Disorder, oscillatory dynamics and state switching: the role of c-Myc

In this paper, using the intrinsically disordered oncoprotein Myc as an example, we present a mathematical model to help explain how protein oscillatory dynamics can influence state switching. Earlier studies have demonstrated that, while Myc overexpression can facilitate state switching and transform a normal cell into a cancer phenotype, its downregulation can reverse state-switching. A fundamental aspect of the model is that a Myc threshold determines cell fate in cells expressing p53. We demonstrate that a non-cooperative positive feedback loop coupled with Myc sequestration at multiple binding sites can generate bistable Myc levels. Normal quiescent cells with Myc levels below the threshold can respond to mitogenic signals to activate the cyclin/cdk oscillator for limited cell divisions but the p53/Mdm2 oscillator remains nonfunctional. In response to stress, the p53/Mdm2 oscillator is activated in pulses that are critical to DNA repair. But if stress causes Myc levels to cross the threshold, Myc inactivates the p53/Mdm2 oscillator, abrogates p53 pulses, and pushes the cyclin/cdk oscillator into overdrive sustaining unchecked proliferation seen in cancer. However, if Myc is downregulated, the cyclin/cdk oscillator is inactivated and the p53/Mdm2 oscillator is reset and the cancer phenotype is reversed. (C) 2015 Elsevier Ltd. All rights reserved.

Stress state in front of a crack perpendicular to bimaterial interface

Using a dislocation simulation approach, the basic equation for a crack perpendicular to a bimaterial interface is formulated in this paper. A novel expansion method is proposed for solving the problem. The complete solution for the problem, including the T stress ahead of the crack tip and the stress intensity factors are presented. The stress field characteristics are analyzed in detail. It is found that ahead of the crack tip and near the interface the normal stress, perpendicular to the crack plane, sigma(x), is characterized by the K fields and the normal stress sigma(y) is dominated by the K field plus T stress in the region of 0 < r/b < 0.4 for b/a(0) less than or equal to 0.1, where b is the distance from the crack tip to the interface.

Steady-state crack growth and fracture work based on the theory of mechanism-based strain gradient plasticity

Mode I steady-state crack growth is analyzed under plane strain conditions in small scale yielding. The elastic-plastic solid is characterized by the mechanism-based strain gradient (MSG) plasticity theory [J. Mech. Phys. Solids 47 (1999) 1239, J. Mech. Phys. Solids 48 (2000) 99]. The distributions of the normal separation stress and the effective stress along the plane ahead of the crack tip are computed using a special finite element method based on the steady-state fundamental relations and the MSG flow theory. The results show that during the steady-state crack growth, the normal separation stress on the plane ahead of the crack tip can achieve considerably high value within the MSG strain gradient sensitive zone. The results also show that the crack tip fields are insensitive to the cell size parameter in the MSG theory. Moreover, in the present research, the steady-state fracture toughness is computed by adopting the embedded process zone (EPZ) model. The results display that the steady-state fracture toughness strongly depends on the separation strength parameter of the EPZ model and the length scale parameter in the MSG theory. Furthermore, in order for the results of steady crack growth to be comparable, an approximate relation between the length scale parameters in the MSG theory and in the Fleck-Hutchinson strain gradient plasticity theory is obtained.

The Oxidative State of Chylomicron Remnants Influences Their Modulation of Human Monocyte Activation

8 p.

Asymptotic analysis of thin plates under normal load and horizontal edge thrust

We consider the radially symmetric nonlinear von Kármán plate equations for circular or annular plates in the limit of small thickness. The loads on the plate consist of a radially symmetric pressure load and a uniform edge load. The dependence of the steady states on the edge load and thickness is studied using asymptotics as well as numerical calculations. The von Kármán plate equations are a singular perturbation of the Fӧppl membrane equation in the asymptotic limit of small thickness. We study the role of compressive membrane solutions in the small thickness asymptotic behavior of the plate solutions.

We give evidence for the existence of a singular compressive solution for the circular membrane and show by a singular perturbation expansion that the nonsingular compressive solution approach this singular solution as the radial stress at the center of the plate vanishes. In this limit, an infinite number of folds occur with respect to the edge load. Similar behavior is observed for the annular membrane with zero edge load at the inner radius in the limit as the circumferential stress vanishes.

We develop multiscale expansions, which are asymptotic to members of this family for plates with edges that are elastically supported against rotation. At some thicknesses this approximation breaks down and a boundary layer appears at the center of the plate. In the limit of small normal load, the points of breakdown approach the bifurcation points corresponding to buckling of the nondeflected state. A uniform asymptotic expansion for small thickness combining the boundary layer with a multiscale approximation of the outer solution is developed for this case. These approximations complement the well known boundary layer expansions based on tensile membrane solutions in describing the bending and stretching of thin plates. The approximation becomes inconsistent as the clamped state is approached by increasing the resistance against rotation at the edge. We prove that such an expansion for the clamped circular plate cannot exist unless the pressure load is self-equilibrating.

High pressure states in condensed matter: I. High pressure behavior of the iron-sulphur system with applications to the earth's core. II. Empirical equation of state for organic compounds at high pressures

Part I:

The earth's core is generally accepted to be composed primarily of iron, with an admixture of other elements. Because the outer core is observed not to transmit shear waves at seismic frequencies, it is known to be liquid or primarily liquid. A new equation of state is presented for liquid iron, in the form of parameters for the 4th order Birch-Murnaghan and Mie-Grüneisen equations of state. The parameters were constrained by a set of values for numerous properties compiled from the literature. A detailed theoretical model is used to constrain the P-T behavior of the heat capacity, based on recent advances in the understanding of the interatomic potentials for transition metals. At the reference pressure of 10⁵ Pa and temperature of 1811 K (the normal melting point of Fe), the parameters are: ρ = 7037 kg/m³, K_S0 = 110 GPa, K_S' = 4.53, K_S" = -.0337 GPa-1, and γ = 2.8, with γ α ρ^-1.17. Comparison of the properties predicted by this model with the earth model PREM indicates that the outer core is 8 to 10 % less dense than pure liquid Fe at the same conditions. The inner core is also found to be 3 to 5% less dense than pure liquid Fe, supporting the idea of a partially molten inner core. The density deficit of the outer core implies that the elements dissolved in the liquid Fe are predominantly of lower atomic weight than Fe. Of the candidate light elements favored by researchers, only sulfur readily dissolves into Fe at low pressure, which means that this element was almost certainly concentrated in the core at early times. New melting data are presented for FeS and FeS₂ which indicate that the FeS₂ is the S-hearing liquidus solid phase at inner core pressures. Consideration of the requirement that the inner core boundary be observable by seismological means and the freezing behavior of solutions leads to the possibility that the outer core may contain a significant fraction of solid material. It is found that convection in the outer core is not hindered if the solid particles are entrained in the fluid flow. This model for a core of Fe and S admits temperatures in the range 3450K to 4200K at the top of the core. An all liquid Fe-S outer core would require a temperature of about 4900 K at the top of the core.

Part II.

The abundance of uses for organic compounds in the modern world results in many applications in which these materials are subjected to high pressures. This leads to the desire to be able to describe the behavior of these materials under such conditions. Unfortunately, the number of compounds is much greater than the number of experimental data available for many of the important properties. In the past, one approach that has worked well is the calculation of appropriate properties by summing the contributions from the organic functional groups making up molecules of the compounds in question. A new set of group contributions for the molar volume, volume thermal expansivity, heat capacity, and the Rao function is presented for functional groups containing C, H, and O. This set is, in most cases, limited in application to low molecular liquids. A new technique for the calculation of the pressure derivative of the bulk modulus is also presented. Comparison with data indicates that the presented technique works very well for most low molecular hydrocarbon liquids and somewhat less well for oxygen-bearing compounds. A similar comparison of previous results for polymers indicates that the existing tabulations of group contributions for this class of materials is in need of revision. There is also evidence that the Rao function contributions for polymers and low molecular compounds are somewhat different.

Conhecimentos pedagógicos como orientação para a "missão docente": a formação na Escola Normal de Niterói na Primeira República (1893-1915)

A dissertação analisa a política de formação docente oferecida pela Escola Normal de Niterói entre 1893 e 1915. O projeto de institucionalização da escolarização de professores representou momento de transformações significativas na profissão, então associada aos ideais de progresso e modernidade republicanos, com destaque para a circulação e apropriação de teorias pedagógicas. Buscou-se conhecer o lugar de tais teorias e dos saberes na formação institucional de professores, visando compreender, em que medida, as representações sobre a missão docente se fez presente nos discursos dos Presidentes de Estado no período. Com esse objetivo, analisamos as reformas de ensino e as frequentes inserções e retiradas de disciplinas escolares, em meio aos intensos debates na esfera governamental sobre o que ensinar ao povo e aos professores. Almejava-se um saber que fosse capaz de ampliar a visão do cidadão brasileiro, modificar seus hábitos e inseri-lo na modernidade, aspectos que condiziam com a construção de um espírito republicano. Para compreender o funcionamento e a contribuição dessa escola para a história da educação fluminense, analisamos a legislação educacional, os programas e as disciplinas, e também alguns exames de admissão e finais dos alunos. Foram utilizadas as mensagens dos presidentes do Estado (1892 a 1918), as leis que reformaram ou regulamentaram a instrução pública (1893, 1895, 1900, 1912 e 1915), em particular a Escola Normal de Niterói, os exames de admissão (1901 a 1908), os exames finais dos alunos (1897 a 1911) e um diário de Geografia (1915). Tais documentos foram analisados à luz de extensa historiografia sobre a formação docente e permitiram conhecer práticas escolares da instituição. As leis que modificaram os programas tentaram imprimir um caráter mais científico ao curso e muito se discutiu sobre a questão prática. Para tanto, as disciplinas tencionavam articular a teoria à experiência corroborando a aptidão do professor. A aprendizagem era verificada por meio de exames finais, que sucediam as sabatinas e as provas. Examinar era um dispositivo de poder que comparava e excluía e não apenas mensurava o conhecimento. Investigar a formação de professores nos levou a olhar as articulações históricas e as relações de forças que a constituíram. A pesquisa documental sugere a necessidade de ampliarmos a visão sobre a formação docente na Primeira República, tendo em vista que houve esforços em se organizar a instrução pública, sobretudo, no que concerne à Escola Normal de Niterói.

A Escola Normal de Juiz de Fora: crises e permanências (1881-1911)

A motivação apresentada nesta dissertação alimentou-se pela instabilidade evidenciada no processo de criação e na tentativa de consolidação da Escola Normal de Juiz de Fora. Sendo alvo de constantes críticas e debates, o papel da escola normal, assim como sua permanência, motivou propostas, reformas e manifestações, que envolveram não só o poder político, mas também a sociedade. Tais apontamentos foram observados tanto em periódicos da cidade, como o Jornal do Commercio e o Correio de Minas, quanto em documentos encontrados no Arquivo Público Mineiro, como relatórios de inspetores e correspondências de professores.Algumas das publicações presentes nesses periódicos expressaram e, de certa forma, mobilizaram a população a tomar atitudes contra a supressão da mesma, através de abaixo-assinados e representações enviadas ao governo do estado, muitas vezes enaltecendo não só a escola normal, mas principalmente a cidade de Juiz de Fora, considerada a principal da Zona da Mata mineira. Assim, foram mapeadas as discussões sobre a instituição, levantando questões sobre o posicionamento dos diferentes atores sociais acerca da instituição que, mesmo após sua supressão, não deixou de ser alvo de debates. Ainda, teceu-se algumas reflexões acerca da Reforma do Ensino Primário e Normal de João Pinheiro (1906), no que se refere ao ensino normal, mais especificamente no contexto juizforano. Para tanto, foram abordadas questões sobre a preferência da mulher para o magistério,o papel do professor e os institutos equiparados à Escola Normal Modelo de Belo Horizonte. Esse estudo concluiu que as determinações políticas não são produzidas apenas pelos discursos e decisões dos governantes, mas também são influenciáveis e podem ser modificadas por pressões de outros grupos sociais. Tais grupos sociais são formados por indivíduos com ideias e objetivos semelhantes, fazendo parte de um lugar e de uma posição social que os permitam circular e se manifestar em espaços que atinjam proporções significativas, como é o caso da imprensa.

Normal-incident SiGe/Si MQWs photodetectors operating at 1.3 mu m

A normal-incident SiGe/Si multiple quantum wells (MQWs) photodetector was reported. The structure and fabrication process of the photodetector were introduced. The photocurrent spectra measurement showed that the response spectra was expanded to 1.3 mu m wavelength. The quantum efficiency of the photodetector was 0.1% at 1.3 mu m and 20% at 0.95 mu m.

Low-lying non-normal parity states in B-8 measured by proton elastic scattering on Be-7

A new measurement of proton resonance scattering on Be-7 was performed tip to the center-of-mass energy of 6.7 MeV using the low-energy RI beam facility CRIB (CNS Radioactive Ion Beam separator) at the Center for Nuclear Study of the University of Tokyo. The excitation function of Be-7 + p elastic scattering above 3.5 MeV was measured Successfully for the first time, providing important information about the resonance structure of the B-8 nucleus. The resonances are related to the reaction rate of Be-7(p.gamma)B-8. which is the key reaction in solar B-8 neutrino production. Evidence for the presence of two negative parity states is presented. One of them is a 2(-) state observed as a broad s-wave resonance, the existence of which had been questionable. Its possible effects on the determination of the astrophysical S-factor of Be-7(p.gamma)B-8 at solar energy are discussed. The other state had not been observed in previous measurements, and its spin and parity were determined as 1(-). (C) 2009 Elsevier B.V. All rights reserved.

Hot Nuclear Matter Equation of State and Finite Temperature Kaon Condensation

We perform a systematic calculation of the equation of state of asymmetric nuclear matter at finite temperature within the framework of the Brueckner-Hartree-Fock approach with a microscopic three-body force. When applying it to the study of hotka on condensed matter, we find that the thermal effect is more profound in comparison with normal matter, in particular around the threshold density. Also, the increase of temperature makes the equation of state slightly stiffer through suppression of kaon condensation.

Electron impact excitation of xenon from the metastable state to the excited states

The electron impact excitation cross sections from the lowest metastable state 5p(5)6sJ = 2 to the six lowest excited states of the 5p(5)6p configuration of xenon are calculated systematically by using the fully relativistic distorted wave method. In order to discuss the effects of target state descriptions on the electron impact excitation cross sections, two correlation models are used to describe the target states based on the multiconfiguration Dirac-Fock (MCDF) method. It is found that the correlation effects play a very important role in low energy impact. For high energy impact, however, the cross sections are not sensitive to the description of the target states, but many more partial waves must be included.

a state-adaptive access control model for web-based idrs system

Huazhong Univ Sci & Technol, Natl Tech Univ Ukraine, Huazhong Normal Univ, Harbin Inst Technol, IEEE Ukraine Sect, I& M/CI Joint Chapter

Adaptive Mixture Modelling Metropolis Methods for Bayesian Analysis of Non-linear State-Space Models.

We describe a strategy for Markov chain Monte Carlo analysis of non-linear, non-Gaussian state-space models involving batch analysis for inference on dynamic, latent state variables and fixed model parameters. The key innovation is a Metropolis-Hastings method for the time series of state variables based on sequential approximation of filtering and smoothing densities using normal mixtures. These mixtures are propagated through the non-linearities using an accurate, local mixture approximation method, and we use a regenerating procedure to deal with potential degeneracy of mixture components. This provides accurate, direct approximations to sequential filtering and retrospective smoothing distributions, and hence a useful construction of global Metropolis proposal distributions for simulation of posteriors for the set of states. This analysis is embedded within a Gibbs sampler to include uncertain fixed parameters. We give an example motivated by an application in systems biology. Supplemental materials provide an example based on a stochastic volatility model as well as MATLAB code.

In vivo inhibition of elevated myocardial beta-adrenergic receptor kinase activity in hybrid transgenic mice restores normal beta-adrenergic signaling and function.

BACKGROUND: The clinical syndrome of heart failure (HF) is characterized by an impaired cardiac beta-adrenergic receptor (betaAR) system, which is critical in the regulation of myocardial function. Expression of the betaAR kinase (betaARK1), which phosphorylates and uncouples betaARs, is elevated in human HF; this likely contributes to the abnormal betaAR responsiveness that occurs with beta-agonist administration. We previously showed that transgenic mice with increased myocardial betaARK1 expression had impaired cardiac function in vivo and that inhibiting endogenous betaARK1 activity in the heart led to enhanced myocardial function. METHODS AND RESULTS: We created hybrid transgenic mice with cardiac-specific concomitant overexpression of both betaARK1 and an inhibitor of betaARK1 activity to study the feasibility and functional consequences of the inhibition of elevated betaARK1 activity similar to that present in human HF. Transgenic mice with myocardial overexpression of betaARK1 (3 to 5-fold) have a blunted in vivo contractile response to isoproterenol when compared with non-transgenic control mice. In the hybrid transgenic mice, although myocardial betaARK1 levels remained elevated due to transgene expression, in vitro betaARK1 activity returned to control levels and the percentage of betaARs in the high-affinity state increased to normal wild-type levels. Furthermore, the in vivo left ventricular contractile response to betaAR stimulation was restored to normal in the hybrid double-transgenic mice. CONCLUSIONS: Novel hybrid transgenic mice can be created with concomitant cardiac-specific overexpression of 2 independent transgenes with opposing actions. Elevated myocardial betaARK1 in transgenic mouse hearts (to levels seen in human HF) can be inhibited in vivo by a peptide that can prevent agonist-stimulated desensitization of cardiac betaARs. This may represent a novel strategy to improve myocardial function in the setting of compromised heart function.