Functional regulation of the Neurofibromatosis 2 tumor suppressor merlin

Neurofibromatosis 2 (NF2) is an autosomal dominant disorder manifested by the formation of multiple benign tumors of the nervous system. Affected individuals typically develop bilateral vestibular schwannomas which lead to deafness and balance disorders. The syndrome is caused by inactivation of the NF2 tumor suppressor gene, and mutation or loss of the NF2 product, merlin, is sufficient for tumorigenesis in both hereditary and sporadic NF2-associated tumors. Merlin belongs to the band 4.1 superfamily of cytoskeletal proteins, which also contain the related ezrin, radixin, and moesin (ERM) proteins. The ERM members provide a link between the cell cytoskeleton and membrane by connecting membrane-associated proteins to actin filaments. By stabilizing complexes in the cell cortex, the ERMs modulate morphology, growth, and migration of cells. Despite their structural homology, overlapping subcellular distribution, direct molecular association, and partial overlap of molecular interactions, merlin and ezrin exert opposite effects on cell proliferation. Merlin suppresses cell proliferation, whereas ezrin expression is linked to oncogenic activity. We hypothesized that the regions which differ between the proteins might explain merlin s specificity as a tumor suppressor. We therefore analyzed the regions, which are most diverse between merlin and ezrin; the N-terminal tail and the C-terminus. To determine the properties of the C-terminal region, we studied the two most predominant merlin isoforms together with truncation variants similar to those found in patients. We also focused on the evolutionally conserved C-terminal residues, E545-E547, that harbor disease causing mutations in its corresponding DNA sequence. In addition to inhibiting cell proliferation, merlin regulates cytoskeletal organization. The morphogenic properties of merlin may play a role in tumor suppression, since patient-derived tumor cells demonstrate cytoskeletal abnormalities. We analyzed the mechanisms of merlin-induced extension formation and determined that the C-terminal region of amino acids 538-568 is particularly important for the morphogenic activity. We also characterized the role of C-terminal merlin residues in the regulation of proliferation, phosphorylation, and intramolecular associations. In contrast to previous reports, we demonstrated that both merlin isoforms are able to suppress cell proliferation, whereas C-terminally mutated merlin constructs showed reduced growth inhibition. Phosphorylation serves as a mechanism to regulate the tumor suppressive activity of merlin. The C-terminal serine 518 is phosphorylated in response to both p21-activated kinase (PAK) and protein kinase A (PKA), which inactivates the growth inhibitory function of merlin. However, at least three differentially phosphorylated forms of the protein exist. In this study we demonstrated that also the N-terminus of merlin is phosphorylated by AGC kinases, and that both PKA and Akt phosphorylate merlin at serine 10 (S10). We evaluated the impact of this N-terminal tail phosphorylation, and showed that the phosphorylation state of S10 is an important regulator of merlin s ability to modulate cytoskeletal organization but also regulates the stability of the protein. In summary, this study describes the functional effect of merlin specific regions. We demonstrate that both S10 in the N-terminal tail and residues E545-E547 in the C-terminus are essential for merlin activity and function.

Kirkkoon kuuluminen Helsingin osa-alueilla

In Helsinki's evangelical lutheran congregations, the share of the people being members of that church compared with all the people living in their specific geographical areas varies from 62,4 per cent in Paavali to 80,7 per cent in Munkkiniemi. The boundaries of the congregations are about to be redrawn to level the differences in the congregations. In this thesis, the reasons of the differences in Helsinki s districts were studied closer. The data consisted of statistical information gathered from the Population Information System of Finland. It included information by age groups about the population register keeper, marital status, native tongue, level of education and gender in the end of 2005. Additional data was gathered from Helsinki Region Statistics web service. It included information about the dwelling, level of income and main activities of the inhabitants in the districts. The main method was stepwise linear regression. Minor methods were crosstabulation and correlation matrixes. The result of the study was a statistical model that explains 72,2 per cent of the variation of the shares in the congregations. The dependent variable was the share of the people being members of evangelical lutheran church in the dirstricts. The independent variables were the share of the people having other than Finnish or Swedish as their native tongue, the share of rented apartments, the shares of apartments including four rooms and a kitchen, the share of detached houses in the districts and the shares of women and people with no income in the districts. The independent variables present in the model depict the amount of foreigners, dwellings, gender and the level of income of the population. The high share of foreigners, people with no income and rented apartments explain the low share of the people being members of evangelical lutheran church. On the contrary, the high share of the people being members of evangelical lutheran church in the district is explained by the large apartments, detached houses and amount of women living there.

Sponge phase transitions from a lattice model

We use Monte Carlo simulations to obtain thermodynamic functions and correlation functions in a lattice model we propose for sponge phases. We demonstrate that the surface-density correlation function dominates the scattering only along the symmetric-sponge (SS) to asymmetric-sponge (AS) phase boundary but not the boundary between the sponge-with-free-edges (SFE) and symmetric-sponge phases. At this second thermodynamic transition the scattering is dominated instead by an edge-density (or seam-density) correlation function. This prediction provides an unambiguous diagnostic for experiments in search of the SS-SFE transition.

Modeling of ternary solubilities of solids in supercritical carbon dioxide in the presence of cosolvents or cosolutes

The investigation of ternary solubilities of solids is essential for the efficient design of extraction processes. The ternary solubilities of solids for cosolvent and cosolute systems are complex functions of temperature, pressure and cosolvent/cosolute composition. The intermolecular interactions between the molecules have a significant role in the solubilities of mixed solids in SCCO2 and cosolvent ternary systems. Two model equations were developed for ternary SCCO2 + cosolvent/cosolute systems by using association and activity coefficient models. Both the model equations consist of five adjustable parameters and correlate the ternary solubilities of solids in terms of temperature, pressure, density and cosolvent/cosolute composition. The model equation for cosolvent systems correlated 43 solid pollutants-cosolvent-SCCO2, while the model equation for cosolute systems correlated 19 solute-cosolute-SCCO2 systems available in literature. The average AARD of the model equations are 4.73% and 4.87% for cosolvent ternary systems and mixed solids in SCCO2, respectively. (C) 2011 Elsevier B.V. All rights reserved.

Prediction of Ground Water Levels in the Uplands of a Tropical Coastal Riparian Wetland using Artificial Neural Networks

Artificial Neural Networks (ANNs) have been found to be a robust tool to model many non-linear hydrological processes. The present study aims at evaluating the performance of ANN in simulating and predicting ground water levels in the uplands of a tropical coastal riparian wetland. The study involves comparison of two network architectures, Feed Forward Neural Network (FFNN) and Recurrent Neural Network (RNN) trained under five algorithms namely Levenberg Marquardt algorithm, Resilient Back propagation algorithm, BFGS Quasi Newton algorithm, Scaled Conjugate Gradient algorithm, and Fletcher Reeves Conjugate Gradient algorithm by simulating the water levels in a well in the study area. The study is analyzed in two cases-one with four inputs to the networks and two with eight inputs to the networks. The two networks-five algorithms in both the cases are compared to determine the best performing combination that could simulate and predict the process satisfactorily. Ad Hoc (Trial and Error) method is followed in optimizing network structure in all cases. On the whole, it is noticed from the results that the Artificial Neural Networks have simulated and predicted the water levels in the well with fair accuracy. This is evident from low values of Normalized Root Mean Square Error and Relative Root Mean Square Error and high values of Nash-Sutcliffe Efficiency Index and Correlation Coefficient (which are taken as the performance measures to calibrate the networks) calculated after the analysis. On comparison of ground water levels predicted with those at the observation well, FFNN trained with Fletcher Reeves Conjugate Gradient algorithm taken four inputs has outperformed all other combinations.

Affinity of a galactose-specific legume lectin from Dolichos lablab to adenine revealed by X-ray cystallography

Crystal structure analysis of a galactose-specific lectin from a leguminous food crop Dolichos lablab (Indian lablab beans) has been carried out to obtain insights into its quaternary association and lectin-carbohydrate interactions. The analysis led to the identification of adenine binding sites at the dimeric interfaces of the heterotetrameric lectin. Structural details of similar adenine binding were reported in only one legume lectin, Dolichos biflorus, before this study. Here, we present the structure of the galactose-binding D. lablab lectin at different pH values in the native form and in complex with galactose and adenine. This first structure report on this lectin also provides a high resolution atomic view of legume lectin-adenine interactions. The tetramer has two canonical and two DB58-like interfaces. The binding of adenine, a non-carbohydrate ligand, is found to occur at four hydrophobic sites at the core of the tetramer at the DB58-like dimeric interfaces and does not interfere with the carbohydrate-binding site. To support the crystallographic observations, the adenine binding was further quantified by carrying out isothermal calorimetric titration. By this method, we not only estimated the affinity of the lectin to adenine but also showed that adenine binds with negative cooperativity in solution.

Reduced graphene oxide induced phase miscibility in polystyrene-poly(vinyl methyl ether) blends

Graphene oxide and reduced graphene oxide (r-GO) were synthesized by wet chemistry and the effect of r-GO in PS-PVME blends was investigated here with respect to phase miscibility, intermolecular cooperativity in the glass transition region and concentration fluctuation variance by shear rheology and dielectric spectroscopy. The spinodal decomposition temperature (T-s) and correlation length were evaluated from isochronal temperature scans in shear rheology. The r-GO is shown to induce miscibility in the blends, which may lead to increased local heterogeneity in the blends, though the length of cooperatively re-arranged regions (xi) at T-g is more or less unaltered. The evolution of the phase morphology as a function of temperature was assessed using polarized optical microscopy (POM). In the case of the 60/40 PS-PVME blends with 0.25 wt% r-GO, apart from significant refinement in the morphology, retention of the interconnected ligaments of PVME was observed, even in the late stages of phase separation suggesting that the coarsening of the phase morphology has been slowed down in the presence of r-GO. This phenomenon was also supported by AFM. Surface enrichment of PVME, owing to its lower surface tension, in the demixed samples was supported by XPS scans. The interconnected network of PVME has resulted in significantly higher permittivity in the bi-phasic blends, although the concentration of r-GO is below the percolation threshold.

Influence of Spatial Variability on Pavement Responses Using Latin Hypercube Sampling on Two-Dimensional Random Fields

Although uncertainties in material properties have been addressed in the design of flexible pavements, most current modeling techniques assume that pavement layers are homogeneous. The paper addresses the influence of the spatial variability of the resilient moduli of pavement layers by evaluating the effect of the variance and correlation length on the pavement responses to loading. The integration of the spatially varying log-normal random field with the finite-difference method has been achieved through an exponential autocorrelation function. The variation in the correlation length was found to have a marginal effect on the mean values of the critical strains and a noticeable effect on the standard deviation which decreases with decreases in correlation length. This reduction in the variance arises because of the spatial averaging phenomenon over the softer and stiffer zones generated because of spatial variability. The increase in the mean value of critical strains with decreasing correlation length, although minor, illustrates that pavement performance is adversely affected by the presence of spatially varying layers. The study also confirmed that the higher the variability in the pavement layer moduli, introduced through a higher value of coefficient of variation (COV), the higher the variability in the pavement response. The study concludes that ignoring spatial variability by modeling the pavement layers as homogeneous that have very short correlation lengths can result in the underestimation of the critical strains and thus an inaccurate assessment of the pavement performance. (C) 2014 American Society of Civil Engineers.

Experimental Study On Liquid Free Surface In Buoyant-Thermocapillary Convection

We investigate the surface deformations of buoyant-thermocapillary convection in a rectangular cavity clue to gravity and temperature gradient between the two sidewalls. The cavity is 52mm x 42mm in horizontal cross section, the thickness of liquid layer h is changed from 2.5mm to 6.5mm. Surface deformations of h = 3.5mm and 6.0mm are discussed and compared. Temperature difference is increased gradually, and the flow in the liquid layer will change from stable convection to unstable convection. Two kinds of optical diagnostic system with image processor are developed for study of the kinetics of buoyant-thermocapillary convection, they give out the information of liquid free surface. The quantitative results are calculated by Fourier transform and correlation analysis, respectively. With the increasing temperature gradient, surface deformations calculated are more declining. It is interesting phenomenon that the inclining directions of the convections in thin and thick liquid layers are different. For a thin layer, the convection is mainly controlled by thermocapillary effect. However, for a thick layer, the convection is mainly controlled by buoyancy effect. The surface deformation theoretically analysed is consistent with our experimental results. The present experiment proves that surface deformation is related to temperature gradient and thickness of the liquid layer. In other words, surface deformation lies on capillary convection and buoyancy convection.

Aquaculture Asia, Vol. 8, No. 2, pp.1-47, April-June 2003

*Table of Contents* Sustainable Aquaculture Peter Edwards writes on rural aquaculture: Peri-urban aquaculture in Kolkata A case of informal shrimp farmers association and its role in sustainable shrimp farming in Tamil Nadu, India M. Kumaran, N. Kalaimani, K. Ponnusamy, V.S. Chandrasekaran, D. Deboral Vimala Diffusion and adoption of shrimp farming technologies M. Kumaran, K. Ponnusamy and N. Kalaimani Farmers as Scientists: Aquaculture education in India - opportunities for global partnership M.C. Nandeesha Information system of fish germplasm resources in China Yang Ningsheng, Ge Chanshui, Ouyang Haiying, Yuan Yongming Status and development needs of freshwater crustacean aquaculture in China Xu Pao Research and Farming Techniques Aquaculture fundamentals: Getting the most out of your feed Part II: The role of macronutrients Simon Wilkinson Fish breeding in captivity - some innovative adaptations of technology by Bengal farmers N.R. Chattopadhyay Scientific guidelines for farmers engaged in freshwater prawn farming in India Vishal Saxena Marine Finfish Section News and publications Status and development of mariculture in Indonesia Ketut Sugama Aquatic Animal Health Use of probiotics in larval rearing of new candidate species Rehana Abidi Advice on aquatic animal health care: Problems in shrimp culture during the wet season (Thai/English languages) Pornlerd Chanratchakool

力学2000

本书收录关于力学领域的论文301篇。内容包括：回顾20世纪力学在中国的发展，描绘了2000年中国和世界在力学各主要领域的发展现状；展望力学在21世纪的发展方向，探论新世纪中可能面临的新的重大力学等问题。

Thermal cracking of aviation kerosene for scramjet applications

Thermal cracking of China No.3 aviation kerosene was studied experimentally and analytically under supercritical conditions relevant to regenerative cooling system for Mach-6 scramjet applications. A two-stage heated tube system with cracked products collection/analysis was used and it can achieve a fuel temperature range of 700-1100 K, a pressure range of 3.5-4.5 MPa and a residence time of approximately 0.5-1.3 s. Compositions of the cracked gaseous products and mass flow rate of the kerosene flow at varied temperatures and pressures were obtained experimentally. A one-step lumped model was developed with the cracked mixtures grouped into three categories: unreacted kerosene, gaseous products and residuals including liquid products and carbon deposits. Based on the model, fuel conversion on the mass basis, the reaction rate and the residence time were estimated as functions of temperature. Meanwhile, a sonic nozzle was used for the control of the mass flow rate of the cracked kerosene, and correlation of the mass flow rate gives a good agreement with the measurements.

Advanced density functional theory methods for materials science

In this work we chiefly deal with two broad classes of problems in computational materials science, determining the doping mechanism in a semiconductor and developing an extreme condition equation of state. While solving certain aspects of these questions is well-trodden ground, both require extending the reach of existing methods to fully answer them. Here we choose to build upon the framework of density functional theory (DFT) which provides an efficient means to investigate a system from a quantum mechanics description.

Zinc Phosphide (Zn₃P₂) could be the basis for cheap and highly efficient solar cells. Its use in this regard is limited by the difficulty in n-type doping the material. In an effort to understand the mechanism behind this, the energetics and electronic structure of intrinsic point defects in zinc phosphide are studied using generalized Kohn-Sham theory and utilizing the Heyd, Scuseria, and Ernzerhof (HSE) hybrid functional for exchange and correlation. Novel 'perturbation extrapolation' is utilized to extend the use of the computationally expensive HSE functional to this large-scale defect system. According to calculations, the formation energy of charged phosphorus interstitial defects are very low in n-type Zn₃P₂ and act as 'electron sinks', nullifying the desired doping and lowering the fermi-level back towards the p-type regime. Going forward, this insight provides clues to fabricating useful zinc phosphide based devices. In addition, the methodology developed for this work can be applied to further doping studies in other systems.

Accurate determination of high pressure and temperature equations of state is fundamental in a variety of fields. However, it is often very difficult to cover a wide range of temperatures and pressures in an laboratory setting. Here we develop methods to determine a multi-phase equation of state for Ta through computation. The typical means of investigating thermodynamic properties is via ’classical’ molecular dynamics where the atomic motion is calculated from Newtonian mechanics with the electronic effects abstracted away into an interatomic potential function. For our purposes, a ’first principles’ approach such as DFT is useful as a classical potential is typically valid for only a portion of the phase diagram (i.e. whatever part it has been fit to). Furthermore, for extremes of temperature and pressure quantum effects become critical to accurately capture an equation of state and are very hard to capture in even complex model potentials. This requires extending the inherently zero temperature DFT to predict the finite temperature response of the system. Statistical modelling and thermodynamic integration is used to extend our results over all phases, as well as phase-coexistence regions which are at the limits of typical DFT validity. We deliver the most comprehensive and accurate equation of state that has been done for Ta. This work also lends insights that can be applied to further equation of state work in many other materials.