tenth grade students. Results showed that high degrees of authenticity and transparency in assessment were associated with positive…

  5. Origins and canons: medicine and the history of sociology.

    PubMed

    Collyer, Fran

    2010-01-01

    Differing accounts are conventionally given of the origins of medical sociology and its parent discipline sociology. These distinct "histories" are justified on the basis that the sociological founders were uninterested in medicine, mortality and disease. This article challenges these "constructions" of the past, proposing the theorization of health not as a "late development of sociology" but an integral part of its formation. Drawing on a selection of key sociological texts, it is argued that evidence of the founders' sustained interest in the infirmities of the individual, of mortality, and in medicine, have been expunged from the historical record through processes of "canonization" and "medicalization."

  6. Discrete linear canonical transforms based on dilated Hermite functions.

    PubMed

    Pei, Soo-Chang; Lai, Yun-Chiu

    2011-08-01

    Linear canonical transform (LCT) is very useful and powerful in signal processing and optics. In this paper, discrete LCT (DLCT) is proposed to approximate LCT by utilizing the discrete dilated Hermite functions. The Wigner distribution function is also used to investigate DLCT performances in the time-frequency domain. Compared with the existing digital computation of LCT, our proposed DLCT possess additivity and reversibility properties with no oversampling involved. In addition, the length of input/output signals will not be changed before and after the DLCT transformations, which is consistent with the time-frequency area-preserving nature of LCT; meanwhile, the proposed DLCT has very good approximation of continuous LCT.

  7. NATIONAL COASTAL CONDITION REPORT IV

    EPA Science Inventory

    The National Coastal Condition Report IV (NCCR IV) is the fourth in a series of environmental assessments of U.S. coastal waters and the Great Lakes. The report includes assessments of all the nation’s estuaries in the contiguous 48 states and Puerto Rico, south-eastern Alaska, ...

  8. Self-report assessment of the DSM-IV personality disorders. Measurement of trait and distress characteristics: the ADP-IV.

    PubMed

    Schotte, C K; de Doncker, D; Vankerckhoven, C; Vertommen, H; Cosyns, P

    1998-09-01

    Self-report instruments assessing the DSM personality disorders are characterized by overdiagnosis due to their emphasis on the measurement of personality traits rather than the impairment and distress associated with the criteria. The ADP-IV, a Dutch questionnaire, introduces an alternative assessment method: each test item assesses 'Trait' as well as 'Distress/impairment' characteristics of a DSM-IV criterion. This item format allows dimensional as well as categorical diagnostic evaluations. The present study explores the validity of the ADP-IV in a sample of 659 subjects of the Flemish population. The dimensional personality disorder subscales, measuring Trait characteristics, are internally consistent and display a good concurrent validity with the Wisconsin Personality Disorders Inventory. Factor analysis at the item-level resulted in 11 orthogonal factors, describing personality dimensions such as psychopathy, social anxiety and avoidance, negative affect and self-image. Factor analysis at the subscale-level identified two basic dimensions, reflecting hostile (DSM-IV Cluster B) and anxious (DSM-IV Cluster C) interpersonal attitudes. Categorical ADP-IV diagnoses are obtained using scoring algorithms, which emphasize the Trait or the Distress concepts in the diagnostic evaluation. Prevalences of ADP-IV diagnoses of any personality disorder according to these algorithms vary between 2.28 and 20.64%. Although further research in clinical samples is required, the present results support the validity of the ADP-IV and the potential of the measurement of trait and distress characteristics as a method for assessing personality pathology.

  9. A qualitative study of the cultural appropriateness of the Diagnostic Interview Schedule for Children (DISC-IV) in South Africa

    PubMed Central

    Skinner, Donald; Serekoane, Motsaathebe; Ross, Michael W.

    2012-01-01

    Background The Diagnostic Interview Schedule for Children (DISC-IV) has been designed for use by trained laypersons. It therefore shows great promise for use in developing countries such as South Africa, where there is a lack of clinically trained and skilled professionals at the primary care level. Against this background, the aim of the current study was to investigate the sociocultural appropriateness of the DISC-IV for use with Sesotho families in South Africa. Methods Qualitative methodology of expert review and contextualized content analyses were used. Ten Sesotho-speaking clinicians were recruited through a snowball sampling technique to the review the DISC through expert review reports. Results Several themes emerged, including the structure of the DISC-IV, its computerized nature, Americanisms, problems in interpretation due to the adversity children live under, language problems, the effect of rural settings and education level, and cultural norms regarding psychiatric symptoms, gender, the experience of time, the expression of emotion, and family structure. Conclusion Recommendations for the sociocultural adaptation and translation of the DISC into Sesotho are made. PMID:20526764

  10. How the 2SLS/IV estimator can handle equality constraints in structural equation models: a system-of-equations approach.

    PubMed

    Nestler, Steffen

    2014-05-01

    Parameters in structural equation models are typically estimated using the maximum likelihood (ML) approach. Bollen (1996) proposed an alternative non-iterative, equation-by-equation estimator that uses instrumental variables. Although this two-stage least squares/instrumental variables (2SLS/IV) estimator has good statistical properties, one problem with its application is that parameter equality constraints cannot be imposed. This paper presents a mathematical solution to this problem that is based on an extension of the 2SLS/IV approach to a system of equations. We present an example in which our approach was used to examine strong longitudinal measurement invariance. We also investigated the new approach in a simulation study that compared it with ML in the examination of the equality of two latent regression coefficients and strong measurement invariance. Overall, the results show that the suggested approach is a useful extension of the original 2SLS/IV estimator and allows for the effective handling of equality constraints in structural equation models. © 2013 The British Psychological Society.

  11. Collagen type IV at the fetal-maternal interface.

    PubMed

    Oefner, C M; Sharkey, A; Gardner, L; Critchley, H; Oyen, M; Moffett, A

    2015-01-01

    Extracellular matrix proteins play a crucial role in influencing the invasion of trophoblast cells. However the role of collagens and collagen type IV (col-IV) in particular at the implantation site is not clear. Immunohistochemistry was used to determine the distribution of collagen types I, III, IV and VI in endometrium and decidua during the menstrual cycle and the first trimester of pregnancy. Expression of col-IV alpha chains during the reproductive cycle was determined by qPCR and protein localisation by immunohistochemistry. The structure of col-IV in placenta was examined using transmission electron microscopy. Finally, the expression of col-IV alpha chain NC1 domains and collagen receptors was localised by immunohistochemistry. Col-IV alpha chains were selectively up-regulated during the menstrual cycle and decidualisation. Primary extravillous trophoblast cells express collagen receptors and secrete col-IV in vitro and in vivo, resulting in the increased levels found in decidua basalis compared to decidua parietalis. A novel expression pattern of col-IV in the mesenchyme of placental villi, as a three-dimensional network, was found. NC1 domains of col-IV alpha chains are known to regulate tumour cell migration and the selective expression of these domains in decidua basalis compared to decidua parietalis was determined. Col-IV is expressed as novel forms in the placenta. These findings suggest that col-IV not only represents a structural protein providing tissue integrity but also influences the invasive behaviour of trophoblast cells at the implantation site. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Non-canonical Wnt signalling modulates the endothelial shear stress flow sensor in vascular remodelling

    PubMed Central

    Franco, Claudio A; Jones, Martin L; Bernabeu, Miguel O; Vion, Anne-Clemence; Barbacena, Pedro; Fan, Jieqing; Mathivet, Thomas; Fonseca, Catarina G; Ragab, Anan; Yamaguchi, Terry P; Coveney, Peter V; Lang, Richard A; Gerhardt, Holger

    2016-01-01

    Endothelial cells respond to molecular and physical forces in development and vascular homeostasis. Deregulation of endothelial responses to flow-induced shear is believed to contribute to many aspects of cardiovascular diseases including atherosclerosis. However, how molecular signals and shear-mediated physical forces integrate to regulate vascular patterning is poorly understood. Here we show that endothelial non-canonical Wnt signalling regulates endothelial sensitivity to shear forces. Loss of Wnt5a/Wnt11 renders endothelial cells more sensitive to shear, resulting in axial polarization and migration against flow at lower shear levels. Integration of flow modelling and polarity analysis in entire vascular networks demonstrates that polarization against flow is achieved differentially in artery, vein, capillaries and the primitive sprouting front. Collectively our data suggest that non-canonical Wnt signalling stabilizes forming vascular networks by reducing endothelial shear sensitivity, thus keeping vessels open under low flow conditions that prevail in the primitive plexus. DOI: http://dx.doi.org/10.7554/eLife.07727.001 PMID:26845523

  13. The ALADIN System and its canonical model configurations AROME CY41T1 and ALARO CY40T1

    NASA Astrophysics Data System (ADS)

    Termonia, Piet; Fischer, Claude; Bazile, Eric; Bouyssel, François; Brožková, Radmila; Bénard, Pierre; Bochenek, Bogdan; Degrauwe, Daan; Derková, Mariá; El Khatib, Ryad; Hamdi, Rafiq; Mašek, Ján; Pottier, Patricia; Pristov, Neva; Seity, Yann; Smolíková, Petra; Španiel, Oldřich; Tudor, Martina; Wang, Yong; Wittmann, Christoph; Joly, Alain

    2018-01-01

    The ALADIN System is a numerical weather prediction (NWP) system developed by the international ALADIN consortium for operational weather forecasting and research purposes. It is based on a code that is shared with the global model IFS of the ECMWF and the ARPEGE model of Météo-France. Today, this system can be used to provide a multitude of high-resolution limited-area model (LAM) configurations. A few configurations are thoroughly validated and prepared to be used for the operational weather forecasting in the 16 partner institutes of this consortium. These configurations are called the ALADIN canonical model configurations (CMCs). There are currently three CMCs: the ALADIN baseline CMC, the AROME CMC and the ALARO CMC. Other configurations are possible for research, such as process studies and climate simulations. The purpose of this paper is (i) to define the ALADIN System in relation to the global counterparts IFS and ARPEGE, (ii) to explain the notion of the CMCs, (iii) to document their most recent versions, and (iv) to illustrate the process of the validation and the porting of these configurations to the operational forecast suites of the partner institutes of the ALADIN consortium. This paper is restricted to the forecast model only; data assimilation techniques and postprocessing techniques are part of the ALADIN System but they are not discussed here.

  14. Role of non-canonical Beclin 1-independent autophagy in cell death induced by resveratrol in human breast cancer cells.

    PubMed

    Scarlatti, F; Maffei, R; Beau, I; Codogno, P; Ghidoni, R

    2008-08-01

    Resveratrol, a polyphenol found in grapes and other fruit and vegetables, is a powerful chemopreventive and chemotherapeutic molecule potentially of interest for the treatment of breast cancer. The human breast cancer cell line MCF-7, which is devoid of caspase-3 activity, is refractory to apoptotic cell death after incubation with resveratrol. Here we show that resveratrol arrests cell proliferation, triggers death and decreases the number of colonies of cells that are sensitive to caspase-3-dependent apoptosis (MCF-7 casp-3) and also those that are unresponsive to it (MCF-7vc). We demonstrate that resveratrol (i) acts via multiple pathways to trigger cell death, (ii) induces caspase-dependent and caspase-independent cell death in MCF-7 casp-3 cells, (iii) induces only caspase-independent cell death in MCF-7vc cells and (iv) stimulates macroautophagy. Using BECN1 and hVPS34 (human vacuolar protein sorting 34) small interfering RNAs, we demonstrate that resveratrol activates Beclin 1-independent autophagy in both cell lines, whereas cell death via this uncommon form of autophagy occurs only in MCF-7vc cells. We also show that this variant form of autophagic cell death is blocked by the expression of caspase-3, but not by its enzymatic activity. In conclusion, this study reveals that non-canonical autophagy induced by resveratrol can act as a caspase-independent cell death mechanism in breast cancer cells.

  15. A Si IV/O IV Electron Density Diagnostic for the Analysis of IRIS Solar Spectra

    NASA Astrophysics Data System (ADS)

    Young, P. R.; Keenan, F. P.; Milligan, R. O.; Peter, H.

    2018-04-01

    Solar spectra of ultraviolet bursts and flare ribbons from the Interface Region Imaging Spectrograph (IRIS) have suggested high electron densities of > {10}12 cm‑3 at transition region temperatures of 0.1 MK, based on large intensity ratios of Si IV λ1402.77 to O IV λ1401.16. In this work, a rare observation of the weak O IV λ1343.51 line is reported from an X-class flare that peaked at 21:41 UT on 2014 October 24. This line is used to develop a theoretical prediction of the Si IV λ1402.77 to O IV λ1401.16 ratio as a function of density that is recommended to be used in the high-density regime. The method makes use of new pressure-dependent ionization fractions that take account of the suppression of dielectronic recombination at high densities. It is applied to two sequences of flare kernel observations from the October 24 flare. The first shows densities that vary between 3× {10}12 and 3× {10}13 cm‑3 over a seven-minute period, while the second location shows stable density values of around 2× {10}12 cm‑3 over a three-minute period.

  16. Predicting DPP-IV inhibitors with machine learning approaches

    NASA Astrophysics Data System (ADS)

    Cai, Jie; Li, Chanjuan; Liu, Zhihong; Du, Jiewen; Ye, Jiming; Gu, Qiong; Xu, Jun

    2017-04-01

    Dipeptidyl peptidase IV (DPP-IV) is a promising Type 2 diabetes mellitus (T2DM) drug target. DPP-IV inhibitors prolong the action of glucagon-like peptide-1 (GLP-1) and gastric inhibitory peptide (GIP), improve glucose homeostasis without weight gain, edema, and hypoglycemia. However, the marketed DPP-IV inhibitors have adverse effects such as nasopharyngitis, headache, nausea, hypersensitivity, skin reactions and pancreatitis. Therefore, it is still expected for novel DPP-IV inhibitors with minimal adverse effects. The scaffolds of existing DPP-IV inhibitors are structurally diversified. This makes it difficult to build virtual screening models based upon the known DPP-IV inhibitor libraries using conventional QSAR approaches. In this paper, we report a new strategy to predict DPP-IV inhibitors with machine learning approaches involving naïve Bayesian (NB) and recursive partitioning (RP) methods. We built 247 machine learning models based on 1307 known DPP-IV inhibitors with optimized molecular properties and topological fingerprints as descriptors. The overall predictive accuracies of the optimized models were greater than 80%. An external test set, composed of 65 recently reported compounds, was employed to validate the optimized models. The results demonstrated that both NB and RP models have a good predictive ability based on different combinations of descriptors. Twenty "good" and twenty "bad" structural fragments for DPP-IV inhibitors can also be derived from these models for inspiring the new DPP-IV inhibitor scaffold design.

  17. 1L Mark-IV Target Design Review

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Koehler, Paul E.

    This presentation includes General Design Considerations; Current (Mark-III) Lower Tier; Mark-III Upper Tier; Performance Metrics; General Improvements for Material Science; General Improvements for Nuclear Science; Improving FOM for Nuclear Science; General Design Considerations Summary; Design Optimization Studies; Expected Mark-IV Performance: Material Science; Expected Mark-IV Performance: Nuclear Science (Disk); Mark IV Enables Much Wider Range of Nuclear-Science FOM Gains than Mark III; Mark-IV Performance Summary; Rod or Disk? Center or Real FOV?; and Project Cost and Schedule.

  18. Structuring an Adult Learning Environment. Part IV: Establishing an Environment for Problem Solving.

    ERIC Educational Resources Information Center

    Frankel, Alan; Brennan, James

    Through the years, many researchers have advanced theories of problem solving. Probably the best definition of problem solving to apply to adult learning programs is Wallas' (1926) four-stage theory. The stages are (1) a preparation, (2) an incubation period, (3) a moment of illumination, and (4) final application or verification of the solution.…

  19. Spectroscopic characterization of zirconium(IV) and hafniumf(IV) gallate phthalocyanines in monolithic silica gels obtained by sol gel method

    NASA Astrophysics Data System (ADS)

    Gerasymchuk, Y. S.; Chernii, V. Ya.; Tomachynski, L. A.; Legendziewicz, J.; Radzki, St.

    2005-07-01

    The Zr(IV) and Hf(IV) phthalocyanines, with gallate as axial ligand coordinated to the central metal atom of phthalocyanine, were incorporated in silica gels during sol-gel process with using tetraethyl orthosilicate (TEOS) as precursor. The obtained mixed inorganic-organic composites were transparent and homogeneous. The absorption and emission properties of these materials in comparison with the spectra of the Zr(IV) and Hf(IV) phthalocyanines in various solvents were investigated. The spectra were correlated with various stage of the sol-gel process. It was established that in the gels concurrence of the monomer and dimer form is different in sol, alco-, hydro- and xerogels. The intensive 700-725 nm fluorescence emission upon relatively long-wavelength excitation and unusually large (about 45 nm) Stokes shift in the Q region, suggest that Zr(IV) and Hf(IV) phthalocyanines could be considered as photosensitizers in the PDT method (photodynamic therapy).

  20. Investigating the reasons of variability in Si IV and C IV broad absorption line troughs of quasars

    NASA Astrophysics Data System (ADS)

    Stathopoulos, Dimitrios; Lyratzi, Evangelia; Danezis, Emmanuel; Antoniou, Antonios; Tzimeas, Dimitrios

    2017-09-01

    In this paper we analyze the C IV and Si IV broad absorption troughs of two BALQSOs (J101056.69+355833.3, J114548.38+393746.6) to the individual components they consist of. By analyzing a BAL trough to its components we have the advantage to study the variations of the individual absorbing systems in the line of sight and not just the variations of the whole absorption trough or the variations of selected portions of BAL troughs exhibiting changes. We find that the velocity shifts and FWHMs (Full Width at Half Maximum) of the individual components do not vary between an interval of six years. All variable components show changes in the optical depths at line centers which are manifested as variations in the EW (Equivalent Width) of the components. In both BALQSOs, over corresponding velocities, Si IV has higher incidence of variability than C IV. From our analysis, evidence is in favour of different covering fractions between C IV and Si IV. Finally, although most of our results favour the crossing cloud scenario as the cause of variability, there is also strong piece of evidence indicating changing ionization as the source of variability. Thus, a mixed situation where both physical mechanisms contribute to BAL variability is the most possible scenario.

  1. SMAD4 impedes the conversion of NK cells into ILC1-like cells by curtailing non-canonical TGF-β signaling.

    PubMed

    Cortez, Victor S; Ulland, Tyler K; Cervantes-Barragan, Luisa; Bando, Jennifer K; Robinette, Michelle L; Wang, Qianli; White, Andrew J; Gilfillan, Susan; Cella, Marina; Colonna, Marco

    2017-09-01

    Among the features that distinguish type 1 innate lymphoid cells (ILC1s) from natural killer (NK) cells is a gene signature indicative of 'imprinting' by cytokines of the TGF-β family. We studied mice in which ILC1s and NK cells lacked SMAD4, a signal transducer that facilitates the canonical signaling pathway common to all cytokines of the TGF-β family. While SMAD4 deficiency did not affect ILC1 differentiation, NK cells unexpectedly acquired an ILC1-like gene signature and were unable to control tumor metastasis or viral infection. Mechanistically, SMAD4 restrained non-canonical TGF-β signaling mediated by the cytokine receptor TGFβR1 in NK cells. NK cells from a SMAD4-deficient person affected by polyposis were also hyper-responsive to TGF-β. These results identify SMAD4 as a previously unknown regulator that restricts non-canonical TGF-β signaling in NK cells.

  2. SMAD4 impedes the conversion of NK cells into ILC1-like cells by curtailing non-canonical TGF-β signaling

    PubMed Central

    Cortez, Victor S; Ulland, Tyler K; Cervantes-Barragan, Luisa; Bando, Jennifer K; Robinette, Michelle L; Wang, Qianli; White, Andrew J; Gilfillan, Susan; Cella, Marina; Colonna, Marco

    2017-01-01

    Among the features that distinguish type 1 innate lymphoid cells (ILC1s) from natural killer (NK) cells is a gene signature indicative of ‘imprinting’ by cytokines of the TGF-β family. We examined mice in which ILC1s and NK cells lacked SMAD4, a signal transducer that facilitates the canonical signaling pathway common to all cytokines of the TGF-β family. While SMAD4 deficiency did not affect ILC1 differentiation, NK cells unexpectedly acquired an ILC1-like gene signature and were unable to control tumor metastasis or viral infection. Mechanistically, SMAD4 restrained non-canonical TGF-β signaling mediated by the cytokine receptor TGF-βR1 in NK cells. NK cells from a SMAD4-deficient person affected by polyposis were also hyper-responsive to TGF-β. These results identify SMAD4 as a previously unknown regulator that restricts non-canonical TGF-β signaling in NK cells. PMID:28759002

  3. Widespread GLI expression but limited canonical hedgehog signaling restricted to the ductular reaction in human chronic liver disease

    PubMed Central

    Tirnitz-Parker, Janina Elke Eleonore; Hamson, Elizabeth Jane; Warren, Alessandra; Maneck, Bharvi; Chen, Jinbiao; Patkunanathan, Bramilla; Boland, Jade; Cheng, Robert; Shackel, Nicholas Adam; Seth, Devanshi; Bowen, David Geoffrey; Martelotto, Luciano Gastón; Watkins, D. Neil; McCaughan, Geoffrey William

    2017-01-01

    Canonical Hedgehog (Hh) signaling in vertebrate cells occurs following Smoothened activation/translocation into the primary cilia (Pc), followed by a GLI transcriptional response. Nonetheless, GLI activation can occur independently of the canonical Hh pathway. Using a murine model of liver injury, we previously identified the importance of canonical Hh signaling within the Pc+ liver progenitor cell (LPC) population and noted that SMO-independent, GLI-mediated signals were important in multiple Pc-ve GLI2+ intrahepatic populations. This study extends these observations to human liver tissue, and analyses the effect of GLI inhibition on LPC viability/gene expression. Human donor and cirrhotic liver tissue specimens were evaluated for SHH, GLI2 and Pc expression using immunofluorescence and qRT-PCR. Changes to viability and gene expression in LPCs in vitro were assessed following GLI inhibition. Identification of Pc (as a marker of canonical Hh signaling) in human cirrhosis was predominantly confined to the ductular reaction and LPCs. In contrast, GLI2 was expressed in multiple cell populations including Pc-ve endothelium, hepatocytes, and leukocytes. HSCs/myofibroblasts (>99%) expressed GLI2, with only 1.92% displaying Pc. In vitro GLI signals maintained proliferation/viability within LPCs and GLI inhibition affected the expression of genes related to stemness, hepatocyte/biliary differentiation and Hh/Wnt signaling. At least two mechanisms of GLI signaling (Pc/SMO-dependent and Pc/SMO-independent) mediate chronic liver disease pathogenesis. This may have significant ramifications for the choice of Hh inhibitor (anti-SMO or anti-GLI) suitable for clinical trials. We also postulate GLI delivers a pro-survival signal to LPCs whilst maintaining stemness. PMID:28187190

  4. Widespread GLI expression but limited canonical hedgehog signaling restricted to the ductular reaction in human chronic liver disease.

    PubMed

    Grzelak, Candice Alexandra; Sigglekow, Nicholas David; Tirnitz-Parker, Janina Elke Eleonore; Hamson, Elizabeth Jane; Warren, Alessandra; Maneck, Bharvi; Chen, Jinbiao; Patkunanathan, Bramilla; Boland, Jade; Cheng, Robert; Shackel, Nicholas Adam; Seth, Devanshi; Bowen, David Geoffrey; Martelotto, Luciano Gastón; Watkins, D Neil; McCaughan, Geoffrey William

    2017-01-01

    Canonical Hedgehog (Hh) signaling in vertebrate cells occurs following Smoothened activation/translocation into the primary cilia (Pc), followed by a GLI transcriptional response. Nonetheless, GLI activation can occur independently of the canonical Hh pathway. Using a murine model of liver injury, we previously identified the importance of canonical Hh signaling within the Pc+ liver progenitor cell (LPC) population and noted that SMO-independent, GLI-mediated signals were important in multiple Pc-ve GLI2+ intrahepatic populations. This study extends these observations to human liver tissue, and analyses the effect of GLI inhibition on LPC viability/gene expression. Human donor and cirrhotic liver tissue specimens were evaluated for SHH, GLI2 and Pc expression using immunofluorescence and qRT-PCR. Changes to viability and gene expression in LPCs in vitro were assessed following GLI inhibition. Identification of Pc (as a marker of canonical Hh signaling) in human cirrhosis was predominantly confined to the ductular reaction and LPCs. In contrast, GLI2 was expressed in multiple cell populations including Pc-ve endothelium, hepatocytes, and leukocytes. HSCs/myofibroblasts (>99%) expressed GLI2, with only 1.92% displaying Pc. In vitro GLI signals maintained proliferation/viability within LPCs and GLI inhibition affected the expression of genes related to stemness, hepatocyte/biliary differentiation and Hh/Wnt signaling. At least two mechanisms of GLI signaling (Pc/SMO-dependent and Pc/SMO-independent) mediate chronic liver disease pathogenesis. This may have significant ramifications for the choice of Hh inhibitor (anti-SMO or anti-GLI) suitable for clinical trials. We also postulate GLI delivers a pro-survival signal to LPCs whilst maintaining stemness.

  5. The canonical nuclear factor-κB pathway regulates cell survival in a developmental model of spinal cord motoneurons.

    PubMed

    Mincheva, Stefka; Garcera, Ana; Gou-Fabregas, Myriam; Encinas, Mario; Dolcet, Xavier; Soler, Rosa M

    2011-04-27

    In vivo and in vitro motoneuron survival depends on the support of neurotrophic factors. These factors activate signaling pathways related to cell survival or inactivate proteins involved in neuronal death. In the present work, we analyzed the involvement of the nuclear factor-κB (NF-κB) pathway in mediating mouse spinal cord motoneuron survival promoted by neurotrophic factors. This pathway comprises ubiquitously expressed transcription factors that could be activated by two different routes: the canonical pathway, associated with IKKα/IKKβ kinase phosphorylation and nuclear translocation RelA (p65)/p50 transcription factors; and the noncanonical pathway, related to IKKα kinase homodimer phosphorylation and RelB/p52 transcription factor activation. In our system, we show that neurotrophic factors treatment induced IKKα and IKKβ phosphorylation and RelA nuclear translocation, suggesting NF-κB pathway activation. Protein levels of different members of the canonical or noncanonical pathways were reduced in a primary culture of isolated embryonic motoneurons using an interference RNA approach. Even in the presence of neurotrophic factors, selective reduction of IKKα, IKKβ, or RelA proteins induced cell death. In contrast, RelB protein reduction did not have a negative effect on motoneuron survival. Together these results demonstrated that the canonical NF-κB pathway mediates motoneuron survival induced by neurotrophic factors, and the noncanonical pathway is not related to this survival effect. Canonical NF-κB blockade induced an increase of Bim protein level and apoptotic cell death. Bcl-x(L) overexpression or Bax reduction counteracted this apoptotic effect. Finally, RelA knockdown causes changes of CREB and Smn protein levels.

  6. Association between personality traits and DSM-IV diagnosis of insomnia in perimenopausal women

    PubMed Central

    Sassoon, Stephanie A.; de Zambotti, Massimiliano; Colrain, Ian M.; Baker, Fiona C.

    2013-01-01

    Objective The aim of this study was to determine the role of personality factors in the development of DSM-IV insomnia coincident with perimenopause. Method Perimenopausal women (35 with DSM-IV insomnia and 28 with self-reported normal sleep) underwent clinical assessments and completed menopause-related questionnaires, the NEO-FFI, and the Structured Interview for DSM-IV Personality (SID-P). Logistic regressions determined whether personality factors and hot flash-related interference were associated with an insomnia diagnosis concurrent with the menopause transition. Results Women with insomnia reported higher neuroticism, lower agreeableness, and lower conscientiousness than controls on the NEO-FFI. Moreover, women with insomnia were more likely to meet DSM-IV criteria for Cluster C personality disorders, particularly obsessive compulsive personality disorder, on the SID-P. Women with insomnia were more likely to have had a past depressive episode and history of severe premenstrual symptoms. Findings from regressions revealed that higher neuroticism and greater interference from hot flashes were associated with insomnia classification even after controlling for history of depression, suggesting that sensitivity to hot flashes and a greater degree of neuroticism are independent contributors toward establishing which women are most likely to have sleep problems during perimenopause. Conclusions Findings show the relevance of personality factors, particularly neuroticism and obsessive-compulsive personality, in influencing a woman’s experience of insomnia as she goes through the menopause transition. PMID:24448105

  7. Single-layer group IV-V and group V-IV-III-VI semiconductors: Structural stability, electronic structures, optical properties, and photocatalysis

    NASA Astrophysics Data System (ADS)

    Lin, Jia-He; Zhang, Hong; Cheng, Xin-Lu; Miyamoto, Yoshiyuki

    2017-07-01

    Recently, single-layer group III monochalcogenides have attracted both theoretical and experimental interest at their potential applications in photonic devices, electronic devices, and solar energy conversion. Excited by this, we theoretically design two kinds of highly stable single-layer group IV-V (IV =Si ,Ge , and Sn; V =N and P) and group V-IV-III-VI (IV =Si ,Ge , and Sn; V =N and P; III =Al ,Ga , and In; VI =O and S) compounds with the same structures with single-layer group III monochalcogenides via first-principles simulations. By using accurate hybrid functional and quasiparticle methods, we show the single-layer group IV-V and group V-IV-III-VI are indirect bandgap semiconductors with their bandgaps and band edge positions conforming to the criteria of photocatalysts for water splitting. By applying a biaxial strain on single-layer group IV-V, single-layer group IV nitrides show a potential on mechanical sensors due to their bandgaps showing an almost linear response for strain. Furthermore, our calculations show that both single-layer group IV-V and group V-IV-III-VI have absorption from the visible light region to far-ultraviolet region, especially for single-layer SiN-AlO and SnN-InO, which have strong absorption in the visible light region, resulting in excellent potential for solar energy conversion and visible light photocatalytic water splitting. Our research provides valuable insight for finding more potential functional two-dimensional semiconductors applied in optoelectronics, solar energy conversion, and photocatalytic water splitting.

  8. Non-canonical NF-κB signalling and ETS1/2 cooperatively drive C250T mutant TERT promoter activation

    PubMed Central

    Li, Yinghui; Zhou, Qi-Ling; Sun, Wenjie; Chandrasekharan, Prashant; Cheng, Hui Shan; Ying, Zhe; Lakshmanan, Manikandan; Raju, Anandhkumar; Tenen, Daniel G.; Cheng, Shi-Yuan; Chuang, Kai-Hsiang; Li, Jun; Prabhakar, Shyam; Li, Mengfeng; Tergaonkar, Vinay

    2016-01-01

    Transcriptional reactivation of TERT, the catalytic subunit of telomerase, is necessary for cancer progression in about 90% of human cancers. The recent discovery of two prevalent somatic mutations—C250T and C228T—in the TERT promoter in various cancers has provided insight into a plausible mechanism of TERT reactivation. Although the two hotspot mutations create a similar binding motif for E-twenty-six (ETS) transcription factors, we show that they are functionally distinct, in that the C250T unlike the C228T TERT promoter is driven by non-canonical NF-κB signalling. We demonstrate that binding of ETS to the mutant TERT promoter is insufficient in driving its transcription but this process requires non-canonical NF-κB signalling for stimulus responsiveness, sustained telomerase activity and hence cancer progression. Our findings highlight a previously unrecognized role of non-canonical NF-κB signalling in tumorigenesis and elucidate a fundamental mechanism for TERT reactivation in cancers, which if targeted could have immense therapeutic implications. PMID:26389665

  9. Non-canonical NF-κB signalling and ETS1/2 cooperatively drive C250T mutant TERT promoter activation.

    PubMed

    Li, Yinghui; Zhou, Qi-Ling; Sun, Wenjie; Chandrasekharan, Prashant; Cheng, Hui Shan; Ying, Zhe; Lakshmanan, Manikandan; Raju, Anandhkumar; Tenen, Daniel G; Cheng, Shi-Yuan; Chuang, Kai-Hsiang; Li, Jun; Prabhakar, Shyam; Li, Mengfeng; Tergaonkar, Vinay

    2015-10-01

    Transcriptional reactivation of TERT, the catalytic subunit of telomerase, is necessary for cancer progression in about 90% of human cancers. The recent discovery of two prevalent somatic mutations-C250T and C228T-in the TERT promoter in various cancers has provided insight into a plausible mechanism of TERT reactivation. Although the two hotspot mutations create a similar binding motif for E-twenty-six (ETS) transcription factors, we show that they are functionally distinct, in that the C250T unlike the C228T TERT promoter is driven by non-canonical NF-κB signalling. We demonstrate that binding of ETS to the mutant TERT promoter is insufficient in driving its transcription but this process requires non-canonical NF-κB signalling for stimulus responsiveness, sustained telomerase activity and hence cancer progression. Our findings highlight a previously unrecognized role of non-canonical NF-κB signalling in tumorigenesis and elucidate a fundamental mechanism for TERT reactivation in cancers, which if targeted could have immense therapeutic implications.

  10. General Relativity without paradigm of space-time covariance, and resolution of the problem of time

    NASA Astrophysics Data System (ADS)

    Soo, Chopin; Yu, Hoi-Lai

    2014-01-01

    The framework of a theory of gravity from the quantum to the classical regime is presented. The paradigm shift from full space-time covariance to spatial diffeomorphism invariance, together with clean decomposition of the canonical structure, yield transparent physical dynamics and a resolution of the problem of time. The deep divide between quantum mechanics and conventional canonical formulations of quantum gravity is overcome with a Schrödinger equation for quantum geometrodynamics that describes evolution in intrinsic time. Unitary time development with gauge-invariant temporal ordering is also viable. All Kuchar observables become physical; and classical space-time, with direct correlation between its proper times and intrinsic time intervals, emerges from constructive interference. The framework not only yields a physical Hamiltonian for Einstein's theory, but also prompts natural extensions and improvements towards a well behaved quantum theory of gravity. It is a consistent canonical scheme to discuss Horava-Lifshitz theories with intrinsic time evolution, and of the many possible alternatives that respect 3-covariance (rather than the more restrictive 4-covariance of Einstein's theory), Horava's "detailed balance" form of the Hamiltonian constraint is essentially pinned down by this framework. Issues in quantum gravity that depend on radiative corrections and the rigorous definition and regularization of the Hamiltonian operator are not addressed in this work.

  11. Comparison of LSS-IV and LISS-III+LISS-IV merged data for classification of crops

    NASA Astrophysics Data System (ADS)

    Hebbar, R.; Sesha Sai, M. V. R.

    2014-11-01

    Resourcesat-1 satellite with its unique capability of simultaneous acquisition of multispectral images at different spatial resolutions (AWiFS, LISS-III and LISS-IV MX / Mono) has immense potential for crop inventory. The present study was carried for selection of suitable LISS-IV MX band for data fusion and its evaluation for delineation different crops in a multi-cropped area. Image fusion techniques namely intensity hue saturation (IHS), principal component analysis (PCA), brovey, high pass filter (HPF) and wavelet methods were used for merging LISS-III and LISS-IV Mono data. The merged products were evaluated visually and through universal image quality index, ERGAS and classification accuracy. The study revealed that red band of LISS-IV MX data was found to be optimal band for merging with LISS-III data in terms of maintaining both spectral and spatial information and thus, closely matching with multispectral LISS-IVMX data. Among the five data fusion techniques, wavelet method was found to be superior in retaining image quality and higher classification accuracy compared to commonly used methods of IHS, PCA and Brovey. The study indicated that LISS-IV data in mono mode with wider swath of 70 km could be exploited in place of 24km LISS-IVMX data by selection of appropriate fusion techniques by acquiring monochromatic data in the red band.

  12. GCF Mark IV development

    NASA Technical Reports Server (NTRS)

    Mortensen, L. O.

    1982-01-01

    The Mark IV ground communication facility (GCF) as it is implemented to support the network consolidation program is reviewed. Changes in the GCF are made in the area of increased capacity. Common carrier circuits are the medium for data transfer. The message multiplexing in the Mark IV era differs from the Mark III era, in that all multiplexing is done in a GCF computer under GCF software control, which is similar to the multiplexing currently done in the high speed data subsystem.

  13. Real-time detection of transients in OGLE-IV with application of machine learning

    NASA Astrophysics Data System (ADS)

    Klencki, Jakub; Wyrzykowski, Łukasz

    2016-06-01

    The current bottleneck of transient detection in most surveys is the problem of rejecting numerous artifacts from detected candidates. We present a triple-stage hierarchical machine learning system for automated artifact filtering in difference imaging, based on self-organizing maps. The classifier, when tested on the OGLE-IV Transient Detection System, accepts 97% of real transients while removing up to 97.5% of artifacts.

  14. Obtaining systematic teacher reports of disruptive behavior disorders utilizing DSM-IV.

    PubMed

    Wolraich, M L; Feurer, I D; Hannah, J N; Baumgaertel, A; Pinnock, T Y

    1998-04-01

    This study examines the psychometric properties of the Vanderbilt AD/HD Diagnostic Teacher Rating Scale (VADTRS) and provides preliminary normative data from a large, geographically defined population. The VADTRS consists of the complete list of DSM-IV AD/HD symptoms, a screen for other disruptive behavior disorders, anxiety and depression, and ratings of academic and classroom behavior performance. Teachers in one suburban county completed the scale for their students during 2 consecutive years. Statistical methods included (a) exploratory and confirmatory latent variable analyses of item data, (b) evaluation of the internal consistency of the latent dimensions, (c) evaluation of latent structure concordance between school year samples, and (d) preliminary evaluation of criterion-related validity. The instrument comprises four behavioral dimensions and two performance dimensions. The behavioral dimensions were concordant between school years and were consistent with a priori DSM-IV diagnostic criteria. Correlations between latent dimensions and relevant, known disorders or problems varied from .25 to .66.

  15. Shannon Entropy of the Canonical Genetic Code

    NASA Astrophysics Data System (ADS)

    Nemzer, Louis

    The probability that a non-synonymous point mutation in DNA will adversely affect the functionality of the resultant protein is greatly reduced if the substitution is conservative. In that case, the amino acid coded by the mutated codon has similar physico-chemical properties to the original. Many simplified alphabets, which group the 20 common amino acids into families, have been proposed. To evaluate these schema objectively, we introduce a novel, quantitative method based on the inherent redundancy in the canonical genetic code. By calculating the Shannon information entropy carried by 1- or 2-bit messages, groupings that best leverage the robustness of the code are identified. The relative importance of properties related to protein folding - like hydropathy and size - and function, including side-chain acidity, can also be estimated. In addition, this approach allows us to quantify the average information value of nucleotide codon positions, and explore the physiological basis for distinguishing between transition and transversion mutations. Supported by NSU PFRDG Grant #335347.

  16. IV&V Project Assessment Process Validation

    NASA Technical Reports Server (NTRS)

    Driskell, Stephen

    2012-01-01

    The Space Launch System (SLS) will launch NASA's Multi-Purpose Crew Vehicle (MPCV). This launch vehicle will provide American launch capability for human exploration and travelling beyond Earth orbit. SLS is designed to be flexible for crew or cargo missions. The first test flight is scheduled for December 2017. The SLS SRR/SDR provided insight into the project development life cycle. NASA IV&V ran the standard Risk Based Assessment and Portfolio Based Risk Assessment to identify analysis tasking for the SLS program. This presentation examines the SLS System Requirements Review/System Definition Review (SRR/SDR), IV&V findings for IV&V process validation correlation to/from the selected IV&V tasking and capabilities. It also provides a reusable IEEE 1012 scorecard for programmatic completeness across the software development life cycle.

  17. The canonical Lagrangian approach to three-space general relativity

    NASA Astrophysics Data System (ADS)

    Shyam, Vasudev; Venkatesh, Madhavan

    2013-07-01

    We study the action for the three-space formalism of general relativity, better known as the Barbour-Foster-Ó Murchadha action, which is a square-root Baierlein-Sharp-Wheeler action. In particular, we explore the (pre)symplectic structure by pulling it back via a Legendre map to the tangent bundle of the configuration space of this action. With it we attain the canonical Lagrangian vector field which generates the gauge transformations (3-diffeomorphisms) and the true physical evolution of the system. This vector field encapsulates all the dynamics of the system. We also discuss briefly the observables and perennials for this theory. We then present a symplectic reduction of the constrained phase space.

  18. Sleep Problems, Comorbid Mental Disorders, and Role Functioning in the National Comorbidity Survey Replication (NCS-R)

    PubMed Central

    Roth, Thomas; Jaeger, Savina; Jin, Robert; Kalsekar, Anupama; Stang, Paul E.; Kessler, Ronald C.

    2007-01-01

    Background Little is known about the population prevalence of sleep problems or whether the associations of sleep problems with role impairment are due to comorbid mental disorders. Methods The associations of four 12-month sleep problems (difficulty initiating or maintaining sleep, early morning awakening, nonrestorative sleep) with role impairment were analyzed in the National Comorbidity Survey Replication controlling 12-month DSM-IV anxiety, mood, impulse-control, and substance disorders. The WHO Composite International Diagnostic Interview was used to assess sleep problems and DSM-IV disorders. The WHO Disability Schedule-II (WHO-DAS) was used to assess role impairment. Results Prevalence estimates of the separate sleep problems were in the range 16.4-25.0%, with 36.3% reporting at least one of the four. Mean 12-month duration was 24.4 weeks. All four problems were significantly comorbid with all the 12-month DMS-IV disorders assessed in the survey (median OR: 3.4; 25th-75th percentile: 2.8-3.9) and significantly related to role impairment. Relationships with role impairment generally remained significant after controlling comorbid mental disorders. Nonrestorative sleep was more strongly and consistently related to role impairment than were the other sleep problems. Conclusions The four sleep problems considered here are of public health significance because of their high prevalence and significant associations with role impairment. PMID:16952333

  19. Dissimilatory Fe(III) and Mn(IV) reduction.

    PubMed Central

    Lovley, D R

    1991-01-01

    The oxidation of organic matter coupled to the reduction of Fe(III) or Mn(IV) is one of the most important biogeochemical reactions in aquatic sediments, soils, and groundwater. This process, which may have been the first globally significant mechanism for the oxidation of organic matter to carbon dioxide, plays an important role in the oxidation of natural and contaminant organic compounds in a variety of environments and contributes to other phenomena of widespread significance such as the release of metals and nutrients into water supplies, the magnetization of sediments, and the corrosion of metal. Until recently, much of the Fe(III) and Mn(IV) reduction in sedimentary environments was considered to be the result of nonenzymatic processes. However, microorganisms which can effectively couple the oxidation of organic compounds to the reduction of Fe(III) or Mn(IV) have recently been discovered. With Fe(III) or Mn(IV) as the sole electron acceptor, these organisms can completely oxidize fatty acids, hydrogen, or a variety of monoaromatic compounds. This metabolism provides energy to support growth. Sugars and amino acids can be completely oxidized by the cooperative activity of fermentative microorganisms and hydrogen- and fatty-acid-oxidizing Fe(III) and Mn(IV) reducers. This provides a microbial mechanism for the oxidation of the complex assemblage of sedimentary organic matter in Fe(III)- or Mn(IV)-reducing environments. The available evidence indicates that this enzymatic reduction of Fe(III) or Mn(IV) accounts for most of the oxidation of organic matter coupled to reduction of Fe(III) and Mn(IV) in sedimentary environments. Little is known about the diversity and ecology of the microorganisms responsible for Fe(III) and Mn(IV) reduction, and only preliminary studies have been conducted on the physiology and biochemistry of this process. PMID:1886521

  20. Tilting the balance between canonical and noncanonical conformations for the H1 hypervariable loop of a llama VHH through point mutations.

    PubMed

    Mahajan, Sai Pooja; Velez-Vega, Camilo; Escobedo, Fernando A

    2013-01-10

    Nanobodies are single-domain antibodies found in camelids. These are the smallest naturally occurring binding domains and derive functionality via three hypervariable loops (H1-H3) that form the binding surface. They are excellent candidates for antibody engineering because of their favorable characteristics like small size, high solubility, and stability. To rationally engineer antibodies with affinity for a specific target, the hypervariable loops can be tailored to obtain the desired binding surface. As a first step toward such a goal, we consider the design of loops with a desired conformation. In this study, we focus on the H1 loop of the anti-hCG llama nanobody that exhibits a noncanonical conformation. We aim to "tilt" the stability of the H1 loop structure from a noncanonical conformation to a (humanized) type 1 canonical conformation by studying the effect of selected mutations to the amino acid sequence of the H1, H2, and proximal residues. We use all-atomistic, explicit-solvent, biased molecular dynamic simulations to simulate the wild-type and mutant loops in a prefolded framework. We thus find mutants with increasing propensity to form a stable type 1 canonical conformation of the H1 loop. Free energy landscapes reveal the existence of conformational isomers of the canonical conformation that may play a role in binding different antigenic surfaces. We also elucidate the approximate mechanism and kinetics of transitions between such conformational isomers by using a Markovian model. We find that a particular three-point mutant has the strongest thermodynamic propensity to form the H1 type 1 canonical structure but also to exhibit transitions between conformational isomers, while a different, more rigid three-point mutant has the strongest propensity to be kinetically trapped in such a canonical structure.

  1. MiRNA-335 suppresses neuroblastoma cell invasiveness by direct targeting of multiple genes from the non-canonical TGF-β signalling pathway

    PubMed Central

    Lynch, Jennifer; Fay, Joanna; Meehan, Maria; Bryan, Kenneth; Watters, Karen M.; Murphy, Derek M.; Stallings, Raymond L.

    2012-01-01

    Transforming growth factor-β (TGF-β) signaling regulates many diverse cellular activities through both canonical (SMAD-dependent) and non-canonical branches, which includes the mitogen-activated protein kinase (MAPK), Rho-like guanosine triphosphatase and phosphatidylinositol-3-kinase/AKT pathways. Here, we demonstrate that miR-335 directly targets and downregulates genes in the TGF-β non-canonical pathways, including the Rho-associated coiled-coil containing protein (ROCK1) and MAPK1, resulting in reduced phosphorylation of downstream pathway members. Specifically, inhibition of ROCK1 and MAPK1 reduces phosphorylation levels of the motor protein myosin light chain (MLC) leading to a significant inhibition of the invasive and migratory potential of neuroblastoma cells. Additionally, miR-335 targets the leucine-rich alpha-2-glycoprotein 1 (LRG1) messenger RNA, which similarly results in a significant reduction in the phosphorylation status of MLC and a decrease in neuroblastoma cell migration and invasion. Thus, we link LRG1 to the migratory machinery of the cell, altering its activity presumably by exerting its effect within the non-canonical TGF-β pathway. Moreover, we demonstrate that the MYCN transcription factor, whose coding sequence is highly amplified in a particularly clinically aggressive neuroblastoma tumor subtype, directly binds to a region immediately upstream of the miR-335 transcriptional start site, resulting in transcriptional repression. We conclude that MYCN contributes to neuroblastoma cell migration and invasion, by directly downregulating miR-335, resulting in the upregulation of the TGF-β signaling pathway members ROCK1, MAPK1 and putative member LRG1, which positively promote this process. Our results provide novel insight into the direct regulation of TGF-β non-canonical signaling by miR-335, which in turn is downregulated by MYCN. PMID:22382496

  2. 21 CFR 880.5025 - I.V. container.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... I.V. container. (a) Identification. An I.V. container is a container made of plastic or glass used... 21 Food and Drugs 8 2014-04-01 2014-04-01 false I.V. container. 880.5025 Section 880.5025 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES...

  3. 21 CFR 880.5025 - I.V. container.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... I.V. container. (a) Identification. An I.V. container is a container made of plastic or glass used... 21 Food and Drugs 8 2013-04-01 2013-04-01 false I.V. container. 880.5025 Section 880.5025 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES...

  4. 21 CFR 880.5025 - I.V. container.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... I.V. container. (a) Identification. An I.V. container is a container made of plastic or glass used... 21 Food and Drugs 8 2012-04-01 2012-04-01 false I.V. container. 880.5025 Section 880.5025 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES...

  5. 21 CFR 880.5025 - I.V. container.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... I.V. container. (a) Identification. An I.V. container is a container made of plastic or glass used... 21 Food and Drugs 8 2011-04-01 2011-04-01 false I.V. container. 880.5025 Section 880.5025 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES...

  6. 40 CFR 144.23 - Class IV wells.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 23 2011-07-01 2011-07-01 false Class IV wells. 144.23 Section 144.23... INJECTION CONTROL PROGRAM Authorization of Underground Injection by Rule § 144.23 Class IV wells. (a) Injection into existing Class IV wells is authorized for up to six months after approval or promulgation of...

  7. 40 CFR 144.23 - Class IV wells.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 24 2012-07-01 2012-07-01 false Class IV wells. 144.23 Section 144.23... INJECTION CONTROL PROGRAM Authorization of Underground Injection by Rule § 144.23 Class IV wells. (a) Injection into existing Class IV wells is authorized for up to six months after approval or promulgation of...

  8. 40 CFR 144.23 - Class IV wells.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 22 2010-07-01 2010-07-01 false Class IV wells. 144.23 Section 144.23... INJECTION CONTROL PROGRAM Authorization of Underground Injection by Rule § 144.23 Class IV wells. (a) Injection into existing Class IV wells is authorized for up to six months after approval or promulgation of...

  9. Non-equilibrium ionization by a periodic electron beam. II. Synthetic Si IV and O IV transition region spectra

    NASA Astrophysics Data System (ADS)

    Dzifčáková, Elena; Dudík, Jaroslav

    2018-03-01

    Context. Transition region (TR) spectra typically show the Si IV 1402.8 Å line to be enhanced by a factor of 5 or more compared to the neighboring O IV 1401.2 Å, contrary to predictions of ionization equilibrium models and the Maxwellian distribution of particle energies. Non-equilibrium effects in TR spectra are therefore expected. Aims: To investigate the combination of non-equilibrium ionization and high-energy particles, we apply the model of the periodic electron beam, represented by a κ-distribution that recurs at periods of several seconds, to plasma at chromospheric temperatures of 104 K. This simple model can approximate a burst of energy release involving accelerated particles. Methods: Instantaneous time-dependent charge states of silicon and oxygen were calculated and used to synthesize the instantaneous and period-averaged spectra of Si IV and O IV. Results: The electron beam drives the plasma out of equilibrium. At electron densities of Ne = 1010 cm-3, the plasma is out of ionization equilibrium at all times in all cases we considered, while for a higher density of Ne = 1011 cm-3, ionization equilibrium can be reached toward the end of each period, depending on the conditions. In turn, the character of the period-averaged synthetic spectra also depends on the properties of the beam. While the case of κ = 2 results in spectra with strong or even dominant O IV, higher values of κ can approximate a range of observed TR spectra. Spectra similar to typically observed spectra, with the Si IV 1402.8 Å line about a factor 5 higher than O IV 1401.2 Å, are obtained for κ = 3. An even higher value of κ = 5 results in spectra that are exclusively dominated by Si IV, with negligible O IV emission. This is a possible interpretation of the TR spectra of UV (Ellerman) bursts, although an interpretation that requires a density that is 1-3 orders of magnitude lower than for equilibrium estimates. Movies associated to Fig. A.1 are available at http://https://www.aanda.org

  10. Fast start-up of the CANON process with a SABF and the effects of pH and temperature on nitrogen removal and microbial activity.

    PubMed

    Yue, Xiu; Yu, Guangping; Liu, Zhuhan; Tang, Jiali; Liu, Jian

    2018-04-01

    The long start-up time of the completely autotrophic nitrogen removal over nitrite (CANON) process is one of the main disadvantages of this system. In this paper, the CANON process with a submerged aerated biological filter (SABF) was rapidly started up within 26 days. It gave an average ammonium nitrogen removal rate (ANR) and a total nitrogen removal rate (TNR) of 94.2% and 81.3%, respectively. The phyla Proteobacteria and Planctomycetes were confirmed as the ammonia oxidizing bacteria (AOB) and anaerobic ammonium oxidation bacteria (AnAOB). The genus Candidatus Brocadia was the major contributor of nitrogen removal. pH and temperature affect the performance of the CANON process. This experimental results showed that the optimum pH and temperature were 8.0 and 30 °C, respectively, which gave the highest average ANR and TNR values of 94.6% and 85.1%, respectively. This research could promote the nitrogen removal ability of CANON process in the future. Copyright © 2018 Elsevier Ltd. All rights reserved.

  11. A non-canonical site reveals the cooperative mechanisms of microRNA-mediated silencing.

    PubMed

    Flamand, Mathieu N; Gan, Hin Hark; Mayya, Vinay K; Gunsalus, Kristin C; Duchaine, Thomas F

    2017-07-07

    Although strong evidence supports the importance of their cooperative interactions, microRNA (miRNA)-binding sites are still largely investigated as functionally independent regulatory units. Here, a survey of alternative 3΄UTR isoforms implicates a non-canonical seedless site in cooperative miRNA-mediated silencing. While required for target mRNA deadenylation and silencing, this site is not sufficient on its own to physically recruit miRISC. Instead, it relies on facilitating interactions with a nearby canonical seed-pairing site to recruit the Argonaute complexes. We further show that cooperation between miRNA target sites is necessary for silencing in vivo in the C. elegans embryo, and for the recruitment of the Ccr4-Not effector complex. Using a structural model of cooperating miRISCs, we identified allosteric determinants of cooperative miRNA-mediated silencing that are required for both embryonic and larval miRNA functions. Our results delineate multiple cooperative mechanisms in miRNA-mediated silencing and further support the consideration of target site cooperation as a fundamental characteristic of miRNA function. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  12. Subcellular Localization of a Plant Catalase-Phenol Oxidase, AcCATPO, from Amaranthus and Identification of a Non-canonical Peroxisome Targeting Signal

    PubMed Central

    Chen, Ning; Teng, Xiao-Lu; Xiao, Xing-Guo

    2017-01-01

    AcCATPO is a plant catalase-phenol oxidase recently identified from red amaranth. Its physiological function remains unexplored. As the starting step of functional analysis, here we report its subcellular localization and a non-canonical targeting signal. Commonly used bioinformatics programs predicted a peroxisomal localization for AcCATPO, but failed in identification of canonical peroxisomal targeting signals (PTS). The C-terminal GFP tagging led the fusion protein AcCATPO-GFP to the cytosol and the nucleus, but N-terminal tagging directed the GFP-AcCATPO to peroxisomes and nuclei, in transgenic tobacco. Deleting the tripeptide (PTM) at the extreme C-terminus almost ruled out the peroxisomal localization of GFP-AcCATPOΔ3, and removing the C-terminal decapeptide completely excluded peroxisomes as the residence of GFP-AcCATPOΔ10. Furthermore, this decapeptide as a targeting signal could import GFP-10aa to the peroxisome exclusively. Taken together, these results demonstrate that AcCATPO is localized to the peroxisome and the nucleus, and its peroxisomal localization is attributed to a non-canonical PTS1, the C-terminal decapeptide which contains an internal SRL motif and a conserved tripeptide P-S/T-I/M at the extreme of C-terminus. This work may further the study as to the physiological function of AcCATPO, especially clarify its involvement in betalain biosynthesis, and provide a clue to elucidate more non-canonic PTS. PMID:28824680

  13. Subcellular Localization of a Plant Catalase-Phenol Oxidase, AcCATPO, from Amaranthus and Identification of a Non-canonical Peroxisome Targeting Signal.

    PubMed

    Chen, Ning; Teng, Xiao-Lu; Xiao, Xing-Guo

    2017-01-01

    AcCATPO is a plant catalase-phenol oxidase recently identified from red amaranth. Its physiological function remains unexplored. As the starting step of functional analysis, here we report its subcellular localization and a non-canonical targeting signal. Commonly used bioinformatics programs predicted a peroxisomal localization for AcCATPO, but failed in identification of canonical peroxisomal targeting signals (PTS). The C-terminal GFP tagging led the fusion protein AcCATPO-GFP to the cytosol and the nucleus, but N-terminal tagging directed the GFP-AcCATPO to peroxisomes and nuclei, in transgenic tobacco. Deleting the tripeptide (PTM) at the extreme C-terminus almost ruled out the peroxisomal localization of GFP-AcCATPOΔ3, and removing the C-terminal decapeptide completely excluded peroxisomes as the residence of GFP-AcCATPOΔ10. Furthermore, this decapeptide as a targeting signal could import GFP-10aa to the peroxisome exclusively. Taken together, these results demonstrate that AcCATPO is localized to the peroxisome and the nucleus, and its peroxisomal localization is attributed to a non-canonical PTS1, the C-terminal decapeptide which contains an internal SRL motif and a conserved tripeptide P-S/T-I/M at the extreme of C-terminus. This work may further the study as to the physiological function of AcCATPO, especially clarify its involvement in betalain biosynthesis, and provide a clue to elucidate more non-canonic PTS.

  14. Personality disorders and psychosocial problems in a group of participants to therapeutic processes for people with severe social disabilities.

    PubMed

    Salavera, Carlos; Tricás, José M; Lucha, Orosia

    2011-12-11

    Homeless people have high dropout rates when they participate in therapeutic processes. The causes of this failure are not always known. This study investigates whether dropping-out is mediated by personality disorders or whether psychosocial problems are more important. Eighty-nine homeless people in a socio-laboral integration process were assessed. An initial interview was used, and the MCMI II questionnaire was applied to investigate the presence of psychosocial disorders (DSM-IV-TR axis IV). This was designed as an ex post-facto prospective study. Personality disorders were very frequent among the homeless people examined. Moreover, the high index of psychosocial problems (axis IV) in this population supported the proposal that axis IV disorders are influential in failure to complete therapy. The outcomes of the study show that the homeless people examined presented with more psychopathological symptoms, in both axis II and axis IV, than the general population. This supports the need to take into account the comorbidity between these two types of disorder among homeless people, in treatment and in the development of specific intervention programs. In conclusion, the need for more psychosocial treatments addressing the individual problems of homeless people is supported.

  15. TGF-β1 activates the canonical NF-κB signaling to promote cell survival and proliferation in dystrophic muscle fibroblasts in vitro

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ma, Zhen-Yu; Department of Neurology, The Second Affiliated Hospital, Guangzhou Medical University, No.250 Changgang East Road, Guangzhou 510260, Guangdong Province; Zhong, Zhi-Gang

    Activated fibroblasts continue to proliferate at injury sites, leading to progressive muscular fibrosis in Duchenne muscular dystrophy (DMD). TGF-β1 is a dominant profibrotic mediator thought to play a critical role in muscle fibrosis; however, the implicated mechanisms are not fully understood. Here we showed that TGF-β1 increased the resistance to apoptosis and stimulated cell cycle progression in dystrophic muscle fibroblasts under serum deprivation conditions in vitro. TGF-β1 treatment activated the canonical NF-κB pathway; and we found that pharmacological inhibition of IKKβ with IMD-0354 and RelA gene knockdown with siRNA attenuated these effects of TGF-β1 on dystrophic muscle fibroblasts. Collectively, our datamore » suggest that TGF-β1 prevents apoptosis and cell cycle arrest in dystrophic muscle fibroblasts through the canonical NF-κB signaling pathway. - Highlights: • TGF-β1 promotes survival and proliferation in dystrophic muscle fibroblasts. • TGF-β1 activated the canonical NF-κB pathway in dystrophic muscle fibroblasts. • Canonical NF-κB pathway mediates these effects of TGF-β1.« less

  16. 45 CFR 1356.70 - E to title IV-B.

    Code of Federal Regulations, 2010 CFR

    1996-10-01

    ... 45 PUBLIC WELFARE 4 1996-10-01 1996-10-01 false E to title IV-B. 1356.70 Sec. 1356.70 Transfer of funds from title IV PUBLIC WELFARE Regulations Relating to Public Welfare (Continued) OFFICE OF HUMAN... APPLICABLE TO TITLE IV-E Sec. 1356.70 Transfer of funds from title IV-E to title IV-B. (a)(1) Funds available...

  17. A genuinely discontinuous approach for multiphase EHD problems

    NASA Astrophysics Data System (ADS)

    Natarajan, Mahesh; Desjardins, Olivier

    2017-11-01

    Electrohydrodynamics (EHD) involves solving the Poisson equation for the electric field potential. For multiphase flows, although the electric field potential is a continuous quantity, due to the discontinuity in the electric permittivity between the phases, additional jump conditions at the interface, for the normal and tangential components of the electric field need to be satisfied. All approaches till date either ignore the jump conditions, or involve simplifying assumptions, and hence yield unconvincing results even for simple test problems. In the present work, we develop a genuinely discontinuous approach for the Poisson equation for multiphase flows using a Finite Volume Unsplit Volume of Fluid method. The governing equation and the jump conditions without assumptions are used to develop the method, and its efficiency is demonstrated by comparison of the numerical results with canonical test problems having exact solutions. Postdoctoral Associate, Department of Mechanical and Aerospace Engineering.

  18. Prevalence of DSM-IV major depression among U.S. military personnel: meta-analysis and simulation.

    PubMed

    Gadermann, Anne M; Engel, Charles C; Naifeh, James A; Nock, Matthew K; Petukhova, Maria; Santiago, Patcho N; Wu, Benjamin; Zaslavsky, Alan M; Kessler, Ronald C

    2012-08-01

    A meta-analysis of 25 epidemiological studies estimated the prevalence of recent Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) major depression (MD) among U.S. military personnel. Best estimates of recent prevalence (standard error) were 12.0% (1.2) among currently deployed, 13.1% (1.8) among previously deployed, and 5.7% (1.2) among never deployed. Consistent correlates of prevalence were being female, enlisted, young (ages 17-25), unmarried, and having less than a college education. Simulation of data from a national general population survey was used to estimate expected lifetime prevalence of MD among respondents with the sociodemographic profile and none of the enlistment exclusions of Army personnel. In this Simulated sample, 16.2% (3.1) of respondents had lifetime MD and 69.7% (8.5) of first onsets occurred before expected age of enlistment. Numerous methodological problems limit the results of the meta-analysis and simulation. The article closes with a discussion of recommendations for correcting these problems in future surveillance and operational stress studies.

  19. Epithelial transformation by KLF4 requires Notch1 but not canonical Notch1 signaling

    PubMed Central

    Liu, Zhaoli; Teng, Lihong; Bailey, Sarah K.; Frost, Andra R.; Bland, Kirby I.; LoBuglio, Albert F.; Ruppert, J. Michael; Lobo-Ruppert, Susan M.

    2009-01-01

    The transcription factors Notch1 and KLF4 specify epithelial cell fates and confer stem cell properties. suggesting a functional relationship, each gene can act to promote or suppress tumorigenesis in a context-dependent manner, and alteration of KLF4 or Notch pathway genes in mice gives rise to similar phenotypes. Activation of a conditional allele of KLF4 in RK3E epithelial cells rapidly induces expression of Notch1 mRNA and the active, intracellular form of Notch1. KLF4-induced transformation was suppressed by knockdown of endogenous Notch1 using siRNA or an inhibitor of γ-secretase. Chromatin immunoprecipitation assay shows that KLF4 binds to the proximal Notch1 promoter in human mammary epithelial cells, and siRNA-mediated suppression of KLF4 in human mammary cancer cells results in reduced expression of Notch1. Furthermore, KLF4 and Notch1 expression are correlated in primary human breast tumors (N = 89; pearson analysis, r > 0.5, p < 0.0001). Like KLF4, Notch1 was previously shown to induce transformation of rat cells immortalized with adenovirus E1A, similar to RK3E cells. We therefore compared the signaling requirements for Notch1- or KLF4-induced malignant transformation of RK3E. As expected, transformation by Notch1 was suppressed by dominant-negative CSL or MaML1, inhibitors of canonical Notch1 signaling. However, these inhibitors did not suppress transformation by KLF4. Therefore, while KLF4-induced transformation requires Notch1, canonical Notch1 signaling is not required, and Notch1 may signal through a distinct pathway in cells with increased KLF4 activity. These results suggest that KLF4 could contribute to breast tumor progression by activating synthesis of Notch1 and by promoting signaling through a non-canonical Notch1 pathway. PMID:19717984

  20. Testing the Canon: Student Responses to Texts by Medieval Women in English Literature Surveys.

    ERIC Educational Resources Information Center

    Hawkins, Ann R.

    While there has been a great deal of debate about enlarging the canon, less attention has been paid to how students respond to "new" literary figures such as Margery Kempe and Julian of Norwich, or to how instructors should incorporate them into an already cramped literature survey course. Instructors must consider some questions that…

  1. A field theoretic generalization of Hajicek and Kuchar's quantization scheme in 3+1 canonical quantum gravity

    NASA Astrophysics Data System (ADS)

    Melas, Evangelos

    2011-07-01

    The 3+1 (canonical) decomposition of all geometries admitting two-dimensional space-like surfaces is exhibited as a generalization of a previous work. A proposal, consisting of a specific re-normalization Assumption and an accompanying Requirement, which has been put forward in the 2+1 case is now generalized to 3+1 dimensions. This enables the canonical quantization of these geometries through a generalization of Kuchař's quantization scheme in the case of infinite degrees of freedom. The resulting Wheeler-deWitt equation is based on a re-normalized manifold parameterized by three smooth scalar functionals. The entire space of solutions to this equation is analytically given, a fact that is entirely new to the present case. This is made possible by exploiting the freedom left by the imposition of the Requirement and contained in the third functional.

  2. Pseudoclassical Foldy-Wouthuysen transformation and canonical quantization of (D-2n)-dimensional relativistic particle with spin in an external electromagnetic field

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Grigoryan, G.V.; Grigoryan, R.P.

    1995-09-01

    The canonical quantization of a (D=2n)-dimensional Dirac particle with spin in an arbitrary external electromagnetic field is performed in a gauge that makes it possible to describe simultaneously particles and antiparticles (both massive and massless) already at the classical level. A pseudoclassical Foldy-Wouthuysen transformation is used to find the canonical (Newton-Wigner) coordinates. The connection between this quantization scheme and Blount`s picture describing the behavior of a Dirac particle in an external electromagnetic field is discussed.

  3. A non-canonical transferred DNA insertion at the BRI1 locus in Arabidopsis thaliana.

    PubMed

    Zhao, Zhong; Zhu, Yan; Erhardt, Mathieu; Ruan, Ying; Shen, Wen-Hui

    2009-04-01

    Agrobacterium-mediated transformation is widely used in transgenic plant engineering and has been proven to be a powerful tool for insertional mutagenesis of the plant genome. The transferred DNA (T-DNA) from Agrobacterium is integrated into the plant genome through illegitimate recombination between the T-DNA and the plant DNA. Contrasting to the canonical insertion, here we report on a locus showing a complex mutation associated with T-DNA insertion at the BRI1 gene in Arabidopsis thaliana. We obtained a mutant line, named salade for its phenotype of dwarf stature and proliferating rosette. Molecular characterization of this mutant revealed that in addition to T-DNA a non-T-DNA-localized transposon from bacteria was inserted in the Arabidopsis genome and that a region of more than 11.5 kb of the Arabidopsis genome was deleted at the insertion site. The deleted region contains the brassinosteroid receptor gene BRI1 and the transcription factor gene WRKY13. Our finding reveals non-canonical T-DNA insertion, implicating horizontal gene transfer and cautioning the use of T-DNA as mutagen in transgenic research.

  4. Purification, identification and molecular mechanism of two dipeptidyl peptidase IV (DPP-IV) inhibitory peptides from Antarctic krill (Euphausia superba) protein hydrolysate.

    PubMed

    Ji, Wei; Zhang, Chaohua; Ji, Hongwu

    2017-10-01

    Dipeptidyl peptidase IV (DPP-IV) played an important role in blood glucose regulation. Inhibition of DPP-IV may improve glycemic control in diabetics by preventing the rapid breakdown of incretin hormones and prolonging their physiological action. In this study, Antarctic krill (Euphausia superba) protein was hydrolyzed using animal proteolytic enzymes. The hydrolysate was purified sequentially by ultrafiltration, gel filtration chromatography and reversed phase high-performance liquid chromatography (RP-HPLC). DPP-IV inhibitory activity of the fractions achieved from Antarctic krill protein was determined by DPP-IV screening reagent kit. Two purified peptides were identified by Xevo G2-XS QTof mass spectrometer (QTOF-MS). One peptide purified was Ala-Pro (AP) with IC 50 values of 0.0530mg/mL, the other Ile-Pro-Ala (IPA) with IC 50 values of 0.0370mg/mL. They both exhibited strong DPP-IV inhibitory activity. The molecular docking analysis revealed that DPP-IV inhibition by AP and IPA was mainly due to formation of a strong interaction surface force with the 91-96 and 101-105 amino acids of the DPP-IV. Our results suggested that the protein hydrolysate from Antarctic krill can be considered as a promising natural source of DPP-IV inhibitory peptides in the management of diabetes. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. On the Importance of the Nonequilibrium Ionization of Si IV and O IV and the Line of Sight in Solar Surges

    NASA Astrophysics Data System (ADS)

    Nóbrega-Siverio, D.; Moreno-Insertis, F.; Martínez-Sykora, J.

    2018-05-01

    Surges are ubiquitous cool ejections in the solar atmosphere that often appear associated with transient phenomena like UV bursts or coronal jets. Recent observations from the Interface Region Imaging Spectrograph show that surges, although traditionally related to chromospheric lines, can exhibit enhanced emission in Si IV with brighter spectral profiles than for the average transition region (TR). In this paper, we explain why surges are natural sites to show enhanced emissivity in TR lines. We performed 2.5D radiative-MHD numerical experiments using the Bifrost code including the nonequilibrium (NEQ) ionization of silicon and oxygen. A surge is obtained as a by-product of magnetic flux emergence; the TR enveloping the emerged domain is strongly affected by NEQ effects: assuming statistical equilibrium would produce an absence of Si IV and O IV ions in most of the region. Studying the properties of the surge plasma emitting in the Si IV λ1402.77 and O IV λ1401.16 lines, we find that (a) the timescales for the optically thin losses and heat conduction are very short, leading to departures from statistical equilibrium, and (b) the surge emits in Si IV more and has an emissivity ratio of Si IV to O IV larger than a standard TR. Using synthetic spectra, we conclude the importance of line-of-sight effects: given the involved geometry of the surge, the line of sight can cut the emitting layer at small angles and/or cross it multiple times, causing prominent, spatially intermittent brightenings in both Si IV and O IV.

  6. A Non-canonical Reticular-Limbic Central Auditory Pathway via Medial Septum Contributes to Fear Conditioning.

    PubMed

    Zhang, Guang-Wei; Sun, Wen-Jian; Zingg, Brian; Shen, Li; He, Jufang; Xiong, Ying; Tao, Huizhong W; Zhang, Li I

    2018-01-17

    In the mammalian brain, auditory information is known to be processed along a central ascending pathway leading to auditory cortex (AC). Whether there exist any major pathways beyond this canonical auditory neuraxis remains unclear. In awake mice, we found that auditory responses in entorhinal cortex (EC) cannot be explained by a previously proposed relay from AC based on response properties. By combining anatomical tracing and optogenetic/pharmacological manipulations, we discovered that EC received auditory input primarily from the medial septum (MS), rather than AC. A previously uncharacterized auditory pathway was then revealed: it branched from the cochlear nucleus, and via caudal pontine reticular nucleus, pontine central gray, and MS, reached EC. Neurons along this non-canonical auditory pathway responded selectively to high-intensity broadband noise, but not pure tones. Disruption of the pathway resulted in an impairment of specifically noise-cued fear conditioning. This reticular-limbic pathway may thus function in processing aversive acoustic signals. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Welding IV.

    ERIC Educational Resources Information Center

    Allegheny County Community Coll., Pittsburgh, PA.

    Instructional objectives and performance requirements are outlined in this course guide for Welding IV, a competency-based course in advanced arc welding offered at the Community College of Allegheny County to provide students with proficiency in: (1) single vee groove welding using code specifications established by the American Welding Society…

  8. TCF3, a novel positive regulator of osteogenesis, plays a crucial role in miR-17 modulating the diverse effect of canonical Wnt signaling in different microenvironments

    PubMed Central

    Liu, W; Liu, Y; Guo, T; Hu, C; Luo, H; Zhang, L; Shi, S; Cai, T; Ding, Y; Jin, Y

    2013-01-01

    Wnt signaling pathways are a highly conserved pathway, which plays an important role from the embryonic development to bone formation. The effect of Wnt pathway on osteogenesis relies on their cellular environment and the expression of target genes. However, the molecular mechanism of that remains unclear. On the basis of the preliminary results, we observed the contrary effect of canonical Wnt signaling on osteogenic differentiation of periodontal ligament stem cells (PDLSCs) in the different culture environment. Furthermore, we found that the expression level of miR-17 was also varied with the change in the culture environment. Therefore, we hypothesized that miR-17 and canonical Wnt signaling may have potential interactions, particularly the inner regulation relationship in different microenvironments. In this paper, we observed that canonical Wnt signaling promoted osteogenesis of PDLSCs in the fully culture medium, while inhibited it in the osteogenic differentiation medium. Interestingly, alteration in the expression level of endogenous miR-17 could partially reverse the different effect of canonical Wnt signaling. Furthermore, the role of miR-17 was because of its target gene TCF3 (transcription factor 3), a key transcription factor of canonical Wnt pathway. Overexpression of TCF3 attenuated the effect of miR-17 on modulating canonical Wnt signaling. Finally, we elucidated that TCF3 enhanced osteogenesis both in vitro and in vivo. In brief, the different level of miR-17 was the main cause of the different effect of canonical Wnt signaling, and TCF3 was the crucial node of miR-17–canonial Wnt signaling regulation loop. This understanding of microRNAs regulating signaling pathways in different microenvironments may pave the way for fine-tuning the process of osteogenesis in bone-related disorders. PMID:23492770

  9. TCF3, a novel positive regulator of osteogenesis, plays a crucial role in miR-17 modulating the diverse effect of canonical Wnt signaling in different microenvironments.

    PubMed

    Liu, W; Liu, Y; Guo, T; Hu, C; Luo, H; Zhang, L; Shi, S; Cai, T; Ding, Y; Jin, Y

    2013-03-14

    Wnt signaling pathways are a highly conserved pathway, which plays an important role from the embryonic development to bone formation. The effect of Wnt pathway on osteogenesis relies on their cellular environment and the expression of target genes. However, the molecular mechanism of that remains unclear. On the basis of the preliminary results, we observed the contrary effect of canonical Wnt signaling on osteogenic differentiation of periodontal ligament stem cells (PDLSCs) in the different culture environment. Furthermore, we found that the expression level of miR-17 was also varied with the change in the culture environment. Therefore, we hypothesized that miR-17 and canonical Wnt signaling may have potential interactions, particularly the inner regulation relationship in different microenvironments. In this paper, we observed that canonical Wnt signaling promoted osteogenesis of PDLSCs in the fully culture medium, while inhibited it in the osteogenic differentiation medium. Interestingly, alteration in the expression level of endogenous miR-17 could partially reverse the different effect of canonical Wnt signaling. Furthermore, the role of miR-17 was because of its target gene TCF3 (transcription factor 3), a key transcription factor of canonical Wnt pathway. Overexpression of TCF3 attenuated the effect of miR-17 on modulating canonical Wnt signaling. Finally, we elucidated that TCF3 enhanced osteogenesis both in vitro and in vivo. In brief, the different level of miR-17 was the main cause of the different effect of canonical Wnt signaling, and TCF3 was the crucial node of miR-17-canonial Wnt signaling regulation loop. This understanding of microRNAs regulating signaling pathways in different microenvironments may pave the way for fine-tuning the process of osteogenesis in bone-related disorders.

  10. A Canonical Correlation Analysis of AIDS Restriction Genes and Metabolic Pathways Identifies Purine Metabolism as a Key Cooperator.

    PubMed

    Ye, Hanhui; Yuan, Jinjin; Wang, Zhengwu; Huang, Aiqiong; Liu, Xiaolong; Han, Xiao; Chen, Yahong

    2016-01-01

    Human immunodeficiency virus causes a severe disease in humans, referred to as immune deficiency syndrome. Studies on the interaction between host genetic factors and the virus have revealed dozens of genes that impact diverse processes in the AIDS disease. To resolve more genetic factors related to AIDS, a canonical correlation analysis was used to determine the correlation between AIDS restriction and metabolic pathway gene expression. The results show that HIV-1 postentry cellular viral cofactors from AIDS restriction genes are coexpressed in human transcriptome microarray datasets. Further, the purine metabolism pathway comprises novel host factors that are coexpressed with AIDS restriction genes. Using a canonical correlation analysis for expression is a reliable approach to exploring the mechanism underlying AIDS.

  11. Paul Weiss and the genesis of canonical quantization

    NASA Astrophysics Data System (ADS)

    Rickles, Dean; Blum, Alexander

    2015-12-01

    This paper describes the life and work of a figure who, we argue, was of primary importance during the early years of field quantisation and (albeit more indirectly) quantum gravity. A student of Dirac and Born, he was interned in Canada during the second world war as an enemy alien and after his release never seemed to regain a good foothold in physics, identifying thereafter as a mathematician. He developed a general method of quantizing (linear and non-linear) field theories based on the parameters labelling an arbitrary hypersurface. This method (the `parameter formalism' often attributed to Dirac), though later discarded, was employed (and viewed at the time as an extremely important tool) by the leading figures associated with canonical quantum gravity: Dirac, Pirani and Schild, Bergmann, DeWitt, and others. We argue that he deserves wider recognition for this and other innovations.

  12. Path integral approach to the Wigner representation of canonical density operators for discrete systems coupled to harmonic baths.

    PubMed

    Montoya-Castillo, Andrés; Reichman, David R

    2017-01-14

    We derive a semi-analytical form for the Wigner transform for the canonical density operator of a discrete system coupled to a harmonic bath based on the path integral expansion of the Boltzmann factor. The introduction of this simple and controllable approach allows for the exact rendering of the canonical distribution and permits systematic convergence of static properties with respect to the number of path integral steps. In addition, the expressions derived here provide an exact and facile interface with quasi- and semi-classical dynamical methods, which enables the direct calculation of equilibrium time correlation functions within a wide array of approaches. We demonstrate that the present method represents a practical path for the calculation of thermodynamic data for the spin-boson and related systems. We illustrate the power of the present approach by detailing the improvement of the quality of Ehrenfest theory for the correlation function C zz (t)=Re⟨σ z (0)σ z (t)⟩ for the spin-boson model with systematic convergence to the exact sampling function. Importantly, the numerically exact nature of the scheme presented here and its compatibility with semiclassical methods allows for the systematic testing of commonly used approximations for the Wigner-transformed canonical density.

  13. Using failure mode and effects analysis to plan implementation of smart i.v. pump technology.

    PubMed

    Wetterneck, Tosha B; Skibinski, Kathleen A; Roberts, Tanita L; Kleppin, Susan M; Schroeder, Mark E; Enloe, Myra; Rough, Steven S; Hundt, Ann Schoofs; Carayon, Pascale

    2006-08-15

    Failure mode and effects analysis (FMEA) was used to evaluate a smart i.v. pump as it was implemented into a redesigned medication-use process. A multidisciplinary team conducted a FMEA to guide the implementation of a smart i.v. pump that was designed to prevent pump programming errors. The smart i.v. pump was equipped with a dose-error reduction system that included a pre-defined drug library in which dosage limits were set for each medication. Monitoring for potential failures and errors occurred for three months postimplementation of FMEA. Specific measures were used to determine the success of the actions that were implemented as a result of the FMEA. The FMEA process at the hospital identified key failure modes in the medication process with the use of the old and new pumps, and actions were taken to avoid errors and adverse events. I.V. pump software and hardware design changes were also recommended. Thirteen of the 18 failure modes reported in practice after pump implementation had been identified by the team. A beneficial outcome of FMEA was the development of a multidisciplinary team that provided the infrastructure for safe technology implementation and effective event investigation after implementation. With the continual updating of i.v. pump software and hardware after implementation, FMEA can be an important starting place for safe technology choice and implementation and can produce site experts to follow technology and process changes over time. FMEA was useful in identifying potential problems in the medication-use process with the implementation of new smart i.v. pumps. Monitoring for system failures and errors after implementation remains necessary.

  14. Dark matter: a problem in relativistic metrology?

    NASA Astrophysics Data System (ADS)

    Lusanna, Luca

    2017-05-01

    Besides the tidal degrees of freedom of Einstein general relativity (GR) (namely the two polarizations of gravitational waves after linearization of the theory) there are the inertial gauge ones connected with the freedom in the choice of the 4-coordinates of the space-time, i.e. in the choice of the notions of time and 3-space (the 3+1 splitting of space-time) and in their use to define a non-inertial frame (the inertial ones being forbidden by the equivalence principle) by means of a set of conventions for the relativistic metrology of the space-time (like the GPS ones near the Earth). The canonical York basis of canonical ADM gravity allows us to identify the Hamiltonian inertial gauge variables in globally hyperbolic asymptotically Minkowskian space-times without super-translations and to define the family of non-harmonic Schwinger time gauges. In these 3+1 splittings of space-time the freedom in the choice of time (the problem of clock synchronization) is described by the inertial gauge variable York time (the trace of the extrinsic curvature of the instantaneous 3-spaces). This inertial gauge freedom and the non-Euclidean nature of the instantaneous 3-spaces required by the equivalence principle need to be incorporated as metrical conventions in a relativistic suitable extension of the existing (essentially Galilean) ICRS celestial reference system. In this paper I make a short review of the existing possibilities to explain the presence of dark matter (or at least of part of it) as a relativistic inertial effect induced by the non- Euclidean nature of the 3-spaces. After a Hamiltonian Post-Minkowskian (HPM) linearization of canonical ADM tetrad gravity with particles, having equal inertial and gravitational masses, as matter, followed by a Post-Newtonian (PN) expansion, we find that the Newtonian equality of inertial and gravitational masses breaks down and that the inertial gauge York time produces an increment of the inertial masses explaining at least

  15. Kirkwood-Buff Approach Rescues Overcollapse of a Disordered Protein in Canonical Protein Force Fields.

    PubMed

    Mercadante, Davide; Milles, Sigrid; Fuertes, Gustavo; Svergun, Dmitri I; Lemke, Edward A; Gräter, Frauke

    2015-06-25

    Understanding the function of intrinsically disordered proteins is intimately related to our capacity to correctly sample their conformational dynamics. So far, a gap between experimentally and computationally derived ensembles exists, as simulations show overcompacted conformers. Increasing evidence suggests that the solvent plays a crucial role in shaping the ensembles of intrinsically disordered proteins and has led to several attempts to modify water parameters and thereby favor protein-water over protein-protein interactions. This study tackles the problem from a different perspective, which is the use of the Kirkwood-Buff theory of solutions to reproduce the correct conformational ensemble of intrinsically disordered proteins (IDPs). A protein force field recently developed on such a basis was found to be highly effective in reproducing ensembles for a fragment from the FG-rich nucleoporin 153, with dimensions matching experimental values obtained from small-angle X-ray scattering and single molecule FRET experiments. Kirkwood-Buff theory presents a complementary and fundamentally different approach to the recently developed four-site TIP4P-D water model, both of which can rescue the overcollapse observed in IDPs with canonical protein force fields. As such, our study provides a new route for tackling the deficiencies of current protein force fields in describing protein solvation.

  16. Induction of CXC chemokines in human mesenchymal stem cells by stimulation with secreted frizzled-related proteins through non-canonical Wnt signaling.

    PubMed

    Bischoff, David S; Zhu, Jian-Hua; Makhijani, Nalini S; Yamaguchi, Dean T

    2015-12-26

    To investigate the effect of secreted frizzled-related proteins (sFRPs) on CXC chemokine expression in human mesenchymal stem cells (hMSCs). CXC chemokines such as CXCL5 and CXCL8 are induced in hMSCs during differentiation with osteogenic differentiation medium (OGM) and may be involved in angiogenic stimulation during bone repair. hMSCs were treated with conditioned medium (CM) from L-cells expressing non-canonical Wnt5a protein, or with control CM from wild type L-cells, or directly with sFRPs for up to 10 d in culture. mRNA expression levels of both CXCL5 and CXCL8 were quantitated by real-time reverse transcriptase-polymerase chain reaction and secreted protein levels of these proteins determined by ELISA. Dose- (0-500 ng/mL) and time-response curves were generated for treatment with sFRP1. Signal transduction pathways were explored by western blot analysis with pan- or phosphorylation-specific antibodies, through use of specific pathway inhibitors, and through use of siRNAs targeting specific frizzled receptors (Fzd)-2 and 5 or the receptor tyrosine kinase-like orphan receptor-2 (RoR2) prior to treatment with sFRPs. CM from L-cells expressing Wnt5a, a non-canonical Wnt, stimulated an increase in CXCL5 mRNA expression and protein secretion in comparison to control L-cell CM. sFRP1, which should inhibit both canonical and non-canonical Wnt signaling, surprisingly enhanced the expression of CXCL5 at 7 and 10 d. Dickkopf1, an inhibitor of canonical Wnt signaling prevented the sFRP-stimulated induction of CXCL5 and actually inhibited basal levels of CXCL5 expression at 7 but not at 10 d post treatment. In addition, all four sFRPs isoforms induced CXCL8 expression in a dose- and time-dependent manner with maximum expression at 7 d with treatment at 150 ng/mL. The largest increases in CXCL5 expression were seen from stimulation with sFRP1 or sFRP2. Analysis of mitogen-activated protein kinase signaling pathways in the presence of OGM showed sFRP1-induced

  17. Induction of CXC chemokines in human mesenchymal stem cells by stimulation with secreted frizzled-related proteins through non-canonical Wnt signaling

    PubMed Central

    Bischoff, David S; Zhu, Jian-Hua; Makhijani, Nalini S; Yamaguchi, Dean T

    2015-01-01

    AIM: To investigate the effect of secreted frizzled-related proteins (sFRPs) on CXC chemokine expression in human mesenchymal stem cells (hMSCs). METHODS: CXC chemokines such as CXCL5 and CXCL8 are induced in hMSCs during differentiation with osteogenic differentiation medium (OGM) and may be involved in angiogenic stimulation during bone repair. hMSCs were treated with conditioned medium (CM) from L-cells expressing non-canonical Wnt5a protein, or with control CM from wild type L-cells, or directly with sFRPs for up to 10 d in culture. mRNA expression levels of both CXCL5 and CXCL8 were quantitated by real-time reverse transcriptase-polymerase chain reaction and secreted protein levels of these proteins determined by ELISA. Dose- (0-500 ng/mL) and time-response curves were generated for treatment with sFRP1. Signal transduction pathways were explored by western blot analysis with pan- or phosphorylation-specific antibodies, through use of specific pathway inhibitors, and through use of siRNAs targeting specific frizzled receptors (Fzd)-2 and 5 or the receptor tyrosine kinase-like orphan receptor-2 (RoR2) prior to treatment with sFRPs. RESULTS: CM from L-cells expressing Wnt5a, a non-canonical Wnt, stimulated an increase in CXCL5 mRNA expression and protein secretion in comparison to control L-cell CM. sFRP1, which should inhibit both canonical and non-canonical Wnt signaling, surprisingly enhanced the expression of CXCL5 at 7 and 10 d. Dickkopf1, an inhibitor of canonical Wnt signaling prevented the sFRP-stimulated induction of CXCL5 and actually inhibited basal levels of CXCL5 expression at 7 but not at 10 d post treatment. In addition, all four sFRPs isoforms induced CXCL8 expression in a dose- and time-dependent manner with maximum expression at 7 d with treatment at 150 ng/mL. The largest increases in CXCL5 expression were seen from stimulation with sFRP1 or sFRP2. Analysis of mitogen-activated protein kinase signaling pathways in the presence of OGM showed s

  18. Non-canonical Phototransduction Mediates Synchronization of the Drosophila melanogaster Circadian Clock and Retinal Light Responses.

    PubMed

    Ogueta, Maite; Hardie, Roger C; Stanewsky, Ralf

    2018-06-04

    The daily light-dark cycles represent a key signal for synchronizing circadian clocks. Both insects and mammals possess dedicated "circadian" photoreceptors but also utilize the visual system for clock resetting. In Drosophila, circadian clock resetting is achieved by the blue-light photoreceptor cryptochrome (CRY), which is expressed within subsets of the brain clock neurons. In addition, rhodopsin-expressing photoreceptor cells contribute to light synchronization. Light resets the molecular clock by CRY-dependent degradation of the clock protein Timeless (TIM), although in specific subsets of key circadian pacemaker neurons, including the small ventral lateral neurons (s-LNvs), TIM and Period (PER) oscillations can be synchronized by light independent of CRY and canonical visual Rhodopsin phototransduction. Here, we show that at least three of the seven Drosophila rhodopsins can utilize an alternative transduction mechanism involving the same α-subunit of the heterotrimeric G protein operating in canonical visual phototransduction (Gq). Surprisingly, in mutants lacking the canonical phospholipase C-β (PLC-β) encoded by the no receptor potential A (norpA) gene, we uncovered a novel transduction pathway using a different PLC-β encoded by the Plc21C gene. This novel pathway is important for behavioral clock resetting to semi-natural light-dark cycles and mediates light-dependent molecular synchronization within the s-LNv clock neurons. The same pathway appears to be responsible for norpA-independent light responses in the compound eye. We show that Rhodopsin 5 (Rh5) and Rh6, present in the R8 subset of retinal photoreceptor cells, drive both the long-term circadian and rapid light responses in the eye. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  19. Persisting behavior problems in extremely low birth weight adolescents.

    PubMed

    Taylor, H Gerry; Margevicius, Seunghee; Schluchter, Mark; Andreias, Laura; Hack, Maureen

    2015-04-01

    To describe behavior problems in extremely low birth weight (ELBW, <1000 g) adolescents born 1992 through 1995 based on parent ratings and adolescent self-ratings at age 14 years and to examine changes in parent ratings from ages 8-14. Parent ratings of behavior problems and adolescent self-ratings were obtained for 169 ELBW adolescents (mean birth weight 815 g, gestational age 26 wk) and 115 normal birth weight (NBW) controls at 14 years. Parent ratings of behavior at age 8 years were also available. Behavior outcomes were assessed using symptom severity scores and rates of scores above DSM-IV symptom cutoffs for clinical disorder. The ELBW group had higher symptom severity scores on parent ratings at age 14 years than NBW controls for inattentive attention-deficit hyperactivity disorder (ADHD), anxiety, and social problems (all p's < .01). Rates of parent ratings meeting DSM-IV symptom criteria for inattentive ADHD were also higher for the ELBW group (12% vs. 1%, p < .01). In contrast, the ELBW group had lower symptom severity scores on self-ratings than controls for several scales. Group differences in parent ratings decreased over time for ADHD, especially among females, but were stable for anxiety and social problems. Extremely low birth weight adolescents continue to have behavior problems similar to those evident at a younger age, but these problems are not evident in behavioral self-ratings. The findings suggest that parent ratings provide contrasting perspectives on behavior problems in ELBW youth and support the need to identify and treat these problems early in childhood.

  20. Disruption of the non-canonical Wnt gene PRICKLE2 leads to autism-like behaviors with evidence for hippocampal synaptic dysfunction

    PubMed Central

    Sowers, L. P.; Loo, L.; Wu, Y.; Campbell, E.; Ulrich, J. D.; Wu, S.; Paemka, L.; Wassink, T.; Meyer, K.; Bing, X.; El-Shanti, H.; Usachev, Y. M.; Ueno, N.; Manak, R. J.; Shepherd, A. J.; Ferguson, P. J.; Darbro, B. W.; Richerson, G. B.; Mohapatra, D. P.; Wemmie, J. A.; Bassuk, A. G.

    2014-01-01

    Autism spectrum disorders (ASDs) have been suggested to arise from abnormalities in the canonical and non-canonical Wnt signaling pathways. However, a direct connection between a human variant in a Wnt pathway gene and ASD-relevant brain pathology has not been established. Prickle2 (Pk2) is a post-synaptic non-canonical Wnt signaling protein shown to interact with post synaptic density 95 (PSD-95). Here we show that mice with disruption in Prickle2 display behavioral abnormalities including altered social interaction, learning abnormalities, and behavioral inflexibility. Prickle2 disruption in mouse hippocampal neurons led to reductions in dendrite branching, synapse number, and post-synaptic density size. Consistent with these findings, Prickle2 null neurons show decreased frequency and size of spontaneous miniature synaptic currents. These behavioral and physiological abnormalities in Prickle2 disrupted mice are consistent with ASD-like phenotypes present in other mouse models of ASDs. In 384 individuals with autism, we identified two with distinct, heterozygous, rare, non-synonymous PRICKLE2 variants (p.E8Q and p.V153I) that were shared by their affected siblings and inherited paternally. Unlike wild-type PRICKLE2, the PRICKLE2 variants found in ASD patients exhibit deficits in morphological and electrophysiological assays. These data suggest that these PRICKLE2 variants cause a critical loss of PRICKLE2 function. The data presented here provide new insight into the biological roles of Prickle2, its behavioral importance, and suggest disruptions in non-canonical Wnt genes such as PRICKLE2 may contribute to synaptic abnormalities underlying ASDs. PMID:23711981