Phosphoinositide 3-kinase induces scattering and tubulogenesis in epithelial cells through a novel pathway

Hepatocyte growth factor/scatter factor (HGF/SF) treatment of the Madin-Darby canine kidney epithelial cell line causes scattering of cells grown in monolayer culture and the formation of branching tubules by cells grown in collagen gels. HGF/SF causes prolonged activation of both the mitogen-activated protein (MAP) kinase extracellular signal-regulated kinase 2 (ERK2) and the phosphoinositide 3-OH kinase (PI 3-kinase) target protein kinase B (PKB)/Akt; inhibition of either the MAP kinase pathway by the MAP kinase/ERK kinase inhibitor PD98059 or the PI 3-kinase pathway by LY294002 blocks HGF/SF induction of scattering, although in morphologically distinct ways. Expression of constitutively activated PI 3-kinase, Ras, or R-Ras will cause scattering, but activated Raf will not, indicating that activation of the MAP kinase pathway is not sufficient for this response. Downstream of PI 3-kinase, activated PKB/Akt and Rac are both unable to induce scattering, implicating a novel pathway. Scattering induced by Ras or PI 3-kinase is sensitive to PD98059, as well as to LY294002, suggesting that basal MAP kinase activity is required, but not sufficient, for the scattering response. Induction of MDCK cell tubulogenesis in collagen gels by HGF/SF is inhibited by PD98059; expression of activated Ras and Raf causes disorganized growth in this system, but activated PI 3-kinase or R-Ras causes branching tubule formation similar to that seen with HGF/SF treatment. These data indicate that multiple signaling pathways acting downstream of Met and Ras are needed for these morphological effects; scattering is induced primarily by the PI 3-kinase pathway, which acts through effectors other than PKB/Akt or Rac and requires at least basal MAP kinase function. Elevated PI 3-kinase activity induces tubulogenesis, but total inhibition and excess activation of the MAP kinase pathway both oppose this effect.     

Influence of Implicit Integration Scheme on Prediction of Shear Band Formation

Implicit integration schemes for elastoplastic constitutive equations have been developed in recent years as an alternative to explicit schemes. The consistent tangent constitutive matrix Dcon that results from implicit schemes makes the global stiffness matrix consistent with the implicit integration procedure and differs from the traditional continuum tangent constitutive matrix Dep that results from explicit schemes. Onset of strain localization and shear banding has been traditionally predicted using the continuum tangent constitutive matrix. It is shown that different criteria for onset of shear-band formation are obtained depending on whether Dcon or Dep is used. It is shown that shear band prediction using Dcon is step-size dependent, and that the use of Dcon influences the predicted onset of strain localization in frictional materials. An analytical equation for prediction of the onset of shear-band formation using Dcon for the Mohr–Coulomb model is developed, and a numerical example is presented.     

Effect of dissolved tungsten on the deformation of 70Ni-30Fe alloys

A series of Ni-Fe alloys containing various levels of tungsten in solid solution have been prepared as a means to assess the influence of solid solution strengthening on the mechanical behavior of monolithic 70Ni-30Fe. In particular, 70Ni-30Fe alloys plus equilibrium concentrations of tungsten in solid solution nominally correspond to the compositions associated with the matrix-only portion of certain tungsten heavy alloys, that is, alloys comprised of a high volume fraction of nominally pure tungsten particles embedded within a minority Ni-Fe-W based matrix. The study shows that the working solubility of tungsten within the 70Ni-30Fe base composition increases slightly with temperature, from approximately 21 wt pct at room temperature to approximately 23 wt pct at 1400 °C. Increasing the level of tungsten in solid solution leads to increases in room-temperature yield strength, tensile strength, and ductility. In contrast, the deformation characteristics of the alloys, as quantified by the power-law work-hardening exponent, n, and the strain-rate-sensitivity exponent, m, show little variation with tungsten solute concentration.     

An analysis of the transition proportion for binarization in handwritten historical documents

In this paper, we will present a mathematical analysis of the transition proportion for the normal threshold (NorT) based on the transition method. The transition proportion is a parameter of NorT which plays an important role in the theoretical development of NorT. We will study the mathematical forms of the quadratic equation from which NorT is computed. Through this analysis, we will describe how the transition proportion affects NorT. Then, we will prove that NorT is robust to inaccurate estimations of the transition proportion. Furthermore, our analysis extends to thresholding methods that rely on Bayes rule, and it also gives the mathematical bases for potential applications of the transition proportion as a feature to estimate stroke width and detect regions of interest. In the majority of our experiments, we used a database composed of small images that were extracted from DIBCO 2009 and H-DIBCO 2010 benchmarks. However, we also report evaluations using the original (H-)DIBCO?s benchmarks.     

An optimization algorithm inspired by the States of Matter that improves the balance between exploration and exploitation

The ability of an Evolutionary Algorithm (EA) to find a global optimal solution depends on its capacity to find a good rate between exploitation of found-so-far elements and exploration of the search space. Inspired by natural phenomena, researchers have developed many successful evolutionary algorithms which, at original versions, define operators that mimic the way nature solves complex problems, with no actual consideration of the exploration-exploitation balance. In this paper, a novel nature-inspired algorithm called the States of Matter Search (SMS) is introduced. The SMS algorithm is based on the simulation of the states of matter phenomenon. In SMS, individuals emulate molecules which interact to each other by using evolutionary operations which are based on the physical principles of the thermal-energy motion mechanism. The algorithm is devised by considering each state of matter at one different exploration–exploitation ratio. The evolutionary process is divided into three phases which emulate the three states of matter: gas, liquid and solid. In each state, molecules (individuals) exhibit different movement capacities. Beginning from the gas state (pure exploration), the algorithm modifies the intensities of exploration and exploitation until the solid state (pure exploitation) is reached. As a result, the approach can substantially improve the balance between exploration–exploitation, yet preserving the good search capabilities of an evolutionary approach. To illustrate the proficiency and robustness of the proposed algorithm, it is compared to other well-known evolutionary methods including novel variants that incorporate diversity preservation schemes. The comparison examines several standard benchmark functions which are commonly considered within the EA field. Experimental results show that the proposed method achieves a good performance in comparison to its counterparts as a consequence of its better exploration–exploitation balance.     

Natural gas and CO2 price variation: impact on the relative cost-efficiency of LNG and pipelines

This article develops a formal model for comparing the cost structure of the two main transport options for natural gas: liquefied natural gas (LNG) and pipelines. In particular, it evaluates how variations in the prices of natural gas and greenhouse gas emissions affect the relative cost-efficiency of these two options. Natural gas is often promoted as the most environmentally friendly of all fossil fuels, and LNG as a modern and efficient way of transporting it. Some research has been carried out into the local environmental impact of LNG facilities, but almost none into aspects related to climate change. This paper concludes that at current price levels for natural gas and CO₂ emissions the distance from field to consumer and the volume of natural gas transported are the main determinants of transport costs. The pricing of natural gas and greenhouse emissions influence the relative cost-efficiency of LNG and pipeline transport, but only to a limited degree at current price levels. Because more energy is required for the LNG process (especially for fuelling the liquefaction process) than for pipelines at distances below 9100 km, LNG is more exposed to variability in the price of natural gas and greenhouse gas emissions up to this distance. If the prices of natural gas and/or greenhouse gas emission rise dramatically in the future, this will affect the choice between pipelines and LNG. Such a price increase will be favourable for pipelines relative to LNG.     

Anisotropy-Based Failure Criterion for Interphase Systems

This paper presents a methodology for estimating the shear strength of interphase systems composed of granular materials and planar inclusions having various degrees of roughness. Existing empirical and semiempirical relationships between strength and surface roughness do not appear to be general and are unable to account for surface-particle interactions at the appropriate scales. The proposed method is based on the contact force anisotropy of those particles that touch the inclusion surface. It was developed using two-dimensional discrete element method simulations of interphase systems constructed within a direct interface shear test device. Particles consist of polydisperse and monodisperse spheres of constant median grain diameter. Surface roughness was varied by using profiles with regular and random asperities, and profiles of manufactured surfaces. Results indicate that the magnitude and direction of average contact total force at the interface controls strength. A bilinear relationship, independent of particle to surface friction coefficient, exists between the principal direction of contact total force anisotropy and strength. Results using the proposed criterion are in good agreement with laboratory results using spheres and subrounded sand.